Virtual Library

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    MO03 - Thymic Malignancies (ID 123)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO03.03 - RYTHMIC: a nationwide network for thymic malignancies in France (ID 2631)

      10:30 - 12:00  |  Author(s): N. Girard, E. Pichon, P. Thomas, H. Léna, E. Dansin, G. Massard, G. Zalcman, J. Mazières, L. Thiberville, V. Westeel, P. Fournel, C. Clément-Duchêne, X. Quantin, J. Bennouna, T. Molina, B. Besse

      • Abstract
      • Presentation
      • Slides

      Background
      RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a nationwide network for thymic malignancies, which was appointed in 2012 by the French National Cancer Institute, as part of its rare cancer program. The objectives of the network include a territorial coverage by regional expert centers, the dissemination of highest standards for the diagnostic and therapeutic management of patients, and the promotion of collaborative research. Registration in RYTHMIC of all patients diagnosed with thymic malignancy is recommended as part of good clinical practice for oncologists.

      Methods
      Starting January 2012, the management of all patients diagnosed with thymic malignancy in France has been discussed on a real-time basis at a reference national multidisciplinary tumor board (MTB), which is organized twice a month using a web-based conferencing system. Decision-making is based on consensual recommendations, that were originally established using available evidence, and are updated and approved each year by all members of the network. A prospective database of all patients is hosted by the French Thoracic Cancer Intergroup. We report the characteristics and treatment modalities of patients included during the first year.

      Results
      From January to December 2012, 257 patients were enrolled in RYTHMIC. There were 126 (49%) men and 131 (51%) women; mean age at diagnosis was 54.5 years. Among 214 cases, histology was thymoma for 146 (56%) patients (11 (5%) type A, 28 (13%) type AB, 22 (10%) type B1, 35 (16%) type B2, 24 (11%) type B3, 26 (12%) mixed type), and thymic carcinoma for 33 (15%) patients, 8 of which were neuroendocrine carcinomas; other histologies were diagnosed for 35 (16%) patients. Among 144 cases, Masaoka-Koga stage was I, IIA, IIB, III, IVA, and IVB in 34 (24%), 19 (13%), 20 (14%), 22 (15%), 35 (24%), and 14 (10%) patients, respectively. 44 (17%) patients presented with autoimmune disorder, consisting of myasthenia gravis in 28 cases. Surgery was performed for 166 patients, mostly using a median sternotomy approach (52% of cases). Postoperative radiotherapy was delivered to 42 patients; 71 patients received perioperative chemotherapy. Exclusive chemotherapy/radiotherapy was administered to 20 and 4 patients, respectively. Mature data will be presented at the meeting.

      Conclusion
      This first analysis of the RYTHMIC prospective cohort demonstrates the feasibility of a national MTB for thymic malignancies, that, besides ensuring all patients an equal access to highly specialized treatment, provides with a comprehensive tool to monitor dedicated actions to improve the management of patients in the future, increase the quality-of-care, and screen patients for future translational research and clinical trials. Supported by Institut National du Cancer

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    MINI 25 - Trials, Radiation and Other (ID 142)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      MINI25.08 - Systemic Treatment in Advanced Thymic Epithelial Tumors. Insights From a Prospective Cohort of 888 Patients Enrolled in RYTHMIC (ID 1166)

      16:45 - 18:15  |  Author(s): N. Girard, E. Dansin, H. Léna, E. Pichon, P. Thomas, J. Mazières, L. Thiberville, V. Westeel, G. Zalcman, C. Clément-Duchêne, G. Massard, X. Quantin, J. Bennouna, P. Fournel, T. Molina, B. Besse

      • Abstract
      • Slides

      Background:
      RYTHMIC (Réseau tumeurs THYMiques et Cancer) is the French nationwide network for thymic malignancies. Starting 2012, all patients diagnosed with thymic tumor had to be enrolled, as recommended by the French National Cancer Institute, part of good clinical practice.

      Methods:
      RYTHMIC prospective database is hosted by the French Thoracic Cancer Intergroup (IFCT), and collects clinical, imaging, treatment, and follow-up data of patients discussed at the reference national multidisciplinary tumor board (MTB). Data cutoff was April 1[st], 2015 for this analysis.

      Results:
      1089 questions were raised at the MTB about the management of 888 patients with thymic epithelial tumor. Among assessable cases, Masaoka-Koga stage III-IV tumors accounted for 42% of cases; histology was thymoma in 82% of cases, and thymic carcinoma in 18% of cases. First-line treatment of locally advanced disease, and management (diagnosis and treatment) of recurrent disease led to raise 227 (21%), and 234 (21%) questions at the MTB, respectively, 312 (68%) of which were about the modalities of systemic treatment. Figure 2 shows the proposed regimens for primary (A) and exclusive (B) chemotherapy in treatment-naïve patients, and chemotherapy (C) and targeted agents (D) for recurrent tumors. Combination of cisplatin, adriamycin, and cyclophosphamide and carboplatine, paclitaxel were the most frequently proposed regimens as first- and second-line treatment, respectively. Figure 1 Figure 2





      Conclusion:
      RYTHMIC is an exhaustive registry of thymic malignancies, which provides unique insights in the management of advanced and recurrent tumors with systemic agents. Meanwhile, limited data have been made available in the literature so far, as clinical trials were conducted in small numbers of patients, and existing databases enrolled a majority of surgically resected, early-stage tumors. Through the use of targeted agents, RYTHMIC allows the rapid implementation of new results in clinical practice, while ensuring patients an equal access to therapeutic innovation. Supported by Institut National du Cancer

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    P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      P1.08-035 - Pan-European Survey on Thymic Malignancies: A Collaboration of the EORTC Lung Cancer Group (LCG) with the RYTHMIC Network (ID 690)

      09:30 - 17:00  |  Author(s): J. Menis, N. Girard, B. Hasan, B. Besse

      • Abstract
      • Slides

      Background:
      Thymic malignancies are rare tumors with an incidence of over 0.15 cases per 100.000 persons/year. Because of the indolent course and sporadic occurrence, the management of this disease has been mainly based on single-institution retrospective, observational studies. Clinical trials have been run in the recent years but no uniformly accepted guidelines are available so far. For advanced disease at diagnosis or with relapse/ progression treatment options are limited in first line and there is no standard treatment for second line treatment. The EORTC Lung Cancer Group (LCG) and French RYTHMIC network developed a survey with the aim of assessing the current treatment strategies and respective outcomes, thus providing an overview on the management of these tumors in advanced stage.

      Methods:
      We conducted a 25-item survey disseminated as dedicated mailing in the EORTC LCG and RYTHMIC network. Descriptive statistical analysis was applied to assess and present the preliminary replies.

      Results:
      At the time of the analysis, a total of 45 physicians from 11 countries participated in the study, the majority of participants were EORTC members (60.8%) and 11.1% were both EORTC and RYTHMIC members. About half of the institutions have a dedicate team for thymic malignancies (46.7%) but almost all of them have in place multidisciplinary meeting to discuss new diagnosed patients (91.1%).Diagnosis is made on surgical sample in 53.4% of the cases flowed by core needle biopsy (33.6%) and open biopsy (13%). For both thymoma and thymic carcinoma, the preferred choice for induction chemotherapy is CAP (cisplatin, doxorubicin and cyclophosphamide) (42.2% and 31.1% respectively) followed by cisplatin and etoposide (13.3% and 13.3% respectively). Also for first line chemotherapy, for both thymoma and thymic carcinoma, the preferred choice is CAP (35.6% and 28.9% respectively). For first line treatment the reported Overall Response Rate (ORR) is about 40% for thymoma and 31% for thymic carcinoma, the median Progression Free Survival (PFS) is 8 months for thymoma and 3 months for thymic carcinoma and the reported median Overall Survival (OS) is 28 months for thymoma and 18 months for thymic carcinoma. For both thymoma and thymic carcinoma, the preferred first choice for second line chemotherapy is carboplatin and paclitaxel (35.6% and 31.1% respectively) and the prefered second choice is cisplatin and etoposide (13.3 and 17.8% respectively). For second line treatment the reported ORR is about 36% for thymoma and 23% for thymic carcinoma, the median reported PFS is 8 months for thymoma and 4 months for thymic carcinoma; the median OS is 15 months for thymoma and 9 months for thymic carcinoma. No testing for c-kit or EGFR mutations is routinely performed.

      Conclusion:
      The survey provides a large, multi-institutional overview of the clinical practice in the management of thymic tumors in Europe, and provides relevant and updated background for the development of future collaborative trials. The survey is still ongoing and final results will be presented at the conference.

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    P2.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 225)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      P2.08-030 - Sunitinib in Patients with Advanced Thymoma and Thymic Carcinoma. Retrospective Analysis from RYTHMIC Database (ID 1160)

      09:30 - 17:00  |  Author(s): J. Remon, N. Girard, J. Mazières, E. Dansin, E. Pichon, J. Biemar, C. Dubos, B. Besse

      • Abstract
      • Slides

      Background:
      Sunitinib is a potent oral tyrosine kinase inhibitor of VEGFR, KIT and PDGFR. In a single arm phase 2 study of sunitinib after at least one previous line of chemotherapy, a 26% of partial response rate (PR) was reported in thymic carcinoma (TC) and 6% in thymoma (T), with a median progression free survival (mPFS) of 7.2 months and 8.5 months, respectively. We investigated if off-labelled prescription of sunitinib in this population induced the same efficacy signal.

      Methods:
      We investigated the database of the French thymic malignancies network. We reviewed advanced T and TC patients (p) who were treated with sunitinib in order to evaluate patient’s outcome.

      Results:
      From October 2011 to January 2015, 28 patients of 7 institutions were identified (20 TC and 8 T). 32% of patients were females and median age was 49.7 y. Fifteen patients (54%) received sunitinib in ≥ 4[th] line of treatment. Two patients received sunitinib in 1[st] line treatment (1 T and 1 TC). The 37.5 mg was the initial dose of sunitinib in 16p. In the whole population, the PR rate was 21% (of 20p with TC, 4 (20%) had a PR; and of 8p with T, 2 (25%) had partial responses). Of note, PR to sunitinib was independent of treatment line (1p at 1[st] lines, 1p at 3[rd] line, 2 p at 4[th] line and 2p at ≥ 5[th] line). 3 TC p were c-KIT positive, without a clear relationship with response rate (1 PR, 2 PD). The mPFS in whole population was 103 days. For TC the mPFS was 87 days and 139 days for T. Sunitinib adverse events were manageable and tolerable. 8p stopped sunitinib due to toxicity. The median overall survival (OS) in the whole population was 175 days, with prolonged OS in T vs. TC (403 days vs. 166 days)

      Conclusion:
      Sunitinib is an active treatment in thymic epithelial malignancies irrespective of histological subtype, even in a heavy pre-treated population, and treatment line, supporting antiangiogenic therapies as an alternative treatment option for these patients.

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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 - 12:30  |  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
      • 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)

      11:00 - 12:30  |  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
      • 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: 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): C. Merveilleux Du Vignaux, M.V. Bluthgen, L. Mhanna, E. Dansin, L. Greillier, E. Pichon, H. Léna, C. Clément-Duchêne, G. Massard, V. Westeel, M. Robert, X. Quantin, G. Zalcman, L. Thiberville, T. Molina, J. Mazieres, B. Besse, N. Girard

      • 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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    OA 03 - Mediastinal and Esophageal Tumor: Insight and New Treatment (ID 654)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      OA 03.01 - Prevalence of Autoimmune Diseases in Thymic Epithelial Tumors (TET) Insights from RYTHMIC (ID 8745)

      11:00 - 12:30  |  Presenting Author(s): Marie-Eve Boucher  |  Author(s): E. Dansin, M. Kerjouan, Julien Mazieres, E. Pichon, F. Thillays, G. Massard, X. Quantin, O. Youssef, Virginie Westeel, L. Thiberville, C. Clement-Duchene, F. Morin, P. Thomas, Nicolas Girard, Benjamin Besse

      • Abstract
      • Presentation
      • Slides

      Background:
      TET have been associated with autoimmune disorders (AID) in up to 30 % of patients. However, there have been wide variations in the reported prevalence of TET associated disorders based mostly on small single center series. RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French network mandated to systematically discuss every case of TET. Using our database, we aimed to describe the prevalence of AID in a large French population with TET.

      Method:
      RYTHMIC database prospectively includes all consecutive patients with a diagnosis of TET discussed in our national tumor board. We calculated the prevalence and described epidemiologic, clinical and pathological characteristics of patients with TET’s related autoimmune diseases.

      Result:
      From January 2012 to May 2017, 1693 patients were included in the registry. Of these, 200 patients (11.8%) had autoimmune disorder. The mean age at diagnosis of TET was 54 years old and 52% were male. 149 had myasthenia gravis (75.3%), 15 Good syndrome (7.6%), 14 pure red cell aplasia (7.1%), 12 systemic erythematous lupus (6.1%) and 12 thyroiditis (6.1%). Some patients (14.5%) eventually developed more than 1 AID. Diagnosis of AID was mostly done at the same time of TET diagnosis (54.6%) but some patient had their AID diagnosed before (19.8%) or during follow up (13.4%). Masaoka Koga stages were overall well balanced with 16.5% stage III, 16% stage IIb, 13.5% stage I, 13% stage IIa and IV. Histologic subtype distribution was in order of frequency; B2 (37%), AB (14.5%), B3 (14%), B1 (10.5%), thymic carcinoma (4.5 %) and A (4%).

      Conclusion:
      In our registry of TET, the prevalence of autoimmune diseases was 11.8% and most diagnosis were established at the same time as TET. The extent of disease, measured by Masaoka Koga staging, does not seem correlated.

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