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L. Thiberville



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    OA18 - New Insights in the Treatment of Thymic Malignancies (ID 408)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      OA18.01 - Postoperative Radiotherapy in Thymic Epithelial Tumors: Insights from the RYTHMIC Prospective Cohort (ID 4271)

      11:00 - 12:30  |  Author(s): L. Thiberville

      • Abstract
      • Presentation
      • Slides

      Background:
      Thymic Epithelial Tumors (TET) are rare intrathoracic malignancies, for which surgery represents the mainstay of the treatment strategy. Current practice for postoperative mediastinal radiotherapy is highly variable, and there is paucity of prospective, multicentre evidence. RYTHMIC is the nationwide network for TET in France, established in 2012. Whether postoperative radiotherapy (PORT) should be delivered was the most frequent question raised at the RYTHMIC multi-disciplinary tumor board (MTB) over the past 3 years, accounting for 494 (35%) of a total of 1401 questions.

      Methods:
      All consecutive patients for whom postoperative adjuvant radiotherapy was discussed at the RYTHMIC MTB from 2012 to 2015 were identified from the RYTHMIC prospective database.

      Results:
      285 patients were identified, 274 (52% men, 48% women) of whom fulfilled inclusion criteria. Average age at time of TET diagnostic was 60 years. TET histology was thymoma in 243 (89%) cases - including type A in 11% of cases, type AB in 28%, type B1 in 17%, type B2 in 29%, and type B3 in 14% -, and thymic carcinoma in 31 (11%) of cases. Complete resection was achieved in 81% of patients. Masaoka-Koga stage was stage I in 29% of cases, IIA in 21%, IIB in 21%, III in 18%, and IVA/B in 11%. Decision of the MTB was consistent with guidelines in 221 (92%) assessable cases. Clinical situations for which PORT was indicated in accordance with guidelines (84 cases) were thymoma/R1 resection (30 patients), thymoma/R0 resection/stage III (22 patients), thymoma/R0 resection/stage IIB/type B2/B3 histology (11 patients), thymic carcinoma/R1 resection (6 patients), thymic carcinoma/R0 resection (13 patients), thymoma/R0 resection/stage IIA/type B3 histology (2 patients). Inconsistencies between decision of the MTB and guidelines – 20 (8%) cases - consisted of abstention related to poor general condition (10 patients), carcinoid histology (2 patients), and discordance in staging (1 patient), and of delivery of radiotherapy related to peroperative tumor fragmentation (2 patients); for 5 patients who received PORT, a clear explanation for inconsistency with guidelines was not found, but those cases actually corresponded to those in a “grey zone” of guidelines. MTB decision for PORT was actually implemented for 99 (85%) of patients; most frequent reason for not delivering radiotherapy was prolonged delay since surgery.

      Conclusion:
      Our data provide with a unique insight into the decision-making process for PORT in thymic epithelial tumors, highlighting the need for a systematic discussion at an expert MTB, while stressing the value of current available guidelines.

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    P2.04 - Poster Session with Presenters Present (ID 466)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      P2.04-003 - Chemotherapy in Advanced Thymic Epithelial Tumors: Insights from the RYTHMIC Prospective Cohort (ID 4275)

      14:30 - 15:45  |  Author(s): L. Thiberville

      • Abstract
      • Slides

      Background:
      Thymic Epithelial Tumors (TET) are rare intrathoracic malignancies, which may be aggressive and difficult to treat. In the advanced setting, chemotherapy may be delivered as a primary/induction therapy before subsequent surgery or definitive radiotherapy, and/or as exclusive treatment in patients for whom no focal treatment is feasible, and/or in the setting of recurrences. As no randomized trial and a limited number of prospective studies are available, there is paucity of prospective, multicentre evidence regarding response rates and survival of patients. RYTHMIC is the nationwide network for TET in France. The RYTHMIC prospective database is hosted by the French Intergroup (IFCT), and collects data for all patients diagnosed with TET, for whom management is discussed at a national multidisciplinary tumor board (MTB) based on consensual recommendations. Primary, exclusive chemotherapy, and chemotherapy for recurrence accounted for 149 (11%), 37 (3%), and 67 (5%) questions of a total of 1401 questions raised at the MTB between 2012 and 2015.

      Methods:
      All consecutive patients for whom chemotherapy and/or systemic treatment was discussed at the RYTHMIC MTB from 2012 to 2015 were identified from the RYTHMIC prospective database. Main endpoints were response rates and progression-free and overall survival.

      Results:
      At the time of analysis, data were available for 156 patients (80 thymic carcinomas, and 76 thymomas), for whom the management led to raise 283 questions at the MTB: 67 (24%) for primary chemotherapy, 35 (11%) for exclusive chemotherapy, and 181 (64%) for recurrences. For primary and exclusive chemotherapy, the most frequently administered regimen was CAP, producing response rates of 70% and 60%, respectively. A total of 104 patients received at least one line of chemotherapy for recurrence; 53 patients received second-line treatment, and 13 and 7 patients received third- and fourth line treatment. In the setting of first recurrence, carboplatine-paclitaxel combination was the most preferred regimen, administered to 54% of patients; overall response and disease control rates to systemic treatments for recurrences were 13% and 42% in thymic carcinomas, and 19% and 43% in thymomas (p=0.38 and p=0.92, respectively). Median recurrence-free survival after primary chemotherapy was 16.6 months; median progression-free survival after exclusive chemotherapy, and first-, second-, and third-line chemotherapy for recurrence were 6.0 months, and 7.6 months, 6.2 months, and 6.0 months.

      Conclusion:
      Our data provide with a unique insight in the efficacy of chemotherapy for advanced thymic epithelial tumors in a real-life setting; our results help the decision-making to better define the optimal therapeutic strategies.

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    P3.02c - Poster Session with Presenters Present (ID 472)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.02c-032 - Interstitial Pneumonitis Associated with Immune Checkpoint Inhibitors Treatment in Cancer Patients (ID 5670)

      14:30 - 15:45  |  Author(s): L. Thiberville

      • Abstract
      • Slides

      Background:
      Immunotherapy is now a standard of care in melanoma, lung cancer and is spreading across other tumours. Immune checkpoint inhibitors (ICI) are generally well tolerated but can also generate immune-related adverse effects. Since the first trials, pneumonitis has been identified as a rare but potentially life-threatening event.

      Methods:
      We conducted a retrospective study over a period of 5 months in centers experienced in ICI use in clinical trials, access programs or following national approval. We report the main features of possibly related pneumonitis occurring in patients treated with ICI with a particular focus on clinical presentation, radiologic patterns (with a double reviewing by radiologists and pulmonologists), pathology and therapeutic strategies.

      Results:
      We identified 71 patients with possibly related pneumonitis including 54 NSCLC and 13 melanoma. They mainly received PD1 inhibitors. Pneumonitis usually occurred in male, former or current smokers with a median age of 59 years. We observed grade 2/3 (n= 45, 65.2%) and grade 5 (n= 6, 8.7%) pneumonitis. The median duration time between the introduction of immunotherapy and the pneumonitis was 2.2 months [0.1-27.4]. Ground glass opacitiy on lung CT-scan were the most predominant lesion 80.9% (n=55), followed by consolidations 44.1% (n=30), reticulations 36.7% (n=25) and bronchiectasis in 20.6% (n=14). When performed, bronchoalveolar lavage (BAL) showed a T-lymphocytic alveolitis and transbronchial biopsy an inflammatory and lymphocytic infiltration. Pneumonitis treatment was steroids (86.6%) and/or antibiotics (67.6%). Immunotherapy was stopped after the pneumonitis for 65 cases (92.9%) and reintroduced for 12 (9.4%) cases. Twenty-four patients (34.3%) were dead at the last follow-up and 46 patients (65.7%) were still alive. Among the living patients, the pneumonitis outcome was a total recovery in 12 patients, improvement in 22 patients, stability in 10 patients, worsening evolution in 1 patient (1 unknown). Causality of immunotherapy was evaluated by investigators as “possible” for 34 patients (49.3%), “probable” for 17 (24.6%), “certain” for 15 (21.7%) other causes for 3 (4.3%) and 2 unknowns. Median overall survival from the onset of pneumonitis was 6 months.

      Conclusion:
      This serie, the largest to date, of immune-related pneumonitis demonstrates that it occurs usually during the first months and displays specific radiologic features. As there is no clearly identified risk factor, oncologists should be able to detect, diagnose (with CT-scan and bronchoscopy) and treat this adverse event. An early management is usually associated with a favourable outcome and requires a close collaboration between pulmonologists, radiologists and oncologists.

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