title: Long-term outcomes of intensity-modulated radiotherapy following extra-pleural pneumonectomy for malignant pleural mesothelioma.
abstract: BACKGROUND
  The purpose was to evaluate safety and efficacy of intensity-modulated radiotherapy (IMRT) following extra-pleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM).
  
  
  METHODS
  Patients with MPM of clinical stage I-III, which were macroscopic completely resected with EPP were eligible for this prospective study. The ipsilateral hemithorax was irradiated with a prescribed dose of 50.4 Gy. When the high-risk surgical margins or FDG-avid regions were identified, simultaneous integrated boost (SIB) with 56.0 Gy or 61.6 Gy was applied.
  
  
  RESULTS
  Twenty-one patients were enrolled. SIB was applied to five patients. The planned IMRT fractions were completed in all, but four patients who suffered from severe fatigue or radiation pneumonitis. With a potential median follow-up of 6.3 years, overall survival was 37.5% at 3 years since the IMRT. The median survival time was 17.5 and 27.0 months since the IMRT and the initial treatment, respectively. Three patients have survived for more than 5 years. Distant metastasis was observed in 15 patients. Local recurrence was also observed in 2 of the 15 patients. Acute toxicities of Grade 3 or worse were observed in 15 patients, including 9 with hematological, 3 with pneumonitis and 6 with fatigue, nausea or vomiting. Five patients developed Grade 3 or worse late toxicities associated with IMRT, consisting of one with persistent Grade 4 thrombocytopenia, one with brain infarction and congestive liver dysfunction, and three with elevation of serum transaminase or biliary enzyme. No Grade 5 toxicity was observed. Patients with N2 showed significantly worse survival than those with N0-1 (18.2% vs. 60.0% at 3 years, p = .014).
  
  
  CONCLUSIONS
  IMRT following EPP achieved excellent local control for MPM, that might lead to the long-term survival in selected patients. However, treatment burden including acute and late toxicities should be considered in this treatment approach.
authors.affiliation: a Department of Radiation Oncology and Image-applied Therapy , Graduate School of Medicine, Kyoto University , Kyoto , Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Matsuo
authors.affiliation: a Department of Radiation Oncology and Image-applied Therapy , Graduate School of Medicine, Kyoto University , Kyoto , Japan.|b Department of Radiation Oncology , Graduate School of Medicine, Yamaguchi University , Ube , Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shibuya
authors.affiliation: c Department of Thoracic Surgery , Graduate School of Medicine, Kyoto University , Kyoto , Japan.|d Department of Thoracic Surgery , Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , Tokyo , Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Okubo
authors.affiliation: a Department of Radiation Oncology and Image-applied Therapy , Graduate School of Medicine, Kyoto University , Kyoto , Japan.
authors.forename: Nami
authors.initials: N
authors.lastname: Ueki
authors.affiliation: c Department of Thoracic Surgery , Graduate School of Medicine, Kyoto University , Kyoto , Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Aoyama
authors.affiliation: c Department of Thoracic Surgery , Graduate School of Medicine, Kyoto University , Kyoto , Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sonobe
authors.affiliation: a Department of Radiation Oncology and Image-applied Therapy , Graduate School of Medicine, Kyoto University , Kyoto , Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: a Department of Radiation Oncology and Image-applied Therapy , Graduate School of Medicine, Kyoto University , Kyoto , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mizowaki
authors.affiliation: c Department of Thoracic Surgery , Graduate School of Medicine, Kyoto University , Kyoto , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
authors.affiliation: a Department of Radiation Oncology and Image-applied Therapy , Graduate School of Medicine, Kyoto University , Kyoto , Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiraoka
mesh_terms: D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D008297:Male; D008654:Mesothelioma / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D010997:Pleural Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D011013:Pneumonectomy / Q000401:mortality*; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies; D017564:Radiation Pneumonitis / Q000453:epidemiology; D050397:Radiotherapy, Intensity-Modulated / Q000401:mortality*; D015996:Survival Rate