title: Preoperative concurrent chemoradiotherapy followed by extrapleural pneumonectomy for patients with non-small cell lung cancer with malignant pleural effusion and/or pleural nodules: Ten-year results of a prematurely terminated single institute phase II trial.
abstract: BACKGROUND
  Malignant pleural effusion and/or pleural nodules are a final stage of disease extension of non-small cell lung cancer (NSCLC), which is currently classified as M1a-Stage IV disease. The role of surgery, especially extrapleural pneumonectomy (EPP) for local disease control and its impact on the survival of patients remains uncertain.
  
  
  METHODS
  This single institute phase II trial was performed from March 1997 to March July 2004 to assess the effects of induction concurrent chemoradiotherapy (CRT) using a pro-drug of 5-FU, uracil-tegafur (UFT(®), Taiho Pharmaceutical Co., Ltd, Tokyo, Japan), plus cisplatin concurrently with 40 Gy hemithorax radiation followed by EPP. Intraoperative hypotonic cisplatin treatment in the pleural cavity before resection of the pericardium and diaphragm was performed. The primary endpoint of this study was the overall survival (OS), and the secondary endpoint was the disease-free survival (DFS), safety, response to the induction CRT, local disease control period in the affected thorax and the type of disease recurrence.
  
  
  RESULTS
  This trial was prematurely terminated because of the slow registration pace. During the study period, 11 patients were enrolled. There were five males and six females, with a median age of 55 (36-64) years. All patients had adenocarcinoma. All patients received the planned induction CRT. Five patients achieved a partial response and five achieved stable disease, and one patient could not be evaluated. One patient underwent exploratory thoracotomy due to unresectable chest wall invasion, and nine patients (81.8%) underwent EPP. No perioperative deaths were encountered. The median follow-up time was matured at 32.1 (range 15.0-100) months. The one-, three- and five-year DFS rates were 77.8% (95%CI: 50.6-100%), 11.1% and 11.1% (95%CI: 95%CI: 0-31.7%), respectively. The one-, three- and five-year OS rates were 100.0%, 33.3% (95%CI: 2.5-64.1%) and 22.2% (95%CI: 0.0-49.4%), respectively. Recurrence developed in eight of nine patients who underwent EPP (88.9%). All first recurrent sites were distant regions, and no ipsilateral local recurrence was identified.
  
  
  CONCLUSIONS
  The trimodality treatment used in this trial appears to be a choice of treatment for highly selected patients. However, the impact on the survival of NSCLC patients with malignant pleural effusion and/or pleural nodules still remains uncertain given the small number of patients enrolled in the study.
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka City 811-1395, Japan. Electronic address: yamaguchi.m@nk-cc.go.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka City 811-1395, Japan.
authors.forename: Yukito
authors.initials: Y
authors.lastname: Ichinose
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka City 811-1395, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Shimamatsu
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka City 811-1395, Japan.
authors.forename: Tsukihisa
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka City 811-1395, Japan.
authors.forename: Gouji
authors.initials: G
authors.lastname: Toyokawa
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka City 811-1395, Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Nosaki
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka City 811-1395, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hirai
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka City 811-1395, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Seto
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka City 811-1395, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Takenoyama
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods / Q000401:mortality; D002945:Cisplatin / Q000627:therapeutic use; D018572:Disease-Free Survival; D057239:Early Termination of Clinical Trials; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D055613:Multiple Pulmonary Nodules / Q000401:mortality / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000209:etiology / Q000401:mortality; D016066:Pleural Effusion, Malignant / Q000401:mortality / Q000628:therapy*; D011013:Pneumonectomy / Q000379:methods* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin
keywords: Extrapleural pneumonectomy; Hemithorax radiation; Malignant pleural effusion and/or pleural nodules; Non-small cell lung cancer; UFT and cisplatin