Systemic Therapy Use and Outcomes After Relapse from Preoperative Radiation and Extrapleural Pneumonectomy for Malignant Pleural Mesothelioma

Abstract

Background 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. Materials and Methods 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. Results 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. Conclusion 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. Implications for Practice 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.

Relapse Patterns and Tailored Treatment Strategies for Malignant Pleural Mesothelioma Recurrence after Multimodality Therapy

“…Regardless, we found local recurrence as a predictor of the longest PRS, maybe due to a less deleterious effect on performance status and, consequently, on survival compared with distant spread. As already stated in the literature [ 6 , 7 ], a long DFS (≥12 months) result was significantly associated with good survival, probably reflecting a slower tumor growth speed associated with a less aggressive recurrent disease. Furthermore, epithelial histology, besides predicting OS and DFS, resulted as a favorable prognostic factor for PRS, as already reported by Kai et al as a trend at multivariate analysis ( p = 0.065).…”

“…Previous reports have highlighted poor prognosis in patients with recurrent MPM after multimodality treatment, with median PRS after EPP ranging from 3 to 6.5 months [ 3 , 4 , 5 , 6 , 8 ], whereas encouraging PRS were reported after PD by Nakamura et al and Kai and collaborators (14.4 and 20 months, respectively) [ 7 , 8 ]. In the present study, overall median PRS was 12 months and 14 and 8 months in the EPP and PD group, respectively.…”

“…Failure, in local and/or distant sites, is one of the major concerns; in fact, there has been no established treatment for recurrence of MPM after the multimodality approach. Post-recurrence outcomes after EPP [ 3 , 4 , 5 , 6 ] and PD [ 7 ] have been reported. However, to the best of our knowledge, only one study [ 8 ] explored post-recurrence outcomes comparing EPP and PD in a multimodality setting.…”

Drug Regimen for Patients after a Pneumonectomy

“…Adjuvant radiotherapy was found to be effective in decreasing the risk of recurrence after EPP, but it could not improve overall survival due to its limited efficacy in distant metastasis [88]. Another recent retrospective analysis evaluated the efficacy of additional chemotherapy in patients with relapsed MPM after previous multimodality therapy [89]. Patients had received preoperative hemithoracic radiation, EPP, and adjuvant chemotherapy before the recurrence [89].…”

“…Another recent retrospective analysis evaluated the efficacy of additional chemotherapy in patients with relapsed MPM after previous multimodality therapy [89]. Patients had received preoperative hemithoracic radiation, EPP, and adjuvant chemotherapy before the recurrence [89]. Among 42 patients who were diagnosed with relapsed diseases, only 15 patients underwent systemic therapy [89].…”