今日の臨床サポート

縦隔腫瘍

著者: 花田豪郎 虎の門病院 呼吸器センター内科

監修: 高橋和久 順天堂大学大学院

著者校正済:2022/11/24
現在監修レビュー中
患者向け説明資料

概要・推奨   

  1. 縦隔腫瘍の臨床において、縦隔の区分は、正確な存在診断を可能にする(推奨度1)
  1. 正岡病期分類は腫瘍の浸潤と播種転移を主たる基準にした分類であり、国際的に最も汎用されている臨床病期分類である(推奨度1)
  1. 胸腺腫では完全切除が不可能な場合には、亜全摘でも生存延長に意義があると考えられており、可能な限りの切除を行う(推奨度2)
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となり
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
花田豪郎 : 特に申告事項無し[2022年]
監修:高橋和久 : 講演料(アストラゼネカ(株),MSD(株)),研究費・助成金など(小野薬品工業(株),中外製薬(株),ブリストル・マイヤーズスクイブ(株)),奨学(奨励)寄付など(杏林製薬(株),サノフィ(株),大鵬薬品工業(株),中外製薬(株),帝人ファーマ(株),日本イーライリリー(株),日本ベーリンガーインゲルハイム(株))[2022年]

改訂のポイント:
  1. 最新のガイドラインに基づき胸腺上皮性腫瘍に対する放射線治療の基本事項について加筆を行った。
  1. 最新のガイドラインに基づき臨床病期Ⅳ期または再発胸腺癌に対する薬物療法について加筆を行った。
  1. 定期レビューを行い、胸腔鏡補助下およびロボット支援下の低侵襲手術について加筆を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 縦隔腫瘍とは、縦隔内臓器・組織から発生した腫瘍、嚢腫で、心疾患や食道腫瘍は除外する。
  1. 縦隔腫瘍のうち、胸腺関連腫瘍、先天性嚢胞、神経原性腫瘍、胚細胞性腫瘍、リンパ性腫瘍、縦隔内甲状腺腫などの頻度が高い。
  1. 縦隔はCT画像を基準に、縦隔上部、前縦隔、中縦隔、後縦隔に区分され(縦隔区分<図表>)、腫瘍占拠部位により起源組織・臓器が推定できる(縦隔腫瘍の好発部位<図表>)。
  1. 症状がないか、あっても軽度の咳嗽、胸痛の場合が多いが、周辺臓器の圧迫、浸潤による症状を呈することもある。
  1. 画像診断には、胸部造影CTが有用である。症例によっては、MRI、FDG-PETが役立つ。
  1. 腫瘍の鑑別が必要な場合や、術前治療の適応の場合、切除不能例の場合は、組織学的な確定診断が必要となり、経皮的針生検や胸腔鏡による組織採取が行われる。
  1. 治療は、原則として外科的切除が行われる。手術不能例や術後再発例では、化学療法や放射線療法が主体となる。
 
  1. 縦隔腫瘍は、胸腺腫、先天性嚢胞、神経原性腫瘍、リンパ性腫瘍、胸腺癌、胚細胞腫瘍、縦隔内甲状腺腫の順で頻度が高い(推奨度2、O(参考文献:[1]
  1. まとめ:2008年胸部外科学会の手術例の集計では、胸腺腫(36.8%)、先天性嚢胞(16.2%)、神経原生腫瘍(11.6%)、リンパ性腫瘍(6.4%)、胸腺癌(5.8%)、胚細胞腫瘍(5.6%)、縦隔内甲状腺腫(3.1%)の順で頻度が高い。
  1. 追記:悪性リンパ腫など手術適応にならない疾患は過小評価されていることを考慮する。
問診・診察のポイント  
問診のポイント:
  1. 縦隔腫瘍はさまざまな症状を呈することがあり、全身症状を含めた問診が必要となる。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

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文献 

Ryuzo Sakata, Yoshitaka Fujii, Hiroyuki Kuwano
Thoracic and cardiovascular surgery in Japan during 2008: annual report by The Japanese Association for Thoracic Surgery.
Gen Thorac Cardiovasc Surg. 2010 Jul;58(7):356-83. doi: 10.1007/s11748-010-0604-0.
Abstract/Text
PMID 20628854
A Masaoka, Y Monden, K Nakahara, T Tanioka
Follow-up study of thymomas with special reference to their clinical stages.
Cancer. 1981 Dec 1;48(11):2485-92.
Abstract/Text Follow-up data were obtained for 96 cases of thymoma. The one-year survival rate was 84.3%, the three-year 77.1%, the five-year 74.1%, and the ten-year 57.1%. The five-year survival rate of total resection group was 88.9%; that of non-radically treated group was 44.4%. Clinical stages were defined: Stage I--macroscopically encapsulated and microscopically no capsular invasion; Stage II--1. macroscopic invasion into surrounding fatty tissue of mediastinal pleura, or 2. microscopic invasion into capsule; Stage III--macroscopic invasion into neighboring organ; Stage IVa--pleural or pericardial dissemination; Stage IVb--lymphogenous or hematogenous metastasis. Five-year survival rates of each clinical stage were 92.6% in Stage I, 85.7% in Stage II, 69.6% in Stage III, and 50% in Stage IV. Recurrence after total resection was found in six of 69 cases. Seven of 13 patients treated by subtotal resection survived more than five years with postoperative radiotherapy.

PMID 7296496
Anya M Litvak, Kaitlin Woo, Sara Hayes, James Huang, Andreas Rimner, Camelia S Sima, Andre L Moreira, Maria Tsukazan, Gregory J Riely
Clinical characteristics and outcomes for patients with thymic carcinoma: evaluation of Masaoka staging.
J Thorac Oncol. 2014 Dec;9(12):1810-5. doi: 10.1097/JTO.0000000000000363.
Abstract/Text BACKGROUND: Thymic carcinomas are rare cancers with limited data regarding outcomes, particularly for those patients with advanced disease.
METHODS: We identified patients with thymic carcinomas diagnosed between 1993 and 2012. Patient characteristics, recurrence-free survival (RFS), and overall survival (OS) were analyzed.
RESULTS: One hundred twenty-one patients with thymic carcinomas were identified. Higher Masaoka stage was associated with worse OS and RFS (5-year OS of 100%, 81%, 51%, 24%, and 17% for stage I, II, III, IVa, and IVb respectively, p < 0.001 and 5-year RFS of 80%, 28%, and 7% for stage I/II, III, and IV respectively, p < 0.001). Patients with stage IVb lymph node (LN) only disease had a better 5-year OS as compared with patients with distant metastasis (24% versus 7%, p = 0.025). Of the 61 patients with stage IVb disease, 22 of 29 patients (76%) with LN-only disease underwent curative intent resection versus 3 of 32 patients (9%) with distant metastasis. Twenty-two patients with LN involvement were treated with multimodality therapy. Three (14%) remain free of disease with long-term follow-up (range, 3.4+ years- to 6.8+ years).
CONCLUSIONS: We describe the clinical features of a large series of patients with thymic carcinoma in North America. The Masaoka staging system effectively prognosticated OS and RFS. Patients with stage IVb LN-only disease had significantly better OS as compared with patients with distant metastasis with a subset of patients sustaining long-term RFS with multimodality therapy. If validated, these data would support a revised staging system with subclassification of stage IVb disease into two groups.

PMID 25393794
Kohei Yokoi, Haruhisa Matsuguma, Rie Nakahara, Tetsuro Kondo, Yukari Kamiyama, Kiyoshi Mori, Naoto Miyazawa
Multidisciplinary treatment for advanced invasive thymoma with cisplatin, doxorubicin, and methylprednisolone.
J Thorac Oncol. 2007 Jan;2(1):73-8. doi: 10.1097/JTO.0b013e31802bafc8.
Abstract/Text BACKGROUND AND OBJECTIVES: Advanced invasive thymomas are not usually manageable by surgical resection and radiotherapy. We reviewed our experience with a multidisciplinary approach and evaluated chemotherapy in the treatment of invasive thymoma.
PATIENTS AND METHODS: Seventeen consecutive patients with invasive thymoma were treated with multimodality therapy consisting of chemotherapy, surgery, and/or radiotherapy. Four patients had stage III disease with superior vena cava invasion, nine had stage IVa disease, and four had stage IVb disease. The chemotherapy regimen consisted of cisplatin, doxorubicin, and methylprednisolone (CAMP). Chemotherapy was administered in a neoadjuvant setting to the 14 patients and in an adjuvant setting to the remaining three patients. Surgical resection was intended in all patients. After those treatments, chemotherapy and/or radiation therapy were performed.
RESULTS: All but one of the 14 patients with induction chemotherapy responded to the CAMP therapy, and the response rate was 92.9%. Seven of these patients underwent complete remission after surgical resection and chemoradiotherapy, and the others underwent partial remission. All three patients treated with surgical resection and then chemotherapy with or without radiotherapy also achieved complete remission. Tumor progression after multimodality therapy occurred in 10 patients. After retreatment, eight of these patients were alive at the time of analysis, with a median survival time after recurrence of 30 months. The 5- and 10-year overall survival rates for all patients were both 80.7%. The major side effect of CAMP therapy was acceptable neutropenia.
CONCLUSIONS: CAMP therapy was highly effective for invasive thymomas, and the multimodality therapy containing this chemotherapy brought about good disease control in the majority of patients. We believe that this multidisciplinary treatment with CAMP therapy, surgery, and radiotherapy is a justifiable initial treatment for patients with advanced invasive thymoma. Furthermore, appropriate treatments are essential for the long-term survival of patients with recurrences after multimodality therapy.

PMID 17410014
A Fornasiero, O Daniele, C Ghiotto, M Piazza, L Fiore-Donati, F Calabró, F Rea, M V Fiorentino
Chemotherapy for invasive thymoma. A 13-year experience.
Cancer. 1991 Jul 1;68(1):30-3.
Abstract/Text From 1977 to 1990, 37 patients with Stage III or IV invasive thymoma (20 men and 17 women; median age, 40 years of age) were referred for chemotherapy to the Padova Medical Oncology Department. All patients initially received the same regimen (50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously (IV) on day 1, 0.6 mg/m2 of vincristine IV on day 3, and 700 mg/m2 of cyclophosphamide IV on day 4 [ADOC]), recycling at monthly intervals. No life-threatening side effects were noted. The overall clinical response rate (complete response plus partial response) was 91.8%, with 43% complete remissions. Median duration of response and survival were 12 months (range, 2 to 96+ months) and 15 months (range, 5 to 96+ months), respectively. Seven of the 16 complete remissions were pathologically confirmed at subsequent thoracotomy. Other chemotherapy combinations and radiation therapy have been applied as second-line treatment, achieving only minimal responses. In the opinion of the authors, such chemotherapy deserves evaluation for adjuvant and neo-adjuvant treatment of invasive (and/or inoperable) thymoma due to the high complete response rate and overall response rate.

PMID 2049749
Kazuya Kondo, Yasumasa Monden
Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan.
Ann Thorac Surg. 2003 Sep;76(3):878-84; discussion 884-5.
Abstract/Text BACKGROUND: Surgery remains the mainstay of treatment for thymic epithelial tumors, and radiation and chemotherapy also have been applied widely as adjuvant and palliative procedures.
METHODS: We compiled records of 1,320 patients with thymic epithelial tumors who were treated from 1990 to 1994 in 115 institutes certified as special institutes for general thoracic surgery by The Japanese Association for Chest Surgery.
RESULTS: Patients with stage I thymoma were treated with only surgery, and patients with stage II and III thymoma and thymic carcinoid underwent surgery and additional radiotherapy. Patients with stage IV thymoma and thymic carcinoma were treated with radiation or chemotherapy. The Masaoka clinical stage is an excellent predictor of the prognosis of thymoma and thymic carcinoma, but not thymic carcinoid. In stage III and IV thymoma, the 5-year survival rates of total resection, subtotal resection, and inoperable groups were 93%, 64%, and 36%, respectively. On the other hand, in thymic carcinoma, the 5-year survival rates of total resection, subtotal resection, and inoperable groups were 67%, 30%, and 24%, respectively. Prophylactic mediastinal radiotherapy could not prevent local recurrences effectively in patients with totally resected stage II and III thymoma. Adjuvant therapy including radiation or chemotherapy did not improve the prognosis in patients with totally resected III and VI thymoma and thymic carcinoma.
CONCLUSIONS: Total resection is the most important factor in the treatment of thymic epithelial tumors. There is value in debulking surgery in invasive thymoma, but not in thymic carcinoma. We doubt that adjuvant therapy is valuable for patients with totally resected invasive thymoma and thymic carcinoma.

PMID 12963221
James Huang, Nabil P Rizk, William D Travis, Venkatraman E Seshan, Manjit S Bains, Joseph Dycoco, Robert J Downey, Raja M Flores, Bernard J Park, Valerie W Rusch
Feasibility of multimodality therapy including extended resections in stage IVA thymoma.
J Thorac Cardiovasc Surg. 2007 Dec;134(6):1477-83; discussion 1483-4. doi: 10.1016/j.jtcvs.2007.07.049. Epub 2007 Oct 26.
Abstract/Text OBJECTIVE: Extended resections for advanced-stage thymomas are not commonly performed because of the potential morbidity in the face of unclear survival or palliative benefit. We reviewed our experience with multimodality treatment for Masaoka stage IVA thymomas for feasibility and outcomes.
METHODS: We conducted a retrospective review of a single-institution surgical database. Data included patient demographics, preoperative staging and treatment, perioperative events, pathologic findings, and postoperative outcomes.
RESULTS: During the period from 1996 to 2006, 18 patients who had Masaoka stage IVA thymoma underwent surgical resection. All patients received preoperative chemotherapy. Four patients with extensive pleural involvement underwent concomitant extrapleural pneumonectomy and postoperative hemithoracic radiation. Complete resection was achieved in 12 (67%) patients. There was no operative mortality. With a median follow-up of 32.2 months (range 1.4-129.9 months), 3-year, 5-year, and 10-year survivals were 91%, 78%, and 65%, respectively, and median survival has not yet been reached.
CONCLUSION: Multimodality therapy including extended surgical resection can be performed in select patients with stage IVA thymoma with low morbidity and mortality and can result in excellent long-term survival.

PMID 18023668
F Hirai, T Yamanaka, K Taguchi, H Daga, A Ono, K Tanaka, Y Kogure, J Shimizu, T Kimura, J Fukuoka, Y Iwamoto, H Sasaki, K Takeda, T Seto, Y Ichinose, K Nakagawa, Y Nakanishi, West Japan Oncology Group
A multicenter phase II study of carboplatin and paclitaxel for advanced thymic carcinoma: WJOG4207L.
Ann Oncol. 2015 Feb;26(2):363-8. doi: 10.1093/annonc/mdu541. Epub 2014 Nov 17.
Abstract/Text BACKGROUND: Thymic carcinoma (TC) is an exceptionally rare tumor, which has a very poor prognosis differing from thymoma. Till date, there has been no report of any results of clinical trials focusing on TC. The role of non-anthracycline-based chemotherapy has not been elucidated since the previous studies included a relatively small number of TC patients. This single-arm study evaluated carboplatin and paclitaxel (CbP) in chemotherapy-naive patients with advanced TC.
PATIENTS AND METHODS: The study treatment consisted of carboplatin (area under the curve 6) and paclitaxel (200 mg/m(2)) every 3 weeks for a maximum of six cycles. The primary end point was objective response rate (ORR) by independent review. The secondary end points included overall survival (OS), progression-free survival (PFS), and safety. Based on the SWOG 2-stage design, the planned sample size of 40 patients was determined to reject the ORR of 20% under the expectation of 40% with a power of 0.85 and a type I error of 0.05.
RESULTS: Forty patients from 21 centers were enrolled for this study from May 2008 to November 2010. Of the 39 patients evaluable for analysis, 36 were pathologically diagnosed by independent review, and 97% patients were eventually TC. There was 1/13 complete/partial responses with an ORR of 36% (95% confidence interval 21%-53%; P = 0.031). The median PFS was 7.5 (6.2-12.3) months, while OS did not reach the median value. Major adverse event was grade 3-4 neutropenia in 34 patients (87%). There was no treatment-related death.
CONCLUSIONS: In this largest trial with TC, CbP showed promising efficacy in advanced TC when compared with anthracycline-based chemotherapy, which is the current standard treatment of thymic neoplasm. Our results established that CbP, one of the standard treatments for non-small-cell lung cancer, might be an option as a chemotherapy regimen for TC.

© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
PMID 25403584
Akira Inoue, Shunichi Sugawara, Masao Harada, Kunihiko Kobayashi, Toshiyuki Kozuki, Shoichi Kuyama, Makoto Maemondo, Hajime Asahina, Akiko Hisamoto, Taku Nakagawa, Katsuyuki Hotta, Toshihiro Nukiwa
Phase II study of Amrubicin combined with carboplatin for thymic carcinoma and invasive thymoma: North Japan Lung Cancer group study 0803.
J Thorac Oncol. 2014 Dec;9(12):1805-9. doi: 10.1097/JTO.0000000000000362.
Abstract/Text BACKGROUND: There has been no standard chemotherapy for advanced or recurrent thymic malignancies including thymic carcinoma (TC) and invasive thymoma (IT), though platinum and anthracycline have been reported as effective agents for the treatment of these diseases. The objective of this study was to evaluate the efficacy and safety of the combination of amrubicin (AMR), a new anthracycline agent, and carboplatin (CBDCA) in patients with advanced thymic malignancies.
METHODS: Patients with histologically confirmed thymic malignancies received AMR (35 mg/m, days 1-3) and CBDCA (area under the curve 4.0, day 1) every 3 weeks. Patients who had received previous chemotherapy were treated with a reduced dose of AMR (30 mg/m). The primary end point was objective response rate (ORR), and secondary endpoints were progression-free survival, overall survival, and toxicity profile.
RESULTS: From December 2008 to October 2012, 51 patients (33 TC and 18 IT) were enrolled. The median number of treatment cycles was four in each group. The ORR and progression-free survival were 30% (95% confidence interval, 14-46) and 7.6 months in the TC group, and 17% (95% confidence interval, 0-34) and 7.6 months in the IT group, respectively. The ORR of TC patients without previous chemotherapy (n = 19) was 42%. Although grade 3 or 4 hematological toxicities were common including neutropenia (82%) and febrile neutropenia (22%), these were transient and manageable. Nonhematological toxicities were moderate and no treatment-related death was observed.
CONCLUSIONS: The combination of AMR with CBDCA was active for TC with acceptable toxicity, although it was not effective for IT. Further investigation of this regimen for advanced TC is warranted.

PMID 25393793
Jun Sato, Miyako Satouchi, Shoichi Itoh, Yusuke Okuma, Seiji Niho, Hidenori Mizugaki, Haruyasu Murakami, Yasuhito Fujisaka, Toshiyuki Kozuki, Kenichi Nakamura, Yukari Nagasaka, Mamiko Kawasaki, Tomoaki Yamada, Ryunosuke Machida, Aya Kuchiba, Yuichiro Ohe, Noboru Yamamoto
Lenvatinib in patients with advanced or metastatic thymic carcinoma (REMORA): a multicentre, phase 2 trial.
Lancet Oncol. 2020 Jun;21(6):843-850. doi: 10.1016/S1470-2045(20)30162-5.
Abstract/Text BACKGROUND: Thymic carcinoma is a rare malignant disease and standard treatment for advanced or metastatic thymic carcinoma previously treated with platinum-based chemotherapy has not been established. Lenvatinib is a novel multi-targeted inhibitor of VEGFR, FGFR, RET, c-Kit, and other kinases. The aim of this trial was to assess the activity and safety of lenvatinib as a second-line treatment in thymic carcinoma.
METHODS: This single-arm, phase 2 trial done in eight institutions in Japan (five cancer centres, two medical university hospitals, and one public hospital) enrolled patients with pathologically confirmed unresectable advanced or metastatic thymic carcinoma that progressed following at least one platinum-based chemotherapy. Key inclusion criteria were age 20 years or older, at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors version 1.1, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 24 mg of lenvatinib orally once daily in 4-week cycles until disease progression or occurrence of unacceptable adverse events. The primary endpoint was objective response rate evaluated at the data cutoff date (Feb 22, 2019), by independent central review in the intention-to-treat population. This trial is registered on JMACCT, JMA-IIA00285, and on UMIN-CTR, UMIN000026777.
FINDINGS: Between April 21, 2017, and Feb 22, 2018, 42 patients were enrolled and all patients were included in the activity and safety analysis. The median follow-up period was 15·5 months (IQR 13·1-17·5). The objective response rate was 38% (90% CI 25·6-52·0, p<0·0001). 16 (38%) of 42 patients had a partial response and 24 (57%) had stable disease. The most frequent grade 3 treatment-related adverse events were hypertension (27 [64%]) and palmar-plantar erythrodysaesthesia syndrome (three [7%]). No patient died from adverse events.
INTERPRETATION: The activity and safety of lenvatinib in patients with advanced or metastatic thymic carcinoma was confirmed. These results suggest that lenvatinib could become a standard treatment option for patients with previously treated advanced or metastatic thymic carcinoma.
FUNDING: Center for Clinical Trials, Japan Medical Association.

Copyright © 2020 Elsevier Ltd. All rights reserved.
PMID 32502444
Olumide B Gbolahan, Ryan F Porter, John T Salter, Constantin Yiannoutsos, Matthew Burns, E Gabriella Chiorean, Patrick J Loehrer
A Phase II Study of Pemetrexed in Patients with Recurrent Thymoma and Thymic Carcinoma.
J Thorac Oncol. 2018 Dec;13(12):1940-1948. doi: 10.1016/j.jtho.2018.07.094. Epub 2018 Aug 16.
Abstract/Text INTRODUCTION: Thymoma and thymic carcinoma (TC) are neoplastic diseases with reported chemosensitivity to a broad range of agents. However, because of the rarity of these diseases, few prospective trials have been conducted in patients with advanced thymic malignancies. We conducted a prospective phase II trial to evaluate the clinical activity of pemetrexed, a multitargeted antifolate agent, in previously treated patients with thymoma and TC.
METHODS: A total of 27 previously treated patients (16 with thymoma and 11 with TC) with advanced, unresectable disease were treated with pemetrexed, 500 mg/m2, intravenously every 3 weeks for a maximum of six cycles or until undue toxicity or progressive disease. All patients received folic acid, vitamin B12, and steroid prophylaxis.
RESULTS: The median number of cycles administered was 6 (range 1-6). Nine patients with a total of 14 events had grade 3 toxicities; no grade 4 toxicities were noted. In 26 fully evaluable patients, two complete and three partial responses (according to the Response Evaluation Criteria in Solid Tumors) were documented (all in patients with stage IVA thymoma, except for one partial response with stage IVA TC). A total of 14 patients completed the full six cycles of treatment, 7 patients progressed while undergoing therapy, 5 patients discontinued therapy because of intolerance, and 1 patient discontinued therapy because of progressive Morvan syndrome. The median progression-free survival time for all patients was 10.6 months (12.1 months for those with thymoma versus 2.9 months for those with TC). With 23 deaths at data cutoff, the median overall survival time was 28.7 months (46.4 months for those with thymoma versus 9.8 months for those with TC).
CONCLUSIONS: Pemetrexed is an active agent in this heavily pretreated population of patients with recurrent thymic malignancies, especially thymoma.

Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
PMID 30121390
Jessica A Hellyer, Matthew A Gubens, Kristen M Cunanan, Sukhmani K Padda, Matthew Burns, A John Spittler, Jonathan W Riess, Melanie San Pedro-Salcedo, Kavitha J Ramchandran, Joel W Neal, Heather A Wakelee, Patrick J Loehrer
Phase II trial of single agent amrubicin in patients with previously treated advanced thymic malignancies.
Lung Cancer. 2019 Nov;137:71-75. doi: 10.1016/j.lungcan.2019.09.015. Epub 2019 Sep 18.
Abstract/Text OBJECTIVES: There are limited treatment options for patients with thymic malignancies. Here we present data supporting treatment with single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor.
MATERIALS AND METHODS: This was a phase 2 open-label, single arm trial of amrubicin in patients with thymoma (T) or thymic carcinoma (TC), conducted at two academic institutions. Patients were included if they had received at least one prior chemotherapy regimen. The first 18 patients received amrubicin at 40 mg/m2 IV days 1-3 repeated every 3-weeks. Due to the high incidence of febrile neutropenia, dosing was subsequently amended to 35 mg/m2 for the final 15 patients.
RESULTS: A total of 33 patients (14 T/19 TC) were enrolled from 2011 to 2014. Median number of prior therapies was 2. Best response included 6 partial responses, 21 stable disease, and 6 progressive disease (all TC). Objective response rate was 18% (90% exact binomial CI 8.2%-32.8%; T = 4/14 (29%), TC = 2/19 (11%)). Median progression-free survival was 7.7 months (T: 8.3 months; TC: 7.3) and median overall survival was 29.7 months (T: 54.1 months; TC: 18 months). There was a high rate of febrile neutropenia (7 patients) that occurred despite a reduction in amrubicin dose and one related death. Five patients had reduction in LVEF below 50% during the course of treatment resulting in treatment discontinuation in one patient.
CONCLUSION: Amrubicin shows promise as a single agent in heavily pre-treated patients with thymic malignancies. Notable side effects include febrile neutropenia and the use of growth factor support is essential. Further investigation of this agent is warranted.

Copyright © 2019 Elsevier B.V. All rights reserved.
PMID 31557562
Yusuke Okuma, Yasushi Goto, Fumiyoshi Ohyanagi, Kuniko Sunami, Yoshiro Nakahara, Satoru Kitazono, Keita Kudo, Yuichi Tambo, Shintaro Kanda, Noriko Yanagitani, Atsushi Horiike, Hidehito Horinouchi, Yutaka Fujiwara, Hiroshi Nokihara, Noboru Yamamoto, Makoto Nishio, Yuichiro Ohe, Yukio Hosomi
Phase II trial of S-1 treatment as palliative-intent chemotherapy for previously treated advanced thymic carcinoma.
Cancer Med. 2020 Oct;9(20):7418-7427. doi: 10.1002/cam4.3385. Epub 2020 Aug 19.
Abstract/Text Thymic carcinoma (TC) is a rare cancer with minimal evidence of survival following palliative-intent chemotherapy. Sunitinib, everolimus, and pembrolizumab have been proposed as active agents based on previous phase II trials. In this phase II study, TC patients previously treated with platinum-based chemotherapy were enrolled. The patients received S-1 orally twice daily at a dose of 40-60 mg/m2 for 4 weeks, followed by 2 weeks off until the progression of the disease or the presence of unacceptable toxicities. The primary endpoint was the objective response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. The sample size of 26 patients was planned to reject the ORR of 10% under the expectation of 30% with a power of 0.80 and a type I error of 0.05 (one-sided). Twenty-six patients were recruited between 2013 and 2016; 23 patients had squamous cell carcinoma and 10 had an ECOG performance status of 0. One patient showed complete response and seven patients showed partial responses, resulting in a 30.8% response rate (90% confidence interval [CI], 18.3-46.9) and an 80.8% disease control rate (90% CI, 65.4-90.3). The median PFS was 4.3 months (95% CI, 2.3-10.3 months) and median OS was 27.4 months (95% CI, 16.6-34.3). Adverse events of grade ≥ 3 included neutropenia (12%), skin rash (8%), elevated alanine aminotransferase, and fatigue (4%). No treatment-related death was observed. S-1 confirmed clinical activity with tolerability in patients with previously treated TC. (UMIN000010736).

© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PMID 32813912
Bryan M Burt, Duy Nguyen, Shawn S Groth, Nihanth Palivela, R Taylor Ripley, Konstantinos I Makris, Farhood Farjah, Lorraine Cornwell, Nader N Massarweh
Utilization of Minimally Invasive Thymectomy and Margin-Negative Resection for Early-Stage Thymoma.
Ann Thorac Surg. 2019 Aug;108(2):405-411. doi: 10.1016/j.athoracsur.2019.03.010. Epub 2019 Apr 3.
Abstract/Text BACKGROUND: Minimally invasive thymectomy (MIT) has demonstrated improved short-term outcomes compared with open thymectomy (OT). Although adoption of MIT for thymoma is increasing, oncologic outcomes have not been well characterized.
METHODS: This was a retrospective cohort study of adult patients from the National Cancer Database who underwent MIT or OT for Masaoka stage I to II thymoma between 2010 and 2014. The primary outcome was R0 resection. Secondary outcomes included MIT use, perioperative mortality, and length of stay.
RESULTS: Nine hundred forty-three patients from 395 hospitals underwent thymectomy for stage I to II thymoma. MIT was performed in 31.3% (59.7% robotic, 40.3% thoracoscopic). Over the study period MIT utilization increased from 21.0% to 40.2% (trend test, p < 0.001). R0 resection was achieved in 83.1% of MITs (86.6% stage I, 72.7% stage II) and 79% of OTs (85.5% stage I, 65.8% stage II). In multivariable analyses, the likelihood of incomplete resection (R1/2) was associated with stage II tumors (odds ratio, 2.51) and World Health Organization B3 histology (odds ratio, 3.66). R0 resection was not associated with surgical approach (p = 0.17) and did not vary with tumor size (trend test, p = 0.90). Mortality rates at 30 and 90 days were 0% and 0.5%, respectively. MIT was associated with significantly shorter lengths of stay than OT (-1.03 days [95% confidence interval, -1.68 to -0.38]).
CONCLUSIONS: The use of MIT for resection of early-stage thymoma is increasing and is not associated with lower rates of R0 resection than OT. Reasons for the relatively low rates of R0 resection among all thymectomies requires further investigation, and long-term outcomes data are needed to better define the oncologic effectiveness of MIT.

Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
PMID 30953650
Mohamed K Kamel, Jonathan Villena-Vargas, Mohamed Rahouma, Benjamin Lee, Sebron Harrison, Brendon M Stiles, Abdelrahman M Abdelrahman, Nasser K Altorki, Jeffery L Port
National trends and perioperative outcomes of robotic resection of thymic tumours in the United States: a propensity matching comparison with open and video-assisted thoracoscopic approaches†.
Eur J Cardiothorac Surg. 2019 Oct 1;56(4):762-769. doi: 10.1093/ejcts/ezz111.
Abstract/Text OBJECTIVES: Despite the recent increased rate of adoption of robotic approaches for the resection of thymic tumours, their use is still limited to large-volume academic centres. To date, a large-scale analysis of the robotic approach has not been performed. We assessed the recent trends and outcomes of robotic thymectomies in the United States compared to those of open and video-assisted thoracoscopic surgical (VATS) approaches.
METHODS: The National Cancer Database was queried for patients who underwent resection for thymic tumours (2010-2014). Predictors of using the robotic approach were estimated by logistic regression analysis. Propensity matching analysis (robotic versus open and robotic versus VATS) was done (1:1-caliper 0.05), controlling for age, gender, comorbidity index, induction treatment, tumour size and tumour extension.
RESULTS: A total of 2558 thymectomies were performed (robotic = 300, VATS = 280, open = 1978). The use of a robotic approach increased from 6% (2010) to 14% (2014). The number of hospitals performing at least 1 robotic thymectomy increased from 22 (2010) to 52 (2014). Independent predictors influencing the choice of a robotic approach included an academic research/integrated cancer programme [odds ratio (OR) 1.66, confidence interval (CI) 1.22-2.27], later year of diagnosis (2014; OR 2.23, CI 1.31-3.80) and a patient's race (Asian) (OR 1.68, CI 1.05-2.69). A robotic approach was less likely to be utilized in midwestern hospitals (OR 0.65, CI 0.42-0.99), in larger tumours (cm) (OR 0.85, CI 0.80-0.90), with invasion of adjacent organs (OR 0.55, CI 0.37-0.82), thymic carcinoma (OR 0.62, CI 0.40-0.97) and following induction chemotherapy (OR 0.22, CI 0.08-0.61). In a propensity-matched analysis, there were no differences in the incidence of positive margins, nodal dissection, 30-day readmission rates and 30-/90-day mortality rates between the groups. However, a robotic approach was associated with fewer conversions compared to VATS, with a trend towards a shorter length of stay compared to an open approach. There were no differences in the 5-year overall survival rate between the matched groups (robotic 93% vs VATS 94%; P = 0.571; robotic 91% vs open 80%; P = 0.094).
CONCLUSIONS: Over a 4-year study period, there was a significant increase in robotic utilization for thymectomies and an increase in the number of hospitals performing the procedure. In a matched analysis, a robotic approach was comparable to a VATS or an open approach. Current trends demonstrate increased robotic utilization for small thymomas with excellent perioperative results.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
PMID 31321412
持田製薬株式会社:抗悪性腫瘍剤ドキシル注20mg 適正使用ガイド.参照日(2022年3月30日).
Takeshi Nagata, Shiro Makutani, Hideo Uchida, Kimihiko Kichikawa, Munehiro Maeda, Tetsuya Yoshioka, Hiroshi Anai, Hiroshi Sakaguchi, Hitoshi Yoshimura
Follow-up results of 71 patients undergoing metallic stent placement for the treatment of a malignant obstruction of the superior vena cava.
Cardiovasc Intervent Radiol. 2007 Sep-Oct;30(5):959-67. doi: 10.1007/s00270-007-9088-4.
Abstract/Text PURPOSE: To retrospectively clarify the utility of metallic stent placement for the treatment of the malignant obstruction of the superior vena cava (SVC) in 71 patients with VC syndrome (SVCS) on the basis of long-term follow-up data.
MATERIALS AND METHODS: Seventy-one patients underwent stent placement and were followed until death. The applicability of the spiral Z-stent (S-Z-stent) mainly used the initial and follow-up results, stent placement for bilateral BCV obstruction and the value of concurrent anticancer therapy were studied.
RESULTS: The technical success rate was 100%, the initial clinical success rate was 87% (62/71), the primary clinical patency rate was 88% (57/65), and the secondary clinical patency rate was 95% (62/65). The obstruction rate of the stent was 12% (8/65), and an additional stent was useful for relief of recurrent SVCS. Survival of 57 patients in whom there was no recurrence of SVCS until death ranged from 1 week to 29 months (mean, 5.4 months and the S-Z-stent appeared to be suitable for the treatment of the malignant obstruction of SVC. Unilateral stent placement was effective for relief of SVCS with bilateral BCV obstruction. Patients who received concurrent anticancer therapy survived 2 months longer than those who did not.
CONCLUSION: Stent placement is an effective treatment for SVCS. Further, the utility of S-Z-stent for SVCS, an additional stent for recurrence, unilateral stent for patients with bilateral BCV obstruction, and anticancer therapy after stent placement were verified.

PMID 17546400

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