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  P3.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session) (ID 983)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 2
  • Moderators:
  • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall

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    P3.17-12 - Phase II Trial of Atezolizumab Before and After Chemoradiation for Unresectable Stage III NSCLC (AFT-16): Trial in Progress (ID 13929)

    12:00 - 13:30  |  Author(s): Terence Williams
    • Abstract
    • Slides

    Background
    

    Cure is possible for a substantial minority of stage III NSCLC patients, but most will relapse after conventional chemoradiation (CRT). Combining checkpoint inhibition through PD-L1 blockade with CRT may attenuate tumor related immunosuppression via depletion of Tregs and clonal expansion of effector T-cells, thereby improving tumor immunogenicity. Further, CRT may reveal hidden antigens that can present additional targets to the reconstituting immune system. Whether anti-PD-L1 therapy before CRT will improve outcomes in this setting is the subject of this trial.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    This phase II single arm Alliance Foundation Trials study (AFT-16, NCT03102242) explores safety and efficacy of atezolizumab before and after definitive CRT. 63 patients with stage III NSCLC, PS 0-1, no active autoimmune disease and no significant organ dysfunction will enroll at 15 Alliance sites. Participants receive 4 cycles of neoadjuvant atezolizumab 1200 mg IV q 21 days with restaging after cycles 2 and 4. Non-progressing patients undergo carboplatin and paclitaxel (C/P) weekly with 60 Gy RT followed by 2 cycles of C/P consolidation and adjuvant atezolizumab to complete one year of therapy. The primary endpoint is disease control rate (CR+PR+SD) after neoadjuvant atezolizumab. Secondary endpoints include ORR, PFS, OS, safety and QoL by the EORTC QLQ-30.

    Correlatives include the role of PD-L1 and tumor mutation burden as predictive biomarkers. Tumor tissue is obtained at study entry, and plasma and immune cells are isolated at study entry, post neoadjuvant atezolizumab, post CRT, during adjuvant atezolizumab and at study end. Explorative endpoints include potential predictive biomarkers development that may define how atezolizumab affects the proportions of immunologic subtypes and immune activation using flow cytometry and T cell receptor immunophenotyping, multiplex immunohistochemistry and cytokine analysis.

    The trial was activated on 11/1/17. As of 5/4/18, the trial is open at 8 centers with 14 patients enrolled.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Section not applicable

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Section not applicable

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    P3.17-20 - Impact of Significant Primary Tumor Size Reduction on Radiation Dose to Normal Structures in Patients Receiving Definitive Chemoradiotherapy (ID 14327)

    12:00 - 13:30  |  Author(s): Terence Williams
    • Abstract

    Background
    

    Kilo-voltage cone beam computed tomography (kV-CBCT) allows for tumor localization and response assessment during definitive chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC). Previously we have analyzed patients with LA-NSCLC treated with definitive CRT accompanied with daily CBCT in our department and found that significant primary tumor volume loss occurs relatively early during treatment; and that greater tumor volume loss during treatment correlates with improved disease control and overall survival. It is not a standard practice to re-simulate patients for smaller target volume; but decreased tumor volume and consequent increase in air density could lead to increased radiation dose to the surrounding normal tissue such as the spinal cord. We hypothesize that increased air density secondary to tumor size reduction leads to increased dose to normal tissue including spinal cord, heart, esophagus and normal lung.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    kV-CBCT images were imported to Eclipse treatment planning system. Primary tumors were re-contoured, and all normal tissue structures were readjusted based on the new images. Doses to the spinal cord, esophagus, normal lung, original planning target volume (PTV) as well as the new, smaller, PTV were re-calculated based on the original prescription dose and compared with the original plan by paired student t-test. The Acuros XB advanced dose calculation algorithm was used for all patients.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Nine patients with greater than 40% target volume reduction after 4 weeks of CRT were analyzed. There is a mean size reduction of 425.1 cc (55.6%) in PTV (p=0.002). Mean dose to the new PTV is 50 cGy (0.8%) less than the prescription dose (average 6088 cGy) (p=0.07). 0.03 cc of PTV receiving the highest dose is 110 cGy (1.8%) less than originally planned. There is no significant dose difference to the normal tissue, including esophagus (D0.03cc, DMean, V105%, V50 Gy and V60 Gy), heart (D0.03cc, DMean, V30Gy and V45Gy), ipsilateral lung (DMean, V5Gy, V10 Gy, V20 Gy, V30 Gy) and total lung (DMean, V5Gy, V10 Gy, V20 Gy, V30 Gy).

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Despite significant primary tumor size reduction, there is no clinically significant difference in dose delivered to the primary tumor or to the radiation sensitive critical organs. Therefore the orinigal treatment plan can be safely used.

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