Department of Hematology and Oncology, CISSS Montérégie Centre/Hôpital Charles-Lemoyne, Université Sherbrooke, Quebec, Canada
Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
Oncologist. 2019 Jul;24(7):e510-e517. doi: 10.1634/theoncologist.2018-0501. Epub 2018 Nov 26.
Multimodality therapy with preoperative radiation (RT) followed by extrapleural pneumonectomy (EP) for patients with operable malignant pleural mesothelioma (MPM) has demonstrated encouraging results. At relapse, there are few data on the tolerance and efficacy of systemic therapies after prior multimodality therapy.
We conducted a retrospective analysis of patients with relapsed MPM after RT and EPP ± adjuvant chemotherapy to determine overall survival (OS; date of relapse to death) and the proportion of patients that received systemic therapy and associated response rate (RR). OS was estimated using Kaplan-Meier method and potential prognostic variables were examined.
Fifty-three patients were included (2008-2016). Median OS was 4.8 months (median follow-up 4.4 months, range 0.03-34.8). Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2, disease-free interval (DFI) <1 year, and hemoglobin ≤110 g/L at recurrence were associated with worse prognosis. Thirty-six percent of patients received any systemic therapy, whereas it was omitted in 62% because of poor PS. RR was 15% (0 complete responses, 15% partial responses) in 13 individuals with response-evaluable disease. Therapy was discontinued because of toxicity (6/15) or disease progression (5/15), and median number of cycles was four.
Patients with relapsed MPM following RT and EPP, especially those with ECOG PS ≥2, DFI <1 year, and hemoglobin ≤110 g/L at recurrence, have poor prognosis and low RR to first-line systemic therapy. Earlier detection and novel diagnostic markers of relapse as well as potential neoadjuvant or adjuvant systemic therapy should be investigated in future studies.
The results of this study have reinforced the importance of careful selection of appropriate candidates for this combined-modality approach and favor prompt detection of recurrence with early and regular postoperative imaging and biopsy of suspected relapsed disease along with rapid initiation of systemic therapy even in patients with very low burden of disease. Furthermore, with the emergence of new systemic agents targeting different histological subtypes of malignant pleural mesothelioma, histological sampling of recurrence could inform therapeutic decisions in the future.
术前放疗（RT）联合胸膜外全肺切除术（EP）治疗可手术的恶性胸膜间皮瘤（MPM）的多模态治疗已显示出令人鼓舞的结果。在复发时，对于先前接受多模态治疗后的系统治疗的耐受性和疗效，仅有很少的数据。
我们对接受 RT 和 EPP±辅助化疗治疗后复发的 MPM 患者进行了回顾性分析，以确定总生存期（OS；从复发到死亡的时间）和接受系统治疗的患者比例及其相关缓解率（RR）。使用 Kaplan-Meier 法估计 OS，并检查了潜在的预后变量。
共纳入 53 例患者（2008-2016 年）。中位 OS 为 4.8 个月（中位随访时间为 4.4 个月，范围 0.03-34.8 个月）。ECOG 表现状态（PS）≥2、无疾病间期（DFI）<1 年以及复发时血红蛋白≤110g/L 与较差的预后相关。36%的患者接受了任何系统治疗，而 62%的患者由于 PS 较差而未接受治疗。13 例可评估疾病患者中 RR 为 15%（0 例完全缓解，15%部分缓解）。由于毒性（6/15）或疾病进展（5/15）而停止治疗，中位治疗周期数为 4 个。
接受 RT 和 EPP 治疗后复发的 MPM 患者，尤其是 ECOG PS≥2、DFI<1 年以及复发时血红蛋白≤110g/L 的患者，预后较差，对一线系统治疗的 RR 较低。未来的研究应探讨更早地检测复发以及新型诊断标志物，以及可能的新辅助或辅助系统治疗。
本研究结果强调了对这种联合治疗方法进行仔细选择合适患者的重要性，并支持通过早期且定期的术后影像学检查和疑似复发疾病的活检来快速检测复发，即使在疾病负担非常低的患者中也是如此，并尽快开始系统治疗。此外，随着针对恶性胸膜间皮瘤不同组织学亚型的新型系统药物的出现，未来对复发组织的采样可以为治疗决策提供信息。
