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. 2022 Nov;11(11):2230-2242.
doi: 10.21037/tlcr-22-199.

Multimodal therapy of epithelioid pleural mesothelioma: improved survival by changing the surgical treatment approach

Laura V Klotz  1   2 , Hans Hoffmann  3 , Rajiv Shah  2   4 , Florian Eichhorn  1   2 , Christiane Gruenewald  1 , Elena L Bulut  1 , Raffaella Griffo  1   2 , Thomas Muley  2   5 , Petros Christopoulos  2   4 , Philip Baum  1 , Peter Huber  6 , Seyer Safi  3 , Marc Kriegsmann  2   7 , Michael Thomas  2   4 , Helge Bischoff  4 , Hauke Winter  1   2 , Martin E Eichhorn  1   2
Affiliations

Multimodal therapy of epithelioid pleural mesothelioma: improved survival by changing the surgical treatment approach

Laura V Klotz et al. Transl Lung Cancer Res. 2022 Nov.

Abstract

Background: The exact role and type of surgery for malignant pleural mesothelioma (MPM) remains controversial. This study aimed at analyzing a 20-year single center perioperative experience in MPM surgery at our high-volume thoracic surgery center and comparing the overall survival after trimodal extrapleural pneumonectomy (EPP) and extended pleurectomy and decortication combined with hyperthermic intrathoracic chemoperfusion (EPD/HITOC) and adjuvant chemotherapy with that after chemotherapy (CTx) alone.

Methods: Patients with epithelioid MPM treated with neoadjuvant chemotherapy, EPP and adjuvant radiotherapy within a trimodal concept or EPD/HITOC in combination with adjuvant chemotherapy between 2001 and 2018 were included in this retrospective analysis. Surgical cohorts were compared to patients treated with standard chemotherapy.

Results: Overall, 182 patients (69 EPP, 57 EPD/HITOC, 56 CTx) were analyzed. Due to occupational exposure to asbestos for most of the patients, 154 patients (84.6%) were male. The patients in the surgical cohorts were significantly younger than those in the CTx cohort. There was no significant difference between the proportion of patient age and side. The median overall survival of the EPD/HITOC cohort with 38.1 months was significantly longer than that of the EPP and CTx cohorts (24.0 and 15.8 months). Better survival was significantly associated with an ECOG 0 performance status, age below 70 years, and negative lymph node status. In the multivariate analysis, EPD/HITOC was significantly associated with improved overall survival. Perioperative morbidity was lower in the EPD/HITOC group than in the EPP cohort.

Conclusions: EPD/HITOC is feasible and safe for localized epithelioid pleural mesothelioma. Changing the surgical approach to a less radical lung-sparing technique may improve overall survival compared to trimodal EPP.

Keywords: Pleural mesothelioma; chemoperfusion; cytoreductive surgery; decortication; extrapleural pneumonectomy.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-199/coif). RS has received honoraria for lectures from Roche and AstraZeneca and an institutional grant from BMS outside the submitted work. FE received consulting fees from the Roche Pharma AG outside the submitted work. CG received consulting fees from Bristol Myers Squibb and speakers honoraria from Astra Zeneca, all outside the submitted work. PC has received research funding from AstraZeneca, Novartis, Roche, and Takeda, speaker’s honoraria from AstraZeneca, Novartis, Roche, Takeda, support for attending meetings from AstraZeneca, Eli Lilly, Gilead, Novartis, Takeda, and personal fees for participating to advisory boards from Boehringer Ingelheim, Chugai, Pfizer and Roche, all outside the submitted work. MT received institutional grants from Astra Zeneca, Bristol-Myers Squibb, Merck, Roche, and Takeda, speakers honoraria from AbbVie, AstraZeneca, Beigene, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Daiichi Sankyo, GlaxoSmithKline, Janssen Oncology, Lilly, MSD, Novartis, Pfizer, Sanofi, Roche, and Takeda as well as support for attendance of meetings from AstraZeneca, Bristol-Myers Squibb, Janssen Oncology, MSD, Pfizer, Roche, and Takeda. For participation in the advisory board, MT received honoraria from AbbVie, AstraZeneca, Beigene, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Daiichi Sankyo, GlaxoSmithKline, Janssen Oncology, Lilly, MSD, Novartis, Pfizer, Sanofi, Roche, and Takeda, all outside the submitted work. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Violin plot of ages of the patients in the CTx, EPP, and EPD/HITOC cohorts, one-way ANOVA and Tukey’s multiple comparison test. CTx, chemotherapy; EPP, extrapleural pneumonectomy; EPD/HITOC, extended pleurectomy and decortication/hyperthermic intrathoracic chemoperfusion.
Figure 2
Figure 2
Kaplan-Meier overall survival curves of the whole MPM cohort and distributed by the three treatment concepts. (A) Kaplan-Meier OS curves with 95% CI (blue line) of total cohort (n=182) with a MOST of 23.2 months. (B) OS for patients stratified according to treatment modality. EPD/HITOC with an OS of 38.1 months compared to patients after trimodal treatment including EPP with an OS of 24.0 months (P=0.01) and compared to patients with chemotherapy alone (MOST 15.8 months). Log-rank test. CTx, chemotherapy; EPD/HITOC, extended pleurectomy and decortication/hyperthermic intrathoracic chemoperfusion; EPP, extrapleural pneumonectomy; MPM, malignant pleural mesothelioma; OS, overall survival; CI, confidence interval; MOST, median overall survival time.
Figure 3
Figure 3
Kaplan-Meier overall survival curves for all patients with MPM (n=182) stratified by ECOG (A) age (B) and nodal involvement (C). Log-rank test. MPM, malignant pleural mesothelioma; ECOG, Eastern Cooperative Oncology Group.
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