今日の臨床サポート

悪性中皮腫

著者: 中野孝司 国家公務員共済組合連合会 大手前病院

監修: 高橋和久 順天堂大学大学院

著者校正/監修レビュー済:2021/07/14
参考ガイドライン:
日本肺癌学会:肺癌診療ガイドライン 2020年版 悪性胸膜中皮腫・胸腺腫瘍含む
NCCN Guidelines:Malignant Pleural Mesothelioma Version 1.2021 – December 4, 2020
患者向け説明資料

概要・推奨   

  1. 悪性胸膜中皮腫壁側胸膜の中皮細胞に初発する難治性腫瘍であ石綿アスベスト曝露と密接に関連して発生する
  1. すべての胸膜を腫瘍化するように発育びまん性悪性胸膜中皮腫とも呼ばれる稀に限局性発育する
  1. 中皮腫は胸膜以外に腹膜心膜および精巣鞘膜に発生する胸膜発生が最も多い[1]
  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
  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
  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
  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ます。閲覧に
  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。
  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
  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
  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ます。
  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ま
  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
  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
閲覧にはご契
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。
※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、実際の保険適用の査定において保険適用及び保険適用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用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:
中野孝司 : 研究費・助成金など(株式会社クボタ)[2021年]
監修:高橋和久 : 講演料(アストラゼネカ(株),MSD(株),中外製薬(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(中外製薬(株),大鵬薬品工業(株),杏林製薬(株),サノフィ(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),帝人ファーマ(株))[2021年]

改訂のポイント:
  1. 日本肺癌学会悪性胸膜中皮腫診療ガイドライン(2020年版)、NCCN悪性胸膜中皮腫ガイドライン(Version 1, 2021)に基づき改定した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. アスベスト曝露を受けてから中皮腫が発症するまでの潜伏期間は約40年である。
  1. アスベストとは珪酸塩よりなる繊維状鉱物の総称で、角閃石石綿のクロシドライト(青石綿)とアモサイト(茶石綿)、蛇紋石石綿のクリソタイル(白石綿:温石綿ともいう)が断熱材などに広く利用されてきた。最も危険なアスベストはクロシドライトである。
  1. 一部の中皮腫は遺伝子変異が発症に関係している。生殖細胞系列(germline)にがん抑制遺伝子であるBAP1遺伝子に変異のある中皮腫多発家系があり[2]、中皮腫の他に腎癌、ぶどう膜黒色腫、皮膚黒色腫を併発することがある。BAP1 tumor predisposition syndrome(または BAP1 cancer syndrome)と呼ばれている。
  1. 中皮腫は急増する傾向があり、わが国の2019年の死亡数(1,466人)はICD-10が導入された1995年の3倍に増えている。2017年~2019年はやや減少しているが、増加は2027年まで続くと予測されている。
 
日本の中皮腫死亡の年次推移(1995~2019年)

ICD-10が導入された1995年の中皮腫死亡数は500人(男子356人、女子144人)であり、2019年は1,466人(男子1,220人、女子246人)に増加している。特に男子での増加が著しい。

出典

img1:  著者提供
 
 
 
  1. 男女比は5:1であり、男子での増加が目立っている。
  1. 世界的な増加傾向がみられるが、アスベスト消費を急速に減少させてから50年近くが経過した米国やスウェーデンでは減少に転じている。
  1. 中皮腫は胸膜(85.5%)以外に、腹膜(13.2%)、心膜(0.8%)、精巣鞘膜(0.5%)に発生する[1]
  1. 中皮腫の組織亜型には上皮型(epithelioid type、60%)、肉腫型(sarcomatoid type、10%)、およびそれらの混在する二相型(biphasic type、30%)がある。
  1. 胸膜腫瘍の組織分類(日本肺癌学会「肺癌診療ガイドライン2020年版」:
 
 
  1. 特殊亜型の線維形成型中皮腫(desmoplastic mesothelioma)は腫瘍組織の50%以上が線維組織で占められ、治療に抵抗しきわめて悪性であるが、良性石綿胸膜炎などの良性胸膜疾患に病理像が類似する。
  1. 日本肺癌学会「肺癌取扱い規約第8版」の中皮腫各組織亜型の定義:<図表>
  1. 二相型悪性胸膜中皮腫の病理像(HE染色):<図表>
  1. 線維形成型中皮腫(desmoplastic mesothelioma)の病理像(HE染色):<図表>
  1. 高分化乳頭状中皮腫は中年女性の腹膜に好発する低悪性度の中皮腫であるが、まれに胸膜に発生する。
  1. 腹膜中皮腫は胸膜中皮腫と全く同じものではない。腹膜中皮腫にはきわめて悪性のものから良性のものまで幅広い病態が含まれている。
  1. 腹膜中皮腫は全中皮腫の約10%を占める稀な腫瘍である。胸膜中皮腫に類似するところもあるが、明らかに異なる点がある。腹膜には高分化乳頭状中皮腫や中皮細胞で嚢胞壁が構成される多嚢胞性中皮腫が発生する。これらは若~中年女性に好発し、低悪性度~良性の経過を示す。一方、胸膜中皮腫と同様に悪性度の高い腹膜中皮腫がある。胸膜中皮腫と同様に三組織亜型に分類するが、肉腫型が非常に少ない。豪州の中皮腫登録では腹膜中皮腫に肉腫型はなく、Yanらの報告では肉腫型はない[3]。アスベスト曝露に関しては、腹膜中皮腫は胸膜中皮腫よりも曝露歴を有する比率が低い反面、曝露歴がある場合は明らかに高濃度曝露である。アスベスト工場では腹膜にも多くの中皮腫が発生する。
  1. すべての中皮腫は公的救済の対象となり、アスベスト関連職歴のある場合は労務災害として、それ以外は石綿健康被害救済制度で給付を受けることができる。環境再生保全機構、環境省地方環境事務所、保健所などに問い合わせる必要がある。
 
問診・診察のポイント  
問診のポイント:
  1. 職業歴、居住歴などアスベスト曝露に関わる問診は必須である。

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。

まずは15日間無料トライアル
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: Kenichi Gemba, Nobukazu Fujimoto, Katsuya Kato, Keisuke Aoe, Yukio Takeshima, Kouki Inai, Takumi Kishimoto
雑誌名: Cancer Sci. 2012 Mar;103(3):483-90. doi: 10.1111/j.1349-7006.2011.02165.x. Epub 2012 Jan 9.
Abstract/Text In the present study, malignant mesothelioma (MM) cases in Japan were investigated retrospectively. We extracted records for 6030 cases of death due to MM between 2003 and 2008 to clarify the clinical features of MM, including its association with asbestos exposure (AE). Of all these cases, a clinical diagnosis of MM was confirmed for 929. The origin of MM included the pleura in 794 cases (85.5%), the peritoneum in 123 cases (13.2%), the pericardium in seven cases (0.8%), and the testicular tunica vaginalis in five cases (0.5%). The histological subtypes of MM included 396 epithelioid (55.9%), 154 sarcomatoid (21.7%), 126 biphasic (17.8%), and 33 cases (4.7%) classified as "other types". Of all the MM cases, AE was indicated in 76.8% and pleural plaques were detected in 34.2%. The number of asbestos particles was determined in 103 cases of MM. More than 1000 asbestos particles per gram dried lung tissue were detected in 74.8% of cases and more than 5000 particles were detected in 43.7% of cases. We compared patient characteristics and the diagnostic procedures for MM before and after the "Kubota shock". Compared with the early phase of this study (2003-2005), the median age at diagnosis of MM was higher, the number of cases without definite diagnosis of MM was lower, the proportion of cases diagnosed by thoracoscopy was higher, and the percentage of cases in which the occupational history was described in the medical records was significantly higher in the later phase (2006-2008). Our study confirmed that more than 70% of MM cases in Japan are associated with AE. The "Kubota shock" may affect some features pertaining to MM.

© 2011 Japanese Cancer Association.
PMID 22126592  Cancer Sci. 2012 Mar;103(3):483-90. doi: 10.1111/j.1349・・・
著者: Joseph R Testa, Mitchell Cheung, Jianming Pei, Jennifer E Below, Yinfei Tan, Eleonora Sementino, Nancy J Cox, A Umran Dogan, Harvey I Pass, Sandra Trusa, Mary Hesdorffer, Masaki Nasu, Amy Powers, Zeyana Rivera, Sabahattin Comertpay, Mika Tanji, Giovanni Gaudino, Haining Yang, Michele Carbone
雑誌名: Nat Genet. 2011 Aug 28;43(10):1022-5. doi: 10.1038/ng.912. Epub 2011 Aug 28.
Abstract/Text Because only a small fraction of asbestos-exposed individuals develop malignant mesothelioma, and because mesothelioma clustering is observed in some families, we searched for genetic predisposing factors. We discovered germline mutations in the gene encoding BRCA1 associated protein-1 (BAP1) in two families with a high incidence of mesothelioma, and we observed somatic alterations affecting BAP1 in familial mesotheliomas, indicating biallelic inactivation. In addition to mesothelioma, some BAP1 mutation carriers developed uveal melanoma. We also found germline BAP1 mutations in 2 of 26 sporadic mesotheliomas; both individuals with mutant BAP1 were previously diagnosed with uveal melanoma. We also observed somatic truncating BAP1 mutations and aberrant BAP1 expression in sporadic mesotheliomas without germline mutations. These results identify a BAP1-related cancer syndrome that is characterized by mesothelioma and uveal melanoma. We hypothesize that other cancers may also be involved and that mesothelioma predominates upon asbestos exposure. These findings will help to identify individuals at high risk of mesothelioma who could be targeted for early intervention.

PMID 21874000  Nat Genet. 2011 Aug 28;43(10):1022-5. doi: 10.1038/ng.9・・・
著者: T D Yan, E Popa, E A Brun, C A Cerruto, P H Sugarbaker
雑誌名: Br J Surg. 2006 Dec;93(12):1536-42. doi: 10.1002/bjs.5377.
Abstract/Text BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is rare and in the past has proved an invariably fatal disease. Female patients have been reported to have an improved survival outcome for reasons that are not understood.
METHODS: The survival of 34 men and 28 women who underwent cytoreduction and perioperative intraperitoneal chemotherapy for DMPM was compared. Twenty-five clinicopathological variables were subjected to univariate analysis.
RESULTS: The women had a 5-year survival rate of 63 per cent and median survival was not reached. The men had a 5-year survival rate of 42 per cent, with a median survival of 32 months (P = 0.045). Women had undergone more extensive previous surgery and had less extensive peritoneal involvement at the time of cytoreduction. Tumours in women more frequently showed a small nuclear size (30 microm or less) and the chromatin pattern was more often granular than clear.
CONCLUSION: Women with DMPM had better survival. This observation may be related to the favourable clinical and histopathological features associated with women.

PMID 17048277  Br J Surg. 2006 Dec;93(12):1536-42. doi: 10.1002/bjs.53・・・
著者: T Nakano, A P Chahinian, M Shinjo, A Tonomura, M Miyake, N Togawa, K Ninomiya, K Higashino
雑誌名: Br J Cancer. 1998 Mar;77(6):907-12.
Abstract/Text The relationship between interleukin 6 (IL-6) levels and clinical parameters was studied in 25 patients with malignant pleural mesothelioma. The serum levels of IL-6, C-reactive protein, alpha1-acid glycoprotein and fibrinogen were significantly higher in mesothelioma than in lung adenocarcinoma with cytology-positive pleural effusion. Serum IL-6 levels correlated with the levels of the acute-phase proteins. We demonstrated a high incidence of thrombocytosis (48%) and a significant correlation between platelet count and the serum IL-6 level. The level of IL-6 in the pleural fluid of patients with mesothelioma was significantly higher than in the pleural fluid of patients with adenocarcinoma, and was about 60-1400 times higher than in the serum. However, even higher levels of IL-6 in the pleural fluid and of thrombocytosis were found in patients with tuberculous pleurisy. These results indicate that large amounts of IL-6 from the pleural fluid of patients with mesothelioma leak into the systemic circulation and induce clinical inflammatory reactions. These profiles are not specific to mesothelioma as similar profiles are found in patients with tuberculous pleurisy. However, the detection of a markedly increased level of IL-6 in pleural fluid argues against a diagnosis of adenocarcinoma.

PMID 9528833  Br J Cancer. 1998 Mar;77(6):907-12.
著者: A Reid, N de Klerk, G Ambrosini, N Olsen, S C Pang, A W Musk
雑誌名: Occup Environ Med. 2005 Oct;62(10):665-9. doi: 10.1136/oem.2004.018531.
Abstract/Text AIMS: To examine the hypothesis that people with benign pleural disease or asbestosis have an increased risk of malignant mesothelioma beyond that attributable to their degree of asbestos exposure.
METHODS: Former workers and residents of the crocidolite mining and milling town of Wittenoom are participating in a cancer prevention programme (n = 1988). The first plain chest radiograph taken at the time of recruitment into the cancer prevention programme was read for evidence of benign pleural disease and asbestosis, using the UICC classification. Crocidolite exposure of former workers was derived from employment records and records of dust measurements performed during the operation of the asbestos mine and mill between 1943 and 1966. Based on fibre counts, exposure for former residents was determined using duration of residence and period of residence (before and after a new mill was commissioned in 1957) and interpolation from periodic hygienic measures undertaken from personal monitors between 1966 and 1992. Cox proportional hazards modelling was used to relate benign pleural disease, asbestosis, asbestos exposure, and mesothelioma.
RESULTS: Between 1990 and 2002, there were 76 cases of mesothelioma (56 of the pleura and 20 of the peritoneum). Cases had more radiographic evidence of (all) benign pleural disease, pleural thickening, blunt/obliterated costophrenic angle, and asbestosis than non-cases. Adjusting for time since first exposure (log years), cumulative exposure (log f/ml-years), and age at the start of the programme, pleural thickening (OR = 3.1, 95% CI 1.2 to 7.6) and asbestosis (OR = 3.3, 95% CI 1.3 to 8.6) were associated with an increased risk of peritoneal mesothelioma. There was no increased risk for pleural mesothelioma.
CONCLUSION: The presence of benign pleural disease, in particular pleural thickening, and asbestosis appears to increase the risk of mesothelioma of the peritoneum, but not of the pleura beyond that attributable to indices of asbestos exposure in this cohort of subjects exposed to crocidolite.

PMID 16169910  Occup Environ Med. 2005 Oct;62(10):665-9. doi: 10.1136/・・・
著者: Jean-Claude Pairon, François Laurent, Mickaël Rinaldo, Bénédicte Clin, Pascal Andujar, Jacques Ameille, Patrick Brochard, Soizick Chammings, Gilbert Ferretti, Françoise Galateau-Sallé, Antoine Gislard, Marc Letourneux, Amandine Luc, Evelyne Schorlé, Christophe Paris
雑誌名: J Natl Cancer Inst. 2013 Feb 20;105(4):293-301. doi: 10.1093/jnci/djs513. Epub 2013 Jan 25.
Abstract/Text BACKGROUND: The association between pleural plaques and pleural mesothelioma remains controversial. The present study was designed to examine the association between pleural plaques on computed tomography (CT) scan and the risk of pleural mesothelioma in a follow-up study of asbestos-exposed workers.
METHODS: Retired or unemployed workers previously occupationally exposed to asbestos were invited to participate in a screening program for asbestos-related diseases, including CT scan, organized between October 2003 and December 2005 in four regions in France. Randomized, independent, double reading of CT scans by a panel of seven chest radiologists focused on benign asbestos-related abnormalities. A 7-year follow-up study was conducted in the 5287 male subjects for whom chest CT scan was available. Annual determination of the number of subjects eligible for free medical care because of pleural mesothelioma was carried out. Diagnosis certification was obtained from the French mesothelioma panel of pathologists. Survival regression based on the Cox model was used to estimate the risk of pleural mesothelioma associated with pleural plaques, with age as the main time variable and time-varying exposure variables, namely duration of exposure, time since first exposure, and cumulative exposure index to asbestos. All statistical tests were two-sided.
RESULTS: A total of 17 incident cases of pleural mesothelioma were diagnosed. A statistically significant association was observed between mesothelioma and pleural plaques (unadjusted hazard ratio (HR) = 8.9, 95% confidence interval [CI] = 3.0 to 26.5; adjusted HR = 6.8, 95% CI = 2.2 to 21.4 after adjustment for time since first exposure and cumulative exposure index to asbestos).
CONCLUSION: The presence of pleural plaques may be an independent risk factor for pleural mesothelioma.

PMID 23355760  J Natl Cancer Inst. 2013 Feb 20;105(4):293-301. doi: 10・・・
著者: A Scherpereel, P Astoul, P Baas, T Berghmans, H Clayson, P de Vuyst, H Dienemann, F Galateau-Salle, C Hennequin, G Hillerdal, C Le Péchoux, L Mutti, J-C Pairon, R Stahel, P van Houtte, J van Meerbeeck, D Waller, W Weder, European Respiratory Society/European Society of Thoracic Surgeons Task Force
雑誌名: Eur Respir J. 2010 Mar;35(3):479-95. doi: 10.1183/09031936.00063109. Epub 2009 Aug 28.
Abstract/Text Malignant pleural mesothelioma (MPM) is a rare tumour but with increasing incidence and a poor prognosis. In 2008, the European Respiratory Society/European Society of Thoracic Surgeons Task Force brought together experts to propose practical and up-to-dated guidelines on the management of MPM. To obtain an earlier and reliable diagnosis of MPM, the experts recommend performing thoracoscopy, except in cases of pre-operative contraindication or pleural symphysis. The standard staining procedures are insufficient in approximately 10% of cases. Therefore, we propose using specific immunohistochemistry markers on pleural biopsies. In the absence of a uniform, robust and validated staging system, we advice use of the most recent TNM based classification, and propose a three step pre-treatment assessment. Patient's performance status and histological subtype are currently the only prognostic factors of clinical importance in the management of MPM. Other potential parameters should be recorded at baseline and reported in clinical trials. MPM exhibits a high resistance to chemotherapy and only a few patients are candidates for radical surgery. New therapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach should be included in a prospective trial at a specialised centre.

PMID 19717482  Eur Respir J. 2010 Mar;35(3):479-95. doi: 10.1183/09031・・・
著者: Aliya N Husain, Thomas V Colby, Nelson G Ordóñez, Thomas Krausz, Alain Borczuk, Philip T Cagle, Lucian R Chirieac, Andrew Churg, Francoise Galateau-Salle, Allen R Gibbs, Allen M Gown, Samuel P Hammar, Leslie A Litzky, Victor L Roggli, William D Travis, Mark R Wick
雑誌名: Arch Pathol Lab Med. 2009 Aug;133(8):1317-31. doi: 10.1043/1543-2165-133.8.1317.
Abstract/Text CONTEXT: Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose.
OBJECTIVE: To develop practical guidelines for the pathologic diagnosis of MM.
DATA SOURCES: A pathology panel was convened at the International Mesothelioma Interest Group biennial meeting (October 2006). Pathologists with an interest in the field also contributed after the meeting.
CONCLUSIONS: There was consensus opinion regarding (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid mesothelioma, (7) use of molecular markers in the differential diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels used is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Immunohistochemical panels should contain both positive and negative markers. The International Mesothelioma Interest Group recommends that markers have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic membranous markers). These guidelines are meant to be a practical reference for the pathologist.

PMID 19653732  Arch Pathol Lab Med. 2009 Aug;133(8):1317-31. doi: 10.1・・・
著者: V W Rusch
雑誌名: Chest. 1995 Oct;108(4):1122-8. doi: 10.1378/chest.108.4.1122.
Abstract/Text STUDY OBJECTIVE: Investigation of the behavior and treatment of the diffuse malignant pleural mesothelioma (MPM) is hindered by the lack of an accurate universally accepted staging system. To address this problem, the International Mesothelioma Interest Group (IMIG) has developed a new TNM-based staging system.
METHODS: The staging system was developed at a consensus meeting of IMIG members involved in clinical research in MPM, including the originators of previously proposed staging systems. The new staging system is based on the analysis of emerging information about the impact of T and N status on survival.
RESULTS: In contrast to five previous staging systems, the T descriptors designated as T1, T2, T3, and T4, provide precise anatomic definitions of the local extent of the primary tumor. The N descriptors, designated as N0, N1, N2, and N3, are virtually identical to those used in the International Lung Cancer Staging System. The stage groupings recognize new data about the better prognosis of T1 and N0 tumors and classify those tumors into stages I and II. The adverse impact of nodal metastases on survival noted in some recent surgical series warrants placing node-positive tumors in stage III. Locally advanced unresectable (T4) tumors and extrathoracic disease (N3 or M1) are classified as stage IV.
CONCLUSION: This proposed staging system reconciles and updates several earlier systems, and can provide the framework for analyzing the results of prospective clinical trials aimed at improving the currently dismal prognosis of MPM.

PMID 7555126  Chest. 1995 Oct;108(4):1122-8. doi: 10.1378/chest.108.4・・・
著者: Nicholas J Vogelzang, James J Rusthoven, James Symanowski, Claude Denham, E Kaukel, Pierre Ruffie, Ulrich Gatzemeier, Michael Boyer, Salih Emri, Christian Manegold, Clet Niyikiza, Paolo Paoletti
雑誌名: J Clin Oncol. 2003 Jul 15;21(14):2636-44. doi: 10.1200/JCO.2003.11.136.
Abstract/Text PURPOSE: Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone.
PATIENTS AND METHODS: Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1. Both regimens were given intravenously every 21 days.
RESULTS: A total of 456 patients were assigned: 226 received pemetrexed and cisplatin, 222 received cisplatin alone, and eight never received therapy. Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm (P =.020, two-sided log-rank test). The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77. Median time to progression was significantly longer in the pemetrexed/cisplatin arm: 5.7 months versus 3.9 months (P =.001). Response rates were 41.3% in the pemetrexed/cisplatin arm versus 16.7% in the control arm (P <.0001). After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxicity, resulting in a significant reduction in toxicities in the pemetrexed/cisplatin arm.
CONCLUSION: Treatment with pemetrexed plus cisplatin and vitamin supplementation resulted in superior survival time, time to progression, and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma. Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time.

PMID 12860938  J Clin Oncol. 2003 Jul 15;21(14):2636-44. doi: 10.1200/・・・
著者: V W Rusch, E Venkatraman
雑誌名: J Thorac Cardiovasc Surg. 1996 Apr;111(4):815-25; discussion 825-6. doi: 10.1016/s0022-5223(96)70342-2.
Abstract/Text OBJECTIVES: Progress in the therapy of malignant pleural mesothelioma is limited by the lack of an adequate staging system and controversy about prognostic factors. This surgical series was analyzed to determine whether a new TNM staging system proposed by the International Mesothelioma Interest Group and certain prognostic factors could stratify patients in future clinical trials.
METHODS: Thoracotomy was performed if computed tomographic scans showed resectable tumor confined to one hemithorax. Pleurectomy/decortication was done if visceral pleural tumor was minimal, and extrapleural pneumonectomy was done for more locally advanced disease. Complete resection was defined as no gross residual tumor. Adjuvant therapy was given as required by serial clinical trials. Patients had computed tomographic scans every 3 months until death. Prognostic factors were examined by log-rank and Cox regression analyses.
RESULTS: From October 1983 to July 1994, a total of 131 thoracotomies were performed, resulting in 101 resections, 72 of which were complete. Extrapleural pneumonectomy was done in 50 patients and pleurectomy/decortication in 51. The ratio of men to women was 108:23. Median age was 63 years (range 32 to 80 years). Operative mortality was five of 131 patients (3.8%), three of 50 in the group having extrapleural pneumonectomy (6%). Ninety-five of the 131 tumors were epithelial. Fifty-one of 89 patients (57%) having node dissections had diseased nodes, 45 (50%) N2. By univariate analysis, type of resection, T and N status, stage, histologic type, and adjuvant therapy, but no gender or age, significantly affected survival. Type of resection, stage, and histologic type were significant in a multivariate analysis. Local recurrence occurred mainly after pleurectomy/decortication, and distant metastases developed after extrapleural pneumonectomy.
CONCLUSIONS: (1) N2 nodal disease is more frequent than previously reported; (2) the prognostic importance of histologic type is confirmed; (3) both T and N status influence outcome, and the International Mesothelioma Interest Group staging system successfully identifies patients whose prognosis is poor; (4) despite more locally advanced disease in most patients with extrapleural pneumonectomy, that approach provided better local control than pleurectomy/decortication but failed to improve survival because of distant metastatic disease. Contrary to past practice, future clinical trials should stratify for histologic type, must control for TNM stage, and must consider the impact of type of surgical resection on the pattern of relapse.

PMID 8614142  J Thorac Cardiovasc Surg. 1996 Apr;111(4):815-25; discu・・・
著者: Bram Balduyck, Delphine Trousse, Apostolos Nakas, Antonio E Martin-Ucar, John Edwards, David A Waller
雑誌名: Ann Thorac Surg. 2010 Mar;89(3):907-11. doi: 10.1016/j.athoracsur.2009.12.041.
Abstract/Text BACKGROUND: Debate remains about the relative prognostic importance of the histologic subtype of malignant pleural mesothelioma.
METHODS: From a prospective database, the details of 312 malignant pleural mesothelioma surgical patients were reviewed. A comparison was made of the survival from the three major cell types.
RESULTS: One hundred ninety-five patients underwent radical surgery, and 117 underwent nonradical surgery. Final histologic subtype was epithelioid in 218 patients, biphasic in 66 patients, and sarcomatoid in 28 patients. The median survival was 15.3 months in the epithelioid group, 10.1 months in the biphasic group, and 5.0 months in the sarcomatoid group. On univariate analysis in the epithelioid group, age (p = 0.005), International Mesothelioma Interest Group stage (p = 0.001), radicality of the procedure (p = 0.001), leukocytosis (p = 0.016), and preoperative or postoperative chemotherapy (p = 0.012) were significant prognostic factors influencing postoperative survival. In the biphasic group, preoperative anemia was the only significant factor (p = 0.007). In sarcomatoid patients, International Mesothelioma Interest Group stage and radicality of the surgical procedure were significant prognostic variables (p = 0.012 and p = 0.015, respectively). Multivariate analysis in the epithelioid group identified International Mesothelioma Interest Group stage (p = 0.001), radicality of the procedure (p = 0.008), and preoperative or postoperative chemotherapy (p = 0.007) as significant prognostic factors, whereas in the sarcomatoid group, only the International Mesothelioma Interest Group stage (p = 0.012) was significant and the radicality of surgery had no effect.
CONCLUSIONS: The extremely poor prognosis of sarcomatoid malignant pleural mesothelioma is independent of the extent of surgery unlike other cell types. Patients with sarcomatoid histology should therefore be considered separately in trials evaluating radical procedures and adjuvant treatment. The treatment of biphasic pleural mesothelioma remains debatable.

2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
PMID 20172152  Ann Thorac Surg. 2010 Mar;89(3):907-11. doi: 10.1016/j.・・・
著者: Cecilia Bech, Jens Benn Sørensen
雑誌名: J Thorac Oncol. 2010 May;5(5):735-40. doi: 10.1097/jto.0b013e3181d86ea9.
Abstract/Text INTRODUCTION: Malignant pleural mesothelioma is a rare aggressive disease with a poor prognosis and usually modest responses to chemotherapy. Complete responses (CRs) to chemotherapy are rare. Evaluation is usually based on radiology, and CR is therefore clinical CR (cCR) and whether this indicates absence of viable tumor cells is unknown. We have observed two cases of CR which at subsequent surgery were histologically verified, thus being pathologic CRs (pCRs). pCR after chemotherapy is thus possible but rare, and we here present the cases from our institution together with a review on the literature available on the subject.
METHODS: A literature search using relevant keywords was performed in PubMed and MedLine.
RESULTS: A larger number of reports on cCR but only five reports on pCR were identified. All published cases of pCR, 16 patients in five trials, are presented and discussed, and larger trials reporting cCR are mentioned. pCR did not in all cases correspond to cCR. The cases having pCR identified all had the epithelial or unknown subtype, and all had early-stage disease before treatment.
CONCLUSION: pCR is possible but rare, and a pCR does not always require a cCR. So far reported cases of pCR have all had the epithelial or unknown subtype and pretreatment stages have been low. The cases in our institution also had epithelial subtype but had stage III disease ,and it thus seems possible to obtain a pCR despite a larger tumor burden.

PMID 20432521  J Thorac Oncol. 2010 May;5(5):735-40. doi: 10.1097/jto.・・・
著者: Andrea S Wolf, William G Richards, Tamara R Tilleman, Lucian Chirieac, Shelley Hurwitz, Raphael Bueno, David J Sugarbaker
雑誌名: Ann Thorac Surg. 2010 Sep;90(3):949-56; discussion 956. doi: 10.1016/j.athoracsur.2010.04.110.
Abstract/Text BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) is higher in men than in women, likely due to increased occupational asbestos exposure among men. Women also appear to experience better long-term survival. This study evaluates the role of gender in relation to established prognostic factors in MPM.
METHODS: We reviewed 715 cases of MPM treated with extrapleural pneumonectomy at our institution between July 1987 and December 2008. Data for patients with epithelial and nonepithelial tumors were analyzed separately. Kaplan-Meier and Cox regression analyses were used to estimate survival for various cohorts to assess the relationship between gender and survival independent of age at surgery, stage, side, and preoperative laboratory studies.
RESULTS: Of the 702 patients with complete data available, 114 out of 450 patients with epithelial tumors and 31 out of 252 patients with nonepithelial histology were women. Women with epithelial (and not nonepithelial) disease were found to differ significantly from men with respect to younger age, higher rate of thrombocytosis, and longer survival after surgery. The effect of gender on survival of patients with epithelial disease persisted when controlling for age, stage, thrombocytosis, leukocytosis, and anemia with a multivariable analysis. No significant differences in survival were seen among patients with nonepithelial disease with regard to gender, age, or anemia.
CONCLUSIONS: In the absence of other negative prognostic factors, women with epithelial MPM demonstrated a survival advantage. These findings support an aggressive approach to treating MPM including extrapleural pneumonectomy in individuals with favorable prognostic predictors, particularly women with epithelial histology and no other risk factors.

2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
PMID 20732523  Ann Thorac Surg. 2010 Sep;90(3):949-56; discussion 956.・・・
著者: Raja M Flores, Harvey I Pass, Venkatraman E Seshan, Joseph Dycoco, Maureen Zakowski, Michele Carbone, Manjit S Bains, Valerie W Rusch
雑誌名: J Thorac Cardiovasc Surg. 2008 Mar;135(3):620-6, 626.e1-3. doi: 10.1016/j.jtcvs.2007.10.054. Epub 2008 Feb 14.
Abstract/Text OBJECTIVE: The optimal procedure for resection of malignant pleural mesothelioma is controversial, partly because previous analyses include small numbers of patients. We performed a multi-institutional study to increase statistical power to detect significant differences in outcome between extrapleural pneumonectomy and pleurectomy/decortication.
METHODS: Patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy or pleurectomy/decortication at 3 institutions were identified. Survival and prognostic factors were analyzed by the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis.
RESULTS: From 1990 to 2006, 663 consecutive patients (538 men and 125 women) underwent resection. The median age was 63 years (range, 26-93 years). The operative mortality was 7% for extrapleural pneumonectomy (n = 27/385) and 4% for pleurectomy/decortication (n = 13/278). Significant survival differences were seen for American Joint Committee on Cancer stages 1 to 4 (P < .001), epithelioid versus non-epithelioid histology (P < .001), extrapleural pneumonectomy versus pleurectomy/decortication (P < .001), multimodality therapy versus surgery alone (P < .001), and gender (P < .001). Multivariate analysis demonstrated a hazard rate of 1.4 for extrapleural pneumonectomy (P < .001) controlling for stage, histology, gender, and multimodality therapy.
CONCLUSION: Patients who underwent pleurectomy/decortication had a better survival than those who underwent extrapleural pneumonectomy; however, the reasons are multifactorial and subject to selection bias. At present, the choice of resection should be tailored to the extent of disease, patient comorbidities, and type of multimodality therapy planned.

PMID 18329481  J Thorac Cardiovasc Surg. 2008 Mar;135(3):620-6, 626.e1・・・
著者: Joseph S Friedberg, Melissa J Culligan, Rosemarie Mick, James Stevenson, Stephen M Hahn, Daniel Sterman, Salman Punekar, Eli Glatstein, Keith Cengel
雑誌名: Ann Thorac Surg. 2012 May;93(5):1658-65; discussion 1665-7. doi: 10.1016/j.athoracsur.2012.02.009.
Abstract/Text BACKGROUND: Radical pleurectomy (RP) for mesothelioma is often considered either technically unfeasible or an operation limited to patients who would not tolerate a pneumonectomy. The purpose of this study was to review our experience using RP and intraoperative photodynamic therapy (PDT) for mesothelioma.
METHODS: Thirty-eight patients (42-81 years) underwent RP-PDT. Thirty five of 38 (92%) patients also received systemic therapy. Standard statistical techniques were used for analysis.
RESULTS: Thirty seven of 38 (97%) patients had stage III/IV cancer (according to the American Joint Committee on Cancer [AJCC manual 7th Edition, 2010]) and 7/38 (18%) patients had nonepithelial subtypes. Macroscopic complete resection was achieved in 37/38 (97%) patients. There was 1 postoperative mortality (stroke). At a median follow-up of 34.4 months, the median survival was 31.7 months for all 38 patients, 41.2 months for the 31/38 (82%) patients with epithelial subtypes, and 6.8 months for the 7/38 (18%) patients with nonepithelial subtypes. Median progression-free survival (PFS) was 9.6, 15.1, and 4.8 months, respectively. The median survival and PFS for the 20/31 (64%) patients with N2 epithelial disease were 31.7 and 15.1 months, respectively.
CONCLUSIONS: It was possible to achieve a macroscopic complete resection using lung-sparing surgery in 97% of these patients with stage III/IV disease. The survival we observed with this approach was unusually long for the patients with the epithelial subtype but, interestingly, the PFS was not. The reason for this prolonged survival despite recurrence is not clear but is potentially related to preservation of the lung or some PDT-induced effect, or both. We conclude that the results of this lung-sparing approach are safe, encouraging, and warrant further investigation.

Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
PMID 22541196  Ann Thorac Surg. 2012 May;93(5):1658-65; discussion 166・・・
著者: Imran Zahid, Sumera Sharif, Tom Routledge, Marco Scarci
雑誌名: Interact Cardiovasc Thorac Surg. 2011 May;12(5):812-7. doi: 10.1510/icvts.2010.256271. Epub 2011 Feb 22.
Abstract/Text A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether pleurectomy/decortication (P/D) is superior to palliative care in the treatment of patients with malignant pleural mesothelioma (MPM). Overall 80 papers were found using the reported search, of which 11 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results are tabulated. We conclude that P/D may lead to superior survival rates but at the expense of higher morbidity rates to palliative treatment. Six studies reported patient outcomes after use of radical P/D to treat patients with MPM. Radical P/D leads to a higher median survival than supportive care (14.5 vs. 4.5 months) and non-radical decortication (15.3 vs. 7.1 months, P < 0.000). However, radical P/D had a complication rate of 30%, hospital stay of 12 days with an operative mortality rate of 9.1%. One-year survival rate was 65% but this fell to 0-24% at three years. Three studies highlighted the use of palliative chemotherapy to manage patients with MPM. Median survival (14 vs. 10 months) was higher in patients who received chemotherapy early compared to those on a delayed protocol. Early chemotherapy had a longer time to disease progression (25 vs. 11 weeks, P = 0.1) and greater one-year survival (66% vs. 36%) than the delayed group. Active symptom control (ASC) alone had lower symptom control rates than the combination of ASC plus MVP (mitomycin+vinblastine+cisplatin) (7% vs. 11%, P = 0.0017) and ASC plus vinorelbine (4% vs. 7%, P = 0.047). Three studies reported results of palliative surgery in patients with known MPM. Median survival period was 213 days with a 30-day mortality rate of 7.8%. Survival rates reduced from 70.6% at three months to 25.5% at one-year post-surgery. Prolonged air-leak and postoperative empyema complicated 9.8% and 4% of patients, respectively. P/D is a morbid operation that is associated with significant perioperative mortality and complication rates. Although a number of retrospective studies have shown a small benefit in survival with P/D, the heavily documented similarity in patient outcomes between P/D and extrapleural pneumonectomy along with the results of the Mesothelioma and Radical Surgery trial, should induce the surgical community to consider the use of P/D only in patients with malignant mesothelioma enrolled in prospective trials.

PMID 21345818  Interact Cardiovasc Thorac Surg. 2011 May;12(5):812-7. ・・・
著者: David Rice, Valerie Rusch, Harvey Pass, Hisao Asamura, Takashi Nakano, John Edwards, Dorothy J Giroux, Seiki Hasegawa, Kemp H Kernstine, David Waller, Ramon Rami-Porta, International Association for the Study of Lung Cancer International Staging Committee and the International Mesothelioma Interest Group
雑誌名: J Thorac Oncol. 2011 Aug;6(8):1304-12. doi: 10.1097/JTO.0b013e3182208e3f.
Abstract/Text INTRODUCTION: Extrapleural pneumonectomy has been well defined; however, surgeons vary regarding the surgical extent and goals of "pleurectomy/decortication" (P/D). We explored mesothelioma surgeons' concepts of P/D with the aim of unifying surgical nomenclature.
METHODS: A web-based survey was administered to surgeons who operated on malignant pleural mesothelioma (MPM) for diagnosis, staging, palliation, or cytoreduction. One hundred thirty surgeons from 59 medical centers were included. Surgeons who did not perform surgery for MPM within the last year were excluded.
RESULTS: There were 62 (48%) respondents from 39 medical centers in 14 countries. The mean number of patients with MPM seen annually at each medical center was 46, and the mean annual number of cytoreductive procedures performed per surgeon was 8. Most (88%) agreed that the goal of cytoreductive surgery should be macroscopic complete resection of tumor. P/D was defined as resection of parietal and visceral pleura with the aim of achieving macroscopic complete resection by 72% of respondents. If the diaphragm or pericardium required resection, 64% preferred the term "radical P/D," whereas "P/D" (40%) or "total pleurectomy" (39%) was preferred if these structures were not removed. Most surgeons believed that extrapleural pneumonectomy (90%) or "radical P/D" (68%) could provide adequate cytoreduction, whereas only 23% thought that P/D could.
CONCLUSIONS: There was significant variation regarding surgical nomenclature for procedures for MPM. The International Staging Committee of the International Association for the Study of Lung Cancer and the International Mesothelioma Interest Group recommend that P/D should aim to remove all macroscopic tumor involving the parietal and visceral pleura and should be termed "extended" P/D when the diaphragm or pericardium is resected.

PMID 21847060  J Thorac Oncol. 2011 Aug;6(8):1304-12. doi: 10.1097/JTO・・・
著者: Tom Treasure, Loic Lang-Lazdunski, David Waller, Judith M Bliss, Carol Tan, James Entwisle, Michael Snee, Mary O'Brien, Gill Thomas, Suresh Senan, Ken O'Byrne, Lucy S Kilburn, James Spicer, David Landau, John Edwards, Gill Coombes, Liz Darlison, Julian Peto, MARS trialists
雑誌名: Lancet Oncol. 2011 Aug;12(8):763-72. doi: 10.1016/S1470-2045(11)70149-8. Epub 2011 Jun 30.
Abstract/Text BACKGROUND: The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study.
METHODS: MARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524.
FINDINGS: Between Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92-3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21-6·26; p=0·016). Median survival was 14·4 months (5·3-18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group.
INTERPRETATION: In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients.
FUNDING: Cancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust.

Copyright © 2011 Elsevier Ltd. All rights reserved.
PMID 21723781  Lancet Oncol. 2011 Aug;12(8):763-72. doi: 10.1016/S1470・・・
著者: Walter Weder, Rolf A Stahel, Paul Baas, Urania Dafni, Marc de Perrot, Brian C McCaughan, Takashi Nakano, Harvey I Pass, Bruce W S Robinson, Valerie W Rusch, David J Sugarbaker, Nico van Zandwijk
雑誌名: Lancet Oncol. 2011 Nov;12(12):1093-4; author reply 1094-5. doi: 10.1016/S1470-2045(11)70307-2.
Abstract/Text
PMID 22041539  Lancet Oncol. 2011 Nov;12(12):1093-4; author reply 1094・・・
著者: Arman Hasani, John M Alvarez, Jenny Ma Wyatt, Sean Bydder, Michael Millward, Michael Byrne, Arthur W Bill Musk, Anna K Nowak
雑誌名: J Thorac Oncol. 2009 Aug;4(8):1010-6. doi: 10.1097/JTO.0b013e3181ae25bf.
Abstract/Text INTRODUCTION: Trimodality therapy (TMT), consisting of extrapleural pneumonectomy (EPP), preoperative or postoperative combination chemotherapy, and high-dose hemithoracic radiotherapy, is the only therapy reported to achieve long-term survival in selected patients with malignant pleural mesothelioma (MPM). Thus, TMT was introduced as an option for such patients in Western Australia in 2004. However, TMT has never been compared with non-TMT therapy in the same patient population, thereby introducing a potential for selection bias.
METHOD: We performed a retrospective review of all patients referred for TMT consisting of EPP, adjuvant chemotherapy, and hemithoracic radiotherapy at a quaternary referral institution. Patient eligibility for referral for TMT was based on patients' tolerability for pneumonectomy, epithelioid subtype, and computed tomography and positron emission tomography scanning indicating operable disease, with the exclusion of extrapleural lymphadenopathy and metastatic disease (clinical stage T1-3N0-1M0). Eligible patients consenting to TMT also underwent a surgical staging procedure (bilateral thoracoscopy, mediastinoscopy, and laparoscopy) to confirm eligibility before EPP.
RESULTS: Thirty-six patients have been referred for TMT since 2004, and there has been a median of 27 months follow-up; of 31 patients having surgical staging, eight were ineligible for EPP and one declined EPP. Of the 22 planned for EPP, 18 underwent EPP and four had unresectable disease at surgery. There was one death in hospital six days post-EPP and another death postdischarge and 28 days post-EPP (30-day mortality 11%); 15 of 16 EPP survivors received adjuvant chemotherapy and 14 completed adjuvant radiotherapy. Pathologic analysis of the 18 resected EPP specimens revealed N2 disease in seven patients (39%) and nonepithelioid subtype in six patients (33%). Local recurrence did not occur among EPP survivors; however, 56% (9 of 16 patients) developed distant recurrence. Median and 1-year survival did not differ between the 18 EPP patients and 18 non-EPP patients (20.4 versus 20.7 months and 76 versus 78%, respectively; p = NS).
DISCUSSION: In this case series, we could not demonstrate a survival benefit for patients in the EPP group compared with that in the non-EPP group. After surgical staging, 26% of patients were ineligible for TMT. Thus, surgical staging is essential before proceeding with EPP. Despite aggressive imaging and surgical staging, 39% of patients will have N2 disease and 18% will have unresectable disease at operation. Although complete locoregional control was achieved with TMT, distant recurrence affected most EPP survivors despite careful patient selection and a high rate of completion of adjuvant therapy. We conclude that TMT for operable epithelioid MPM requires further assessment in randomized controlled trials.

PMID 19546819  J Thorac Oncol. 2009 Aug;4(8):1010-6. doi: 10.1097/JTO.・・・
著者: V W Rusch, K Rosenzweig, E Venkatraman, L Leon, A Raben, L Harrison, M S Bains, R J Downey, R J Ginsberg
雑誌名: J Thorac Cardiovasc Surg. 2001 Oct;122(4):788-95. doi: 10.1067/mtc.2001.116560.
Abstract/Text BACKGROUND: Surgical resection of malignant pleural mesothelioma is reported to have up to an 80% rate of local recurrence. We performed a phase II trial of high-dose hemithoracic radiation after complete resection to determine feasibility and to estimate rates of local recurrence and survival.
METHODS: Patients were eligible if they had a resectable tumor, as determined by computed tomographic scanning, and adequate cardiopulmonary function for extrapleural pneumonectomy or pleurectomy/decortication. After complete resection, patients received hemithoracic radiation (54 Gy) and then were followed up with serial computed tomographic scanning.
RESULTS: From 1995 to 1998, 88 patients (73 men and 15 women; median age, 62.5 years) were entered into the study. The operations performed included 62 extrapleural pneumonectomies (70%) and 5 pleurectomies/decortications; procedures for exploration only were performed in 21 patients. Seven (7.9%) patients died postoperatively. Adjuvant radiation administered to 57 patients (54 undergoing extrapleural pneumonectomy and 3 undergoing pleurectomy/decortication) at a median dose of 54 Gy was well tolerated (grade 0-2 fatigue, esophagitis), except for one late esophageal fistula. The median survival was 33.8 months for stage I and II tumors but only 10 months for stage III and IV tumors (P =.04). For the patients undergoing extrapleural pneumonectomy, the sites of recurrence were locoregional in 2, locoregional and distant in 5, and distant only in 30.
CONCLUSION: Hemithoracic radiation after complete surgical resection at a dose not previously reported is feasible. This approach dramatically reduces local recurrence and is associated with prolonged survival for early-stage tumors. Stage III disease has a high risk of early distant relapse and should be considered for trials of systemic therapy added to this regimen of resection and radiation.

PMID 11581615  J Thorac Cardiovasc Surg. 2001 Oct;122(4):788-95. doi: ・・・
著者: Marc de Perrot, Ronald Feld, B C John Cho, Andrea Bezjak, Masaki Anraku, Ronald Burkes, Heidi Roberts, Ming S Tsao, Natasha Leighl, Shaf Keshavjee, Michael R Johnston
雑誌名: J Clin Oncol. 2009 Mar 20;27(9):1413-8. doi: 10.1200/JCO.2008.17.5604. Epub 2009 Feb 17.
Abstract/Text PURPOSE: Malignant pleural mesothelioma (MPM) remains associated with poor outcome. We examined the results of trimodality therapy with cisplatin-based chemotherapy followed by extrapleural pneumonectomy (EPP) and adjuvant high-dose (50 to 60 Gy) hemithoracic radiation therapy for MPM.
PATIENTS AND METHODS: We conducted a retrospective review of all patients prospectively evaluated for trimodality therapy protocol between January 2001 and December 2007 in our institution.
RESULTS: A total of 60 patients were suitable candidates. Histology was epithelioid (n = 44) or biphasic (n = 16). Chemotherapy regimens included cisplatin/vinorelbine (n = 26), cisplatin/pemetrexed (n = 24), cisplatin/raltitrexed (n = 6), or cisplatin/gemcitabine (n = 4). EPP was performed in 45 patients, and hemithoracic radiation therapy to at least 50 Gy was administered postoperatively to 30 patients. Completion of the trimodality therapy in the absence of mediastinal node involvement was associated with the best survival (median survival of 59 months v CONCLUSION: This large, single-center experience with induction chemotherapy followed by EPP and adjuvant high-dose hemithoracic radiation for MPM shows that half of the patients are able to complete this protocol. The results are encouraging for patients with N0 disease. However, N2 disease remains a major factor impacting on survival, despite completion of the entire trimodality regimen.

PMID 19224855  J Clin Oncol. 2009 Mar 20;27(9):1413-8. doi: 10.1200/JC・・・
著者: W Weder, R A Stahel, J Bernhard, S Bodis, P Vogt, P Ballabeni, D Lardinois, D Betticher, R Schmid, R Stupp, H B Ris, M Jermann, W Mingrone, A D Roth, A Spiliopoulos, Swiss Group for Clinical Cancer Research
雑誌名: Ann Oncol. 2007 Jul;18(7):1196-202. doi: 10.1093/annonc/mdm093. Epub 2007 Apr 11.
Abstract/Text BACKGROUND: The aim of this multicenter trial was to prospectively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and radiotherapy, including quality of life as outcome.
PATIENTS AND METHODS: Eligible patients had malignant pleural mesothelioma of all histological types, World Health Organization performance status of zero to two and clinical stage T1-T3, N0-2, M0 disease considered completely resectable. Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP. Postoperative radiotherapy was considered for all patients.
RESULTS: In all, 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy. Forty-five patients (74%) underwent EPP and in 37 patients (61%) the resection was complete. Postoperative radiotherapy was initiated in 36 patients. The median survival of all patients was 19.8 months [95% confidence interval (CI) 14.6-24.5]. For the 45 patients undergoing EPP, the median survival was 23 months (95% CI 16.6-32.9). Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82% (N = 36) at baseline and 76% (N = 26) at 3 months after surgery (P = 0.5).
CONCLUSIONS: The observed rate of operability is promising. A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery. This approach was not associated with an increase in psychological distress.

PMID 17429100  Ann Oncol. 2007 Jul;18(7):1196-202. doi: 10.1093/annonc・・・
著者: Rolf A Stahel, Oliver Riesterer, Alexandros Xyrafas, Isabelle Opitz, Michael Beyeler, Adrian Ochsenbein, Martin Früh, Richard Cathomas, Kristiaan Nackaerts, Solange Peters, Christoph Mamot, Alfred Zippelius, Carlo Mordasini, Clemens B Caspar, Katrin Eckhardt, Ralph A Schmid, Daniel M Aebersold, Oliver Gautschi, Wolfgang Nagel, Michael Töpfer, Jerome Krayenbuehl, Karin Ribi, Ilja Ciernik, Walter Weder
雑誌名: Lancet Oncol. 2015 Dec;16(16):1651-8. doi: 10.1016/S1470-2045(15)00208-9. Epub 2015 Nov 2.
Abstract/Text BACKGROUND: Postoperative hemithoracic radiotherapy has been used to treat malignant pleural mesothelioma, but it has not been assessed in a randomised trial. We assessed high-dose hemithoracic radiotherapy after neoadjuvant chemotherapy and extrapleural pneumonectomy in patients with malignant pleural mesothelioma.
METHODS: We did this phase 2 trial in two parts at 14 hospitals in Switzerland, Belgium, and Germany. We enrolled patients with pathologically confirmed malignant pleural mesothelioma; resectable TNM stages T1-3 N0-2, M0; WHO performance status 0-1; age 18-70 years. In part 1, patients were given three cycles of neoadjuvant chemotherapy (cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 given every 3 weeks) and extrapleural pneumonectomy; the primary endpoint was complete macroscopic resection (R0-1). In part 2, participants with complete macroscopic resection were randomly assigned (1:1) to receive high-dose radiotherapy or not. The target volume for radiotherapy encompassed the entire hemithorax, the thoracotomy channel, and mediastinal nodal stations if affected by the disease or violated surgically. A boost was given to areas at high risk for locoregional relapse. The allocation was stratified by centre, histology (sarcomatoid vs epithelioid or mixed), mediastinal lymph node involvement (N0-1 vs N2), and T stage (T1-2 vs T3). The primary endpoint of part 1 was the proportion of patients achieving complete macroscopic resection (R0 and R1). The primary endpoint in part 2 was locoregional relapse-free survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00334594.
FINDINGS: We enrolled patients between Dec 7, 2005, and Oct 17, 2012. Overall, we analysed 151 patients receiving neoadjuvant chemotherapy, of whom 113 (75%) had extrapleural pneumonectomy. Median follow-up was 54·2 months (IQR 32-66). 52 (34%) of 151 patients achieved an objective response. The most common grade 3 or 4 toxic effects were neutropenia (21 [14%] of 151 patients), anaemia (11 [7%]), and nausea or vomiting (eight [5%]). 113 patients had extrapleural pneumonectomy, with complete macroscopic resection achieved in 96 (64%) of 151 patients. We enrolled 54 patients in part 2; 27 in each group. The main reasons for exclusion were patient refusal (n=20) and ineligibility (n=10). 25 of 27 patients completed radiotherapy. Median total radiotherapy dose was 55·9 Gy (IQR 46·8-56·0). Median locoregional relapse-free survival from surgery, was 7·6 months (95% CI 4·5-10·7) in the no radiotherapy group and 9·4 months (6·5-11·9) in the radiotherapy group. The most common grade 3 or higher toxic effects related to radiotherapy were nausea or vomiting (three [11%] of 27 patients), oesophagitis (two [7%]), and pneumonitis (two [7%]). One patient died of pneumonitis. We recorded no toxic effects data for the control group.
INTERPRETATION: Our findings do not support the routine use of hemithoracic radiotherapy for malignant pleural mesothelioma after neoadjuvant chemotherapy and extrapleural pneumonectomy.
FUNDING: Swiss Group for Clinical Cancer Research, Swiss State Secretariat for Education, Research and Innovation, Eli Lilly.

Copyright © 2015 Elsevier Ltd. All rights reserved.
PMID 26538423  Lancet Oncol. 2015 Dec;16(16):1651-8. doi: 10.1016/S147・・・
著者: Kenneth E Rosenzweig, Marjorie G Zauderer, Benjamin Laser, Lee M Krug, Ellen Yorke, Camelia S Sima, Andreas Rimner, Raja Flores, Valerie Rusch
雑誌名: Int J Radiat Oncol Biol Phys. 2012 Jul 15;83(4):1278-83. doi: 10.1016/j.ijrobp.2011.09.027. Epub 2012 May 18.
Abstract/Text PURPOSE: In patients with malignant pleural mesothelioma who are unable to undergo pneumonectomy, it is difficult to deliver tumoricidal radiation doses to the pleura without significant toxicity. We have implemented a technique of using intensity-modulated radiotherapy (IMRT) to treat these patients, and we report the feasibility and toxicity of this approach.
METHODS AND MATERIALS: Between 2005 and 2010, 36 patients with malignant pleural mesothelioma and two intact lungs (i.e., no previous pneumonectomy) were treated with pleural IMRT to the hemithorax (median dose, 46.8 Gy; range, 41.4-50.4) at Memorial Sloan-Kettering Cancer Center.
RESULTS: Of the 36 patients, 56% had right-sided tumors. The histologic type was epithelial in 78%, sarcomatoid in 6%, and mixed in 17%, and 6% had Stage I, 28% had Stage II, 33% had Stage III, and 33% had Stage IV. Thirty-two patients (89%) received induction chemotherapy (mostly cisplatin and pemetrexed); 56% underwent pleurectomy/decortication before IMRT and 44% did not undergo resection. Of the 36 patients evaluable for acute toxicity, 7 (20%) had Grade 3 or worse pneumonitis (including 1 death) and 2 had Grade 3 fatigue. In 30 patients assessable for late toxicity, 5 had continuing Grade 3 pneumonitis. For patients treated with surgery, the 1- and 2-year survival rate was 75% and 53%, and the median survival was 26 months. For patients who did not undergo surgical resection, the 1- and 2-year survival rate was 69% and 28%, and the median survival was 17 months.
CONCLUSIONS: Treating the intact lung with pleural IMRT in patients with malignant pleural mesothelioma is a safe and feasible treatment option with an acceptable rate of pneumonitis. Additionally, the survival rates were encouraging in our retrospective series, particularly for the patients who underwent pleurectomy/decortication. We have initiated a Phase II trial of induction chemotherapy with pemetrexed and cisplatin with or without pleurectomy/decortication, followed by pleural IMRT to prospectively evaluate the toxicity and survival.

Copyright © 2012 Elsevier Inc. All rights reserved.
PMID 22607910  Int J Radiat Oncol Biol Phys. 2012 Jul 15;83(4):1278-83・・・
著者: Gérard Zalcman, Julien Mazieres, Jacques Margery, Laurent Greillier, Clarisse Audigier-Valette, Denis Moro-Sibilot, Olivier Molinier, Romain Corre, Isabelle Monnet, Valérie Gounant, Frédéric Rivière, Henri Janicot, Radj Gervais, Chrystèle Locher, Bernard Milleron, Quan Tran, Marie-Paule Lebitasy, Franck Morin, Christian Creveuil, Jean-Jacques Parienti, Arnaud Scherpereel, French Cooperative Thoracic Intergroup (IFCT)
雑誌名: Lancet. 2016 Apr 2;387(10026):1405-14. doi: 10.1016/S0140-6736(15)01238-6. Epub 2015 Dec 21.
Abstract/Text BACKGROUND: Malignant pleural mesothelioma is an aggressive cancer with poor prognosis, linked to occupational asbestos exposure. Vascular endothelial growth factor is a key mitogen for malignant pleural mesothelioma cells, therefore targeting of vascular endothelial growth factor might prove effective. We aimed to assess the effect on survival of bevacizumab when added to the present standard of care, cisplatin plus pemetrexed, as first-line treatment of advanced malignant pleural mesothelioma.
METHODS: In this randomised, controlled, open-label, phase 3 trial, we recruited patients aged 18-75 years with unresectable malignant pleural mesothelioma who had not received previous chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0-2, had no substantial cardiovascular comorbidity, were not amenable to curative surgery, had at least one evaluable (pleural effusion) or measurable (pleural tumour solid thickening) lesion with CT, and a life expectancy of >12 weeks from 73 hospitals in France. Exclusion criteria were presence of central nervous system metastases, use of antiaggregant treatments (aspirin ≥325 mg per day, clopidogrel, ticlopidine, or dipyridamole), anti-vitamin K drugs at a curative dose, treatment with low-molecular-weight heparin at a curative dose, and treatment with non-steroidal anti-inflammatory drugs. We randomly allocated patients (1:1; minimisation method used [random factor of 0·8]; patients stratified by histology [epithelioid vs sarcomatoid or mixed histology subtypes], performance status score [0-1 vs 2], study centre, or smoking status [never smokers vs smokers]) to receive intravenously 500 mg/m(2) pemetrexed plus 75 mg/m(2) cisplatin with (PCB) or without (PC) 15 mg/kg bevacizumab in 21 day cycles for up to six cycles, until progression or toxic effects. The primary outcome was overall survival (OS) in the intention-to treat population. Treatment was open label. This IFCT-GFPC-0701 trial is registered with ClinicalTrials.gov, number NCT00651456.
FINDINGS: From Feb 13, 2008, to Jan 5, 2014, we randomly assigned 448 patients to treatment (223 [50%] to PCB and 225 [50%] to PC). OS was significantly longer with PCB (median 18·8 months [95% CI 15·9-22·6]) than with PC (16·1 months [14·0-17·9]; hazard ratio 0·77 [0·62-0·95]; p=0·0167). Overall, 158 (71%) of 222 patients given PCB and 139 (62%) of 224 patients given PC had grade 3-4 adverse events. We noted more grade 3 or higher hypertension (51 [23%] of 222 vs 0) and thrombotic events (13 [6%] of 222 vs 2 [1%] of 224) with PCB than with PC.
INTERPRETATION: Addition of bevacizumab to pemetrexed plus cisplatin significantly improved OS in malignant pleural mesothelioma at the cost of expected manageable toxic effects, therefore it should be considered as a suitable treatment for the disease.
FUNDING: Intergroupe Francophone de Cancérologie Thoracique (IFCT).

Copyright © 2016 Elsevier Ltd. All rights reserved.
PMID 26719230  Lancet. 2016 Apr 2;387(10026):1405-14. doi: 10.1016/S01・・・
著者: Morihito Okada, Takashi Kijima, Keisuke Aoe, Terufumi Kato, Nobukazu Fujimoto, Kazuhiko Nakagawa, Yuichiro Takeda, Toyoaki Hida, Kuninobu Kanai, Fumio Imamura, Satoshi Oizumi, Toshiaki Takahashi, Mitsuhiro Takenoyama, Hiroshi Tanaka, Jun Hirano, Yoshinobu Namba, Yuichiro Ohe
雑誌名: Clin Cancer Res. 2019 Sep 15;25(18):5485-5492. doi: 10.1158/1078-0432.CCR-19-0103. Epub 2019 Jun 4.
Abstract/Text PURPOSE: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with poor prognosis. Patients with MPM who do not respond to standard first-line chemotherapy have limited treatment options. We evaluated the efficacy and safety of nivolumab, an immune checkpoint inhibitor, for the treatment of advanced or metastatic MPM.
PATIENTS AND METHODS: Japanese patients with unresectable, advanced, or metastatic MPM resistant or intolerant to ≤2 regimens of chemotherapy and ≥1 measurable lesion(s) were enrolled. Patients received nivolumab 240 mg intravenously every 2 weeks until progressive disease or unacceptable toxicity. The primary endpoint was objective response rate by central assessment according to the Modified Response Evaluation Criteria in Solid Tumors. Adverse events (AEs) and treatment-related AEs (TRAEs) were evaluated.
RESULTS: Thirty-four patients were enrolled between July 2016 and October 2016. Median follow-up was 16.8 (range: 1.8-20.2) months. Ten (29%, 95% confidence interval, 16.8-46.2) patients showed a centrally assessed objective response. The objective response rates were 26% (7/27), 67% (2/3), and 25% (1/4) patients for epithelioid, sarcomatoid, and biphasic histologic subtypes, respectively. Median duration of response was 11.1 months with a 68% disease control rate. Median overall survival and progression-free survival were 17.3 and 6.1 months, respectively. The objective response rate was 40% with programmed death-ligand 1 expression ≥1% and 8% with <1%. Thirty-two patients (94%) experienced AEs and 26 (76%) experienced TRAEs.
CONCLUSIONS: Nivolumab met the primary endpoint as second- or third-line treatment for patients with MPM and showed promising efficacy with manageable toxicity.See related commentary by Mansfield and Zauderer, p. 5438.

©2019 American Association for Cancer Research.
PMID 31164373  Clin Cancer Res. 2019 Sep 15;25(18):5485-5492. doi: 10.・・・
著者: Pasi A Jänne, George R Simon, Corey J Langer, Robert N Taub, Afshin Dowlati, Panos Fidias, Matthew Monberg, Coleman Obasaju, Hedy Kindler
雑誌名: J Clin Oncol. 2008 Mar 20;26(9):1465-71. doi: 10.1200/JCO.2007.14.7611.
Abstract/Text PURPOSE: Pemetrexed and gemcitabine have single-agent activity in malignant pleural mesothelioma (MPM). The combination of pemetrexed/gemcitabine has not previously been studied in MPM to our knowledge.
PATIENTS AND METHODS: Patients with histologic or cytologic diagnosis of MPM were included. Cohort 1 received gemcitabine 1,250 mg/m(2) on days 1 and 8, with pemetrexed 500 mg/m(2) on day 8, and cohort 2 received gemcitabine 1,250 mg/m(2) on days 1 and 8, with pemetrexed 500 mg/m(2) on day 1. Cycles were repeated every 21 days; all patients were supplemented with folic acid and vitamin B(12) and received dexamethasone.
RESULTS: One hundred eight patients (cohort 1, n = 56; cohort 2, n = 52) with pleural mesothelioma were enrolled. Among assessable patients, response rate was 26.0% in cohort 1 and 17.1% in cohort 2. Median time to disease progression was 4.34 months for cohort 1 and 7.43 months for cohort 2. Median survival was 8.08 months for cohort 1 (1-year survival = 31.14%) and 10.12 months for cohort 2 (1-year survival = 45.80%). In cohorts 1 and 2, incidence of grade 4 neutropenia was 25.0% and 29.4%, grade 4 thrombocytopenia was 14.3% and 3.9%, grade 3 or 4 anemia was 5.4% and 5.9%, and grade 3 or 4 fatigue was 23.2% and 15.7%, respectively.
CONCLUSION: The combination of pemetrexed and gemcitabine resulted in moderate clinical activity in MPM. However, the median survival times are similar to those with single-agent pemetrexed and inferior to outcomes observed with cisplatin in combination with an antifolate.

PMID 18349397  J Clin Oncol. 2008 Mar 20;26(9):1465-71. doi: 10.1200/J・・・
著者: T Berghmans, M Paesmans, Y Lalami, I Louviaux, S Luce, C Mascaux, A P Meert, J P Sculier
雑誌名: Lung Cancer. 2002 Nov;38(2):111-21.
Abstract/Text The role of chemotherapy for unresectable malignant mesothelioma is unclear. The aims of the present study were to evaluate the methodological quality of published papers relative to chemotherapy or immunotherapy in malignant mesothelioma and to aggregate, for trials having a similar methodology, the response rates in order to identify the most active chemotherapeutic drugs and regimens. The literature relative to this topic, published between 1965 and June 2001 was reviewed. A methodological qualitative evaluation was performed according to the European Lung Cancer Working Party scale, specifically designed for phase II trials. A study was considered as potentially positive if the upper limit of the 95% confidence interval (CI) of the response rate was greater than 20% and positive if the lower limit of the 95% CI was > 20%. Eighty-three studies (88 treatment arms) were eligible for the systematic review. Fifty-three arms were considered as positive or potentially positive. No statistically significant difference in the methodological quality was observed between negative and positive studies. Studies were aggregated in four groups according to the presence of cisplatin and/or doxorubicin in the treatment regimen. The combination of cisplatin and doxorubicin had the highest response rate (28.5%; P < 0.001). Cisplatin was the most active single-agent regimen. Our systematic qualitative and quantitative overview of the literature suggests that the most active chemotherapeutic regimen, in term of objective response rate, is the combination of cisplatin and doxorubicin and the best single-agent is cisplatin. The combination of these two drugs can be recommended as control arm for future randomised phase III trials.

Copyright 2002 Elsevier Science Ireland Ltd.
PMID 12399121  Lung Cancer. 2002 Nov;38(2):111-21.
著者: Myura Nagendran, Athanasios Pallis, Kruti Patel, Marco Scarci
雑誌名: Interact Cardiovasc Thorac Surg. 2011 Jul;13(1):66-9. doi: 10.1510/icvts.2011.267252. Epub 2011 Mar 30.
Abstract/Text A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether patients diagnosed with mesothelioma by video-assisted thoracoscopic surgery should have their intervention sites irradiated to prevent metastatic seeding. Altogether 334 papers were found using the reported search, of which nine represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. There is no general consensus in the literature. Four studies recommend prophylactic irradiation therapy (PIT), while three studies stated that PIT was unnecessary. A systematic review identified only three suitable randomized controlled trials (RCTs) from the literature. One trial found that 23% of radiotherapy (RT) patients developed tract metastases compared to 10% of control patients (P=0.748) with an estimated hazard ratio (RT to control) of 1.28 (95% CI: 0.29-5.73). Time from procedure to tract metastases was in fact shorter in patients treated with RT (2.4 months RT vs. 6.4 months control, non-significant). Another trial found that seeding of metastatic tumour to the intervention site occurred in 7% of RT sites vs. 10% of control sites (P=0.53). Freedom from tract metastasis survival was also non-significant between RT and control arms (P=0.82). However, the third trial reported a significantly greater incidence of intervention site metastases in control vs. RT patients (40% vs. 0%, respectively, P<0.001). Non-randomised studies found mixed results. One reported that median survival between patients with and without local metastases was not significantly different (P=0.64) while another article described no local metastases in PIT sites. None of the studies reported significant skin or side reactions and treatment was generally well tolerated. Based on the available evidence, we conclude that PIT is not currently justified.

PMID 21451088  Interact Cardiovasc Thorac Surg. 2011 Jul;13(1):66-9. d・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから