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INTRODUCTION

Malignant pleural mesothelioma (MPM) is a rare cancer commonly associated with asbestos exposure.1 Recently, it was determined that germline mutations in BRCA1-associated protein 1 (BAP1) may predispose to mesothelioma development in non-asbestos-exposed patients.2 Although basic biologic knowledge about MPM has increased during the past decade, and many new potentially active agents have reached various stages of development, the number of novel treatments that have been approved for MPM patients is limited.

The increasing evidence from phase 2 trials assessing the efficacy of surgery-based multimodal treatment of MPM has reached the point where consistent overall survival data ranging between a median survival of 14 and 25.5 months is demonstrated for extrapleural pneumonectomy (EPP).3 To date, combined multimodality treatment is the most commonly used treatment for MPM in many centers. One particular approach involves sequencing the surgery to follow induction therapy—a concept that has been adapted from Stage III NSCLC with the goal of downstaging the tumor or eradicating the outer tumor layer for better resectability.4 Further justification for sequencing chemotherapy before surgery is the expectation that the chemotherapy regimen will be better tolerated prior to surgery, and the full required dose will be applied.

GENERAL PRINCIPLES (TECHNICAL, CLINICAL, ONCOLOGIC) THAT SUPPORT THIS APPROACH (EASE AND EFFICIENCY OF CARE)

Generally, the goal of cure requires the incapacitation of all proliferating, viable tumor clonogens. This can be achieved through a variety of methods, including ablative (removal of clonogens), tumoricidal (killing of clonogens), and tumoristatic (stunning of clonogens). Surgical ablation (resection) is the oldest and most straightforward way of incapacitating tumor clonogens. Tumors that are small, locally confined, and completely resected are most suitable for ablative treatments. On the other hand, locally extensive, metastatic, infiltrative, or technically difficult-to-resect tumors are usually not adequately addressed by resection alone. This provides the rationale of adding adjuvant (supportive) therapy to help address occult microscopic residual clonogens that remain following resection. The term neoadjuvant or induction therapy describes preoperative treatment prior to surgery in order to downstage the tumor and make surgery more effective. The definitive therapy is surgery whose aim is to address as a minimum macroscopic complete resection.

Originally, the aim of induction therapy was downstaging of the primary tumor to make for an easier and more complete resection.5 This required sufficient time to allow for tumor regression, often requiring 4 to 6 weeks (or longer), depending on the number of cycles of chemotherapy and weeks of radiotherapy, alone or in combination. One major advantage with induction therapy is that the response is often prognostic and can help in patient selection, avoiding treatment in those who are unlikely to benefit from additional major surgery. In fact, response to chemotherapy is one parameter of our multimodality prognostic score that allows better selection of patients for surgery. We have implemented this score in our daily practice for patient selection to avoid futile ...

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