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  • WCLC 2018

    19th World Conference on Lung Cancer

    Access to all presentations that occur during the 19th World Conference on Lung Cancer in Toronto, ON

    Presentation Date(s):
    • Sept 23 - 26, 2018
    • Total Presentations: 2384

    To review abstracts of the presentations below, narrow down your search by using the Filter options below, and then select the session listing of your choice. Click the "+" for a presentation to expand & view the corresponding Abstract details.

    Presentations will be available 24 hours after their live presentation time

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    MTE10 - Emerging Technologies for Small and Smaller Lesions - Update on Ablation via Endoscopy vs Percutaneous (Ticketed Session) (ID 820)

    • Type: Meet the Expert Session
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 07:00 - 08:00, Room 201 BD
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      MTE10.01 - Emerging Technologies for Small and Smaller Lesions - Update on Ablation via Endoscopy vs Percutaneous (Now Available) (ID 11563)

      07:00 - 08:00  |  Presenting Author(s): Felix JF Herth

      • Abstract
      • Presentation
      • Slides

      Abstract

      A solitary pulmonary nodule (SPN) is a round or oval opacity smaller than 3 cm in diameter that is completely surrounded by pulmonary parenchyma.

      Workup of these nodules is rather expensive and emotionally burdensome, especially when the patient has risk factors for bronchial carcinoma.

      SPNs are noted in up to 0.2% of chest radiograph, whereas 27.3% of patients undergoing the national lung screening trial (NLST) had at least one SPN with a diameter of more than 4mm on their CT examination.

      Numerous articles/papers have been published addressing the optimal strategy of evaluating individuals with lung nodules, including the published ACCP guideline for the diagnosis and management of lung cancer. Those strategies are generally based on the individuals’ risk of developing lung cancer, the pulmonary nodule characteristics and the capability of the current diagnostic and therapeutic approaches.

      Standard bronchoscopy has been limited in the evaluation of the peripheral pulmonary nodules, with diagnostic yields ranging from 19% to 68%. The addition of tools such as electromagnetic navigational bronchoscopy (ENB), radial endobronchial ultrasound (r-EBUS), and several other navigation technologies have been used and increased the diagnostic yield. Actual, The Transbronchial Parenchymal nodule access (TPNA) has shown the best results.

      Radiofrequency ablation (RFA) and Microwaves (MW) are promising alternative treatment method for early-stage lung cancer in non-surgical patients. They can also be used for oligometastasis from distant cancer or as a therapy for the local control

      of tumors.

      Compared to their percutaneous approach, in the lung, percutaneous ablation is associated with severe complications, including pneumothorax, hemothorax, bronchopleural fistulas, and pleural effusions.

      Therefore a bronchoscopic approach seems to be as effective with reduced complications.

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    PL01 - Patients First (ID 849)

    • Type: Plenary Session
    • Track:
    • Presentations: 6
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 08:15 - 09:45, Plenary Hall
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    MA01 - Early Stage Lung Cancer: Questions and Controversies (ID 894)

    • Type: Mini Oral Abstract Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 12
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 202 BD
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      MA01.01 - Proposal on Incorporating Lymphovascular Invasion as a T-Descriptor for Stage I Non-Small Cell Lung Cancer (Now Available) (ID 12754)

      10:30 - 10:35  |  Presenting Author(s): Shuyuan Wang  |  Author(s): Bo Zhang, Jianlin Xu, Rong Qiao, Baohui Han, Bo Yan, Yu Dong

      • Abstract
      • Presentation
      • Slides

      Background

      Lymphovascular invasion (LVI) and Visceral Pleural Invasion(VPI) have been reported to be risk factors for stage I Non-Small Cell Lung Cancer (NSCLC). However, only VPI was incorporated into the current 8th Tumor–Node–Metastasis(TNM) classification. This study aimed at exploring the prognostic impact of LVI on TNM staging in Pathological Stage I NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively reviewed 2600 consecutive p-stage I NSCLC patients in the Shanghai Chest Hospital (2008-2012). By using the Kaplan–Meier method and Cox proportional hazard regression model, we identified the correlations between LVI, VPI and clinical outcomes in p-stage I NSCLC.

      4c3880bb027f159e801041b1021e88e8 Result

      Of all p-stage I NSCLC 2600 patients, 221 were pathologically diagnosed with LVI and 815 pathologically with VPI, respectively. It was observed that patients with LVI had an unfavorable lung cancer specific survival (LCSS) (hazard ratio [HR]: 1.883; 95% confidence interval [CI]: 1.351-2.625; P < 0.001) and recurrence-free survival (RFS) (HR: 2.025; 95% CI: 1.560-2.630; P < 0.001). The 5-year RFS rates of patients with LVI was significantly worse than those without LVI (61.2% VS 82.7%, P< 0.001). Patients with LVI exhibit similar prognosis (HR: 2.538; 95% CI: 1.570-4.098; P < 0.001) compared with that of VPI in pN0 non-small-cell lung cancer and a tumor diameter of 3cm or smaller. When tumor size was between 3-4cm, patients with LVI and VPI were associated with inferior prognosis than those with only LVI or VPI (P < 0.001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The presence of LVI independently and significantly affects LCSS and RFS in patients with stage I NSCLC. Our results suggest that stage T1a-1c(IA) patients with LVI should be upstaged to T2a(IB), meanwhile, stage T2a(IB) patients coexist with LVI and VPI should be upstaged again in the TNM classification.

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      MA01.02 - Histologic Subtyping in Pathologic Stage I Lung Adenocarcinoma Provides Risk-Based Stratification for Surveillance (Now Available) (ID 13400)

      10:35 - 10:40  |  Presenting Author(s): Yusuke Takahashi  |  Author(s): Takashi Eguchi, Koji Kameda, Shaohua Lu, Raj G. Vaghjiani, Kay See Tan, David R. Jones, William D Travis, Prasad S. Adusumilli

      • Abstract
      • Presentation
      • Slides

      Background

      Current national practice guidelines (NCCN, ACCP, ESMO) recommend a uniform follow-up protocol with intensive surveillance within the first two years following lung resection for stage I NSCLC. We hypothesize that the recurrence hazard following lung resection for stage I lung adenocarcinoma (ADC) varies according to histologic subtype.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A total of 1572 patients with resected pathologic stage I lung ADC were investigated. Two thoracic pathologists reviewed all tumor H&E slides (range 1-8, median 3) for histologic subtyping and percentage of each subtype. Recurrence hazard was estimated using the Kernel-Epanechnikov smoothing procedure. Association between recurrence hazard and high-grade histologic subtypes (micropapillary [MIP] and solid [SOL]) was assessed.

      4c3880bb027f159e801041b1021e88e8 Result

      Presence (≥5%) of these high-grade subtypes (MIP and/or SOL) was associated with significant increase of recurrence hazard compared to high-grade pattern negative (<5%) tumors (Figure): 1) patients with presence of either MIP or SOL had significant recurrence hazard peaks within two years after surgery; 2) SOL was associated with early hazard peak at the first year after surgery especially in distant recurrence hazard; 4) one-third of patients (515/1572, 33%) had no high-grade subtypes, in which the recurrence hazard was consistently very low (<2% risk each year) during the 10-year period after surgery without any hazard peak (red arrow).

      hazard fig 300.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our data suggest the utility of histologic subtyping for identifying patients with very low recurrence hazard, and provide foundation for establishing risk-based follow-up protocols. A potential option for low-risk patients may be omission of intensive follow-up during the first two years after surgery.

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      MA01.03 - An Externally Validated Nomogram for Predicting Distant Metastasis After SBRT for Early Stage Non-Small Cell Lung Cancer (Now Available) (ID 11182)

      10:40 - 10:45  |  Presenting Author(s): Aditya Juloori  |  Author(s): Alexander Zajichek, Michael Kattan, Daniel J. Mullen, Pamela Samson, Neil M Woody, Mike Roach, Jeffrey Bradley, Gregory M.M. Videtic, Cliff Robinson, Kevin L Stephans

      • Abstract
      • Presentation
      • Slides

      Background

      SBRT is a standard option for patients with early stage NSCLC who are medically inoperable. While SBRT is associated with excellent local control, distant metastases (DM) represent the primary pattern of failure. Adjuvant systemic therapy has not traditionally been used in this patient population due to medical comorbidities. With the advent of immunotherapy that may be better tolerated, there has been a renewed interest in identifying patients that may derive benefit. We developed and internally validated a nomogram to predict the likelihood of DM after SBRT for early stage NSCLC which was then externally validated.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Our lung SBRT registry was queried for patients with early stage NSCLC treated with definitive intent from 2003-2017 and 1002 patients were identified for analysis to develop the model. A dataset from an external institution was used to similarly identify patients and 737 were used for the validation cohort. Random Survival Forest was used to assess importance, interactivity, and overall predictive ability with respect to DM for 14 variables. A Fine-Gray competing-risks regression model was formulated where apparent interactions were examined with likelihood-ratio tests. Backward variable selection was implemented to reduce to a parsimonious model. The concordance probability (C-index) of the model was internally validated with 10-fold cross validation.

      4c3880bb027f159e801041b1021e88e8 Result

      The median overall survival was 1.71 years internally and 1.92 years externally. Median follow-up was 18.3 months and 21.1 months. 1-year incidence of DM was 16% and 12.1% in the internal and external cohorts, respectively. Random Forest analysis suggested that tumor size and PET SUV are the most important predictors of distant failure. The 1-year cumulative incidence (CI) of DM was 18.5% for PET SUV ≥4.1 vs 8.4% for <4.1. 1-year CI for tumor size >3 cm was 26% vs 12.6% for ≤3 cm. The median time to DM was 0.86 years internally and 1.1 years externally. The final nomogram included tumor size, histology, PET SUV, age, KPS, and active smoking status, and had a cross-validated C-index of 0.62. The nomogram provides predictive value for probability of DM at 1-year between 10 and 70%.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This novel nomogram with external validation can be used to predict the 1-yr DM risk after SBRT for patients with early-stage NSCLC, accounting for the competing risk of death. This nomogram may help define patient subsets for stratification in future clinical trials to help identify who may benefit from adjuvant systemic therapy after SBRT to reduce the incidence of DM and disease-related death.

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      MA01.04 - Discussant - MA01.01, MA01.02, MA01.03 (Now Available) (ID 14572)

      10:45 - 11:00  |  Presenting Author(s): Deepali Jain

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA01.05 - Opioids and Sleep Medication Use After Surgery for Early Stage Lung Cancer: A SEER-Medicare Analysis (Now Available) (ID 12961)

      11:00 - 11:05  |  Presenting Author(s): Stephanie Tuminello  |  Author(s): Juan Wisnivesky, Rebecca Schwartz, Bian Liu, Grace Mhango, Raja Flores, Emanuela Taioli

      • Abstract
      • Presentation
      • Slides

      Background

      More than 50% of patients undergoing surgery for early stage lung cancer experience persistent post-operative pain, which can prevent their returning to normal daily activities and cause disruptions in sleep. Whether Video-Assisted Thoracoscopic Surgery (VATS), a minimally invasive surgical technique, reduces long-term opioid and sleep medication use compared to traditional open surgery has not yet been established.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The Surveillance, Epidemiology and End Results data linked to Medicare data (SEER-Medicare) database was queried to identify patients with stage I primary non-small cell lung cancer (NSCLC) who had VATS or open resection between 2007 to 2013, and had no record of opioid medication in the 30 days before surgery. Long-term opioid and sleep medication use were defined as having fulfilled one or more prescriptions in the first 90 days after surgery as well another prescription in the 90-180 days post-surgery. Logistic regression was used to investigate the associations between surgical type and long-term opioid and sleep medication use. Models were adjusted for relevant clinical and socioeconomic covariates.

      4c3880bb027f159e801041b1021e88e8 Result

      There were 3,900 NSCLC patients included in this analysis; 1,987 (51.0%) VATS and 1,913 (49.0%) open surgery patients; 15.5% of patients had a record of opioid use and 9.7% of sleep medication use long-term postoperatively.

      In the adjusted model, patients were less likely to use opioids long-term if they had VATS (ORadj 0.69, 95% CI: 0.57-0.84), were older (ORadj 0.96, 95% CI: 0.94-0.98), diagnosed in a later year (ORadj 0.86, 95% CI: 0.82-0.90), and had higher income (ORadj 0.77, 95% CI: 0.60-0.99). Long-term opioid use was more likely in those with a higher comorbidity score (ORadj 1.10 , 95% CI: 1.05-1.16), large cell histology (ORadj 1.88, 95% CI: 1.17-3.00), using sleep medication before surgery (ORadj 1.72, 95% CI: 1.28-2.32) and with a previous psychiatric condition (ORadj 1.64, 95% CI: 1.28-2.09).

      After adjustment, only those with a previous psychiatric condition (ORadj 1.95, 95% CI: 1.40-2.71) and previous sleep medication use (ORadj 37.36, 95% CI: 27.92-50.00) were more likely to use sleep medications long-term; no significant difference were observed with type of surgery (ORadj 1.01, 95% CI: 0.76-1.33).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Patients who were not previous opioid users became long-term opioid users after surgery. VATS might offer NSCLC patients a better quality of life than open surgery, and therefore minimize the risk of longer-term opioid use.

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      MA01.06 - Evaluation of Safety and Efficacy in Surgical Treatment for Octogenarian Lung Cancer Patients by Multicenter Prospective Study: JACS1303 (Now Available) (ID 13117)

      11:05 - 11:10  |  Presenting Author(s): Tomohiro Haruki  |  Author(s): Hisashi Saji, Takahiko Ueno, Morihito Okada, Hiroshige Nakamura, Masayuki Chida

      • Abstract
      • Presentation
      • Slides

      Background

      The percentage of octogenarian lung cancer patients have increased on the background of the aging of Japan’s demographics. Although some retrospective studies reported clinicopathological scoring systems for predicting postoperative complications and survival outcomes for elderly lung cancer patients, optimized scoring systems remain controversial. This study (JACS1303) aims to evaluate the clinical factors to develop a comprehensive operative risk scoring (RS) system for octogenarian patients with lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      JACS conducted a nationwide multicenter prospective cohort and enrolled a total of 1,019 octogenarians with medically operable lung cancer. Details of the clinical factors, comorbidities, and comprehensive geriatric assessment were recorded for 895 patients to develop a comprehensive risk scoring (RS) system capable of predicting severe complications.

      4c3880bb027f159e801041b1021e88e8 Result

      Operative (30 days) and hospital mortality rates were 1.0% and 1.6%, respectively. Complications were observed in 308 (34%) patients, of whom 81 (8.4%) had grade 3–4 severe complications. Pneumonia was the most common severe complication, observed in 27 (3.0%) patients. The following five predictive factors: gender, comprehensive geriatric assessment (CGA)75: memory, Simplified Comorbidity Score (SCS): diabetes mellitus, Alb, and %VC were identified as independent predictive factors for severe postoperative complications (odds ratio = 2.73, 1.86, 1.54, 1.66, and 1.61, respectively) through univariate and multivariate analyses. A 5-fold cross validation was performed as an internal validation to reconfirm these five predictive factors (average AUC: 0.70). We developed a simplified RS system as follows: RS = 3 (Gender: male) + 2 (CGA75: memory: yes) + 2 (Alb: <3.8 ng/ml) + 1 (%VC: ≤90) + 1 (SCS: Diabetes mellitus: yes).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The current study shows that octogenarians can be successfully treated for lung cancer with surgical resection with an acceptable rate of severe complications and mortality. We propose a simplified RS system to predict severe complications in octogenarian patients with medically operative lung cancer.

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      MA01.07 - Validation of RTOG 0813 Normal Tissue Constraints for Pulmonary Toxicity in SBRT for Central Non-Small Cell Lung Cancer (Now Available) (ID 11318)

      11:10 - 11:15  |  Presenting Author(s): Kyle Verdecchia  |  Author(s): Bindu Manyam, Gregory M.M. Videtic, Tingliang Zhuang, Neil M Woody, Kevin L Stephans

      • Abstract
      • Presentation
      • Slides

      Background

      Stereotactic body radiation therapy (SBRT) yields excellent local control rates for medically inoperable early stage "central" non-small cell lung cancer. Normal tissue constraints provided in RTOG 0813, which tested safety and efficacy of lung SBRT for central tumors, were largely based on expert estimates, and clinical validation of constraints is limited. We sought to identify the sensitivity and specificity of the current RTOG constraints for predicting pulmonary toxicity in a large institutional data set.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We identified 136 lesions within 2 cm of the proximal bronchial tree (PBT), treated from 2005 to 2014 from a prospective registry of 1,462 patients. Dose was 50 or 60 Gy given in 5 fractions. Pulmonary toxicity was categorized as pneumonitis or non-pneumonitis (fistula, bronchial stenosis or necrosis, atelectasis, hemoptysis, or clinically significant pleural effusion). A series of dose endpoints for the PBT was generated based on dose volume histograms, where dose levels ranged from 0 Gy to 80 Gy in increments of 0.1 Gy, and volumes ranged from 0.03 cc to 50 cc in increments of 0.03cc. A total of 1,333,600 dosimetric endpoints were analyzed. The sensitivity and specificity of these endpoints in predicting pulmonary toxicity was calculated. The optimal dosimetric endpoint was chosen by identifying the highest F-score.

      4c3880bb027f159e801041b1021e88e8 Result

      We observed nine Grade 2 pneumonitis and 10 Grade ≥ 2 non-pneumonitis toxicities, of which three were Grade 5 (broncho-pleural fistula, left mainstem bronchus necrosis, and bronchial stenosis). The optimal dosimetric endpoint to avoid Grade 2-5 non-pneumonitis toxicity was D0.03cc<50 Gy to the PBT, with 90% sensitivity and 77% specificity. The optimal point dose to avoid Grade 3-5 non-pneumonitis toxicity was D0.3cc<46.5 Gy, with 100% sensitivity and 85% specificity. Applying PBT RTOG constraints to our dataset achieved 18% sensitivity and 91% specificity for D4cc<18 Gy and 29% sensitivity and 93% specificity for D0.03cc<52.5 Gy.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Clinical results from this large institutional data set validate current RTOG constraints for PBT as predictive for pulmonary toxicity. The results also suggest that RTOG constraints D4cc<18 Gy and D0.03cc<52.5 Gy to PBT have moderate sensitivity but excellent specificity for pulmonary toxicity. We identified D0.03cc <50 Gy to PBT as having the largest sensitivity and specificity for toxicity prediction, and this value parallels current RTOG constraint of D0.03cc <52.5 Gy. This analysis suggests that an additional volume/dosimetric constraint of D0.3cc<46.5 Gy may be considered for avoidance of Grade 3-5 non-pneumonitis pulmonary toxicity.

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      MA01.08 - Discussant - MA01.05, MA01.06, MA01.07 (Now Available) (ID 14573)

      11:15 - 11:30  |  Presenting Author(s): Biniam Kidane

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA01.09 - Risk Factors of Radiation-Induced Lymphopenia (RIL) and Its Prognostic Significance in Small Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy (Now Available) (ID 14426)

      11:30 - 11:35  |  Presenting Author(s): Xiaomei Gong  |  Author(s): Qianqian Zhao, Jian He

      • Abstract
      • Presentation
      • Slides

      Background

      The decrease in peripheral blood lymphocytes induced by radiation lessens the antitumour effect of the immune response, which might cause immunosuppression. This reduction might be affected by fractionation scheme. The purpose of this study was to assess the effect of fractionation scheme (consecutive daily fractions or nonconsecutive fractions) of SBRT on clinical outcomes in early-stage peripheral non-small cell lung cancer (NSCLC). We also analyzed the different effect of these two fractionation schemes in reducing peripheral blood lymphocytes during SBRT treatment period.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Data from a total of 61 early-stage peripheral NSCLC patients who had received SBRT were retrospectively analyzed. A total dose of 50 Gy in 5 fractions over 5-7 days was delivered for all patients. Peripheral blood lymphocytes were measured before and after SBRT. We used the Kaplan-Meier method, the log-rank test, and Cox proportional hazards regression to determine whether radiation treatment schedule associated with clinical outcomes.

      4c3880bb027f159e801041b1021e88e8 Result

      Figure 1 showed Kaplan–Meier estimates for progression free survival (PFS) (Figure A) and overall survival (OS) (Figure B) for entire cohort stratifying for fractionation regimen. Multivariate analysis showed that nonconsecutive fractionation was an independent predictor of a longer PFS (P = 0.002). OS trended toward improvement in the non-consecutive group, but this was not statistically significant (P = 0.181). Development of any grade 3 or higher toxicity was not significantly different between the two groups (P = 0.813). The average circulating lymphocyte counts of consecutive group patients significantly declined after RT (1977.27 versus 1368.18 cells/µl, P < 0.001) while the nonconsecutive group patients did not (1700.00 versus 1450.00 cells/µl, P = 0.155).
      figure 1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Five-fraction SBRT delivered over non-consecutive days achieved superior clinical outcomes and similar toxicity compared to consecutive fractionation. Consecutive daily fractions of SBRT might cause worse immunosuppression by the more severe damage of peripheral lymphocytes.

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      MA01.10 - Toxicity and Local Control in “Ultra-Central” Lung Tumors Treated With SBRT or High-Dose Hypofractionated RT (Now Available) (ID 13969)

      11:35 - 11:40  |  Presenting Author(s): Chunyu Wang  |  Author(s): Baho Sidiqi, Ellen Yorke, Dominique McKnight, Rosalind Dick-Godfrey, Danielle Torres, Daphna Gelblum, Andreas Rimner, Abraham J. Wu

      • Abstract
      • Presentation
      • Slides

      Background

      Stereotactic body radiation therapy (SBRT) for central lung tumors has been associated with higher rates of severe toxicity. Data suggests that tumors with specific high-risk features, namely GTV abutting proximal bronchial tree (PBT), trachea or PTV intersecting esophagus (“ultra-central” tumors), are at risk of severe complications. We sought to evaluate toxicity and efficacy for high-risk lung tumors treated with SBRT in our institution.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      All patients treated with SBRT for central lung tumors during 2008 to 2017 were reviewed to identify ultra-central tumors. Patients who received more than 4 Gy per fraction and BED10≥84 were included in the analysis. The primary endpoint was grade 3+ adverse events potentially attributable to RT, based on CTCAE 4.0. Secondary endpoints were local control (LC) and overall survival (OS) for primary lung cancer patients, Kaplan-Meier analysis was used to estimate LC and OS.

      4c3880bb027f159e801041b1021e88e8 Result

      We identified 88 patients who met the inclusion criteria (76 with abutment of PBT, 8 with abutment of trachea, 22 with overlap of esophagus, and 17 with multiple structures at risk). The median follow-up was 21.5 (95%CI, 12.5 to 30.5) months. Forty-six patients had primary NSCLC, 7 had locally recurrent NSCLC and 35 had lung metastases. The prescription doses were 400cGy x 15 (n=21), 750cGy x 8 (n=13), 1000cGy x 5 (n=29) and 900cGy x 5 (n=25). Eight patients (9.1%), all abutting the PBT, experienced fatal complications potentially related to RT. Four patients developed fatal pulmonary hemorrhage. Maximum point doses to PBT were 54.9Gy, 51.4Gy, 49.4Gy (in 5 fractions) and 63.8Gy (8 fractions) and 2 of them had received bevacizumab in close proximity to RT. Four patients developed fatal pneumonia/radiation pneumonitis (all had pre-existing COPD). No Grade 4 toxicity was identified. Grade 3 overall toxicity rate was 12.5%. Only 3 of 22 (13.6%) patients whose PTV overlapped with esophagus had Grade 3 toxicity. The 1-year and 2-year LC for the whole cohort were 87.5% and 79.1%, respectively. The 1, 2-year OS for primary NSCLC patients were 77.8% and 62.6%, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      To our knowledge, this is the largest reported series of patients who received SBRT for ultra-central tumors. RT achieves high rates of local control in these patients, but the rate of severe or fatal toxicity is substantial. Further studies are needed to establish the relationship between SBRT and toxicity in these patients.

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      MA01.11 - Salvage SBRT for Local Recurrence After Primary Surgical Resection of Early Stage Non-Small Cell Lung Cancer (Now Available) (ID 11284)

      11:40 - 11:45  |  Presenting Author(s): Sarah Sittenfeld  |  Author(s): Aditya Juloori, Chandana A. Reddy, Kevin L Stephans, Gregory M.M. Videtic

      • Abstract
      • Presentation
      • Slides

      Background

      To report on the patient, tumor and treatment characteristics of patients treated with salvage lung SBRT (sSBRT) for non-metastatic NSCLC that has relapsed after previous surgical resection, and the resulting clinical outcomes.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We surveyed our IRB-approved prospective lung SBRT registry for patients who received sSBRT for local recurrence after previous resection of an early stage NSCLC. Following sSBRT, outcomes of interest included local control (LC), overall survival (OS), and treatment-related toxicity graded per CTCAE version 4.0.

      4c3880bb027f159e801041b1021e88e8 Result

      For the interval 2004-2017, 50 (3.4%) pts, of a total of 1,461 lung SBRT cases, met criteria for analysis. Pre-sSBRT surgical approaches were: 23 (46%) wedge resection, 2 (4%) segmentectomy, 20 (40%) lobectomy, 2 (4%) bilobectomy, 1 (2%) pneumonectomy and 1 (2%) with unspecified surgery. At the time of resection, disease stage was: 34 (68%) stage I, 4 (8%) stage II, 5 (10%) stage III and for 3 (6%) pts, pre-operative stage was unknown. Median time to local recurrence after surgery was 27.45 months. At sSBRT, 38 (76%) pts had biopsy-proven recurrence while 12 (24%) had recurrence diagnosed only by radiographic findings. Forty seven (94%) pts could not have surgical salvage due to pulmonary (60%), cardiac (2%), technical unresectability (4%), poor KPS (2%), or multifactorial reasons (26%), with 3 (6%) refusing re-resection. Median age and KPS at salvage treatment was 74 years (range 50-89) and 80 (range 60-100) respectively. The most common sSBRT schedule was 50Gy in 5 fractions (68%), with all schedules having a BED of at least 100 Gy10. Median follow up after sSBRT was 22.2 months (3.8-108.8 months). Eight pts subsequently experienced local or lobar failure (16%), and 9 patients had nodal failure (18%). Median time to local failure after sSBRT was 12.5 months (2-66.1 months). At analysis, 11 (22%) pts remain alive and free from disease progression. At 24 months, LC and OS were 83.6% (95% CI 71.1-96) and 66.7% (95% CI 53.3-80.1). Median OS after sSBRT was 29.3 months. Twenty one (42%) pts failed distantly at a median time of 11.4 months and 12 (24%) pts received systemic therapy following distant failure. 74% of pts experienced no toxicity after sSBRT and three patients (6%) developed grade III toxicity (cough, atelectasis or soft tissue necrosis).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Similar to SBRT for primary early stage NSCLC, sSBRT for local relapse following initial surgical resection of NSCLC offers high rates of LC with limited toxicity. Distant failure remains the primary pattern of failure.

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      MA01.12 - Discussant - MA01.09, MA01.10, MA01.11 (Now Available) (ID 14574)

      11:45 - 12:00  |  Presenting Author(s): Drew Moghanaki

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    MA02 - Improving Outcomes for Patients with Lung Cancer (ID 895)

    • Type: Mini Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 12
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 201 BD
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      MA02.01 - ROS1 Gene Rearrangements Are Associated with an Exaggerated Risk of Peri-Diagnosis Thromboembolic Events (Now Available) (ID 12442)

      10:30 - 10:35  |  Presenting Author(s): Terry L. Ng  |  Author(s): Derek E Smith, Rao Mushtaq, Tejas Patil, Anastasios Dimou, Shuo Yang, Qian Liu, Xuefei Li, Caicun Zhou, Flora Yan, I. Alex Bowman, Stephen V Liu, Robert C. Doebele, Dara L. Aisner, Shengxiang Ren, Ross Camidge

      • Abstract
      • Presentation
      • Slides

      Background

      Based on clinical observation, we hypothesized that ROS1 gene-rearranged non-small cell lung cancer (ROS1+ NSCLC) has a higher than expected thromboembolic event (TEE) rate. A multicenter, retrospective cohort study of TEE in advanced ROS1+, KRAS+, ALK+ and EGFR+ NSCLC was conducted.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Venous (DVT / PE) and arterial (MI/TIA/CVA) TEE within +/- 365 days of diagnosis of ROS1+, KRAS+, ALK+ or EGFR+ advanced NSCLC at 4 academic centers in USA and China from October 2002 to January 2018 were captured. The primary endpoint was the incidence of TEE in ROS1+ compared to KRAS+ NSCLC as a control group within +/- 90 days of diagnosis. Secondary endpoints compared TEE incidence between ROS1+ and ALK+, and ROS1+ and EGFR+. Fine-Gray Model was used to detect differences in TEE incidence while accounting for death as a competing risk.

      4c3880bb027f159e801041b1021e88e8 Result

      105 ROS1+, 101 ALK+, 112 EGFR+, and 114 KRAS+ NSCLC patients were enrolled. Incidence rate of TEE within +/- 90 days of diagnosis was 30.5% (32/105), 12.9% (13/101), 7.1% (8/112), and 12.3% (14/114) in the respective molecular cohorts. Compared to the ROS1+ cohort, the risk of TEE was significantly lower in the three other cohorts (KRAS+ HR 0.334, 95% CI: 0.18-0.62, p=0.001; ALK+ HR 0.357, 95% CI: 0.188-0.68, p=0.002; EGFR+ HR 0.193, 95% CI: 0.089-0.421, p<0.001) (Figure 1). First event TEEs were venous as opposed to arterial in 59.5% (22/37) ROS1+, 87.1% (27/31) ALK+, 80.6% (25/31) EGFR+, and 80% (16/20) KRAS+ cases. The median time (Interquartile Range) to TEE from the time of diagnosis for ROS1+/ALK+/EGFR+/ KRAS+ was 0 days (-6.75 to 7.0), 0 days (-20.0 to 35.0), 0.50 days (-43.7 to 21.3), and 13 days (0.49 to 32.0), respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Among common molecular subtypes of NSCLC, ROS1+ oncogene is associated with a significantly higher risk of developing TEE within +/- 90 days of advanced NSCLC diagnosis.

      figure 1 ros1 90 day.tif

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA02.02 - Multistate Healthcare Network Underutilizes Valuable End-of-Life Resources in Stage IV Non-Small Cell Lung Cancer (Now Available) (ID 13935)

      10:35 - 10:40  |  Presenting Author(s): Candice Leigh Wilshire  |  Author(s): Joshua Robert Rayburn, Christopher R Gilbert, Roshanthi K Weerasinghe, Brian E Louie, Ralph W Aye, Alexander S Farivar, Eric Vallieres, Jed A Gorden

      • Abstract
      • Presentation
      • Slides

      Background

      Early implementation of outpatient palliative care (OPC) in stage IV non-small cell lung cancer (NSCLC) patients has been associated with increased survival, improved quality of life and reduction in unnecessary health care. However, medical systems have struggled with the adoption of end-of-life resources. We aimed to determine the utilization of OPC services in stage IV NSCLC patients within our multistate, community-based healthcare network.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We reviewed 4,298 stage cIV NSCLC patients diagnosed between 1/2013-12/2017, in a community-based healthcare network encompassing 34 centers in Alaska, California, Montana, Oregon and Washington. We excluded 899 patients managed at 9 sites without OPC services, and 92 patients who received inpatient palliative care only. Eligible patients were stratified by whether or not they received OPC; then further by early OPC, which was defined as within 11 weeks of diagnosis. Survival was compared using Kaplan-Meier with log rank tests.

      4c3880bb027f159e801041b1021e88e8 Result

      Of the 3,307 patients reviewed, only 8% (252/3,307) received OPC and 6% (182/3,307) early OPC. Median time from diagnosis to death was significantly longer for OPC patients (347 days, 95% CI 273-421) versus no PC (151 days, 95% CI 138-164), p<0.001; and similarly for early OPC (216 days, 95% CI 167-265) versus no PC, p=0.008. Documentation of advance directive/living will/power of attorney was low in all categories, with rates of documentation at 32%, 31% and 27% for patients receiving OPC, early OPC and no OPC, respectively.

      figure iaslc days dx to death.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      We identified that OPC services are broadly underutilized in stage cIV NSCLC patients across our multistate, community-based healthcare network. In addition, end-of-life documents were rarely completed in all clinical settings regardless of OPC. We confirmed prolonged survival associated with OPC in the community setting, but greater utilization is required to increase this benefit. These findings, as well as the additional benefits/value of OPC, require further study.

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      MA02.03 - ASTRIS: A Real World Treatment Study of Osimertinib in Patients with EGFR T790M-Positive NSCLC (Now Available) (ID 12972)

      10:40 - 10:45  |  Presenting Author(s): Yi-Long Wu  |  Author(s): Byoung Chul Cho, Qing Zhou, Gee-Chen Chang, Liyan Jiang, Giulio Metro, Claudio Martin, Gilberto De Castro, Johan F. Vansteenkiste, David Vicente, Alvin Milner, James R. Rigas, Yuh-Min Chen, Mariano Provencio

      • Abstract
      • Presentation
      • Slides

      Background

      Osimertinib is a third-generation, CNS-active EGFR-TKI that potently and selectively inhibits both EGFR-TKI sensitizing and EGFR T790M resistance mutations. We report results from a second planned protocol, optimal interim analysis of the ongoing ASTRIS study (NCT02474355).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Eligible patients receive osimertinib 80 mg once daily. Inclusion criteria: stage IIIB/IV T790M-positive non-small cell lung cancer (NSCLC); T790M status confirmed locally by validated test, not restricted by sample type; prior EGFR-TKI therapy received; WHO performance status (PS) 0−2; acceptable organ and bone marrow function and no history of interstitial lung disease (ILD) or QTc prolongation. Asymptomatic, stable CNS metastases are permitted. The primary efficacy outcome is overall survival (OS).

      4c3880bb027f159e801041b1021e88e8 Result

      From Sept 18, 2015, first patient in, to Oct 20 2017 data cut-off (DCO), 3014 patients were enrolled across 16 countries and received ≥1 dose of osimertinib (full analysis set [FAS]): median follow-up 7.9 months (range <1−24), median age 62 yrs (27–92), 64% female, 69% Asian, 30% White, 11% WHO PS 2, 45% prior chemotherapy, 34% prior radiotherapy. All patients had T790M-positive status, identified from tissue in 1610 patients (53%), plasma ctDNA in 1241 patients (41%) and from other sources in 162 patients (5%). At DCO, 1276 patients (42%) had discontinued treatment (1738 [58%] ongoing); median duration of exposure 7.4 months (<1–25); 1289 patients (43%) had a progression-free survival (PFS) event, 1276 (42%) had a time to treatment discontinuation (TTD) event, and 593 (20%) had died. In patients evaluable for response, the investigator-assessed clinical response rate was 56.6% (1625/2872; 95% confidence interval [CI] 54.7, 58.4). In the FAS, estimated median PFS was 11.0 months (95% CI 10.6, 11.1), median TTD was 12.6 months (95% CI 12.2, 13.7), and median OS was not reached (OS at 12 months was 75.8% (95% CI 73.7, 77.8). Adverse events (AEs) leading to dose modification and treatment discontinuation were reported in 321 patients (11%) and 147 patients (5%), respectively. Serious AEs were reported in 505 patients (17%). ILD/pneumonitis-like events were reported in 41 patients (1%), and QTc prolongation in 48 patients (2%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      ASTRIS, the largest reported study of osimertinib in T790M-positive NSCLC, demonstrates clinical activity similar to that observed in the osimertinib clinical trial program with no new safety signals.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA02.04 - Discussant - MA 02.01, MA 02.02, MA 02.03 (Now Available) (ID 14575)

      10:45 - 11:00  |  Presenting Author(s): Alona Zer

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA02.05 - A Double-Blind, Randomized, Placebo-Controlled Phase 3 Noninferiority Study of Darbepoetin Alfa for Anemia in Advanced NSCLC (Now Available) (ID 13816)

      11:00 - 11:05  |  Presenting Author(s): Rajnish Nagarkar  |  Author(s): Pere Gascón, Martin Šmakal, Kostas Syrigos, Carlos Barrios, Jesús Cárdenas Sánchez, Li Zhang, Dianne Tomita, Joseph Park, Cisio De Oliveira Brandao

      • Abstract
      • Presentation
      • Slides

      Background

      The effect of erythropoiesis-stimulating agents on overall survival (OS) in patients with chemotherapy-induced anemia has long been debated. This study (NCT00858364) evaluated noninferiority of darbepoetin alfa (DAR) versus placebo for OS and progression-free survival (PFS) in anemic patients with NSCLC treated to a 12.0-g/dL hemoglobin ceiling.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Adults with stage IV NSCLC expected to receive ≥2 cycles of myelosuppressive chemotherapy, life expectancy >6 months, ECOG 0–1, and hemoglobin ≤11.0 g/dL were randomized 2:1 to DAR (500 µg SC) or placebo Q3W. Patients were stratified by region, histology, and hemoglobin. Primary endpoint was OS; a Cox proportional hazards model, stratified by randomization factors, was used to evaluate noninferiority (margin based on upper confidence limit [CL] for hazard ratio [HR] ˂1.15). Secondary endpoints were PFS (noninferiority) and incidence of transfusions or hemoglobin ≤8.0 g/dL from week 5 to end of efficacy treatment period (EOETP).

      4c3880bb027f159e801041b1021e88e8 Result

      4161 patients were screened, 2549 enrolled, and 2516 included in the primary analysis set: 1680 randomized to DAR and 836 to placebo. The study was stopped early per independent DMC recommendation. Patients were well matched between arms for age (mean 61.8 years), sex (66.0% male), and race (47.5% white). DAR was noninferior to placebo for OS (HRadj 0.92; 95%CL 0.83–1.01) and PFS (HRadj 0.95; 95%CL 0.87–1.04). DAR was superior to placebo for transfusion or hemoglobin ≤8.0 g/dL from week 5 to EOETP (OR 0.70; 95%CL 0.57–0.86; P<0.001). Objective tumor response was similar between arms (DAR 36.2%; placebo 32.6%). Incidence of serious adverse events was the same in both arms (31.1%). No unexpected adverse events or cases of antibody-mediated PRCA were observed (Table).

      DAR (n=1685)

      %

      Placebo (n=833)

      %
      All treatment-emergent adverse events 84.5 86.3
      Serious adverse events 31.1 31.1
      Fatal adverse events 12.2 13.6
      Adverse events leading to discontinuation of blinded drug 2.8 4.2
      Adverse events of interest (standardized MedDRA query)
      CNS vascular disorders 1.5 1.0
      Hypersensitivity 10.6 9.0
      Severe cutaneous adverse reactions 2.1 1.3
      Embolic and thrombotic events 5.3 4.1

      8eea62084ca7e541d918e823422bd82e Conclusion

      DAR dosed to a 12.0-g/dL hemoglobin ceiling was noninferior to placebo for OS and PFS and significantly reduced odds of transfusion or hemoglobin ≤8.0 g/dL in anemic patients with NSCLC receiving myelosuppressive chemotherapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA02.06 - A Randomized, Double-Blind, Placebo-Controlled Trial of Chemotherapy Combined with Yangzheng Xiaoji in Advanced NSCLC (Now Available) (ID 13562)

      11:05 - 11:10  |  Presenting Author(s): Ligang Xing  |  Author(s): Junsheng Wang, Luming Li, Zhiyong Ma, Changlu Hu, Haibo Zhang, Li Shan, Zhendong Chen, Jiandong Zhang, Qin Zhou, Shegan Gao, Xuezhen Ma, Ping Sun, Qinyou Ren, Meina Wu, Jin Wu, Jingao Li, Juntao Yao, Hongbing Ma, Wei Wang, Wenxiu Yao, Delin Wang, Jingbo Kang, Guixin Li, Xiuwen Wang, Wanqi Zhu, Jie Wang, Jinming Yu

      • Abstract
      • Presentation
      • Slides

      Background

      Yangzheng Xiaoji (YZXJ) is a Chinese medicine formulation made of 16 herbs and used in patients with solid cancers. The aim of this randomized, double-blind and placebo-controlled multi-center trial (YANG-1,ClinicalTrials.gov registration No. NCT02195453) is to evaluate the impact of Yangzheng Xiaoji capsule on the quality of life (QoL) and treatment-related side effects in patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with advanced NSCLC and with Eastern Cooperative Oncology Group performance status 0 to 1, who receive first-line chemotherapy (gemcitabine or pemetrexed and cisplatin), were randomized (1:1) to Yangzheng Xiaoji (YZXJ) or placebo combined with chemotherapy. The primary endpoint was QoL (Functional Assessment of Cancer Therapy-Lung (FACT-L) and Lung Cancer Symptom Scale (LCSS)) after two or four cycles of chemotherapy. The second endpoints included overall response rate, progression free survival and toxicity.

      4c3880bb027f159e801041b1021e88e8 Result

      Between 10/2014 and 4/2017, the trial enrolled and randomized 504 patients from 25 centers in China. 397 patients received at least two cycles of chemotherapy and were included for final analysis. Baseline characteristics, including FACT-L and LCSS scores, were well balanced between two groups. The mean FACT-L scores were significantly changed in both groups from the baseline to that after chemotherapy (97.58 increase to 100.89 in YZXJ/chemotherapy arm, P<0.001; 93.83 decrease to 97.93 in placebo arm, P<0.001). The mean score of LCSS from baseline was significantly changed in YZXJ/chemotherapy groups(25.84 decrease to 22.31, P<0.001), but there was no statistical difference in the placebo group(25.59 vs. 26.45, P=0.136). The YZXJ/chemotherapy arm had a better QoL than the placebo/chemotherapy arm (FACT-L, 3.30 vs. -4.09; P<0.001) as well as improved lung cancer symptoms compared with placebo (LCSS, -3.53 vs. -0.86; P<0.001). There was no statistical difference in chemotherapy completion rate, ORR and PFS between two groups. The most common adverse events were bone marrow toxicity (70.92% vs. 67.59%) and gastrointestinal reaction (34.66% vs. 63.24%) (YZXJ vs. Placebo, P=0.441 and P<0.001, respectively). The rate of fatigue was significantly lower in YZXJ group than placebo group (4.38% vs. 30.04%, P<0.001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      For patients with advanced NSCLC who received platinum-based chemotherapy, Yangzheng Xiaoji Capsule significantly improved the quality of life and symptoms, especially fatigue and gastrointestinal reaction.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA02.07 - Aprepitant for Cough Suppression in Advanced Lung Cancer: A Randomized Trial (Now Available) (ID 14540)

      11:10 - 11:15  |  Presenting Author(s): Kumar Prabhash  |  Author(s): Vanita Noronha, A Bhattacharjee, Vijay Patil, Amit Joshi, Srushti Shah, S Kannan, Sandeep Ishi

      • Abstract
      • Presentation
      • Slides

      Background
      Cough is a distressing symptom in patients with lung cancer. Effective management of cough leads to improvement in quality of life (QoL) and optimal palliative care. Aprepitant, a centrally acting neurokinin-1 inhibitor, has been shown in a pilot study to significantly decrease the cough frequency. a9ded1e5ce5d75814730bb4caaf49419 Method
      A randomized open-label study in patients with advanced lung cancer with cough for over 2 weeks despite therapy with a cough suppressant, with an ECOG performance status 0 to 2. Patients were randomized 1: 1 to Arm A: aprepitant 125 mg orally on day 1, followed by 80 mg orally on days 2 to 7 along with physician’s choice of antitussive therapy. Patients on Arm B received physician’s choice of antitussive therapy. Patients were evaluated at baseline and then on days 3, 7, 9 and 12. Primary efficacy endpoint was subjective improvement in cough, measured with the Visual Analog Scale (VAS) and the Manchester Cough in Lung Cancer Scale (MCLCS). Secondary endpoints included toxicity and QoL, measured by the EORTC QLQ-C30 and LC13. The trial was approved by the` institutional IEC and registered with (CTRI/2017/05/008691). 4c3880bb027f159e801041b1021e88e8 Result
      Between June 2017 and June 2018, 128 patients were randomized: 64 to each arm. The median age was 53 yrs, 65% male, 64% never-smokers, 82% had adenocarcinoma. 88% had Stage IV disease; 80% had PS 1 and 20% PS 2. The median duration of cough was 90 days. VAS scores at baseline and day 9 was 67.93, 38.50 in Arm A and 63.15, 48.57 Arm B , with p<0.001 and the MCLCS scores at baseline and day 9 was 30.03, 22.32 in Arm A and 27.53, 23.80 Arm B , with p<0.001. Overall, there was no significant difference in the QoL scores in patients in the two arms, however there was a significant improvement in the cough-specific QoL domain in the patients on the aprepitant arm, p=0.017. There was no increase in the grade 3 and higher adverse events in the patients on the aprepitant arm. 8eea62084ca7e541d918e823422bd82e Conclusion
      Aprepitant led to a significant improvement in cough in patients with advanced lung cancer, with no increase in severe side-effects. Aprepitant should be considered as one of the treatment options for cough in lung cancer patients. 6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA02.08 - The Effect of Nabilone on Appetite, Nutritional Status, and Quality of Life in Lung Cancer Patients: A Randomized, Double-Blind Clinical Trial (Now Available) (ID 13428)

      11:15 - 11:20  |  Presenting Author(s): Jenny G. Turcott  |  Author(s): María del Rocío Guillen- Núñez, Diana Flores, Luis F Oñate, Zyanya Lucia Zatarain-Barrón, Feliciano Barrón, Oscar Arrieta

      • Abstract
      • Presentation
      • Slides

      Background

      Over one half of the patients diagnosed with advanced lung cancer experience anorexia. In addition to its high incidence, cancer-induced anorexia promotes the development of the anorexia-cachexia syndrome, which is related to poor clinical outcomes. Recently, drugs derived from cannabinoids, such as Nabilone, have been recognized for their appetite improvement properties; however, clinical trials to support their use in cancer patients are necessary.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a randomized, double-blind, placebo-controlled clinical trial to assess the effect of Nabilone vs. placebo on the appetite, nutritional status, and quality of life in patients diagnosed with advanced Non-small cell lung cancer (NSCLC) (NCT02802540).

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 65 patients from the outpatient clinic at the National Institute of Cancer (INCan) were assessed for eligibility and 47 were randomized to receive Nabilone (0.5 mg/2 weeks followed by 1.0 mg/6 weeks) or placebo. After 8 weeks of treatment, patients who received Nabilone increased their energy intake (342-kcal) and had a significantly improvements in Quality of life parameters.

      diapositiva1.jpgdiapositiva1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Nabilone is an adequate and safe therapeutic option to aid in the treatment of patients diagnosed with anorexia. Larger trials are necessary in order to draw robust conclusions in regard to its efficacy in lung cancer patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA02.09 - Discussant - MA 02.05, MA 02.06, MA 02.07, MA 02.08 (Now Available) (ID 14576)

      11:20 - 11:35  |  Presenting Author(s): Paul Wheatley-Price

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA02.10 - The First Year of Implementing a Lung Cancer Screening Program in an Urban Safety-Net Health System (Now Available) (ID 13436)

      11:35 - 11:40  |  Presenting Author(s): Heidi Hamann  |  Author(s): Simon Lee, Travis Browning, Claudia Chavez, Joanne Sanders, Suhny Abbara, David Balis, Hsienchang Chiu, Brett Moran, Noel Santini, David E Gerber

      • Abstract
      • Presentation
      • Slides

      Background

      Little is known about implementing low-dose computed tomography (LDCT) -based screening for lung cancer in settings that care for minority and underinsured populations. These patients may benefit most from guideline-based screening but may also be least likely to complete this multi-step process.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Parkland Health & Hospital system provides care through a combination of federal, state, and county-supported funding for more than one million, racial/ethnically diverse residents of Dallas County, Texas.

      A systematic protocol for LDCT screening was implemented in February 2017. We report initial screens and follow-up procedures for this first year through June 2018.

      4c3880bb027f159e801041b1021e88e8 Result

      844 LDCTs were ordered; 528 (63%) were completed, 68 (8%) had been scheduled. We detail demographics of completers and non-completers (Table 1) and proportion of LungRADS scores (Figure 1). For every year older, patients are 3% more likely to complete their scan. Of 249 completers requiring some form of follow-up (47%), only 3 required CT biopsy.

      table1_-1.jpgfigure1 (1).jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      While a systematic screening program in an urban safety-net setting generates high volume, a significant percentage of patients do not complete their initial screen. Of those who complete, many require follow-up procedures. More long-term data are needed to understand non-completion trends and subsequent annual screening.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA02.11 - Achieving Value in Cancer Diagnostics: Blood Versus Tissue Molecular Profiling - A Prospective Canadian Study (VALUE) (Now Available) (ID 13611)

      11:40 - 11:45  |  Presenting Author(s): Doreen Anuli Ezeife  |  Author(s): Jason S Agulnik, Rosalyn Juergens, Janessa Laskin, Scott A. Laurie, Lisa Le, Desiree Hao, Gwyn Bebb, Jennifer H Law, Stan Skrzypczak, Daniela Juri, Richard B Lanman, Natasha B Leighl

      • Abstract
      • Presentation
      • Slides

      Background

      Cell-free DNA (cfDNA) next-generation sequencing (NGS) has emerged as an effective molecular profiling technique that is potentially faster and cost-saving in comparison to standard-of-care (SOC) tumour biopsy and tissue-based profiling. In a public payer system, the added value of cfDNA blood-based profiling compared to SOC remains unknown. This study will determine the incremental clinical utility and cost of cfDNA NGS versus SOC genotyping in patients with advanced non-squamous non-small cell lung cancer (NSCLC).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This multicentre, non-randomized, longitudinal study will be conducted at 6 sites across Canada (BC, Alberta, Ontario, Quebec). The Guardant360® assay will be used to perform plasma-based cfDNA testing, and includes mutations, rearrangements and copy number variations in 73 known cancer associated genes. Two patient cohorts will be recruited: (1) treatment naïve patients with ≤10 pack year smoking history; and (2) patients with known abnormalities of EGFR, ALK, ROS-1 or BRAF after disease progression on all standard targeted therapies. SOC tissue profiling will be performed for all patients per institutional standards. The study will begin recruiting in May 2018, with estimated completion in 12 months. The primary endpoints are comparison of response rate (RR), progression-free survival (PFS) and time-to-treatment failure (TTF) using cfDNA versus tissue genomic testing. Secondary endpoints include time to treatment initiation, number of actionable genomic abnormalities identified, result turnaround time, potentially avoidable repeat tissue biopsies, costs, patient-reported quality of life (EQ-5D) and willingness-to-pay. Exploratory analyses of treatment outcomes in selected molecular subgroups will also be undertaken, including response to immunotherapy in those with KRAS/STK11 co-mutations. A decision-analytic model will be developed to perform cost-consequence analyses using a cfDNA versus tissue-based approach.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 210 patients will be recruited across Canada, (Cohort 1 N=150, Cohort 2 N=60). Based on testing with either blood-based GUARDANT360TM or tissue-based profiling, the costs and benefits of blood-based profiling either at initial diagnosis or upon TKI progression will be determined versus initial or repeat tumour biopsy and tissue-based profiling. Data from patients accrued until 08/2018 will be presented at the meeting.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study will determine the added value of cfDNA blood-based genotyping compared to SOC from the perspective of a public payer system (Canada).

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA02.12 - Discussant - MA 02.10, MA 02.11 (Now Available) (ID 14577)

      11:45 - 12:00  |  Presenting Author(s): William Kenneth Evans

      • Abstract
      • Presentation
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      Abstract not provided

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    MA03 - Lung Cancer Screening - Next Step (ID 896)

    • Type: Mini Oral Abstract Session
    • Track: Screening and Early Detection
    • Presentations: 11
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 206 AC
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      MA03.01 - Manchester Lung Cancer Screening: Results of the First Incidence Screening Round (Now Available) (ID 12568)

      10:30 - 10:35  |  Presenting Author(s): Haval Balata  |  Author(s): Phillip Crosbie, Matthew Evison, Richard Booton

      • Abstract
      • Presentation
      • Slides

      Background

      The European position on lung cancer (LC) screening has recommended planning for implementation to commence throughout Europe (1). The Manchester lung cancer screening pilot is one of the first real world implementation projects to take place in Europe and to publish baseline results (2). In this abstract we share, for the first time, the results from the first incidence screening round of the Manchester pilot.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The methodology and results of the baseline round of the Manchester screening pilot have been published previously (2). In brief, ever smokers, aged 55-74, from deprived areas of Manchester were invited to a free ‘Lung Health Check’ (LHC) in mobile units located at their local shopping centres. The PLCOm2012 LC risk stratification model was incorporated into the LHC and those at high risk of LC (PLCOm2012 ≥1.51%) were offered immediate LDCT in a co-located mobile scanner. At baseline, 75% of attendees were ranked in the lowest deprivation quintile; 56% were at high risk and 1384 screened with LDCT. 3% had LC diagnosed of which 80% were early stage (I+II) and 90% offered curative treatment.

      In this round of screening, all high risk individuals screened at baseline with no subsequent diagnosis of LC (screening or non-screening) were invited back for an annual LDCT scan at the same community locations. Exclusion criteria included death, other malignancies under follow-up and CT thorax within 3-months of due screening date. National and GP specific registries were checked for interval LC diagnosis.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 1,194 LDCT scans were performed as part of the first incidence round of screening. Overall 28 (2.3%) individuals received a positive scan result and were referred to the MDT. Of these, 18 (1.5%) individuals were diagnosed with LC of which 78% (n=14/18) were lower stage (I-II) and 89% (n=16/18) offered curative treatment. The false positive rate was 0.8% of the screened population as a whole and 36% of those with a positive scan result. There were no interval LCs diagnosed at one year.

      The cumulative LC detection rate over the first 12 months of the programme was 4.3% (n=60/1384) of which 80% (n=51/64) were stage I-II.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Annual LDCT screening of high risk individuals in this real world lung cancer screening implementation project continues to identify a significant number of early stage lung cancers amenable to curative treatment. No interval lung cancers were diagnosed at one year suggesting the baseline selection criteria for screening was appropriate.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA03.02 - Prospective Evaluation of the Clinical Utility of the International Lung Screen Trial Lung Nodule Management Protocol (Now Available) (ID 14043)

      10:35 - 10:40  |  Presenting Author(s): Stephen Lam  |  Author(s): Renelle L Myers, Sukhinder Atkar-Khattra, Ren Yuan, John Yee, John English, Kyle Grant, Alex Lee, Anna McGuire, Annette Maree McWilliams, Fraser Brims, Emily Stone, Venessa Chin, Lorraine Chantrill, Mark Connellan, Marhsall Plitt, Henry Marshall, Ian Yang, Rayleen Bowman, Kwun M Fong, John Mayo

      • Abstract
      • Presentation
      • Slides

      Background

      Several protocols are available to guide management of lung nodules identified by low-dose screening CT. It is important to objectively assess their clinical utility in order to weigh the potential harm versus potential beneficial impacts of the following: early recall imaging studies/biopsy and health care resource utilization. We aimed to prospectively evaluate clinical utility of the PanCan lung nodule management protocol in the International Lung Screen Trial (ILST).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Ever smokers age 55 to 80 years were enrolled into ILST if they has a ≥30 pack-years smoking history and smoked within 15 years or if their PLCO m2012 6 year lung cancer risk was ≥1.51%. Figure 1 shows the ILST lung nodule management protocol based on the PanCan nodule malignancy risk calculator (NEJM 2013;369:908 & BMJ 2014;348:g2253).

      4c3880bb027f159e801041b1021e88e8 Result

      Since July 2016, 757 ever smokers (mean age 65 years, 44% female, 15% non-Caucasian) had been enrolled. The distribution of malignancy risk categories (CAT) were: CAT1 70%, CAT2 15%, CAT3 11%, CAT4 3.5%, CAT5 0.4%. CT biopsy or bronchoscopic biopsy for diagnosis/staging was done in 16/26 CAT 4 (62%) and 7/84 CAT 3 (8%) participants. Lung cancer was confirmed in 15/757 (2%). Thus far, surgery was performed in 9 CAT 4 and 2 CAT 3 participants, with one benign resection (9%) for a growing FDG avid nodule. Of the 3 CAT5 participants, one was found to have granulomatous changes in an enlarged paratracheal lymph node and two had segmental atelectasis due to mucoid impaction.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The ILST protocol triaged 70% of the screening cohort with low malignancy risk to biennial screening instead of annual repeat screening. Participants with high malignancy risk (CAT 4+5) were triaged to a diagnostic pathway (4%). Our preliminary results suggest the ILST protocol may decrease resource utilization and potentially minimize risk of screening for participants.

      figure1 ilst lung nodule management protocol.jpg

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA03.03 - Prolonged Low-Dose Computed Tomography (LDCT) Screening Beyond 5 Years Reduces Overall and Lung Cancer Specific Mortality (Now Available) (ID 13227)

      10:40 - 10:45  |  Presenting Author(s): Ugo Pastorino  |  Author(s): Federica Sabia, Stefano Sestini, Mario Silva, Mattia Boeri, Anna Cantarutti, Nicola Sverzellati, Gabriella Sozzi, Giovanni Corrao, Alfonso Marchianò

      • Abstract
      • Presentation
      • Slides

      Background

      The National Lung Screening Trial (NLST) showed that lung cancer screening (LCS) by low-dose computed tomography (LDCT) improves the overall survival. The NLST and most of the LCS trials were limited to a 5-year period, therefore there is no prospective evidence about the optimal duration of LCS. The aim of this study was to assess the potential benefit of long term LC screening beyond 5 years, notably its effect in 10-year overall and LC specific mortality.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The Multicenter Italian Lung Detection (MILD) trial prospectively enrolled 4,099 participants, randomized to either LDCT arm (n=2,376) or control arm (n=1,723); 38,561 person-years of follow-up were accumulated between 2005 and March 2017. The primary outcomes were 10-year overall and LC specific mortality. Moreover, a Landmark Analysis was used to test the long-term effect of LCS, beyond 5 years (notably by selective exclusion of events that occurred < 5 years). Cumulative mortality were evaluated using Kaplan-Meier estimator and differences among groups were tested using Log-rank test, adjusted for sex, age and pack-years. The prognostic value of assigned arm in predicting mortality was investigated by Cox’s proportional-hazard’s regression adjusted for the above variables.

      4c3880bb027f159e801041b1021e88e8 Result

      In the whole 10-year LCS, LDCT arm showed a protective non-statistically significant trend for reduction of overall mortality (HR: 0.82, 95% CI 0.63 to 1.07) and a significant 41% reduced risk of LC mortality (HR 0.59, 95% CI 0.38 to 0.92), compared to the control arm.

      Beyond the 5th year of screening, LDCT arm showed a significant 29% reduction of overall mortality (HR: 0.71, 95% CI 0.50 to 0.99), and a significant 62% reduced risk of LC mortality (HR 0.38, 95% CI 0.20 to 0.74) (Figure 1).

      figure1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Prolonged LDCT screening beyond 5 years reduces overall mortality, and it is most beneficial in further reduction of LC specific mortality.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA03.04 - Discussant - MA 03.01, MA 03.02, MA 03.03 (Now Available) (ID 14578)

      10:45 - 11:00  |  Presenting Author(s): Denise Aberle

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA03.05 - New Subsolid Pulmonary Nodules in Lung Cancer Screening: The NELSON Trial (Now Available) (ID 11998)

      11:00 - 11:05  |  Presenting Author(s): Marjolein A Heuvelmans  |  Author(s): Joan E Walter, Uraujh Yousaf-Khan, Monique Dorrius, Erik Thunnissen, Anna Schermann, Harry J.M. Groen, Carlijn M. Van Der Aalst, Kristiaan Nackaerts, Rozemarijn Vliegenthart, Harry J De Koning, Matthijs Oudkerk

      • Abstract
      • Presentation
      • Slides

      Background

      A central challenge in low-dose computed tomography (LDCT) lung cancer screening is the identification of clinically relevant lung cancer, while preventing overdiagnosis and overtreatment. Subsolid nodules are particularly challenging as they carry a relatively high malignancy rate but possess a slow growth rate. Current guidelines propose a watchful waiting approach with CT surveillance. While new solid nodules after baseline screening have a high lung cancer probability at small size and require lower size cutoff values than baseline nodules, there only is limited evidence on management of new subsolid nodules. Aim of this study was to assess the occurrence and lung cancer frequency of new subsolid nodules and to determine whether a more aggressive follow-up approach is necessary for new subsolid nodules.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Within the Dutch-Belgian randomized controlled LDCT lung cancer screening trial (NELSON), 7557 participants underwent baseline screening between April 2004 and December 2006. Three incidence screening rounds took place 1 year, 3 years, and 5.5 years after baseline screening. Participants with new subsolid nodules detected after the baseline screening round were included. A nodule was classified as (pre-)malignancy when it was diagnosed as lung cancer during diagnostic workup including histologic assessment.

      4c3880bb027f159e801041b1021e88e8 Result

      In the three incidence screening rounds 60 new subsolid nodules not visible in retrospect (43 [72%] part-solid, 17 [28%] nonsolid) were detected in 51 participants (0.7% [51/7295] of participants with at least one incidence screening). Eventually, 6% (3/51) of participants with a new subsolid nodule was diagnosed with a (pre-)malignancy in such a nodule. The (pre-)malignancies were adenocarcinoma (in situ) and diagnostic work-up (referral 950, 364, and 366 days after first detection respectively) showed favorable staging (stage I). Overall, 65% (33/49) of subsolid nodules with follow-up screening were resolving.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Less than 1% of participants in LDCT lung cancer screening presents with a new subsolid nodule after baseline. Contrary to new solid nodules, new subsolid nodules do not require a more aggressive follow-up approach than baseline nodules.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA03.06 - Descriptive Epidemiology of Significant Incidental Findings in a Large Clinical Lung Cancer Screening Program (Now Available) (ID 12313)

      11:05 - 11:10  |  Presenting Author(s): Shawn M Regis  |  Author(s): Andrea Katalin Borondy Kitts, Andrea B McKee, Carla R Lamb, Kimberly R Christ, Jacob M Sands, Brady J McKee

      • Abstract
      • Presentation
      • Slides

      Background

      The identification and reporting of significant incidental (non-lung cancer) findings in CT lung screening (CTLS) has not been standardized, though there is an available modifier in the LungRADS structured reporting system to identify a scan as including a significant incidental finding. In this study, we describe the significant incidental findings and follow-up in a large, established clinical CTLS program.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively reviewed all of the clinically significant or potentially significant non-lung cancer findings, which we will refer to as significant incidental findings, for patients undergoing clinical CTLS in our program from January 2012 through December 2016 with follow-up through December 2017. Significant incidental findings were defined as any unexpected new and/or unknown non-lung cancer finding requiring clinical or imaging evaluation prior to the next CTLS exam. Given the high prevalence of coronary artery calcifications and emphysema in the CTLS population, these findings were not classified as signifi­cant incidentals. We describe the site of the incidental finding, the follow-up intervention, and the outcome. We also calculate the cancer detection rate for non-lung cancers.

      4c3880bb027f159e801041b1021e88e8 Result

      Of the 6482 scans performed during the study window, 286 (4.4%) reported a significant incidental finding. These findings were reported in 276 (9.4%) of the 2927 patients screened during that time. Nine patients had more than one CTLS exam with a significant incidental finding. The majority of incidental findings were found in the kidneys (18%), liver (14%), and thyroid (11%). There were 15 non-lung cancers diagnosed for a cancer detection rate of 5.4%. The most common intervention, 43%, involved additional imaging, while 26% had a follow-up phone call or consult with a physician. Biopsy was performed in 9.1% and 6.7% had surgery. Surveillance was recommended for 43.4% of the findings, medical intervention was required for 12.3% of non-cancer findings and 12.9% of findings required no additional follow-up. There were 25 (8.7%) significant incidental findings with unknown follow up and outcomes and 31 (10.8%) that resulted in not finding anything on follow-up to explain the finding seen on the CTLS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Only 4.4% of all scans in our CTLS program reported a significant incidental finding. Almost 70% of the 286 significant incidental findings identified conditions requiring medical treatment, surgical intervention, or surveillance. There was one non-lung cancer diagnosis for every 7.5 lung cancers diagnosed in our screening program.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA03.07 - Development and Validation of Deep Learning Model for Recognition of Histologic Subtype of Lung Adenocarcinoma from CT Images (Now Available) (ID 14412)

      11:10 - 11:15  |  Presenting Author(s): Yunlang She  |  Author(s): Jiajun Deng, Dong Xie, Chang Chen

      • Abstract
      • Presentation
      • Slides

      Background

      The clinical decision to either follow-up or resection from radiologic features for lung adenocarcinoma (atypical adenomatous hyperplasia [AAH], adenocarcinoma in situ [AIS], minimally invasive adenocarcinoma [MIA] and invasive adenocarcinoma [IA]) appearing as Sub-solid nodules (SSNs) is still challenge, and currently more relies on measures of diameter, solid component ratio. With the successful application of deep learning neuro-network (DLNN) for the classification of skin or common treatable blinding retinal diseases, we hypothesized that DLNN might help the histologic subtype classification of SSNs from CT images. The purpose of this study is to develop and validate a deep neuro-network model to classify AAH, AIS, MIA and IA or define a feasible classification for follow-up or treatment decision.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A total of 869 patients with 1344 pathologic confirmed nodules (AAH: 75, AIS: 340, MIA:321, IA: 608) were enrolled into this study. Two 3D mixed-scale dense-connected convolutional neuro network models (3D MS-DenseNet) were developed for 2 classification tasks: 4-class (AAH, AIS, MIA, IA), 3-class (AAH, AIS/MIA, IA). Eighty percent of whole datasets were randomly selected for training set, while other 20% were used for testing set. The nodules were firstly selected using a bounding box in 3D Slicer, and then cropped into 128 x 128 x 128 matrix size as the input to MS-DenseNet, and the output layer from the network was a 4-node or 3-node softmax classifier. Confusion matrix were used for the performance evaluation of both models and the classification accuracy for each class were reported.

      4c3880bb027f159e801041b1021e88e8 Result

      The classification accuracy of AAH, AIS, MIA, IA in testing set were 0.75, 0.45, 0.52, 0.85 respectively by 4-class, suggesting that the differentiation between AIS and MIA from CT images by neuro-network is challenge. While in the 3-class classification task with purpose of decision supporting for treatment, the classification accuracy of AAH, AIS/MIA, IA were 0.70, 0.73, 0.88 in the same testing set.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The DLNN showed potential capability in differentiating AAH, IA from other adenocarcinoma subtypes, while failed to differentiate AIS and MIA. When combing AIS and MIA for reclassify adenocarcinoma subtypes from the perspective of treatment, the DLNN achieved reasonable performance, suggesting that DLNN might be useful in supporting clinical treatment decision whether to follow-up or take different resection for SSNs.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA03.08 - Discussant - MA 03.05, MA 03.06, MA 03.07 (Now Available) (ID 14579)

      11:15 - 11:30  |  Presenting Author(s): Richard Booton

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA03.10 - Population-Based Relative Risks for Lung Cancer Based on Complete Family History of Lung Cancer  (Now Available) (ID 11268)

      11:30 - 11:35  |  Presenting Author(s): Shamus R Carr  |  Author(s): Lisa A Cannon-Albright, Wallace Akerley

      • Abstract
      • Presentation
      • Slides

      Background

      Published risk estimates for diagnosis of lung cancer based on family history are typically focused on close relatives, rather than a more diverse or complete family history. This study provides relative risks (RR) for lung cancer based on comprehensive family history data obtained from a statewide Cancer Registry linked to a high quality genealogy data resource. Risk estimates presented avoid common recall, recruitment, ascertainment biases, and are based on an individual’s (proband’s) lung cancer family history constellation (pattern of lung cancer affected relatives).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A population-based genealogical resource linked to a statewide electronic SEER cancer registry estimated relative risk (RR) for lung cancer for an individual based upon their lung cancer family history. Family history data available for a proband included degree of relationship (first to third-degree), paternal or maternal family lung cancer history, number of lung cancer affected relatives and age at diagnosis of affected relatives. Over 1.3M probands probands with specific constellations of lung cancer were analyzed. To estimate RRs, the observed number of lung cancer cases among probands with a specific family history constellation was compared to the expected number using internal cohort-specific rates.

      4c3880bb027f159e801041b1021e88e8 Result

      5,048 lung cancer cases were identified. Significantly elevated RR was observed for any number of lung-cancer-affected relatives among first-, second-, or third-degree relatives. RRs for lung cancer were significantly elevated for each additional lung cancer first-degree relative (FDR) ranging from RR=2.57 (2.39, 2.76) for >= 1 FDR to RR=4.24 (1.56, 9.23) for ≥3 FDRs affected. In an absence of FDR family history, increased risk for lung cancer was significant for increasing numbers of affected second-degree relatives (SDR) ranging from 1.41 (1.30, 1.52) for ≥ 1 SDR to 4.76(1.55, 11.11) for ≥ 4 SDRs. This was also seen in the absense of FDRs and SDRs for affected third-degree relatives (TDR) ranging from 1.18 (1.11, 1.24) for ≥1 affected TDR to 1.55 (1.03, 2.24) for ≥ 4 affected TDRs. RRs were significantly increased with earlier age at diagnosis of a first degree relative, and equivalent risks for maternal compared to paternal history were observed.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study provides unbiased, population-based estimates of lung cancer risk based on a proband’s complete family history that can be 2-5+ times increased. Estimates of RR for lung cancer based on family history are arguably very relevant clinically. The constellation RR estimates presented could serve in individual decision making to direct resource utilization, and could be pivotal in decision making for screening, treatment, and post treatment surveillance.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA03.11 - Trained Dogs Can Identify Malignant Pulmonary Nodules in Exhaled Gas (Now Available) (ID 13056)

      11:35 - 11:40  |  Presenting Author(s): Angela Guirao  |  Author(s): Laureano Molins, Ingrid Ramon, Gemma Sunyer, Nuria Vinolas, Ramon Marrades, David Sanchez, Juan J. Fibla, Jorge Hernandez, Marc Boada, Rudith Guzman, Alejandra Libreros, Alvaro Agusti

      • Abstract
      • Presentation
      • Slides

      Background

      After our recent report that trained dogs can identify the presence of lung cancer (LC) in exhaled air samples of patients with and without large LC(1), we designed a prospective controlled study to investigate if such trained dog can also discriminate between the exhaled gas samples of individuals with and without malignant pulmonary nodules.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We collected samples of exhaled air from 30 patients with indeterminate pulmonary nodules before the diagnostic and therapeutic surgery, and from 77 individuals without LC and without pulmonary nodules. Exclusion criteria were other neoplasm, and chemotherapy treatment. Participants refrained to eat, drink and smoke 30 minutes before they exhaled inside a crystal tube filled with hidrophilic and hidrophovic wool and closed with silicon taps, as we used in our previous report. Likewise, the training method of the dog was also based on a progressive prize-dependent learning method. Tubes containing the samples were introduced in wood boxes with an open side to enable the smelling of the sample. The dog was confronted to samples with and without pulmonary nodules in a proportion of 1/4 in order to discriminate malignant ones.

      4c3880bb027f159e801041b1021e88e8 Result

      The dog was confronted with 90 samples with indeterminate pulmonary nodules (3 per patient) and 372 samples without pulmonary nodules and without LC. The dog was confronted 10 times to each sample of pulmonary nodules with different combinations of “no LC” exhaled gas samples, which represents a total of 900 attempts. The dog must mark the samples he identifies as malignant ones. He achieved successful results with a sensitivity of 0,97, a specificity of 0,99, a PPV of 0,97 and a PNV of 0,99. Out of 30 patients with indeterminate pulmonary nodules the dog recognized 27 of them as positive for LC and 3 as negative for LC. Those results matched with the anatomical pathology surgery report.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Trained dogs can discriminate the presence of malignant pulmonary nodules from exhaled gas samples with an extraordinarily high degree of reliability.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA03.12 - Discussant - MA 03.10, MA 03.11 (Now Available) (ID 14580)

      11:40 - 11:55  |  Presenting Author(s): Luis M Montuenga

      • Abstract
      • Presentation
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      Abstract not provided

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    MS01 - Cancer Pathways, Targeted Therapy and Resistance (ID 780)

    • Type: Mini Symposium
    • Track: Biology
    • Presentations: 4
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 206 F
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      MS01.01 - Defects of the SWI/SNF OR MYC/MAX Pathways: Effects in Cell Differentiation and Therapeutic Opportunities (Now Available) (ID 11401)

      10:30 - 10:50  |  Presenting Author(s): Montse Sanchez-Cespedes

      • Abstract
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      Abstract

      The SWI/SNF complexes are ATP-dependent remodelers of the chromatin structure, by disrupting of DNA–histone interactions to activate or repress gene expression (Wilson et al. 2011). In healthy adults and during embryonic development, the complex is involved in the control of cell differentiation and in the specification of different tissues. Components of the SWI/SNF complex bind to various nuclear receptors, such as those of estrogen, progesterone, androgen, glucocorticoids and retinoic acid, thereby adapting the gene expression programs to the demands of the cell environmental requirements. The effect of the SWI/SNF complex on some of these processes is, at least in part, related to its involvement in regulating hormone-responsive promoters (reviewed Romero et al. 2014).

      A few years ago, we discovered that, in lung cancer, the SWI/SNF component, SMARCA4 (also called BRG1), is genetically inactivated in about thirty per cent of non-small cell lung cancers (NSCLC), and that its inactivation occurs in a background of wild type MYC (Medina et al. 2008). Nowadays, it is well established that other components of the complex are also commonly inactivated in most cancer types, including lung cancer (reviewed in Romero et al. 2014). Gene alterations of the SWI/SNF complex are significantly more common in NSCLC, as compared to small cell lung cancers (SCLC), and tend to associated with smoking habit. In addition, we reported the presence of tumor-specific inactivation of the MYC-associated factor X gene, MAX, in about ten percent of SCLC (Romero et al. 2014). The two events are mutually exclusive among them and with alterations at the MYC-family of genes. We also demonstrated that SMARCA4 regulates the expression of MAX and that depletion of SMARCA4 specifically in MAX-deficient cells strongly decreased cell growth, heralding a synthetic lethal interaction with potential therapeutic implications. Furthermore, MAX required of SMARCA4 to activate neuroendocrine transcriptional programs and to up-regulate MYC-targets, such as glycolytic-related genes. Finally, we observed genetic inactivation of the MAX dimerization protein, MGA, in lung cancers with wild type components of the SWI/SNF or MYC pathways.

      The widespread occurrence of alterations at genes encoding different components of the SWI/SNF complex reveals an important new feature that sustains cancer development. Retinoic acid (RA) and glucorticoids (GC) are well known modulators of cell differentiation, embryonic development and morphogenesis. GCs and RA are part of the curative treatment of some malignancies, mostly leukemias (Collins et al. 2002; Rutz et al. 2002; Pottier et al. 2008). However, most solid tumors, including lung cancers, are refractory to GC- and RA-based therapies. Underlying some cases of refractoriness to GC and RA is a dysfunctional SWI/SNF complex, for example due to alterations at SMARCA4 (Romero et al. 2002). On the other hand, compounds that modulate the structure of the chromatin are currently used to treat cancer. These include histone deacetylase (HDAC) inhibitors, in hematological malignancies and cutaneous T-cell lymphomas, and inhibitors of DNA methylation such as azacytidine for myelodysplasic syndrome (Liu et al. 2013). HDACs and DNA methylation inhibitors promote gene transcription by increasing DNA accessibility through the inhibition of histone deacetylation and DNA methylation, respectively. In a preliminary study, these drugs, in combination, have shown promising results in the treatment of lung cancer patients. In lung cancer cell lines, we observed that GC plus RA (GC/RA) in combination with the epigenetic drugs azacytidine and SAHA (A/S) reduced growth, triggered pro-differentiation gene expression signatures and downregulated MYC, in MYC-amplified but not in most SMARCA4-mutant cells (Romero et al. 2017). In vivo, treatments with GC/RA improved overall survival of mice implanted with MYC-amplified cells and reduced tumor-cell viability and cell proliferation. We also found some effect of the SAHA treatment, alone in reducing the cell growth of MYC-amplified lung cancer cells but not those that are SMARCA4-deficient. Thus, we propose that the combination of retinoids, corticoids and epigenetic treatments of lung tumors with MYC amplification constitute a strategy for therapeutic intervention in this otherwise incurable disease.

      Altogether, the genetic observations coupled with the functional evidence demonstrate that an aberrant SWI/SNF-MYC network is essential for lung cancer development and open novel therapeutic possibilities for the treatment of lung cancer patients.

      REFERENCES

      Collins SJ. The role of retinoids and retinoic acid receptors in normal hematopoiesis. Leukemia 2002; 16, 1896–905.

      Liu SV, Fabbri M, Gitlitz BJ, Laird-Offringa IA. Epigenetic therapy in lung cancer. Front Oncol 2013; 3, 135.

      Medina PP et al. Frequent BRG1/SMARCA4-inactivating mutations in human lung cancer cell lines. Hum Mut 2008; 29, 617-22a.

      Pottier N et al. The SWI/SNF chromatin-remodeling complex and glucocorticoid resistance in acute lymphoblastic leukemia. J Natl Cancer Inst 2008; 100, 1792-803.

      Romero OA et al. The tumour suppressor and chromatin-remodelling factor BRG1 antagonizes Myc activity and promotes cell differentiation in human cancer. EMBO Mol Med 2012; 4, 603-16.

      Romero OA et al. MAX inactivation in small cell lung cancer disrupts MYC-SWI/SNF programs and is synthetic lethal with BRG1. Cancer Discov 2014; 4, 292-303.

      Romero OA, Sanchez-Cespedes M. The SWI/SNF genetic blockade: effects in cell differentiation, cancer and developmental diseases. Oncogene 2014; 33, 2681-9.

      Romero OA et al. Sensitization of retinoids and corticoids to epigenetic drugs in MYC-activated lung cancers by antitumor reprogramming. Oncogene 2017; 36, 1287-96.

      Rutz HP. Effects of corticosteroid use on treatment of solid tumours. Lancet 2002; 360, 1969–70.

      Wilson GB, Roberts CWM. SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer 2011; 11, 481-92.

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      MS01.02 - Targeting Negative Feedback Regulators to Hyperactivate Oncogenic Signaling (Now Available) (ID 11402)

      10:50 - 11:10  |  Presenting Author(s): William Lockwood

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      Abstract not provided

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      MS01.03 - Stimulating Anti-Tumor Immunity Through Enhancing T-Cell Activation (Now Available) (ID 11403)

      11:10 - 11:30  |  Presenting Author(s): Kwok-Kin Wong

      • Abstract
      • Presentation
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      Abstract not provided

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      MS01.04 - Addressing Drug Resistance Beyond Kinase Domain Mutations (Now Available) (ID 11404)

      11:30 - 11:50  |  Presenting Author(s): Robert C. Doebele

      • Abstract
      • Presentation
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      Abstract not provided

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    MS02 - The Future of IO (ID 781)

    • Type: Mini Symposium
    • Track: Immunooncology
    • Presentations: 5
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 106
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      MS02.01 - What Is/Will Be the Optimal Duration of Therapy with IO? (Now Available) (ID 11405)

      10:30 - 10:45  |  Presenting Author(s): David R. Spigel

      • Abstract
      • Presentation
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      Abstract not provided

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      MS02.02 - Combination Therapies: Where Are We in 2018? (Now Available) (ID 11406)

      10:45 - 11:00  |  Presenting Author(s): Martin Reck

      • Abstract
      • Presentation
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      Abstract not provided

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      MS02.03 - Next Generation IO in Lung Cancer (Now Available) (ID 11407)

      11:00 - 11:15  |  Presenting Author(s): Solange Peters

      • Abstract
      • Presentation
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      Abstract not provided

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      MS02.04 - Optimizing Clinical Trial Designs in Immunotherapy (Now Available) (ID 11408)

      11:15 - 11:30  |  Presenting Author(s): Vassiliki A Papadimitrakopoulou

      • Abstract
      • Presentation
      • Slides

      Abstract

      Anti-PD (L)1 therapy is part of the standard of care approaches in 1st line and 2nd line therapy for NSCLC either as monotherapy (1) or in combination with chemotherapy (2) and has shown benefit for a subset of NSCLC defined as tumors with high tumor mutation burden (TMB) in combination with anti-CTLA4 therapy (3).

      Several questions remain though about how to optimally integrate immunotherapy in the standard of care setting. These include questions on the optimal biomarker testing, questions on whether immunotherapy should be sequenced with chemotherapy, optimal duration of therapy and the role of maintenance therapy and finally and most importantly evaluation of novel regimens for tumors that either refractory to immunotherapy or acquire resistance.

      Clinical trials with targeted therapy have demonstrated the power of biomarker integration in clinical trial design in settings where a matched driver mutation and a targeted therapy addressing that mutation is used. It is therefore envisioned that as novel biology emerges we will be able to characterize tumors and their microenvironment and define subsets that would be predicted to benefit from rational combinations. New trial design mandates partitioning patients into more select, precise populations, and identification of these unique groups requires clinical trials to evolve quickly to provide clinically relevant outcomes

      Therefore clinical trial designs that are envisioned to accelerate knowledge and expand the benefit to larger patient populations include:a)clinical trials in early NSCLC-neoadjuvant therapy providing the advantage of obtaining surgical specimens for biological correlates and potentially enhancing the cure rates b)Biopsy driven-clinical trials where biopsies are obtained pre and on therapy and possibly at progression to characterize biologic correlates of response or resistance c) umbrella clinical trials which allow for simultaneous enrollment of several subsets of patients and allocation to appropriate therapies. This latter category allows for modular designs with ineffective agents being replaced by more potent agents based on smaller signal-seeking studies. This paradigm is well represented by the LUNG-MAP (SWOG S1400) study using a multidrug, targeted screening approach to match patients in one of multiple trial substudies, each testing a different drug. This study, has recently incorporated a major focus for immunotherapy-resistant tumors and a new platform has been integrated in this public-private collaboration between the National Cancer Institute, academic institutions, and private industry (4). For the design of randomized phase III studies using overall survival (OS) as the primary endpoint, there is a shift from the conventional approach based on a proportional hazards model to those that account for the unique survival kinetics observed in immuno-oncology trials, such as long-term survival and delayed clinical effect.

      References

      1.Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015 May 21;372(21):2018-28. doi: 10.1056/NEJMoa1501824. Epub 2015 Apr 19.

      2. Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC; KEYNOTE-189 Investigators. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer.N Engl J Med. 2018 May 31;378(22):2078-2092. doi: 10.1056/NEJMoa1801005. Epub 2018 Apr 16.

      3. Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden.

      N Engl J Med. 2018 May 31;378(22):2093-2104. doi: 10.1056/NEJMoa1801946. Epub 2018 Apr 16.

      4. LUNG-MAP. lung-map.org/about-lung-map. Accessed June 17, 2018

      e353dbe42c8654f33588d4da0b517469

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      MS02.05 - Convincing Policy Makers to Afford Immunotherapy (Now Available) (ID 11409)

      11:30 - 11:45  |  Presenting Author(s): Carlos Gil Ferreira

      • Abstract
      • Presentation
      • Slides

      Abstract

      Immunotherapy has revolutionized the field of oncology in an increasing number of tumor indications [1]. The challenge is how to incorporate these into the toolbox of medical oncologists, given the complexity and inequities of the distinct healthcare system throughout the globe, limiting financial resources and numerous health needs. Here we provide a series of recommendations that are likely to improve access and reduce the cost of these medications. Nonetheless, there are numerous challenges that must be overcome if the entire cancer population eligible to receive immunotherapy is to benefit from this remarkable advancement in health care.

      In the last 15 years cancer drugs prices have been escalating and have become an issue for patients and the entire healthcare system. Earlier to 2000, the average price for a year of therapy or total treatment was less than $10,000. By 2012, this had increased tenfold, with 92% of the new drugs approved for cancer indications that year costing more than $100,000 per year of treatment. Globally, the costs of oncology therapeutics and supportive care increased 11.5% from 2010 to 2015 [2]. Predictions that integrate trends in incidence, survival, oncology practice patterns, and cost of cancer therapeutics estimate that the total cost of cancer care in the U.S. will rise to $173 billion in 2020 [3].

      Under the present system, drug manufacturers regulate pricing. The rapid approval of new immuno-oncology (I-O) agents, all of which carry substantial price tags, has pulled this issue clearly into view, since payers are key stakeholders in determining coverage and reimbursement for this treatment. Payers through the world are dealing with how to assess these drugs and determining whether they are worth the cost of making them available to patients [4].

      The growing number of drugs combinations that are already expensive leaves payers even more worried. In a recent investigation done by “Precision for Value”20 payers representing 75 million lives and 10 integrated delivery systems secure were inquired about their concerns around combination immunotherapy regimens. The results were: 33% of respondents said it was either very or extremely important whether an immunotherapy was used as part of a combination treatment; 37% said they were more concerned about a particular combination as opposed to another. Of these, almost 75% said a combination of immunotherapies was more concerning than an immunotherapy-chemotherapy combination; 55% of respondents cited cost as their biggest concern around immunotherapy combinations [5].

      In general payers focus on monitoring the use of this drugs applying severe precertification criteria [4]. Their main argument regards that payers articulates that the population is still not relatively wide-ranging, even if there are incredible response rates with some, and so, at the end, they are paying for all [6]. Solid data on patient selection and health economics aspects of I-O indications are eagerly needed. At this purpose the use of biomarkersappears as a significant therapeutic tool since it could predict the benefit from a specific treatment and consequently may help to reduce the cost of pharmacotherapy by enabling the selection of a drug that will offer greater benefit in a distinct population [7]. In fact, some studies have been showing that the use of biomarkers reduces the cost effectiveness of immuno-oncologic therapy [6]. Moreover, studies that include a biomarker-driven health economics analysis may show a value-based pricing strategy for immune-oncologic drugs [1].

      The discussion on access to costly cancer drugs is global. The cost of a drug could directly influence the access and successively the number of patients treated; increasing the access would enable a growth in both economic and health outcomes for all stakeholders. The value-based delivery and reimbursement in oncology are also a cause for discussion. For instance, should a similar medication have distinctive costs for different indications if the results are not the same? Another pricing indication would constrain pharmaceutical producers to contend on costs and results [1, 7].

      Whether the idea is move from a standard capitalism-based pricing model towards value-based oncology care an innovative model for interface between government, pharmaceutical industry, healthcare providers and society should be set up [7]. Moreover, payers should be committed with the provider community. Clear policies based on the most recent data available must be presented. The challenge may be the speed with which science is advancing and this can in any way hamper the updating of the policies.In addition to payers communicating with oncologists and provider networks, drug manufacturers can keep payers up to date on their products [7].

      Finally, there should be some mechanism for all stakeholders to interact and develop strategies, such as what is occurring in Brazil in the context of the Health Industrial Complex Executive Group and Forum (GECIS [8]). This Forum foster the appreciation and utilization of new technologies in healthcare, including the immuno-oncology area. Furthermore, the greater the number of information and dissemination of knowledge important to recognize, understand and accept the introduction of new therapies, the closer we will be of being able to convince stakeholders and then introduce immuno-oncology drugs in the roll of available treatments.

      REFERENCES

      1. Ferreira CG, et al. Increasing Access to Immuno-Oncology Therapies in Brazil. Journal of Cancer Policy. 2018;(16), June, 1-5pp.

      2. Quintiles IMS Institute. Global Oncology Trend Report a Review of 2015 and Outlook to 2020.http://www.imshealth.com/en/thought-leadership/ quintilesims-institute/reports/global-oncology-trend-report-a-review-of-2015- and-outlook-to-2020. Accessed 16 Dec 2016.

      3. Mariotto AB, et al. Projections of the cost of cancer care in the United States: 2010–2020.J Natl Cancer Inst. 2011;103(2):117–28.

      4. Institute for Clinical Immuno-Oncology (2015). Commentary From the Field: Payers as Key Players in the Access and Availability of Immuno-Oncology Therapy. Retrieved June 24, 2018, from https://accc-iclio.org

      5. Precision for Value (2017). Education, Data Are Needed on Combination Immunotherapies. Specialty Pharmacy News, Volume 14, Number 5.

      6. Institute for Clinical Immuno-Oncology (2015). Communicate Effectively with Immuno-Oncology Payers. Retrieved June 24, 2018, fromhttps://accc-iclio.org

      7. Ferreira CG et al.The Value of Biomarkers in Optimizing the Use of Immuno-oncologic Therapy. Journal of Current Drug Targets (2018). In press.

      8. Unified Health System (SUS). Executive Group of the Health Industrial Complex-GECIS. 15 April 2014. Available at: www.portaldasaude.gov.br

      e353dbe42c8654f33588d4da0b517469

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    MS03 - New Frontiers in Oligometastases (ID 782)

    • Type: Mini Symposium
    • Track: Oligometastatic NSCLC
    • Presentations: 5
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 203 BD
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      MS03.01 - The Biology of Oligometastases: What Have We learned? (Now Available) (ID 11410)

      10:30 - 10:45  |  Presenting Author(s): David Palma

      • Abstract
      • Presentation
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      Abstract not provided

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      MS03.02 - Biomarkers in Oligometastatic Patients i. Monitoring Diseases Response - Imaging vs Serum (Now Available) (ID 11411)

      10:45 - 11:00  |  Presenting Author(s): Max Diehn

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MS03.03 - Investigations into Alternative Clinical Endpoints for OM Beyond Survival (Now Available) (ID 11412)

      11:00 - 11:15  |  Presenting Author(s): Alexander Louie

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MS03.04 - Treatment of Oligoprogression: Real Progress or False Hope? (Now Available) (ID 11413)

      11:15 - 11:30  |  Presenting Author(s): Fiona McDonald

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MS03.05 - Integration of Immunotherapy in the Oligometastatic Paradigm (Now Available) (ID 11414)

      11:30 - 11:45  |  Presenting Author(s): Shankar Siva

      • Abstract
      • Presentation
      • Slides

      Abstract

      Radiotherapy is a treatment modality commonly used in efforts to manage oligometastatic disease. It is now recognised that radiotherapy does not only directly kill tumour cells, but it also changes the tumour microenvironment, enhancing tumour cell recognition by the immune system, therefore acting as an in situ vaccine. Radiotherapy increases expression of tumour-associated antigens, causes the release of cytokines, stimulates recruitment of dendritic cells and most importantly stimulates the proliferation and priming of cytotoxic CD8+ T-cells in the tumour microenvironment. This immunologic cascade specifically generates activated T-cells able to induce immunogenic cell death directed against cancer cells bearing those antigens. The cellular changes induced by radiotherapy are becoming increasingly important as it is recognised that the majority of patients do not respond to currently available therapies based on immune checkpoint inhibitors. The benefit of those agents is limited to patients who have pre-existing active immune microenvironment that can be re-activated by immunotherapeutic agents. By its ability to overcome some tumour immune escape mechanisms, radiation provides a non-pharmacological and cost-effective approach to potentially improve the systemic response to immune checkpoints inhibitors. In the context of oligometastatic disease, it is unclear what the ideal integration of immunotherapy and radiotherapy should be. Most studies are currently investigating ‘abscopal’ effects with combination radio/immunotherapy strategies in patients with widespread metastases. In the oligometastatic state, does this make sense? Given the local efficacy of radiotherapy, treatment of all macroscopic sites of disease if safe would appear to be a prudent strategy in combination with immunotherapy. Additionally, what is the optimal duration of immunotherapy in this context? What is the ideal timing of radiotherapy, and should it be given upfront or as consolidation? These are some of the issues that will be explored in this short lecture.

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    MS04 - Joint GLCC/IASLC Session: Exploring Hot Topics for Advocates (ID 783)

    • Type: Mini Symposium
    • Track: Advocacy
    • Presentations: 4
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 206 BD
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      MS04.01 - Collecting Data in the Real World - How Can Patient Groups Work with Researchers in Defining and Collecting Real-World Evidence? (Now Available) (ID 11415)

      10:30 - 10:45  |  Presenting Author(s): Taofeek Owonikoko

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MS04.02 - How Is Lung Cancer Screening Evolving to Be More Efficient and Effective? (Now Available) (ID 11416)

      10:45 - 11:00  |  Presenting Author(s): David Raymond Baldwin

      • Abstract
      • Presentation
      • Slides

      Abstract

      At the time of writing this summary, only the US and Canada had approved national screening with low radiation dose computed tomography (LDCT) and this was based primarily on the US National Lung Screening trial (NLST).[1]Since this landmark study, there has been much debate and further research work to clarify the best way to undertake a screening programme. Initially, uncertainty about the detail of an optimal programme that ensures that benefits outweigh harms in a cost-effective manner, was a reason to delay initiation of programmes in other countries.[2] However, many now believe that there is sufficient evidence to design a programme that will deliver a substantial reduction in mortality well within the commonly quoted willingness to pay thresholds in developed countries.[3]What is making policy makers cautious is the fact that the results of the only other randomised trial powered to detect a lung cancer mortality difference, the Dutch-Belgian NELSON trial, are still awaited.

      Figure 1 shows some of the factors that may be crucial in producing a favourable balance between benefits and harms and these are summarised below.

      Selecting people at high risk of lung cancer, who are more likely to benefit than those at low risk makes the intervention more cost effective. The use of multivariable risk prediction models increases the cost effectiveness over simple age and smoking criteria used in NLST. It is important that people who are at too low risk, some being the 10-15% of people who develop lung cancer but have never smoked, understand why they should not be screened. There is also an intermediate risk group where cost is the main consideration.

      Modelling has shown that annual scanning is more cost effective than biennial. However, where a previous CT is negative (no significant pulmonary nodules) the risk of cancer a year later is low, allowing a 2-year interval and cost savings. Imaging and reporting standards are well-developed.

      Indeterminate findings need to be managed according to guidelines that employ initial interval LDCT, recognising that the risk of malignancy is low, avoiding overdiagnosis, higher radiation dose imaging and false positive diagnostic tests[4, 5]. The false positive rate is 1-3% where this patient-centred definition is applied.

      Clinical work-up and treatment should also follow modern pulmonary nodule management and other clinical guidelines[4, 5]to reduce overdiagnosis and harms from biopsies and surgery by reducing intervention where the risk of malignancy is low or when cancers are indolent and unlikely to cause harm. Applying this “intelligent” approach yields a benign resection rate of around 10% and the in most recent UK pilot it was 2%. [6-8]

      Smoking cessation support should be integral as the overall quit rates are greater than in the general population and further increased by intermediate findings.

      Some issues are unresolved and could further improve cost-effectiveness. Participation in screening has been disappointing in the US and active research into ways to increase this is needed to ensure an impact at population level. The value of add-on health interventions and addressing incidental findings needs to be carefully evaluated using the same principle of benefit outweighing harm. Information to support people to make an informed decision about whether screening is right for themis an area of continuing research and relies heavily on the input of patients and the public. An undoubted challenge to implementation in some countries is the demand on human and physical resources.

      Screening for lung cancer makes logical sense and has a strong evidence base but delivering an optimum programme is dependent on attention to detail. It is important that country-specific pilot programmes now underway adhere to best practice so we see detection of early stage disease and high curative treatment rates with low rates of intervention for benign disease. This will help clinicians and opinion leaders, in partnership with advocates, to convince policy makers and governments of the need for investment.

      References

      1. National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, et al: Reduced lung-cancer mortality with low-dose computed tomographic screening.New England Journal of Medicine 2011, 365:395-409.

      2. Field JK, Aberle DR, Altorki N, Baldwin DR, et al: The International Association Study Lung Cancer (IASLC) Strategic Screening Advisory Committee (SSAC) Response to the USPSTF Recommendations.J Thorac Oncol 2014, 9:141-143.

      3. Matthijs Oudkerk AD, Rozemarijn Vliegenthart, Thomas Henzler, et al: European position statement on lung cancer screening.Lancet Oncology 2017, 18:e754–e766.

      4. Callister ME, Baldwin DR, Akram AR, et al: British Thoracic Society guidelines for the investigation and management of pulmonary nodules.Thorax 2015, 70 Suppl 2:ii1-ii54.

      5. MacMahon H, Naidich DP, Goo JM, et al: Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017.Radiology 2017,284:228-243.

      6. Field JK, Duffy SW, Baldwin DR, et al: UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening.Thorax 2016, 71:161-170.

      7. Flores R, Bauer T, Aye R, et al: Balancing curability and unnecessary surgery in the context of computed tomography screening for lung cancer.J Thorac Cardiovasc Surg 2014, 147:1619-1626.

      8. Crosbie PA, Balata H, Evison M, et al: Implementing lung cancer screening: baseline results from a community-based 'Lung Health Check' pilot in deprived areas of Manchester.Thorax 2018.doi: 10.1136/thoraxjnl-2017-211377.

      slide1.jpg

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      MS04.03 - Exploring Smoking Stigma, Negativity and Lung Cancer - What Can Be Done? (Now Available) (ID 11417)

      11:00 - 11:15  |  Presenting Author(s): Stefania Vallone

      • Abstract
      • Presentation
      • Slides

      Abstract

      Misinformation or false myths about cancer generate fear and a negative perception of a person affected by this disease. Lung cancer patients experience a higher level of cancer-related stigma than other cancer patients, because the general negative attitude about smoking, recognized as one of the main risk factors, contributes to the stigmatization of people who live with this condition. Although the relation between tobacco use and lung cancer is established, worldwide lung cancer patients are affected by a noteworthy and unjustified stigma and considered responsible of their disease in a different way from other cancer patients. For it, they are often reluctant to disclose the disease, because of fear to be discriminated, and patients' stories show that stigma could be harmful and detrimental to them and their loved ones and may cause limitations in working toward a cure. The lack of public empathy and support adds an emotional burden to an already frustrating situation that can affect quality of life and may contribute to depression, anxiety, poor self-esteem, guilt, shame, blame, negatively impacting psychological adjustments and interpersonal communication. Low public support for lung cancer is not restricted to popular perceptions and attitudes, but can also be seen in research funding. Lung cancer remains an underfunded disease and despite the higher mortality, it received less funding compared to other common cancers, such as breast cancer.

      What can be done?

      Stigma impacts all spheres of a person’s life and patients, caregivers, advocates and healthcare professionals have started years ago actively working in this area developing programs and campaigns that can help to change this situation, partly persisting because smoking is still considered more as a bad habit rather than a serious addiction. It’s important to motivate and encourage smokers to quit rather than blaming them, and even when the lung cancer has already been diagnosed, smoking cessation is important for a better quality of life. Providing smoke-free policies and tailored and effective campaigns is essential for improving the people awareness about the issue that smoking contributes to a number of diseases and cancers even if most people associate it exclusively with lung cancer. But, lung cancer is not just a smoker's disease, there are additional factors to consider and the education of patients, the general public and the health care personnel on these topics plays a valuable role. To help dispel stigma it is crucial the dissemination of correct and up-to-date information, the commitment of celebrities, patient families and friends, doctors in campaigning and advocating on their behalf, sharing the stories of lung cancer patient’s in order to increase the visibility of this disease and to generate a movement able to create a support network more sympathetic with these people, because they need and deserve care and support, not an evaluation of the possible causes of the disease. Raising the awareness is one of the main goals of any Lung Cancer Advocate worldwide and in conjunction with Lung Cancer Awareness Month, observed annually in November, many advocacy groups improve their efforts independently or in cooperation for promoting public campaigns about prevention, screening, new treatments and other issues. With the purpose of harmonizing the action, some years ago the International Association for the Study of Lung Cancer (IASLC) proposed and lead a unified effort among a consortium of non-profit lung cancer patient organizations and individuals to produce a coordinated public awareness campaign for Lung Cancer Awareness Month (LCAM) in November in order to reach the maximum amount of impact on media coverage, policy makers and public support.

      Reducing stigma is also one of pillar of the global action of GLCC (Global Lung Cancer Coalition) that in 2010, commissioned a research carried out by Ipsos MORI, which surveyed over 16,000 people in 16 countries, and found some evidence that sympathy levels were influenced by rates of smoking in each country. Between 10% and 29% of people admitted to feeling less sympathetic towards lung cancer sufferers because of its association with smoking.

      In 2017, GLCC commissioned a new multi-national study to Populus agency to undertake an online survey of adults across 25 countries for understanding attitudes towards lung cancer among the public. The results confirmed that 21% of people, out of least 1,000 adults per country still agree that they have less sympathy for people with lung cancer than other forms of cancer.

      In conclusion, in lung cancer there is a strong need to overcome many challenges to ensure that all of the patients may have the same hope and equal chances to fight against this disease. Lung cancer patients and caregivers still face a number of significant challenges and more has to be done to increase public awareness, to provide diagnostic tools and access to safe and effective treatments, to support efficient research and to combat the stigma. We’ve come a long way, and we certainly have a long way to go. We should work all together to effectively diminish the stigma that surrounds lung cancer and move forward in a positive way.

      References:

      1) Lung cancer stigma, depression, and quality of life among ever and never smokers Janine K. Cataldo, Thierry M. Jahan, and Voranan L. Pongquan

      2) Public attitudes about lung cancer: stigma, support, and predictors of support Jared Weiss,1Briana J Stephenson, Lloyd J Edwards, Maureen Rigney, and Amy Copeland

      3) Lung cancer in never smokers: clinical epidemiology and environmental risk factors Jonathan M. Samet, Erika Avila-Tang, Paolo Boffetta, Lindsay M. Hannan, Susan Olivo-Marston, Michael J. Thun and Charles M. Rudin

      4) Global Perception of Lung Cancer: An Ipsos MORI report for the Global Lung Cancer Coalition

      5) Based on WHO data (2005) on prevalence of tobacco used by country (full data and further information can be found at http://www.who.int/mediacentre/factsheets/fs297/en/index.html

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      MS04.04 - E-Cigarettes - What Do Lung Cancer Advocates Need to Know? (Now Available) (ID 11418)

      11:15 - 11:30  |  Presenting Author(s): Carolyn Dresler

      • Abstract
      • Presentation
      • Slides

      Abstract

      Since the release of the IASLC Statement on e-cigarettes in 2014(1), opinion in relation to their role has become more not less polarised. E-cigarettes are not going away as an issue and advocates should be aware of the state of knowledge generally and of reputable information to which they can refer. Lung cancer advocates and patient supporters should have enough knowledge to assist individual patients to make an informed decision, to educate if that is their role and to advocate for the best care environment for those who have lung cancer or are at elevated risk for the development of lung cancer in the future. Some scenarios are worthy of consideration.

      The smoker who needs surgical resection.

      Smoking cessation is standard-of-care before thoracic surgery. Cessation reduces respiratory and cardiac morbidity and improves wound healing. Almost all smokers in this situation quit easily. Limited studies suggest an adverse effect of e-cigarettes on wound healing that is similar to smoking. More disturbingly, a bronchoscopy study found severe bronchial inflammation(2). There is sufficient, reasonable concern about impaired healing of the bronchial stump and compromised sputum clearance to explicitly recommend against the use of e-cigarettes before surgery even if smoking cessation is achieved.

      Patients with advanced lung cancer

      Advanced lung cancer is no longer rapidly and uniformly fatal. In the previous era, before recent treatment advances, with targeted small molecules and immunotherapy, it was difficult to show a survival advantage but continued smoking was associated with impaired quality of life and longer periods in hospital stay in cancer patients. There are no similar data for the complete substitution of smoking for e-cigarettes. Cessation should still be the aim. There are also practical problems with few health-care providers permitting e-cigarette use in enclosed spaces. NRT in contrast can be used in any location.

      Current smokers involved in lung cancer screening programs or with incidental nodules

      This is unquestionably a high value group for effective smoking cessation intervention. The considerations are those for the availability and recommendation for e-cigarettes in the community generally.

      What is the benefit of e-cigarettes in promoting cessation

      In its report, NASEM concluded that there is limited evidence that e-cigarettes are effective aids to promote smoking cessation, moderate evidence from randomized controlled trials that e-cigarettes with nicotine are more effective than e-cigarettes without nicotine and that There is insufficient evidence from randomized controlled trials about the effectiveness of e-cigarettes as cessation aids compared with no treatment or FDA–approved smoking cessation treatments(3). Since that report was released, the largest RCT of e-cigarettes vs other treatment options published in NEJM found no benefit for e-cigarettes(4).

      What are the harms especially long-term when long term use is encouraged

      There are probably few harms of a short-course (6 weeks or less) of e-cigarette use but a statistically significant decline in lung function is detected at 3 months. Airway inflammation is also seen rapidly. Some Much attention has been focussed on the claim that e-cigarettes are 95% safer than smoking. This claim is supported by no evidence. It is true that tobacco smoke contains putative cancer-causing chemicals that are at low levels in e-cigarette vapour but the real situation is more complex. In the bronchoscopy study looking at airway protein levels, there was a cluster of adverse changes seen only with smoking, another seen with smoking and e-cigarette use and a third seen only with e-cigarette vapour(2). Whether these are from the base chemicals, nicotine or flavourings is uncertain. Long-term studies are few. Use of e-cigarettes for two years in a study sponsored by a tobacco-company subsidiary detected very rapid (5%/year) loss of lung function(6). There are no meaningful long-term studies for CV risk and smoking-related cancers.

      What are the wider harms in promoting smoking in youths and young adults?

      The NASEM report concludes that there is “substantial evidence that e-cigarette use increases risk of ever using combustible tobacco cigarettes among youth and young adults”. Based on a meta-analysis, after adjustment for all reasonable confounders the risk is about 3-fold. It is inevitable that promotion amongst children and young adults will occur generating concerns as now seen with the JUUL product.

      Where is the role of e-cigarettes at the present time as a smoking cessation aid?

      E-cigarettes represent an intuitive solution for some smokers and there is a wealth of non-evidence-based information accessible on the internet. It is challenging for health advocates to accede to the use of a treatment that appears to be ineffective yet having this evidence-based approach is seen by many wedded to harm reduction as negative. Subject to the regulatory environment in each country, it may be reasonable to tolerate, under supervision, e-cigarette use where an individual will only attempt smoking cessation with e-cigarette use. This should be time-limited to perhaps 6-8 weeks with cessation of e-cigarettes if smoking continues; leading to a consideration of other options. If cessation is achieved, e-cigarette use should be withdrawn. There should be no compromise on the question of concurrent smoking/e-cigarette use that offers no health benefit and is unstable with many patients reverting to smoking.

      References:

      1. Cummings KM, Dresler CM, Field JK et al. E-cigarettes and cancer patients. J Thorac Oncol. 2014; 9: 438-41

      2. Ghosh A, Coakley RC, Mascenik T et al. Chronic E-Cigarette Exposure Alters the Human Bronchial Epithelial Proteome. Am Rev Resp Crit Care Med 2018; 198: 67-76.

      3. National Academies of Sciences and Engineering and Medicine. Public health consequences of e-cigarettes. Washington. DC: The National Academies Press, 2018.

      4. Halpern SD, Harhay MO, Saulsgiver K, et al. A Pragmatic Trial of E-Cigarettes, Incentives, and Drugs for Smoking Cessation. N Engl J Med 2018; 378:2302-2310

      5. McNeill A, Brose LS, Calder R et al. Evidence review of e-cigarettes and heated tobacco products 2018. A report commissioned by Public Health England. London: Public Health England.

      6. Walele T, Bush J, Koch A et al. Evaluation of the safety profile of an electronic vapour product used for two years by smokers in a real-life setting. Regulatory Toxicology and Pharmacology 2018; 92:226–238.

      e353dbe42c8654f33588d4da0b517469

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    OA01 - Improving Outcomes in Locoregional NSCLC I (ID 892)

    • Type: Oral Abstract Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 8
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 107
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      OA01.01 - 10-Year Updated Analysis of NRG Oncology/RTOG 0214: A Phase III Comparison of PCI vs. Observation in Patients with LA-NSCLC. (Now Available) (ID 14189)

      10:30 - 10:40  |  Presenting Author(s): Alexander Sun  |  Author(s): Chen Hu, Elizabeth Gore, Stuart Wong, Gregory M.M. Videtic, Swati Dutta, Mohan Suntharalingam, Yuhchyau Chen, Laurie Gaspar, Hak Choy

      • Abstract
      • Presentation
      • Slides

      Background

      To determine if prophylactic cranial irradiation (PCI) improves survival in locally advanced non–small-cell lung cancer (LA-NSCLC), we conducted a prospective randomized phase III trial. Previously we reported that compared to observation, PCI significantly increased disease-free survival and reduced brain metastases. With extended follow-up, we sought to determine whether PCI conferred an overall survival benefit.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with stage III NSCLC without disease progression after treatment with surgery and/or radiation therapy (RT) with or without chemotherapy were eligible. Participants were stratified by stage (IIIA v IIIB), histology (nonsquamous v squamous), and therapy (surgery v none) and were randomly assigned to PCI or observation. PCI was delivered to 30 Gy in 15 fractions. The primary end point of the study was overall survival (OS). Secondary end points were disease-free survival (DFS), neurocognitive function (NCF), and quality of life. Kaplan-Meier and log-rank analyses were used for OS and DFS. The incidence of brain metastasis (BM) was evaluated with the logistic regression model.

      4c3880bb027f159e801041b1021e88e8 Result

      Among 356 patients entered to this study, 340 are eligible for analysis. The median follow-up time was 2.1 years for all patients, and 9.2 years for living patients. The survival estimates and hazard ratio indicate that there appears to be no improvement in survival with the use of PCI (p=0.12, HR=1.23, 95% CI: 0.95-1.59). Of note, with the current data there is only 45% power to detect the hypothesized difference HR=1.25 at 1-sided significance level of 0.025. The DFS estimates are better in the PCI arm (p=0.03, HR=1.32, 95% CI: 1.03-1.69). Patients in the observation arm were 2.33 times more likely to develop BM than those in the PCI arm (p= 0.004). On multivariate analysis PCI was significantly associated with decreased BM and improved DFS, but not OS. However, among the 225 non-surgical patients, use of PCI was associated with higher OS (p=0.026, HR=1.42, 95% CI: 1.04-1.94) and DFS (p=0.014), and lower BM (p=0.003). NCF was previously published (Sun, JCO 2011 and Gondi, IJROBP 2013), however, with longer follow-up, there is insufficient data for further analysis.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this 10-year updated analysis, use of PCI continued to significantly improve DFS and reduce brain metastases. However, the early accrual closure failed to provide adequate power to detect the hypothesized difference in OS and the survival rates were not significantly different between PCI and observation. Subgroup analyses based on stratification factors suggest that PCI may improve survival among non-surgical patients.

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      OA01.02 - The Estimate of Shrinking Field and SIB Radiotherapy Guided by 18F-FDG PET/CT in Locally Advanced NSCLC Patients: A Phase 2 Randomized Clinical (Now Available) (ID 14474)

      10:40 - 10:50  |  Presenting Author(s): Yaping Xu  |  Author(s): Yaoyao Zhu, Chenxue Jiang, Feiying Gu, Qingren Lin, Xiaojiang Sun

      • Abstract
      • Presentation
      • Slides

      Background

      Tumor control remains suboptimal in locally advanced lung cancer. Radiation dose acceleration has a positive effect to local tumor control, but is limited by radiation-induced lung injury (RILI). The aim of this study was to evaluate the safety and efficacy of adaptive radiation therapy guided by functional imaging 18F-FDG PET/CT in patients with locally advanced non-small lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A total number of 72 patients with locally advanced NSCLC were enrolled between November 2012 and June 2017. After signing the inform consent form, 36 patients were randomized into the shrinking field and simultaneous integrated boost radiotherapy group, others were in the conventional radiotherapy group. The Objective Response rate (ORR), progression-free survival (PFS) and overall survival (OS) were compared, as well as the safety of shrinking field and simultaneous integrated boost radiotherapy (radiological dosimetry parameters and the incidence of grade 2 or higher radiotherapy-related toxicity). T-test was utilized to compare the differences between the quantitative data of two groups, while chi-square test or Fisher exact test were utilized to compare the differences between the count data of two groups. Kaplan-Meier curve was utilized to show PFS and OS, and the log-rank test analysis was utilized to compare the survival difference between two groups. P value less than 0.05 was considered statistical difference.

      4c3880bb027f159e801041b1021e88e8 Result

      All the patients in both two groups had completed their treatment according to the study protocol. The shrinking field and simultaneous integrated boost radiotherapy group was significantly greater than the conventional radiotherapy group in ORR (77.8% vs. 52.8%, P=0.026). The median OS and PFS in shrinking field and simultaneous integrated boost radiotherapy group was 22.0 months (95%CI:18.1~25.9) and 12.4 months (95%CI:10.4~14.3), which is significantly longer than 18.1 months (95%CI:12.4~23.8) and 8.2 months (95%CI:5.2~11.2) in the conventional radiotherapy group (P=0.045 and P=0.013). There was no significant difference between the two groups in radiological metrological parameters and organ at risk (OAR). The incidence of grade 2 or higher RILI, radiation-induced esophagitis, radiation-related myocardial damage and myelosuppression between two groups has no statistically significant difference.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Shrinking field and simultaneous integrated boost radiotherapy guided by function imaging 18F-FDG PET/CT is a safe and operable technique in practice. It can improve ORR, OS and PFS without increasing the risk of radiotherapy-related toxicity in patients with locally advanced NSCLC.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      OA01.03 - Interaction Between Dose and Calcifications Is a Predictor for Overall Survival in Lung Cancer Patients Receiving Radiotherapy (Now Available) (ID 13920)

      10:50 - 11:00  |  Presenting Author(s): Alan McWilliam  |  Author(s): Eliana Vasquez Osorio, Frank Brewster, David Catharina Petrus Cobben, Corinne Faivre-Finn, Anna Scaife, Marcel Van Herk

      • Abstract
      • Presentation
      • Slides

      Background

      Recently, incidental dose to the heart was found to be predictive for overall survival in lung cancer patients receiving radiotherapy [McWilliam et al EJC 2017, Johnson et al Radiother Oncol 2018]. These patients often present with multiple comorbidities that should be incorporated in survival analysis. However, such data is often missing. We investigated whether calcifications, identified on the radiotherapy planning CT, can be used as a surrogate for cardiac health. In particular, we investigated the interaction between calcifications, dose and survival.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Data from 814 unselected non-small cell lung cancer patients was used, all treated with 55Gy in 20 fractions. Methodology was developed to automatically segment calcifications within the heart, the aortic arch and their surroundings. The 3D planning CT scans, and the associated lung and spinal cord delineations were processed using well-established image processing algorithms, e.g., convex hull, thresholding, morphological operations, connected pixel analysis and flood filling to detect calcifications. Moreover, shape analysis was included to enhance regions that presented tubular or plate-like appearance. The detection algorithm was validated in a small subset of 10 patients, and this group was used to determine the success and error rate of the automatic segmentation. Finally, a Cox-proportional hazards multivariate analysis was performed for overall survival of all patients accounting for tumour size, total calcification volume, mean dose across all identified calcifications, and interaction between calcification volume and dose.

      4c3880bb027f159e801041b1021e88e8 Result

      The success rate of the algorithm for identifying calcifications was 81.8%, its error rate was 8.8%. The multivariate survival analysis identified tumour size (continuous, p<<0.0001) and the interaction of calcification volume and their mean dose (continuous, p=0.029) as significant. Calcification volume (p=0.57) or mean calcification radiation dose alone (p=0.269) were not found to be significant.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Multivariate analysis shows a significant interaction between volume of the identified calcifications and their mean radiotherapy dose predicting survival. Further improvements to identify calcifications in the descending thoracic aorta and validation of our methodology are required. Further work linking our results with the established Agatston or Coronary Artery Calcium score is in progress.

      * EVO-FB share first authorship

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      OA01.04 - Discussant - OA 01.01, OA 01.02, OA 01.03 (Now Available) (ID 14546)

      11:00 - 11:15  |  Presenting Author(s): John Armstrong

      • Abstract
      • Presentation
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      Abstract not provided

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      OA01.05 - Phase II Study of Neo-Adjuvant Chemo/Immunotherapy for Resectable Stages IIIA Non-Small Cell Lung Cancer- Nadim Study-SLCG (Now Available) (ID 12907)

      11:15 - 11:25  |  Presenting Author(s): Mariano Provencio  |  Author(s): Ernest Nadal, Amelia Insa, Rosario García Campelo, Gerardo Huidobro, Manuel Domine, Margarita Majem, Delvys Rodríguez-Abreu, Virginia Calvo, Alex Martinez-Marti, Javier De Castro, Manuel Cobo Dols, Guillermo Lopez-Vivanco, Elvira Del Barco, Reyes Bernabé, Nuria Vinolas, Isidoro Barneto, Bartomeu Massuti

      • Abstract
      • Presentation
      • Slides

      Background

      The combination of chemotherapy and immunotherapy (CT-IO) has a high response rate and longer survival in unselected patients (pts) with metastatic non-small cell lung cancer (NSCLC). There are no data about this combination in the neoadjuvant setting.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A Phase II, single-arm, open-label multicenter study of local-advanced resectable stage IIIA N2-NSCLC adult patients with CT plus IO (nivolumab (NV)) followed by adjuvant treatment for 1 year. Neoadjuvant treatment: Three cycles of NV 360mg IV Q3W + paclitaxel 200mg/m2 + carboplatin AUC 6 IV Q3W. After completing neoadjuvant therapy, tumor assessment is performed in patients prior to surgery. Surgery is performed in the 3rd or 4th week after day 21 of the third cycle of neoadjuvant treatment. Adjuvant treatment: NV 240mg IV Q2W for 4 months and NV 480mg IV Q4W for 8 months (total one year) after surgical resection. The study aims to recruit 46 pts. The primary endpoint is Progression-Free Survival (PFS) at 24 months. Efficacy is explored using objective pathologic response criteria. We present preliminary data on patients that completed 3 cycles and underwent surgical resection.

      4c3880bb027f159e801041b1021e88e8 Result

      At the time of submission, 46 pts had been included and 20 underwent surgery. CT-IO was well-tolerated and surgery was not delayed in any patient. None of the pts was withdrawn from the study preoperatively due to progression or toxicity.

      Twenty surgeries had been performed and all tumors were deemed resectable. The overall clinical response rate was 5% complete (CR) and 65% PR. The pathological response evaluated after surgery: 13 cases (65.0%) achieved CR (CPR) (95% CI 40.8-84.6%), and 3 (15.0%) had a major pathologic response (MPR), defined as <10% viable tumor cells in the resection specimen. Considering both CPR and MPR, the overall response rate was 80.0% (95% CI 56.3-94.3%) and 60% of complete responses were unsuspected

      8eea62084ca7e541d918e823422bd82e Conclusion

      This is the first multicentric study testing CT-IO in the neoadjuvant setting with promising antitumor activity in locally advanced, potentially resectable NSCLC yields an unprecedented complete pathologic response rate. The data will be updated at the time of the congress. EudraCT Number: 2016-003732-20

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      OA01.06 - DETERRED:  Phase II Trial Combining Atezolizumab Concurrently with Chemoradiation Therapy in Locally Advanced Non-Small Cell Lung Cancer (Now Available) (ID 12842)

      11:25 - 11:35  |  Presenting Author(s): Steven H Lin  |  Author(s): Xiuyan Lin, Debora Clay, Luyang Yao, Isabel Mok, Daniel Gomez, Jonathan M Kurie, George R. Simon, George R Blumenschein, Jenean Young, See Phan, Alan Sandler, Vassiliki A Papadimitrakopoulou, John V Heymach, Anne S. Tsao

      • Abstract
      • Presentation
      • Slides

      Background

      While consolidation immunotherapy after chemoradiation (CRT) is the current standard of care for locally advanced NSCLC (LA-NSCLC), the effectiveness of immunotherapies may be enhanced when combined concurrently with CRT. We report on the safety and preliminary efficacy of combining PD-L1 blockade using atezolizumab (atezo) and concurrent CRT followed by consolidation full dose carboplatin/paclitaxel (CP) with atezo and maintenance atezo up to 1 year for LA-NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a single institution phase II study in LA-NSCLC assessing the safety and feasibility of adding atezo to CRT in two parts: I) sequentially (N=10) with CP after completing CRT, or II) concurrently (N=30) with CRT followed by consolidation atezo with CP. Atezo was given at 1200 mg IV Q3 weeks for up to one year from the first dose. Radiation dose at 60-66 Gy in 30-33 fractions was combined with weekly low dose CP, followed by 2 cycles of full dose CP. Severe adverse events (AEs) ≥ grade 3 are defined within 15 weeks of start of therapy or any immune-related AEs during atezo treatment. Evaluable patients (pts) have received at least one dose of atezo.

      4c3880bb027f159e801041b1021e88e8 Result

      From February 2016 to April 2018, we accrued 40 evaluable pts. For part 1, any grade 3+ AEs was seen in 6 pts (60%), with most common being pneumonia (2 of 10, 20%). Three grade 3+ AEs (30%) were attributed to atezo, including dyspnea, arthralgia and a grade 5 TE fistula. Grade 2 radiation pneumonitis (RP) was seen in 3 pts. Four progressed with disease during atezo maintenance and have died, ranging from 0.93 to 1.86 years. Four pts completed atezo and are in follow up without recurrence. For part 2, 17 of 30 pts had any grade 3+ AEs (57%), with pneumonia being the most common (6 of 30, 20%). Three (10%) were attributed to atezo (dyspnea, fatigue and heart failure). RP was seen in 3 pts, with 2 grade 2 and 1 grade 3, which led to atezo discontinuation. So far, 4 pts have progressed and 4 have died, 2 due to disease and 2 due to treatment (neutropenic sepsis and gastric hemorrhage). All others have completed CRT and are on maintenance atezo, ranging from 5 to 19 doses. Updated efficacy results will be presented.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Concurrent atezo with CRT followed by consolidation and maintenance atezo appears safe without increased toxicities compared to CRT alone followed by consolidation and maintenance atezo.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      OA01.07 - Updated Results of a Phase II Trial of Concurrent Chemoradiation with Consolidation Pembrolizumab in Patients with Unresectable Stage III NSCLC (Now Available) (ID 13961)

      11:35 - 11:45  |  Presenting Author(s): Greg Durm  |  Author(s): Sandra Althouse, Ahad Sadiq, Shadia Jalal, Salma Jabbour, Robin Zon, Goetz H Kloecker, William Fisher, Karen L. Reckamp, Ebenezer Kio, Robert Langdon, Bamidele Adesunloye, Ryan Gentzler, Nasser Hanna

      • Abstract
      • Presentation
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      Background

      Concurrent chemoradiation (CRT) has been the standard Rx for pts with unresectable stage III NSCLC. A recent phase III trial (PACIFIC) of consolidation durvalumab [PDL-1 inhibitor] demonstrated improved median PFS vs. placebo (16.8 vs. 5.6 mo, HR 0.52, p<0.001). 12-mo (55.9% vs. 35.3%) and 18-mo (44.2% vs. 27%) PFS were also improved. Toxicity was manageable with a grade 3-4 pneumonitis rate of 3.4%, and 4 patients experienced grade 5 pneumonitis. We report updated results of a phase 2 trial of consolidation pembrolizumab [PD-1 inhibitor] following concurrent CRT in patients with unresectable stage III NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      After completion of CRT with carboplatin/paclitaxel, cisplatin/etoposide, or cisplatin/pemetrexed + 59-66.6 Gy XRT, those pts w/o PD after 4-8 weeks off CRT received pembro 200 mg IV q3wk for up to 1 yr. The primary endpoint was time to metastatic disease or death [TMDD]. Key secondary endpoints included PFS, OS, and toxicity.

      4c3880bb027f159e801041b1021e88e8 Result

      93 pts enrolled [92 eligible for efficacy analysis]. Median f/u was 18.6 mo and median age 66 (45-84). 64.1% male and 35.9% female. Stages were 59.8% IIIA and 40.2% IIIB. 55.4% non-SqCC and 43.5% SqCC with 1 mixed histology. 94.6% were current/former smokers. Chemo regimens included carbo/pac (71.7%), cis/etop (26.1%), cis/pemetrexed (2.2%). Median number of cycles of pembro was 13.5 [1-19]. 16% received < 4 cycles; 84% received > 4 cycles; 37% completed 1 yr pembro. Median TMDD was 22.4 months (95% CI 17.9-NR). Median OS was NR (95% CI 22.4-NR), and the estimates of 1-yr and 2-yr OS were 81% and 61.9% respectively. Median PFS was 17 months (95% CI 11.9-NR). 12, 18, and 24-month PFS were 60.2%, 49.9%, and 44.6% respectively. 16 (17.2%) pts developed G2 pneumonitis, 5 (5.4%) had G3-4 pneumonitis. There was 1 pneumonitis-related death. In those developing G2 pneumonitis, the median time was 8.4 wks [1.1-48.3]. No other G 3/4 toxicities exceeded 5% except dyspnea (5.4%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Consolidation pembrolizumab following CRT substantially improves TMDD and PFS compared with historical controls. Prelim OS data is promising and suggests a substantial gain in outcomes of patients with stage III NSCLC is possible with consolidation pembrolizumab. These data will be updated further prior to the World Conference on Lung Cancer Meeting.

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      OA01.08 - Discussant - OA 01.05, OA 01.06, OA 01.07 (Now Available) (ID 14547)

      11:45 - 12:00  |  Presenting Author(s): Corey J Langer

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      Abstract not provided

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