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S.B. Watzka
Moderator of
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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: 8
- Moderators:N. Girard, S.B. Watzka
- Coordinates: 12/07/2016, 11:00 - 12:30, Schubert 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): C. Basse, S. Thureau, S. Bota, E. Dansin, P.A. Thomas, E. Pichon, H. Léna, C. Massabeau, C. Clément-Duchêne, G. Massard, V. Westeel, F. Thillays, X. Quantin, Y. Oulkhouir, S. Danhier, D. Lerouge, L. Thiberville, B. Besse, N. Girard
- Abstract
- Presentation
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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OA18.02 - Evaluation of a Modified Dosing Regimen (2-Weeks on/1-Week off) of Sunitinib as Part of a Phase II Trial in Thymic Carcinoma (ID 6289)
11:10 - 11:20 | Author(s): A. Rajan, C. Kim, U. Guha, E. Szabo, A. Berman, L. Sciuto, A..J. Spittler, J.B. Trepel, S.M. Steinberg, P. Harris, R. Hassan, P.J. Loehrer, Sr.
- Abstract
- Presentation
Background:
Sunitinib is active in patients with recurrent thymic carcinoma (TC). We have previously reported an objective response rate of 26% and disease control rate (partial response and stable disease) of 91% in patients with TC when sunitinib is administered at a dose of 50 mg once daily for 4 weeks followed by 2 weeks off (4/2 dosing schedule). Grade 3 or 4 treatment-related adverse events (TEAEs) occurring in more than 10% of patients included fatigue, oral mucositis and lymphocytopenia (20% each), and hypertension (13%). Grade 3 decrease in left ventricular ejection fraction (LVEF) was observed in 8% of patients. Alternative dosing schedules have been evaluated in solid tumors to improve tolerability. As part of an ongoing phase II study (NCT01621568), we evaluated the clinical activity and tolerability of sunitinib in patients with TC using a 2-weeks-on/1-week-off (2/1) dosing regimen.
Methods:
Patients with progressive TC after at least one prior platinum-containing chemotherapy regimen, measurable disease, and adequate end organ function were enrolled and received sunitinib at a dose of 50 mg orally once daily using a 2/1 schedule until disease progression or development of intolerable adverse events. The primary objective was evaluation of response rate. Tumor assessments were performed every 6 weeks using RECIST version 1.1 and toxicity was assessed every 3 weeks using CTCAE version 4.0. Exploratory correlative studies including evaluation of immune cell subsets will be reported separately.
Results:
Between July 8, 2014 and January 14, 2016, 15 patients were enrolled. Median age was 62 years (range, 41-76), and 33% were male. A median of 4 (range, 1 – 33+) cycles of sunitinib was administered. Among 13 evaluable patients, there was 1 (8%) partial response, 11 (85%) stable disease and 1 (8%) progressive disease. After a median follow-up of 16 months, the median progression-free survival was 5 months and median overall survival was 16 months. Grade 3 or 4 TEAEs occurring in more than 10% of patients included lymphocytopenia (40%), neutropenia and leucopenia (20% each), thrombocytopenia and oral mucositis (13% each). Grade 3 decrease in LVEF was observed in 1 (7%) patient.
Conclusion:
Sunitinib, administered using a 2/1 dosing schedule, has clinical activity in patients with TC, and the frequency of clinically significant TEAEs (fatigue, mucositis, hypertension) is acceptable. Studies are ongoing to identify novel immunological biomarkers of activity.
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OA18.03 - Safety and Clinical Activity of Avelumab (MSB0010718C; Anti-PD-L1) in Patients with Advanced Thymic Epithelial Tumors (TETs) (ID 6141)
11:20 - 11:30 | Author(s): A. Rajan, C.R. Heery, A.L. Mammen, S. Pittaluga, L.M. Lepone, R.N. Donahue, I. Grenga, J. Schlom, J.L. Gulley, R. Hassan
- Abstract
Background:
Avelumab (MSB0010718C) is a fully human, IgG1 anti-PD-L1 antibody under clinical development. We report safety and clinical activity in patients with relapsed TETs enrolled in a phase I trial (NCT01772004).
Methods:
Patients previously treated with one or more standard therapies, no prior immune checkpoint inhibitors, and with no history of autoimmune disease were eligible. Treatment consisted of avelumab at doses of 10-20 mg/kg iv q2 weeks until disease progression or toxicity. Responses were assessed q6 weeks by RECIST 1.1. Correlative studies included evaluation of tumor cell PD-L1 expression and peripheral blood immune subset analysis.
Results:
7 patients with thymoma and 1 with thymic carcinoma (TC) were treated with avelumab; 3 patients with thymoma (2 B3, 1 B2/B3) received avelumab 20 mg/kg; 4 patients with thymoma (1 B1, 3 B2) and 1 TC received 10 mg/kg. Two (29%) patients with thymoma had a confirmed partial response (PR;1 at 20 mg/kg, and 1 at 10 mg/kg), 2 (29%) had unconfirmed PRs, 2 (29%) stable disease (SD) and 1 (14%) progressive disease; the TC patient had SD. Most adverse events (AEs) were mild (grade 1 or 2). Grade 3 and 4 AEs were observed in 3 (38%) patients each, and included potential immune-related AEs (irAEs) in 5 cases. irAEs resolved completely with oral steroids in 3 patients, and incompletely in 1 patient. One patient required cyclosporine A for treatment of irAEs. All 4 responders experienced irAEs (myositis in 3 patients, all after 1 dose of avelumab, and enteritis in 1 patient). Pre- and post-treatment tumor biopsies were available for analysis of PD-L1 expression and intratumoral immune infiltrates from three patients treated at 20 mg/kg. In one case the post-treatment biopsy showed necrotic tissue with no viable tumor. In the other two cases diffuse, membranous PD-L1 staining of epithelial cells was seen in both pre- and post-treatment biopsies. The immune infiltrate consisted of immature T cells in pre-treatment tumor samples in both cases. The post-treatment biopsy showed continued presence of immature T cells in one case and a mature CD8+ T cell phenotype in the other case. Decreased CTLA4+ regulatory T cells and decreased ratio of granulocytic vs. monocytic myeloid-derived suppressor cells was seen post-treatment at the 20mg/kg dose.
Conclusion:
Avelumab is active in patients with recurrent thymoma. Strategies need to be developed to reduce the risk of development of irAEs in response to immune checkpoint inhibitor therapy in patients with thymoma.
Information from this presentation has been removed upon request of the author.
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OA18.04 - Discussant for OA18.01, OA18.02, OA18.03 (ID 7044)
11:30 - 11:45 | Author(s): A. Rimner
- Abstract
- Presentation
Abstract not provided
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OA18.05 - FDG-PET in Thymic Epithelial Tumors: An Evaluation of Only Resected Tumors (ID 5635)
11:45 - 11:55 | Author(s): K. Nakagawa, S. Takahashi, Y. Ohde, H. Kurihara, T. Terauchi
- Abstract
- Presentation
Background:
[18]F-Fluorodeoxy glucose positron emission tomography (FDG- PET) is thought to be useful for predicting the histologic grade in thymic epithelial tumors (TETs). Although there have been many reports on the use of FDG-PET for evaluating TETs, no previous studies have included only resected cases. Therefore, we investigated the relationship between the degree of FDG-uptake in the tumor and either the WHO histologic subtype or the tumor stage in patients with resected TETs.
Methods:
We retrospectively reviewed FDG-PET findings in 112 patients with TETs (92 with thymomas and 20 with thymic carcinomas) resected at 2 institutes in Japan. The Spearman rank correlation coefficient was used to assess the association between the maximum standardized uptake value (SUV max) in the tumor and both the histologic subtype and tumor stage. The cut-off value of SUV max for differentiating thymoma from thymic carcinoma was calculated using a receiver operating characteristic (ROC) curve analysis.
Results:
The Table shows the relationship between SUV max in the tumor and the WHO histologic subtype. SUV max according to each tumor stage was 3.9 ± 1.7 (mean ± SD) in stage I (n = 89), 4.7 ± 1.7 in stage II (n = 3), 7.4 ± 5.3 in stage III (n =11), and 7.6 ± 3.9 in stage IV (n = 9). SUV max was strongly related to both the WHO histologic subtype and tumor stage (Spearman rank correlation coefficient = 0.485 and 0.432; p = 0.000 and 0.000, respectively). The optimal cut-off value of SUV max for differentiating thymoma from thymic carcinoma was 4.6, with a sensitivity of 80% and a specificity of 70%.SUV max ~Histologic subtype~ No. of patients ~Mean ± SD~ Range A 12 ~3.5 ± 1.3~ ~1.3 – 6.3~ AB 45 ~3.5 ± 1.3~ [1.2 – 6.9] B1 19 ~4.1 ± 0.9~ [2.5 – 6.5] B2 10 [4.2 ± 1.0] [2.7 – 5.9] B3 6 [4.8 ± 2.6] [2.4 – 8.6] Thymic carcinoma 20 [8.0 ± 4.7] [3.0 – 21.8] Total 112 [4.5 ± 2.8] [1.2 – 21.8]
Conclusion:
Our results suggest that FDG-PET is useful for differentiating thymoma from thymic carcinoma. Further studies will be needed to assess other potential clinical applications of FDG-PET for the evaluation of TETs.
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OA18.06 - Treatment, Outcome and Prognostic Factors of Patients with Thymic Epithelial Tumors at First Recurrence (ID 5594)
11:55 - 12:05 | Author(s): G.L. Banna, A. Sheel, V. Sheel, A. Bille, T. Routledge, S. Fernando, A. Nair, R. Lal
- Abstract
- Presentation
Background:
The treatment of patients with recurrent thymic tumors remains uncertain due to limited data because of the rare nature of this disease. This retrospective analysis was conducted to investigate clinical characteristics, outcomes and possible prognostic factors of patients presenting with a first recurrence of thymic tumors.
Methods:
107 patients with thymic neoplasms registered as C37 by ICD10 coding at Guy’s Hospital during the 2007-2016 period with first recurrence following primary treatment were selected and retrospectively reviewed via descriptive analysis. Differences in survival were assessed using Kaplan-Meier analysis and uni & multivariate Cox proportional hazards regression analyses.
Results:
25 patients (14 male & 11 female) with a median age of 51 years (range 36-80 years) experienced a first recurrence of thymoma (20 patients – 80%) or thymic carcinoma (5 patients – 20%) with a median time from diagnosis of 36 months (range, 7-270). At diagnosis, modified Masaoka disease stage was IIA/IIB/IIIA/IIIB/IVA/IVB in 4/0/8/2/6/5 patients; 18 patients’ (72%) primary resection was R0/R1/R2 in 11/3/4 patients; 9 patients (36%) received radiotherapy; 19 received chemotherapy (76%); CAP (n=10) and platinum-etoposide (n=6) regimens. At first relapse, 19 patients (76%) had thoracic recurrence and 6 patients (24%) extrathoracic recurrence. Nine patients (26%) underwent redo surgery, 3 of which recieved chemotherapy prior to resection. Overall resection status was 2/5/1 (1 patient’s data is not yet assessable) R0/R1/R2. Chemotherapy was administered in 17 patients (68%) with a median cycle of 4 (range, 1-6): 16 patients received combination chemotherapy consisting of platinum etoposide (n=10) or cisplatin-anthracycline based (CAP/CAV/AC n=5). Dose reduction and withdrawal were reported in 3 (18%) and 7 (41%) patients, respectively. In 4 out of these 7 patients withdrawal was due to PD; disease control rate (=CR+PR+SD) was 67% (in 10 out of 15 assessable patients). Three patients (12%) received radiotherapy of which one was treated exclusively with radiotherapy. Time to progression since the first recurrence was 12 months (range 2-52 months); in 16 patients extrathoracic recurrence was seen in 4 patients (25%) and thoracic in 12 patients (75%). Eight recurring patients (50%) received further chemotherapy. With a median follow-up of 32.5 months, 19 patients (75%) are alive and 2 (8%) disease-free; median OS has not been reached, median PFS was 29.5 months (range, 26.3-33.2). Analysis of possible prognostic factors will be presented.
Conclusion:
Patients with first recurrence of thymic tumors may benefit from combination chemotherapy and surgery when feasible.
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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): M.V. Bluthgen, E. Dansin, D. Ou, H. Léna, J. Mazieres, E. Pichon, F. Thillays, G. Massard, X. Quantin, Y. Oulkhouir, T. Nguyen, L. Thiberville, C. Clément-Duchêne, C. Lindsay, P. Missy, T. Molina, N. Girard, B. Besse, P.A. Thomas
- Abstract
- Presentation
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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OA18.08 - Discussant for OA18.05, OA18.06, OA18.07 (ID 7103)
12:15 - 12:30 | Author(s): E. Ruffini
- Abstract
- Presentation
Abstract not provided
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Author of
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OA15 - Sublobar Resections for Early Stage NSCLC (ID 396)
- Event: WCLC 2016
- Type: Oral Session
- Track: Surgery
- Presentations: 1
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OA15.04 - Discussant for OA15.01, OA15.02, OA15.03 (ID 7090)
16:30 - 16:45 | Author(s): S.B. Watzka
- Abstract
- Presentation
Abstract not provided
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