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.
J Thorac Oncol. 2014 Mar;9(3):397-402. doi: 10.1097/JTO.0000000000000078.
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).
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.
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).
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.
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。
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。
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）。
SMART 在可切除的 MPM 患者中是可行的。这种创新方案取得了令人鼓舞的结果，支持未来研究观察上皮样亚型患者的长期预后。
