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

Our plain-English summary of Disease-Related Outcomes and Toxicities of Intensity Modulated Radiation Therapy After Lung-Sparing Pleurectomy for Malignant Pleural Mesothelioma: A Systematic Review, by R. Patel, E.B. Ludmir, J.A. Miccio, et al (Practical Radiation Oncology, 2020).

The study

• Authors: R. Patel, E.B. Ludmir, J.A. Miccio, H. Menon, A.R. Barsky, S.M. Mesko, M. Kodali, T. Lautenschlaeger, S. Adeberg, C.B. Simone, V. Verma
• Journal: Practical Radiation Oncology
• Published: 2020;10(6):423-433
• Type of article: Systematic review
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

In plain English

This article was a systematic review, not a new study of patients. The authors searched PubMed for studies published through June 2019 that reported results of intensity modulated radiation therapy (IMRT) given after lung-sparing pleurectomy surgery for malignant pleural mesothelioma. Ten studies were included. In those studies, between 3 and 111 patients received this treatment. The article does not discuss asbestos exposure. In the 9 studies that reported side effects, rates of grade 3 pneumonitis (lung inflammation) ranged from 0% to 16%. Grade 4 and 5 pneumonitis were seen in 3 studies, and only one of those was above 1.5%. That study used hypofractionated radiation and reported 2 grade 5 (fatal) toxicities among 51 patients, both in patients given a boost dose. Crude local failure rates ranged from 19% to 60%. Median progression-free survival ranged from 12 to 16 months, and median overall survival from 19 to 28 months. The authors concluded that the approach is safe and can be considered in well-selected patients. They noted that many studies grouped these patients with others, and that most data came from high-volume centers.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Systematic review of published studies, following PRISMA guidelines; no meta-analysis was performed
• Who was studied: 10 published studies, found through PubMed searches with no start date, up to June 2019, of patients with malignant pleural mesothelioma treated with IMRT after pleurectomy. The number of patients receiving this treatment in each study ranged from 3 (of 14) to 111 (of 286).
• Exposure: The 'exposure' studied was a treatment, not asbestos: intensity modulated radiation therapy given after lung-sparing pleurectomy. The most commonly prescribed doses were 45 to 54 Gy, and 6 studies used an additional boost dose. The article does not address asbestos or fiber exposure.
• Main results:
  • Across the 9 studies that reported toxicities, grade 3 pneumonitis rates ranged from 0% to 16%. All but 2 studies had rates below 9%.
  • Grade 4 and 5 pneumonitis were seen in only 3 studies, and only one study had a rate above 1.5%.
  • In the hypofractionated study (Fodor et al), 2 of 51 patients had grade 5 toxicities, both among patients who received a boost.
  • In the Minatel et al study, 1 of 69 patients had a grade 4 pericardial effusion and 1 of 69 had fatal pneumonitis. In the Shaikh et al study, there was one case each of grade 4 and grade 5 pneumonitis among 78 patients.
  • Across studies, crude local failure ranged from 19% to 60%, median progression-free survival from 12 to 16 months, and median overall survival from 19 to 28 months.
• The authors' conclusion: The authors concluded that IMRT after pleurectomy produced relatively few higher-grade toxicities, especially with conventionally fractionated doses of 45 to 54 Gy, and had reasonable disease-control outcomes. They stated that the approach is safe and can be considered in well-selected patients.
• Limitations the authors state:
  • Many of the included studies grouped patients who received IMRT after pleurectomy with other patients, including non-operated patients.
  • Boost doses were used non-uniformly, so the authors could not comment reliably on their usefulness.
  • Dose constraints varied widely between studies, so the review could not recommend specific dose constraints.
  • Chemotherapy was given before or after surgery depending on the study, and some studies did not report its timing.
  • The data came largely from high-volume, specialized centers, so the conclusions may not apply to patients treated at centers with less experience.
  • A meta-analysis could not be reliably conducted because surgical techniques varied and data could not be adequately extracted.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Systematic Review, Pleurectomy/Decortication (P/D), Pneumonitis, Median Overall Survival, Chemotherapy.

Related studies

• Geometric dose prediction model for hemithoracic intensity-modulated radiation therapy in mesothelioma patients with two intact lungs — L. Kuo, E.D. Yorke, et al. (2016)
• Intensity-Modulated Radiation Therapy Improves the Target Coverage Over 3-D Planning While Meeting Lung Tolerance Doses for All Patients With Malignant Pleural Mesothelioma — S. Ulger, E. Cetin, et al. (2017)
• Patterns of failure, toxicity, and survival after extrapleural pneumonectomy and hemithoracic intensity-modulated radiation therapy for malignant pleural mesothelioma — D.R. Gomez, D.S. Hong, et al. (2013)
• Current readings: improvements in intensity-modulated radiation therapy for malignant pleural mesothelioma — K.E. Rosenzweig (2013)
• Intensity modulated radiation therapy after extra-pleural pneumonectomy for malignant pleural mesothelioma is feasible without fatal pulmonary toxicity and provides good survival — S. Jhavar, J. Pruszynski, et al. (2018)
• Intensity-modulated radiation therapy with simultaneous integrated boost in unresected left-sided pleural mesothelioma: a case report — S. Cilla, C. Digesú, et al. (2010)

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