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Purpose: This review explores the use of intensity modulated radiation therapy (IMRT) after lung-sparing surgery in malignant pleural mesothelioma (MPM). Because severe toxicities have been documented after radiation therapy for MPM, its use remains controversial, especially as modern surgical management has shifted toward lung-sparing pleurectomy/decortication. IMRT is an advanced technique that may allow for safer radiation therapy delivery, but there remains limited data (including no summative data) to support this notion., Methods and Materials: We performed a systematic review evaluating the safety and efficacy of post-pleurectomy IMRT (P-IMRT). A systematic review of PubMed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted for publications of all dates that specifically reported clinical outcomes and/or toxicities of P-IMRT in patients with MPM. Ten original studies were included in this review., Results: The incidence of grade 3 pneumonitis ranged from 0% to 16%, with all but 2 studies reporting rates below 9%. Grade 4 and 5 pneumonitis were observed in less than 1.5% of cases, except in one publication that used hypofractionated radiation therapy to doses >60 Gy. Crude local failure rates ranged from 19% to 60%, median progression free survival ranged from 12 to 16 months, and median overall survival ranged from 19 to 28 months., Conclusions: P-IMRT produces relatively few higher-grade toxicities and has reasonable disease-related outcomes, especially when delivered using conventionally fractionated regimens to doses of 45 to 54 Gy and exercising careful attention to dose constraints during treatment planning. IMRT can thus be considered in well-selected patients in whom adequate survival after pleurectomy is expected. These data also support the initiation of the phase III NRG-LU006 trial of extended pleurectomy/decortication and chemotherapy with or without IMRT., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Posterior intercostal lymph nodes, previously undescribed for cancer staging, are part of the lymphatic drainage of the pleural space. This study assessed the impact of posterior intercostal lymph nodes on survival in patients undergoing extended pleurectomy/decortication for malignant pleural mesothelioma., Methods: As part of the thoracic lymphadenectomy, posterior intercostal lymph nodes were accessed by incising the endothoracic fascia at the level of the rib heads. These nodes were systematically harvested in 56 consecutive patients undergoing extended pleurectomy decortication in a clinical trial. The impact of these nodes on progression-free (PFS) and overall survival (OS) was analyzed by multiple statistical methods., Results: Median PFS and OS were 11.6 and 25.5 months, respectively. In 6 of 56 patients (11%), posterior intercostal lymph nodes were the only positive nodes, and overall, 48.2% had posterior intercostal lymph node metastases. Patients with N2 disease had significantly poorer prognosis if the posterior intercostal lymph nodes were involved: PFS (7.3 vs 14.9 months, P = .002) and OS (14.4 vs 26.1 months, P = .028). In the multivariable models, after adjustment for nodal stage and other prognostic factors, intercostal nodes remained associated with a 2.5-fold elevated risk of progression (P < .001) and a 2.3-fold elevated risk of death (P < .001)., Conclusions: Metastases to posterior intercostal lymph nodes independently more than doubled the risk of progression and death and were the only site of nodal metastases in 11% of patients. These nodes warrant further investigation, including nonoperative techniques to identify and factor them into treatment decision making., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to assess survival for patients with malignant pleural mesothelioma (MPM), epithelial subtype, utilizing extended pleurectomy-decortication combined with intraoperative photodynamic therapy (PDT) and adjuvant pemetrexed-based chemotherapy., Methods: From 2005 to 2013, 90 patients underwent lung-sparing surgery and PDT for MPM. All patients had a preoperative diagnosis of epithelial subtype, of which 17 proved to be of mixed histology. The remaining 73 patients with pure epithelial subtype were analyzed. All patients received lung-sparing surgery and PDT; 92% also received chemotherapy. The median follow-up was 5.3 years for living patients., Results: Macroscopic complete resection was achieved in all 73 patients. Thirty-day mortality was 3% and 90-day mortality was 4%. For all 73 patients (89% American Joint Commission on Cancer stage III/IV, 69% N2 disease, median tumor volume 550 mL), the median overall and disease-free survivals were 3 years and 1.2 years, respectively. For the 19 patients without lymph node metastases (74% stage III/IV, median tumor volume 325 mL), the median overall and disease-free survivals were 7.3 years and 2.3 years, respectively., Conclusions: This is a mature dataset for MPM that demonstrates the ability to safely execute a complex treatment plan that included a surgical technique that consistently permitted achieving a macroscopic complete resection while preserving the lung. The role for lung-sparing surgery is unclear but this series demonstrates that it is an option, even for advanced cases. The overall survival of 7.3 years for the node negative subset of patients, still of advanced stage, is encouraging. Of particular interest is the overall survival being approximately triple the disease-free survival, perhaps PDT related. The impact of PDT is unclear, but it is hoped that it will be established by an ongoing randomized trial., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)