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X. Quantin



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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: 2
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      OA18.01 - Postoperative Radiotherapy in Thymic Epithelial Tumors: Insights from the RYTHMIC Prospective Cohort (ID 4271)

      11:00 - 11:10  |  Author(s): X. Quantin

      • 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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      OA18.07 - Quality of Resection and Outcome in Stage III TETs: The French RYTHMIC Network Experience (ID 6173)

      12:05 - 12:15  |  Author(s): X. Quantin

      • Abstract
      • Presentation
      • Slides

      Background:
      Stage III TET represents a heterogeneous population and their optimal approach remains unclear; most of the available literature is composed of small series spanned over extended periods of time. RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French nationwide network for TET with the objective of territorial coverage by regional expert centers and systematic discussion of patients management at national tumor board. We reviewed our experience in stage III thymic tumors in order to evaluate the value of tumor board recommendations and multidisciplinary approach.

      Methods:
      We conducted a retrospective analysis of patients (pts) with stage III TET discussed at the RYTHMIC tumor board from January 2012 to December 2015. Clinical, pathologic and surgical data were prospectively collected in a central database. Survival rates were based on Kaplan-Meier estimation. Cox proportional hazard models were used to evaluate prognostic factors for disease free survival (DFS) and overall survival (OS).

      Results:
      150 pts were included in the analysis. Median age was 64 years [18 – 91], 56% males, thymoma A-B2/ B3-thymic carcinoma in 52% and 47% respectively; 12% presented with autoimmune disorder (76% myasthenia). Local treatment was surgery in 134 pts (90%) followed by radiotherapy (RT) in 90 pts; 26 pts received preoperative chemotherapy (CT). Complete resection rate (R0) was 53%. Among 38 pts considered non-surgical candidates at diagnosis, 26 pts became resectable after induction CT with a R0 rate of 58%; 12 pts received CT-RT and/or CT as primary treatment. Recurrence rate was 38% (n=57), first sites were pleural (n=32) and lung (n=12). The 5-year OS and DFS were 88% and 32% respectively. Gender (HR: 0.2 [95%CI 0.04 - 0.97] p=0.04), histology (HR: 0.19 [95%CI 0.05 - 0.70] p=0.02) and surgery (HR: 0.4 [95%CI 0.01 - 0.20] p<0.001) as primary treatment modality were significant prognostic factors for OS in multivariate analysis. Histology (HR: 0.5 [95%CI 0.30 - 0.90] p=0.02) and adjuvant RT (HR: 0.4 [95%CI 0.20 – 1.00] p=0.05) were significantly associated with DFS. Completeness of resection was not associated with survival in our cohort.

      Conclusion:
      Surgery followed by radiotherapy improves outcome irrespectively of R0. Stage III TET not candidate to surgery should be reassessed for resection after induction chemotherapy.

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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: 2
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      P2.04-003 - Chemotherapy in Advanced Thymic Epithelial Tumors: Insights from the RYTHMIC Prospective Cohort (ID 4275)

      14:30 - 14:30  |  Author(s): X. Quantin

      • 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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      P2.04-006 - Updated Incidence of Thymic Epithelial Tumors (TET) in France and Clinical Presentation at Diagnosis (ID 5952)

      14:30 - 14:30  |  Author(s): X. Quantin

      • Abstract
      • Slides

      Background:
      TETs are rare malignancies with an overall described incidence of 0.13 per 100.000 person-years. Given this, most of our knowledge is largely derived from small single-institution series. RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French network for TET with the objective of territorial coverage by 14 regional expert centers, systematic discussion of patients at national tumor board and collection of nationwide data within a centralized database. We reviewed our activity in 2015 in order to describe the epidemiology and main characteristics at diagnosis of thymic malignancies in France.

      Methods:
      Through RYTHMIC, we prospectively collected all patients (pts) with new diagnosis of primary TET in France in 2015. Epidemiologic, clinical, pathologic and surgical data were prospectively collected within a centralized database. Histologic subtype was centrally reviewed according to the WHO classification and stage by modified Masaoka-Koga classification.

      Results:
      A total of 234 cases with new diagnosis of primary thymoma (T) or thymic carcinoma (TC) have been discussed at RYTHMIC between Jan to Dec 2015. Among them, 58% were males; median age was 62 years [range 27; 86] for males and 61 years for females [range 24; 84]; 20% of the pts presented an autoimmune disorder (AI); myasthenia gravis was the most common in 76% of them. History of previous malignancies was described in 15% of the pts, being melanoma, prostate and breast cancer the most frequently observed. Any potentially relevant environmental exposure was declared for most of the pts. Histology was characterized as follows: A / AB / B1 / B2 / B3 / TC / neuroendocrine tumors and rare variants in 7% / 23% / 13% / 24% / 9% / 16% / 8% respectively. Stage I-II / III-IV tumors were observed in 63% / 37% respectively. Mediastinal pleura, mediastinal nodes and lung were the most common metastatic sites. Significant correlations were found between histologic sub-type (T vs TC) and presence of AI (p=0.01) and stage (I-II vs III-IV, p=0.004); no significant correlations were seen with gender (p=0.27).

      Conclusion:
      The estimated incidence of TETS in France in 2015 is 0.35 per 100.000 persons, based in our activity. The inclusion in the RYTHMIC network is mandatory but is still based on physician’s request. Although we might underestimate the incidence, it seems to be higher compared to other countries’ registries. The high occurrence of previous cancer might underlie variations in environmental or genetic risk factors.

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