Scientific Program

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Show Only CME Accredited Sessions

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    MTE07 - Management of Pleural Recurrence (Ticketed Session)

    • Type: Meet the Expert Session
    • Track: Thymoma/Other Thoracic Malignancies
    • Moderators:
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      MTE07.02 - From Surgical Perspective

      07:00 - 07:30  |  Presenting Author(s): Robert J Korst

      • Abstract

      Abstract not provided

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      MTE07.01 - From Radiation Oncology Perspective

      07:30 - 08:00  |  Presenting Author(s): Andreas Rimner

      • Abstract

      Abstract not provided

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    MTE08 - Enhancing the Nurse's Role in Tobacco Prevention and Cessation: New Challenges (Ticketed Session)

    • Type: Meet the Expert Session
    • Track: Nursing and Allied Professionals
    • Moderators:
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      MTE08.01 - Enhancing the Nurse's Role in Tobacco Prevention and Cessation: New Challenges

      07:00 - 08:00  |  Presenting Author(s): Linda Sarna

      • Abstract

      Abstract not provided

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    MTE09 - Management of Advanced Wild-Type Lung Cancer in Special Situations (Ticketed Session)

    • Type: Meet the Expert Session
    • Track: Advanced NSCLC
    • Moderators:
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      MTE09.01 - Evidence Based Management of the Patient over 80

      07:00 - 07:30  |  Presenting Author(s): Elisabeth Quoix

      • Abstract

      Abstract not provided

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      MTE09.02 - Management of the PS 2 Patient

      07:30 - 08:00  |  Presenting Author(s): Joan Schiller

      • Abstract

      Abstract not provided

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

    • Type: Meet the Expert Session
    • Track: Interventional Diagnostics/Pulmonology
    • Moderators:
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      MTE10.01 - Emerging Technologies for Small and Smaller Lesions - Update on Ablation via Endoscopy vs Percutaneous

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

      • Abstract

      Abstract not provided

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    PL01 - Patients First

    • Type: Plenary Session
    • Track:
    • Moderators:
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      PL01.01 - When Breath Becomes Air

      08:15 - 08:25  |  Presenting Author(s): Lucy Kalanithi

      • Abstract

      Abstract not provided

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      PL01.02 - Science that Matters

      08:25 - 08:40  |  Presenting Author(s): David P Carbone

      • Abstract

      Abstract not provided

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      PL01.03 - Trials that Matter!

      08:40 - 08:55  |  Presenting Author(s): Tony S. Mok

      • Abstract

      Abstract not provided

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      PL01.04 - Getting Drugs to Patients Faster: A Global View

      08:55 - 09:10  |  Presenting Author(s): Solange Peters

      • Abstract

      Abstract not provided

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      PL01.05 - Conquering Lung Cancer - The IASLC Vision

      09:10 - 09:25  |  Presenting Author(s): Giorgio Vittorio Scagliotti

      • Abstract

      Abstract not provided

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      PL01.06 - Patients First

      09:25 - 09:40  |  Presenting Author(s): Tish Vigna

      • Abstract

      Abstract not provided

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    Media Availability

    • Type: Press Conference
    • Track:
    • Moderators:
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      Summarize Plenary Themes/Key Results/News

      09:45 - 09:50  |  Presenting Author(s): Andrea Bezjak

      • Abstract

      Abstract not provided

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      IMpower132: PFS and Safety Results with 1L Atezolizumab + Carboplatin/Cisplatin + Pemetrexed in Stage IV Non-Squamous NSCLC

      09:50 - 09:55  |  Presenting Author(s): Vassiliki A Papadimitrakopoulou

      • Abstract

      Abstract not provided

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      Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small Cell Lung Cancer (NSCLC)

      09:55 - 10:00  |  Presenting Author(s): Robert C. Doebele

      • Abstract

      Abstract not provided

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      When Breath Becomes Air

      10:00 - 10:05  |  Presenting Author(s): Lucy Kalanithi

      • Abstract

      Abstract not provided

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      Association Between Outdoor Air Pollution And Lung Cancer in Female Never Smokers

      10:05 - 10:10  |  Presenting Author(s): Renelle L Myers

      • Abstract

      Abstract not provided

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      Case-Series Study in Ever- and Never-Smoking Females and Males with NSCLC: Exposures, Tumor Factors, Biology and Survival (SWOG S0424)

      10:10 - 10:15  |  Presenting Author(s): Kathy S. Albain

      • Abstract

      Abstract not provided

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      Acceptance of Smoking Cessation Services in Cancer Care Ontario’s Lung Cancer Screening Pilot for People at High Risk

      10:15 - 10:20  |  Presenting Author(s): William Kenneth Evans

      • Abstract

      Abstract not provided

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      Q&A

      10:20 - 10:30

      • Abstract

      Abstract not provided

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    MA01 - Early Stage Lung Cancer: Questions and Controversies

    • Type: Mini Oral Abstract Session
    • Track: Treatment of Early Stage/Localized Disease
    • Moderators:
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      MA01.01 - Proposal on Incorporating Lymphovascular Invasion as a T-Descriptor for Stage I Non-Small Cell Lung Cancer

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

      • Abstract

      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

      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

      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

      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

      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.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA01.04 - Discussant - MA01.01, MA01.02, MA01.03

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

      • Abstract

      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

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

      • Abstract

      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

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

      • Abstract

      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

      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

      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.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA01.08 - Discussant - MA01.05, MA01.06, MA01.07

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

      • Abstract

      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

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

      • Abstract

      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

      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

      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

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

      • Abstract

      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

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

      • Abstract

      Abstract not provided

  • +

    MA02 - Improving Outcomes for Patients with Lung Cancer

    • Type: Mini Oral Abstract Session
    • Track: Advanced NSCLC
    • Moderators:
    • +

      MA02.01 - ROS1 Gene Rearrangements Are Associated with an Exaggerated Risk of Peri-Diagnosis Thromboembolic Events

      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

      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

      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

      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.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA02.03 - ASTRIS: A Real World Treatment Study of Osimertinib in Patients with EGFR T790M-Positive NSCLC

      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

      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.

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      MA02.04 - Discussant - MA 02.01, MA 02.02, MA 02.03

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

      • Abstract

      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

      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

      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

      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

      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.

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      MA02.07 - Aprepitant for Cough Suppression in Advanced Lung Cancer: A Randomized Trial

      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

      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

      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

      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

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

      • Abstract

      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

      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

      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)

      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

      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

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

      • Abstract

      Abstract not provided

  • +

    MA03 - Lung Cancer Screening - Next Step

    • Type: Mini Oral Abstract Session
    • Track: Screening and Early Detection
    • Moderators:
    • +

      MA03.01 - Manchester Lung Cancer Screening: Results of the First Incidence Screening Round

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

      • Abstract

      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.

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      MA03.02 - Prospective Evaluation of the Clinical Utility of the International Lung Screen Trial Lung Nodule Management Protocol

      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

      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

      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

      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

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

      • Abstract

      Abstract not provided

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      MA03.05 - New Subsolid Pulmonary Nodules in Lung Cancer Screening: The NELSON Trial

      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

      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

      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

      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.

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      MA03.07 - Development and Validation of Deep Learning Model for Recognition of Histologic Subtype of Lung Adenocarcinoma from CT Images

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

      • Abstract

      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.

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      MA03.08 - Discussant - MA 03.05, MA 03.06, MA 03.07

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

      • Abstract

      Abstract not provided

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      MA03.10 - Population-Based Relative Risks for Lung Cancer Based on Complete Family History of Lung Cancer 

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

      • Abstract

      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.

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      MA03.11 - Trained Dogs Can Identify Malignant Pulmonary Nodules in Exhaled Gas

      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

      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.

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      MA03.12 - Discussant - MA 03.10, MA 03.11

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

      • Abstract

      Abstract not provided

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      MA03.12a - Q&A

      11:55 - 12:00

      • Abstract

      Abstract not provided

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    MS01 - Cancer Pathways, Targeted Therapy and Resistance

    • Type: Mini Symposium
    • Track: Biology
    • Moderators:
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      MS01.01 - Defects of the SWI/SNF OR MYC/MAX Pathways: Effects in Cell Differentiation and Therapeutic Opportunities

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

      • Abstract

      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

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

      • Abstract

      Abstract not provided

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      MS01.03 - Stimulating Anti-Tumor Immunity Through Enhancing T-Cell Activation

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

      • Abstract

      Abstract not provided

    • +

      MS01.04 - Addressing Drug Resistance Beyond Kinase Domain Mutations

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

      • Abstract

      Abstract not provided

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      MS01.05 - Q&A

      11:50 - 12:00

      • Abstract

      Abstract not provided