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Alexander Sun



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    IBS13 - How to Identify and Manage Toxicity in Stage III (Ticketed Session) (ID 44)

    • Event: WCLC 2019
    • Type: Interactive Breakfast Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
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      IBS13.01 - Radiation Related Toxicities in Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC) (Now Available) (ID 3354)

      07:00 - 08:00  |  Presenting Author(s): Alexander Sun

      • Abstract
      • Presentation
      • Slides

      Abstract

      Dr. Alexander Sun, MD, FRCPC

      Addie MacNaughton Chair in Thoracic Radiation Oncology

      Princess Margaret Cancer Centre/University of Toronto

      Lung Cancer Site Group Leader, Radiation Medicine Program

      Associate Professor, University of Toronto

      Principal Investigator for PMH – RTOG/NRG Oncology

      Co-Chair, Lung Disease Site Committee, Canadian Cancer Trials Group (CCTG)

      Radical radiotherapy is uesd as definitive therapy in locally advanced non-small cell lung cancer (LA-NSCLC), either alone or in combination with chemotherapy and/or surgery. However, definitive doses of radiotherapy are associated with potential toxicity related to the organs at risk (OAR). The major OAR’s related to radical radiotherapy for LA-NSCLC include the lung and esophagus. Therefore, we need to be able to identify and manage radiation pneumonitis and esophagitis during and after a course of definitive radiotherapy.

      For good performance status, unresectable stage III NSCLC, radical radiotherapy is delivered either concurrently or sequentially with chemotherapy to total doses of 60Gy or higher. Although the best outcomes have been obtained with concurrent chemoradiotherapy, higher rates of toxicity have also been observed. With the advent of the establishment of adjuvant durvalumab after definitive concurrent chemoradiotherapy, the management of pneumonitis in particular has become even more of a challenge given the potential overlapping toxicities. For poorer performance status patients, radical radiotherapy may be used alone.

      For resectable patients with LA-NSCLC, radical radiotherapy can be given concurrently with chemotherapy prior to surgical resection as part of trimodality therapy. In other instances, radical radiotherapy can be given adjuvantly post-operatively for positive margins and can be considered in pathological N2 disease.

      Prophylactic Cranial Irradiation (PCI) has also been delivered in LA-NSCLC, although mostly in clinical trials as PCI has not been established as part of routine standard of care in stage III NSCLC.

      In this session, a discussion as well as case presentations will be used to illustrate how to identify and manage the above toxicities in stage III NSCLC.

      References (max 10)

      Baker S, Fairchild A. Radiation-induced esophagitis in lung cancer. Lung Cancer: Targets and Therapy 2016:7 119–127. (Review Article).

      Mehmood Q, Sun A, Becker N, et al. Predicting Radiation Esophagitis Using 18F-FDG PET During Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer. J Thorac Oncol. 2016: 1;11(2):213-21.

      Verma V, Simone CB, Werner-Wasik M. Acute and Late Toxicities of Concurrent Chemoradiotherapy for Locally-Advanced Non-Small Cell Lung Cancer. Cancers. 2017; 9:120. (Review Article).

      Jain V and Berman AT. Radiation Pneumonitis: Old Problem, New Tricks. Cancers (Basel). 2018 Jul 3; 10(7). (Review Article).

      Antonia SJ, Villegas A, Daniel D, et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med 2018; 2018 Sep 25.

      Shaverdian, N, Lisberg AE, Bornazyan, K et al. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: A secondary analysis of the KEYNOTE-001 phase I trial. Lancet Oncol. 2017, 18(7), 895–903.

      Chuzi S, Tavora F, Cruz M, et al. Clinical features, diagnostic challenges, and management strategies in checkpoint inhibitor related pneumonitis. Cancer Manag Res. 2017;9:207-213. (Review Article).

      Sun A, Bae K, Gore EM, et al. Phase III trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung cancer: neurocognitive and quality-of-life analysis. J Clin Oncol 2011; 29: 279–86.

      Le Pechoux C, Sun A, Slotman BJ, et al. Prophylactic cranial irradiation for patients with lung cancer. Lancet Oncol 2016; 17(7): e277–293. (Review Article).

      Sun A, Hu C, Wong SJ, et al. Prophylactic Cranial Irradiation vs Observation in Patients With Locally Advanced Non-Small Cell Lung Cancer: A Long-term Update of the NRG Oncology/RTOG 0214 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2019 Mar 14.

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    OA12 - Profiling the Multidisciplinary Management of Stage III NSCLC (ID 144)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
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      OA12.01 - PCI for Radically Treated Non-Small Cell Lung Cancer: A Meta-Analysis Using Updated Individual Patient Data of Randomized Trials (Now Available) (ID 2624)

      15:45 - 17:15  |  Author(s): Alexander Sun

      • Abstract
      • Presentation
      • Slides

      Background

      In localized non-small cell lung cancer (NSCLC), prophylactic cranial irradiation (PCI) reduced the incidence of brain metastases (BM) (relative risk 0.35), but without a demonstrated effect on overall survival (OS). This may be due to the small sample size in these individual randomized clinical trials (RCTs).

      Therefore, we aimed to assess the impact of PCI on long term OS for radically treated stage III NSCLC patients compared to observation using updated individual patient data (IPD) from RCTs.

      Method

      The main endpoint was OS and secondary endpoints were progression-free survival (PFS), BM-free survival (BMFS) and toxicity. All analyses were performed based on the intention-to-treat principle. The median follow-up was estimated using the inverse Kaplan-Meier method. The log-rank observed minus expected number of events and its variance were used to calculate individual and overall pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) with a fixed effects model. Heterogeneity was studied using the Cochrane test and I2. Survival curves and 5-year difference between arms were estimated using the Peto method. Interaction between prognostic factors (age, performance status, and histology) and treatment allocation were assessed using Cox proportional hazards models. Toxicities grade ≥ 3 were reported descriptively.

      Result

      Data on four of the seven eligible trials (SWOG 8300, RTOG 0214, Guangzhou 2005 and NVALT-11) were available for this IPD meta-analysis. In total, 924 patients were analyzed of which 68% was male, median age was 61 years, 94% of the patients had a performance status ≤ 1 and 37% had squamous histology. The median follow-up was 8.1 years. All trials provided sufficient IPD for the three endpoints, except for the SWOG 8300 trial (OS only). This trial explained inter-trial heterogeneity. Because of the qualitative interaction with the other trials (p=0.0062) it was separately analyzed (N=254). Compared to observation, OS was significantly lower for PCI in the SWOG 8300 trial (HR 1.38, 95% CI [1.07 to 1.79] p=0.013, 5-year absolute difference -0.9%, 95% CI [-5.9 to 4.1]). However, for the other trials (N=670) no significant OS difference was observed (HR 0.90, 95% CI [0.76 to 1.07] p=0.228, 5-year absolute difference 1.8%, 95% CI [-5.2 to 8.8]). PFS (HR 0.78, 95% CI [0.65 to 0.92] p=0.004, 5-year absolute difference 4.8%, 95% CI [-1.2 to 10.8]) and BMFS (0.38, 95% CI [0.27 to 0.53] p<0.001, 5-year absolute difference 20.7%, 95% CI [12.2 to 29.2]) were significantly higher in the PCI arm. There was no interaction between prognostic factors and treatment allocation for OS. Toxicity data for the PCI arm was available in all trials except the SWOG 8300 trial. The total number of patients with at least one grade ≥3 toxicity (for the adverse events pre-specified in the protocol) in the PCI arm was 19/456, including 11/86 in the NVALT-11 trial. Toxicity for the observation arm was only available in the NVALT-11 trial, including 4/88 patients with at least one grade ≥3 toxicity.

      Conclusion

      Although PFS and BM-free survival were improved for patients who received PCI, no significant PCI benefit for OS was observed.

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