Matsuo Yukinori, Shibuya Keiko, Okubo Kenichi, Ueki Nami, Aoyama Akihiro, Sonobe Makoto, Nakamura Mitsuhiro, Mizowaki Takashi, Date Hiroshi, Hiraoka Masahiro
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.
Acta Oncol. 2017 Jul;56(7):957-962. doi: 10.1080/0284186X.2017.1279749. Epub 2017 Jan 24.
The purpose was to evaluate safety and efficacy of intensity-modulated radiotherapy (IMRT) following extra-pleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM).
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.
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).
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.
本研究旨在评估胸膜外全肺切除术（EPP）后行调强放射治疗（IMRT）治疗恶性胸膜间皮瘤（MPM）的安全性和有效性。
临床分期为I - III期、经EPP肉眼下完全切除的MPM患者符合本前瞻性研究的条件。同侧半胸接受50.4 Gy的处方剂量照射。当发现高风险手术切缘或FDG摄取区域时，采用56.0 Gy或61.6 Gy的同步整合加量（SIB）。
共纳入21例患者。5例患者采用了SIB。所有患者均完成了计划的IMRT分割，但有4例患者出现严重疲劳或放射性肺炎。中位随访时间潜在为6.3年，IMRT后3年总生存率为37.5%。IMRT后和初始治疗后的中位生存时间分别为17.5个月和27.0个月。3例患者存活超过5年。15例患者出现远处转移。15例患者中有2例出现局部复发。15例患者出现3级或更严重的急性毒性反应，包括9例血液学毒性、3例肺炎和6例疲劳、恶心或呕吐。5例患者出现与IMRT相关的3级或更严重的晚期毒性反应，包括1例持续性4级血小板减少、1例脑梗死和充血性肝功能障碍，以及3例血清转氨酶或胆汁酶升高。未观察到5级毒性反应。N2期患者的生存率明显低于N0 - 1期患者（3年时分别为18.2%和60.0%，p = 0.014）。
EPP后行IMRT对MPM实现了良好的局部控制，这可能使部分患者长期生存。然而，在这种治疗方法中应考虑包括急性和晚期毒性在内的治疗负担。
