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    P1.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session)

    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Moderators:
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      • Abstract

      Background

      The combination of RT and programmed death 1 (PD-1) inhibitors seems augment antitumor immune responses. The aim of this study was to assess the outcome of patients (pts) with NSCLC previously undergone to RT before receiving nivolumab, a PD-1 inhibitor

      Method

      We conducted an observational, retrospective analysis of 95 consecutive pts with advanced NSCLC who received any RT within 10 months prior nivolumab, as clinically indicated, at seven Italian institutions. Tumor response to treatment was defined according to RECIST criteria version 1.1. Median overall survival (OS) and the 95% confidence interval (CI) were estimated with the Kaplan -Meier method.

      Result

      95 pts (median age 66 years [range 41-82]; male:63.2%) with advanced NSCLC (adenocarcinoma [adc]:66.3%; squamous cells [sqc]:33.7%) were treated with nivolumab after RT. Median OS was 11.9 months (mo) [95% CI, 6.6-17.2 (adc: 13.0 mo [95% CI,6.7-19.3], sqc 10.5 mo [95%CI,3.9-17.1]). Median progression free survival (PFS) was 6.3mo [95% CI,4.6-8.0] (adc: 6.4 mo[ 95% CI,4.5-8.3]; sqc: 3.7 mo [95% CI,0.0-8.3]). A better performance status (PS) according to ECOG scale was associated with an improved OS (PS 0[38 pts]: 17.9 mo [95% CI,12.3-23.5; p<0.0001]; PS1[50pts]: 6.9 mo [95%CI,3.2-10.6]; PS2[7pts]: 4.4 mo [95% CI,3.9-4.9]). Median OS in 70 pts who received ≤ 1 previous systemic therapy was 13.0 mo [95% CI, 10.4-15.6] and in 25 pts who received ≥2 prior lines was 7.4 mo [95% CI, 1.8-12.9]. Median OS in 69 pts (72.6%) receiving extracranical RT was 12.0 mo [95%CI,6.6-17.4] and in 26 (27.4%) pts with cranial RT was 11.7 mo [95%CI,NE]; p=0.31. Median OS was shorter in 36 pts receiving bone-RT [7.3 mo; 95% CI, (0-15.3)] when compared with 59 pts receiving extra-bone RT [14.4 mo; 95% CI, (10.3-18.5); p=0.007]. Median OS in 68 pts aged < 70 years was 11.9 mo [95% CI,6.5-17.3] and in 27 elderly (≥ 70 years) was 12.0 mo [95% CI, 3.8-20.1]. 1 (1.0%) complete response, 25(26.3%) partial response, 28(29.5%) stable disease and 41 (43.2%) progressive disease have been observed.

      Conclusion

      This study shows that combining irradiation with nivolumab for the treatment of advanced NSCLC leads to improve OS and promote tumor control both locally and distantly.This potentially synergistic effect was comparable among pts regardless previous lines of therapy, histology, type of RT and age.

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      P1.15-02 - Migration Differences in Small Cell vs Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Shruti Bhandari  |  Author(s): Danh C Pham, Christina Pinkston, Malgorzata Oechsli, Goetz H Kloecker

      • Abstract

      Background

      Every year there is a population diagnosed with lung cancer (LC) that does not receive initial treatment upon diagnosis and then “migrates” to other hospital systems before ultimately getting treatment. We aimed to compare migration rates between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) and potential factors associated with migration.

      Method

      As part of the Kentucky Lung Cancer Education Awareness Detection Survival (LEADS) Collaborative, 29 of 32 Kentucky hospital registries contacted provided LC data of 7660 patients from 2012-2014. Data collected included age at diagnosis, stage, overall survival (OS), sex, race, insurance and treatment history. Treatment included any combination of surgery, radiation, or chemotherapy. Hospital records were matched to Kentucky Cancer Registry records to determine the number of hospitals visited for treatment. Patient treatment and migration patterns were analyzed with a logistic regression model along with additional post-hoc analysis. Difference in rates was calculated by chi-square test.

      Result

      Among the 7660 LC patients, 81% were NSCLC and 19% were SCLC. Most patients were treated at their initial hospital - NSCLC (73%) and SCLC (82%) (p value<0.01). However, among the untreated patients, 616 (36%) of NSCLC patients migrated to a different hospital compared to only 23 (8%) of SCLC patients (p value<0.01). Migration of NSCLC patients to another hospital was associated with Stage I-III disease, younger age (66.4 vs 72.2 years), with initial hospitals missing treatment modalities and patients having private insurance. In NSCLC, compared to patients treated initially, patients treated after migration lived longer (591 vs 505 days) and particularly had longer survival with stage III (563 vs 495 days) and IV disease (379 vs 300 days). Too few patients with SCLC migrate to assess association with OS and other patient characteristics.

      Conclusion

      There is a significant difference in rates of initial treatment between NSCLC and SCLC that could be due to perceived urgency to treat SCLC. This analysis shows highly significant 4-fold increase in migration rate of NSCLC as compared to SCLC. This could be explained by newer and better treatment options available at referral centers for NSCLC and a lack of these options for SCLC. Increasing research and new innovations in NSCLC will likely drive more patients to migrate in future.

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      P1.15-03 - Clinical Characteristics of Long-Term Survivors With Nivolumab in Pretreated Advanced NSCLC<br /> from Real-World Data (RWD)

      16:45 - 18:00  |  Presenting Author(s): Antonio Calles  |  Author(s): Miguel Garcia, Miriam Lobo, Rosa Álvarez Álvarez

      • Abstract

      Background

      We have previously analyzed real-world data (RWD) from patients with metastatic NSCLC that progressed to chemotherapy and were subsequently treated with immune-checkpoint inhibitors (ICI). This included patients with performance status of 2, brain metastases, concomitant use of steroids, unknown PD-L1 status, systemic antibiotics during the previous month, and without restriction in the number of previous lines received. Now, with a longer follow-up, we aimed to analyze the baseline clinical characteristics in long-term survivor patients.

      Method

      We performed a retrospective study of previously treated advanced NSCLC patients that received nivolumab at 3 mg/kg every 2 weeks outside clinical trials from our institution in Madrid (Spain) between January 2015 and April 2018. We used RWD to analyze the clinical characteristics of patients who were alive 2 years after the start of ICI.

      Result

      A total of 38 pts fulfilled inclusion criteria. 7 pts (18%) where alive 2 years after the first dose of nivolumab. Median age at diagnosis was 63 years (53-72 years). 6 pts (86%) had history of tobacco smoking, and 6 pts (86%) had non-squamous histology. 3 pt had ECOG 0 (43%), 3 pts had ECOG 1 (43%) and one pt had ECOG 2 (14%). Median number of previous lines was 3; 3 pts received nivolumab in second line, 3 pts in fourth line and one pt in fifth line. All pts were diagnosed with primary advanced disease. 2 of the pts (29%) had brain metastases and 1 pt (14 %) had ≥ 4 metastatic locations. 2 pts had use antibiotics in the month before and 1 pt used steroids. Best response to nivolumab per RECIST 1.1 criteria included 3 partial responses (43%), and 2 each (29%) had stable and progressive disease. Only 2 pts had no evidence of disease progression during > 2 years at last follow-up when the database was lock (April 2018). Five pts discontinued treatment due to disease progression.

      After progression, 1 pt continued treatment with nivolumab, 1 pt started osimertinib (EGFR mutant previously treated with TKI and chemotherapy, and confirmed T790M+), and 3 pts started chemotherapy followed by retreatment with ICI. No patients discontinued due to adverse events.

      Conclusion

      In our RWD experience, nivolumab resulted in a 2-years survival rate of 18% in previously treated advanced NSCLC patients. Clinical characteristics from real world patients do not predict for long term benefit of nivolumab. Immunological biomarkers are necessary to better select pts who will derive long-term benefit from immunotherapy.

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      P1.15-04 - Practice Patterns Regarding Multidisciplinary Cancer Management for NSCLC and implemetantion: Results of National Survey in México

      16:45 - 18:00  |  Presenting Author(s): Saul Campos-Gomez  |  Author(s): Karen A Campos-Gomez, Omar Macedo-Pérez, Juan J Valdéz Andrade, Oscar Arrieta

      • Abstract

      Background

      To manage patients with advanced lung cancer in the most effective way, experts from different disciplines need to be engaged. This has resulted in introduction of the multidisciplinary team (MDT) approach. Because of these advantages, current clinical guidelines recommend discussing the diagnostic and therapeutic plan with an MDT for localized or locally advanced Non-Small Cell Lung Cancer (NSCLC). However, studies suggest despite the advantages of multidisciplinary care, the proportion of new lung cancer diagnoses that are formally discussed in Lung Cancer MDM are disappointing low, in the order of 28–29%. An Australian survey suggests that only one third of hospitals have a multidisciplinary team.

      Method

      However, it is unclear how specialists view current evidence about multidisciplinary team (MDT) approach and how they would incorporate into practice. We sought to understand specialist opinions about evidence regarding treatment of NSCLC and how this translates into clinical practice implementation.This study was conducted to explore specialist opinions about multidisciplinary team approach of NSCLC, how this translates into practice and the implementation in Mexico.

      Result

      We collected a total of 60 completed responses (50%), 77% were medical oncologist, 7% surgical oncologist and 17% radiation oncologists. Of these 34% mainly worked in private and 66% in public healthcare Systems. Seventy two percent of all physicians were < 40 years, 25% between 40 and 50 years of age and 22% were 50 years of age or older. Young doctors (up to 5 years of service) accounted for 45 %, with a median length of practice of 12 years. More than two-thirds of physicians were male. Approximately 58% of respondents stated that exist a MDTs for NSLC in their institutions. The Core members of the multidisciplinary cancer team usually include an oncologist (medical, surgical, radiation), pathologist and radiologist in the 65% of the teams. Approximately 55% of respondents stated that MDTs met regularly. Forty two of survey responders do not have a MDT but can discusses new cases directly with surgical oncologist o radiologist.

      Conclusion

      While multidisciplinary care has emerged as the standard of care for lung cancer management. The challenge for the future is how to more fully integrate multidisciplinary care into the management of all patients with lung cancer in México.

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      P1.15-05 - The Frequency and Spectrum of EGFR Exon 20 Insertions in NSCLC: A Global Literature Review

      16:45 - 18:00  |  Presenting Author(s): Victoria Crossland  |  Author(s): Shuanglian Li, Aaron Galaznik

      • Abstract

      Background

      There are limited epidemiological data on non-small cell lung cancer (NSCLC) patients with non-classical (uncommon) epidermal growth factor receptor (EGFR) mutations. In light of ongoing development of TAK-788, we describe the global frequency and spectrum of EGFR exon 20 insertions in NSCLC based on a comprehensive literature review as well as highlight possible regional variations.

      Method

      A literature search was conducted to identify publications reporting the frequency of EGFR exon 20 insertions in unselected NSCLC patients. PubMed and ASCO, ESMO, and IASLC meeting abstracts were searched up to April 2018 using the following keywords: non-small cell lung cancer, epidermal growth factor receptor, exon 20, insertions and uncommon mutations. Only publications in English were included. The pooled frequency of EGFR exon 20 insertions for each country were determined, and insertion variants (where available) were described at the global level.

      Result

      A total of 26 studies from 25 countries were included, reporting on 569 patients with EGFR exon 20 insertions among 41,321 NSCLC patients. The highest mutation frequency was seen in China (2.9%) and the lowest in Indonesia (0.1%). When pooled by country, exon 20 insertions were found in 0.1−2.1% of all NSCLC.

      frequency of egfr exon 20 insertions in patients with nsclc.jpg

      Over 50 insertion variants were reported, covering amino acids 761−774. The most commonly detected mutations included D770_N771insSVD, V769_D770InsASV, H773_V774InsH, H773_V774insNPH, and A763_Y763insFQEA.

      Conclusion

      The frequency of EGFR exon 20 insertions was 0.1−2.1% of NSCLC patients, with a high variability in both length and position of insertions within exon 20. Currently, available data are sparse and come primarily from studies based on single-center experiences, with data gaps across several large geographic regions and populations. Results also indicate a need to further explore underlying geographic variations in epidemiology. Larger, multi-center global studies will further help to refine the frequency of exon 20 insertions and other uncommon mutations in NSCLC.

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      P1.15-06 - Integrative Quality Improvement for Management of Lung Cancer in Uganda

      16:45 - 18:00  |  Presenting Author(s): Semujju David

      • Abstract

      Background

      Uganda is currently engaged in quality improvement initiatives for cancer patients. One of them is the creation of an integrative quality system, consisting of guideline development, quality indicators definition and feedback to hospitals. This approach has already been successfully implemented for five types of cancers: rectum (in collaboration with development partners), breast, testis, oesophagus and stomach. Building on previous experience, the study presents the development of a set of quality indicators (QIs) for the management of lung cancer.

      Method

      We followed the standardized MOH methodology to identify, select, test and measure the indicators. Because patients may be in contact with different hospitals (for instance, be diagnosed in one hospital but receive treatment – surgery or radiotherapy – in another), we developed a specific algorithm to attribute each patient to the centre where he/she was diagnosed or received treatment (surgical centre or centre of radiotherapy). The method to test the feasibility of identifying comorbidities of patients based on their pharmaceutical billing data during the year before the cancer diagnosis is also described.

      Result

      The results of this project made clear that we need more complete and accurate reporting of data to allow more precise and correct evaluation of the quality of care for lung cancer patients in Uganda. Quick and fluent data collection would make it possible to provide comprehensive feedback to care providers on a regular and timely basis. To make this happen, investments in data registration and analysis will be necessary.

      Conclusion

      When benchmarking results between hospitals, cautious interpretation is warranted. The use of funnel plots avoids spurious ranking of hospitals and outlier dots can reliably designate either good or bad performers. Statistical modeling can often only partially account for differences in case-mix and other biases. Judging quality of care delivered by a hospital is further hindered by the often small number of patients treated per hospital. Hence, from a sheer statistical point of view, small volumes of activity make it impossible to offer an acceptable level of assurance about the quality delivered to the patient.

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      P1.15-07 - Geriatric Oncology - Lung Cancer in Elderly Patients and Palliative Treatment: Prospective Analysis of A. C. Camargo Cancer Center

      16:45 - 18:00  |  Presenting Author(s): Mauro DS Donadio  |  Author(s): Audrey CF de Oliveira, Luciana M Leite, Malu VR Barbosa, Tiago C Felismino, Marcelo P Corassa, Vladmir CC de Lima, Victor HF de Jesus, Aldo LA Dettino

      • Abstract

      Background

      Special attention is required by elderly population, due to chemotherapy (ch) risks and comorbidities, which may limit the capacity to deliver optimal cancer care. We aimed to describe the clinical features and survival outcomes of elderly patients (pts) with lung adenocarcinoma (ADC) treated with non-curative intent at A. C. Camargo Cancer Center.

      Method

      We evaluated all pts aged 70+ with lung ADC treated with ch or target therapy in 1st or 2nd-line from 2007 to 2015 who underwent a comprehensive geriatric assessment (CGA), in a convenient prospective series. We used summary statistics to describe the population. Overall survival (OS) was calculated according to Kaplan-Meier method, from CGA date to last follow-up or death. We performed univariate and multivariate analysis in order to look for potential prognostic factors for OS.

      Result

      CGA was done in 55 pts aged ≥70y with lung ADC. The median age was 76y and 22% had ECOG ≥ 2. Half of pts were male. 51% had polypharmacy (≥5 drugs). Pts were functionally classified according to activities of daily living (ADL): 76% as Katz A and 50% as Lawton ≤27. 68.5% were at risk for malnutrition or malnourished. The median age-adjusted Charlson Comorbidity score was 10 – remembering that 4+ is considered clinically significant. 61% had ≥2 comorbidities and 26 pts had at least 2 metastatic sites. CNS was affected in 7.5% of the cases and liver in 9.2%. 79.6% of the pts underwent ch and the others received target therapy. After follow-up of 29m, median OS was 17.1 months (13.5-27.8m). In univariate analysis, significantly worse survival outcomes were observed for pts with ECOG 2-4 (HR 10.6; p < 0.001), increasing number of sites of metastases (HR 2.2; p = 0.04) and hepatic metastasis (HR 6.03; p < 0.001). In the multivariate analysis, male gender, ECOG 2-4 and liver metastasis were associated with higher risk of death.

      Conclusion

      ADL, an important part of CGA, showed little prognostic value in our small population. Pts with ECOG 2-4 or hepatic metastasis were those that presented the highest risk of death. CGA is a good tool to help in stratifying risk of elderly cancer pts and is mandatory in cost-benefit analysis to identify the best treatment to each individual patient.

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      P1.15-08 - Implementation and Feasibility of the Assessment of EGFR Mutation in NSCLC Using Liquid Biopsy at an Argentinean University Hospital

      16:45 - 18:00  |  Presenting Author(s): Carolina Gabay  |  Author(s): Nazareth Rusjan, Krasnapolski Martin, Mara Bonet, Erica Rojas Bilbao, Monica Castro

      • Abstract

      Background

      Molecular characterization of lung cancer is standard of care. Almost 85% of NSCLC patients have advanced disease at diagnosis, being a challenge get enough tissue for diagnosis. That´ s why using less invasive methods as liquid biopsy by determining cftDNA (circulating free tumor DNA) represents a promising tool. The detection of EGFR mutations in plasma by Therascreen (EGFR RGQ Mutation Kit) showed a sensitivity and specificity of 65.4% and 100 % respectively. It is also useful to detect TKI´s resistance previous to clinical progression. The advantages of using PCR, even there are more sensitive methods available, are its simplicity and cost.

      Method

      We will prospectively recruit EGFR mutation-positive (n=40) NSCLC patients. Plasma samples are collected: baseline, after three months of treatment, every six months and at the time of progression. We report our first interim analysis. We evaluate the concordance of EGFRm in tissue and plasma with the implementation of the Therascreen test (Qiagen). We test other available plasma EGFRm detection kit (EGFR Plasma Mutation Analysis Kit, Entrogen) (n=10)

      Result

      Since February 2017, plasma EGFRm status could be determined in 17 out of 22 NSCLC patients with EGFRm in tissue. L858R was present in 9 (53%), del19 in 7 (42%), del19+T790M in 1 (5%). Baseline plasma analyzed with Therascreen and Entrogen kits showed similar sensitivity of 61.1% and 66% respectively. Only 1/11 pt had discordance between both kits (Therascreen negative , entrogen DEL19+T790M ).

      In 17 analyzed ptes, median age was 59 (51-76) years. Most of the population were women (88%), were never smokers (58%), had stage IV disease (58%). Frequent site of metastasis was bone (n=7). With a median follow up of 18 months (12-23), 7/15 (56%) patients who experienced clinical progression were detected also in plasma. Two patients presented T790M in plasma without evidence of disease progression until last follow-up (July 2018). We also observed two patients with mutations detected out of range to be considered as positive which became positive for these mutations during the follow up.

      Conclusion

      This is the first work showing a cohort of EGFRm patients prospectively analyzed by successive liquid biopsies in a public institution in Argentina. We could successfully obtain cftDNA and analyze it by two commercial kits. The sensitivity of both kits was comparable to previous reports. The study is ongoing and more samples will be analized to shed light about the plasma dynamics of EGFRm related to clinical behavior.

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      P1.15-09 - Trends in Lung Cancer Survival in Lithuania

      16:45 - 18:00  |  Presenting Author(s): Vaida Gedvilaite  |  Author(s): Edvardas Danila, Saulius Cicenas, Giedre Smailyte

      • Abstract

      Background

      Lung cancer is the most common cancer-related death worldwide. The prognosis of lung cancer is unfavourable and improvements in survival in recent decades have been minimal. The aim of this study is to describe the most recent survival rates by sex, age group, extent of disease and histology of lung cancer in Lithuania.

      Method

      The study is based on the Lithuanian Cancer Registry database covering a population of around 3 million residents according to 2011 census. The analysis included patients with primary invasive lung cancer diagnosed in 1998-2012 who were at least 15 years old at the time of diagnosis. Patients were followed-up with respect to vital status until December 31, 2012. Cases notified by the death certificate only were excluded. Five-year relative survival estimates were calculated using period analysis. Relative survival was calculated as the ratio of the observed survival of cancer patients and the expected survival of the underlying general population. The latter was calculated according to the Ederer II method using national life tables for Lithuanian population stratified by age, gender and calendar year.

      Result

      In our study the overall 5-year relative survival was low, but increased slightly from 6,4% in 2003-2008 to 7.9 % 2009-2012. Positive changes in survival were evident in both sexes, in almost all age groups and for all histological groups and disease stages. Adenocarcinoma relative survival increased from 6.7% in 2003-2008 to 12.8% in 2009-2012 and squamous cell carcinoma increased from 7.4% in 2003-2008 to 11.1% in 2009-2012. Patients with small cell carcinoma had the worst survival (2.9% in 2003-2008 and 3.6% in 2009-2012). Only less than 10% of lung cancer cases were diagnosed localised and proportion of those tumours decreased slightly (from 8.5% to 7.6%). In 2009-2012 relative survival of localised stage lung cancer was 43 %, locally advanced – 19,9%, regional disease - 6% and metastatic disease – 0.7%.The highest number of lung cancer was diagnosed with distant metastases and proportion of metastatic tumours increased from 35.1% to 37.8%. 5-year relative survival was higher in women (9.4 % in 2003-2008 and 12.6 % in 2009-2012) than in men (5.8 % in 2003-2008 and 7% in 2009-2012).

      Conclusion

      Despite low overall survival, there were positive changes in survival in both sexes, in almost all age groups and for all histological groups and disease stages. The high proportion of metastatic disease at the time of diagnosis was the main factor that influenced low survival rates.

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      P1.15-10 - Comparison of Selected Colombian National Administrative Cancer Registry (NACR) Data in Lung Cancer with the U.S.

      16:45 - 18:00  |  Presenting Author(s): Robert Hsu  |  Author(s): Lizbeth Acuna Merchan, Gilberto de Lima Lopes

      • Abstract

      Background

      Lung cancer (LC) is the seventh leading cause of cancer in Colombia and the leading cause of cancer mortality in the United States. In Colombia, previous estimates of lung cancer have been limited to city specific cancer registry (Cali Cancer Registry) and broad estimates from GLOBOCAN. The Colombian Health Ministry in 2015 created the National Administrative Cancer Registry (NACR) to obtain national cancer data. We investigated selected 2016 NACR data and compared it to data from the U.S. to gauge for areas of improvement in lung cancer delivery.

      Method

      We obtained NACR data compiled from the Colombian Department of Health Ministry regarding lung cancer from 2015-2016. We compared this to U.S. data consisting of Surveillance, Epidemiology, and End Results (SEER) and National Cancer Database (NCDB) data from 2003-2015.

      Result

      NACR data in 2016 shows incidence of 1.7 cases per 100,000 and mortality of 2.5 cases per 100,000. SEER data from 2015 shows incidence of 47.2 cases per 100,000 and mortality of 40.6 cases per 100,000. NACR data shows average age of 66 (IQR = 65.7-66) while NCDB data shows median age to be in the age 60-69 category. NACR data in 2016 shows that 14.02% of 849 diagnosed LC patients received surgery compared to 24.83% of 168,093 diagnosed non-small cell lung cancer and small cell lung cancer patients in 2015 from the NCDB. NACR data demonstrates that of those receiving chemotherapy with documented regimens (n=275), 52% received carboplatin, 28.3% received pemetrexed, 27.6% received cisplatin, 25.4% received paclitaxel, 10.9% received bevacizumab, and 5.1% received erlotinib. In comparison, SEER data from 2000-2011 show metastatic NSCLC patients receiving antineoplastic agents (n = 2022) with increasing use of pemetrexed (39.2%), erlotinib (20.3%), and bevacizumab (18.9%) and declining use of paclitaxel (38.7%), gemcitabine (17.0%), and vinorelbine (5.7%). NACR data shows median wait time from diagnosis to first treatment of 31 days (IQR=14-62, n=346) compared to NCDB data showing median wait time of 35 days from diagnosis to first treatment.

      Conclusion

      Data shows significantly higher incidence and mortality in the U.S.; this is multifactorial due to screening and data reporting. Comparison shows higher rates of surgery and use of biologics in the U.S. There were similar wait times from diagnosis to first treatment and age of LC patients. Limitations include limited reporting on chemotherapy, radiation, and staging. Future improvements from a Colombian standpoint will include outcomes data collection, increased screening, resources for surgery, and updated access to antineoplastic agents.

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      P1.15-11 - Lung Cancer as One of Multiple Cancers: A Population-Based Study in Estonia 1995-2015

      16:45 - 18:00  |  Presenting Author(s): Jana Jaal  |  Author(s): Marju Kase, Katrin Sak, Marika Saar, Markus Vardja, Margit Mägi

      • Abstract

      Background

      Due to recent developments in cancer prevention, early diagnosis and treatment, more cancers are detected at earlier stages and more patients are cured. As a result, the burden of second and further primary malignancies in a growing and ageing population has remarkably increased over the last decades. Lung cancer is one of the most frequent but most deadly types of cancer. Whether this type of malignancy has a considerable role among multiple cancers is not known. Therefore, the aim of the present study was to assess lung cancer cases as one of the multiple cancers in Estonia.

      Method

      We used the data from the Estonian Cancer Registry (ECR), a population-based registry with nationwide coverage (total 1.3 million inhabitants). The ECR provided data on all lung cancer cases and associated multiple cancer cases diagnosed in Estonia 1995‒2015.

      Result

      During the time period of 20 years, 146541 cancer cases (ICD-10 C00-C97 and in situ cancers D00-D09) were recorded. Lung cancer cases (n=16350) comprised 11% of all malignancies. Out of all diagnosed lung cancer cases, 10% of patients had multiple cancers (n=1619). Lung cancer as first multiple cancer was diagnosed in 398 patients (25%; 338 men, 60 women; median age 67 years, range 31-87 years). Lung cancer as second cancer was diagnosed in 1130 patients (70%; 851 men, 279 women; median age 67 years, range 32-91 years). Ninety one patients had lung cancer as their third cancer (5%; 67 men, 24 women; median age 66 years, range 32-79 years). None of the patients had lung cancer as fourth or further multiple cancers. Next to lung cancer, patients had mostly melanoma and other malignant tumors of skin (18%), malignant neoplasms of digestive organs (18%), male genital organs (18%) and urinary tract (13%) as well as respiratory tract cancers including new lung primaries (10%). Other types of cancers represented 23% of malignancies. After first diagnosis of lung cancer, second tumor was diagnosed approximately 5 months (median) later. As second multiple cancer, lung cancer was diagnosed 7 years (median) after the first cancer diagnosis. Lung cancer as third cancer developed approximately 2 years (median) after the second diagnosis of malignant tumor.

      Conclusion

      Multiple cancers are common among lung cancer patients in Estonia. Particular attention is needed, when patient with lung cancer develops skin changes, gastrointestinal and genitourinary symptoms or presents with newly developed respiratory tract complaints.

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      P1.15-12 - Real World Applications of Next-Generation Sequencing of Non-Small Cell Lung Cancer in the Veteran Population

      16:45 - 18:00  |  Presenting Author(s): Jeremy Kratz  |  Author(s): Gil Harmon, David Kosoff, Doug Wubben, Ryan Laughlin, Anne Traynor, Dustin Deming, Mark Burkard, Ticiana A. Leal

      • Abstract

      Background

      Population studies to date have demonstrated decreased rates of driver mutations in non-small cell lung cancer (NSCLC) for veterans with prior tobacco use who receive care at Department of Veterans Affairs (VA) facilities. Causes of this reduced rate have not been identified, but may result in underutilization of broadly based genetic tumor profiling. The VA recently expanded next-generation sequencing (NGS) to include both tissue and liquid biopsies for comprehensive genetic profiling for patients (pts) with advanced malignancy. Herein, we describe clinical utility of NGS from our retrospective cohort of a rural-based NSCLC veteran population.

      Method

      We performed a retrospective cohort analysis of 79 veterans with metastatic NSCLC from 07/2015-04/2018. A trainee-initiated quality improvement initiative in 07/2017 disseminated education at the VA facility about the role of NGS testing for non-squamous NSCLC, with support from the University of Wisconsin Precision Medicine and Molecular Tumor Board. Baseline demographics, time to tissue biopsy, and genetic tumor profiling were analyzed; clinical outcome data were collected including overall survivial and progression-free survival.

      Result

      As expected, the cohort was predominantly male (91.1%), with tobacco use (median 45 pk-yrs, 95% >5 pk-yrs) and median age 69 yrs. For molecular profiling, 52% had sufficient tissue at metastatic diagnosis, 20% underwent repeat biopsy within 30 days, 17% underwent biopsy after 30 days, and 11% presented with comorbidity resulting in empiric or palliative management. After implementation of the quality improvement project, the frequency of genetic profiling increased compared to pre-expanded NGS availability in the following targets: EGFR (59% v. 90%), ALK (65% v. 90%), ROS1 (35% v. 90%), and BRAF (8% v. 60%). Actionable targets were identified in EGFR 15.4% (5/39 pts), ALK (1/41), ROS1 (1/24), and BRAF (1/11); additional mutations in NTRK1, NTRK3, ERBB2, and FGFR1 were detected.

      Conclusion

      Our preliminary results demonstrate that the availability and use of NGS was associated with increased rates of comprehensive genetic profiling in a largely rural veteran population. Ongoing work will expand this retrospective cohort to more thoroughly characterize barriers to diagnosis and target-specific frequency over historical advances in precision oncology. We will review how these genetic profiles may offer both prognostic and predictive value by reporting clinical outcomes between targeted therapy and early applications of immunotherapy within the veteran population.

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      P1.15-13 - Wait Times for Diagnosis and Treatment of Lung Cancer Across the Province of Quebec, Canada

      16:45 - 18:00  |  Presenting Author(s): Catherine Labbe  |  Author(s): Simon Martel, Brigitte Fournier, Carole Saint-Pierre

      • Abstract

      Background

      Multiple clinical practice guidelines recommend rapid evaluation of patients with suspected lung cancer. Diagnostic pathways and wait times vary considerably from one centre to another.

      Method

      We retrospectively reviewed medical records of all patients (n=1217) across the province of Quebec who had a biopsy-proven diagnosis of lung cancer between February 1st and April 30th, 2017. Median wait times for diagnosis and treatment were calculated.

      Result

      Patient characteristics are shown in Table 1. Median wait times for investigation and treatment are shown in Table 2. There were variations between centres and regions.

      Characteristic

      No (%)

      Age, years, mean (range)

      68.5 (20-94)

      Male sex

      585 (48)

      Smoking status

      Former or current smoker

      Never smoker

      Unknown

      1120 (92)

      60 (5)

      37 (3)

      ECOG performance status

      0

      1

      ≥2

      Missing

      416 (34)

      358 (30)

      393 (32)

      50 (4)

      Histology

      Adenocarcinoma

      631 (52)

      Squamous cell carcinoma

      284 (23)

      NSCLC NOS

      70 (6)

      SCLC

      178 (15)

      Other

      54 (4)

      TNM stage

      I

      213 (18)

      II

      114 (9)

      III

      227 (19)

      IV

      475 (39)

      Limited SCLC

      40 (3)

      Extensive SCLC

      138 (11)

      Missing

      10 (1)

      Known positive EGFR mutation status (n=395 tested)

      Known positive ALK translocation status (n=387 tested)

      PD-L1 TPS (n=386 tested)

      <1%

      1-49%

      ≥50%

      Number of investigations per patient, median (IQR)

      28 (7)

      6 (2)

      85 (22)

      151 (39)

      150 (39)

      7 (6, 8)

      Tumor board review

      194 (16)

      Final diagnostic procedure

      Flexible bronchoscopy

      338 (28)

      EBUS/EUS

      223 (18)

      Transthoracic needle biopsy

      301 (25)

      Thoracoscopy

      139 (11)

      Biopsy of metastatic site

      145 (12)

      Sputum cytology

      1 (0)

      Thoracentesis

      61 (5)

      Mediastinoscopy

      Missing

      2 (0)

      7 (1)

      ECOG = Eastern Cooperative Oncology Group; NSCLC = non-small cell lung cancer; NOS = not otherwise specified; SCLC = small cell lung cancer; EGFR = epidermal growth factor receptor; ALK = anaplastic lymphoma kinase; TPS = tumor proportion score; IQR = interquartile range; EBUS = endobronchial ultrasonography; EUS = endoscopic ultrasonography.

      Table 2 – Median wait times for investigation and treatment

      Investigation or treatment interval

      Pts (n)

      Median wait, days (IQR)

      Referral to first appointment with specialist

      972

      2 (0, 7)

      First appointment to diagnosis

      1152

      18 (8, 43)

      Diagnosis to first treatment

      930

      22 (5, 42)

      Referral to first treatment

      737

      58 (28, 89)

      Abnormal imaging to first treatment

      902

      72 (39, 111)

      Surgery

      268

      109 (80, 142)

      Radiation

      362

      59 (28, 98)

      Systemic therapy

      330

      62 (35, 92)

      Conclusion

      To our knowledge, this is the largest multicentre review of wait times for diagnosis and treatment of lung cancer with detailed characteristics of patients. Data will be completed and updated prior to the meeting, to try to identify specific factors associated with longer wait times.

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      P1.15-14 - Pneumonia in Patients with Lung Cancer of South Korea: A Nationwide Population Based Study

      16:45 - 18:00  |  Presenting Author(s): Hyun Woo Lee  |  Author(s): Joonho Jung, Jaesung Heo

      • Abstract

      Background

      We analyzed the prevalence of pneumonia in lung cancer survivors using claims data from the Health Insurance Review and Assessment Service (HIRA) in South Korea.

      Method

      We defined pneumonia among a nationwide cohort of 173,390 patients who were diagnosed with lung cancer and underwent surgery from January 1, 2010 to December 31, 2014, based on HIRA claim data. Descriptive statistics were calculated to estimate the frequency of pneumonia using diagnostic code and utilization pattern at medical institutions.

      Result

      Thirty two thousand five hundred lung cancer survivors (19.8%) were diagnosed with pneumonia. The overall frequency of influenza increased from February (n=8089) and peaked in May (n=9,654). Over 59.06% (57,979) of claims for pneumonia treatment were in the clinic, whereas general hospitals accounted for 40.94% (40,184). Among 101,351 claims, admission rate increased as patients get older and the average length of hospitalization was 4.8 days. Elderly breast cancer survivors over 70 years old had the longest length of hospitalization at 6.2 days.

      Conclusion

      Lung cancer survivors are more susceptible to pneumonia than non-cancer survivors. It is important not only to raise the vaccination rate among young cancer survivors, but also to quickly identify symptoms and begin treatment for pneumonia in elderly cancer survivors.

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      P1.15-15 - Real-World Experience with Afatinib after Failure of First-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor

      16:45 - 18:00  |  Presenting Author(s): Chong-Kin Liam  |  Author(s): Gwo-Fuang Ho, Chee-Shee Chai, Adlinda Bt Alip, Yong-Kek Pang

      • Abstract

      Background

      Afatinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is the recommended first-line treatment for patients with advanced non-small cell lung cancer harbouring sensitizing EGFR mutations. The role of afatinib after failure of first-generation EGFR-TKIs is controversial.

      Method

      A retrospective observational study of patients with EGFR mutant advanced NSCLC receiving second-line afatinib after failure of first-generation EGFR-TKI in University Malaya Medical Center from 1st December 2014 to 30th April 2018.

      Result

      The demographic and clinical characteristics of 27 patients treated with afatinib after failure of first-generation EGFR-TKI are shown in Table 1. Twenty-three patients received gefitinib and 4 patients received erlotinib as first-line treatment. The mPFS with first-line treatment was 11.9 months. Fifteen patients had progression of disease (PD) following second-line afatinib with mPFS of 4.2 months and median time-to-treatment failure of 5.7 months. The mPFS2 conferred by first-line first-generation EGFR-TKI and second-line afatinib was 18.4 months. The overall response rate to second-line afatinib was 18.5% (5/27) while the disease control rate as 70.3% (19/27).

      Two patients who had PD on first-generation EGFR-TKI due to T790M mutation received second-line afatinib while waiting for compassionate access to osimertinib. Nine of the 15 patients (69.2%) with PD on afatinib underwent investigations for resistance mechanisms. Three patients had T790M mutation, one of whom had concomitant small cell lung cancer transformation. c-MET amplification was detected in another 3 patients. One patient each had EML4-ALK rearrangement and epithelial mesenchymal transition.

      table 1.jpg

      Conclusion

      Afatinib conferred a modest mPFS benefit after failure of first-generation EGFR-TKI. The mPFS of sequential treatment with first-generation EGFR-TKI followed by afatinib seems longer than the mPFS of first-line afatinib in phase 3 randomised controlled trials. Apart from T790M mutation, the resistance mechanisms to second-line afatinib in our patients are more heterogenous.

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      P1.15-16 - ALKConnect: An Anaplastic Lymphoma Kinase Positive (ALK+) Non-Small Cell Lung Cancer (NSCLC) Patient Insights Network

      16:45 - 18:00  |  Presenting Author(s): Huamao M Lin  |  Author(s): Xiaoyun Pan, Hui Huang, Gabriella Salvatore, Scott Clarke, Howard West

      • Abstract

      Background

      ALK+ NSCLC is a subset of NSCLC present in ~3-5% of NSCLC patients. Little is known about ALK+ NSCLC patients’ unique journeys, their perspectives on the burden of disease, and their ‘real-world’ treatment experiences. Online patient networks provide opportunities to gain valuable insights into outcomes meaningful to patients, directly from patients. The objective of this study is to develop an ALK+ NSCLC patient network to facilitate patient interaction and to conduct patient-centered research including understanding unmet needs, patient preferences, health-related quality of life (HRQoL), and product differentiation.

      Method

      The ALKConnect Patient Insights Network (www.alkconnect.com) will be a patient-focused registry that directly collects information from patients living with ALK+ NSCLC. Patients meeting study criteria will be enrolled in the online survey over a 2-year period. Inclusion criteria are US, adult, English-speaking patients with ALK+ NSCLC providing written, informed consent, internet access, and willing to answer regular e-surveys. Retrospective and cross-sectional ‘real-world’ data that will be collected include demographics, clinical characteristics including ALK+ NSCLC disease history and status, comorbidities, past and present treatment experiences and outcomes, quality of life, patient preferences, healthcare resource use, and work productivity. Supplementary data may be collected through uploading of electronic medical records.

      Result

      The ALKConnect Patient Insights Network will systematically characterize the natural history of ALK+ NSCLC and its treatment and the overall impact on patients. The data collected will be reported descriptively for the population overall and by subgroups of interest (e.g., age, sex) where sample sizes permit. The associations between treatment history/disease status and patient-reported outcomes including symptom severity, HRQoL (e.g., responses to the MD Anderson Symptom Inventory lung cancer module [MDASI-LC]), healthcare resource use, and work productivity will be analyzed. Longitudinal trends will be evaluated to enable a better understanding of the impact of ALK+ NSCLC over time. All de-identified information gathered from ALKConnect will be shared with the ALK+ NSCLC community, including patients, caregivers, healthcare professionals, advocacy organizations, and fellow researchers.

      Conclusion

      We present ALKConnect, an online ALK+ NSCLC patient insights network directly from patients. ALKConnect will provide patients with ALK+ NSCLC opportunities to share their treatment experiences, disease burden, HRQoL, and preferences. Through dissemination to scientific and medical communities, researchers will gain first-hand insights into ALK+ NSCLC patients’ experiences of care, and into opportunities for addressing patients’ unmet needs.

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      P1.15-17 - Risk Factors of Local Recurrence in EGFR-Mutant Stage III-pN2 Adenocarcinoma After Complete Resection: A Multi-Center Real-World Cohort Study

      16:45 - 18:00  |  Presenting Author(s): Hui Liu  |  Author(s): Qi-Wen Li, Bo Qiu, Wenhua Liang, Jun-Ye Wang, Wan-Ming Hu, Shuang-Bing Xu, Steven H Lin, José Luis López, Nai-Bin Chen, Tian Zhang, Minzhang Guo, Yi Zhao, Song-Ran Liu, Qianwen Liu, Jin-Yu Guo, Ling-Zhi Cai, Si-Yu Wang, Xin Wang, Lan-Jun Zhang, Tie-Hua Rong, Zhen-Tao Yu, Jing-Ping Yun, Gang Wu, Li Zhang, Vincent (Wentao) Fang, Hao Long, Qing-Song Pang

      • Abstract

      Background

      Postoperative radiotherapy (PORT) of complete resected stage IIIA non-small cell lung cancer with N2 nodal involvement remained contentious. Our previous study suggested low locoregional recurrences in epidermal growth factor receptor (EGFR) mutant patients. We sought to launch a multi-center large cohort study to evaluate the risk factors of locoregional recurrence in R0 resected EGFR mutant III-pN2 patients without PORT, producing evidence for the design of adjuvant regimens.

      Method

      Three-hundred and fifty-nine consecutive patients with complete resected, pathological approved stage III-pN2 lung adenocarcinoma with sensitive EGFR mutation (exon 19 or exon 21) have been investigated. Patients were excluded if they received induction therapy (7.5%) or PORT (9.6%). Three hundred cases have been analyzed. Clinicopathologic characteristics, pretreatment work-ups, EGFR mutant status and patterns of failure were documented. Patients were sub-staged by the International Association for the Study of Lung Cancer (IASLC)/ the Union for International Cancer Control (UICC) 7th classification on N2 disease. Risk factors of locoregional recurrence-free survival (LRFS) were evaluated by univariate and multivariate analyses.

      Result

      According to IASLC/UICC 7th classification, there were 198 (66.0%) patients with unforeseen N2 (N2a), 36 (12.0%) with minimal/single station N2 (N2b), 41 (13.7%) with selectively centrally located N2 (N2c) and 25 (8.3%) with bulky and/or multilevel N2 (N2d). After surgery, 70 (23.3%) patients were treated with adjuvant tyrosine-kinase inhibitors (TKIs), while other 230 (76.7%) were free from adjuvant TKIs. With median follow-up of 28.5 (range:6-133) months, the 2-year LRFS, distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were 88.3%, 65.3%, 57.7% and 89.7%. Ultimately, 15.7% (47/300) patients developed locoregional recurrences. Distant metastasis was the predominant failure pattern. Multivariate analysis indicated that N2d disease (HR: 2.65, p=0.030) and extranodal extension (HR: 3.48, p<0.001) were risk factors of LRFS.

      Conclusion

      R0 resected stage III-pN2 NSCLC patients with sensitive EGFR mutation (exon 19 or exon 21) tended to present limited N2 disease and low locoregional recurrences. Patients without bulky N2, multilevel N2, and extranodal extension might be refrained from PORT. Further studies evaluating the optimal radiotherapy approach for completely resected N2-positive NSCLC are required for validation.

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      P1.15-18 - The Impact of Patient Age on Clinical Outcomes in NSCLC: A National Study

      16:45 - 18:00  |  Presenting Author(s): Yanyan Lou  |  Author(s): Rami Manochakian, Jordan Cochuyt, David Hodge, Sikander Ailawadhi

      • Abstract

      Background

      Treatment of NSCLC is rapidly advancing. Clinical outcomes and treatment modalities for patients in each age group remain unknown. This study investigates the treatment modalities in each age group and the impact of patients’ age on survival.

      Method

      The National Cancer Database with NSCLC between 2004-2014 was used. Overall survival (OS) and treatments were analyzed by age groups, accounting for multivariates.

      Result

      A total of 2,327,158 NSCLC patients were included. Median OS is 114.6, 76.7, 52.6 and 33 months for stage I lung cancer patients at age <60, 60-69, 70-79 and ≥ 80 respectively (p<0.0001). Median OS is 7, 5.9, 4.6 and 3.3 months for stage IV patients at age <60, 60-69, 70-79 and ≥ 80 respectively (p<0.0001). The impact of age on survival is cross all stages. Younger patients are associated with larger tumor size and higher percentage of stage V at time of diagnosis. Patients with age ≥ 80 are associated with high income, high education and pacific region. Despite comparable comorbidity, patients with age ≥ 80 are treated differently and received much less aggressive therapy at each stage (p<0.0001).

      Conclusion

      The overall survival of NSCLC is significantly impacted by patient’s age. Under-treatment in elderly patients might contribute to poor survival.

      figure 1.jpg

      final tabel 1.jpg

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      P1.15-19 - Treatment of Choice for First-Line Therapy of EGFR-Mutated Stage IIIB Lung Adenocarcinoma Based on the Real World Data

      16:45 - 18:00  |  Presenting Author(s): Shun Lu  |  Author(s): Xiangyun Ye, Ding Ding, Ziming Li, Xiaomin Niu, Gu Linping

      • Abstract

      Background

      There is a lack of consensus on the choice of first-line therapy for stage IIIB EGFR-mutated lung adenocarcinoma.

      Method

      A prospectively maintained database at the Shanghai Chest Hospital was used to identify patients who received therapy for stage IIIB EGFR-mutated lung adenocarcinoma between 2015 and 2017. Clinicopathological data were extracted from the database and analyzed. Patients were stratified into four groups based on the therapy they received; chemotherapy alone, chemoradiation (concurrent or sequential), first-generation EGFR-TKI, or surgical resection with or without chemoradiation. Log-rank test and Kaplan-Meier method were used to determine significant differences in the progression free survival (PFS) between treatment groups

      Result

      Of the 114956 patients treated at the institution during the study period 85 (0.07%) were eligible for the study. 12 patients (14.1%) received chemotherapy, while 19 (22.4%), 30 (35.3%) and 24 (28.2%) received chemoradiation, EGFR-TKI and surgery respectively. The common mutations included Del19 (N=35, 41.18%), L858R (N=42, 49.41%), G719X (N=4, 4.71%) and S768I (N=2, 2.35%).

      The median PFS was shorter in patients who only received chemotherapy (8.5 months) as compared to those managed with chemoradiation (14.6 months), EGFR-TKI (16.2 months) or resection (18.6 months) (p=0.04,figure 1b). No statistically significant difference was observed in PFS between EGFR-TKI and chemoradiation (p=0.86), or EGFT-TKI and resection (p=0.90). A subgroup analysis of patients with N3 disease resulted in similar findings (figure1c).

      20180504143009.jpg

      Conclusion

      In conclusion, when used as a first-line therapy chemoradiation, EGFR-TKI and resection with or without chemoradiation can achieve similar PFS, which is superior to that of patients receiving chemotherapy alone. Further studies are required to elucidate the efficacy of EGFR-TKI as a first-line or as maintenance therapy for these patients.

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      P1.15-20 - Diagnosis and Treatment Delay Among Patients with Lung Cancer in Mexican Population

      16:45 - 18:00  |  Presenting Author(s): Omar Macedo-Pérez  |  Author(s): Fernando Talavera-Caro, Iván Lyra-González, Katya Campos-Peralta, Nora Sobrevilla-Moreno, Miguel Angel Alvarez-Avitia, Edgardo Jiménez-Fuentes

      • Abstract

      Background

      In Mexico, lung cancer is the seventh in incidence and first in mortality. Diagnosis in advanced stages accounts >70% of cases. We analyze factors associated with a late diagnosis and delay in the beginning of treatment.

      Method

      Observational, cross-sectional study carried-out from August to October 2017 in the National Cancer Institute of Mexico (INCan). An interview was conducted to identify: 1) onset of symptoms, 2) time elapsed to seek medical attention, 3) number of doctors visited, 4) diagnosis established prior to cancer diagnosis pulmonary, 5) time elapsed from diagnosis of cancer until admission to INCan and 6) Time elapsed from diagnosis to start treatment.

      Result

      414 patients included and main characteristics are included in the next table

      Mean age 64 years (±12.98)
      Genre 58% females
      Histology

      Adenocarcinoma - 74.6%

      Epidermoid - 9.7%

      Other – 15.7%
      Clinical Stage

      I - 5.5%

      II - 3.7%

      III - 16.2%

      IV - 74.6%
      Physicians/Clinical Assessments Before Diagnosis

      1 physician – 25%

      2 physicians – 22.9%

      ≥3 physicians – 33.1%
      Risk factor

      Smoker – 44.7%

      Wood smoke – 32%

      Asbestos – 6%

      Passive smoker – 6%

      Median time from beginning of symptoms to start of oncologic treatment are shown in the next image

      image1.2.tif

      Conclusion

      In Mexico, lung cancer is diagnosed in advanced stages due to a lack of clinical suspicion in primary care physicians. Delay from initial medical assessment to specialized center referral is considered an opportunity window. Identification of these factors will lead to establishment of public health policies that ensures improvement of diagnostic approach and the timely reference and initiation of treatment in specialized centers to improve the prognosis.

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      P1.15-21 - Creating an Optimal Care Coordination Model to Improve Multidisciplinary Care for Lung Cancer Patients on Medicaid

      16:45 - 18:00  |  Presenting Author(s): Amanda Kramar  |  Author(s): Amy M Marbaugh, Thomas Asfeldt, Randall A Oyer, Christopher S Lathan, Matthew P Smeltzer, Vikki G Nolan, Meredith A Ray, Nicholas R. Faris, Mary Catherine Nalan, Walter I Stevens, Lorna Lucas, Raymond U. Osarogiagbon

      • Abstract

      Background

      The Association of Community Cancer Centers (ACCC) created an Optimal Care Coordination Model (OCCM), which provides a comprehensive self-assessment tool designed to orient cancer programs to achieving patient-centered, multidisciplinary care. The OCCM is designed to help cancer programs, regardless of resources, location, or population, improve care for lung cancer patients, especially those on Medicaid.

      Method

      Using findings from an environmental scan (April 2016) and visits to 5 US cancer programs to explore current care models (July-October 2016), a Technical Expert Panel developed the OCCM, which has 13 defined Assessment Areas and utilizes an evaluation matrix (Table 1).

      To validate the OCCM, a competitive application process among ACCC’s membership used a comprehensive institutional quantitative and qualitative questionnaire. Applicants completed a self-assessment using the OCCM and then developed quality improvement projects designed to move their OCCM-scored care delivery performance from baseline to a higher level over a 12-month implementation period. Seven US community cancer centers were selected as Testing Sites. Quantifiable outcome measures were identified for each site, standardized across sites, and collected by a centralized data coordinating center.

      Table 1

      OCCM Assessment Areas

      1. Patient Access to Care

      8. Survivorship Care

      2. Prospective Multidisciplinary Case Planning

      9. Supportive Care

      3. Financial, Transportation, and Housing

      10. Tobacco Cessation

      4. Management of Comorbid Conditions

      11. Clinical Trials

      5. Care Coordination

      12. Physician Engagement

      6. Treatment Team Integration

      13. Quality Measurement and Improvement

      7. Electronic Health Records and Patient Access to Information

      Level 1:

      Optimal care coordination for lung cancer care has a low priority as evidenced by fragmented care.

      Level 2:

      Early progress in coordinating care is underway.

      Level 3:

      Reflects average or typical care coordination.

      Level 4:

      Exceeds the average and reflects a cancer program’s ongoing commitment to the pursuit of optimal care coordination.

      Level 5:

      Defined by optimal care coordination with a patient-centered focus. Depending on the assessment area, achieving Level 5 performance will require significant time, effort, and resources.

      Patient Focus:

      Optimal care coordination must be patient-centered, which requires understanding of what is important to patients and their caregivers, including their knowledge, goals, needs, desires, social connections, and resources for care. This requires the cancer program to educate and engage patients and caregivers to facilitate shared decision-making and patients’ participation in their care.

      Quality Measures and Metrics:

      Each assessment area requires at least one measurable parameter. Optimal care coordination requires analysis and development of an action plan for continuous improvement. These parameters should include both evidence-based and institution-specific benchmarks that address patient outcomes, patient experience, and cost effectiveness. These measures and metrics should be continuously measured and fed back to key institutional stakeholders for ongoing quality improvement.

      Result

      Table 2 shows Assessment Areas being validated and patient demographics.

      Table 2

      Site 1

      Site 2

      Site 3

      Site 4

      Site 5

      Site 6

      Site 7

      TOTAL

      Project # 1 Selected Assessment Area(s)

      #2

      #7

      #10

      #2

      #1

      #5 & #9

      #1

      Project # 2 Selected Assessment Area

      #8

      #11

      n/a

      #10

      n/a

      n/a

      #2

      8 of 13 Assessment Areas being validated

      N=50

      N=29

      N=77

      N=53

      N=76

      N=101

      N=35

      N=421

      Age

      Median

      (IQR)

      70

      (57-76)

      74

      (63-76)

      71

      (57-76)

      65

      (60-71)

      68

      (61-75)

      61

      (55-65)

      66

      (60-73)

      68

      (61-74)

      n (%)

      n (%)

      n (%)

      n (%)

      n (%)

      n (%)

      n (%)

      n (%)

      Sex

      Male

      29 (58)

      14 (48)

      40 (52)

      27 (51)

      49 (64)

      48 (48)

      18 (51)

      225 (53)

      Female

      21 (42)

      15 (52)

      37 (48)

      26 (49)

      27 (36)

      52 (51)

      17 (49)

      195 (46)

      Race

      Caucasian

      46 (92)

      23 (79)

      76 (99)

      51 (96)

      73 (96)

      47 (47)

      27 (77)

      343 (81)

      African American

      4 (8)

      1 (3)

      2 (4)

      5 (5)

      6 (17)

      18 (4)

      Asian

      4 (14)

      8 (8)

      12 (3)

      Other/

      Unknown

      1(1)

      1 (1)

      8(8)

      2 (6)

      12 (3)

      Not reported

      1 (3)

      2 (3)

      29 (29)

      32 (8)

      Insurance

      Commercial

      7 (14)

      7 (24)

      13 (17)

      8 (15)

      29 (38)

      8 (8)

      9 (26)

      81 (19)

      Medicare

      38 (76)

      20 (69)

      55 (71)

      37 (70)

      40 (53)

      28 (28)

      21 (60)

      239 (57)

      Medicaid

      4 (8)

      2 (7)

      6 (8)

      8 (15)

      6 (8)

      63 (62)

      4 (11)

      93 (22)

      None/Self-Pay

      2 (3)

      1 (1)

      3 (1)

      Smoking Status

      Active Smoker

      14 (28)

      10 (34)

      27 (35)

      17 (32)

      38 (50)

      34 (34)

      11 (31)

      151 (36)

      Former Smoker

      20 (40)

      15 (52)

      44 (57)

      34 (64)

      28 (37)

      51 (50)

      23 (66)

      215 (51)

      Never Smoker

      7 (14)

      3 (10)

      2 (3)

      2 (4)

      7 (9)

      9 (9)

      30 (7)

      Not reported

      2 (3)

      1 (1)

      3 (1)

      Stage at Diagnosis

      Stage 0

      2 (3)

      2 (<1)

      Stage I

      9 (18)

      4 (14)

      21 (27)

      1 (2)

      9 (12)

      9 (9)

      2 (6)

      55 (13)

      Stage II

      1 (2)

      2 (7)

      10 (13)

      5 (9)

      3 (4)

      7 (7)

      28 (7)

      Stage III

      6 (12)

      5 (17)

      11 (14)

      3 (6)

      4 (5)

      13 (13)

      2 (6)

      44 (10)

      Stage IV

      6 (12)

      3 (10)

      8 (10)

      14 (26)

      13 (17)

      18 (18)

      4 (11)

      66 (16)

      Not reported/ Missing

      28 (56)

      15 (52)

      25 (32)

      30 (57)

      47 (62)

      54 (53)

      27 (77)

      226 (54)

      *Percentages may not add to 100 due to missing data

      Conclusion

      Project implementation and patient accrual are ongoing at all Testing Sites through September 2018.

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      P1.15-22 - Patterns of Palliative and Psychosocial Care in Stage IV Non-Small Cell Lung Cancer (NSCLC) Patients

      16:45 - 18:00  |  Presenting Author(s): Tahir Mehmood

      • Abstract

      Background

      The primary goals of management of stage IV NSCLC patients are palliation of symptoms and maintenance of quality of life. Patients need adequate access to specialist palliative care (PC) and psychosocial care (PSC) in order to achieve these goals. The aims of this study were to evaluate referrals to PC and PSC services with Stage IV NSCLC and identify factors associated with utilization of these services.

      Method

      Research findings of >150 published, peer-reviewed research articles including quantitative and qualitative studies of stage IV NSCLC patients and their families, were summarized around the realities of living with disease. 13 surveys of ~8,000 stage IV NSCLC patients were examined for common concerns. Modified Poisson regression was used to analyze significant factors associated with referrals to PC and PSC. Cox regression was used for multivariate survival analysis.

      Result

      A total of 923 patients were identified. The median age was 69 years, 63% were male. Active treatment was received by 65% of patients with 34% receiving chemotherapy and 65% receiving radiotherapy. Eighty-three percent of patients were referred to PC, with 67% occurring within 8 weeks of diagnosis. Eighty-two percent of patients were referred to PSC, with referrals to social workers being most frequent (76%) followed by specialist nursing (26%) and psychology/psychiatry (16%). On multivariate analysis, radiotherapy treatment, M1b disease and residential location were associated with PC referrals, and radiotherapy treatment, PC referral and residential location were associated with PSC referrals. Age, language spoken, country of birth, socioeconomic status, year of diagnosis and multidisciplinary team discussion were not significant factors in referral to either service. The median overall survival was 4.3 months and one year survival was 19%. On multivariate analysis, factors associated with improved survival were active treatment, chemotherapy and multidisciplinary team discussion.

      Conclusion

      Rates of referral to PC and PSC services were high in this cohort suggesting good access to care. Greater referrals were particularly associated with patients undergoing radiotherapy. There were no sociodemographic barriers to referral. Some geographic differences were noted in referrals to both services. Further investigation into referral gaps will guide service delivery to improve quality of life and care for future patients.

    • +

      P1.15-23 - Factors Affecting Treatment in Non-Small Cell Lung Cancer Patients

      16:45 - 18:00  |  Presenting Author(s): Phuong T Ngo  |  Author(s): Christina Pinkston, Danh C Pham, Goetz H Kloecker

      • Abstract

      Background

      Lung cancer continues to be the leading cause of cancer deaths with Kentucky having the highest incidence of lung cancer. Despite advances in treatment and subsequent survival improvements, a significant number of non-small cell lung cancer (NSCLC) patients remain untreated. Factors such as age, stage at diagnosis and insurance status appear to play an important role in this disparity.

      Method

      In the Kentucky LEADS Collaborative, 27 of 31 (81%) Kentucky hospital registries provided all NSCLC data from 2012-2015. Variables collected included hospital accreditation by the Commission on Cancer (CoC), patient age at diagnosis, stage, race, number of comorbidities, insurance status, and overall survival (OS). Treatment included combinations of surgery, radiation, chemotherapy or immunotherapy. Hospital records were matched to the Kentucky Cancer (KCR) records and analyzed with a logistic regression model along with additional post-hoc analysis.

      Result

      Of the 13,975 patients diagnosed with NSCLC, 10,367 (74.2%) were treated leaving 3,608 (25.8%) untreated. Overall survival reported as person-days was significantly longer for the treated versus untreated patients (593 days vs 161 days). Neither race nor gender showed statistical significance while age at the time of diagnosis was significant with the untreated patients being diagnosed at a mean age of 72 and the treated patients at a mean age of 66 (p=<0.001). The mean average of comorbidities reported was 4.1 for treated patients and 4.4 for untreated patients though the specific comorbidities were not discernable. Treatment versus lack of treatment was also significantly associated with stage at the time of diagnosis with 87.9% vs 12.1% for stage I, 88.2% vs 11.8% for stage II, 73.9% vs 26.1% for stage III, and 64.2% vs 35.8% in stage IV; untreated patients tended to present at a later stage than those who received treatment with OR 2.91 (95% CI 2.57-3.28) for stage III and OR 4.28 (95% CI 4.29-5.41) for stage IV. Lastly, insurance proved to be an important factor with untreated patients more likely to have Medicaid, Medicare or be uninsured.

      Conclusion

      Treatment for lung cancer is correlated with improved outcomes and yet a large number of patients are still untreated. We aimed to assess these barriers to treatment and found untreated patients were more likely to be older, diagnosed at a later stage, and not have private insurance. While therapies are constantly changing and improving, it is important to factor in the many barriers that still exist in preventing patients from being treated.

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      P1.15-24 - Small Cell Lung Cancer: Clinical Characteristics and Survival of a Spanish Cohort of 221 Patients

      16:45 - 18:00  |  Presenting Author(s): Virginia Calvo  |  Author(s): Beatriz Núñez, Raquel Gómez, Juan Cristobal Sánchez, Blanca De La Puente, Cristina Alfaro, Laura Núñez, Mariola Blanco, Isabel Curto, Maria Soriano, Miriam Méndez, Ana María Morito, Fabio Franco, Mariano Provencio

      • Abstract

      Background

      Lung cancer is the leading cause of death from cancer, of which 15% corresponds with small cell lung cancer (SCLC) subtype, directly related with tobacco. SCLC is the most aggressive subtype with an elevated percentage of metastatic patients at diagnosis and a poor prognosis.

      Method

      A cohort of 221 patients diagnosed of SCLC were retrospectively analyzed in our center between 2008-2016.

      Patient data was analyzed for baseline demographics and stage at diagnosis.

      Progression free survival (PFS) and overall survival (OS) analysis were made comparing SCLC stage at diagnosis.

      Result

      The median age at diagnosis was 64 years and 74% were male, of whom 33% were older than 70 years. Only 0.5 % were never smokers and 16% had history of other malignancies, mostly related with tobacco. At diagnosis, 67% were metastatic and 88% symptomatic.

      Complete baseline characteristics shown at Table 1.

      PFS was 13.5 versus 6.83 months in located versus metastatic disease (p = 0.000) and median OS was 21.2 versus 8.5 months comparing located and metastatic stage (p = 0.000).

      Kaplan-Meier curves shown at Image 1.

      Table 1. Complete baseline characteristics.
      BASELINE CHARACTERISTICS ALL PATIENTS (n=221)
      SEX 164 (74%) male; 57 (26%) female
      AGE AT DIAGNOSIS 64 years (IQR 58-71); 65 years (IQR 59-73) male; 61 years (IQR 55-68) female.
      PATIENTS OLDER THAN 70 YEARS 72 (33%); 60 males and 12 females
      SMOKING HABIT

      Smoker --> 137 (61.9%)

      Former smoker --> (> 365 days without smoking) à 81 (36.65%)

      Never smoker --> 1 (0.45%)

      Unknown --> 2 (0.9%)
      SMOKING PACK YEAR 58 pack/year; 60 pack/year male and 50 pack/year female

      AGE AT THE BEGINNING OF TOBACCO HABIT

      16 years
      STAGE

      Stage I --> 10 (5%)

      Stage II --> 8 (4%)

      Stage III --> 53 (24%)

      Stage IV --> 150 (67%)

      ECOG

      0-1--> 191 (86.4%)

      2--> 23 (10.4%)

      3--> 7 (3.2%)

      CARDIOPULMONARY DISEASE

      COPD 23%

      HBP 47%

      DM 25%

      DL 43%

      Cardiopathy 19%
      HISTORY OF OTHER MALIGNANCIES 16%, most frequent: bladder cancer 7 (20.6%); head and neck cancer 6 (17.7%); lung cancer 4 (11.8%)
      FAMILIAR HISTORY OF LUNG CANCER 39%
      SYMPTOMS AT DIAGNOSIS Cough 42%; weight loss 30%; pain 28%; dyspnoea 27%; asthenia 21%
      TREATMENT

      8.2% palliative treatment

      91.8% active treatment (98.8% standard treatment with platinum-based chemotherapy and 1.2% clinical trial)
      PROGRESSION FREE SURVIVAL

      13.5 (IQR 7.4-40.8) months in located and 6.8 (IQR 4.8-10.2) in metastatic disease compared with (p = 0.000)

      OVERALL SURVIVAL

      21.2 (IQR 10.8-39.6) months in located and 8.5 (IQR 3.9-15.5) in metastatic disease with (p = 0.000)

      12 AND 24-MONTHS OVERALL SURVIVAL

      Located: 73% and 42% respectively

      Metastatic: 33% and 15% respectively

      overall survival.png

      Conclusion

      SCLC is mostly diagnosed at metastatic stage, but even in located disease prognosis is poor, so investigation is needed to improve PFS and OS.

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      P1.15-25 - Has Lung Cancer Radiotherapy Utilisation Changed over Time in New South Wales, Australia?

      16:45 - 18:00  |  Presenting Author(s): Shalini K Vinod  |  Author(s): Andrew Oar, Gabriel Gabriel, Jesmin Shafiq, Michael Barton, Geoff Delaney

      • Abstract

      Background

      Evidence based indications suggest that 73% of all Australian lung cancer patients would benefit from radiotherapy at diagnosis. In 2001-2002, the radiotherapy utilisation (RTU) rate in NSW for lung cancer was 39%. Since then a number of new radiation oncology centres have opened and the number of linear accelerators increasing from 29 to 46. There has also been an increase in the number of lung cancer multidisciplinary teams. We aimed to evaluate whether there had been any change in RTU for lung cancer in NSW from 2001-2002 to 2009-2011.

      Method

      All patients diagnosed with lung cancer in NSW between 1/1/2009 and 31/12/2011 were identified from the NSW Central Cancer Registry (NSWCCR). Data linkage with the Admitted Patients Data Collection, Retrospective Radiotherapy Data and Clinical Cancer Registry was performed to ascertain radiotherapy treatment within 1 year of diagnosis. Patients with non-lung cancer pathologies and those who lived closer to interstate radiotherapy centres were excluded. Patients with a clinical diagnosis of lung cancer (no pathological confirmation (NPC)) were included.

      Result

      A total of 10,712 patients were identified through NSWCCR of which 947 patients were excluded leaving 9,765 patients for analysis. The median age was 71 years and 60% were males. Histopathology was NSCLC, SCLC and NPC in 76%, 12% and 13% respectively. Stage was I&II in 12%, III in 12%, IV in 28% and unknown in 47%. The overall RTU for lung cancer was 40%. RTU was 43% for NSCLC, 56% for SCLC and 8% for NPC. RTU by stage compared to previous figures is shown in Table 1.

      Table-1 Radiotherapy utilisation rate by stage of lung cancer, NSW 2001-2002 and 2009-2011

      Histology

      Stage

      RTU N (%) (2001-2002)

      RTU (%) (2009-2011)

      NSCLC

      I

      76(26)

      201(27)

      II

      35(39)

      164(41)

      III

      170(55)

      753(72)

      IV

      258(49)

      1,497(66)

      Unknown

      17(22)

      544(18)

      Total

      556(43)

      3,159(43)

      SCLC

      I-III

      39(47)

      157(80)

      IV

      61(32)

      280(61)

      Unknown

      1(17)

      202(41)

      Total

      101(36)

      639(56)

      NPC

      I

      12(22)

      12(43)

      II

      4(33)

      3(50)

      III

      11(35)

      17(71)

      IV

      20(27)

      37(60)

      Unknown

      5(8)

      25(2)

      Total

      52(23)

      94(8)

      OVERALL

      Total

      709(39)

      3,892(40)

      Conclusion

      Increased RTU was seen in some groups of patients including Stage III-IV NSCLC, Stage I-IV SCLC and Stage I-IV NPC. Despite an increase in resources, overall RTU for lung cancer has remained unchanged over the last decade.

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      P1.15-26 - A Review of Colombian National Administrative Cancer Registry (NACR) Data to Evaluate Healthcare Delivery and Biologics Use

      16:45 - 18:00  |  Presenting Author(s): Brian Anthony Pico  |  Author(s): Robert Hsu, Jaime Gonzalez Diaz, Lizbeth Acuna Merchan, Gilberto de Lima Lopes

      • Abstract

      Background

      The Office of High Cost of the Colombian Health Ministry created the National Administrative Cancer Registry (NACR) data first in 2015 to provide comprehensive cancer data to improve cancer outcomes while serving as a model for other resource-limited countries. Despite new targeted therapies throughout the world, the benefits of these therapies have not reciprocated in lower resource settings, notably in Latin America. The purpose of this study is to investigate aspects of the NACR data that underscore some of the health care limitations of lung cancer treatment in Colombia.

      Method

      We obtained National Administrative Cancer Registry (NACR) data from the High-Cost Diseases Office (Cuenta de Alto Costo [CAC]) collected in 2015 and released in 2016. All cancer cases diagnosed in the country are reported by payers and providers otherwise there are no payments for services rendered, assuring that the registry is representative. We use descriptive statistics for presentation of data and comparisons.

      Result

      A total of 3,082 patients were analyzed of which 2,043 (66.29%) had contributive insurance, 820 (26.60%) had subsidized insurance, and 98 (3.18%) had special or exempt insurance. Four patients (0.12%) had no insurance. Of newly diagnosed patients, the median number of days from suspicion to diagnosis was 27 days (IQR = 12-45 days, n = 491) with the predominant range of patients with contributive insurance being 30-59 days, and for subsidized insurance being 15-29 days. The median number of days from diagnosis to first treatment was 31 days (IQR=14-62, n=346) with the predominant range for patients with both contributive and subsidized insurance being 30-59 days. There was a greater percentage of Stage IV cancers in patients with subsidized (34%) than contributive (23%) insurance. Of those receiving chemotherapy (n=275), 52% received carboplatin, 28.3% received pemetrexed, 27.6% received cisplatin, 25.4% received paclitaxel, 10.9% received bevacizumab, and 5.1% received erlotinib; no patients received nivolumab or pembrolizumab.

      Conclusion

      Based on findings from NACR, the wait time from suspicion to treatment took nearly two months underscoring the need for better streamline of lung cancer care. Also, data shows a low percentage of use of newer therapies, including EGFR-targeted agents despite a high prevalence of mutations, which are present in around a quarter of patients in Colombia (Raez, 2017). Colombia can strongly benefit from increased access to molecular testing and biologics given the future direction of lung cancer therapy.

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      P1.15-27 - Patient Characteristics, Treatment Patterns and Survival for Unresectable Stage III NSCLC in Ontario, Canada.

      16:45 - 18:00  |  Presenting Author(s): Soo Jin Seung  |  Author(s): Manjusha Hurry, Ryan N. Walton, William Kenneth Evans

      • Abstract

      Background

      In anticipation of new treatment strategies for unresectable stage III NSCLC, we undertook a retrospective study to determine how these patients have been managed in Ontario, Canada and their survival by treatment approach.

      Method

      Individuals diagnosed with stage III NSCLC between April 1, 2010 and March 31, 2015 were identified in the Ontario Cancer Registry (OCR). Patients with stage III disease were considered to be unresectable if no surgery was undertaken within 3 months of diagnosis. Initial treatments included: radiation (classified as curative or palliative based on treatment intent, body region, dose/fraction, number of fractions); chemotherapy categorized as single or doublet IV chemotherapy, single chemo+RT, doublet chemo+RT, oral targeted therapy. Concurrent chemo+RT (cCRT) was defined as an overlap between chemotherapy and RT, while sequential chemo+RT (sCRT) had no overlap and a 30-day window between treatments. Survival was calculated from date of diagnosis to death.

      Result

      24,729 individuals were diagnosed with NSCLC in Ontario during the study period; 5,243 (21.2%) were stage III and 4,542 (18.4%) were stage III unresectable. Mean age of the unresectable group was 69.7±10.3 years; 54.2% were male. 64.2% of patients were treated within 3 months of diagnosis. The frequency of treatment approach was: cCRT (21.6%), palliative RT (21.3%), curative RT (20.2%), no treatment (19.6%), chemotherapy (11.6%), sCRT (4.9%) and targeted therapy (0.7%). Median survival (IQR) was 2.9 yrs (1.7-4.8) for targeted therapy, 2.0 yrs (1.0-5.5) for cCRT, 1.4 yrs (0.7-3.4) for curative RT, 1.4 yrs (0.7-3.1) for chemotherapy, 1.2 yr (0.6-2.9) for sCRT, 0.6 yrs (0.3-1.2) for palliative RT and 0.5 yrs (0.2-1.2) for no treatment (Figure 1).

      Figure 1. Kaplan-Meier survival curves for stage III unresectable lung cancer patients based on treatment type.

      stage iii survival curve.jpg

      Conclusion

      Although cCRT is generally considered standard of care for stage III unresectable NSCLC, patients in Ontario receive various treatment approaches. Survival outcomes vary widely.

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      P1.15-28 - Real World Treatment Patterns and Survival of Stage IV Non-Small Cell Lung Cancer (NSCLC) in Ontario, Canada.

      16:45 - 18:00  |  Presenting Author(s): Soo Jin Seung  |  Author(s): Manjusha Hurry, Ryan N. Walton, William Kenneth Evans

      • Abstract

      Background

      The majority of NSCLC patients are diagnosed with stage IV disease. With the development of targeted therapies for advanced NSCLC, it has become important to understand which patients are being treated with systemic therapies and to what benefit.

      Method

      We conducted a longitudinal, population-level study to determine the treatment patterns and survival in patients with stage IV NSCLC in Ontario, Canada between April 1, 2010 and March 31, 2015 from the Ontario Cancer Registry (OCR). Individuals were further identified as having non-squamous disease, and those who received an EGFR-TKI (afatinib, erlotinib, gefitinib) were assumed to be EGFR mutation-positive (EGFR+). Survival was calculated from date of diagnosis to death.

      Result

      24,729 individuals were diagnosed with NSCLC. Approximately half (12,159; 49.2%) had stage IV disease, including 10,103 with non-squamous disease, of whom 508 were categorized as EGFR+. The mean age for the stage IV non-squamous and EGFR+ cohorts were 68.7±11.0 years and 69.1±10.4 years, respectively; 49.3% and 60.8% were female, respectively. The most frequent treatments for stage IV non-squamous patients were palliative radiotherapy (RT) (46.7%) and systemic therapy (14.9%). Patients received no treatment in 26.7% of cases. 75.6% of the EGFR+ cohort received gefitinib, with the majority receiving no subsequent treatment (44.6%). Of EGFR+ patients receiving a second-line treatment, 20.1% received palliative RT and 18.7% received chemotherapy. Mean and median survival times (IQR) for the stage IV non-squamous patients were 0.9±0.0 years and 0.4 (0.2-1.0) years, respectively. Substantial variation in survival was noted by treatment (Figure 1). Mean and median survival times (IQR) for the EGFR+ cohort were 1.9±0.1 years and 1.5 (0.9-3.0) years, respectively.

      Figure 1. Kaplan-Meier survival curves for stage IV non-squamous NSCLC patients based on treatment

      stage iv survival curve.jpg

      Conclusion

      Relatively few patients with stage IV non-squamous NSCLC receive any systemic therapy. Survival is generally very poor, but best in the subgroup of EGFR+ patients.

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      P1.15-29 - Impact of Radiation Therapy Quality Assurance on Progression-Free and Overall Survival in Randomized Trials of Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Yu Yang Soon  |  Author(s): Aidan Tan, Ivy Ng, Teng Hwee Tan, Jeremy Chee Seong Tey

      • Abstract

      Background

      To evaluate if the estimates of treatment effect differ between randomized trials (RCTs) that reported radiation therapy quality assurance (RTQA) and RCTs, which did not report RTQA, for treatment of lung cancer (LC) [C1] using curative intent thoracic radiation therapy (TRT).

      Method

      We searched MEDLINE for eligible meta-analyses (MAs) of RCTs of LC. For each trial in the selected MAs, we reviewed if RTQA was performed and extracted the hazard ratios (HR) with 95% confidence interval (CI) for progression-free (PFS) and overall survival (OS). We quantify the differences in the estimated intervention effect on PFS and OS by a ratio of HRs (rHRs): the HR for trials that performed RTQA to that of trials that did not perform or report RTQA. An rHR more than 1 would indicate a larger HR for trials that performed RTQA compared to trials that did not perform or report. We estimated a combined rHR across MAs using a random effects MA model. We performed a meta-regression analysis to adjust for potential confounders including cancer type, comparisons type, sample size and single-vs-multi center trial .

      Result

      We included six MAs that comprised of six comparisons and 50 RCTs (22 reported RTQA; 28 did not). Trials that performed RTQA showed similar intervention effect on PFS (rHR 0.96, 95% CI 0.82 to 1.12, P value (P) = 0.57, I squared (I2) = 0%) and OS (rHR 1.00, 95% CI 0.88 to 1.15, P = 0.94, I2 = 0%) compared to trials that did not perform or report RTQA, with low heterogeneity across individual MAs. There was no significant change in the summary rHRs after adjusting for potential confounders.

      Conclusion

      The conduct of RTQA did not modify the estimates of intervention effects on progression-free and overall survival in randomized trials of lung cancer treated with curative intent thoracic radiation therapy.

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      P1.15-30 - Survival of Patients with Advanced NSCLC Treated with First-Generation EGFR-TKIs at a Cancer Hospital in Thailand, 2011-2016

      16:45 - 18:00  |  Presenting Author(s): Sitthi Sukauichai  |  Author(s): Chokaew Tovanabutra, Sirentra Wanlikitkul, Kittisak Chomprasert

      • Abstract

      Background

      This study was to find the survival in advanced NSCLC patients treated with an EGFR-TKI in a real-life practice.

      Method

      The researcher conducted this retrospective study by review medical records in stage IIIB-IV NSCLC patients treated with first-generation EGFR-TKIs at Chonburi Cancer Hospital from January, 2011 to December, 2016 and follow up until December, 2017.

      Result

      This study enrolled 50 patients with median follow up time 16.78 months. The median age of patients was 58.5. There were female (46%), non-smoking (62%) and adenocarcinoma (90%). The patients received an EGFR-TKI by purchase by themselves (52%), reimbursement system (32%) and compassionate use (14%), additionally Eastern Cooperative Oncologic Group (ECOG) performance statuses were 0-1 (54%), 2-4 (28%) and non-available (NA) (18%).Treatment responses stratified by line of therapy and EGFR status were shown (table)

      EGFR-TKIs

      treatment

      EGFR

      mutation status

      Response to

      an EGFR-TKI

      Total

      (N)

      PR SD PD NA

      First-line (1L)+ maintenace (MN)

      (n=16+2)

      Sensitive 3 1 0 0 4
      Wild-type 0 2 0 0 2
      Unknown 4 4 2 2 12

      Second-line (2L)

      (n=18)

      Sensitive 1 3 0 0 4
      Wild-type 0 0 1 1 2
      Unknown 5 2 4 1 12

      Third-ine or more (>/=3L)

      (n=14)

      Sensitive 2 1 0 0 3
      Wild-type 0 0 1 1 2
      Unknown 1 1 5 2 9
      Total (N) 16 14 13 7 50

      The overall survivals (OS) of the patient receiving an EGFR-TKI as 1L or MN (n=18), 2L (n=18) and >/=3L (n=14) were 15.86 (95%CI, 10.26-21.46), 10.87 (95%CI, 0.00-28.29) and 20.23 (95%CI, 6.26-34.21) months (p=0.392), respectively. Regarding EGFR status, the OS of patients with EGFR sensitive mutation (n=11), wild-type (n=6) and unknown (n=33) were 30.75 (95% CI, 13.76-47.74), 7.91 (95% CI, 0.00-20.45) and 13.99 (95%CI, 9.17-18.82) months (p=0.086), respectively.

      Multivariate analysis indicated that age >/=70 years old (p=0.047) ,current or former smoking (p=0.012), ECOG performance status 2-4 or NA (p<0.001), received EGFR-TKIs by payment (p=0.033) or compassionate use (p<0.001) were the unfavorable prognostic factors for the OS.

      Conclusion

      The OS of the patients harboring EGFR sensitive mutation at our hospital was comparable to those of other pivotal studies. Clearly, patients harboring EGFR wild-type had the OS much shorter than those of the sensitive mutation group. In real practice at that time, two-third of patients still have not been proved their EGFR statuses before starting an EGFR-TKI and often received it as second-line or more.

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      P1.15-31 - Survival and Patterns of Care Comparing Black and White Patients With All Stages of NSCLC: An NCDB Analysis

      16:45 - 18:00  |  Presenting Author(s): Melissa Ana Liriano Vyfhuis  |  Author(s): Søren M. Bentzen, Surbhi Grover, Charles B. Simone, Pranshu Mohindra

      • Abstract

      Background

      Race and other socioeconomic factors continue to influence survival in patients with non-small cell lung cancer (NSCLC). Recent population-based studies have paradoxically shown a survival advantage in the black population compared to white patients with stage III NSCLC. To further investigate this, we analyzed stage-wise overall survival (OS) and patterns of care in black patients as compared to white patients with NSCLC using the National Cancer Database (NCDB).

      Method

      All black and white patients within the NCDB with biopsy-proven, stages I-IV NSCLC from 2004-2013 were analyzed. Associations between demographics was assessed using c2-tests. Guideline concordant care (GCC) and non-guideline concordant care (NGCC) were defined for each stage as per NCCN guidelines. OS between the races were analyzed using the log-rank test and the multivariable Cox proportional hazards regression.

      Result

      When compared to white patients, black patients were younger at presentation (</=60years: 36.2% vs. 22.5%, p<0.001), had a lower household income (<$30,000: 37.9% vs. 11.5%, p<0.001), twice as likely to not have insurance (6.4% vs. 2.9%, p<0.001) and were diagnosed with more advanced disease (stage I: 18% vs. 24.9%, stage II: 6.1% vs. 6.9%, stage III: 25.9% vs. 23.7%, stage IV: 50% vs. 44.5%, p<0.001).

      White patients were more likely to undergo GCC in stages I-III when compared to black patients (stage I: 77% vs. 69.6%; stage II: 68.5% vs. 65.3%; stage III: 52.8% vs. 51.9%) but had a very similar incidence of GCC in stage IV (stage IV: 66.7% vs. 67.3%, p<0.001).

      Black race was associated with a 17%, 5%, and 3% increase risk of NGCC in stage I (OR: 0.835, 95% CI: 0.817-0.852, p<0.001), stage II (OR: 0.947, 95% CI: 0.916-0.978, p=0.001) and stage III (OR: 0.970, 95% CI: 0.954-0.985, p<0.001) disease, respectively, when compared to white patients in multivariate analysis (MVA). While in stage IV, being black predicted for a 4% greater receipt of appropriate treatment (OR: 1.041, 95% CI: 1.028-1.054, p<0.001).

      In the Cox MVA, race was not linked to OS in stage I or II disease, but being black predicted for a 3% lower risk of death in stage III and IV (stage III: HR: 0.973, 95% CI: 0.965-0.982, p<0.001; stage IV: HR: 0.967, 95% CI: 0.961-0.973, p<0.001).

      Conclusion

      Black patients with NSCLC had similar or slightly improved OS when compared to white patients after accounting for socioeconomic demographics, staging and patterns of care. To explain this contradictory finding, further research should investigate biological differences between the two races.

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      P1.15-32 - Real World EGFR Mutation Profile from 1699 Non-Small Cell Lung Cancer Patients in Eastern China

      16:45 - 18:00  |  Presenting Author(s): Wei Wang  |  Author(s): Minhua Ye, Xiaomai Wu, Dongqing Lv, Feng-Ming Spring Kong, Haihua Yang

      • Abstract

      Background

      The EGFR mutation frequency and mutation types had significant geographic differences. The purpose of this study was to evaluate prevalence, clinical characteristic in eastern China which has not been reported.

      Method

      From March 2016 to March 2018 who were newly diagnosed or postoperative recurrence NSCLC received EGFR mutation detect were included analysis. Commercially available ARMS-PCR kits were used to detect EGFR mutations.

      Result

      A total of 1699 consecutive NSCLC patients included in our study. The median age was 64 years (range 23-91), with 892 (52.5%) were male and 807 (47.5%) male. There were 852 (50.2%) with EGFR mutations out of 1699 patients in the total population. EGFR mutations were more frequent in female (64.9%) patients than in males (36.8%). Considering the frequency of mutations according to histology, adenocarcinomas (835/1495, 55.9% ) show mutations more often than squamous carcinoma (4/142, 2.82%), other NSCLC histology (13/62, 21.0%). The rate of EGFR mutation in total was lower in biopsy specimen (246/613, 40.1%) than in surgical specimen (557/993, 56.1%) or cytology specimen(49/93, 52.69%). A total of 755 (88.6%) harboring a common EGFR mutation were identified: among the 755, the most EGFR mutation type was the point mutation L858R at 21 exon (49.5%), followed by exon 19 deletion (39.1%). Ninety-seven (11.48%) patients harboring uncommon EGFR mutation, the exon 20 INS (34.0%) was the most frequently observed mutation among the uncommon EGFR mutations. The detailed EGFR mutation type were show in table1.

      Table1. The detailed EGFR mutation type

      Mutation type

      Case number

      Percentage of all cases

      Percentage of uncommon mutation

      common mutation

      L858R

      422

      49.53%

      19-del

      333

      39.08%

      uncommon mutation

      20-Ins

      33

      3.87%

      34.0%

      L858R/T790M

      18

      2.11%

      18.6%

      G719X

      14

      1.64%

      14.4%

      L861Q

      11

      1.29%

      11.3%

      G719X/S768I

      5

      0.59%

      5.2%

      L858R+S768I

      5

      0.59%

      5.2%

      S768I

      4

      0.47%

      4.1%

      19-del/T790M

      3

      0.35%

      3.1%

      G719C

      1

      0.12%

      1.0%

      L858R/19-del

      1

      0.12%

      1.0%

      L858R/20-Ins

      1

      0.12%

      1.0%

      T790M

      1

      0.12%

      1.0%

      EGFR: Epidermal growth factor receptor.

      Conclusion

      In our eastern China cohort, the most common EGFR mutation was L858R, differing from previous reported data in Asian population describing 19 deletion was the most common EGFR mutation. The frequency of EGFR mutations in biopsy specimen population was lower than both in surgical specimen and cytology specimen.

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      P1.15-33 - Real-World Data on Prognostic Factors for Overall Survival in NSCLC Patients Treated with Bevacizumab Combination Therapy

      16:45 - 18:00  |  Presenting Author(s): Shang-Gin Wu  |  Author(s): Wei-Yu Liao, Chao-Chi Ho, Jin-Yuan Shih, Chong-Jen Yu

      • Abstract

      Background

      Bevacizumab is used as combination with chemotherapy as 1st-line treatment for non-squamous cell carcinoma. In order to understand the influence of bevacizumab on different combination medication response, this study aimed to identify independent prognostic factors for overall survival (OS) of NSCLC patients receiving bevacizumab treatment in real-world practice.

      Method

      We performed retrospective collected non-squamous cell carcinoma patients undergoing bevacizumab treatment and analyzed their response and overall survival to bevacizumab. Demographic data, TTF-1 stain status, EGFR mutation status, and survival data were collected. Survival data analysis were plotted by the Kaplan–Meier method and compared by the log-rank test.

      Result

      From November 2009 to October 2015, 114 non-squamous cell carcinoma patients treated with bevacizumab were enrolled for analysis. The median overall survival was 21.9 months. There were 11 patients who received continuous bevacizumab beyond disease progress of 1st-line treatment and in all treatment courses. They had longer overall survival than those (N = 103) who did not received bevacizumab in all treatment courses (p = 0.003). The patients harboring positive TTF-1 tumor also had a longer overall survival than those harboring negative TTF-1 tumors (p = 0.025). Multivariate analysis revealed that patients harboring tumor with positive staining of TTF-1 (p < 0.001) and those received bevacizfig-2(20180226).jpgumab in all treatment course (p = 0.013) had a longer median OS.

      Conclusion

      Non-squamous cell carcinoma patients receiving bevacizumab beyond 1st-line treatment failure, as all treatment course, had a longer median OS than those received bevacizumab in partial course.

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      P1.15-34 - Treatment Patterns and Outcomes of Stage III Non-Small Cell Lung Cancer (NSCLC): Real World Evidence of How our Patients Fare

      16:45 - 18:00  |  Presenting Author(s): Dimas Yusuf  |  Author(s): Ryan N. Walton, Manjusha Hurry, Winson Y Cheung

      • Abstract

      Background

      Most patients withstage III non-small cell lung cancer (NSCLC) develop metastases and succumb to their cancer. New treatment strategies, including concurrent chemo–RT (cCRT) followed by adjuvant immunotherapy, are improving outcomes, but need to be contextualized with real world data. In this study, we described population-based treatment patterns and outcomes for stage III NSCLC in a large Canadian province.

      Method

      Through the provincial cancer registry, patients diagnosed with stage III NSCLC from April 1st 2010 to March 31st 2015 were identified. Using electronic medical records and administrative claims, stage III patients were merged with treatment and survival information. Patient characteristics, treatment patterns, and outcomes were analyzed.

      Result

      6,438 patients were diagnosed with NSCLC, including 1,151 (17.9%) with stage III disease. Median age at diagnosis was 70 years (22–94); 50.2% were male. The majority were stage IIIA (61.2%); the remainder was stage IIIB (36.4%) or unspecified (2.4%). Most patients received palliative RT (32.8%), supportive care until progression (24.8%), or palliative chemotherapy (14.8%) as initial treatments. Relatively few underwent cCRT (11.7%) or trimodality therapy (1.7%). Resection was performed on 14.8% of patients. Within the resected cohort, the majority (47.6%) did not receive further perioperative treatment, while others had surgery as part of trimodality (11.2%) or alongside perioperative chemotherapy (37.1%). Overall, the median OS (mOS) was 13.3 months (0–NR). Initial treatment strategy predicted outcomes (p< 0.05). Patients who underwent cCRT had mOS of 23.8 months (1.1–not reached [NR]). mOS for patients who initially received palliative chemotherapy or RT was 11.1 months (0.3–NR), and 6.2 (0–NR) with supportive care (Figure 1).

      Figure 1: Kaplan–Meier curves for stage III NSCLC stratified by treatment class

      wclc stage iii abstract figure 1.png

      Conclusion

      Treatment rates for cCRT and trimodality therapy in our cohort appear lower than expected despite evidence supporting the benefits of these strategies. Use of other treatment options was associated with poorer outcomes.

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      P1.15-35 - Real World Outcome of Different Administrations Endostar Combined With Chemotherapy in Driver Gene Mutation Negative Advanced NSCLC

      16:45 - 18:00  |  Presenting Author(s): Yongchang Zhang  |  Author(s): Zhongtai Wang, Chunhua Zhou, Nong Yang

      • Abstract

      Background

      To compare the efficacy and safety of different administration endostar combined with platinum-based chemotherapy with first-line treatment of driver gene mutation negative advanced NSCLC patients, and provides real-world evidence for optimum administration of endostar.

      Method

      From April 2014 to April 2017, 88 driver gene mutation negative patients who received platinum-based chemotherapy alone or combined with endostar were retrospectively enrolled in this project. All the patients were divided to three groups, including platinum-based chemotherapy alone (arm A), combined with 14 days endostar (7.5 mg/m2, d1-14, q21d, arm B) and 7 days endostar (15 mg/m2, d1-7, q21d, arm C). The primary endpoint was median overall survival (OS). The secondary endpoints were median progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). The efficacy and safety was evaluated every 2 cycles.

      Result

      Of all the 88 enrolled patients, the median OS was 20 months in endostar groups (arm B and arm C) and 10 months in chemotherapy alone group (arm A, P<0.001). The median PFS was months and 4.5 months respectively (P=0.073). The median OS was 22 months (arm B) and 14 months (arm C, P = 0.01). The median PFS was 6 months in arm B, 6.5 months in arm C, and 4.5 months in arm A. The ORR were 44.4%, 22.2% and 20.6% for arm B (P=0.046), arm C (P=0.877) and arm A respectively. The DCR were 88.9%, 77.8% and 64.7% for arm B (P=0.046), arm C (P=0.266) and arm A respectively. There is no meaningful difference in OS between arm B and arm C (P=0.111), as well as ORR (P=0.074) and DCR (P=0.234), but a meaningful difference in PFS (P=0.044). The incidence of adverse event in the three groups was 22.2%, 3.7%, and 11.6%, respectively. There was no new occurring intolerant adverse event.

      Conclusion

      Endostar plus platinum-based doublet chemotherapy can significantly improve short-term and long-term outcomes in driver gene mutation negative advanced NSCLC. The administration of 14 days endostar compared to 7 days has no significant improvement in efficacy, but results in a higher incidence of adverse events.

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      P1.15-36 - A Better Real World Practice for Pemetrexed in First-Line Treatment of Advanced Mon-Squamous Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Yongchang Zhang  |  Author(s): binjie Yan, Haiyan Yang, Nong Yang

      • Abstract

      Background

      To investigate the real world practice of first-line pemetrexed combined with different drugs in patients with advanced Non-squamous non-small cell lung cancer.

      Method

      A total number of 164 patients from February 2012 to August 2017 in Hunan Cancer Hospital in the combination of pemetrexed with cisplatin were enrolled in this study. All the patients were divided into 5 groups: PC-P (pemetrexed combined with platinum for 4 cycles and pemetrexed maintenance, arm A), PCA-PA (Pemetrexed plus platinum and bevacizumab 4cycles, pemetrexed combined with bevacizumab maintenance, arm B), PC (pemetrexed combined with platinum chemotherapy 4 cycles, arm C), PCA (pemetrexed with platinum chemotherapy, plus bevacizumab 4 cycles without maintenance, arm D), PC-EGFR TKI (pemetrexed plus platinum chemotherapy 4 cycles, and then EGFR TKI as maintenance treatment, arm E). Efficacy and safety of pemetrexed was performed in each group comparing with each major clinical data.

      Result

      According to retrospective study , the median PFS for arm A, B, C, D and E were 13 months, 12 months, 5 months, 5 months, 15.8 months respectively; the median OS was 27 month, 21 months, 15 months, 11 months and 31 months respectively. Arm A and Arm C, Arm B and Arm D achieved statistically different on PFS (p<0.05). And Arm A and Arm C, Arm B and Arm D also achieved statistical differences between OS (p<0.05). In the multivariate regression analysis of all patients, we found that the ECOG PS score may be an independent prognostic factor for death from lung cancer patients. Among all the patients, 35 (21.4%) patients presented with non-hematologic serious adverse event (grade 3 and 4). There was no new occurring intolerant adverse event comparing with other clinical trials.

      Conclusion

      In this real world study, pemetrexed proved to be high efficacy and well tolerant in advanced NSCLC. The efficiency of maintenance pemetrexed treatment group achieved significantly better outcome than the non-maintenance treatment group. In addition, ECOG PS score may be an independent prognostic factor for the death of patients in lung cancer. There was no new occurring intolerant adverse event comparing with previous clinical trials, the main adverse events in this study were also focused on non-hematologic toxicity. This is consistent with clinical trials.

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      P1.15-36a - Assessment of Depression Among Advanced Stage Lung Cancer Patients in Developing Country

      16:45 - 18:00  |  Presenting Author(s): Guru Sharan Sah  |  Author(s): Ashok Sapkota, Jay Ram Adhikari, Jayananda Prasad Singh, Nirdesh Pokhrel

      • Abstract

      Background

      Lung cancer is most common cancer and leading cause of death in developing country. Among lung cancer patients, depression is common and has been associated with increased morbidity and mortality.

      Method

      The study was conducted in 79 patients diagnosed with advanced stage lung cancer attending medical oncology department of B. P. Koirala Memorial Cancer Hospital, Nepal. A set of questionnaire was used to interview and collect the data. Beck’s Depression Inventory (BDI-II) and its Nepali translated transcript was used to assess the depressive symptoms of patient. Based on score, depression was classified as Minimal depression, Mild Depression, Moderate Depression and Severe Depression. Verbal consent was taken before each interview to address the rights of the patient.

      Result

      This study revealed lung cancer was predominant in male patients (55.7%). Patients age ranged from 42 years to 81 years with mean age 65.59 years. Among all the patients evaluated only 45/79 (57%) patients were aware of their disease status. 34 patients were unknown about their diagnosis. All the patients evaluated were found to be depressed in several degrees. 11/79 (13.9 %) of the patients had minimal, 27/70 (34.2%) had mild, 12/79(32.30%) had moderate and 29/79 (36.7%) had severe forms of depression. Depression was common in both sexes. Interestingly most of patients who were explained about their disease status had moderate to severe depression but those patients who were unknown about their disease status tend to have minimal to mild depression (table 1). The association between awareness of disease status and severity of depression were statistically significant.
      img_6194.jpg

      Conclusion

      The study reveals that there is high prevalence of depression among lung cancer patients in developing country. Thus all lung cancer patients need screening and appropriate management for depression also.

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    P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session)

    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Moderators:
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      P1.16-01 - Prognostic Variables Associated with Improved Outcomes in Stage III NSCLC Patients Treated with Consolidation Pembrolizumab

      16:45 - 18:00  |  Presenting Author(s): Bilal Anouti  |  Author(s): Sandra Althouse, Greg Durm, Tim Breen, Nasser Hanna

      • Abstract

      Background

      HCRN LUN 14-179 is a phase II trial of consolidation pembrolizumab following concurrent chemoradiation for the treatment of patients with stage III NSCLC. Time to metastatic disease, PFS, and OS appear superior to historical controls of chemoradiation alone. Unfortunately, not all patients benefit from consolidation immunotherapy. We performed a univariate analysis evaluating variables associated with PFS, metastatic disease, and OS.

      Method

      We conducted a retrospective analysis from patients enrolled on HCRN LUN14-179. Data collected included age, sex, stage, smoking status, PD-L1 status, >G2 vs <G1 adverse event, <G2 vs. >G3 pneumonitis, duration of pembrolizumab (<4 vs. >4 cycles), chemotherapy regimen, PS 0 vs 1, time to start pembrolizumab (<6 vs. >6 weeks from radiation), V20 (<20% vs. >20%), and total radiation dose. Univariate Cox regression was performed to determine the variables associated with 3 endpoints: time to metastatic disease/death; progression free survival; and overall survival.

      Result

      From April 2015 to December 2016, 93 patients were enrolled and 92 were included in the efficacy analysis (1 patient was ineligible). For time to metastatic disease or death, improved outcomes may be associated (p<0.1) with stage IIIA, non-squamous cell, >4 cycles of pembrolizumab, and V20< 20%. For PFS, improved outcomes (p<0.1) may be seen for females, stage IIIA, non-squamous histology, PD-L1 [-] tumors, >4 cycles of pembrolizumab, and V20< 20%. For OS, improved outcomes (p<0.1) may be seen for non-squamous histology, PD-L1 [-], >4 cycles of pembrolizumab, V20< 20%, and <G2 pneumonitis.

      Conclusion

      Non-squamous NSCLC, PD-L1 [-] tumors, and V20 <20% may be associated with prolonged time to metastatic disease or death, PFS, and OS for patients with stage III NSCLC treated with chemoradiation followed by pembrolizumab.

      Variable

      Alive without metastatic disease

      Alive without progression

      Alive

      IIIA (n=55)

      IIIB (n=37)

      69% p=0.12

      51%

      56% p=0.21

      41%

      69% p=0.13

      59%

      Non-SCCA (n=51)

      SCCA (n=41)

      69% p=0.11

      54%

      55% p=0.21

      44%

      75% p=0.16

      61%

      PD-L1 [-] (n=11)

      PD-L1 [+] (n=42)

      82% p=0.13

      57%

      64% p=0.19

      40%

      91% p=0.07

      62%

      > 4 pembro (n=77)

      < 4 pembro (n=15)

      67% p=0.01

      33%

      55% p=0.04

      27%

      75% p=0.001

      33%

      V20 < 20% (n=19)

      V20> 20% (n=59)

      79% p=0.07

      54%

      63% p=0.08

      39%

      79% p=0.15

      61%

      G < 2 pneumonitis (n=87)

      G > 3 pneumonitis (n=5)

      63% p=0.28

      40%

      51% p=0.61

      40%

      70% p=0.16

      40%

      Female (n=33)

      Male (n=59)

      67% p=0.37

      59%

      67% p=0.11

      59%

      73% p=0.51

      66%

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      P1.16-02 -  Support and Information Needs for Patients with NSCLC Receiving Concurrent Chemo-Radiotherapy: Findings from the INSIGHT Study.

      16:45 - 18:00  |  Presenting Author(s): Jackie Fenemore  |  Author(s): Grant Punnett, Janelle Yorke, Fiona Blackhall, Delyth McEntee, Marie Eaton, Hilary Neal

      • Abstract

      Background

      The curative intent pathway for patients with non-small cell lung cancer (NSCLC) is complex and burdensome. Concurrent chemotherapy and radiotherapy (chemo-radiotherapy) is used as first line treatment for inoperable stage 3 cancer,and requires the patient to attend multiple investigational procedures, separate appointments for chemotherapy and radiotherapy, intensive monitoring during treatment and multiple follow-up visits post treatment for up to 5 years to monitor late-toxicities and disease recurrence.The aims of this study are to identify the information needs of patients and their carers at key points along the treatment pathway and the preferred methods for information provision. A grant was awarded by the NLCFN to fund this patient experience, qualatative research study.

      Method

      Semi-structured interviews were conducted with 15 patients, and their carer dyads where appropriate, recruited from a cancer centre in Manchester, U.K.

      Result

      Data collection is now complete with 15 patients recruited, of whom 6 were interviewed with a carer dyad. Thematic analysis is on-going and has been employed inductively to identify some of the emerging themes and key issues from the data collected. These include; preferred means of receiving information and level of information given, burden of treatment and earlier access to supportive care, information about life after treatment and the after effects of treatment, and preferred methods to access appropriate support.

      Conclusion

      Further research is needed into the on-going needs of this patient cohort and data collection so far highlights areas for consideration when providing information to this patient cohort.

      Emerging themes highlight that a specific booklet on concurrent chemo/radiotherapy would be preferred, covering all aspects of treatment, including a personalised treatment plan to include, where relevant mask wearing, the impact of side effects of treatment and how assess support. Early indications are that patients prefer a combination of verbal, written and visual information giving.

      Collaboration work to link these patients on the concurrent treatment pathway in with early supportive care is optimal.Implementation of this service as part of the Concurrent treatment pathway will commence as a pilot study in July 2018, to assess the impact of earlier intervention to manage disease burden and treatment side effects, with an aim to reduce hospital admissions.

      The evidence suggests further work is needed to improve information giving and support to these patients both pre and post treatment. Additional advice is required to support proactive management, to enhance recovery, whilst addressing the fear and anxiety patients and carers experience due to uncertain outcomes.

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      P1.16-03 - Prognostic Significance of PD-L1 in Stage II/III Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Mustafa Karaca  |  Author(s): Deniz Tural, Ahmet Özet

      • Abstract

      Background

      Prognostic significance of PD-1/PD-L1 axis expression in non-small cell lung cancer (NSCLC) remains uncertain despite being a predictive biomarker for novel immunotherapeutics. In this study, we have investigated PD-1/PD-L1 expression and its effect on disease prognosis and overall survival in stage II-III NSCLC patients.

      Method

      Clinic and pathologic features of stage II and stage III NSCLC patients were retrospectively analyzed from patients’ records in this study. PD-1 and PD-L1 immunohistochemistry staining were carried out to archived tumor specimens of the eligible patients. Percentages of PD-1 positive lymphocytes, PD-L1 positive tumor cells and PD-L1 positive tumor infiltrating immune cells were evaluated and considered as positive if ≥1% of the cells displayed staining.

      Result

      Sixty-six male (89,2%) and 8 female (10,8%) of total 74 patients were eligible for the study. Thirty-three (44,6%) patients were diagnosed as stage II disease while 41 patients (55,6%) were diagnosed as stage III. PD-1 expression, PD-L1 expression in tumor cells and PD-L1 expression in tumor infiltrating immune cells were positive in 83,8% (n = 62), 45,9% (n = 34), 67,6% (n = 50) of total 74 patients, respectively.Three-year overall survival (OS) rate was calculated as 57,7%. Univariate analyses did not reveal any significant difference in 3-years OS between those with PD-1 and PD-L1 expression in tumor infiltrating immune cells and those without expression. (p = 0,413 and p = 0,099; respectively) However, 3-years OS was more favorable in those with PD-L1 expression in tumor cells than in those without PD-L1 expression (76,6% vs %41%, p = 0.031). In multivariate analyses, a positive trend was revealed in 3-years OS between those with PD-L1 expression in tumor cells and those without expression. (HR: 0,405; 95% CI: 0,153, 1,074; p = 0,069)

      Conclusion

      Conclusions: In this study, better prognosis was obtained with positivity of PD-L1 in tumor cells. Therefore, it should be taking into consideration while designing adjuvant immunotherapy trials which are generally formed with stage I-III NSCLC patients, that expression of PD-1/PD-L1 pathway may have a positive prognostic effect.

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      P1.16-04 - Outcomes of Patients < 70 or ≥70 Years of Age in PACIFIC

      16:45 - 18:00  |  Presenting Author(s): Mark A Socinski  |  Author(s): Mustafa Özgüroğlu, Augusto Villegas, Davey Daniel, David Vicente, Shuji Murakami, Rina Hui, Jhanelle Elaine Gray, Keunchil Park, Mark David Vincent, Francesco Perrone, Lynne Poole, Catherine Wadsworth, Phillip A. Dennis, Scott J Antonia

      • Abstract

      Background

      In the Phase 3 PACIFIC study of durvalumab versus placebo in patients with stage III, unresectable NSCLC without progression after concurrent chemoradiotherapy (cCRT), the co-primary endpoint PFS was significantly longer with durvalumab (stratified HR 0.52, 95% CI, 0.42–0.65; P<0.0001). In a prespecified analysis, PFS benefit with durvalumab was observed regardless of a 65-year age cutoff. However, median age at NSCLC diagnosis is 70 (CA Cancer J Clin, 2014). We therefore performed subgroup analyses to explore outcomes using a 70-year age cutoff.

      Method

      PACIFIC (NCT02125461) was a Phase 3, randomized, double-blind, all-comers study of patients with WHO PS 0/1 who did not progress following ≥2 cycles of platinum-based cCRT. Patients were stratified by age, sex, and smoking history and randomized (2:1) 1–42 days after cCRT to receive durvalumab 10 mg/kg IV Q2W or placebo up to 12 months. Co-primary endpoints were PFS (BICR, RECIST v1.1) and OS (not available). Secondary endpoints included ORR, time to death/distant metastasis (TTDM), and safety. Between-treatment endpoint comparisons were performed for patients <70 and ≥70 years.

      Result

      As of Feb 13, 2017, 713 patients were randomized; 78% and 22% were <70 and ≥70 years, respectively. Baseline patient and tumor characteristics were generally well balanced across subgroups. However, patients ≥70 were more likely to be male, have PS 1, and, within the placebo arm, to be Asian. Older patients more commonly received carboplatin-based CT than younger patients. Durvalumab demonstrated PFS benefit compared with placebo, regardless if patients were <70 years (median 16.9 vs 5.6 months, HR=0.53, 95% CI: 0.42–0.67) or ≥70 years (median 12.3 vs 6.1 months, HR=0.62, 95% CI: 0.41–0.95). Durvalumab improved TTDM (<70 years: HR=0.53, 95% CI: 0.39–0.71; ≥70 years: HR=0.66, 95% CI: 0.39–1.13) and ORR (<70 years: 27.6% vs 15.4%; ≥70 years: 31.9% vs 17.6%) regardless of age. Younger patients on durvalumab received treatment longer (median total duration 45.5 vs 36.0 weeks). Regardless of treatment, older patients discontinued more due to AEs (durvalumab: 22.0% vs 13.7%; placebo: 16.1% vs 7.8%) and had more grade 5 AEs (durvalumab: 10.9% vs 2.7%; placebo: 9.1% vs. 4.5%). Among patients receiving durvalumab, older patients experienced more all-cause SAEs (42.6% vs 24.9%) and grade 3/4 AEs (41.6% vs 29.4%) but fewer AESIs (56.4% vs 67.9%) than younger patients.

      Conclusion

      Patients achieved clinical benefit with durvalumab regardless of age. Increased AEs/SAEs observed in older patients across treatments may reflect age/cCRT related morbidity.

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      P1.16-05 - Effect of Induction Chemotherapy in the PACIFIC Study

      16:45 - 18:00  |  Presenting Author(s): David R. Spigel  |  Author(s): Johan F. Vansteenkiste, Martin Reck, Heather A Wakelee, Mustafa Özgüroğlu, Davey Daniel, Augusto Villegas, David Vicente, Rina Hui, Shuji Murakami, Luis Paz-Ares, Lynne Poole, Catherine Wadsworth, Phillip A. Dennis, Scott J Antonia

      • Abstract

      Background

      The Phase 3 PACIFIC study of patients with stage III, unresectable NSCLC without progression after concurrent chemoradiotherapy (cCRT) demonstrated significantly longer PFS with durvalumab versus placebo (stratified HR 0.52; 95% CI 0.42–0.65; P<0.0001). Overall, 26% and 29% in the durvalumab and placebo groups, respectively, received induction chemotherapy (ICT) before cCRT. Here, we report exploratory analyses of baseline characteristics, disposition, and outcomes from this study based on the presence or absence of prior ICT.

      Method

      PACIFIC (NCT02125461) was a Phase 3, randomized, double-blind study of patients with WHO PS 0/1 and any tumor PD-L1 status without progression after ≥2 cycles of platinum-based cCRT. Patients were stratified by age, sex and smoking history and randomized (2:1) to durvalumab 10 mg/kg IV Q2W or placebo up to 12 months. Co-primary endpoints were PFS (blinded independent central review, RECIST v1.1) and overall survival (not available). We investigated associations between the presence/absence of ICT and disposition, baseline characteristics, and efficacy and safety endpoints.

      Result

      As of February 13, 2017, 713 patients were randomized; 27% had prior ICT. Baseline characteristics were similar between treatment arms; however, patients with ICT were generally younger, less frequently Asian, had lower incidence of squamous histology, and more often had stage IIIB disease. There were no differences between groups in terms of prior RT dose. PFS benefit with durvalumab was demonstrated irrespective of ICT use (ICT: HR=0.61, 95% CI, 0.41–0.88; no ICT: HR=0.54, 95% CI, 0.42–0.69). Similarly, ORR with durvalumab was numerically higher than with placebo irrespective of ICT use (ICT: 16.1% vs 13.1%; no ICT: 32.9% vs 17.1%). ICT did not affect treatment duration for durvalumab or placebo. Between-treatment safety differences were minimal across subgroups; however, patients with ICT experienced fewer SAEs, treatment-related SAEs and pneumonitis/radiation pneumonitis regardless of treatment arm.

      Conclusion

      Durvalumab demonstrated clinical benefit irrespective of ICT. The safety profile of durvalumab was consistent in patients with or without ICT. A lower rate of toxicity was observed in patients with ICT regardless of treatment arm.

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      P1.16-06 - Expanded Efficacy and Safety Analysis of PACIFIC Based on a PD-L1 Cutpoint of 25%

      16:45 - 18:00  |  Presenting Author(s): Alexander Spira  |  Author(s): David Planchard, Byoung Chul Cho, Mustafa Özgüroğlu, Davey Daniel, Augusto Villegas, David Vicente, Rina Hui, Shuji Murakami, Luis Paz-Ares, Anne-Marie Boothman, Lynne Poole, Catherine Wadsworth, Phillip A. Dennis, Scott J Antonia

      • Abstract

      Background

      In the Phase 3 PACIFIC study of patients with stage III, unresectable NSCLC without progression after concurrent chemoradiotherapy (cCRT), PFS was significantly longer with durvalumab versus placebo (stratified HR 0.52; 95% CI 0.42–0.65; P<0.0001). We report exploratory analyses of PACIFIC outcomes by PD-L1 expression assessed in tumor samples collected prior to cCRT.

      Method

      PACIFIC (NCT02125461) was a Phase 3, randomized, double-blind study of patients with WHO PS 0/1 without progression after ≥2 cycles of platinum-based cCRT. Eligibility was irrespective of PD-L1 expression; archived samples were optional for testing (VENTANA PD-L1 [SP263] assay). No samples were obtained after cCRT, prior to infusion with durvalumab or placebo. Patients were randomized (2:1) to durvalumab 10 mg/kg IV Q2W or placebo up to 12 months, stratified by age, sex and smoking history. Co-primary endpoints were PFS (blinded independent central review, RECIST v1.1) and OS (not available). Secondary endpoints included ORR and safety. We investigated associations between subgroups of patients with PD-L1 expression on tumor cells (TC) of <25% or ≥25% and efficacy.

      Result

      As of February 13, 2017, 713 patients were randomized; 451 (63.3%) had known PD-L1 status (TC<25%, 64.7%; TC≥25%, 35.3%; Table). Baseline characteristics and prior therapy (including best response to prior therapy) were generally well balanced between arms across both PD-L1 subgroups. PFS benefit with durvalumab was demonstrated irrespective of PD-L1 status (HR 0.59; 95% CI, 0.43–0.82 for TC<25% and HR 0.41; 95% CI, 0.26–0.65 for TC≥25%) (Table). ORR was greater with durvalumab compared to placebo regardless of PD-L1 status (Table). The overall safety profile of durvalumab in each PD-L1 subgroup was consistent with the ITT population treated with durvalumab.

      Conclusion

      Durvalumab demonstrated clinical benefit and had a well-tolerated, manageable safety profile irrespective of PD-L1 status obtained from archival tumor samples prior to cCRT.

      PD-L1 TC<25%

      PD-L1 TC≥25%

      Durvalumab (n=187)

      Placebo
      (n=105)

      Durvalumab (n=115)

      Placebo
      (n=44)

      Completed 12 months treatment, n (%)

      74 (39.6)

      35 (33.3)

      55 (47.8)

      13 (29.5)

      PFS*

      Median (95% CI), months

      16.9 (11.0–NR)

      6.9 (5.0–11.0)

      17.8 (11.1–NR)

      3.7 (2.0–13.2)

      HR (95% CI)

      0.59 (0.43–0.82)

      0.41 (0.26–0.65)

      ORR

      n=170

      n=96

      n=108

      n=40

      n (%)

      [95% CI]

      50 (29.4)

      [22.7–36.9]

      19 (19.8)

      [12.36–29.17]

      31 (28.7)

      [20.4–38.2]

      6 (15.0)

      [5.71–29.84]

      *In the overall ITT population, median PFS was 16.8 months (95% CI, 13.0–18.1) with durvalumab (n=476) vs. 5.6 months (95% CI, 4.6–7.8) with placebo (n=237), with an HR of 0.52 (95% CI, 0.42–0.65; P<0.001) (stratified log-rank); PD-L1 assessment was not required in the study; in PD-L1 unknown patients, median PFS was 14.0 months (95% CI, 9.2–NR) with durvalumab (n=174) vs. 6.4 months (95% CI, 3.8–9.0) with placebo (n=88), with an HR of 0.59 (95% CI, 0.42–0.83) (unstratified Cox proportional hazards model); ORR for n evaluable patients included unconfirmed responses. ITT, intention-to-treat; NR, not reached; ORR, objective response rate; PFS, progression-free survival.

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      P1.16-07 - Cost-Effectiveness of Pembrolizumab as 1st Line Treatment for Metastatic NSCLC Patients with High PD-L1 Expression in Singapore

      16:45 - 18:00  |  Presenting Author(s): Wan Ling Tan  |  Author(s): Min Huang, Sheenu Chandwani, Tun-Ying Hsu, Seng Chuen Tan, Daniel S.W. Tan

      • Abstract

      Background

      Pembrolizumab, an immune checkpoint inhibitor, has been approved as monotherapy for 1st line treatment of metastatic NSCLC with PD-L1 tumor proportion score (TPS) ≥50% based on the pivotal Keynote (KN)-024 study. This study aims to evaluate the cost-effectiveness of pembrolizumab compared with standard-of-care (SoC) platinum-based chemotherapy in patients with TPS≥50% from a societal perspective in Singapore based on results from KN024.

      Method

      A known partitioned-survival model was adapted to estimate progression-free survival, overall survival, costs of treatments, adverse events and disease management, and health utilities over a time horizon of 20 years. The maximum treatment duration of 2 years was applied for pembrolizumab. Clinical and resource utilization inputs were based on data from KN024 study and input from local oncologists. Unit costs captured both patients’ payments and government subsidies. Utility scores in different health states were based on EQ-5D data from KN024 with weighting indices suggested by a local quality-of-life study. An annual discount rate of 3% was applied and a series of sensitivity and scenario analyses were conducted to address uncertainty.

      Result

      For 1st line treatment for NSCLC patients with TPS≥50%, pembrolizumab monotherapy is estimated to result in 0.91 quality-adjusted-life-years (QALY) gained. The projected incremental cost for pembrolizumab is S$141,979 compared to SoC, leading to an incremental cost-effectiveness ratio (ICER) of S$155,630 per QALY gained. A similar ICER of S$156,862 is observed in a scenario analysis whereby all patients are tested for PD-L1 and those with high PD-L1 expression are treated with pembrolizumab. With a Pembrolizumab Patient Access Program (PAP), the ICER is estimated to be S$95,279 per QALY. In another scenario analysis where government subsidies and claim limits of Medishield / Medisave are considered, the estimated ICER is S$46,308 per QALY from the Ministry of Health (MOH) perspective.

      Conclusion

      For NSCLC patients with TPS≥50%, the ICER in the base-case for pembrolizumab as 1st-line treatment is $155,630 – which is between 2-3x gross domestic product (GDP) per capita of Singapore (S$73,167) in 2016, whereas the estimated ICER with Pembrolizumab PAP is 1-2x GDP per capita. Depending on threshold boundaries adopted, 1st line pembrolizumab for patients with similar profile (TPS ≥50%) as those in KN024, would be a cost-effective treatment compared to SoC in Singapore.

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      P1.16-08 - Weekly Nab-Paclitaxel Plus Carboplatin as Neoadjuvant Therapy for IIIA-N2 Lung Squamous Cell Carcinoma: A Prospective Phase II Study

      16:45 - 18:00  |  Presenting Author(s): Changli Wang  |  Author(s): Yu Zhang, Jian Quan Zhu, Dongsheng Yue, Xiaoliang Zhao, qiang Zhang, Hui Chen

      • Abstract

      Background

      To evaluate the safety and antitumor activity of weekly nab-paclitaxel combined with carboplatin in patients with advanced stage IIIA-N2 NSCLC patients with squamous histology

      Method

      From April 2015 to August 2017, 36 treatment-naive, pathologically diagnosed IIIA-N2 lung squamous cell carcinoma patients were enrolled and given two cycles of weekly nab-paclitaxel (100mg/m2, day1,8,15 of a 21-day cycle) plus Carboplatin (AUC = 5 at day 1, q3w) as neoadjuvant therapy. Then resectability was assessed and surgery was performed for resectable lesions. Post-operative adjuvant chemotherapy regimens is the combination of Nab-paclitaxel (100mg/m2, qw x 6) and carboplatin (AUC 5, Q3W x 2) for patients with PD, adjuvant chemotherapy regimen will be changed. The primary objective is the safety and efficacy, and the secondary objectives are quality of life and the role of prognostic biomarker SPARC.

      Result

      Of 36 patients, 3 stopped treatment due to patient decision. 33 were finally evaluated and 1 is still on treatment. Significant tumor volume shrinkage was seen in some patients after the neoadjuvant therapy. 66.7% patients achieved partial response (PR), 21.2% patients achieved stable disease (SD). Disease control (PR +SD) rate was 87.9%. Finally, 23 patients underwent surgical resection, the respectability rate was 69.7%. 12.1% occurred disease progress and failed to achieve resection, including 3 with local progress and 1 with pulmonary metastatic nodule; Among 22 PR pts, 4 failed to achieve resection, in which 1 was due to heart function, the other 3 due to personal unwillingness. 2 of 7 with stable disease failed to achieve resection; the pathological improvement in T stage and N stage before and after treatment was 81.8% (18/22) and 50% (11/22) respectively. The major adverse event was neutropenia (grade I and II) and no serious AE was found.

      Conclusion

      Nab-paclitaxel in combination with Carboplatin showed promising ORR rate and resection rate in of IIIA-N2 lung squamous cell carcinoma. The regimen could be a new chemo option as the neoadjuvant treatment. PFS and OS data will be reported after follow up completing.

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      P1.16-09 - Surgical Result of Pathologic Stage III a Non Small Cell Lung Cancer: Have We Improved?

      16:45 - 18:00  |  Presenting Author(s): Ching-Yang Wu

      • Abstract

      Background

      Non small cell lung cancer was the leading cause of cancer death worldwide. five-year survival of pathologic stage IIIa still remain poor and the management remain controversial. Many new medicines and surgical techniques were utilized as treatment for pathologic stage IIIIa patient. The aim of study was tried to analyzed the survival impact of these treatment modalities and the stage migration effect during new TNM staging classification system.

      Method

      From Jan 2005 to Jun 2014, there were 166 pathologic stage IIIa patients were enrolled into study. All patients were follow up till 2016/7. Patients were divided into two groups since year 2010 because of difference of surgical technique switch. Medical records were reviewed retrospectively and survival status were analyzed.

      Result

      From January 2005 to May 2014, 166 patients who had received tumor resection and were confirmed as pathologic stage IIIa by 7th AJCC stage classification system were included for further analysis. The 5-year disease free and overall survival rates were 24.9% and 38.2%, respectively. Patients who received neoadjuvant therapy showed inferior disease free survival compared with those without neoadjuvant therapy. ( p< 0.0001). Patients who presented as adenocarcinoma and received tumor resection showed better overall survival than non-adenocarcinoma patients. (p=0.0011) Because the operation method was shifted to video-assisted thoracoscopic surgery in the year 2010, we analyzed survival status separately before and after 2010. In addition, we found that patients who received tumor resection and were conformed as pathologic stage IIIa adenocarcinoma has had better overall survival than other subgroups. (p =0.0005) 28 patients who were identified stage migration had worse disease-free and overall survival.

      Conclusion

      Disease free survival of pathologic stage IIIa patients remain unchanged but overall survival had much improvement. Patients who presented with adenocarcinoma who received tumor resection during 2010 to 2014 has better survival. This may be related to medical improvement but further investigation was warranted. Stage migration and worse disease and overall survival for those presented as 3b in new stage classification were identified. Different treatment strategy was needed for these patients who were identified stage migration.

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      P1.16-10 - Marginal Features Analyses of Lung Adenocarcinoma for Survival Prediction

      16:45 - 18:00  |  Presenting Author(s): Geewon Lee  |  Author(s): Ho Yun Lee, Hyunjin Park

      • Abstract

      Background

      Tumor microenvironment is a complex mixture of assorted cells and extra-cellular components which make up an amazingly dynamic area that includes signaling interactions between cancer cells and their surrounding tissue. Tumor microenvironment makes up the peripheral portion of the tumor and major changes in this area has been reported to be associated with a poor prognosis. However, very few studies have investigated the tumor marginal features quantitatively extracted from CT images using a radiomics approach. We aimed to clarify the relationship between tumor marginal features and the micropapillary pattern and correlated with survival.

      Method

      We enrolled 334 patients who underwent complete resection for lung adenocarcinoma. Quantitative histologic subtyping was performed for the whole tumor. Using a radiomics approach, quantitative CT analysis was performed and 82 marginal features were extracted. Clinical variables and marginal features were correlated with survival. Using selected clinical variables and marginal features a prognostic model was calculated with subsequent internal and external validation.

      Result

      Among various subtypes, solid predominant adenocarcinomas had the lowest proportion (6.9%) of combined micropapillary pattern. At univariate analysis, patient age, tumor size, and multiple marginal features (convexity, surface area, compactness, maximum 3D diameter, sphericity, surface-to-volume ratio, mean pixel value, median pixel value, entropy, uniformity, skewness, kurtosis, roundness factor, solidity, and lacunarity)were predictive of survival. At multivariate cox proportional analysis, convexity (P=0.017), kurtosis (P<0.001), and patient age (P=0.006) were identified as being predictive of survival. Ten-fold cross-validation tests demonstrated that our prediction model significantly classified patients according to survival (P<0.001). Although lower than internal validation, the prediction model also worked at external validation.figure.jpg

      Conclusion

      Marginal radiomics features of convexity and kurtosis reflect the tumor microenvironment and were predictive of patient survival in lung adenocarcinomas.

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      P1.16-11 - Monitoring of Early Stage Lung Cancer Using Liquid Biopsies.

      16:45 - 18:00  |  Presenting Author(s): Alexander Dobrovic

      • Abstract

      Background

      This study aims to validate the use of chromosome rearrangements as tumour-specific biomarkers for the detection of circulating tumour DNA (ctDNA) to enable monitoring of cancer using digital PCR.We consider that rearrangements are the best source of robust disease markers that can be used for every lung cancer patient without a clear truncal mutation. The current high cost of the whole genome sequencing required for identification of chromosome rearrangements is offset by the low cost, high sensitivity and specificity of the subsequent assays.

      Method

      Methods for ctDNA detection using chromosome rearrangements that leverage advances in next generation sequencing (NGS), bioinformatics and droplet digital PCR (ddPCR) have now been developed by our laboratory.

      Result

      We are using whole genome sequencing and bioinformatic analysis of lung tumour samples. The genomic sequence was aligned to the human reference genome (hg19). Rearrangements were identified using the GRIDSS algoriths. Large numebers of potential genomic rearrangements ithat could be used as a biomarker to detect ctDNA were identified in each tumour. These were used to design primers which were used to monitor the success of surgical resection and to detect early relapse.

      Conclusion

      Patients with early-stage primary tumours are the group in which appropriately timed therapeutic intervention is most likely to make a clinical difference. Our study assesses ctDNA in a large cohort of lung cancer patients with early-stage primary tumours that are being treated with the primary aim of cure. In addtion, whole genome sequencing also identifies genomic information such as rare functional rearrangements and mutational burden which can also be used in patient management.

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      P1.16-12 - Identification of a Biomarker Panel in Resected NSCLC That Predicts Patient Outcomes and Benefit from Adjuvant Chemotherapy

      16:45 - 18:00  |  Presenting Author(s): Stacy Grieve  |  Author(s): Matthew Finniss, Ayush Ray, Jonathan Moore, Alli Muragesan, Jane Agar, Cenk Acar, Tony Reiman

      • Abstract

      Background

      Adjuvant chemotherapy for resected NSCLC improves overall survival by approximately 10%. Physicians need tools to predict which patients are most likely to benefit from chemotherapy, sparing those unlikely to benefit. A 15-gene expression profile (GEP) published by Zhu et al is both prognostic and predictive of benefit from adjuvant chemotherapy. The aim of this study is to translate this GEP into a readily applicable immunohistochemistry (IHC) panel.

      Method

      We constructed NSCLC tissue microarrays at the Saint John Regional Hospital and semiquantitatively assessed the IHC expression and prognostic significance of proteins encoded by 7 of the genes in the Zhu panel for which commercial antibodies were available.

      Result

      In 62 patients with resected stage II-III NSCLC, the prognostic significance of IHC assays for four proteins were concordant with the Zhu GEP results. Low FOSL2 (OS, HR = 2.6; p = 0.0231; PFS, HR = 3.3; p = 0.0052), and low ATP1B1 (PFS, HR = 2.0; p = 0.0338) were adverse prognostic factors. High STMN2 and low TRIM14 expression trended towards worse OS and PFS. Multivariate analysis verified the prognostic impact of the four assays. These markers could also be integrated as a panel with retained prognostic value (OS, HR=2.1, p=0.03).

      Conclusion

      An IHC panel with results concordant to the Zhu GEP is prognostic. Ongoing studies will examine the prognostic and predictive impact of this IHC panel in larger, independent datasets. If the panel turns out to be robust and predictive, it will have potential clinical application as a tool to select patients for adjuvant chemotherapy.

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      P1.16-13 - Photo Dynamic Therapy (PDT) in Our Hospital

      16:45 - 18:00  |  Presenting Author(s): Fumihiko Hoshi  |  Author(s): Akira Sakurada, Masafumi Noda, Tetsu Sado, Yasushi Matsuda, Hisashi Oishi, Shunsuke Eba, Yoshinori Okada

      • Abstract

      Background

      Lung cancer is the leading cause of cancer death worldwide. A large part of lung cancer is diagnosed at an advanced stage, but the number of lung cancer diagnosed at an early stage are increasing due to improved diagnostic imaging techniques. In Japan, sputum cytology for mass screening provides chances to detect very early stage centrally located lung cancer which is good adaptation of PDT.

      Although PDT is less invasive therapy which enable us to treat the patients with poor pulmonary function or poor performance status. It is important to clarify the therapeutic outcome and the morbidity after PDT such as airway narrowing, pneumonia, and sunlight hypersensitivity.

      Method

      We analyzed 14 patients who received PDT in Tohoku University Hospital between January 2010 and April 2017 retrospectively and evaluated the therapeutic outcome of PDT.

      Result

      14 cases were all male and the average age was 71. Nine cases were detected in cancer screening examinations and other 5 cases were detected accidentally while observing other diseases. Lung cancer existed in trachea 1, in segmental bronchi 4, in sub segmental bronchi 7, and more peripheral lesion 2. All 14 cases were pathologically squamous cell carcinoma. In 2 cases, we performed PDT twice. In 3 cases, we performed surgical resection after PDT. Within follow-up period after PDT, 5 cases developed metachronous lung cancer and were treated with surgical resection or radiation therapy. After these therapies 11 cases alive without recurrence, 1 case alive with recurrence, 1 case died from original disease, and 1 case died from other disease. Only one case suffered airway narrowing after PDT, but other 13 cases had no morbidity.

      Conclusion

      We concluded PDT is a good treatment in early stage centrally located lung cancer with good outcomes and little morbidity rates.

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      P1.16-14 - Impact of Smoking on Treatment Outcome in Early Squamous Cell Lung Cancer (T1N0)

      16:45 - 18:00  |  Presenting Author(s): Junghee Lee  |  Author(s): Tae Ho Kim, Byung Jo Park, Jong Ho Cho, Hong Kwan Kim, Yong Soo Choi, Jae Ill Zo, Young Mog Shim, Jhingook Kim

      • Abstract

      Background

      Smoking is the major risk factor for squamous cell lung cancer. However, squamous cell lung cancer in never-smoker is known to have poor survival outcomes. We compared clinicopathologic features and outcomes between smokers and never-smokers in resected early squamous cell lung cancer (T1N0).

      Method

      An institutional database was reviewed retrospectively between 1994 and 2016 (N = 445). Eligible patients included completely resected squamous cell lung cancer, less than 3 cm in tumor size, and without N1 or N2 involvements. Patients were stratified by gender and smoking status.

      Result

      423 (95%) smokers and 20 (5%) never-smokers were identified. The median age of never-smokers was 66 years (range, 39 - 83), and 11 of these patients were female (55%). The median age of smokers was 66 (range, 42 - 84), and most of them were male (97.9%). The T stage were distributed equally in both groups. In smokers, 84 (19.9%) patients experienced recurrence whereas only 1 patient (5%) of never-smokers occurred distant metastasis (p < 0.001). Distant metastasis was most frequent recurrence pattern in smokers (n= 40), but locoregional recurrence also a fairly frequent pattern (n = 30). The 5-year overall survival rates and recurrence free survival rates were 70.9% and 61.5% in smokers and were 64.1% and 64.1% in never-smokers respectively (p = 0.65, and 0.34, respectively).

      Conclusion

      There was no significant differences in clinicopathologic features and outcomes between smokers and never-smokers in early squamous cell lung cancer.

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      P1.16-15 - Evaluation of Emphysema Severity by 3D-CT for Predicting Postoperative Respiratory Complications and Prognosis of Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Yojiro Makino  |  Author(s): Yoshihisa Shimada, Sachio Maehara, Junichi Maeda, Masatoshi Kakihana, Naohiro Kajiwara, Tatsuo Ohira, Norihiko Ikeda

      • Abstract

      Background

      Emphysema is one of the main causes of respiratory complications and perioperative mortality and morbidity in lung cancer patients. We have used 3D-CT for depicting emphysematous areas as low attenuation areas (LAAs) and visual scores based on Goddard classification (Goddard score: GS). This study aimed to investigate the effectiveness of the 3D-CT function analysis of emphysema severity and its association with respiratory complications and prognostic outcomes.

      Method

      The study included 504 patients who underwent preoperative 3D-CT for surgical simulation followed by resection for lung cancer from October 2010 to March 2015. GS and LAA% (LAA / total lung volume) were measured using 3D-CT data. We studied the relationship between the development of postoperative respiratory complications/ overall survival (OS) and independent variables including age, sex, forced expiratory volume in 1 second as percent forced vital capacity (FEV1%), histology, smoking status, surgical procedure, GS, and LAA%.

      Result

      Postoperative respiratory complications were observed in 69 patients (13.6%). These included prolonged air leakage > 7 days (n = 22), pneumonia (n = 13), bronchial fistula (n = 4), atelectasis (n = 5), pulmonary fibrosis (n = 3), empyema (n = 5), recurrent nerve paralysis (n = 2), chylothorax (n = 5), pleural effusion (n = 3) and other respiratory-related adverse events (n = 7). The ROC curves for respiratory complications determined using the GS and LAA% dichotomized at each cut-off level (1 and 0.7%, respectively) showed that the events were observed in 32% of the patients with GS ≥ 1 and in 25% of the patients with LAA% ≥ 0.7. On multivariate analyses, the GS or LAA% was significantly correlated with postoperative respiratory complications (p < 0.001 and p = 0.016, respectively). Univariate and multivariate analysis using the Cox regression model for prognosis also showed GS was significantly associated with unfavorable OS among 362 patients with pathological Stage I NSCLC patients (p = 0.039). Five-year OS rates in these patients with or without emphysema were 84.0% and 94.1%, respectively (p < 0.001).

      Conclusion

      Preoperative measurement of GS and LAA% using 3D-CT in patients with lung cancer, particularly with the coexistence of emphysema, was beneficial for predicting postoperative respiratory complications and prognosis in lung cancer patients.

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      P1.16-16 - Automatic Intratumor Segmentation in CT of NSCLC: An Alternative to PET Metabolic Subregions

      16:45 - 18:00  |  Presenting Author(s): Qintao Qiu  |  Author(s): Jinghao Duan, Xue Sha, Guanzhong Gong, Yong Yin

      • Abstract

      Background

      PET images provide heterogeneous metabolic information in precision radiation treatment planning and the radiation dose given to high metabolic volumes should be escalated. However, PET scanning will increase the radiation dose received by patients. The aim of this study was to evaluated the feasibility of automatic intratumor segmentation in CT of NSCLC patients based on level-set evolution and cell automaton algorithm and assess the consistency with PET metabolic subregions.

      Method

      The PET and plan-CT imaging data set of 17 patients who have diagnosed with NSCLC were randomly collected. First, the gross tumor volume (GTV) was defined using a threshold of 40% SUVmax on PET. Then, rigid registration was used to align PET images to plan-CT images and the GTV was mapped to the CT image subsequently. The subregions which describe heterogeneity of voxel gray-level intensities were then automatic segmented using an algorithm combined level-set evolution and cell automaton in GTVCT. Meanwhile, the three metabolic subregions in GTVPET were delineated using threshold interval a) 40%-60% SUVmax, b) 60%-80% SUVmax, and c) 80%-100% SUVmax. To evaluate the consistency with PET metabolic subregions, we calculated the spatial overlap by Dice’s similarity coefficient (DSC).

      Result

      wclc-figure-jpg.jpg

      In total, 21 GTV pairs acquired from CT and PET data set were used to evaluate the feasibility of method proposed in this study. The GTVCT was automatically divided into three heterogenous subregions based on its difference on grays-level intensities and regional connectivity of voxel and 63 subregions were acquired. The average DSC value calculated from subregion in CT and PET is 0.725 with interval (0.321,0.905).

      Conclusion

      Our study revealed that there is a significant correlation between PET metabolic information and CT gray-level intensity. The automatic segmentation of subregion in CT images may can serve as an alternative to the metabolic region delineated in PET.

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      P1.16-17 - The Role of Quantitative Metabolic Metrics on FDG-PET/CT in Predicting Pathological Invasive Factors in cN0 Lung Adenocarcinoma

      16:45 - 18:00  |  Presenting Author(s): Takehiko Tanaka  |  Author(s): Yoshihisa Shimada, Yojiro Makino, Junichi Maeda, Masaru Hagiwara, Tetsuya Okano, Masatoshi Kakihana, Naohiro Kajiwara, Tatsuo Ohira, Jun Matsubayashi, Norihiko Ikeda

      • Abstract

      Background

      Growing evidence suggests that FDG-PET/CT has greatly contributed the preoperative investigation of early-stage lung cancer. The maximum standardized uptake values (SUVmax) of the primary lesion is widely reported to be associated with prognosis in NSCLC while other metabolic metrics, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been explored as a measure of metabolic tumor burden in recent years. The purpose of this study is to investigate the role of quantitative metabolic metrics in predicting the incidence of pathological invasive factors including microscopic vascular invasion, pleural invasion, and lymph node metastasis in cN0 lung adenocarcinoma.

      Method

      We examined 265 patients with clinical stage 0-II(cN0) adenocarcinoma. Pre-operative PET/CT and subsequent complete resection was performed for all the patients during the period from August 2012 to July 2017. The maximum tumor and solid-part diameter on HRCT and the three metabolic metrics on PET/CT measured by the SYNAPSE VINCENT (Fujifilm Medical, Tokyo, Japan) as the volume viewer softwarewere observed. In the current study, MTV was defined as the total tumor volume with an SUV > 2.5 while TLG was calculated as meanSUV x MTV. We assessed the relationship between these parameters and the incidence of pathological invasive factors.

      Result

      Among 265 patients, 18 (7%) patients were clinically staged as 0, 205 (77%) as IA, 32 (12%) as IB, and 10 (4%) as II, respectively. Pathological vascular invasion, pleural invasion, and lymph node metastasis were found in 100 (38%), 53 (20%), and 45 (17%) patients, respectively. SUVmax, MTV, and TLG were dichotomized at cut-off level by the receiver operating characteristic (ROC) curves for pathological invasive factors (SUVmax of 4.4, MTV of 0.75mm3, and TLG of 2.6, respectively). ROC curve yielded area under the curve values of 0.812, 0.915, and 0.882 for SUVmax, MTV, and TLG, respectively. Univariate analysis showed that SUVmax (Hazard Ratio (HR), 27.185; p<0.001), MTV (HR, 24.580; p<0.001), TLG (HR, 24.580; p<0.001), maximum tumor size (HR, 2.495; p<0.001), solid-tumor size (HR, 7.830; p<0.001), c-stage (HR, 14.418; p<0.001), and sex (HR, 1.882; p=0.013) were significantly associated with the incidence of pathological invasive factors. Multivariate analysis showed that SUVmax was the independent predictor (HR, 7.006; p=0.001). The frequency of pathological invasive factors of patients with SUVmax > 4.4, MTV > 0.75mm3, and TLG > 2.6 were 82%, 84%, and 84%, respectively.

      Conclusion

      In cN0 early-stage lung adenocarcinoma, the measurement of SUVmax, MTV, and TLG on FDG-PET/CT was beneficial for the prediction of pathological invasive factors.

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      P1.16-18 - Role of ERCC1/2 Single Nucleotide Polymorphism (SNP) on Treatment Response in Patients with Lung Cancer Undergoing Radiation Therapy

      16:45 - 18:00  |  Presenting Author(s): Yaping Xu  |  Author(s): Yaoyao Zhu, Chenxue Jiang, Yun Chen, Qinghua Xu, Jianguo Feng, JianYue Jin

      • Abstract

      Background

      Radiation therapy plays an important role in the treatment of lung cancer. The protein excision-repair cross-comlementation 1 (ERCC1) and protein excision-repair cross-comlementation 2 (ERCC2) are the key enzymes in NER pathway. Studies showed that ERCC1/2 were associated with susceptibility and efficacy of chemotherapy in lung cancer, but the association between ERCC1/2 SNPs and radiotherapy were seldom reported.

      Method

      Eighty-seven peripheral blood samples were collected from patients with NSCLC before they received radiotherapy in our department from November 2014 to October 2017. The peripheral blood leukocyte DNA was isolated and SNP genotypes were detected by competitive allele-specific PCR. Seven SNPs in ERCC1/2 were analyzed. Data was collected both before and after radiotherapy from blood serum. Elisa was used to detect ERCC1 expression. The association between the changes of expression of ERCC1 during radiotherapy and efficacy, risk of RILI and SNPs in ERCC1 was analyzed.

      Result

      ERCC1 re3212961 minor allele A was associated with a better response to radiotherapy in NSCLC patients. Survival analyses showed that G/G genotype had favorable OS than A/A genotype (P=0.012). Cox regression analysis indicated that ERCC1 rs11615 G/G genotype was associated with decreased risk of death. Subgroup analyses indicated that patients with G/G genotype who received high BED radiotherapy had better OS (median not reached vs. 21.5 months, 95%CI:15.3-27.7,P=0.011) and PFS (median not reached vs. 19.9 months, 95%CI:8.6-31.2,P<0.001) than low BED subgroup. There was no significant association between ERCC1/2 SNPs and RILI. The ERCC1 expression in serum was significantly increased after radiotherapy. However, the changes of ERCC1 expression showed no association with efficacy of radiotherapy, risk of RILI or SNPs of ERCC1/2.

      Conclusion

      ERCC1 rs3212961 was related with short-term curative efficacy. ERCC1 rs11615 was an independent prognostic factor in NSCLC, which could serve as biomarker, because G/G genotype had favorable OS and PFS, and was associated with decreased risk of death. There was no significant correlation between ERCC1/2 SNPs and RILI. The changes of ERCC1 expression after radiotherapy showed no association with efficacy of radiotherapy, risk of RILI or SNPs of ERCC1/2.

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      P1.16-19 - Neither Maximum Tumor Size nor Solid Component Size Was the Best Prognosticator for Subsolid Nodule

      16:45 - 18:00  |  Presenting Author(s): Erjia Zhu  |  Author(s): Chang Chen

      • Abstract

      Background

      Solid component size is used to define the T stage of subsolid nodule in the eighth edition TNM stage classification. Our study aimed to explore whether solid component size was the best parameter for T staging.

      Method

      We retrospectively reviewed the clinical data of 431 cTis-T3N0M0 subsolid nodule from Shanghai Pulmonary Hospital. Maximum tumor size, solid component size and tumor size in mediastinal window were carefully recorded. Prognostic ability of different turmor size was compared by time-dependent receiver operating curve.

      Result

      Survival revealed maximum tumor size, solid component size and tumor size in mediastinal window were statistical significant predictors. However, solid component size performed the worst of them, relatively.wclc 3.tiffwclc 2.jpg

      Conclusion

      Tumor size remains a common used parameter for nodule evaluation. Solid component size maybe not the best parameter for T staging.

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      P1.16-20 - A Systematic Review and Meta-Analysis of Stereotactic Body Radiation Therapy Versus Surgery for Patients with Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Christopher Cao  |  Author(s): Andreas Rimner, James Huang, David R. Jones

      • Abstract

      Background

      Stereotactic body radiation therapy (SBRT) is the preferred treatment modality for patients with inoperable early-stage NSCLC. However, comparative outcomes of SBRT versus surgery for high-risk patients remain controversial. The primary aim of the present meta-analysis was to assess the overall survival of SBRT versus surgery in matched and unmatched patient cohorts. Secondary endpoints included cancer-specific survival, disease-free survival, disease recurrence, and perioperative outcomes.

      Method

      A systematic review was performed through online databases using predefined criteria. The most updated studies were selected for meta-analysis according to unmatched and matched patient cohorts.

      Result

      Thirty-two studies were identified in the systematic review. Surgery was associated with superior overall survival in both unmatched (OR 2.49, 95% CI 2.10–2.94, p<0.00001) and matched (OR 1.71, 95% CI 1.52–1.93, p<0.00001) cohorts. Cancer-specific survival, disease-free survival, and freedom from locoregional recurrence were found to be superior after surgery compared to SBRT, in both unmatched and matched cohorts. However, SBRT was associated with fewer perioperative mortalities.

      figure 1.png

      pic final.png

      Conclusion

      Current evidence suggests that surgery is superior to SBRT in mid- and long-term clinical outcomes. However, improved outcomes after surgery may at least be in part due to an imbalance of baseline characteristics. Mortality outcomes for SBRT were also more favorable in the perioperative period.

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      P1.16-21 - Phase I / II Study of Carboplatin, Nab-Paclitaxel, and Concurrent Radiotherapy for Patients with Locally Advanced NSCLC

      16:45 - 18:00  |  Presenting Author(s): Yuko Kawano  |  Author(s): Tomonari Sasaki, Hiroyuki Yamaguchi, Katsuya Hirano, Makoto Nishio, Miyako Satouchi, Shinobu Hosokawa, Ryotaro Morinaga, Kazutoshi Komiya, Kouji Inoue, Yuka Fujita, Ryo Toyozawa, Tomoki Kimura, Kosuke Takahashi, Kazuo Nishikawa, Junji Kishimoto, Yoichi Nakanishi, Isamu Okamoto

      • Abstract

      Background

      We performed an open-label, multicenter phase I/II study (UMIN ID 000012719) to prospectively evaluate the efficacy and safety of the combination of nab-paclitaxel plus carboplatin (nab-P/C) with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer.

      Method

      In the phase I study (standard 3+3 design), escalating doses of weekly nab-paclitaxel were given along with weekly carboplatin area under the plasma concentration time curve (AUC) 2 and concurrent radiotherapy 60 Gy in 30 fractions, followed by 2 cycles of nab-paclitaxel (100 mg/m2 on Days 1, 8 and 15) plus carboplatin (AUC 6 on Day 1). In the phase II study, nab-P/C at recommend dose (RD) was administered.

      Result

      In the Phase I study, 11 patients were enrolled with 9 evaluable for dose limiting toxicity (DLT). At level 1 (nab-paclitaxel 40mg/m2), none of 3 patients experienced DLT. At level 2 (nab-paclitaxel 50mg/ m2), 1 of 6 patients experienced DLT: grade 3 leukopenia requiring a second consecutive skip in the administration of weekly nab-P/C. Level 2 was defined as the RD. A total of 56 patients including 6 patients who received at dose of RD, were evaluable for the efficacy and safety. Of the 56 patients for safety analysis, common toxicities in the concurrent phase included grade 3/4 leukopenia (60.7 %), neutropenia (26.8 %), anemia (7.1 %), anorexia (7.1 %), esophagitis (5.4 %) and febrile neutropenia (1.8 %). In one patient, grade 3 pneumonitis was observed. There were no treatment-related deaths. The objective response rate was 76.8 % (95% confidence interval (CI), 64.2 to 85.9 %). The median progression-free survival was 11.8 months (60% CI, 10.6 to 16.2 months, 95% CI, 8.2 to 20.8 months), and the median overall survival was not reached.

      Conclusion

      This is the first study to demonstrate encouraging feasibility and activity for concurrent chemoradiation with nab-paclitaxel 50 mg/m2 and CBDCA AUC 2 in patients with locally advanced NSCLC.

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      P1.16-22 - Meta-Analysis of Stereotactic Ablative Radiotherapy Versus Surgery for Early Stage Lung Cancer.

      16:45 - 18:00  |  Presenting Author(s): Janusz Kowalewski  |  Author(s): Maciej Dancewicz, Mariusz Kowalewski

      • Abstract

      Background

      The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 randomized controlled trials (RCTs) included few patients and closed early due to slow accrual. We aimed to assess overall survival with SABR versus surgery by pooling data from RCTs and adjusted observational studies.

      Method

      We performed a systematic review and meta-anaysis according to PRISMA (Preferred Items Reporting for Systematic Reviews and Meta Analyses) guidelines. The search process covered a period untill 28th of February 2018. Search terms were: SABR, stereotactic body radiation therapy, radiotherapy, lung-, pulmonary- cancer. Studies comparing SABR vs surgery for NSCLC were ellegible if reported adjusted survival data. Approaches including propensity scoring, inverse probability weighting and multivariate regressions were only considered. Survival was calculated by pooling available Hazard Ratios (HRs) in random-effects model. Studies were then stratified based on their design (RCT[s] vs Adjusted nRCT[s]). HRs were digitized from the available Kaplan-Meier curves.

      Result

      12031.jpgNineteen studies were retrieved that enrolled 23,534 patients. Among them two RCTs (N=58 pts). In overall analysis SABR was associated with significantly worsened survival as compared to surgery group: HR (95%CIs): 1.64 (1.38-1.94); p<0.001; when analyzed separately, adjusted nRCT[s] favored surgery: HR for comparison SABR vs surgery: 1.66 (1.40-1.97); p<0.001; among RCTs only, SABR was associated with a statistical trend for improved survival: HR (95%CIs): 0.14 (0.02-1.17); p=0.07. There were significant statistical differences between RCTs and adjusted nRCTs Pinteraction=0.02.

      Conclusion

      SABR could be an option for treating early stage NSCLC but there was significant discrepancy between RCTs and non-RCTs regarding survival after SABR as compared to surgery; more adequately powered randomized studies are needed before conclusions on efficacy of SABR can be drawn.

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      P1.16-23 - Long-Term Survival Analysis of Surgery in Potential Stereotactic Ablative Radiotherapy Candidates of Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Shaolei Li  |  Author(s): Shanyuan Zhang, Yuanyuan Ma, Yue Yang

      • Abstract

      Background

      The aims of this study were to evaluate the long-term survival outcomes and strengthen the primacy of surgery in potential stereotactic body radiotherapy candidates.

      Method

      A total of 541 patients with clinical stage I peripheral non-small cell lung cancer from January 2005 to December 2014 were enrolled in the current study. All patients who were potential stereotactic ablative radiotherapy candidates underwent lobectomy and systematic lymph node dissection including level 13 and 14 without preoperative therapy. According to the recommendation of the 8th edition of TNM stage, combined with our own experience, we divided the N stage into N1a (only level 13-14 positive), N1b (level 10-12 positive), N2a1 (skip single N2), N2a2 (single N2 with N1) and N2b (multiple N2). Survival curves were estimated by the Kaplan–Meier method.

      Result

      Among all patients, 25.0% had occult lymph node involvement, 12.8% were N1 and 12.2% were N2. Among 32 T1a patients only 1 case (3.0%) patients had N1a positive without other N positive. In 104 cases of T1b, the positive rates of N1a, N1b, N2a1, N2a2 and N2b were 0.8%, 5.9%, 0.8%, 2.5% and 1.7%, respectively. Among the 86 patients with T1c, the positive rate of each station was 5.4%, 11.5%, 3.8%, 8.5%, and 4.6%, respectively. Of the 184 patients with T2a, N1 accounted for 14.6% , and N2 accounted for 11.5%. The 3-year, 5-year and 10-year disease free survival (DFS) of all 541 clinical stage I patients were 82.8%, 74.0%, 64.7%, and the overall survival (OS) were 91.3%, 85.4% and 77.0% respectively. The 3-year, 5-year and 10-year DFS of postoperatively pathological stage I patients were 90.0%, 81.0%, 72.5%, and the OS were 94.4%, 91.1% and 85.0%, respectively.

      T /N category

      N0

      N1a

      N1b

      N2a1

      N2a2

      N2b

      1a

      32(97.0%)

      1(3.0%)

      0

      0

      0

      0

      1b

      104(88.1%)

      1(0.8%)

      7(5.9%)

      1(0.8%)

      3(2.5%)

      2(1.7%)

      1c

      86(66.2%)

      7(5.4%)

      15(11.5%)

      5(3.8%)

      11(8.5%)

      6(4.6%)

      2a

      184(70.8%)

      13(5.0%)

      25(9.6%)

      8(3.1%)

      12(4.6%)

      18(6.9%)

      Conclusion

      In view of the high rate of lymph node metastasis in clinical stage I lung cancer, surgical resection is still the preferred treatment.

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      P1.16-24 - Impact of Tumor Location &amp; Dosimetric Predictors for Chest Wall Toxicity in Single Fraction SBRT for Stage I Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Gregory M.M. Videtic  |  Author(s): Bindu Manyam, Kyle Verdecchia, Chandana A. Reddy, Neil M Woody, Tingliang Zhuang, Kevin L Stephans, Aditya Juloori

      • Abstract

      Background

      Single fraction stereotactic body radiation therapy (SF-SBRT) is an acceptable regimen for treatment of peripheral Stage I Non-Small Cell Lung Cancer (NSCLC). Rates of chest wall toxicity (CWT) are not stratified by distance of tumor to chest wall (CW) and dosimetric parameters are not well defined. We sought to determine the relationship of tumor location and dosimetric parameters with CWT in SF-SBRT.

      Method

      An IRB-approved prospective SBRT registry of 1,462 patients (pts) was used to identify pts treated with 30 Gy or 34 Gy in one fraction. Tumors were ≤ 5 cm, node-negative, and ≥ 2 cm from the proximal tracheo-bronchial tree. The CW was retrospectively contoured (3 cm soft-tissue structure). Gross tumor volume was measured as abutting, ≤ 1 cm, 1-2 cm or > 2 cm from the CW. CWT was graded according to CTCAE 3.0 criteria. Rates of CWT were compared using unpaired t-test. Logistic regression analysis was used to identify tumor and dosimetric parameters associated with CWT.

      Result

      This study included 146 lesions treated with SF-SBRT. Median follow-up was 23.8 months. There were 80 pts (55%) treated with 30 Gy and 66 pts (45%) treated with 34 Gy. The rate of CWT was 30.6% for lesions abutting CW, 8.2% for ≤ 1 cm from CW, 3.8% for 1-2 cm from CW, and 5.7% for > 2 cm from CW. Grade ≥ 3 CWT was modest (1.4%). Tumor abutment (OR 6.5; p=0.0005), BMI (OR 1.1; p= 0.02), rib D1cc (OR 1.01 per Gy; p= 0.03), CW D1cc (OR= 1.08 per Gy; p=0.03), and CW D5cc (OR 1.10 per Gy; p= 0.01) were significant predictors for CWT on univariate analysis. Tumor abutment was the only significant predictor for CWT (OR 7.5; p= 0.007) on multivariate analysis. CWT occurred in only 1 out of 40 pts with CW D5cc < 18 Gy, while our model suggested a 15% risk of CWT with D5cc of 27.2 Gy to CW.

      Conclusion

      The rate of CWT is significantly associated with distance from the CW. When considering lesions adjacent to the CW, the rate of CWT in this series (30.6%) does not appear to exceed rates in the published fractionated SBRT literature (20-33%). Location adjacent to CW should not be a contraindication to SF-SBRT. CW D1cc and D5cc may be used as predictors of CWT rates. As most CWT is low-grade and self-limited, these dosimetric parameters should be utilized as a guideline, rather than an absolute constraint.

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      P1.16-25 - A Propensity Score Model for Appropriate Treatment Selection (Sublobar Resection vs. SBRT) In Patients With cStage I NSCLC

      16:45 - 18:00  |  Presenting Author(s): Yukinori Matsuo  |  Author(s): Toyofumi Fengshi Chen-Yoshikawa, Masatsugu Hamaji, Takamasa Mitsuyoshi, Takashi Shintani, Yusuke Iizuka, Makoto Sonobe, Hiroshi Date, Takashi Mizowaki

      • Abstract

      Background

      Stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) are current treatment options for patients with cStage I non-small-cell lung cancer (NSCLC) who are operable, but at high risk for lobectomy. However, optimal selection of the two treatments remains controversial. Purposes of this study are to identify pre-treatment factors affecting treatment decision and to evaluate their impact on outcomes.

      Method

      We retrospectively reviewed patients who underwent SBRT or SLR for cStage I NSCLC because of medical comorbidity between 2003 and 2009. Patients who were with performance status of 2 or worse, those who had no data on pre-treatment pulmonary function test, or those who had no histological confirmation of NSCLC were excluded. A propensity score (PS) model of treatment decision (0 toward SBRT, and 1 toward SLR) was generated using stepwise logistic regression incorporating pre-treatment factors.

      Result

      Ninety-two and 65 patients who underwent SBRT and SLR, respectively, were enrolled into this analysis. Median potential follow-up period was 8.6 years. The following factors remained in the PS model after stepwise selection: age, sex, Charlson comorbidity index (CCI), body mass index (BMI), forced expiratory volume in 1 second (FEV1) and tumor diameter. Old age, male, CCI of 1 or more, underweight BMI and large tumor had coefficients toward SBRT (Table).

      In a cohort with PS of 0.5 or more, overall survival was significantly better in SLR patients than in SBRT patients (79.5% and 47.5% at 5 years, respectively; P = 0.004). In a cohort with PS<0.5, whereas, overall survival was similar between SLR and SBRT (43.3% and 39.7% at 5 years, respectively; P = 0.805).

      Coefficients for propensity score
      Factors Coefficients
      (Intercept) (3.95)
      Age per 10y -0.53
      Sex female 0 (ref)
      male -0.62
      CCI 0 0 (ref)
      1 -0.41
      >=2 -0.97
      BMI underweight -0.98
      normal 0 (ref)
      overweight 0.44
      FEV1 per 1L 0.84
      Tumor diameter per 1cm -0.34

      Conclusion

      The PS model would help appropriate treatment selection for high-risk operable patients. Although patients with PS of 0.5 or more benefit from SLR, SBRT provides comparable outcomes for patients with PS<0.5.

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      P1.16-26 - Safety of SABR (Stereotactic Ablative Body Radiotherapy) for Central Non-Small Cell Lung Cancers (cNSCLC) with 50 Gray in 5 Fractions (50Gy/5f)

      16:45 - 18:00  |  Presenting Author(s): Robert Rulach  |  Author(s): Jonathan Hicks, Graeme Lumsden, Stephen McKay, Vivienne Maclaren, Jennifer Macphee, Karen Moore, Margaret Omand, Michael Sproule, Suzanne Currie, Andrew Aitken, Richard Ferguson, Peter Houston, Ronan Valentine, Stephen James Harrow

      • Abstract

      Background

      SABR using 60Gy/3f (or equivalent) caused high toxicity when used for cNSCLC. To determine a safe SABR dose for cNSCLC, the phase I/II RTOG 0813 trial used 50Gy/5f as a baseline. From 2013, 50Gy/5f was adopted for inoperable early-stage cNSCLC at the West of Scotland Cancer Centre, a tertiary-level oncology unit. We report our prospectively collected toxicity and efficacy data.

      Method

      Patients with cNSCLC were identified from the radiotherapy database. cNSCLC was defined as lung cancers within 2cm of the proximal bronchial tree, or the planning target volume (PTV) abutting the mediastinal pleura/pericardium. Patient and treatment characteristics were obtained from electronic medical records. All patients received 50Gy/5f on alternate days with a volumetric arc therapy plan using TrueBeam linear accelerators. Toxicity was assessed in a centralised follow-up clinic 2 weeks, 6 weeks, 3 months, 6 months, 1 and 2 years after treatment using Common Toxicity Criteria Adverse Events version 3. Patients had a CT scan at 3 months post-treatment. Subsequent CT scans were at the discretion of the treating clinician.

      Result

      50 patients (31 females, 19 males, median age 75.1 years old) were identified with T1-2N0M0 cNSCLC. 84% were medically unfit for surgery. 40% had biopsy-proven NSCLC. All patients completed treatment on schedule. Two patients died within 90 days of treatment, one from a chest infection, the other cause of death was unknown. Table 1 describes the early and late toxicity. Over a median follow-up of 24 months, there were 20 deaths, 8 unrelated to cancer, and 12 due to cancer recurrence. The median progression free survival and overall survival are 26.0 months (95% confidence interval: 16.4, 35.6 months) and 28.6 months (95% confidence interval: 21.3, 35.8 months) respectively.

      world lung abstract table 1.jpg

      Conclusion

      This study has demonstrated that 50Gy/5f is a safe dose and fractionation for early-stage inoperable cNSCLC, with outcomes comparable to other series.

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      P1.16-27 - Using Rates of Clinical Brachial Plexopathy after Lung SBRT to Better Characterize the Tolerance of the Brachial Plexus

      16:45 - 18:00  |  Presenting Author(s): Kyle Verdecchia  |  Author(s): Bindu Manyam, Chandana A. Reddy, Kevin Rogacki, Tingliang Zhuang, Gregory M.M. Videtic, Kevin L Stephans

      • Abstract

      Background

      Treatment of apical lung tumors with stereotactic body radiation therapy (SBRT) can be challenging due to proximity to the brachial plexus (BP). We retrospectively investigated outcomes after treatment of apical lung tumors to compare the rate of brachial plexopathy (BPX) with what would be estimated based on published protocol-derived BP constraints.

      Method

      Apical lung tumors were defined in this analysis as those whose lung SBRT target had a planning-derived PTV edge <1cm from the anatomic BP. We surveyed an IRB-approved prospective registry of 1,462 patients treated with SBRT for the interval 2003-2017 and included all patients who received definitive or salvage SBRT using dose/fractionation schedules of 50 Gy/5 fx, 60 Gy/5 fx, or 48 Gy/4 fx. Salvage SBRT included patients with local recurrence after conventional fractionation radiotherapy. Per RTOG protocols, the subclavian vein (SCV) ipsilateral to target was contoured as the BP surrogate. In this study, the ipsilateral subclavian artery (SCA), and BP were also contoured to characterize dosimetric differences between structures. Statistical analysis involved repeated measures ANOVA.

      Result

      Sixty-four patients, which includes six patients (9.4%) receiving salvage SBRT, met inclusion criteria (median follow up of 21 months). No significant differences (p=0.77) were observed between maximum point doses to BP, SCV, and SCA. Within one year post-SBRT, two patients (3%) developed BPX (grade 2); both patients had exceeded 32 Gy to the BP and were treated with salvage SBRT. No patient treated with definitive SBRT (91%) developed BP, despite 17 of these exceeding recommended maximum doses.

      Conclusion

      No BPX was observed for patients that exceeded a maximum dose of 32 Gy to the BP, unless they were treated as salvage SBRT. This suggests higher doses to the BP may be considered when clinically required for definitive SBRT. However, salvage SBRT may require more conservative BP constraints than used in the definitive setting.

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      P1.16-28 - The Impact of Spironolactone on the Lung Injury Induced by Concomitant Trastuzumab and Thoracic Radiotherapy

      16:45 - 18:00  |  Presenting Author(s): Guler Yavas  |  Author(s): Cagdas Yavas, Esin Celik, Erdem Sen, Ozlem Ata, Deniz Yuce, Rengin Elsurer-Afsar

      • Abstract

      Background

      Radiation-induced lung injury (RILI) is a potentially life-threatening and dose-limiting side effect of thoracic irradiation. Trastuzumab (T), a monoclonal antibody directed against HER2, improves overall survival in patients with HER2 positive breast cancer. T concurrently with radiation thus increases the antitumor effect of radiation. There are same clinical evidences in the literature that T also radiosensibilizes human healthy tissues and in this way it could increase the toxicity of the treatment. The incidence of T-induced pneumonitis is 0.4–0.6%. Although infrequent; pulmonary toxicity due to T may be life-threatening. Aldosterone, which is a physiological activator of MR, is partially responsible for increases in the extracellular matrix turnover, as observed in fibrosis of the cardiac, kidney and lung tissues, and exerts its effects primarily on lung epithelium. Spironolactone (S), an aldosterone receptor antagonist, may have the ability to ameliorate pulmonary fibrosis.We hypothesized that S would be effective in the treatment of both RT and T-induced lung injury by correcting pulmonary fibrosis

      Method

      This study included 80 female Wistar-Albino rats (250-300 g); use of which was approved by the Ethical Committee. Rats were divided into eight groups: group (G) 1 was control group; G2, G3 and G4 were RT, S and T groups; G5, G6, G7 and G8 were RT+T, T+S, RT+S and RT+T+S groups respectively. RT was applied under general anesthesia with intraperitoneally administered 90 mg/kg ketamine hydrochloride and 10 mg/kg xylazine. A single dose of 15 Gy was applied to the both lungs. T (6 mg/kg) was administered intraperitoneally and S (80 mg/kg) was administered by oral gavage. Rats were sacrificed via cervical dislocation at 6th hour, 21st day and 100th day after RT and the lung samples were taken for microscopical examination.

      Result

      By 100th days of RT inflammation score, lung fibrosis score and TGF- expression were significantly different within study groups (p values were 0.002, 0.001 and 0.043 respectively). Inflammation score of G8 was significantly lower than inflammation scores of G2 and G5 (p values: G2-G8= 0.004, and G5-G8=0.022). Inflammation score of G2 was significantly higher than G7 (p=0.028). There were significant differences regarding to fibrosis scores between G2-G8 (p=0.015), G2-G7 (p=0.017) and G5-G8 (p=0.011). TGF-β expression was higher in both G2 and G5 when compared to G8 (p = 0.038).

      Conclusion

      Our results suggested that S is an effective treatment option for improving radiation-induced pulmonary fibrosis. These findings should be clarified with further preclinical and clinical studies.

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      P1.16-29 - Accelerated Hypofractionated Radiotherapy for Central Lung Tumors Unsuitable for Stereotactic Body Radiotherapy Or Concurrent CRT

      16:45 - 18:00  |  Presenting Author(s): K. Liang Zeng  |  Author(s): Ian Poon, Yee Ung, Liying Zhang, Patrick Cheung

      • Abstract

      Background

      In our institution, accelerated hypofractionated radiotherapy is a treatment option for 1) stage I lung non-small cell lung cancer (NSCLC) patients whose tumors are too bulky or central for SBRT; and 2) select stage II-III NSCLC patients not candidates for concurrent CRT. The purpose of this project was to review the clinical outcomes of a large single institutional experience of treating such patients with a dose of 60 Gy in 15 fractions in an era when SBRT was routinely used in clinical practice for early stage lung cancer.

      Method

      Central tumors were defined as the gross target volume being in contact with mainstem bronchi, trachea, esophagus, great vessels, or heart. All patients who received 60 Gy in 15 fractions treated between 2008 and 2017 were reviewed. Competing risk analysis was used to calculate the cumulative incidence of local failure (LF), regional failure (RF), and distant failure (DF). Kaplan-Meier methodology was used to calculate overall survival (OS). Univariate analyses were used to look for potential predictive factors.

      Result

      Eighty-nine patients were treated. Median follow-up was 24.0 months (range: 6.1-94.2 months). Median age was 79.4 years and most tumors were adenocarcinoma (n=47, 52.8%), followed by squamous cell carcinoma (n=31, 34.8%). Thirty patients (33.7%) had stage I disease, 47 patients (52.8%) had stage II-III disease, and 12 patients (13.5%) had stage 4 disease (mostly oligometastatic). Cumulative incidence of LF was 15.3% at 2 years. In those with stage I-III disease, cumulative incidence of RF and DF were 12.9%, and 28.5%, respectively at 2-years. OS was 74.9% at 2 years, with a median OS of 39.4 months for those with stage I-III disease. In the subset with stage II-III disease, median OS was 38.1 months and 2 year OS was 67.7%. Tumor stage, histology, EGFR mutation status, and location were not statistically significant predictors for any outcomes, although tumor size >3.5cm was borderline significant in predicting for a higher cumulative incidence of LF (subdistribution hazard ratio = 2.726; 95% confidence interval 0.995-7.469; p=0.051). The most common toxicity was radiation pneumonitis (n=6, 6.4%). The cumulative incidence of any grade 3 toxicity was 10.8% at ≥ 1 year. There were no deaths or hospitalizations directly attributed to treatment.

      Conclusion

      Accelerated hypofractionated radiotherapy to a dose of 60 Gy in 15 fractions resulted in favorable outcomes in NSCLC patients who were not suitable for SBRT or concurrent CRT. Patients with Stage II-III disease had good OS despite not receiving concurrent chemotherapy. Severe toxicities were uncommon.

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      P1.16-30 - Quality of Lymphadenectomy During Lobectomy for Non-small Cell Lung Cancer: VATS Versus Thoracotomy

      16:45 - 18:00  |  Presenting Author(s): Raquel Sâmia Gonzaga Alves  |  Author(s): Etienne Bourdages-Pageau, Charles-Antoine Paradis-Garneau, Arthur Vieira, Paula Ugalde

      • Abstract

      Background

      Lobectomy by video-assisted thoracoscopic surgery (VATS) is preferred over thoracotomy in patients with early-stage non-small cell lung cancer (NSCLC). However, controversy still exists regarding the quality of the lymph node dissection accomplished using VATS. This study analyzed the lymphadenectomy by surgical approach and applied the International Association of the Study of Lung Cancer (IASLC) criteria of lobe-guided lymphadenectomy.

      Method

      We performed a retrospective review of patients with stage I or II NSCLC who underwent lobectomy via thoracotomy (2003-2007, n=408) or VATS (2014-2017, n=754) at our institution. We compared the lymph node stations dissected by lobe-specific and the outcomes between the two approaches.

      Result

      VATS was equal or superior to thoracotomy for dissection of all lymph node stations except stations 8R (p=0.0018) and 8L (p=0.0002) and was superior for subcarinal lymphadenectomy (p=<.0001). When examined by lung lobe(s), VATS was superior for lymphadenectomy during right upper lobectomies (p=<.0001) and at least equal to thoracotomy for all other lobes. Additionally, VATS was associated with less blood loss (p=<.0001), pneumonia (p=0.0008) and acute respiratory distress syndrome (p=0.0082), fewer air leaks (p=<.0001) and lower 30-day mortality (p=0.0308).

      results table.png

      Conclusion

      At our institution, the transition from thoracotomy to VATS lobectomy for early-stage NSCLC did not negatively impact the quality of the lymph node dissection. Moreover, VATS significantly improved surgical outcomes.

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      P1.16-31 - Surgically Resected Acinar Adenocarcinoma of the Lung: Analysis of Different Prognostic Groups.

      16:45 - 18:00  |  Presenting Author(s): Pietro Bertoglio  |  Author(s): Andrea Viti, Giuseppe Salvatore Bogina, Carlo Pomari, Giuseppe Zamboni, Alberto Terzi

      • Abstract

      Background

      Adenocarcinoma has become the most frequently diagnosed histotype of Non-Small cell Lung Cancer (NSCLC). Nevertheless, the latest classification of lung adenocarcinoma issued by IASLC/ATS/ERS identified different subtypes with different prognostic impact; concurrently, different subtypes might mingle influencing biological features and behavior. We focused on surgically treated stage I and II predominantly acinar lung adenocarcinoma analyzing outcomes and prognostic factors according to the second main histological pattern.

      Method

      We retrospectively collected all lung adenocarcinoma with a predominant acinar histological pattern operated on between October 2012 and September 2017 in our institution. We selected all patients in pathological stage I A-B and II A-B with full preoperative staging procedures performed at our institution. All clinical and pathological features were registered. We analyzed outcomes according to the histological sub pattern and we focused on main prognostic factors.

      Result

      During the study period we performed 153 lung resections for patients affected by NSCLC. Among them we found 93 adenocarcinoma and 55 had a predominant acinar pattern. Among selected patients, there were 33 female and the mean age was 68.2 (SD±9.3) years. The histology report showed a solely acinar pattern in 11 cases (20.0%), while a second main sub-pattern was seen in the remaining cases: papillary or micropapillary in 7 cases (12.7%); lepidic in 27 cases (49.1%) and solid in 10 (18.2%). Mean Overall Survival (OS) and Disease-Free Survival (DFS) of all the cohort of patients were 66.1 (CI 95% 59.7-72.4) and 51.9 (CI 95% 42.7-61.2) months respectively. According to the secondary histological pattern, papillary and micropapillary subtypes showed a significant worse OS (p=0.029) and DFS (p=0.015) compared to all the other subtypes; concurrently they showed a significant higher mean Standard Uptake Value of T component at the preoperative PET-CT (11.8 vs 6.4, p=0.007) and had a higher rate of vascular invasion at the specimen (P=0.002). Beyond papillary and micropapillary subtypes, vascular invasion showed to be a significant prognostic factor both for OS and DFS.

      Conclusion

      Lung adenocarcinoma encompasses different sub-histotypes. In our experience, stage I and II resected predominantly acinar adenocarcinoma with papillary or micropapillary component showed higher rate of vascular invasion in the specimen and worse long-term outcomes compared to other subtypes, which might be related with a higher aggressiveness. In conclusion, our results suggest that different postoperative management should be adopted according to adenocarcinoma histological subtypes pattern; histology patterns should also be considered as a prognostic factor to be included in the NSCLC staging system.

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      P1.16-32 - Lung Cancer Completeness of Resection in Uniportal Versus Multiportal Video-Assisted Thoracoscopic Surgery Lobectomy

      16:45 - 18:00  |  Presenting Author(s): Etienne Bourdages-Pageau  |  Author(s): Raquel Sâmia Gonzaga Alves, Arthur Vieira, Charles-Antoine Paradis-Garneau, Yves Lacasse, Paula Ugalde

      • Abstract

      Background

      In 2005, the International Association for the Study of Lung Cancer (IASLC) added a new category to complete and incomplete resection for residual tumor classification (R): uncertain resection (R(un)). R status has a major prognostic impact, and the prognosis of patients with a R(un) resection differs from that of patients with either complete (R0) or incomplete resection (R1 or R2). The aim of this study was to measure R status with the expanded classification system when performing lobectomy for non-small cell lung cancer (NSCLC) using a uniportal (U-VATS) or multiportal (M-VATS) video-assisted thoracoscopic surgery.

      Method

      From August 2014 through December 2017, 672 VATS lobectomies were performed for the primary treatment of clinical stage I and II NSCLC, 43 patients with ground glass opacity or complex cases were excluded. Patients were analyzed according to ports used (one or multiple), R status, lobe-specific lymphadenectomy, subcarinal lymphadenectomy, length of hospital stay and length of thoracic drainage. A propensity-matched analysis was planned however, all variables were evenly distributed in both groups.

      Result

      Of 629 VATS lobectomies, 234 (37%) were performed with U-VATS and 395 (63%) with M-VATS. Most resections were classified as R(un) (84%); 2% were incomplete. When compared with M-VATS, U-VATS was associated with superior completeness of resection (p=0.0159), superior lobe-specific lymphadenectomy (p=0.0004), and superior subcarinal lymphadenectomy (p=0.0064). The highest mediastinal lymph node station dissected was not different between the approaches. The patients who underwent U-VATS had shorter hospital stays (mean: 4.4 days vs 6.2 days, p=0.0001) and less thoracic drainage (mean: 4.7 days vs 5.8 days, p=0.0004). There was no difference in operative mortality (p=0.3024) (Table 1).

      results.png

      Conclusion

      In our institution, most VATS lobectomies were uncertain resections due to the lymph node evaluation by IASLC definition. Using U-VATS is not inferior to M-VATS in accomplishing a complete oncologic resection thoracoscopically.

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      P1.16-33 - Occult Lymph Node Metastases in Early Stage NSCLC Patients: Where Do We Stand Now? A Proposal for a Preoperative Risk Model

      16:45 - 18:00  |  Presenting Author(s): Giuseppe Cipollone  |  Author(s): Mirko Barone, Decio Di Nuzzo, Massimo Ippoliti, Barbara Maggi, Luigi Guetti, Pierpaolo Camplese, Duilio Divisi, Piergiorgio Solli, Roberto Crisci, Felice Mucilli

      • Abstract

      Background

      Notwithstanding mediastinal lymphadenectomy is a cornerstone of surgical management of primary lung tumors, results and evidences are still debated for clinical stage I disease. In this aspect, current guidelines appear conflicting, as being both radical lymph node dissection and systematic node sampling equally advocated by several Authors. However, though lymphadenectomies are not risk-free procedures, N-status is an undoubted and significant prognostic factor in NSCLC patients. For these reasons, the adoption of a preoperative predictive non-invasive model should be clinically useful to stratify patients according to risk of lymphatic metastases.

      Method

      A multicentre retrospective study from January 2014 to June 2017 enrolling 2502 early stage NSCLC patients (up to cIB disease) with a mean age of 67.35 ± 8.89 years was conducted by analysing demographic, radiological and pathological features and correlating themselves to pN+ disease through a bivariate analysis, relative risk estimation and Receiver Operative Curves estimation. Diagnostic performance of a derived risk coefficient (RC = Σ factors) was finally evaluated.

      Result

      With a mean Charlson’s Comorbidity Score of 4.34 ± 1.80 and an excellent ECOG Status (ECOG 0-1) in 98.1%, 66.2% presented a very early stage disease (cT1a/b N0 M0) with predominant solid nodule density at chest CT (n. 1992 – 79.6%) and a mean SUVmax of 4.37± 4.95. Each patient underwent a R0 video-assisted thoracoscopic lobectomy with a radical node dissection in 69.9% and a systematic lymph node sampling in remaining cases. Concerning with histology, primary pulmonary invasive adenocarcinoma was the predominant pattern (n. 1417 56.6%) and a cumulative incidence of occult hilar-mediastinal lymph node metastases of 8.8% was reported. At bivariate analysis and relative risk estimation, male gender (p=0.033), clinical T-stage (p=0.000), nodule diameter (p=0.000), nodule density (p=0.005), the presence of visceral pleura or bronchial invasion (p=0.000) and a SUV max >3.5 (p=0.001) significantly correlated with pN+ disease. By deriving a risk coefficient function and adopting it to general population through a ROC curve, a RC > 58 presented a not negligible predictive value (sensibility: 82.73%, specificity 74.36%, PPV 23.73%, NPV 97.81%).

      Conclusion

      Although a prospective study is needed, a preoperative clinically easily reproducible predictive model for early stage NSCLC patients should represent a useful tool for a proper stratification of pN+ high risk patients. In particular, by considering its high negative predictive value, the aforementioned risk coefficient could allow to discriminate low risk cohort patients amenable to limited lymph node assessment rather than radical dissections with their fearsome related risks.

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      P1.16-34 - The Impact of Pathology, Staging and Operative Resection on Survival and CT Evidence of Recurrence of Early NSCLC

      16:45 - 18:00  |  Presenting Author(s): Richard John Finley  |  Author(s): John Mayo, Carol Donagh, Joyce Leo, Kyle Grant, Stephen Lam, John English

      • Abstract

      Background

      The purpose of this study is to determine the impact of histopathology, staging and extent of operative resection on survival and CT evidence of recurrence of early NSCLC excised with VATS wedge resection guided by preoperative CT-guided microcoil localization (CTML) and intra-operative fluoroscopic guidance.

      Method

      Between April 2003, to June 2012, 106 of 154 patients who underwent CTML and VATS resection of suspicious pulmonary nodules were found to have NSCLC. Serial chest CTs of the 106 patients with confirmed NSCLC were reviewed by 2 chest radiologists for development of recurrence of the original cancer at the resection margin, lung or mediastinum and the development of new primary lung cancer. 53 patients underwent CTML and VATS resection alone and 53 had CTML, VATS diagnostic resection followed by VATS therapeutic lobectomy. An experienced chest pathologist determined pathologic resection margins, histological subtype and staging.

      Result

      The male/female ratio was 47/59. Median age was 63 (34-81) years. Smoking history obtained in 91/106. Median follow-up was 82 (32-136) months. Histology consisted of 99 adenocarcinomas and 7 squamous carcinomas. Staging (AJCC 8th edition) was Stage 0 (11), IA1 (77), IA2 (2), IA3 (3) IB (8), IIB (4) & IV (1). Both surgical groups were similar for demographics, tumor characteristics, histopathology and stage at surgery; there was no 90-day mortality. Multivariate analysis showed adverse effects on: 1) Local recurrence of cancer (n=3) by positive resection margin (n=2) ***. 2) Any recurrence of original cancer (n=10) by lymph node stage ***, positive resection margin ***, visceral pleural invasion (VPI) *** but not age, gender, smoking history, nodule shape on CT, histopathology, tumor invasive size, STAS, lymphovascular invasion or extent of resection. 3) Development of a new primary NSCLC (n=19) by wedge resection alone* (12/19). The new primary was resected in 13/19 patients. 4) Disease free survival at 3 (89%), 5 (74%) & 9 years (61%) by a positive resection margin ***, VPI **, lymph node stage*, or wedge resection alone *. Overall 5-year survival was 85%. (p<.05 *,p<.01 **, p<.001***)

      Conclusion

      In patients with early NSCLC, CTML accurately identifies the cancer margins resulting in a low radiologic local recurrence rate of 3%. Ten patients had recurrence of their original cancer associated with lymph node involvement, positive resection margin, and VPI. Second primary lung cancers are prevalent in long-term survivors, particularly if treated with wedge resection. Completion therapeutic lobectomy following diagnostic wedge resection of NSLC improves disease-free survival.

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      P1.16-35 - Sleeve Lobectomy Versus Pneumonectomy for Non-Small Cell Lung Cancer, a Cumulative Updated Meta-Analysis

      16:45 - 18:00  |  Presenting Author(s): Zhihua Guo  |  Author(s): Xuewei Chen, Hui Pan, Wenhua Liang, Jiaxi He, Yibin Hu, Fengnan Wang, Dongyun He, Weiqiang Yin, Jianxing He

      • Abstract

      Background

      Sleeve lobectomy (SL) is an appealing alternative to pneumonectomy (PN) for central or locally advanced non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the benefits of SL versus PN for NSCLC through cumulative meta-analysis.

      Method

      A systematic review and cumulative analysis of comparative studies reporting both postoperative and survival outcomes of SL and PN was performed through a comprehensive search of PubMed, EMBASE and the Cochrane library electronic databases from inception to April 2018

      Result

      A total of 9153 patients (SL: 3658, PN: 5495) from thirty-two studies were included. Meta-analysis was conducted for hazard ratio (HR), postoperative mortality, postoperative morbidity, local recurrence, and overall survival. PN was inferior to SL in terms of hazard ratio (HR=0.66, 95% confidence interval [CI]=0.59 to 0.75, I2=56%). Lower postoperative mortality was found in SL group (OR=0.45, 95% CI=0.36 to 0.56, I2=0.0%). While SL and PN showed no significant difference in local recurrence (OR=0.86, 95% [CI]=0.69 to 1.07, I2=45.0%) or postoperative morbidity (OR=0.92, 95% [CI]=0.78 to 1.09, I2=29.0%). Moreover, the 1-, and 5-years survival rates (1-yr: OR=2.19, 95% CI=1.93 to 2.5, I2=14.0%) (5-yrs: OR=1.94, 95% CI=1.61 to 2.35, I2=52.0%) and survival in patients with pN0 or pN1 at 5-years (OR=1.79, 95% CI=1.19 to 2.67, I2=3.0%) in the SL group were significantly higher than that in the PN group. As demonstrated in our cumulative meta-analysis, these effects were consistent over the years.

      Conclusion

      SL could be considered an acceptable alternative to PN for the treatment of NSCLC.

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      P1.16-36 - Real-Time Ct Guided Video Assisted Thoracoscopic Partial Resection of Peripheral Small-Sized Lung Tumors.

      16:45 - 18:00  |  Presenting Author(s): Taisuke Kaiho  |  Author(s): Hidemi Suzuki, Kota Ohashi, Yuki Shiina, Yuki Sata, Takahide Toyoda, Atsushi Hata, Takahiro Yamamoto, Junichi Morimoto, Yuichi Sakairi, Hironobu Wada, Takahiro Nakajima, Ichiro Yoshino

      • Abstract

      Background

      As pulmonary resection for small and grand-grass opacity (GGO) dominant pulmonary nodules have been increasing, various navigation systems to detect these nodules have been reported. The aim of this study is to evaluate feasibility of real-time CT guided pulmonary resection for impalpable small pulmonary nodules.

      Method

      From July to November in 2017, 11 patients were eligible for pulmonary resection for lung cancer or malignancy suspected lesions, which was expected to be difficult to detect during operation. These nodules were defined as GGO-dominant (>50%) tumor with a diameter of 3cm or lower (GGO-dominant type), and tumor with a diameter of 2cm or lower, which is located deeper than the diameter of the tumor from visceral pleura (deep solid type). First, we put several surgical clips as first marker on the visceral pleura of the tumor-located lobethrough 3-ports VATS approach. The tumor and the first markers were visualized by cone beam CT, then the second marker was put just on the tumor based on the image. Pulmonary resection was performed according to second marker guided by automated staplers. CT scanning was also performed for confirmation of the complete resection.

      Result

      These procedures were performed for 4 men and 7 women (mean age: 58 years (39-71)). Tumors were located in the right upper lobe/right lower lobe/left upper lobe/left lower lobe in 5/2/2/2 patients. Diameters of tumors were 1.5cm or less. Six tumors were GGO-dominant types whereas 5 were solid types located in the deep from the visceral pleura; therefore all tumors couldn’t be detected by video-scopic observation. The average number of cone beam CT scanning is 2.7 times. All patients accomplished macroscopic and microscopic complete resection with no adverse events during perioperative periods.

      Conclusion

      This feasibility study suggested that cone beam CT was safe and useful guide forvideo assisted thoracoscopic partial resection for impalpable peripheral pulmonary nodules.

      figure.jpg

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      P1.16-37 - Clinicopathological Characteristics and Prognostic Factors of Operable Non-Small Cell Lung Cancer Patients with the Diabetes Mellitus

      16:45 - 18:00  |  Presenting Author(s): Kaoru Kaseda  |  Author(s): Kyohei Masai, Tomoyuki Hishida, Takashi Ohtsuka, Yuichiro Hayashi, Hisao Asamura

      • Abstract

      Background

      Lung cancer patients have a high frequency of comorbidity. The diabetes mellitus (DM) has been reported to be associated with postoperative complication and survival in several types of cancers. The aim of this study was to investigate the impact of DM on postoperative complication and survival in operable non-small cell lung cancer (NSCLC) patients.

      Method

      We retrospectively reviewed 1231 patients who underwent surgical resection for NSCLC between 1996 and 2012. The outcomes were compared between the patients with DM (DM group, n=139) and without it (Non-DM group, n=1092). Patients were assigned to DM group if following conditions were identified; 1) a history of DM or medication use, and 2) preoperatively elevated fasting glucose (>126 mg/dL) or hemoglobin A1c (National Glycohemoglobin Standardization Program) level (≥ 6.5 %) in spite of the unrevealed history of DM. However, diabetes of all patients in DM group was controlled by dietary or sliding-scale insulin therapy. Postoperative complications were defined as events of grade 2 or more according to the Clavien-Dindo classification. A multivariate Logistic regression model was used to identify clinical factors associated with postoperative complication. Survival was evaluated by overall, relapse-free, and disease-specific survivals using Kaplan-Meier method, and a multivariate Cox proportional hazard model was used to identify prognostic factors.

      Result

      DM group included more elderly patients, males, smokers, patients with ischemic heart disease, patients taking antiplatelet or anticoagulant drugs, squamous cell carcinomas than non-DM group. DM group showed higher incidence of postoperative complications than non-DM group (28% vs. 21%, p=0.047). Logistic regression analysis showed that DM was an independent predictor for postoperative complication (OR: 1.851, 95% CI: 1.189-2.884). But, no significant difference was observed in thirty-day mortality between the two groups (2% vs. 1%, p=0.061). DM group showed a worse overall survival than non-DM group (p=0.024), and multivariate Cox analysis showed that DM was identified as an independent poor prognostic factor for overall survival (HR: 1.492, 95% CI: 1.053-2.113). DM group included more death from other disease than non-DM group (50% vs. 35%, p=0.048), and there was no significant difference in relapse-free and disease-specific survival between the two groups.

      Conclusion

      The present study demonstrated that operable NSCLC patients with DM have distinct clinicopathological features. Although the presence of preoperative DM was associated with postoperative morbidity and worse overall survival, it did not increase perioperative and lung cancer-related mortalities. Operable NSCLC patients with DM can be still indicated for curative surgery if their perioperative diabetes was controlled.

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      P1.16-38 - Meta-Analysis of Unplanned Readmissions Following Thoracoscopic Versus Open Lung Cancer Resection

      16:45 - 18:00  |  Presenting Author(s): Janusz Kowalewski  |  Author(s): Maciej Dancewicz, Mariusz Kowalewski

      • Abstract

      Background

      Approximately 7.4% of patients experience unplanned readmission within 30 days following pulmonary resection. Although video-assisted thoracic surgery (VATS) is able to improve short-term outcomes in both cancer patients and noncancer patients, surprisingly, several recent big registry studies showed significantly increased readmission rates.

      Method

      We performed a systematic review and meta-anaysis according to PRISMA (Preferred Items Reporting for Systematic Reviews and Meta-Analyses) guidelines. The search process covered a period untill 31st of March 2018. Search keywords were: VATS, lobectomy, segmentectomy, open, thoracotomy, readmission*, readmit*. Studies were to compare VATS vs open thoracotomy and reporting 30-90 days readmission rates. Only reports in English were included and retrieved as full-txts. Data were pooled in DerSimmonian and Laird Inverse Variance random effects model and reported as Risk Ratios (RR) with corresponding 95% Confidence Intervals (CIs).

      Result

      A systematic search yielded 16 potentially elegible reports, of which 5 were further excluded because they did not report crude readmission rates across VATS vs open thoracotomy. Eleven studies remained enrolling 60,146 patients undergoing VATS (39.3%) and open thoracotomy (60.7%). Unplanned readmissions followed in 7.8% (1,843/23,632) and 8.1% (2,944/36,514) of patienst undergoing VATS and open thoracotomy respectively; there was no statistical differences between two appraoches: RR (95%CIs): 0.94 (0.75-1.19); p=0.63. Substantial heterogeneity was present (p<0.001, I2=87%) in the analysis though. No single study influenced direction nor magnitude of the estimates in number of sensitivity analyses. In meta-regression analyses we demonstrated that patients' age, disease's local advancement and centre volume did not influence the results (p>0.05). On the other hand number of complications across single study pooled n. of patients was negatively correlated with readmissions.

      forest plot.png

      Conclusion

      There was no apparent difference between VATS and open thoracotomy with regard to number of unplanned readmissions. Future studies should focus on reducing complication rates in the open thoacotomy group rather than reducing readmission rates after VATS.

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      P1.16-39 - A Nomogram for Predicting Survival Of TNM8 Stage I Non-Small Cell Lung Cancer Patients to Tailor Potential Chemotherapy Candidates

      16:45 - 18:00  |  Presenting Author(s): Wenhua Liang  |  Author(s): Yuan Zeng, Nicholas Mayne, Chi-Fu Jeffrey Yang, Jianxing He, Thomas A. D'Amico

      • Abstract

      Background

      The 8th TNM stage I non–small-cell lung cancer (NSCLC) patients are not considered as candidates for adjuvant chemotherapy (ad-Chemo). This study aimed to develop a nomogram for predicting cancer specific survival (CSS) of these patients and identifying those who might benefit from ad-Chemo.

      Method

      NSCLC cases between 1998 and 2013 were extracted from the SEER database and randomly divided into training and validation cohorts. We identified and integrated the recurrence-associated factors to build a nomogram. We determined the cut-off for the high-risk group by matching the nomogram-predicted 5-year CSS with that of the current 4-5 cm stage IIA cases. The difference in benefit from chemotherapy between risk groups was examined using both SEER and NCDB cohort.

      Result

      A total of 30,475 patients with stage I were included for analysis. Six independent prognostic factors were identified and integrated into the model. The calibration curves showed good agreement. The C-index of the nomogram was higher than that of the staging system (IA1, IA2, IA3, IB) (training set, 0.59 vs. 0.56, P < 0.01; validation set, 0.62 vs. 0.57, P < 0.01). Specifically, 26.9% stage IB patients (8.1% of all stage I) were categorized into the high-risk group (score>29) and had inferior CSS compared with stage IIA patients. In addition, chemotherapy was associated with significantly better OS (HR, 0.739; P = 0.047) than no-chemotherapy in the high-risk group.

      figure1-2.jpg

      Conclusion

      We established a practical and economical nomogram to predict CSS for 8th edition stage I NSCLC, and identified a subset of patients at relatively high risk for recurrence who might benefit from ad-Chemo.

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      P1.16-40 - Evaluating the Tumor Heterogeneity in Lung Cancer by Constructing Tumor Heterogeneity Index (THI) from Magnetic Resonance Imaging

      16:45 - 18:00  |  Presenting Author(s): Hui Liu  |  Author(s): Qi-Wen Li, Nanjie Gong, Bo Qiu, Hao-Qiang He, Ji-Hong Wang, Yong-Quan Ye, Jin-Yu Guo, Steven H Lin, Pei-Qiang Cai, Qun Chen, Hong-Di Li, Chuanmiao Xie

      • Abstract

      Background

      To improve the evaluation of primary lung cancer heterogeneity using clinical routine magnetic resonance imaging (MRI), we proposed a method based on basic measurements from T1- and T2-weighted MRI.

      Method

      As a novel technique of magnetic resonance imaging analysis, we investigated a total of 203 patients with biopsy-proven primary lung cancer and with different T stages. All patients previously received positron emission tomography/computed tomography (PET/CT) scan. Gross lesions were manually contoured on T1-weighted, T1-enhanced, T2-weighted and T2 fat suppression (T2fs) images. The ratios of standard deviation (SD) / mean tumor value from each sequence were calculated. Correlation analyses were performed between T stages and the ratios. P value <0.05 was defined as statistical significant. Then a linear regression was performed to determine the weight of each related ratio. A model was built to calculate Tumor Heterogeneous Index (THI). One hundred and one patients were analyzed as the training set and another 102 as validating set.

      Result

      There were 56 patients diagnosed with T1 disease, 60 with T2 disease, 51 with T3 disease and 36 with T4 disease. Pair matching was performed between training set and validating set. As a result of the correlation analyses, SD/mean ratio showed significantly correlations with T stages in T1-enhanced (p=0.003), T2-weighted (p<0.0001) and T2fs sequences (p=0.002). Based on a linear regression model, THI was established for assessing the heterogeneity of lung tumor, consisting the three ratio measurements. Correlation analysis demonstrated that Higher THI was significantly related to more advanced T stages (p<0.0001).

      fig.1.jpg

      Conclusion

      The proposed SD/mean ratio measurements and the calculation of THI according to clinical routine MR images could be clinical biomarkers that correlated with T stages, and were capable of evaluating heterogeneity of lung cancers.

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      P1.16-41 - The Role of Surgery in Pulmonary Large Cell Neuroendocrine Carcinoma: A Propensity-Score Matching Analysis of SEER Database

      16:45 - 18:00  |  Presenting Author(s): Zhichao Liu  |  Author(s): Hengrui Liang, Guanping Qiu, Yaokai Wen, Jianxing He, Wenhua Liang

      • Abstract

      Background

      Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive subset of non-small-cell lung cancer with poor prognosis. Due to its rarity, the optimal therapy strategy for pulmonary LCNEC remains undefined. We aimed to evaluate the role of surgery for stage I-III LCNEC using the Surveillance, Epidemiology, and End Results (SEER) database.

      Method

      Patients with stage I-III LCNEC were extracted from the SEER database (2004-2014). Propensity-score matching was performed to reduce the effect of potential confounders. Kaplan-Meier curves were constructed for overall survival (OS) and cancer-specific survival (CSS) for patient strata based on surgery use or nonuse. Multivariable Cox-regression was used to explore the efficacy of different treatment strategies.

      Result

      A total of 944 LCNEC patients were identified, of which 674 (71.4%) received surgery. Both OS and CSS of surgery use group were superior to surgery nonuse group in the whole cohort (HR=0.48, P<0.001 and HR=0.41, P<0.001, respectively). Among matched cohort, significantly greater benefits in OS and CSS (Figure 1) from surgery was observed in both stage I-II (HR=0.47, P=0.001 and HR=0.43 P<0.001, respectively) and stage III (HR=0.66, P=0.039 and HR=0.63, P=0.031, respectively). On multivariable analysis of surgical group, there was no significant difference in either OS or CSS between surgery alone and the addition of chemotherapy or (and) radiation for stage I-II patients, whereas favorable survival outcomes of surgery plus chemotherapy (OS: HR=0.26, P<0.001; CSS: HR=0.30, P=0.001) and surgery plus chemotherapy and radiation (OS: HR=0.33, P<0.001; CSS: HR=0.34, P=0.002) were significantly evident for stage III patients.

      figure-abstract 12772.jpg

      Conclusion

      This is the largest study exploring the benefit of surgery for stage I-III pulmonary LCNEC. Regardless of stage, surgery showed remarkable survival benefits for LCNEC patients. It is suggested that surgery alone may be sufficient for stage I-II, whereas the multimodal combination of surgery and other therapies should be considered for stage III disease.

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      P1.16-42 - Indocyanine Green Intersegmental Visualization During Fluorescence Imaging of Thoracoscopic Anatomic Segmentectomy: A Novel Approach

      16:45 - 18:00  |  Presenting Author(s): Takuya Matsui  |  Author(s): Hiroaki Kuroda, Yusuke Sugita, Shin Koyama, Keita Nakanishi, Takaaki Arimura, Tetsuya Mizuno, Noriaki Sakakura, Yukinori Sakao

      • Abstract

      Background

      Anatomic segmentectomy (AS) of the lung is a more complex operative procedure than standard lobectomy, especially when performed as a complete thoracoscopic surgery. Identification of the intersegmental boundary line (IBL) is a technical imperative, allowing surgeons to develop this plane during segmentectomy. Although several methods of IBL identification (IBL-ID) have been reported, our general usage of an intravenous indocyanine green (ICG) fluorescence system is alternative. In examining 83 patients by conventional ICG method (CIM), the IBL-ID success rate was high (98.8%), but intersegmental visibility was diminished due to smoking and emphysema. We also examined 29 patients using the Spectra A method (SAM), which heightened intersegmental contrast (IC) and preserved segment brightness (PB), compared with CIM, thus improving intersegmental visibility. To effect further improvement, a trial of the novel SAM with xenon light (SAM-X) was undertaken.

      Method

      We prospectively studied 106 consecutive patients who underwent complete thoracoscopic AS of 111 lung segments (including subsegments) at our Hospital between October 2015 and October 2017. Following intraoperative transection of the segmental artery, vein and bronchi, 5 mg/body weight of ICG was administered intravenously, and fluorescence images were generated using the ICG system. Both the CIM with xenon light (CIM-X) and the SAM-X were simultaneously obtained in concert for IBL-ID, quantifying intersegmental visibility for histogram representation.

      Result

      The patient population (men, 50; women, 56) had a mean age of 67.4±10.7 years and a mean Brinkman index of 446.6±650.7, harboring malignant lung tumors (primary, 77; metastatic, 29, other, 5) as follows: right upper, 28; right middle, 1; right lower, 20; left upper, 38; left lower, 24. IBL-ID was achieved in all patients (100%). As with the SAM apparatus, the SAM-X provided significantly better accentuation of green fluorescence in RGB light analysis, compared with the CIM-X (p<0.01). Furthermore, both IC and PB showed significant increases (p<0.01 each), whether comparing SAM-X with CIM-X or with SAM; and SAM-X was strong (R=0.8), surpassing that of CIM-X (R=0.39) as for the correlation between IC and PB.

      Conclusion

      The SAM-X device stabilized visibility and improved contrast between resected and non-resected segments and brightness of both resected and non-resected segments during thoracoscopic intersegmental identification.

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      P1.16-43 - Analyses of Long-Term Outcomes and Prognostic Factors in Surgically Resected ALK-Rearranged Lung Adenocarcinoma

      16:45 - 18:00  |  Presenting Author(s): Yosuke Matsuura  |  Author(s): Junji Ichinose, Masayuki Nakao, Mingyon Mun, Ken Nakagawa, Hironori Ninomiya, Yuichi Ishikawa, Makoto Nishio, Sakae Okumura

      • Abstract

      Background

      Anaplastic lymphoma kinase (ALK)-rearrangement (ALK+) in lung cancer has made an epoch in the molecular classification. Specific inhibitors of the kinase activity of ALK have been developed as therapeutic drugs for lung cancer with ALK+. Long-term outcomes and prognostic factors, however, in surgically resected cases are unclear. We evaluated the survival rate, and investigated association between prognosis of surgically resected lung adenocarcinoma (AC) with ALK+ and clinicopathological features.

      Method

      From 1996 to 2013, clinical data of 62 AC patients with ALK+ were retrospectively analyzed. The median follow up time was 73 months. Relationships between the patients’ clinicopathological features (i.e. age, gender, smoking history, operative procedure, administration of adjuvant therapy, tumor size, c-stage, p-stage, pleural invasion, Ly/V invasion, intrapulmonary metastasis, histologic predominant subtypes, and histologic grade), and their recurrence-free survival (RFS), post-recurrence survival (PRS) and overall survival (OS) rates were assessed.

      Result

      The 5-year RFS and OS were 69% and 92%, respectively. For OS, advanced p-stage (IIIA and IV) and pleural invasion were independent poor prognostic factors in multivariate analyses, but 5-year OS for even Stage IIIA was 85%, nevertheless (Figure).figure. os for each stages..jpg

      20 patients had recurrence. 8 of the 20 patients were treated with ALK-tyrosine kinase inhibitors (TKIs), and 12 were without. The median PRS was 54 months. Patients treated with AKL-TKIs had longer PRS and OS than without (65 vs. 38 months, p=0.01, and 80 vs. 74 months, p=0.04, respectively).

      Conclusion

      Long-term outcomes in surgically resected ALK+ AC were excellent even so advanced stage. ALK-TKIs are certainly effective for post-recurrence status. For the resectable ALK+ AC treatment strategy, ALK-TKIs might play an important role.

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      P1.16-44 - Minute Ventilation-To-Carbon Dioxide Slope is Associated with Early and Long Term Survivals Following Anatomical Pulmonary Resection

      16:45 - 18:00  |  Presenting Author(s): Takuro Miyazaki  |  Author(s): Alessandro Brunelli, Padma Dimesh, Matthew Callster, Kevin Franks, Takeshi Nagayasu

      • Abstract

      Background

      The aim of study was to identify that ventilation-to-carbon dioxide output (VE/V CO2) slope obtained from cardiopulmonary exercise test (CPET) was an independent prognostic factor of short and long term survival after lobectomy or segmentectomy.The aim of study was to identify that ventilation-to-carbon dioxide output (VE/V CO2) slope obtained from cardiopulmonary exercise test (CPET) was an independent prognostic factor of short and long term survival after lobectomy or segmentectomy.

      Method

      974 patients including lobectomy (n=887) or segmentectomy (n=87) were performed from April 2014 to March 2018. 209 (22%) underwent CPET, and pulmonary function and several clinical factors including age, sex, performance status and comorbidities were retrospectively investigated to identify the prognostic factors with a multivariable Cox regression analysis.

      Result

      Among patients with CPET, 95 patients (46%) had VO2max<15 mL/kg/min. Compared to patients with higher VO2max, they had similar cardiopulmonary complication rates (32% vs. 29%, p=0.68) and 90 day mortality (9.5% vs. 6.2%, p=0.43). 172 patients had measured VE/V CO2. The incidence of cardiopulmonary complications in patients with VE/V CO2 slope >40 was 37% (19 of 51) vs. 27% (33 of 121) in those with lower slope values (p=0.19). However, 90-day mortality in patients with high VE/V CO2 slope (n=8) was 3-fold higher (16% vs. 5.0%) compared to those with lower (n=6) values (p=0.03). Cox regression analysis showed that higher VE/V CO2 values were significantly associated with poorer 2-year survival (HR 1.07, 95% CI 1.01-1.13, p=0.009)

      Conclusion

      We found VE/V CO2 slope was associated with increased 90-day mortality and poorer 2-year survival in patients submitted to anatomical pulmonary resection for non-small cell lung cancer. These findings may assist the multidisciplinary team in selecting the most appropriate radical treatment in high-risk patients.

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      P1.16-45 - Thoracoscopic Stapler-Based Complex Segmentectomy Assisted by Virtual Assisted Lung Mapping

      16:45 - 18:00  |  Presenting Author(s): Jun-ichi Nitadori  |  Author(s): Masaaki Sato, Kentaro Kitano, Kazuhiro Nagayama, Masaki Anraku, Jun Nakajima

      • Abstract

      Background

      Anatomical segmentectomies play an important role for the patients with small ground-glass lung cancer and metastatic lung tumors. Virtual assisted lung mapping (VAL-MAP) assists to localize hardly palpable lung tumors and to define the resection lines. VAL-MAPhas been found to be useful in thoracoscopic segmentectomies, particularly complex segmentectomies.

      VAL-MAP is a novel preoperative bronchoscopic multi-spot dye-marking technique to provide “geometric information” to the lung surface, using three-dimensional virtual images.The multiple spots (tattooing) of VAL-MAP assists not only to localize hardly palpable lung tumors but to define appropriate resection lines in sublobar lung resections including wedge resections and segmentectomies. The purpose of the study is to evaluate the role of VAL-MAP in simple and complex thoracoscopic segmentectomy.

      Method

      VAL-MAP was conducted before surgery as follows: the target bronchi were identified using radiology workstation; 1 ml of indigo carmine was injected through a catheter by bronchoscopy under fluoroscopy; another CT scan was taken to confirm marking locations. Segmentectomies were conducted thoracoscopically and intersegmental planes were made using staplers (Figure). Anatomical segmentectomies using VAL-MAP conducted were retrospectively analyzed (2014-2017). Simple segmentectomy was defined as a resection of anatomical single segment or combined segments. Other anatomical segmentectomies were defined as complex segmentectomy (Table). Successful resection rates, surgical margins, and post-operative course were compared between simple segmentectomy and complex segmentectomy.

      Result

      Atotal of 43 patients were included in the study (42% women; median age 68 yr (48-83 yrs.). The median tumor size was 12 mm. The average number of markings via VAL-MAP was 4.2 (1-8) points. Post-VAL-MAP complications identified in CT included 5 pneumothorax, 3 airway bleeding, and 2 mediastinal emphysema, although none needed additional treatment.Simple segmentectomy was conducted in 18 patients, while complex segmentectomy was conducted in 25 patients. There was no significant difference in operation time (simple vs. complex; 233±100 vs. 266±8 min), length of chest tube drainage (2.3±0.33 vs. 2.5±0.25 days), or margin/tumor diameter ratio (2.10±0.28 vs. 1.89±0.23). Minor postoperative complicationswere found in 4 patients (2 collapse lung after removed chest tube; 2 pneumonia and inflammatory reaction). No pleurodesis was needed postoperatively.Final pathology included 24 lung cancer, 15 metastatic tumors, and 3 others.

      Conclusion

      VAL-MAP-assisted stapler-based thoracoscopic segmentectomies were safely and effectively conducted even in complex ones. The bronchoscopic approach of VAL-MAP made the anatomical liberty available to surgeons. The “map” drawn with VAL-MAP not only helps to identify the tumor, but also helps to determine oncologically appropriate resection lines.

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      P1.16-46 - A Population-Based Validation Study of the Proposed ‘R-Factor’ Classification in a Lung Cancer-Endemic Region of the US.

      16:45 - 18:00  |  Presenting Author(s): Raymond U. Osarogiagbon  |  Author(s): Matthew P Smeltzer, Nicholas R. Faris, Meredith A Ray, Carrie L Fehnel, Olawale Akinbobola, Cheryl Houston-Harris, Philip Ojeabulu, Yu-Sheng Lee, Edward Owen, Richard Eubanks, Hector Dox, David Talton, Horace Lynn Wiggins, Bradley Wolf, Paul Steven Levy, Edward Todd Robbins

      • Abstract

      Background

      The IASLC has proposed a definition of completeness of surgical resection beyond margin status. We sought to validate the proposed classification in a US cohort, and evaluated the impact of a lymph node (LN) specimen collection kit on resection status.

      Method

      The population-based Mid-South Quality of Surgical Resection cohort includes >95% of lung cancer resections in 4 contiguous US Dartmouth Hospital Referral Regions from 2009-2018. Resections were classified as Complete (R0), Uncertain (R[un]), or Incomplete (R1-R2) based on the proposed classifications. We evaluated overall survival (OS) using the Kaplan-Meier method and proportional hazards models. Adjusted models included age, sex, histology, extent of resection, pTNM categories, and co-morbidities. A subset of resections used a LN specimen collection kit.

      Result

      Of 3,099 resections, 18% were R0, 76% R(un), and 6% R1-R2. 5-year OS was 69%/54%/35% for R0/R(un)/R1-R2 (p<0.0001, Figure 1A). Compared to R0, the increased hazard of death for R(un)/R1-R2 was 1.6/3.0 overall, 1.5/2.3 in node negative patients, 1.7/3.1 in node positive patients, and 1.5/1.9 in fully adjusted models (all p<0.0001).

      Of 2,351 R(un) resections, the highest mediastinal LN positive increased the hazard of death 1.6 times (vs. negative, p=0.0008). However, 626 (27%) had no mediastinal LN examined (MLE). R(un) resections with 0 MLE had 1.2 times the hazard of death compared to R(un) with >1 MLE (p=0.0212, Figure 1B).

      Use of the LN kit intervention resulted in R0 in 40% of cases, compared to 6% without the kit (p<0.0001). Kit cases had improved OS across the entire cohort (p=0.0002), but when restricted to R0 patients, OS did not differ based on kit use (p=0.96).

      figure 1 5-3-18 final.png

      Conclusion

      The proposed ‘R-factor’ classifications are prognostic. R(un) rates were high, but significantly lower in cases where a LN collection kit was used. Further delineation of R(un) cases based on MLE should be considered.

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      P1.16-47 - Adjuvant Targeted Therapy Following Standard Adjuvant Therapy for Resected NSCLC: An Initial Report from ALCHEMIST (Alliance A151216)

      16:45 - 18:00  |  Presenting Author(s): Geoffrey R. Oxnard  |  Author(s): Sumithra Mandrekar, Shauna Hillman, Angelina Tan, Ramaswamy Govindan, Dennis Wigle, Shakun Malik, Colleen Watt, David E Gerber, Jamie E Chaft, Suzanne Dahlberg, Karen Kelly, Meredith Faggen, Philip Stella, Karim Tazi, David R. Gandara, Suresh S. Ramalingam, Thomas E. Stinchcombe

      • Abstract

      Background

      The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) was launched in 2014 across the National Clinical Trials Network (NCTN) of the National Cancer Institute (NCI). This trial platform aims to enroll up to 8300 patients with resected high-risk non-small cell lung cancer (NSCLC) to facilitate enrollment to adjuvant targeted therapy trials following completion of standard adjuvant therapy, and to collect biospecimens for clinical and investigational genomics. On 5/1/2016, the study was expanded to include squamous NSCLC and PDL1 testing to facilitate enrollment to a new immunotherapy study.

      Method

      Eligible patients have completely resected NSCLC, stage IB (>4cm) to IIIA by AJCC 7. Eligibility window extends 75-285 days post-op depending upon receipt of adjuvant chemotherapy and/or radiation. Molecular testing of EGFR, ALK, PDL1 is performed centrally (depending on the histology and testing results) and results are returned to sites within 7-21 days. FFPE tissue and blood are collected by the NCI for genomic analysis. Appropriate patients may then enroll to one of three therapeutic trials studying single agent adjuvant targeted therapy (erlotinib NCT02193282, crizotinib NCT02201992, or nivolumab NCT02595944) versus observation.

      Result

      As of March 19, 2018, 2945 patients have been enrolled from 575 sites within the US, with a median enrollment of 98/month (range: 71-133) in 2017. Central molecular testing was completed in 83%-92% of appropriate patients: EGFR L858R/19del was detected in 395 of 2468 patients (16.0%), ALK FISH was positive in 106 of 2458 patients (4.3%), and PDL1 IHC was >1% in 902 of 1464 patients (61.6%). Adequate tissue and blood for whole exome sequencing (WES) was collected on 1928 patients (65.5%), and enrollment plasma (added January 2017) has been collected on 885 patients (30.1%). Of 1960 patients deemed to be eligible for the adjuvant treatment trials with sufficient follow-up, 560 (28.6%) were enrolled; those enrolled were younger (p=0.01) and had higher N stage (<0.01) than those not enrolled. The primary reason for eligible patients not enrolling to treatment trials was lack of interest in further adjuvant therapy (53%).

      Conclusion

      ALCHEMIST has achieved an enrollment of ~100 patients/month with resected high-risk NSCLC. This initial report demonstrates the feasibility of central molecular testing for enrollment to adjuvant targeted therapies. Efforts are ongoing to plan clinically-informed genomic analyses of tumor and plasma, as well as the planning of new treatment arms that leverage this ongoing trial platform.

      Support: U10CA180821, U10CA180882, U10CA180820, U10CA180868, U10CA180888; ClinicalTrials.gov Identifier: NCT02194738

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      P1.16-48 - The Impact of Segmentectomy Versus Lobectomy on Pulmonary Function of Patients with Non-Small Cell Lung Cancer: A Meta-Analysis

      16:45 - 18:00  |  Presenting Author(s): Guanping Qiu  |  Author(s): Yaokai Wen, Hengrui Liang, Zhichao Liu, Jianxing He, Wenhua Liang

      • Abstract

      Background

      Lobectomy (Lob) and lymph node dissection is considered as the standard surgical procedure for non-small cell lung cancer (NSCLC). Segmentectomy (Seg) has been recently regarded as an alternative in early peripheral NSCLC owing to its advantages of lung function reservation. Thus, we performed a meta-analysis with the aim of evaluating whether Seg offers a better lung functional advantage over Lob.

      Method

      A comprehensive search of online databases was performed. Perioperative outcomes and lung functional index and were synthesized. The odds ratio (OR) or SMD and its 95% CI was calculated using a random effects model. Subgroup was conducted according to different time points. Single-arm meta-analysis was conducted for lung function at each visit time. Repeated-measures analysis of variance (ANOVA) was used to compare the lung function between at each visit.

      Result

      A total of 5 eligible studies including 958 patients were recruited. There were no significant differences according to baseline characteristics before surgery between groups (Seg and Lob). Seg correlated with a greater postoperative preserved pulmonary function than Lob in FVC (SMD=0.23, p=0.009) (Figure A) and FEV1 (SMD=0.27, p=0.002) (Figure B), especially before 12 months. ANOVA showed there were no differences between two groups in FVC (p=0.647) and FEV1 (p=0.468) according to each visit time (Figure C). Seg group showed significantly less postoperative complications compared with the Lob. (OR=0.64, p=0.045) and the recurrence rate were same between groups (OR=0.89, p=0.623).

      figure.tif

      Conclusion

      Seg offers a better lung functional preservation in short time and reduces postoperative complication compared with Lob. However, two groups showed no significant difference on lung function and tumor relapse according to long follow up.

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      P1.16-49 - Treatment of NSCLC Patients with Clinical N1 Disease: Is There an Advantage to Neoadjuvant Therapy?

      16:45 - 18:00  |  Presenting Author(s): Brendon Stiles  |  Author(s): Mohamed Rahouma, Mohamed Kamel, Abu Nasar, Sebron Harrison, Benjamin Lee, Jeffrey L. Port, Nasser Altorki

      • Abstract

      Background

      Treatment options for clinical N1 patients with non-small cell lung cancer (NSCLC) include neoadjuvant therapy and surgery, surgery with adjuvant therapy, or definitive chemoradiation (dCRT). We sought to evaluate the rates of use of each strategy and associated outcomes in patients in the National Cancer Database (NCDB).

      Method

      The NCDB (2004-2014) was reviewed for patients with clinical N1 NSCLC, excluding those with multiple primary tumors, unknown treatment modality/sequence, and clinical M1 disease. Overall survival (OS) of different treatment modalities was compared using log rank test in Kaplan Meier curves. Logistic and Cox regressions were performed to identify predictors of OS among cN1 cohorts respectively.

      Result

      We identified 14,934 cN1 patients undergoing curative treatment. Median age was 67 (IQR 59-73) and median tumor size 4.5 cm (IQR 3-6.4). This included 1,040 patients (7%) undergoing neoadjuvant therapy followed by surgery, 4,398 patients (29.4%) undergoing surgery +/- adjuvant therapy, and 9,496 patients (63.6%) undergoing dCRT. Predictors of neoadjuvant therapy were age (OR=0.96,CI=0.95-0.96), white race (OR=1.54,CI=1.23-1.93), year of diagnosis (OR=0.92,CI=0.90-0.94), Charlson Comorbidity Index (CCI)<2 (OR=1.282,CI=1.004-1.637), adenocarcinoma (OR=1.30,CI=1.12-1.51), larger tumor size (OR=1.002,CI=1.001-1.003, and private insurance (OR=1.51, CI=1.29-1.77). Superior OS was achieved following neoadjuvant therapy and surgery (median-OS=42.1±3.4 months) compared to surgery ± adjuvant therapy (38.4±1.5 months, p=0.002). dCRT was associated with the worst survival (18.9± 0.30 months). By MVA, predictors of poor survival in the cohort were older age (HR=1.015,CI=1.012-1.018), male gender (HR=1.20,CI=1.13-1.26), lack of insurance (HR=1.26,CI=1.08-1.46), higher comorbidities (CCI=2, HR=1.29, CI=1.19-1.40), larger tumors (HR=1.002, CI=1.001-1.002), and the use of dCRT (HR=1.75,CI=1.58-1.95).

      Conclusion

      Neoadjuvant therapy followed by surgery is associated with superior survival compared to upfront surgery +/- adjuvant therapy in this large cohort of patients. dCRT, although used most commonly in patients with cN1 disease, demonstrates the worst survival rates.

      cn1 km os.png

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      P1.16-50 - The Role of Adjuvant Therapy for Patients with Early Stage Large Cell Neuroendocrine Lung Cancer: A National Analysis

      16:45 - 18:00  |  Presenting Author(s): Vignesh Raman  |  Author(s): Chi-Fu Jeffrey Yang, Oliver Kayden Jawitz, Cherie Parungo Erkmen, Betty Tong, Thomas A. D'Amico, Mark Berry, David Harpole

      • Abstract

      Background

      Although large cell neuroendocrine lung cancer (LCNEC) generally has a worse prognosis than other non-small cell lung cancer histologies, data regarding the role of adjuvant therapy in completely resected stage I LCNEC are extremely limited and current guidelines do not routinely recommend adjuvant therapy. This U.S. National Cancer Data Base (NCDB) analysis was performed to improve the evidence guiding decision-making regarding postoperative therapy for early stage LCNEC.

      Method

      Overall survival of patients with pathologic T1-2aN0 LCNEC who underwent resection in the NCDB from 2003 to 2015 was evaluated using Kaplan-Meier and multivariable Cox proportional hazard analysis. Patients who died within 30 days of surgery were excluded. These prospective data were acquired by certified tumor registrars, and include over 80% of cancer diagnoses annually in the U.S.

      Result

      Of the 5,177 patients who met study criteria, adjuvant therapy was given to 31% of patients (n=1585): 20% received chemotherapy (n=1039), 8% chemoradiation (n=400), and 3% radiation (n=146). In stage IA LCNEC, adjuvant chemotherapy was associated with improved survival when compared to no adjuvant therapy in unadjusted analysis (five-year survival 55% vs. 53%; p=0.03) but not after multivariable adjustment (hazard ratio [HR] 0.81; 95% CI 0.64 to 1.02). Of note, adjuvant chemoradiation (HR 1.66; 95% CI 1.11 to 2.48) and adjuvant radiation (HR 1.55; 95% CI 1.06 to 2.25) were associated with worse survival when compared to no adjuvant therapy. In stage IB LCNEC, adjuvant chemotherapy was associated with improved survival when compared with no adjuvant therapy in both univariate (five-year survival 60% vs. 43%; p<0.0001; Figure) and multivariable (HR 0.65; 95% CI 0.48 to 0.88) analyses.

      final wlc lcnec figure 05.04.18.jpg

      Conclusion

      In this NCDB study of resected stage I LCNEC, adjuvant chemotherapy was associated with improved survival after resection of stage IB but not stage IA LCNEC.

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      P1.16-51 - Preop Nutrition-Enhanced Recovery After Surgery Protocol for Thoracic Cancer Resections Decreases Hospital Days and Charges

      16:45 - 18:00  |  Presenting Author(s): Lary A. Robinson  |  Author(s): Tawee Tanvetyanon, Deanna Grubbs, Rosemarie Garcia Getting, Sephalie Patel

      • Abstract

      Background

      Numerous studies over the last decade have documented that the preoperative nutritional status strongly influences perioperative outcomes. Based on published surgical studies, we instituted a preoperative enhanced nutritional support protocol for thoracic cancer resection patients and compared the results to a historical control cohort from the year immediately prior to starting this nutrition program.

      Method

      Patients undergoing thoracic cancer resections from July 15, 2016 to July 14, 2017 underwent a preoperative nutritional-enhanced recovery after surgery protocol (N-ERAS) of daily probiotics, five days of an oral immunonutrition drink and a complex carbohydrate loading drink the night prior to surgery. Historical controls were from patients undergoing surgery the 12 months prior (Pre-N-ERAS), all operated on by the same surgical team. Non-parametric statistical tests were employed for this retrospective analysis.

      Result

      Data from 234 patients were analyzed. For the Pre-N-ERAS group, there were 121 patients (48/73 men/women), mean age 67.5 (range 24-88), mean post-bronchodilator %FEV1 86.7±19.9 (range 41-126), mean serum albumin 4.3±0.3gm/dl (range 3.2-5.1) and mean Charlson Co-Morbidity Index 4.3±2.2 (range 0-11). For the N-ERAS group, there were 113 patients (50/63 men/women), mean age 67.5 (range 43-85), mean post-bronchodilator %FEV1 89.4±19.7 (range 43-146), mean serum albumin 4.3±0.3gm/dl (range 3.3-5.0) and mean Charlson Co-Morbidity Index 4.8±2.2 (range 1-11). There were no significant differences among the groups for demographics. For both groups, no mortalities, empyemas, wound infections or reoperations for any cause were reported. The N-ERAS nutrition protocol patient compliance was 100% with no toxicity. Compared to the Pre-N-ERAS patients, the N-ERAS group had significantly less time to return of bowel function (mean 1.30 days versus 1.11 days, p<0.001), shorter hospital stays (mean/median 4.57/4 days versus 3.63/3 days, p=0.001) and less total hospital mean charges/patient ($47,403 versus $42,979, p=0.037), respectively. This translated into approximately a 9.3% decrease ($4,424) in mean charges/patient using the N-ERAS protocol. Consequently, for the N-ERAS cohort, hospital charges were likely $499,912 lower than expected for the 113 patients.

      Conclusion

      Use of this patient-compliant N-ERAS preoperative nutrition protocol in normally nourished thoracic cancer surgical patients is associated with accelerated bowel function recovery, decreased hospital stays and lower charges. While a prospective clinical trial is warranted, thoracic surgeons should consider using N-ERAS in their major surgical patients with an expectation of improved clinical results at a lower cost--an important consideration when exploring ways to decrease charges in the prospective payment environment.

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      P1.16-52 - Long-Term Impact of Postoperative Complications Following Lung Resection Among Patients with Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Shuichi Shinohara  |  Author(s): Takamitsu Onitsuka, Masakazu Sugaya

      • Abstract

      Background

      Postoperative complications following lung resection are fatal and common. The immediate effects of postoperative complications are clearly associated with poor prognosis; however, the long-term effects remain unclear. The aim of this study was to investigate the long-term effect of postoperative complications in patients with non-small cell lung cancer following lung resection.

      Method

      This investigation was designed as a retrospective cohort study including 345 consecutive patients with non-small cell lung cancer who underwent lung resection as the curative surgery at a single institution between 2007 and 2016. Three patients who had surgery related deaths which is defined as the event within hospital stay or within 30days after surgery was excluded. Postoperative complications were graded according to the Clavien-Dindo classification. Postoperative complications included a grade of greater than and equal to 2. We devided two groups among patients with complications(n=109) and without complications (n=233), and evaluate the deta between two groups. Clinical characteristics, pathological features, and causes of death were analysed. Survival analysis was conducted by the Kaplan-Meier method. Prognostic factors were analysed by a Cox proportional hazard model.

      Result

      Throughout the study, 253 patients (74.0%) survived and 89 died (26.0%). The median length of follow-up was 51.8 months. Postoperative complications were observed in 109 patients (31.9%). Operation time, smoking index (pack-year), the rate of COPD, and lymphatic invasion were significantly higher in patients with complications than those withtout complications (p=0.001, <0.001, <0.001 and 0.02, respectively). FEV1.0% was lower in the complications group (p <0.001). In comparison to an absence of complications, the presence of complications resulted in worse 5-year overall survival (68.3% vs. 79.5%; p=0.001), worse recurrence-free survival (48.4% vs. 71.0%; p<0.001), and worse cause-specific survival (84.4% vs. 90.5%; p=0.003). There are no significant differences between two groups in concerning non-cause-specific survival (81.0% vs. 94.7%; p=0.095). Patients with complications had higher rates of lung cancer death (15.6% vs. 9.0%; p=0.030). The 5-year overall survival in patients with pulmonary complications tended to be poorer than among those without them, although the difference was not significant (64.2% vs. 70.4%; p=0.072). The Cox proportional hazards model for OS adjusted for age, sex, pathological staging, Charlson comorbdity index, COPD, vascular invasion, lymphatic invasion, pleural invasion, CEA ≥5 ng/ml, and lobectomy showed that postoperative complications are associated with a poorer overall survival (hazard ratio 1.78; 95%CI=1.15–2.19; p =0.010).

      Conclusion

      Our findings indicate that postoperative complications were associated with poor overall survival due to the increase in cause-specific deaths.

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      P1.16-53 - County-Level Variations and Contributing Factors in Receipt of Surgery for Early-Stage Non-Small Cell Lung Cancer in the US

      16:45 - 18:00  |  Presenting Author(s): Raymond U. Osarogiagbon  |  Author(s): Helmneh M Sineshaw, Liora Sahar, Ahmedin Jemal

      • Abstract

      Background

      Previous studies have reported geographic variations in receipt of curative-intent surgery for early-stage non-small cell lung cancer (NSCLC) across states or regions in the United States. However, little is known about the extent of county-level variations in the receipt of care within and across states, and factors contributing to these variations. We examined county-level variations in receipt of curative-intent surgical treatment, and factors contributing to such variations, for patients with early-stage NSCLC in the United States.

      Method

      Patients with stage I or II NSCLC diagnosed in 2007–2014 were identified from 40 states and the District of Colombia population-based cancer registries compiled by the North American Association of Central Cancer Registries. A total of 179,189 patients residing in 2,263 counties were included. Percentage of patients who underwent curative-intent surgery was calculated for each county with 20 or more cases. Adjusted means were generated using mixed effects model accounting for covariates that were significant in three sequential models (model 1: age, sex, race/ethnicity; model 2: race/ethnicity, tumor size, grade; model 3: race/ethnicity, percent below poverty level, urban/rural status, surgeon-to-population ratio). Surgeon-to-population ratio was calculated using the 2010 county-level data from the Area Health Resources Files, by dividing the total number of surgeons (general and thoracic surgeons) by the total population age 35 years and older in the county.

      Result

      Receipt of curative-intent surgery for early-stage NSCLC during 2007-2014 by county ranged from 12.8% to 91.7% (sevenfold difference), with a median of 64.5% (interquartile range, 58.8%-71.2%). Higher proportion of non-Hispanic blacks, uninsured patients, and patients residing in high poverty census tracts and in low surgeon-to-population ratio counties were at the lowest quartile of county-level percentage in receipt of curative-intent surgery. In the adjusted means, poverty level, surgeon-to-population ratio, and urban/rural status were independent predictors of receipt of surgery by county. For example, there was a 12% significant difference in adjusted mean between patients residing in affluent and poor neighborhoods.

      Conclusion

      Receipt of curative-intent surgery for early-stage NSCLC varied substantially across counties in the United States. Area-level socioeconomic status and surgeon availability were significantly associated with this variation, which may therefore be amenable to corrective intervention. Further studies are needed to identify and address gaps in access to surgical treatment of early-stage NSCLC.

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      P1.16-54 - The Significance of Multiple Lung Cancer Occurrence in Surgically-Treated Clincal Stage I Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Hiroshi Sugimura  |  Author(s): Yue Cong, Shuji Mishima, Hiroaki Nomori, Akihiko Takeshi

      • Abstract

      Background

      Advancements in lung cancer early detection and treatment are leading to an increase in patients with diagnoses of multiple primary lung cancers or lung cancers with multiple pulmonary sites of involvement. While lobectomy is considered the standard for surgical treatment in early stage non-small cell lung cancer, the optimal treatment strategies in such cases are not well known.

      Method

      From February 2012 to February 2017, 370 consecutive c-stage I non-small cell lung cancer patients were surgically treated with lobectomy or segmentectomy and systematic lymph node dissection. A retrospective review was conducted for cases with multiple lung cancers. Multiple lung cancers (MLC) were defined as multiple pulmonary nodules with no clear evidence of either lesion to be a metastasis from the other, and with no lymph node or distant metastases at presentation of the secondary lesion. Cases with multiple pulmonary nodules with ground glass features were also considered MLC if they met the above criteria. Clinical characteristics and outcomes were reviewed.

      Result

      Sixty-five cases (17%) were considered (synchronous and/or metachronous) MLC. The secondary lesion occupied the opposite lung in 32 cases, the same lobe in 24 cases, and other lobes of the same lung in 17 cases. Multiple adenocarcinomas with ground glass features were frequently seen as synchronous lesions (33/40), and the majority (69%) of synchronous cases were found in the same lobe.

      MLC were resected in a single surgical procedure in 22 cases. A second procedure was given in 21, and a third in 2. The initial surgery was lobectomy in 53% of cases and segmentectomy in 47%. The second procedure was segmentectomy in 14 (67%) cases, partial resection in 6, and lobectomy in 1. In 12 cases, multiple sites of lung cancer were treated with initial surgery and a subsequent non-surgical procedure (SBRT, cryotherapy, etc.).

      Lung cancer recurrence following surgical resection for MLC occurred in 3 cases, two of which had lymph node involvement at time of surgery. Three-year survival following final surgery was 89.5% (median follow-up 1142 days) in all cases, and was 94.6% in cases with MLC.

      Conclusion

      Multiple lung cancer occurrence is not rare among c-stage I lung cancer cases. Repeated lung-sparing resections seem feasible as part of their treatment. Aggressive local therapy may lead to prolonged survival.

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      P1.16-55 - Surgical Treatment for Lung Cancer. Subaortic (Para-Aortic) Lymph Nodes Involvement - N1 or N2 Disease?

      16:45 - 18:00  |  Presenting Author(s): Magdalena Szczęsna  |  Author(s): Piotr Rudzinski, Tadeusz Orłowski

      • Abstract

      Background

      In patients with cN2 disease surgical treatment alone is not recommended because it often indicates systemic disease. Qualification to undergo a surgery patients with clinical manifestation of subaortic (#5)/para-aortic (#6) nodes malignant involvement remains controversial. The aim of this study is to compare survivals of patients with single station metastases to #5(#6) lymph nodes, patients with interlobar (#11) and lobar (#12) nodes involvement (pN1) and patients with right lower paratracheal (#4R) and subcarinal (#7) nodes involvement (pN2) after received lung resection.

      Method

      Material was collected rectospectively from an online-survey-based database of the Polish Lung Cancer Group and included patients who underwent a surgical treatment due to lung cancer at multi-institution in Poland between 2007 and 2017. The 8th Edition of the Staging Classification System (TNM, 2017) was used to determine staging.

      Result

      There were 34 870 patients (35,52% females and 64,48% males) who received surgical treatment for lung cancer. 27 321 (78,35%) underwent lobectomy, 1 063 (3,04%) segmentectomy, 4 658 (13,35%) pneumonectomy, 1 768 (5,07%) wedge resection. Histologic types included: non-small cell lung cancer (n= 475), adenocarcinoma (n=13 515), squamous cell carcinoma (n=14 273), large cell carcinoma (2 127), carcinoid (n=1 428) and others (n=2 934). Stage IA1 disease presented 683 (1,97%) patients, IA2 - 4442 (12,79%), IA3 - 3674 (10,58%), IB - 7150 (20,59%). Stage IIA disease presented 2493 (7,18%) patients, IIB - 7442 (21,43%). 6804 (19,59%) patients were in stage IIIA disease, 1529 (4,4%) in IIIB and 475 (1,37%) in IVA, 12 (0,03%) in IVB disease. The majority of patients were diagnosed with N0 disease (n: 24388, 70,23%). N1 disease was reported in 5913 (17,03%) cases, N2 disease in 4 412 (12,71%).

      Among patients with N1 disease there were 3543 cases with confirmed metastases only in #11 or #12 nodes. 3-, 5-, 7- and over 7-year survivals in this group were 70,03%, 15,33%, 8,41%, 6,24%. Among patients with N2 disease there were 1202 cases with exclusive involvement of #4R or #7 nodes. 3-, 5-, 7- and over 7-year survivals in this group were 73,21%, 14,14%, 7,74%, 4,91%. Malignant involvement of #5 or #6 nodes were reported in 1047 cases. 3-, 5-, 7- and over 7-year survivals here were 75,17%, 14,04%, 6,59%, 4,2%.

      Conclusion

      According to the study there is no significant difference in survival of patients with #5(6) nodes invasion comparing to those with N2 and N1 disease. Controversy followed from classification #5(6) nodes as N2 remains unsettled.

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      P1.16-56 - Prognostic Ability of New T1 Descriptors in the TNM Classification of Surgically Treated Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Tomoyoshi Takenaka  |  Author(s): Koji Yamazaki, Sadanori Takeo

      • Abstract

      Background

      In the tumor, node, and metastasis (TNM) classification (8th edition) of non-small cell lung cancer (NSCLC), T (tumor size) is determined solely according to the size of the solid component determined using computed tomography (CT). However, it is unclear if tumors of equal size but with differing solid and part-solid components should be similarly treated. Here we assessed the prognostic significance of the newly proposed T1 descriptors with respect to the size of the solid component.

      Method

      We analyzed overall survival (OS) and disease-free survival (DFS) between groups of patients (n = 255) with solid or part-solid tumors. Propensity score matching (PSM) was added as an exploratory analysis of survival among patients with solid tumors and part-solid tumors to balance the size of the solid. The new staging system was used for classification and comparison of survival.

      Result

      figure.jpgChest CT detected 7 non-solid tumors, 123 part-solid tumors and 125 solid tumors. All patients underwent pulmonary lobectomy. The 5-year OS and DFS rates differed significantly between the solid tumor (OS, 71.2%; DFS, 65.4%) and part-solid tumor (OS, 83.2%; DFS, 78.2%) groups. However, among 81 PSM pairs, their 5-year survival rates did not significantly differ as follows: 5-year OS, solid tumor group = 75.1% vs part-solid group = 79.6% (P=0.39); and 5-year DFS, solid tumor group = 68.2% vs part-solid group = 71.9% (P=0.37). Using the 8th TNM edition, 5-year OS rates were patients diagnosed with cIA1 disease: 88.0%; cIA2: 79.4%; and cIA3: 67.6%.

      Conclusion

      PSM did not detect a significant difference in survival between the groups with solid tumors and those with part-solid tumors when matched according to the size of the solid component. The new T descriptors included in the 8th edition of the TNM provide a detailed classification of patients with NSCLC ≤3 cm in diameter.

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      P1.16-57 - Outcomes of Pulmonary Resection in Elderly Non-Small Cell Lung Cancer Patient

      16:45 - 18:00  |  Presenting Author(s): Apichat Tantraworasin  |  Author(s): Sophon Siwachat, Narumon Tanatip, Nirush Lertprasertsuke, Sarawut Kongkarnka, Juntima Euathrongchit, Yutthaphan Wannasopha, Thatthan Suksombooncharoen, Busayamas Chewaskulyong, Emanuela Taioli, Somcharoen Saeteng

      • Abstract

      Background

      Because of increasing in life span and more than third-fourth of lung cancer patients being age > 60-65 years old, appropriate treatment of old lung cancer patients has become an important issue. The aim of this study is to evaluate the short and long-term surgical outcomes in elderly patients, and to identify prognostic factors of overall mortality.

      Method

      Medical records of patients with non-small cell lung cancer (NSCLC) who underwent pulmonary resection at Chiang Mai University Hospital from January 2002 through December 2016 were retrospectively reviewed. Patients were divided into two groups; age less than 70 years (non-elderly group) and 70 years or more (elderly group). Primary outcome was major post-operative complications and in-hospital death; secondary outcome was long-term survival. Logistic regression and cox proportional hazard model were used to analyze data.

      Result

      This study included 583 patients; 167 in elderly group, and 416 in non-elderly group. Patients in elderly group were more likely to have government insurance, be active smoker, and have a diagnosis of COPD, an abnormal ECG, to undergo a sublobar resection, lymph node sampling, and no chemotherapy treatment than those in the non-elderly group. There were no differences in term of in-hospital mortality, composite post-operative complications, and overall mortality. At multivariable analysis, the composite post-operative complications in the elderly group was not statistically different from the non-elderly group (Adjusted odd ratios = 0.52, 95% CI=0.21-1.28), however the elderly group was more likely to die (HRadj)=2.44, 95%CI=1.26-4.74). Adverse prognostic factors for overall mortality in elderly patients were a poorly differentiated tumor (HRadj=3.53, 95%CI=1.45-8.61) and the presence with perineural invasion (HRadj=3.95, 95%CI=1.14-13.77)

      Table 1 prognostic factors for overall mortality of elderly NSCLC patients after pulmonary resection

      Variables

      Hazard Ratio

      95% CI

      p-value

      Male vs Female

      1.43

      0.62-3.26

      0.401

      Smoking amount

      ≥20 pack-year

      0.91

      0.45-1.82

      0.783

      Stage of cancer

      Stage I

      1.00

      Reference

      Stage II

      0.76

      0.36-1.57

      0.452

      Stage III

      2.18

      0.92-5.16

      0.077

      Stage IV

      1.70

      0.53-5.46

      0.373

      Grading of cell differentiation

      Well

      1.00

      Reference

      Moderately

      0.80

      0.39-1.67

      0.558

      Poorly

      3.53

      1.45-8.61

      0.006

      Undifferentiated

      1.72

      0.41-7.31

      0.462

      Intratumoral lymphatic invasion

      2.73

      0.99-7.52

      0.052

      Intratumoral vascular invasion

      1.76

      0.91-3.39

      0.092

      Perineural invasion

      3.95

      1.14-13.77

      0.031

      SLND versus SLNS

      0.51

      0.24-1.10

      0.084

      Chemotherapy

      No chemotherapy

      1.00

      Reference

      Adjuvant or induction therapy

      0.69

      0.33-1.46

      0.330

      1st-line treatment

      0.76

      0.15-3.80

      0.734

      Sublobar resection versus lobectomy

      1.78

      0.65-4.90

      0.261

      Conclusion

      Surgery in elderly NSCLC is a safe procedure. Patients presenting with perineural invasion and poorly differentiated tumor should be further considered for possible adjuvant treatment.

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      P1.16-58 - Hospital Lung Surgery Volume and Patient Outcomes in Victoria

      16:45 - 18:00  |  Presenting Author(s): Alesha A Thai  |  Author(s): Ella Stuart, Luc Te Marvelde, Simon Knight, Roger L Milne, Kathryn Whitfield, Paul Mitchell

      • Abstract

      Background

      Surgical resection remains the primary curative option for early stage non-small cell lung cancer (NSCLC) with lobectomies considered the gold standard due to a reduction in local recurrence and improved overall survival. There has been growing evidence of an association between patient outcomes and the number of cancer surgeries performed at a hospital since the seminal paper by Luft et al in 1979.

      To our knowledge, there are no Australian data on hospital cancer surgery volumes and patient outcomes by procedure, and few data worldwide on specific lung surgery procedures and outcomes. We evaluated the relationship between hospital NSCLC surgery volume and patient outcomes in Victoria.

      Method

      Victorians with a primary diagnosis of NSCLC between 2008 and 2014 were identified in the Victorian Cancer Registry (n=15,469), 3,420 (22%) of whom had surgery. Primary outcome was death within 90 days of surgery and secondary outcomes were overall survival, use of postoperative ventilation, ≥24hours spent in ICU and length of stay >17days. Hospital volume was measured as the average number of lung surgeries performed per year, with quartiles Q1: 1-17, Q2: 18-34, Q3: 35-58 and Q4: 59+.

      Result

      57% (1,941/3,420) lung cancer patients underwent lobectomy, 38% (1,299/3,420) sub-lobar resection and 5% (180/3,420) pneumonectomy. The overall 90-day mortality after lung surgery was 3.5%, and was 2.6% for patients undergoing lobectomy compared with 4.5% for those undergoing sub-lobar resection. There was no difference in 90-day mortality between low- and high-volume centres regardless of procedure. Patients operated in lower volume centres had more admissions to ICU ≥24hours (Q1. 55% vs. Q4. 11%, p-trend <0.001). Median overall survival was 6.2 years, 5.4 years and 5.8 years for lobectomy, sub-lobar resection and pneumonectomy, respectively. The distribution of ASA scores differed between patients attending public and private hospitals. A higher proportion of patients attending private hospitals (19%) had an ASA score of 4 compared with patients attending a public hospital (9%).

      Conclusion

      We observed no evidence of survival differences between lung cancer patients attending low- and high-volume hospitals for surgery, regardless of surgical procedure. Median overall survival in Victorian is substantially better compared to interstate and international data. Of interest, a higher proportion of patients had an ICU admission ≥24hours in lower volume centres. We also observed a higher proportion of patients with an ASA score of 4 in private hospitals compared to public hospitals; the reasons for this are unclear and warrant further investigation.

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      P1.16-59 - A Phase II Study of Adjuvant Chemotherapy with Tegafur-Uracil for Vessel Invasion Positive Stage IA Non-Small Cell Lung Cancer (LOGIK0602)

      16:45 - 18:00  |  Presenting Author(s): Tomoshi Tsuchiya  |  Author(s): Takeshi Nagayasu, Ryotaro Kamohara, Masashi Muraoka, Sho Saeki, Yukito Ichinose, Makoto Suzuki, Kazuo Inada, Shoji Tokunaga, Tomayoshi Hayashi, Shogo Urabe, Takaomi Koga, Shinji Akamine, Kenji Sugio

      • Abstract

      Background

      Vessel invasion, which includes vascular or lymphatic invasions, is a representative prognostic factor in lung cancer therapy. Even in the patients with resected stage IA non-small cell lung cancer (NSCLC), vessel invasion is a significant poor prognostic factor. The pathological analysis of 322 cases of resected stage IA NSCLC in Oita Prefectural Hospital revealed that the 5-yr overall survival rate was 71.8% in the vessel invasion-positive group and significantly worse than the 89.6% in the vessel invasion-negative group. Interestingly, the 5-yr overall survival rate of the oral tegafur-uracil adjuvant chemotherapy group was 93.3% and significantly better than the 66.6% of the untreated group. Tegafur-uracil is known to affect vascular endothelial growth factor overexpressing tumours. Therefore, to estimate the positive effect of adjuvant tegafur-uracil in patients with vessel invasion-positive stage IA NSCLC, we conducted a multi-center single-arm phase II study (LOGIK0602).

      Method

      The patients with completely resected vessel invasion-positive stage IA NSCLC were registered at the Lung Oncology Group in Kyushu (LOGIK). Vessel invasion was diagnosed by two of the three pathologists. Adjuvant chemotherapy consisted of 2 years of oral tegafur-uracil at 250 mg/m2/day. Fifty-five patients from 7 institutions were enrolled from June 2007 to September 2012. The primary endpoint was the 5-yr overall survival rate. Secondary endpoints were the rate of accomplishment of scheduled adjuvant chemotherapy, incidence and grade of adverse reactions, 3-yr overall and relapse-free survival rates, and 5-yr relapse-free survival rate.

      Result

      Among the 52 eligible patients, 16 (30.8%) discontinued tegafur-uracil administration and 36 (69.2%) completed the treatment course. The observation period was calculated as 562 to 3107 days and median observation period as 1947 days using the reverse Kaplan-Meier method. There were 39 male and 13 female patients. The 3-yr and 5-yr overall survival rates were 96.2% and 94.2% respectively, which were obviously better than the historical data of 28% to 78.7% in 8 reports. The 3-yr and 5-yr relapse-free survival rates were 92.3% and 88.5%, respectively. Eighteen adverse reactions were observed including 4 cases of grade 3 hepatic function disorder (7.7%) and 5 cases of grade 2 anorexia (9.6%). No grade 4 adverse effect was encountered. Five recurrences were observed including 1 distant metastasis (adrenal) and 4 local recurrences (lung: 2, lymph node: 2).

      Conclusion

      A 2-year course of oral tegafur-uracil administration is feasible and might have a significant benefit in the adjuvant treatment of vessel invasion-positive stage IA NSCLC.

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      P1.16-60 - A High Risk of Recurrence After the Resection of Lower Lobe Adenocarcinoma

      16:45 - 18:00  |  Presenting Author(s): Kazuhiro Ueda  |  Author(s): Toshiki Tanaka, Sota Yoshimine, Tamami Nakamura, Junichi Murakami, Kimikazu Hamano

      • Abstract

      Background

      According to previous reports, non-small cell lung cancers arising in the lower lobe are associated with a worse prognosis than those arising in the upper lobe; however, the reason remains to be elucidated. Thus, we attempted to identify high-risk population in patients with lower lobe disease, that may substantially cause poor prognosis of lower lobe disease.

      Method

      We retrospectively reviewed a consecutive series of 400 patients with completely resected lung adenocarcinoma who were treated between January 2006 and December 2015. All patients underwent major lung resection and lymph node dissection. The clinicopathological factors that were investigated included the solid component size, the pathological subtype (pre-invasive, minimally invasive/invasive), the epidermal growth factor receptor (EGFR) mutation status, and some other characteristics (TNM 8th edition).

      Result

      fig 1.jpgThe proportion of never-smokers among patients with lower lobe disease was significantly higher than that among those with upper lobe disease. According to a multivariate proportional hazards analysis, primary site (upper/lower) was an independent predictor of early recurrence, along with the solid component size, pleural lavage cytology results, pathological pleural invasion, and pathological lymph node metastasis. However, although lower lobe disease was associated with early recurrence in never smokers (Fig 1A), it was not in smokers (Fig 1B). Furthermore, although lower lobe disease was associated with early recurrence in never smokers with EGFR wild-type tumors (Fig 1C), it was not in never smokers with EGFR mutant tumors (Fig 1D). EGFR wild-type tumors were more frequently detected in patients with lower lobe disease than in those with upper lobe disease when the analysis was restricted to never smokers.

      Conclusion

      Patients with lower lobe cancer, particularly those without a smoking history or those with EGFR wild-type tumors, showed a higher risk of recurrence than their counterparts with upper lobe disease. Further studies that include the molecular profiling of such aggressive lesions, are warranted.

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      P1.16-61 - Intermittent Chest Tube Clamping Shortens Chest Tube Duration After Lung Cancer Surgery: An Interim Analysis of Randomized Clinical Trial

      16:45 - 18:00  |  Presenting Author(s): Shi Yan  |  Author(s): Yaqi Wang, Xing Wang, Shaolei Li, Chao Lv, Yuzhao Wang, Jia Wang, Yue Yang, Wu Nan

      • Abstract

      Background

      Postoperative pleural drainage markedly influences the length of hospital stay and the financial costs of medical care. Our previous retrospective study proved the safety and effectiveness of chest tube clamping in the term of shortening chest tube duration. This study aims to determine if intermittent chest tube clamping could decrease chest tube duration and total drainage volume after lung cancer surgery in randomized clinical trial. This trial is registered with ClinicalTrials.gov (NCT03379350).

      Method

      All the patients were managed with gravity drainage (water seal only, without suction) during the first 12–24 h (depending on the time of surgery completion) after surgery. Once a radiograph confirmed re-expansion of the lung on the morning of the POD1 and no air leak was detected, patients were randomly assigned to intermittent chest tube clamping as study arm or traditional chest tube management as control arm. Patients in control arm were unchangeably managed with gravity drainage. In clamping arm, the chest tube would be clamped, and the nurses would check the patient every 6 h. If the patient had no problems with compliance, the clamp was removed for 30 minutes in the morning to record the drainage volume every 24 h. The criterion for chest tube removal was drainage volume <250 mL in 24 h.

      Result

      Seven-two consecutive patients with operable lung cancer treated using lobectomy were randomized, all of them were eligible and evaluable. Thirty-seven and 35 patients were randomly assigned to clamping arm and control arm, respectively. There were no significant differences between two groups in terms of demographics, such of age, gender and the percentage of neoadjuvant treatment. Analyses were performed to compare drainage duration between two groups. Chest tube drainage duration was significantly shorter in clamping group than in control group (2.3±0.5 days vs. 2.7±0.9 days, p = 0.011). Total drainage volume was significantly less in clamping group than in control group (411.0±183.1 ml vs. 553.7±333.6 ml, p = 0.030). Only one patient in clamping group underwent thoracocentesis after chest tube removal due to chylothorax, which was probably caused by excess high-fat diet. No pyrexia relevant to chest tube clamping occurred. There was some degree of improvement on plasma albumin declination at discharge in clamping group over control group (7.5±2.5 g/L vs. 8.6±3.6 g/L, p = 0.119), but without a significant statistical difference.

      Conclusion

      Intermittent postoperative chest tube clamping decreases chest tube duration and total drainage volume while maintaining patient safety. Further investigation is warranted.

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      P1.16-62 - A Nomogram to Predict Disease-Free Survival After Curative Resection of Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Ziping Wang  |  Author(s): Xiaoyu Zhai, Qiwen Zheng

      • Abstract

      Background

      The aim of this study was to find clinicopathologic variables associated with disease-free survival (DSF) and develop a prognostic nomogram for patients with curative resected non-small-cell lung cancer (NSCLC) and compare the value of the nomogram to the seventh AJCC TNM classification.

      Method

      A nomogram to predict DFS following surgical resection of NSCLC was constructed using a single-institutional cohort of 805 patients who underwent curative resection of lung adenocarcinoma in the Cancer Hospital of the Chinese Academy of Medical Sciences (Beijing, China) between January 2003 and December 2013. For nomogram construction and validation, we randomly assigned two thirds of the patients to the training cohort (n=605) and one third to the validation cohort (n=260). The median age of training cohort was 57 years (range, 25-76) and the proportion of male and female patients was 64.8% vs. 35.2%. Half of the patients (49.8%) presented with early-stage disease and 85.3% patients received adjuvant chemotherapy alone. The predictive discriminative and calibration were measured by concordance index (C-index), risk group stratification and calibration plot.

      Result

      The median disease-free survival for the total cohort was 23.2 months (95% CI, 21.3-26.4 months). The 1-, 3- and 5-year disease-free survival was 71.3%, 39.5% and 32.3%, respectively. The nomogram included 8 important variables based on a Cox proportional hazards regression modeling of the training cohort: histology, differentiation, nodal status, AJCC T category, primary tumor location, type of surgical resection, adjuvant radiotherapy and regimen. Each patient with a higher score had a worse prognosis. Prognostic discrimination was performed by dividing the predicted nomogram score into quartiles that were then used to plot Kaplan-Meier curves. The nomogram was able to stratify patients into 4 distinct incremental 3-year prognostic groups (quartile 1, 73.0%; quartile 2, 49.6%; quartile 3, 30.6%; and quartile 4, 9.3% [P <0.001]). Both in the training and validation cohort, the C-index of the nomogram for DFS prediction was superior to the TNM category prediction (training cohort, 0.694 vs. 0.640; P<0.01 and validation cohort, 0.662 vs. 0.602; P<0.01). The 200-sample bootstrapped calibration curves for probability of 3- and 5-year disease-free survival (PFS) showed optimal agreement between nomogram prediction and actual observation.

      Conclusion

      This novel nomogram provides an individualized prediction of DFS in NSCLC patients after radical surgery and may assist the clinical treatment decision making and clinical trials designing.

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      P1.16-63 - The Value of Adjuvant Chemotherapy in Patients with Resected Stage IB Solid Predominant and Solid Non-Predominant Lung Adenocarcinoma

      16:45 - 18:00  |  Presenting Author(s): Shuhui Cao  |  Author(s): Hua Zhong, Jianlin Xu

      • Abstract

      Background

      The adjuvant chemotherapy(ACT) of stage IB lung adenocarcinoma remain controversial. We are intended to explore the benefits adjuvant chemotherapy made on patients in IB with solid ingredients.

      Method

      A number of 334 completely resected patients with lung adenocarcinoma in stage IB from 2006 to 2015 were reviewed. All the pathological slides were evaluated with solid ingredients composed.

      Result

      Our data showed that although disease-free survival (DFS)(p=0.661) and overall survival (OS)(p=0.130) were not significantly different in solid growth pattern with or without ACT, patients with solid predominant patterns tend to have longer DFS [hazard ratio (HR) 0.403, p=0.021)]and OS (HR 0.286, p=0.009) with ACT. In patients with solid non-predominant patterns, receiving ACT had no influence in DFS(p=0.231) and OS (p=0.611).

      未标题-1.jpg

      1disease  free survival (a) and overall survival (b) of in all patients involved surgical intervention alone and adjuvant chemotherapy and disease free survival(c) and overall survival(.jpg

      Conclusion

      The solid predominant pattern in postoperative patients of stage IB could benefit from adjuvant, and solid non-predominant pattern couldn’t.

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      P1.16-64 - The Histological Predominant Pattern Could Predict Site of Recurrence and Metastasis in Surgically Treated Stage I Adenocarcinoma of the Lung

      16:45 - 18:00  |  Presenting Author(s): Francesco Guerrera  |  Author(s): Valentina Marchese, Filippo Lococo, Ottavio Rena, Luca Ampollini, Jacopo Vannucci, Luca Errico, Pietro Bertoglio, Paolo Olivo Lausi, Luigi Ventura, Andrea Viti, Massimiliano Paci, Pier Luigi Filosso, Alberto Oliaro, Caterina Casadio, Francesco Puma, Francesco Ardissone, Enrico Ruffini

      • Abstract

      Background

      Pattern-based subtyping of adenocarcinoma of the lung is currently recommended due to prognostic implications. We aimed to evaluate whether predominant pattern subtype in surgically treated stage I adenocarcinoma of the lung can predict first site of recurrence or metastasis.

      Method

      We retrospectively reviewed clinical information, radiological findings, PET/CT-records, and pathological features (classified by IASLC/ATS/ERS subtyping criteria) of 906 Stage-I adenocarcinoma of the lung, who underwent surgery in 7 Centers. Patients were classified by histologic grade according to the IASLC/ATS/ERS classification as follow: intermediate grade (Invasive Lepidic, Acinar, Papillary) vs. high grade (Micropapillary, Solid) vs. NOS. The date of recurrence or metastases was defined as the first radiographic evidence of cancer relapse upon imaging or pathological tumour evidence from a biopsy. Univariate and multivariate logistic analysis were used to identify predictors of first site of recurrence or metastasis.

      Result

      A total of 248 (27%) patients developed recurrence or distant metastasis. The most commonly observed first location of recurrence was ipsilateral thorax (133 cases, 44%), followed by brain (27, 11%), contralateral lung (24, 10%), bones (11, 4%), liver and adrenal gland (10, 4%). Forty-three patients (17%) presented recurrence or metastasis in multiple sites simultaneously at the time of diagnosis. At multivariate analysis, patients with intermediate-grade histology developed intra-thoracic recurrence more frequently compared to the remainder of the cohort (odds ratio (OR) 1.85, 95% confidence interval (CI): 1.1– 3.18, P=0.038). Patients with high-grade histology developed contralateral lung metastasis (OR 2.1, 95%CI 1.1-4.2, P= 0.044) and brain metastasis (OR 2.5, 95%CI 1.3-5.1, P<0.01) more frequently compared to the low-grade ones.

      Conclusion

      Predominant pattern subtype seems to predict site-specific recurrence and metastasis in surgically treated Stage I adenocarcinoma of the lung.

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    P1.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session)

    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Moderators:
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      P1.17-01 - Robustness of an Image-Based Data Mining Approach in Lung Cancer Patients

      16:45 - 18:00  |  Presenting Author(s): Alan McWilliam  |  Author(s): Eliana Vasquez Osorio, Marianne C Aznar, Andrew Green, Corinne Faivre-Finn, Marcel Van Herk

      • Abstract

      Background

      Image-based data mining (IBDM) enables exploring the correlation of dose distributions and outcomes in large cohorts of patients without the requirement of additional contouring. IBDM has recently identified the dose to the base of the heart as an important predictor for overall survival (OS) in lung cancer patients receiving radiotherapy [McWilliam et al EJC 2017]. IBDM relies on non-rigid registration to set inter-patient dosimetric data into a common reference anatomy or reference patient. Here, we investigated the uncertainties associated with the choice of reference patient, and their influence on the correlation between incidental dose to the base of the heart and OS.

      Method

      In previous work, 1101 NSCLC patients (55Gy / 20 fractions) were randomly selected, and their planning CT images non-rigidly registered to a reference patient CT scan using NiftyReg (http://cmictig.cs.ucl.ac.uk/wiki/) as part of IBDM process. In this work, 5 additional patients with small cell lung cancer (i.e. without a large tumour burden) were used as “reference patients” and the IBDM analysis in the whole cohort was repeated for each reference patient. Permutation testing with 100 iterations was applied to assess statistical significance.

      Result

      slide1.jpg

      Figure 1 shows the regions of highly significant correlation between dose and OS for each reference patient. In spite of large variations in anatomy between the reference patients, each analysis identified similar anatomical regions as significantly associated with OS (t>5). Moreover, permutation testing was consistent with the original findings.

      Conclusion

      IBDM is a robust approach and, in this analysis, does not appear to be sensitive to the choice of reference patient for the investigated dose-effect correlation. Prospective studies are necessary to confirm the correlation between dose to the base of the heart and OS in NSCLC patients. Methodological studies are needed to determine the level of effect strength and region size that this general technique can identify.

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      P1.17-02 - Low Prognostic Nutritional Index Predicts Poor Survival in Stage IIIB Non-Small Cell Lung Cancer Patients Treated with Chemoradiotherapy

      16:45 - 18:00  |  Presenting Author(s): Ali Ayberk Besen  |  Author(s): Erkan Topkan, Yurday Ozdemir, Ozan Cem Guler, Berna Yıldırım, Ugur Selek, Fatih Kose, Ozgur Ozyılkan

      • Abstract

      Background

      The prognostic role of prognostic nutritional index (PNI) has been widely investigated and showed in many types of cancer. However, to our best knowledge, the significance of PNI has never been investigated in locally advanced non-small cell lung cancer (NSCLC) who were treated with concurrent chemoradiotherapy ( CCRT). Therefore in this current study, we aimed to investigate the prognostic impact of PNI on survival outcomes of locally advanced NSCLC undergoing CCRT.

      Method

      The data of 358 patients with stage IIIB NSCLC treated with CCRT were analyzed retrospectively. All patients received 60 to 66 Gy (2 Gy per fraction) thoracic radiotherapy and at least one course of platinum-based doublet chemotherapy concomitantly. For each patient PNI was calculated by the known formula in blood samples those were available prior to CCRT: [PNI=10×serum albumin (g/dl) + 0.005×total lymphocyte count (mm3)]. The primary endpoint was the association between PNI and overall survival (OS). Secondary endpoints were locoregional progression-free survival (LPFS) and progression-free survival (PFS). The survival curves were calculated by Kaplan-Meier method and log-rank test. The cutoff value of the PNI was analyzed by receiver operating curve (ROC).

      Result

      At a median follow-up of 22.5 months (2.4-123.5 months) 108 patients (30.2%) were still alive. For the whole study cohort median OS was 25.2 months (95 % CI: 22.7-27.7). The median LPFS and PFS were 15.4 months (95% CI: 14.4-16.4) and 10.7 months (95% CI: 9.7-11.7) respectively. In ROC analysis, calculated cutoff value of PNI was 40.1 (AUC: 67.8% (62.0-73.6); sensitivity: 73.1; specificity: 68.4, p<0.001). According to this, patients were grouped as follows, group 1: PNI>40 and group 2: PNI<40. Accordingly, for the patients in group 1, OS (36.7 vs. 16.8 months, p<0.001), LPFS (19.5 vs. 11.5 months, p<0.001) and PFS (13.6 vs. 8.6 months, p<0.001) times were significantly better as compared to patients in group 2. Results of the multivariate analysis demonstrated that the prognostic worth of PNI was independent of the other covariates (p<0.001, for each survival endpoints).

      Conclusion

      Being the first of its kind study the result of this current investigation revealed that the PNI which is easy to calculate, easily achievable with no additional cost has a strong prognostic value in prognostic stratification of the stage IIIB NSCLC patients undergoing to CCRT.

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      P1.17-03 - Potential Associated SNPs by GWAS with Radiation Pneumonitis (RP) in Patients with Lung Cancer Treated with Radiotherapy

      16:45 - 18:00  |  Presenting Author(s): Lehui Du  |  Author(s): Baolin Qu, Na Ma, Xiang Huang, Wei Yu, Shouping Xu, Xiangkun Dai

      • Abstract

      Background

      Lung cancer is one of the most prevalent cancers and the leading cause of cancer-related deaths in China and worldwide. Radiation therapy plays a remarkable role in lung cancer treatment, and approximately 60%~70% lung cancer patients receive radiation treatment. Whereas, radiation pneumonitis is one of the most critical dose-limiting toxicities of thoracic radiation. Single nucleotide polymorphisms (SNPs) in inflammation-related, DNA repair-related, oxidative stress response-related and angiogenesis-related genes and so on were proved to be associated with RP, with different underlying mechanisms. Previous limited studies reported few SNP sites that may be used a biomarker for prediction of RP risk. However these studies mainly focused on previously reported sites and only limited sites were tested. Here, the purpose of this study was to evaluate the potential related SNPs by whole genome sequencing and radiation pneumonitis (RP) development.

      Method

      We recruited a total of 132 patients with lung cancer receiving intensity modulated radiation therapy (IMRT). We collected the blood sample and sequenced the whole genomes in all patients. RP events were prospectively scored using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Kaplan-Meier analysis was used to determine the cumulative probability of RP of grade ≥ 2. Genomes-Wide Association Study (GWAS) was carried out to look for potential SNPs associated with risk of RP grade ≥ 2.

      Result

      The incidence of RP of grade ≥ 2 was 29.2%. Using SNP information by Genomes-Wide Association Study (GWAS), we discovered 73 SNPs that showed significant difference with cutting off p-value of 0.001. Most of them are previously not reported.

      Conclusion

      This result established a set of biomarkers which can be used for prognosis predictions for radiation-induced pneumonitis.

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      P1.17-04 - Curative Intent Treatment for Stage III NSCLC in England

      16:45 - 18:00  |  Presenting Author(s): Susan V Harden  |  Author(s): Aamir Khakwani, Paul Beckett, Jana Bhavani Adizie

      • Abstract

      Background

      The National Lung Cancer Audit (NLCA) produces annual reports detailing standards of care for lung cancer. This further analysis investigates the use of curative intent multi-modality treatment for people in England diagnosed with stage III NSCLC during 2016, including, for the first time, details about use of concurrent and sequential chemoradiation (cRT).

      Method

      Data on patients diagnosed during 2016 with stage III NSCLC in England were extracted from the National Cancer Registration and Analysis Service (NCRAS); information submitted through the Cancer Outcome and Services Dataset (COSD) were linked to other NCRAS datasets, including Hospital Episode Statistics (HES), the National Radiotherapy Dataset (RTDS) and the Systemic Anti-Cancer Dataset (SACT).

      Result

      6,288 cases of stage III NSCLC were analysed, 3839 Stage IIIA and 2449 Stage IIIB (Table 1).

      813 (13%) people underwent surgery with 447 (7%) of these also receiving chemotherapy (predominantly adjuvant).

      1047 (17%) people were treated with radical radiotherapy with 676 (11%) of these also receiving chemotherapy.

      For the 589/676 cRT cases where complete treatment dates were available, 199 (34%) received concurrent and 390 (66%) received sequential chemoRT (37% and 63% for stage IIIA).

      For 481/589 cases with performance status (PS) available, 171 (36%) PS0-1 cases received concurrent and 310 (64%) received sequential cRT (38% and 62% for stage IIIA)

      Of note, 2148 (34%) people received anti-cancer treatment of palliative intent and 2290 (36%) received supportive care only.

      Survival data will also be presented.

      Table 1
      wclc 2018 abstract 14010 table.png

      Conclusion

      Multi-modality treatment with either surgery or radical radiotherapy combined with chemotherapy was delivered to 1123 (18%) patients with stage III NSCLC. Concurrent cRT, optimal cRT based on meta-analysis, was delivered to just over one third of people receiving cRT, including for patients of good PS0-1. This analysis provides a baseline for future quality improvement initiatives to optimise treatment and outcomes for patients with stage III NSCLC.

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      P1.17-05 - Accelerated Radiotherapy for Non-Small Cell Lung Cancer: A 12 Year Retrospective Review of Two Dose Fractionation Schedules

      16:45 - 18:00  |  Presenting Author(s): Matthew Hatton  |  Author(s): Stephen D Robinson, Bilal Tahir, K Absalom, Dev Tripathi, Patricia Fisher, T Das, Caroline Lee, Emma Bates

      • Abstract

      Background

      Numerous dose fractionation regimes have been used for inoperable NSCLC patients and there is evidence that accelerated schedules can produce better outcome than conventionally fractionated treatment (1). Continuous hyperfractionated accelerated radiotherapy (CHART, 54Gy in 36 fractions over 12 days) and accelerated hypofractionated radiotherapy (55Gy in 20 fractions over 4 weeks) have been routinely used in Sheffield over the past decade, with schedule selection largely down to patient choice (in-patient vs out-patient treatment). In this single-centre retrospective analysis, we present the outcomes for all patients treated with these two schedules between 2003 to 2015.

      Ref

      1. LePechoux C, Mauguen A, Baumann M, et al. Hyperfractionated or Accelerated Radiotherapy in Lung Cancer: An Individual Patient Data Meta-Analysis. JCO 2012;30:2788-2797.

      Method

      In this audit details on patient demographics, tumour characteristics and survival data was collected from the electronic hospital records and supplemented by information from patient notes. Dosimetric data for tumour and organs at risk were collated automatically via the Varian Eclipse Scripting application programming interface. Descriptive statistical analysis was performed using the SSPS package with clinical and dosimetric variables assessed using independent samples t-tests and survival via a log-rank test. Multivariate survival analysis was performed using Cox regression.

      Result

      We identified 883 eligible patients, of which 45% received CHART and 55% hypofractionated radiotherapy. Mean age was 70 years and 58% were male. PET staging was performed in 87% with 30%, 15%, 51% and 4% being stage I, II, III and IV, respectively. 63% had a WHO performance status of 0-1. 38% of patients underwent induction chemotherapy. 99% completed their prescribed radiotherapy treatment with an overall response rate of 60%. Relapse was observed in 50% of patients with median disease-free survival of 19.4 months. 2-year overall survival was 47% with a median overall survival of 23.2 months. Multivariate analysis identified histology, stage, performance status, use of chemotherapy as independent predictors of survival. No significant differences between the two radiotherapy regimes was seen for any parameters.

      Conclusion

      This audit has confirmed that both CHART and hypofractionated accelerated radiotherapy are deliverable and well tolerated schedules when used in day to day practice. We have detected no significant difference in outcome between the two schedules and there is the need to explore avenues, eg dose escalation, that develop these schedules to match outcomes reported by recent concurrent chemo-radiation studies.

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      P1.17-06 - Salvage Surgery After Chemotherapy and/or Radiotherapy Including SBRT and Proton: Consecutive Analysis of 46 Patients  

      16:45 - 18:00  |  Presenting Author(s): Aki Katarina Kobayashi  |  Author(s): Hidehito Horinouchi, Yuko Nakayama, Yuichiro Ohe, Masaya Yotsukura, Shinsuke Uchida, Keisuke Asakura, Yukihiro Yoshida, Kazuo Nakagawa, Shun-ichi Watanabe

      • Abstract

      Background

      Local recurrence after definitive chemotherapy and/or radiotherapy with curative intent is frequently experienced in patients with locally advanced lung cancer. We evaluated the frequency, feasibility, and efficacy of salvage pulmonary resection after definitive chemotherapy and/or radiotherapy.

      Method

      We analyzed the characteristics and medical courses of consecutive patients who had undergone salvage pulmonary resection after local relapse or progression after chemotherapy, chemoradiotherapy and radiotherapy including stereotactic body radiation therapy (SBRT) and proton beam therapy (PBT). In this analysis, local relapse or progression were defined as increase in remaining tumor size or detection of new lesions by CT and/or FDG/PET-CT. Indications of resectability was assessed by multidisciplinary tumor board.

      Result

      Between January 2000 and January 2018, 46 patients (0.63%) received salvage surgery out of 7,290 patients underwent surgery for primary lung cancer at National Cancer Center Hospital, Tokyo, Japan. Median follow-up time was 24.5 months (range, 2-157.6). Of 46 patients evaluated, 30 (65.2%) were men, the median age was 64.5 years (range, 20-78 years), 22 (47.8%) underwent chemotherapy, 18 (39.1%) underwent resection after definitive chemoradiotherapy, 3 (6.5%) underwent resection after SBRT and 3 (6.5%) underwent resection after PBT. The number of patients undergoing salvage surgery has increased in recent years: 9 patients were between 2000 and 2009, whereas 37 patients were between 2010 and 2018. Method of surgical resection was as follows: 28 lobectomies (2 bilobectomy, 15 right upper, 1 right middle, 6 right lower, 2 left upper, 2 left lower), 10 pneumonectomies (left:right=7:3). One patient received a wedge resection, and one recieved wedge resection with chest well resection, and 2 segmentectomy and lymphadectomy for residual lymph nodes respectively. A complete resection (R0) was achieved in 42 cases (91.3%). Postoperative complications were observed in 3 patients (6.5%): prolonged air leakage, bronchopleural fistula, and atrial fibrillation. There were no post-operative deaths within 30 days after surgery. The five-year progression free and overall survival rate after surgical resection was 39.1% (95% CI.: 19.9-57.9) and 64.1% (95% CI.: 39.3-80.9), respectively.

      Conclusion

      The frequency of salvage surgery after initial treatment has been increasing possibly due to a better treatment course using novel medical and radiation oncology technique. Salvage pulmonary resections demonstrated acceptable morbidity and mortality with promising long-term efficacy in selected patients.

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      P1.17-07 - The Prognostic Value of Volumetric Changes of the GTV Measured on CBCT During Radiotherapy for CCRT in NSCLC Patients

      16:45 - 18:00  |  Presenting Author(s): Jose Belderbos  |  Author(s): Margriet Kwint, Barbara Stam, Matthew La Fontaine, Else Aalbersberg, Maddalena Rossi, Jan-Jakob Sonke, Iris Walraven

      • Abstract

      Background

      To pursue personalized cancer care, it is important to determine tumor response during treatment and associate these with outcomes. Previously published literature reported that adenocarcinoma and squamous cell carcinoma have different treatment response and outcome. Therefore, the aim of this study is to examine the prognostic value of volumetric changes of the primary tumor measured on Cone Beam-CT (CBCT) during radiotherapy for locally advanced NSCLC patients treated with concurrent chemoradiation (CCRT).

      Method

      394 NSCLC-patients treated with CCRT between 2007-2013 were included. To determine GTV during treatment, deformable image registration of the planning-CT to all CBCTs was performed. To assess the association of volumetric changes of the gross tumor volume (GTV) with overall survival (OS), progression free survival (PFS) and local regional control (LRC), multivariate cox regression analyses were performed, accounting for potential confounders. Furthermore, the entire group was stratified based on adenocarcinoma and non-adenocarcinoma and an additional log rank and multivariate cox regression analysis based on pathology was performed.

      Result

      In patients with adenocarcinoma, GTV reduction during CCRT was significantly associated with worse OS (HR=1.55, Figure 1). GTV reduction was not significantly associated with PFS and LRC in either subgroup. For the entire group no significant association was found between GTV volume change and OS, PFS or LRC.figure1_wclcabstract2018.jpg

      Conclusion

      Surprisingly, no associations between GTV changes and outcomes were found for the entire treatment group. In patients with adenocarcinoma, GTV changes during concurrent chemoradiaton measured on CBCT were a significant predictor for OS.

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      P1.17-08 - Genetic Predictors of Response to Chemoradiation in Stage III Non-Small-Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Leo Luo  |  Author(s): Robert Samstein, Rosalind Dick-Godfrey, Baho Sidiqi, Chunyu Wang, Federica Oro, Mark Sonnick, Paul K. Paik, Jamie E Chaft, Andreas Rimner, Abraham J. Wu

      • Abstract

      Background

      Radiation with platinum-based doublet chemotherapy is the standard of care for patients with unresectable stage III non-small-cell lung cancer (NSCLC). Despite aggressive treatment, progression-free survival and overall survival remain poor. It is unclear whether any tumor genetic alterations are associated with response to therapy.

      Method

      We retrospectively reviewed clinical outcomes of patients with stage III NSCLC treated with definitive radiation, who had undergone tumor molecular profiling through an institutional next-generation sequencing platform. This platform is an FDA-approved, targeted-DNA-sequencing panel that contains 341 (now expanded to 468) somatic mutations and other genetic alterations. Basic patient and tumor characteristics, clinical outcomes including loco-regional recurrence, distant recurrence, and overall survival, were collected. Overall and recurrence-free survivals were estimated using the Kaplan-Meier method. Cox proportional hazards model was used to investigate association between clinical outcome and genetic alterations.

      Result

      We identified 110 patients with stage III NSCLC who were treated with definitive radiation between 2013 and 2017 and underwent tumor molecular profiling. Fifty-one patients (46%) had stage IIIA disease and 59 patients (54%) had stage IIIB disease. Median radiation dose delivered was 60Gy in 30 fractions (range 48.6Gy to 74Gy). Either concurrent or sequential chemotherapy was given in 104 patients (95%) with 83 patients (75%) receiving concurrently. One patient received induction crizotinib and one patient died before start of chemotherapy. With a median follow-up time of 15.3 months, the median overall survival was 31.2 months. Several genetic mutations were significantly associated with worse overall survival after therapy, including AKT2 any mutation (Hazard ratio 13.71, p<0.001), KMT2C truncating mutations (HR 13.42, p<0.001), KMT2D truncating mutations (HR 6.97, p<0.001), ARID1A frameshift mutations (HR 8.54, p<0.001), and FLT1 any mutation (HR 6.62, p<0.001). These genes were also associated with increased loco-regional recurrence. Mutation in the PIK3C2G gene was significantly associated with improved overall survival. Association of other common genetic alterations such as EGFR mutation with response to therapy was not observed.

      Conclusion

      This study coupled multiplex targeted sequencing with clinical outcome information to identify several potential genetic predictors of response to chemotherapy and radiation in locally advanced NSCLC. KMT2C and KMT2D encode two subunits of a histone methyltransferase, and mutations of KMD2 have been shown to correlate with worse survival in locally advanced and advanced NSCLC patients. Further studies including in vitro validations are necessary to confirm the findings.

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      P1.17-09 - V30 May Better Predict Radiation Pneumonitis After Intensity-Modulated Radiation Therapy for Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Yinnan Meng  |  Author(s): Changhui Yu, Xingni Tang, Wei Wang, Caiping Jiang, Feng-Ming Spring Kong, Haihua Yang

      • Abstract

      Background

      V20 and MLD are the most commonly used dose constraints for radiation pneumonitis (RP) prediction. However, intensity-modulated radiation therapy (IMRT) has unrestricted beam arrangements, an infinite number of very different dose distributions could be generated in the lung volume outside the planning target volume (PTV). Conventional dose constraints from traditional 3D conformal RT may not be valid for IMRT treatment. We hypothesize that lung dosimetric parameters may have different RP predictive values from that of traditional constraints (largely generated from 3D treatment) in IMRT treated lung cancer patients.

      Method

      We retrospectively enrolled184 IMRT treated lung cancer patients from January 2014 to October 2017. The primary endpoint was acute grade 2 or higher symptomatic radiation pneumonitis (RP2), based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events (version 4.03). Vdose (from V5 to V50) and MLD were generated from the lung volume outside PTV. Univariate and multivariate logistic regression analysis was used to evaluate the association between the dose parameters outside PTV to RP2. We employed area under the curve (AUC) for the receiver operating characteristic curve (ROC) to assess prediction accuracy for the single or multi-variate model.

      Result

      26 out of 184 lung cancer patients (14.1%) developed RP2 within 3 months after the end of IMRT treatment. In univariate logistic regression, although none of the clinical parameters was significantly associated with RP2, female gender (P=0.051) and chemotherapy (P=0.151) had a trend of correlation. V5 (P=0.007), V10(P=0.012) V20 (P=0.004), V30 (P=0.003) and MLD (P=0.004) were significantly associated with RP2 incidence. From ROC curve, the largest AUC of 0.67 was generated from V30, which showed a better predictive value compared with other dosimetric factors. Multivariate logistic regression analysis showed the only significant dosimetric factor is V30 (P=0.021). Combining gender and chemotherapy factors, V30 has an AUC of 0.71 which is the largest among all the other dosimetric factors.

      Conclusion

      For IMRT treated lung cancer patients, V30 generated from lung volume outside PTV may predict RP more accurately than traditional dosimetric parameters.

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      P1.17-10 - Consolidation Chemotherapy in Stage III Non-Small Cell Lung Cancer: Still a Critical Piece of the Puzzle

      16:45 - 18:00  |  Presenting Author(s): Pranshu Mohindra  |  Author(s): Melissa Ana Liriano Vyfhuis, Katherine Scilla, Josephine Feliciano, Martin J. Edelman, Whitney Burrows, Shahed Badiyan, Mohan Suntharalingam, Steven J Feigenberg, Charles B. Simone

      • Abstract

      Background

      Despite lack of proven survival benefit, national guidelines recommend that patients with stage III non-small cell lung cancer (NSCLC) treated with chemoradiation (CRT) using weekly regimens receive two additional cycles of full dose consolidation chemotherapy (cCT). We seek to explore the benefit of cCT in our mature annotated cohort of stage III NSCLC patients treated with modern radiation therapy (RT) and predominantly weekly carboplatin/paclitaxel-based CRT.

      Method

      In this retrospective analysis, 355 consecutive patients with stage III NSCLC treated with either definitive CRT alone (bimodality) or followed by surgery (trimodality), between the years 2000-2013 were analyzed. Median age of the patients was 60 years (range: 30-86). Stage grouping was IIIA: 56.3%, T3/4: 49%, N2: 61.4%; N3: 21.4%. Histology was evenly distributed between squamous, adenocarcinoma, other or not specified. Concurrent CRT was delivered in 92.1% of the patients, 74% receiving weekly carboplatin/paclitaxel. Median radiation dose was 63Gy (range 10.8-81.6Gy). Data on cCT use was available in 304 patients, 69.7% receiving cCT. Logistic regression was performed to assess predictors for the use of cCT. Kaplan-Meier method and Cox proportional hazards model was used to estimate the overall (OS) and freedom-from-recurrence (FFR) adjusted for age, gender, marital status, insurance status, smoking history, COPD diagnosis, performance status, Charlson score, year of diagnosis, concurrent vs sequential CRT, RT technique, RT dose and surgery.

      Result

      With a median follow up of 15 months (range: 1-184 months), OS (median/5-year) with and without cCT was 30.2 months/ 30.5% and 15.3 months/ 12.9%, respectively (multivariate adjusted HR for death: 0.50; 95% CI: 0.37-0.69, p < 0.001). Corresponding values for FFR were 19 months/ 27% and 11.2 months/ 11.4% (adjusted HR: 0.54; 95% CI: 0.37-0.77, p = 0.001).

      On subset analysis, the OS benefit was seen in patients undergoing bimodality therapy (HR: 0.57; 95% CI: 0.40-0.83, p = 0.003) but not for trimodality therapy (p = 0.124). Similarly, an OS benefit was seen in stage IIIA (HR: 0.35; 95% CI: 0.23-0.55, p < 0.001) but not for stage IIIB patients (p = 0.071). The only factor predicting the use of cCT was primary treatment: bimodality vs trimodality (OR: 2.2; 95% CI: 1.1-4.3, p = 0.018 favoring bimodality).

      Conclusion

      Consolidation chemotherapy should continue to be strongly considered for stage III NSCLC patients, especially those undergoing bimodality therapy receiving weekly sensitizing doses of carboplatin-paclitaxel and with stage IIIA disease. The relative benefit of cCT in the setting of maintenance durvalumab (or other immunotherapy) needs further evaluation.

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      P1.17-11 - Pattern and Survival Impact of Neoadjuvant Treatment of Non-Small Cell Lung Cancer (NSCLC) in a Prospective Lung Resection Cohort

      16:45 - 18:00  |  Presenting Author(s): Meredith A Ray  |  Author(s): Matthew P Smeltzer, Nicholas R. Faris, Yu-Sheng Lee, Carrie L Fehnel, Cheryl Houston-Harris, Olawale Akinbobola, Philip Ojeabulu, Edward Owen, Richard Eubanks, Hector Dox, David Talton, Ganpat Valaulikar, Horace Lynn Wiggins, Bradley Wolf, Paul Steven Levy, Edward Todd Robbins, Raymond U. Osarogiagbon

      • Abstract

      Background

      Neoadjuvant therapy may benefit locally-advanced NSCLC patients. We evaluated patterns of neoadjuvant therapy and the impact on stage-shift and survival.

      Method

      All curative-intent NSCLC resections were collected from 12 hospitals in 4 contiguous Dartmouth Hospital Referral Regions in mid-Southern USA from 2009-2018. Comparisons made using Chi-square tests and non-parametric t-tests, survival impact assessed using Cox-proportional hazard models.

      Result

      182 of 3,297 resections (5.5%) had neoadjuvant therapy: 118 (64.8%) chemoradiation, 47 (25.8%) chemotherapy, and 17 (9.3%) radiation. Neoadjuvantly treated patients were younger, more likely to be commercially insured, have immediate preoperative brain MRI, and invasive mediastinal staging than those with primary resection (p<0.001 for all, Table 1). They also had more advanced stage, but 27% were clinical stage IA/IB.

      Despite evidence of more difficult surgery, perioperative complications, hospital length of stay and postoperative mortality rates were similar to the primary resection cohort. Despite delay to surgery, they had significantly greater down-staging (p<0.001). However, down-staging had no impact on survival, regardless of type of neoadjuvant therapy (Table 2).

      Table 1. Demographic and clinical characteristics between patients who received neoadjuvant therapy and those who did not.

      Demographic Variables

      Neoadjuvant Therapy

      Primary Resection Only

      N

      N=182

      N=3115

      Race (p: 0.0324)

      Caucasian

      125 (69)

      2425 (78)

      Black or AA

      56 (31)

      651 (21)

      Asian

      0 (0)

      16 (1)

      AI/AN

      0 (0)

      2 (0)

      Other/NR

      1 (1)

      19 (1)

      Age (p: <0.001)

      63 (56, 69)

      68 (61, 74)

      Sex (p: 0.4323)

      Male

      104 (57)

      1686 (54)

      Female

      78 (43)

      1427 (46)

      Insurance (p: <0.001)

      Medicare

      45 (25)

      1417 (45)

      Medicaid

      42 (23)

      438 (14)

      Commercial

      91 (50)

      1148 (37)

      Self/ None

      4 (2)

      112 (4)

      Non-Invasive Staging

      CT Scan ϯ

      135 (74)

      2879 (92)

      PET/CT ϯ

      106 (58[RO2] )

      2553 (82)

      Brain Scan (p: <0.001)

      98 (54)

      877 (28)

      Invasive staging tests (p: <0.001)

      No

      144 (79)

      2778 (89)

      Yes

      38 (21)

      337 (11)

      Histology (p: <0.001)

      Adenocarcinoma

      65 (40)

      1547 (54)

      Squamous

      57 (35)

      985 (34)

      Other including but limited to Adenosqamous, large cell, carcinomas, and other

      40 (22)

      339 (11)

      Grade (p: <0.001)

      Well/Moderately

      50 (30)

      1684 (54)

      Poorly/Undifferentiated

      60 (33)

      1040 (34)

      Not Reported

      66 (36)

      390 (13)

      Tumor Size (p: 0.50312)

      <= 3 cm

      123 (68)

      1984 (64)

      >3-5 cm

      36 (20)

      733 (24)

      >5-7 cm

      17 (9)

      255 (8)

      >7 cm

      6 (3)

      143 (5)

      8th Clinical T (p: <0.001)

      Tx

      0 (0)

      2 (0)

      T0

      14 (8)

      184 (6)

      Tis

      1 (1)

      0 (0)

      T1a(mi)

      0 (0)

      1 (0)

      T1b

      25 (14)

      865 (28)

      T1c

      24 (13)

      621 (20)

      T2a

      27 (15)

      521 (17)

      T2b

      18 (10)

      201 (6)

      T3

      39 (22)

      321 (10)

      T4

      25 (14)

      228 (7)

      T1a

      5 (3)

      156 (5)

      Insufficient Records

      3 (2)

      11 (0)

      8th Clinical N (p: <0.001)

      Nx

      0 (0)

      1 (0)

      N0

      130 (71)

      2709 (87)

      N1

      13 (7)

      196 (6)

      N2

      35 (19)

      176 (6)

      N3

      1 (1)

      20 (1)

      Insufficient

      3 (2)

      9 (0)

      8th Clinical M (p: <0.001)

      M0

      131 (73)

      2525 (87)

      M1a

      9 (5)

      116 (4)

      M1b

      30 (17)

      208 (7)

      M1c

      9 (5)

      61 (2)

      8th Clinical Stage (p: <0.001)

      Occult Carcinoma

      0 (0)

      2 (0)

      Stage 0

      13 (7)

      167 (5)

      Stage IA1

      2 (1)

      141 (5)

      Stage IA2

      15 (8)

      807 (26)

      Stage IA3

      12 (7)

      537 (17)

      Stage IB

      21 (12)

      424 (14)

      Stage IIA

      10 (5)

      160 (5)

      Stage IIB

      29 (16)

      373 (12)

      Stage IIIA

      41 (23)

      364 (12)

      Stage IIIB

      15 (8)

      63 (2)

      Stage IVA

      0 (0)

      3 (0)

      Stage Unknown

      21 (12)

      59 (2)

      Extent of resection (p: <0.001)

      Pneumonectomy

      24 (13)

      174 (6)

      Bilobectomy

      13 (7)

      145 (5)

      Lobectomy (+/-wedge)

      131 (72)

      2338 (75)

      Segmentectomy(+/-wedge)

      4 (2)

      146 (5)

      Wedge

      10 (5)

      307 (10)

      Surgical Technique (p: 0.1280)

      Open

      124 (68)

      1926 (62)

      RATS

      39 (21)

      701 (23)

      VATS

      19 (10)

      484 (16)

      Margin Status (p: <0.001)

      Positive

      15 (8)

      142 (5)

      Negative

      152 (84)

      2880 (93)

      Not Reported

      15 (8)

      88 (3)

      Peri- and Post-Operative Characteristics

      Surgery duration (in minutes, med, IQR) (p: 0.0172)

      156 (109, 221)

      135 (97, 186)

      Estimated blood loss (CCs, med, IQR) (p: <0.001)

      250 (100, 500)

      150 (100, 300)

      Duration of chest tube (in days, med, IQR) (p: 0.1364)

      4 (2, 6.5)

      4 (3, 7)

      ICU duration (in days, med, IQR) (p: 0.0282)

      2 (1, 3)

      1 (1, 3)

      Hospital duration (in days, med, IQR) (p: 0.7868)

      6 (4, 9)

      6 (4, 9)

      Rate of blood transfusions (p: <0.001)

      38 (21)

      215 (7)

      Rate of cardiac arrhythmias (p: 0.8513)

      27 (15)

      478 (15)

      Rate of any post-op complications (p: 0.1323)

      102 (56)

      1567 (50)

      Rate of ICU re-admittance prior to discharge (p: 0.0560)

      14 (8)

      143 (5)

      Rate of hospital re-admittance within 30 days (p: 0.1285)

      29 (17)

      378 (13)

      Clinical to pathologic T-Category Migration (<0.001)

      Down stage

      76 (42)

      742 (24)

      No change

      40 (22)

      1019 (33)

      Up stage

      66 (36)

      1354 (43)

      Unknown

      0 (0)

      0 (0)

      Clinical to pathologic N Category Change (p: <0.001)

      Down stage

      48 (26)

      566 (18)

      No change

      112 (62)

      2122 (68)

      Up stage

      22 (12)

      422 (14)

      Unknown

      0 (0)

      1 (0)

      Clinical to pathologic aggregate stage Migration (p: <0.001)

      Down stage

      89 (49)

      879 (28)

      No change

      49 (27)

      953 (31)

      Up stage

      41 (23)

      1268 (41)

      Unknown

      3 (2)

      11 (0)

      Postoperative Mortality Rates

      30 Day (p: 0.5109)

      11 (6)

      154 (5)

      60 Day (p: 0.4222)

      16 (9)

      224 (7)

      90 Day (p: 0.2216)

      22 (12)

      291 (9)

      120 Day (p: 0.1850)

      26 (14)

      345 (11)

      ϯ CT and PET/CT scan are after neo-adjuvant therapy for neoadjuvant patients.

      Table 2. Survial impact of downstaging among neo-adjuvant patients.

      Prediction Variables

      Hazard Ratio

      95% Confidence Interval

      P-value

      T-category

      Up-staged vs Down-staged

      1.69

      0.955, 2.977

      0.0715

      No change vs Down-staged

      1.64

      0.971, 2.4757

      0.0642

      N Category (among all patients)

      Up-staged vs Down-staged

      0.73

      0.45, 1.20

      0.2191

      No change vs Down-staged

      1.26

      0.62, 2.58

      0.5270

      N Category (among clinical N2 disease patients)

      Up-staged vs Down-staged

      NA

      NA

      NA

      No change vs Down-staged

      1.44

      0.47, 4.43

      0.5261

      NA – not applicable due to small sample size

      Conclusion

      Neoadjuvant therapy was safe, but had no survival impact in this cohort, despite increased down-staging, possibly because of an inexplicably high proportion of stage I patients.

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      P1.17-12 - Colleague Peer Review of Radical Lung Radiotherapy Treatment Plans: The Impact on Interval from Decision to Treat to Treatment Delivery

      16:45 - 18:00  |  Presenting Author(s): Gerard M Walls  |  Author(s): Claire Mary Rooney, Jonathan McAleese, Linda Young, Ruth L Eakin, Jacqueline Harney, Gerard G Hanna

      • Abstract

      Background

      Quality assurance by colleague-led peer review (CPR) is recommended in the radiotherapy treatment planning of curative intent treatments such as for lung cancer. Previous studies have demonstrated a proportion of radiotherapy plans are amended following CPR resulting in enhanced quality and uniformity of treatment approached. CPR is an extra step in the radiotherapy planning process, and it may affect the timeliness of commencing radiotherapy. CPR was initiated in our centre in 2011. This study considers the temporal impact of adding an additional step to the planning process.

      Method

      Using our institutional lung radiotherapy database we recorded the timescales between decision to treat (DTT) and commencement of radical lung radiotherapy, pre-peer review and post-peer review initiation at a single institution. The data for all patients was analysed for the years 2007 to 2017.

      Result

      Prior to peer review for the calendar year of 2007, 71% of the 63 patients receiving curative intent radiotherapy for lung cancer commenced treatment within 28 days of the DTT (median 26 days, range 0-61). In 2016, 80% of the 133 patients receiving curative intent radiotherapy had treatment initiated within 28 days (median 25 days, range 6-41). There was a notable reduction in the variability in planning time making booking of appointments with a reduction in extreme wait times to start treatment (figure 1).

      Figure 1 Box and whisker plot of the time from the decision to treat until the commencement of radiotherapy for the representative years available for analysis.

      time from dtt to tx.png

      Conclusion

      In our institutional series, CPR does not prolong planning time with the median number of days taken to commence treatment remaining comparable, but may standardise radiotherapy start times due to enhanced team working via the CPR meetings. We recommend that peer review is performed as standard practice as it improves treatment quality without a detrimental prolongation of planning time.

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      P1.17-13 - The Role of Post-Operative Radiation Therapy in Patients with Locally Advanced NSCLC after Nodal Down-Staging with Systemic Chemotherapy

      16:45 - 18:00  |  Presenting Author(s): Annemarie Shepherd  |  Author(s): Daphna Gelblum, Abraham J. Wu, Andreas Rimner

      • Abstract

      Background

      Post-operative Radiation Therapy (PORT) has been shown to improve local-regional control and overall survival in patients with non-small cell lung cancer (NSCLC) undergoing surgical resection with pathologic N2 nodal involvement. It is unclear if PORT is needed in patients with clinical N2 involvement who are downstaged with neoadjuvant chemotherapy.

      Method

      The National Cancer Database was queried for patients diagnosed between 2006-2015 with clinical N2, Stage IIIA NSCLC and treated with neoadjuvant chemotherapy followed by R0 surgical resection with either a lobectomy or pneumonectomy. Patients were included if they were alive for at least 3 months following their diagnosis.

      Kaplan Meier method was used for overall survival (OS) analysis.

      Result

      A total of 1,174 patients were evaluated. The median age was 65 years (range: 33-89). Most patients were treated with lobectomy (90%). The median radiation (RT) dose was 50.4 Gy (range: 45-54 Gy). Pathologic downstaging and OS rates with and without PORT are demonstrated in Table and Figure.

      Survival Rates
      ypN STAGE PORT (N=303) No PORT (N=871) p-value

      ypN0 (N=477)

      Median OS

      1 yr OS

      2 yr OS

      5 yr OS

      N=63

      73.1 months

      100%

      89.9%

      62.6%

      N=414

      67.5 months

      93.6%

      78.2%

      52.6%
      0.089

      ypN1 (N=182)

      Median OS

      1 yr OS

      2 yr OS

      5 yr OS

      N=39

      71.0 months

      89.7%

      68.6%

      58.7%

      N=143

      43.8 months

      82.4%

      67.0%

      38.3%
      0.172

      ypN2 (N=512)

      Median OS

      1 yr OS

      2 yr OS

      5 yr OS

      N=198

      46.1 months

      89.9%

      71.5%

      39.5%

      N=314

      39.8 months

      84.8%

      63.2%

      35.9%
      0.072

      All patients (N=1,174)

      Median OS

      1 yr OS

      2 yr OS

      5 yr OS

      N=303

      55.0 months

      91.7%

      74.8%

      46.9%

      N=871

      50 months

      88.6%

      71.3%

      44.3%
      0.211

      ncdb nodal downstaging survival curves for wclc 2018.png

      Conclusion

      Our data demonstrate a trend for improved OS with PORT. Although this is a population-based study, this lack of statistical significance may be attributable to a small sample size as the OS curves indicate a consistent benefit with PORT.

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      P1.17-14 - Outcomes of Hypofractionated Radiation Therapy (HFRT) with Concurrent Chemotherapy in Patients with Stage III Non Small Cell Lung Cancer (NSCLC)

      16:45 - 18:00  |  Presenting Author(s): Annemarie Shepherd  |  Author(s): Daphna Gelblum, Abraham J. Wu, Andreas Rimner

      • Abstract

      Background

      Patients with unresectable locally advanced NSCLC are often treated with concurrent chemoradiation. HFRT regimens are becoming increasingly common due to convenience and healthcare costs. A database analysis was performed to evaluate the outcomes of HFRT with concurrent chemotherapy.

      Method

      The National Cancer Database (NCDB) was queried for patients with stage III NSCLC who received RT (50 Gy-80 Gy) with concurrent chemotherapy without surgery from 2004-2015. Patients were defined as receiving concurrent chemotherapy if chemotherapy was started within 3 weeks of the start of radiation. Patients received conventionally fractionated RT (CFRT): 180-200 cGy/fraction (fx) or HFRT: 210-400 cGy/fx. Baseline characteristics were compared. Kaplan Meier method was used for overall survival (OS) and Cox-proportional hazards were used for uni- and multivariable analyses (UVA/MVA).

      Result

      A total of 54,559 patients were evaluated: 50,938 CFRT and 3,621 HFRT. Patients treated with HFRT were more likely to receive RT at an academic center (32.6% vs. 27.2%, p<0.01), more likely to have higher T-stage (cT3/T4: 56.5 vs. 49.2%, p<0.01) but lower N-stage (cN2/3: 77.6% vs. 81.4%, p<0.01). There was no difference in age (median 66 yo), sex, race, insurance, education, Charlson-Deyo Comorbidity Score (CDCS), tumor location, or grade. For the CFRT and HFRT groups, the median RT dose, Biologic Equivalent Dose (BED) and dose/fx were 64 Gy; 76.4; 185 cGy/fx and 65 Gy; 80.5; 235 cGy/fx, respectively.

      The median and 2-yr rates of OS were 19.8 mos and 43.2% for CFRT vs 16 mos and 36.1% for HFRT (p<0.01).

      On UVA and MVA, (data shown for MVA: HR, p-value), age (1.01, <0.01), male gender (1.2, <0.01), white race (1.09, <0.01), Medicare (1.04, <0.01), urban dwelling (0.93, <0.01), distance from treatment center (0.999, <0.01), treatment at an academic center (0.91, <0.01), CDCS (1: 1.11, <0.01, 2: 1.21, <0.01, 3: 1.29, <0.01), diagnosed 2010-2014 (0.85, <0.01), upper lobe location (0.89, <0.01), T3/T4 stage (1.15, <0.01), N2/N3 stage (1.12, <0.01), stage IIIB (1.11, <0.01), HFRT (1.26, <0.01) and BED (0.99, 0.01) were associated with OS.

      Conclusion

      Patients who received HFRT had slightly inferior OS rates, which may be due to toxicity (not captured in the NCDB) or unaccounted confounders such as baseline performance status and aggressiveness of disease.

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      P1.17-15 - Perioperative Prognostic Nutrition Index for Induction Chemoradiotherapy Followed by Surgery in Locally Advanced Non-Small Lung Cancers

      16:45 - 18:00  |  Presenting Author(s): Junichi Soh  |  Author(s): Shunsaku Miyauchi, Kota Araki, Akihiro Miura, Yuta Takahashi, Eisuke Kurihara, Yusuke Ogoshi, Kazuhiko Shien, Hiromasa Yamamoto, Seiichiro Sugimoto, Masaomi Yamane, Katsuyuki Kiura, Susumu Kanazawa, Shinichi Toyooka

      • Abstract

      Background

      The perioperative nutritional and immunological statuses significantly associated the clinical outcome of the surgery, especially for the extended surgery. Induction chemoradiotherapy (iCRT) followed by surgery is one of treatment options for locally advanced (LA) non-small cell lung cancers (NSCLCs) although there is a risk for increasing postoperative complications. A prognostic nutritional index (PNI), calculated using serum albumin levels and peripheral lymphocyte count, has been used to predict the clinical outcome of various cancers including early stage NSCLCs but not LA-NSCLC after iCRT. In this study, we investigated the impact of PNI on clinical outcome of iCRT followed by surgery in the patients with LA-NSCLCs.

      Method

      During 1999 to 2016, 173 patients underwent iCRT followed by surgery in Okayama University Hospital. Among them, 128 patients who matched to inclusion criteria were studied. We retrospectively calculated the PNI at (1) pre-iCRT (median 5 days before administration), (2) pre-operation (Ope) (median 5 day before surgery), and (3) post-Ope (median 30 days after surgery) and reviewed the medical records.

      Result

      The median age was 62 years old (range 31 – 79) and 100 patients were male. Seventy patients were adenocarcinomas and 46 were squamous cell carcinomas. Clinical stages were IIA / IIB (n = 15), IIIA (n = 87), IIIB (n = 25), and IV (n = 1). Main regimen of iCRT was CDDP / DOC with concurrent radiotherapy (46 gray). Treatment responses were CR/PR (n = 99), SD (n = 27), and PD (n = 2). Lung resections were lobectomy (n = 109), bi-lobectomy (n = 14), and pneumonectomy (n = 5) and additional procedures were performed in 93 patients. Based on the invasiveness of surgery, we categorized into three groups: 1) highly invasive group (n = 60), 2) intermediate group (n = 33), and 3) standard group (n = 35). Pathological complete responses were present in 37 patients. The PNI were significantly decreased during treatment course [49 (24 – 71) in pre-ICRT, 44 (30 – 58) in pre-Ope, and 41 (22 – 58) in post-Ope]. Among the entire cohort, the perioperative PNI values showed some effect on overall survival. However, among the highly invasive group, the poor preoperative PNI values significantly correlated with worse overall survival.

      Conclusion

      Peri-treatment nutritional evaluation using PNI is important to predict clinical outcome of the patients who received the iCRT followed by surgery with LA-NSCLCs especially when highly invasive surgery is required.

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      P1.17-16 - Correlation of Tumor Volume Reduction During Neoadjuvant Chemoradiotherapy with Pathological Complete Response of Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Shigeo Takahashi  |  Author(s): Tetsuhiko Go, Takamasa Nishide, Masahide Anada, Toshifumi Kinoshita, Hiroyasu Yokomise, Toru Shibata

      • Abstract

      Background

      A study has reported that tumor volume (TV) reduction after neoadjuvant chemoradiotherapy (NACRT) was associated with pathological complete response (pCR) in patients with non-small cell lung cancer (NSCLC). We think that the prediction of pCR during NACRT may be able to assist clinical decisions. Therefore, we retrospectively investigated the relationship between TV reduction during NACRT and pCR.

      Method

      We evaluated patients who received NACRT followed by surgery between 2007 and 2017. The eligibility criteria of this study were as follows: NACRT was performed with a dose of 50 Gy in 25 fractions with the platinum-doublet regimen, and contrast enhanced computed tomography (CECT) was obtained before and during NACRT. TVs before and during NACRT (TVpre and TVduring, respectively) were measured with the sums of the primary tumor and clinically involved lymph node volumes. Relative changes in the TVs were calculated as %(TVduring – TVpre)/TVpre. The factors affecting pCR were evaluated in a univariate analysis, by Fisher’s exact test or Wilcoxon rank-sum test, and in a multivariate analysis using the multiple logistic regression test.

      Result

      In total, 31 patients met the eligibility criteria: 52%, 42%, and 52% of patients had squamous cell carcinoma, cT3, and cN2 disease, respectively. CECT during NACRT (CECTduring) was obtained at a median dose of 40 Gy (range, 24-50 Gy). The median TVpre and TVduring were 45.1 cc (range, 11.4-584.2 cc) and 27.0 cc (range, 5.9-195.0 cc), respectively. The median relative change in the TVs was –49% (range, –83 to –10%), and after surgery, pCR was confirmed in 11 patients (35%). Relative change in the TVs (p = 0.002) and TVpre (p = 0.039) were significant factors affecting pCR in the univariate analysis. No significances were observed in histology, cT, cN, RT dose at the time of CECTduring, and TVduring factors (p = 0.458, 0.449, 1.000, 0.547, and 0.984, respectively). In the multivariate analysis, relative change in the TVs remained an independent predictor of pCR (p = 0.003). The cut-off value for the relative change in the TVs affecting pCR was –64%, which was determined by a receiver operating characteristic curve (area under the curve = 0.841): 8 of 9 patients (89%) whose tumors shrunk more than this cut-off value achieved pCR.

      Conclusion

      TV reduction during NACRT seems to be associated with pCR in patients with NSCLC. A cut-off value of –64% in relative change in the TVs at a dose of around 40 Gy may be promising to predict pCR.

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      P1.17-17 - The Impact of Induction Chemoradiotherapy Followed by Surgery for N1 Involved Non-Small Cell Lung Cancer

      16:45 - 18:00  |  Presenting Author(s): Yuta Takahashi  |  Author(s): Junichi Soh, Shunsaku Miyauchi, Kota Araki, Akihiro Miura, Eisuke Kurihara, Yusuke Ogoshi, Kazuhiko Shien, Hiromasa Yamamoto, Seiichiro Sugimoto, Masaomi Yamane, Katsuyuki Kiura, Susumu Kanazawa, Shinichi Toyooka

      • Abstract

      Background

      Induction chemoradiotherapy (iCRT) followed by surgery is usually selected for locally advanced non-small cell lung cancer (NSCLC) patients with mediastinal lymph node (LN) metastasis or invasion to adjacent organs, whereas it is occasionally performed for clinical N1 (cN1) NSCLC patients harboring such as a centrally located primary tumor or a bulky LN to improve local control rate and secure a cancer-free surgical margin. However, the survival benefit of iCRT followed by surgery for NSCLC patients with N1 LN involvement remains controversial. Furthermore, the accuracy of the radiological examination for N1 metastasis is unsatisfactory. In this study, we investigated the clinical outcomes of surgery with or without iCRT based on the estimation of the pretreatment LN metastatic status from fibrotic or necrotic changes of resected LNs in the cN1 NSCLC patients.

      Method

      cN1 NSCLC patients who underwent complete resection with or without iCRT at our institution between January 1999 and December 2016 were subjected. We divided the enrolled patients into two groups as the primary surgery (PS) group and the iCRT followed by surgery (IC) group. As for IC group, we determined the pretreatment LN metastatic status based on the pathological features of resected LNs. We compared the clinical outcomes of pretreatment N1 involved patients with or without iCRT.

      Result

      Among 127 cN1 NSCLC patients, 40 patients were considered as pretreatment N1 involvement, consisting of 26 and 14 patients in the PS and IC groups, respectively. The central type tumor and the continuous type of LN, which frequently required the extended surgical procedures, were significantly more frequent in the IC group than in the PS group (P < 0.01). Although there was no significant difference in the recurrence pattern between the two groups, none of patients developed local recurrence in the IC group. Regarding the patients with a centrally located tumor or a bulky LN (> 2.0cm), the 5-year recurrence-free survival was significantly better in the IC group than in the PS group (74.1% vs, 36.4%; P =0.03).

      Conclusion

      Our study demonstrated that iCRT followed by surgery could suppress the disease recurrence in the N1-involved NSCLC patients especially for the patients harboring a centrally located tumor or bulky LNs at N1 level, suggesting that these patients may be good candidates for iCRT followed by surgery to avoid extended resections and to suppress the local recurrence.

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      P1.17-18 - Treatment for Patients with T4 Superior Sulcus Non-Small Cell Lung Cancer: A Propensity-Matched Analysis of SEER Database

      16:45 - 18:00  |  Presenting Author(s): Min Fan  |  Author(s): Junmiao Wen, Donglai Chen, Jiayan Chen, Di Liu, Yongbing Chen, Chang Chen

      • Abstract

      Background

      Superior sulcus tumors (SSTs), a unique subgroup of locally advanced non–small-cell lung carcinoma (NSCLC), remain a great challenge for clinicians. T4 SSTs used to be a contraindication for operations, and the optimal treatment modality for T4 SS NSCLCs remains uncertain. The aim of our study is to evaluate the roles of surgical treatment and radiotherapy for patients with T4 SSTs.

      Method

      We used the SEER database [1973-2015] to identify patients diagnosed with T4 stage SS NSCLC (according to 7th edition AJCC staging system) between 2004 and 2015, those with M1 disease were excluded. Propensity score matching with Kaplan-Meier and Cox proportional hazards model were performed to estimate prognosis.

      Result

      A total of 384 patients were included (mean 66.4±11.71 years-of-age). Among them, the majority was male (59.4%) with lesions located in the left lung (52.3%) and diagnosed with IIIB stage (56.6%). 47 patients underwent cancer-directed surgery, and radiotherapy was received by 66.9% of patients. Median overall survival (OS) and lung cancer specific survival (LCSS) was 12 and 17 months, and 5-year OS, LCSS was 15.8%, 25.4%, respectively. In the matched population, the median survival outcomes were better with receipt of surgery (OS: 51.3 vs 35.1 months; p=0.049 LCSS: 67.1 vs 36.3 months; p=0.003). Multivariate Cox analysis showed that age ≧ 66 years (hazard ratio [HR] = 1.639, 95% confidence interval [CI] 1.214-2.213, p=0.001), unmarried status (HR = 1.356, 95% CI 1.023-1.798, p=0.034), tumor sized ≧ 6.0 cm (HR = 1.694, 95% CI 1.263-2.273, p<0.001) were associated with inferior OS. Cancer-directed surgery (HR = 0.537, 95% CI 0.337-0.855, p=0.009) and radiotherapy (HR = 0.644, 95% CI 0.472-0.878, p=0.006) were independent protective factors for patients with T4 superior sulcus NSCLC. However, neither adjuvant nor neoadjuvant radiotherapy was independent prognostic factor for those received surgery (p>0.05). Conversely, in the subgroup analysis, favorable impacts of radiotherapy were observed for non-surgery patients (OS: HR = 0.58, 95% CI 0.42-0.79, p<0.001; LCSS: HR = 0.55, 95% CI 0.37-0.75, p<0.001).

      Conclusion

      Our study shows superior sulcus NSCLC patients with T4 stage have dismal prognosis. Surgical resection remains the optimal option for those with resectable disease. Moreover, for non-surgery tumors, the use of radiotherapy should be considered.

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      P1.17-19 - Correlation of Dosimetric and Clinical Factors with Radiation Pneumonitis in Lung Cancer Patients Received Involved-Field IMRT

      16:45 - 18:00  |  Presenting Author(s): Lehui Du  |  Author(s): Baolin Qu, Na Ma, Qiduo He, Wei Yang, Qianqian Wang

      • Abstract

      Background

      Radiation pneumonitis is a potentially fatal complication in lung cancer patients treated with definitive radiotherapy. The ability to identify patients at risk for this complication would be of value to clinicians. The objective of this study was to identify significant predictors of grade 2 or higher radiation pneumonitis. Previous reported studies mostly focused on extended-field three-dimensional conformal radiotherapy without image guided. The purpose of the study was to correlate clinical and dosimetric factors with the development of radiation pneumonitis in patients with lung cancer treated with involved-field image guided intensity modulated radiation therapy (IMRT).

      Method

      149 lung cancer patients treated with involved-field image guided IMRT were recruited. Potential predictive factors examined included age, gender, histology, stage, pulmonary function, KPS, radiation dose, surgery history, usage of chemotherapy. RP events were prospectively scored using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Kaplan-Meier analysis was used to determine the cumulative probability of RP of grade ≥ 2. Univariate and mutivariate analysis was used to determine predictors of grade 2 or higher pneumonitis.

      Result

      Of the 149 patients, Median prescription dose was 60Gy. With a median follow-up of 9 months, 10 cases (6.7%) developed RP of grade 3 or higher level, 57 (38.3%) developed RP of grade ≥ 2 RP, and 90 (62.7%) of grade 1 or lower level. The median time of grade ≥ 2 RP was 2.6 months (range from 1 to 6 months). Grade ≥ 2 RP pneumonitis was correlated with age and volume of lung receiving 20 Gy (V20). Surgery had a bordline significant association with risk of grade≥ 2 RP pneumonitis.

      Conclusion

      Age and V20 were significant predictors of grade≥2RP radiation pneumonitis in lung cancer patient treated with involved-field image guided IMRT, Surgery also had a bordline significant predictive value.

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      P1.17-20 - Excluding PTV From Lung Volume May Better Predict Radiation Pneumonitis For IMRT Treated Lung Cancer Patients

      16:45 - 18:00  |  Presenting Author(s): Yinnan Meng  |  Author(s): Changhui Yu, Wei Wang, Xingni Tang, Caiping Jiang, Feng-Ming Spring Kong, Haihua Yang

      • Abstract

      Background

      Lung dose-volume histogram(DVH) could be calculated from multiple normal lung definitions. These dose differences have a direct impact on lung cancer radiotherapy treatment planning. Earlier study from 3D conformal radiation therapy suggested dose computation from total normal lung excluding gross tumor volume (GTV) may be more accurate than that of excluding planning target volume (PTV). It is unclear which definition should be used to more accurately predict radiation pneumonitis (RP) in lung cancer patients treated with intensity-modulated radiation therapy (IMRT). We aim to determine a superior normal lung volume to more accurately predict symptomatic RP in lung cancer patients treated with IMRT.

      Method

      This is a retrospective study. All patients treated with IMRT with at least 3 months follow-up are eligible. The normal lungs are defined by total lung volume excluding GTV, PTV or directly using the total lung volume. V5, V20, and MLD have been extracted for all three definitions. RP was diagnosed and graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events, version 4.03. The primary endpoint was grade 2 or higher RP (RP2). Correlation between RP2 and dose parameters were analyzed by logistic regression. We compared RP prediction performance of each lung volume using area under the receiver operating characteristic curve (AUC).

      Result

      A total of 184 consecutive patients treated between January 2014 and October 2017 were eligible, 26 patients (14%) developed RP2 within 3 months after treatment. Significant dosimetric difference was found between any 2-paired lung volumes (Ps<0.0001). All dose parameters from Lung-PTV method had significant correlation with RP2, with greater AUCs than the other two definitions. The best RP prediction performance was found in Lung-PTV volume MLD (AUC=0.649), which is significantly better than Lung-GTV volume MLD (AUC=0.611, P=0.006).

      Conclusion

      There were significant dosimetric differences from various normal lung definitions. Excluding PTV method may accurately predict acute symptomatic radiation pneumonitis for IMRT treated lung cancer patients.

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    PA01 - Patients and Advocacy DRIVING Research Together

    • Type: Patient and Advocacy Panel
    • Track: Advocacy
    • Moderators:
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    ISS10 - Symposium Supported by Boehringer Ingelheim: Overcoming Challenges in Thoracic Malignancies: Expert Insights (Not IASLC CME Accredited)

    • Moderators:
    • +

      Meeting Welcome and Introductions

      18:00 - 18:05  |  Presenting Author(s): David R. Gandara

      • Abstract

      Abstract not provided

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      Clinical considerations in EGFR mutation–positive NSCLC: does treatment sequence matter?

      18:05 - 18:20  |  Presenting Author(s): Barbara Melosky

      • Abstract

      Abstract not provided

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      Clinical considerations in EGFR mutation–positive NSCLC: the challenge of preventing and managing brain metastases

      18:20 - 18:35  |  Presenting Author(s): Noemi Reguart

      • Abstract

      Abstract not provided

    • +

      Panel discussion: treatment considerations in adenocarcinoma

      18:35 - 18:50  |  Presenting Author(s): David R. Gandara, Barbara Melosky, Noemi Reguart

      • Abstract

      Abstract not provided

    • +

      Maximising the clinical potential of TKIs for patients with squamous NSCLC

      18:50 - 19:10  |  Presenting Author(s): David R. Gandara

      • Abstract

      Abstract not provided

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      Panel discussion: treatment considerations in SqCC of the lung

      19:10 - 19:25  |  Presenting Author(s): David R. Gandara, Barbara Melosky, Noemi Reguart

      • Abstract

      Abstract not provided

    • +

      Meeting close

      19:25 - 19:30

      • Abstract

      Abstract not provided

  • +

    Faculty Dinner (By Invitation Only)

    • Type: Networking Opportunity
    • Track:
    • Moderators:
    • +

      Faculty Dinner (By Invitation Only)

      19:30 - 22:00

      • Abstract

      Abstract not provided

  • +

    ISS11 - Symposium Supported by Pfizer: Future Options for ALK+ Metastatic NSCLC (Not IASLC CME Accredited)

    • Moderators:
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      Welcome and Introduction

      07:00 - 08:00  |  Presenting Author(s): Geoffrey Liu

      • Abstract

      Abstract not provided

    • +

      Recent advances in treating ALK+ NSCLC: An evolving landscape

      08:00 - 08:00  |  Presenting Author(s): Ben J Solomon

      • Abstract

      Abstract not provided

    • +

      Navigating the spectrum of resistance mutations in ALK+ NSCLC: How to identify and treat them

      08:00 - 08:00  |  Presenting Author(s): Alice T. Shaw

      • Abstract

      Abstract not provided

    • +

      Panel Q&A

      08:00 - 08:00  |  Presenting Author(s): Geoffrey Liu, Ben J Solomon, Alice T. Shaw

      • Abstract

      Abstract not provided

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    ISS12 - Symposium Supported by Roche: Selecting the Right Cancer Immunotherapy Regimen for the Right Patient in First-line Lung Cancer (Not IASLC CME Accredited)

    • Moderators:
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      Spotlight on cancer immunotherapy: scientific advances and evolving clinical practice in first-line lung cancer

      07:00 - 07:00  |  Author(s): Suresh S. Ramalingam

      • Abstract

      Abstract not provided

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      Optimising treatment for first-line NSCLC

      07:00 - 07:00  |  Presenting Author(s): Vassiliki A Papadimitrakopoulou  |  Author(s): Ross Soo

      • Abstract

      Abstract not provided

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      Putting it all into perspective: what does this mean for our patients?

      07:00 - 07:00  |  Presenting Author(s): Suresh S. Ramalingam, Vassiliki A Papadimitrakopoulou, Ross Soo

      • Abstract

      Abstract not provided

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    ISS13 - Symposium Supported by Medscape: Progress of the NSCLC Revolution: Questioning the Experts (Not IASLC CME Accredited)

    • Moderators:
    • +

      Welcome and Introductions

      07:00 - 07:05  |  Presenting Author(s): Tony S. Mok

      • Abstract

      Abstract not provided

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      Molecular Testing in NSCLC: Where Are We Going?

      07:05 - 07:20  |  Presenting Author(s): Fabrice Barlesi

      • Abstract

      Abstract not provided

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      Treating New Molecular Targets in NSCLC: How Are We Progressing?

      07:20 - 07:35  |  Presenting Author(s): Sanjay Popat

      • Abstract

      Abstract not provided

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      Immunotherapy in NSCLC: Where Have We Got to?

      07:35 - 07:45  |  Presenting Author(s): Edward B Garon

      • Abstract

      Abstract not provided

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      How Are We Doing in the Delivery of the NSCLC Revolution?

      07:45 - 07:57  |  Presenting Author(s): Tony S. Mok, Fabrice Barlesi, Edward B Garon, Sanjay Popat

      • Abstract

      Abstract not provided

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    MTE11 - Biology of Small Cell Lung Cancer (Ticketed Session)

    • Type: Meet the Expert Session
    • Track: Biology
    • Moderators:
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      MTE11.01 - Novel Therapeutic Targets in SCLC

      07:00 - 07:30  |  Presenting Author(s): Julien Sage

      • Abstract

      Abstract

      Small cell lung cancer (SCLC) remains the most lethal form of lung cancer, in part because of its rapid growth and dissemination, and also because of its ability to evade therapy. In the last few years, however, a number of studies have taken advantage of improved pre-clinical mouse models of SCLC as well as increased access to primary human samples to identify novel candidate therapeutic targets against SCLC. Some of these new therapeutic targets include activation of the immune system (T cells, NK cells, or macrophages), as well as cell-intrinsic signaling pathways that often act in autocrine or paracrine manners (e.g. Hedgehog or Notch signaling). This presentation will put these different approaches in context and discuss signaling pathways that may not be mutated in SCLC but can still significantly contribute to the proliferation and the survival of SCLC cells during SCLC progression and metastasis.

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      MTE11.02 - Biological Subsets of SCLC

      07:30 - 08:00  |  Presenting Author(s): Charles M. Rudin

      • Abstract

      Abstract

      Small cell lung cancer (SCLC) is an exceptionally lethal cancer for which new therapeutic approaches are needed. Over the past few years several research teams have applied global profiling approaches to characterize the SCLC genome, epigenome, transcriptome, and proteome. Despite the seemingly homogeneous microscopic appearance of SCLC, these studies have consistently suggested the presence of biologically distinct subsets of disease. Parallel studies across libraries of patient-derived xenografts and in a diversity of genetically engineered mouse models of SCLC have validated these subset distinctions. Some models suggest that these subsets reflect parallel programs of oncogenesis, perhaps emerging from distinct cells of origin. Conversely, other data imply a temporal hierarchy among disease subsets, or at least that transition from one phenotypic subset to another is possible. Most exciting from a treatment perspective, several research groups have reported unique therapeutic vulnerabilities among these subsets. Several of these therapeutic strategies are being actively tested in SCLC patients, and emerging correlative data further confirm the predicted differential sensitivities among SCLC subsets. Together, these studies advocate for a very different approach to clinical translation in SCLC than that taken to date. Rather than treating all SCLC the same, a more successful approach may be to consider focused trials among biomarker-selected subsets of disease, exploiting the distinct dependencies and vulnerabilities of biologically relevant subsets. This presentation will highlight some of the recent preclinical studies that have defined determinants of these subsets, together with recent clinical work emphasizing their importance to the field, and to our patients.