ORIGINAL ARTICLE
European Journal of Cardio-Thoracic Surgery 49 (2016) 835–841 doi:10.1093/ejcts/ezv239 Advance Access publication 26 June 2015
Cite this article as: Hishida T, Nomura S, Yano M, Asamura H, Yamashita M, Ohde Y et al. Long-term outcome and prognostic factors of surgically treated thymic carcinoma: results of 306 cases from a Japanese Nationwide Database Study. Eur J Cardiothorac Surg 2016;49:835–41.
Long-term outcome and prognostic factors of surgically treated thymic carcinoma: results of 306 cases from a Japanese Nationwide Database Study Tomoyuki Hishidaa,*, Shogo Nomurab, Motoki Yanoc, Hisao Asamurad,e, Motohiro Yamashitaf, Yasuhisa Ohdeg, Keishi Kondoh, Hiroshi Datei, Meinoshin Okumuraj and Kanji Nagaia on behalf of the Japanese Association for Research on the Thymus ( JART) a b c d e f g h i j
Department of Thoracic Surgery, National Cancer Centre Hospital East, Chiba, Japan Center for Research Administration and Support, National Cancer Centre, Chiba, Japan Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Department of Thoracic Surgery, National Cancer Centre Hospital, Tokyo, Japan Present address: Division of Thoracic Surgery, Keio University School of Medicine, Tokyo, Japan Department of Thoracic Surgery, Shikoku Cancer Centre, Ehime, Japan Division of Thoracic Surgery, Shizuoka Cancer Centre, Shizuoka, Japan Department of Thoracic Surgery, Hokkaido Cancer Centre, Sapporo, Japan Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan Department of Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
THORACIC
* Corresponding author. Department of Thoracic Surgery, National Cancer Centre Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. Tel: +81-4-71331111; fax: +81-4-71314724; e-mail:
[email protected] (T. Hishida). Received 13 April 2015; received in revised form 2 June 2015; accepted 8 June 2015
Abstract OBJECTIVES: Thymic carcinoma is a rare thymic malignancy. The purpose of this study was to evaluate the prognostic impact of clinicopathological variables and perioperative therapy for surgically treated thymic carcinoma using a nationwide database. METHODS: Of 2835 patients with surgically treated thymic epithelial tumours collected from 32 Japanese institutions, a total of 306 patients with thymic carcinomas, excluding neuroendocrine tumours, were enrolled in this retrospective study. Multivariable Cox regression analyses were performed for overall (OS) and recurrence-free survival (RFS) after R0 resection. RESULTS: Of 306 patients, 228 (75%) patients presented with Masaoka stage III–IV. Squamous cell carcinoma was the most common histological type (n = 216, 71%). R0 resection was performed in 181 (61%) patients, R1 in 46 (16%), R2 sub-total (≥80% tumour resection) in 43 (14%) and R2 non-resection in 27 (9%). The 5-year OS rate was 61%. Prognostic factors for OS were Masaoka stage and resection status. R0 resection was associated with most improved OS; however, both R1 and R2 sub-total resection resulted in superior OS compared with R2 non-resection [hazard ratio (95% confidence interval) for R0, R1 and R2 sub-total, 0.27 (0.15–0.48), 0.40 (0.22–0.74) and 0.38 (0.20–0.72), respectively]. Histological type and perioperative therapy did not affect OS, whereas tumour size and postoperative radiotherapy were associated with improved RFS after R0 resection. CONCLUSIONS: R0 resection is essential for prolonged OS for surgically treated thymic carcinoma, but maximal debulking surgery might be beneficial and worth evaluating for advanced disease deemed difficult for R0 resection. The benefit of postoperative radiotherapy after R0 resection should also be evaluated prospectively. Keywords: Thymic carcinoma • Surgery • Masaoka stage • Resection status • Radiation therapy
INTRODUCTION Thymic carcinoma is a rare thymic neoplasm that accounts for 10–15% of all thymic epithelial tumours [1–3]. Previous studies have shown that surgical resection is the mainstream treatment for thymic carcinoma [4–10]. However, due to the rarity of the disease, most of these studies have been derived from small
retrospective series. Thus, multicentre studies have been needed globally to determine the modern surgical outcome and prognostic factors of thymic carcinoma. The Japanese Association for Research of the Thymus ( JART) developed a nationwide retrospective database to clarify disease profiles of thymic tumours, including thymic carcinoma. The purpose of this study was to clarify the clinical, pathological and
© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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treatment factors associated with survival of surgically treated thymic carcinoma using the information from the nationwide database.
PATIENTS AND METHODS
cause or the last follow-up for living patients. RFS was calculated from the time of R0 resection to the time of recurrence, death or the last follow-up if the patient remained recurrence-free. PRS was calculated from the date of recurrence to the date of any death or the last follow-up.
Study cohort Statistical analysis JART developed a nationwide database in 2012, and retrospectively collected the data of 2835 thymic epithelial tumour patients who underwent surgical management between 1991 and 2010 at 32 Japanese institutions. The JART database included patient characteristics, preoperative and final pathological Masaoka stage, preoperative and pathological tumour size, histological type, type of resection, resection status, perioperative therapies including chemotherapeutic regimens and radiation dose, pattern and treatment of recurrence and survival. Patients who were mainly treated by modalities other than surgery were essentially not included in the database. The study was approved by the respective institutional review boards, and the need for obtaining informed consent from each patient was waived. From this database, a total of 306 (10.8%) patients with a pathological diagnosis of thymic carcinoma were identified and enrolled into the current study. Type B3 thymomas (well-differentiated thymic carcinomas, n = 321) were strictly excluded from the study cohort. We also excluded neuroendocrine tumours (NETs, n = 64), since, although the current WHO classification defines them as the same entity as thymic carcinoma, NETs have distinct features from those of typical thymic carcinomas [11].
Clinicopathological analysis The preoperative and final pathological stage classification was based on the Masaoka staging system [12]. Histological type was diagnosed at each institution according to the latest WHO classification [11], collected by a questionnaire survey and classified into the following three groups by the previously proposed histological grade [4]: (i) low-grade thymic carcinoma (LG-TC; squamous cell carcinoma, mucoepidermoid carcinoma and basaloid carcinoma), (ii) high-grade thymic carcinoma (HG-TC; lymphoepithelioma-like carcinoma, clear-cell carcinoma, sarcomatoid carcinoma and adenocarcinoma) and (iii) thymic carcinoma with unclassified/ unspecified histology (NOS-TC; thymic carcinoma, not otherwise specified). The resection status was classified into four groups: R0 (complete resection as determined macroscopically and microscopically), R1 (microscopically incomplete resection), R2 sub-total [macroscopically incomplete but sub-total (≥80%) tumour resection] and R2 non-resection (
