Elsevier

Practical Radiation Oncology

Volume 10, Issue 6, November–December 2020, Pages 423-433
Practical Radiation Oncology

Critical Review
Disease-Related Outcomes and Toxicities of Intensity Modulated Radiation Therapy After Lung-Sparing Pleurectomy for Malignant Pleural Mesothelioma: A Systematic Review

https://doi.org/10.1016/j.prro.2020.02.007Get rights and content

Abstract

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.

Introduction

Malignant pleural mesothelioma (MPM) is a rare neoplasm, with an annual incidence of approximately 2660 cases in the United States,1 and remains associated with dismal outcomes.2 The current standard of care for patients with resectable disease involves gross macroscopic resection and chemotherapy, with or without intraoperative pleural therapy or radiation therapy (RT).3,4 Although extrapleural pneumonectomy (EPP) has been the historic technique for gross resection, severe consequences can arise owing to the profound physiological changes from removal of an entire lung.5 As a result, in the contemporary era, management has shifted toward lung-sparing approaches, such as partial pleurectomy, pleurectomy/decortication (P/D), or extended P/D (eP/D).6 These techniques may be associated with lower operative mortality or improved overall survival (OS) compared with EPP,7 although no randomized studies comparing both approaches have been completed to date.

The use of RT for MPM is controversial. A randomized trial failed to detect clinical outcome benefits for RT8; this is complicated by the fact that the trial was underpowered, confounding any conclusions derived from the study.8,9 In the post-EPP setting, RT may be associated with improved local control,10,11 although with well-documented potential for severe radiation pneumonitis.12 Given these toxicity concerns, intensity modulated radiation therapy (IMRT), a newer technique that may offer improved conformality and lower doses to surrounding organs-at-risk, has been used to potentially improve the therapeutic ratio.13 IMRT after EPP has been associated with promising clinical outcomes,14 but even with improved conformality, fatal toxicities can occur.15

As in the post-EPP setting, the role of RT (including IMRT) in patients with intact lungs remains controversial. Three-dimensional conformal RT (3DCRT) can produce severe toxicities in the post-pleurectomy setting,12,16 and as a result, the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology remains equivocal on whether RT should be delivered for postpleurectomy patients. Furthermore, the NCCN notes that IMRT may be allowable in select cases, but akin to the importance of surgeon experience for mesothelioma,17 the experience of the radiation oncology team remains important: “RT under such circumstances after P/D is usually not recommended. Hemithoracic IMRT after P/D may be considered in centers with experience and expertise in these methods.”4 Despite the ambiguity in this setting, there have been no summative data to date reporting on the safety and efficacy of postpleurectomy IMRT (P-IMRT). Thus, the aim of this study is to perform a systematic review of the disease-related outcomes and toxicities of IMRT after P-IMRT for malignant pleural mesothelioma.

Section snippets

Methods and Materials

We conducted this systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.18 Eligibility criteria included articles published in English examining adjuvant RT in patients status post pleurectomy for MPM. Applicable techniques included partial pleurectomy, P/D, eP/D, and pleurectomy not otherwise specified. The PubMed search engine was used as the primary means of data collection. Searches served to identify articles addressing this

Results

The characteristics of the patient populations and therapies for the 10 studies included in this systematic review are detailed in Table 1. Taken together, most patients had advanced disease, received chemotherapy, and had epithelioid histology. Table 2 demonstrates the characteristics of RT in each study and the dose constraints therein. The most commonly prescribed doses ranged from 45 to 54 Gy, and 6 studies used an additional boost. Tables 3 and 4 illustrate the toxicity profiles and

Discussion

This systematic review comprehensively assessed data regarding toxicities and outcomes of IMRT after pleurectomy for MPM and found that this approach produced relatively few higher-grade toxicities with reasonable disease-related outcomes. Although current NCCN guidelines remain equivocal regarding P-IMRT, largely on account of sparse data, our study suggests that this approach is safe and can be considered in well-selected patients.4 Other guidelines continue to move toward this conclusion,

Conclusions

This systematic review comprehensively assessed data regarding toxicities and disease-related outcomes from IMRT after pleurectomy for malignant pleural mesothelioma, and found that this approach (especially when delivering conventionally fractionated IMRT with doses of 45-54 Gy) produced relatively few higher-grade toxicities (grade 3 pneumonitis ranging from 0%-16%, and grades 4 and 5 pneumonitis in <1.5%), and had reasonable disease-control outcomes. Although current NCCN guidelines remain

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Sources of support: none.

Disclosures: Dr Mesko reports consultations fees with Oscar Health care; all other authors declare that conflicts of interest do not exist.

Data Sharing: This systematic review was based on previously published literature and no additional meta-analyses were conducted. The authors do not own these publications; however, they may be available online.

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