Department of Thoracic Surgery, University Hospitals KU Leuven, Leuven, Belgium.
Department of Chronic Disease, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
Eur J Cardiothorac Surg. 2019 May 1;55(5):934-941. doi: 10.1093/ejcts/ezy385.
Combined modality treatment (CMT) for malignant pleural mesothelioma (MPM) remains a matter of debate regarding the choice of surgical procedure: extrapleural pneumonectomy (EPP) or pleurectomy/decortication.
We performed a prospective interventional cohort study between 2003 and 2014. All consecutive patients with any histological MPM subtype, ≤70 years old, World Health Organization performance status ≤1, medically fit for pneumonectomy and stage cT1-2cN0-2cM0 (TNM7) or lower were included. Eligibility for CMT was discussed by the multidisciplinary tumour board. Our local CMT protocol consisted of induction chemotherapy, followed by EPP and hemithoracic radiotherapy. Induction chemotherapy consisted of 3 cycles of cisplatin (75 mg/m2 day 1) and pemetrexed (500 mg/m2 day 1), each administered once every 3 weeks. If non-progressive, EPP was performed followed by hemithoracic radiotherapy (most frequently, intensity-modulated radiotherapy; dose 54 Gy/1.8 Gy ± boost). Feasibility and long-term survival analyses were performed. Overall survival and disease-free survival (DFS) were calculated from histological confirmation of a diagnosis of MPM.
Out of 197 patients, 97 started with CMT (79 epithelioid, 15 mixed and 3 sarcomatoid tumours, based on histological analysis). Clinical TNM was IA (n = 9)/IB (n = 8)/II (n = 57)/III (n = 23). A total of 76 patients underwent surgery (EPP: n = 56; exploratory thoracotomy: n = 20). The in-hospital mortality rate was 3.6%. Out of 56 patients who underwent surgery, 47 completed the entire CMT protocol. The intent-to-treat median and 5-year OS were 22.4 [95% confidence interval (CI) = 15.5-27.9] months and 11.2% (95% CI = 6.9-23.4). In patients who completed the CMT protocol (n = 47), these values were 33.2 (95% CI = 23.0-45.0) months and 24.2% (95% CI = 13.4-43.8). The intent-to-treat median and 5-year DFS were 15.6 (95% CI = 14.0-17.3) months and 9.9% (95% CI = 5.1-19.2), 19.8 (95% CI = 16.8-27.7) months and 17.2% (95% CI = 8.6-34.1) in those who had the full CMT. The Cox proportional hazards model showed a significantly lower DFS in positive lymph nodes (HR 2.79, 95% CI=1.35-5.78; P=0.006). In 30 (64%) patients with epithelioid type MPM without positive lymph nodes (pN0) after EPP, the 5-year DFS was 27.0% (95% CI=14.1-51.7).
CMT with EPP for MPM is feasible, with an acceptable surgical mortality rate, and results in a 5-year survival rate of 24%. Careful patient selection (staging and physical performance) is extremely important.
恶性胸膜间皮瘤（MPM）的联合治疗（CMT）在手术方式的选择上仍存在争议：胸膜外全肺切除术（EPP）或胸膜切除术/剥脱术。
我们在 2003 年至 2014 年期间进行了一项前瞻性干预性队列研究。所有组织学任何类型的 MPM 亚型、≤70 岁、世界卫生组织表现状态≤1、适合进行全肺切除术且分期为 cT1-2cN0-2cM0（TNM7）或更低的患者均被纳入研究。多学科肿瘤委员会讨论了 CMT 的适应证。我们的局部 CMT 方案包括诱导化疗，随后是 EPP 和半胸部放疗。诱导化疗包括顺铂（75mg/m2，第 1 天）和培美曲塞（500mg/m2，第 1 天）各 3 个周期，每 3 周给药 1 次。如果非进展性，则进行 EPP，随后进行半胸部放疗（最常为调强放疗；剂量 54Gy/1.8Gy± 增敏剂量）。进行了可行性和长期生存分析。总生存和无病生存（DFS）从 MPM 的组织学诊断确认开始计算。
197 例患者中，97 例开始接受 CMT（79 例上皮样，15 例混合性和 3 例肉瘤样肿瘤，基于组织学分析）。临床 TNM 分期为 IA（n=9）/IB（n=8）/II（n=57）/III（n=23）。共有 76 例患者接受了手术（EPP：n=56；探查性剖胸术：n=20）。院内死亡率为 3.6%。56 例接受手术的患者中，47 例完成了整个 CMT 方案。意向治疗的中位总生存时间和 5 年生存率分别为 22.4 个月（95%置信区间 [CI]：15.5-27.9）和 11.2%（95%CI：6.9-23.4）。完成 CMT 方案的患者（n=47），这些值分别为 33.2 个月（95%CI：23.0-45.0）和 24.2%（95%CI：13.4-43.8）。意向治疗的中位和 5 年 DFS 分别为 15.6 个月（95%CI：14.0-17.3）和 9.9%（95%CI：5.1-19.2），19.8 个月（95%CI：16.8-27.7）和 17.2%（95%CI：8.6-34.1），在那些有完整 CMT 的患者中。Cox 比例风险模型显示，淋巴结阳性（HR 2.79，95%CI=1.35-5.78；P=0.006）与 DFS 显著相关。在 30 例（64%）EPP 后无阳性淋巴结（pN0）的上皮样 MPM 患者中，5 年 DFS 为 27.0%（95%CI=14.1-51.7）。
EPP 联合 CMT 治疗 MPM 是可行的，手术死亡率可接受，5 年生存率为 24%。仔细的患者选择（分期和体力状况）非常重要。
