评估放疗后行胸膜间皮瘤手术的可行性研究：可切除恶性胸膜间皮瘤的 SMART 方法。

A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the "SMART" approach for resectable malignant pleural mesothelioma.

机构信息

Departments of *Radiation Oncology, †Medical Oncology, and §Pathology, ‡Division of Thoracic Surgery, Princess Margaret Cancer Centre and Toronto General Hospital, University Health Network, University of Toronto, Ontario, Canada.

出版信息

J Thorac Oncol. 2014 Mar;9(3):397-402. doi: 10.1097/JTO.0000000000000078.

DOI:10.1097/JTO.0000000000000078

PMID:24445595

Abstract

INTRODUCTION

We developed an innovative approach for malignant pleural mesothelioma (MPM) with a short accelerated course of high-dose hemithoracic intensity-modulated radiation therapy (IMRT) followed by extrapleural pneumonectomy (EPP). This phase I/II study assessed the feasibility of Surgery for Mesothelioma After Radiation Therapy (SMART).

METHODS

All resectable clinical T1-3N0M0 histologically proven, previously untreated MPMs were eligible. Patients received 25 Gy in five daily fractions during 1 week to the entire ipsilateral hemithorax with concomitant 5 Gy boost to areas at risk followed by EPP within 1 week of completing neoadjuvant IMRT. Adjuvant chemotherapy was offered to ypN2 patients on final pathologic findings. The primary end point was treatment-related mortality and secondary end points were overall survival, disease-free survival, treatment-related morbidity, and patterns of failure.

RESULTS

Targeted accrual of 25 patients was completed between November 2008 and October 2012. All patients completed SMART. IMRT was well tolerated with no grade 3+ toxicities. EPP was performed 6 ± 2 days after completing IMRT without any perioperative mortality. Thirteen patients developed grade 3+ surgical complications. One patient (4%) died from treatment-related toxicity (empyema) during follow-up. All but one patient had stage III or IV disease on final pathologic findings. Five of 13 ypN2 patients received adjuvant chemotherapy. After a median follow-up of 23 months (range, 6-51), the cumulative 3-year survival reached 84% in epithelial subtypes compared with 13% in biphasic subtypes (p = 0.0002).

CONCLUSIONS

SMART is feasible in resectable MPM patients. This innovative protocol presents encouraging results and supports future studies looking at long-term outcome in patients with epithelial subtypes.

摘要

简介

我们开发了一种针对恶性胸膜间皮瘤（MPM）的创新方法，采用短疗程加速高剂量半胸部强度调制放疗（IMRT），随后进行胸膜外肺切除术（EPP）。这项 I/II 期研究评估了放疗后胸膜间皮瘤手术（SMART）的可行性。

方法

所有可切除的临床 T1-3N0M0 组织学证实、未经治疗的 MPM 患者均符合条件。患者在 1 周内接受 25 Gy 的 5 次每日分割照射，同侧半胸部全剂量照射，同时对危险区域进行 5 Gy 的推量照射，随后在完成新辅助 IMRT 后 1 周内进行 EPP。根据最终病理结果，对 ypN2 患者提供辅助化疗。主要终点是治疗相关死亡率，次要终点是总生存率、无病生存率、治疗相关发病率和失败模式。

结果

2008 年 11 月至 2012 年 10 月期间，目标入组 25 例患者。所有患者均完成了 SMART。IMRT 耐受性良好，无 3 级以上毒性反应。EPP 在完成 IMRT 后 6 ± 2 天进行，围手术期无死亡。13 例患者发生 3 级以上手术并发症。1 例（4%）患者在随访期间因治疗相关毒性（脓胸）死亡。所有患者最终病理分期均为 III 期或 IV 期，除 1 例患者外均为上皮样亚型。13 例 ypN2 患者中有 5 例接受了辅助化疗。中位随访 23 个月（范围 6-51 个月）后，上皮样亚型的 3 年累积生存率达到 84%，而双相亚型为 13%（p=0.0002）。