Induction Chemotherapy Followed by Pleurectomy Decortication and Hyperthermic Intraoperative Chemotherapy (HITHOC) for Early-Stage Epitheliod Malignant Pleural Mesothelioma-A Prospective Report.

Stefano Bongiolatti,Francesca Mazzoni,Carlo Ammatuna,Enrico Caliman,Lorenzo Antonuzzo,Ottavia Salimbene,Camilla E Comin,Luca Voltolini

doi:10.3390/jcm10235542

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive disease with poor prognosis and the current treatment for early-stage MPM is based on a multimodality therapy regimen involving platinum-based chemotherapy preceding or following surgery. To enhance the cytoreductive role of surgery, some peri- or intra-operative intracavitary treatments have been developed, such as hyperthermic chemotherapy, but long-term results are weak. The aim of this study was to report the post-operative results and mid-term outcomes of our multimodal intention-to-treat pathway, including induction chemotherapy, followed by surgery and Hyperthermic Intraoperative THOracic Chemotherapy (HITHOC) in the treatment of early-stage epithelioid MPM. Since 2017, stage I or II epithelioid MPM patients have been inserted in a surgery-based multimodal approach comprising platinum-based induction chemotherapy, followed by pleurectomy and decortication (P/D) and HITHOC with cisplatin. The Kaplan–Meier method was used to estimate overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). During the study period, n = 65 patients affected by MPM were evaluated by our institutional Multidisciplinary Tumour Board; n = 12 patients with stage I-II who had no progression after induction chemotherapy underwent P/D and HITHOC. Post-operative mortality was 0, and complications developed in n = 7 (58.3%) patients. The median estimated OS was 31 months with a 1-year and 3-year OS of 100% and 55%, respectively. The median PFS was 26 months with 92% of a 1-year PFS, whereas DFS was 19 months with a 1-year DFS rate of 83%. The multimodal treatment of early-stage epithelioid MPM, including induction chemotherapy followed by P/D and HITHOC, was well tolerated and feasible with promising mid-term oncological results.

Highlights

Malignant pleural mesothelioma (MPM) is an aggressive, fatal disease with a very poor prognosis [1]
There has been a general shift in surgery for MPM from extra pleural pneumonectomy (EPP) to pleurectomy and decortication (P/D), because more evidence is available in favour of lung-sparing techniques [7,8,9,10]
From January 2017 to December 2020, all patients affected by clinical stage I or II epithelioid MPM were inserted in a surgery-based multimodal approach consisting of platinum-based iCT [2] followed by P/D and Hyperthermic Intraoperative THOracic Chemotherapy (HITHOC) with cisplatin [13]

Summary

Introduction

Malignant pleural mesothelioma (MPM) is an aggressive, fatal disease with a very poor prognosis [1]. Since surgical cytoreduction is not expected to yield an R0 resection, surgery has to be part of a multimodality treatment, including chemotherapy and/or radiotherapy. For early stage MPM, current treatment options always integrate multimodality concepts, include chemotherapy [2] before or after surgery [3], surgery with or without intraoperative local treatments, radiation therapy and, more recently, immunotherapy [4,5,6]. Surgery still remains the cornerstone in the multimodal management of early-stage MPM, its precise role and type are highly controversial. Few studies have shown favourable post-operative outcomes from the association between cytoreductive surgery and intra-operative intracavitary treatments, such as hyperthermic chemotherapy, hyperthermic povidone iodine and photodynamic therapy [12,13,14,15,16]. The long-term results of these integrated approaches suffered from the typical biases of single-centre retrospective analyses, with the inclusion of patients treated on and off protocols during the long study period

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