Intensity-modulated radiotherapy after extrapleural pneumonectomy in the combined-modality treatment of malignant pleural mesothelioma

Our plain-English summary of Intensity-modulated radiotherapy after extrapleural pneumonectomy in the combined-modality treatment of malignant pleural mesothelioma, by A. Chi, Z. Liao, N.P. Nguyen, et al (Journal of Thoracic Oncology, 2011).

The study

• Authors: A. Chi, Z. Liao, N.P. Nguyen, C. Howe, D. Gomez, S.Y. Jang, R. Komaki
• Journal: Journal of Thoracic Oncology
• Published: 2011;6(6):1132-41
• Type of article: Systematic review
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Local therapy is becoming increasingly important as a part of the definitive treatment for malignant pleural mesothelioma after extrapleural pneumonectomy (EPP) because of the emergence of trimodality therapy consisted of chemotherapy, EPP, and adjuvant radiotherapy. Herein, we explore the current evidence and indications for adjuvant intensity-modulated radiotherapy (IMRT), as well as how to further improve this technique and adapt new technology in the delivering adjuvant radiotherapy in the setting of trimodality therapy.

Methods: A systematic review of relevant studies identified through PubMed, ISI Web of Knowledge (Web of Science), the Cochrane Library, and the National Guideline Clearinghouse search engines was performed.

Results: Local control remains poor despite the inclusion of conventional adjuvant radiation therapy in trimodality therapy. This can be improved by the delivery of adjuvant IMRT. However, IMRT can be associated with severe pulmonary toxicity if the radiation dose to the remaining lung is not kept to a very low level. This is especially true when patients are receiving chemotherapy. New advances in technology can allow for lower doses to the contralateral lung, decreased treatment delivery time, and improved target dose coverage.

Conclusion: Excellent local control can be achieved through adjuvant IMRT after EPP for malignant pleural mesothelioma. Severe pulmonary toxicity may be avoided by setting stringent dose constraints for the contralateral lung. This can be aided by the advances in technology. Post-treatment surveillance may be reliably conducted by periodical [18F]-fluorodeoxyglucose-positron emission tomography imaging.

In plain English

This article was a review, not a new study of patients. The authors searched PubMed, Web of Science, the Cochrane Library and the National Guideline Clearinghouse for published studies of patients with malignant pleural mesothelioma treated with extrapleural pneumonectomy (EPP) and radiation after surgery, with or without chemotherapy. After selection, 60 references remained. These included 15 studies on combined chemotherapy, surgery and radiation, 7 on the outcomes and side effects of intensity-modulated radiotherapy (IMRT) after EPP, and 12 on technical aspects. Among the reviewed studies, Rice et al. reported 13% locoregional recurrence among 63 patients given IMRT after EPP. Buduhan et al. reported local recurrence of 14.3% after IMRT versus 41.7% after conventional radiation. Allen et al. reported that 6 of 13 patients (46%) developed grade 5 radiation pneumonitis. Tan et al. reported that PET/CT detected recurrent disease with 94% sensitivity in 25 patients. The authors concluded that IMRT after EPP can improve local control but that strict radiation dose limits for the remaining lung must be followed. They proposed a set of dose limits as a guideline. They noted that the studies involved small numbers of patients.

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
• Who was studied: Published studies of patients with histologically proven malignant pleural mesothelioma treated with EPP and adjuvant radiotherapy, with or without chemotherapy. Physics studies of IMRT technique were also included. 60 references were assessed: 15 on trimodality therapy, 7 on outcomes and toxicity of IMRT after EPP, and 12 on physics and technical aspects. Searches were limited to English-language studies in humans.
• Exposure: Not an asbestos exposure study. The treatments examined were intensity-modulated radiotherapy (and conventional radiotherapy) given after extrapleural pneumonectomy, with or without chemotherapy. Asbestos is mentioned only in the background.
• Main results:
  • The search left 60 references for assessment: 15 reported clinical outcomes of trimodality therapy, 7 reported outcomes and toxicity of adjuvant IMRT after EPP, and 12 explored physics and technical aspects.
  • In the reviewed study by Rice et al. (M. D. Anderson Cancer Center), 63 mostly stage III–IV patients were treated with IMRT after EPP. In this group, locoregional recurrence was 13% and in-field recurrence was 5%. Median survival was 14.2 months, 3-year overall survival was 20%, and the distant metastasis rate was 54%.
  • In the reviewed study by Buduhan et al., patients who underwent EPP had local recurrence of 14.3% after IMRT and 41.7% after conventional radiotherapy. The review describes this difference as significant, after a median follow-up of 20.6 months.
  • In the reviewed study by Allen et al., 13 patients received cisplatin and pemetrexed, EPP and IMRT to 54 Gy. Of these, six (46%) developed grade 5 radiation pneumonitis.
  • The review reports four grade 5 radiation pneumonitis cases after trimodality therapy in 13 patients in the study by Kristensen et al.
  • In the reviewed study by Tan et al. of 25 patients after trimodality therapy, PET/CT detected recurrent disease with sensitivity of 94%, specificity of 100%, positive predictive value of 100% and negative predictive value of 88%.
• The authors' conclusion: The authors concluded that further improvement in local control can be achieved through adjuvant IMRT. They also concluded that strict radiation dose limits for the remaining (contralateral) lung must be carefully followed. They proposed a set of dose limits as a guideline for planning adjuvant IMRT. They said newer technologies and FDG-PET surveillance need further study in prospective studies.
• Limitations the authors state:
  • The studies of severe lung toxicity involved small numbers of patients.
  • Because the disease is rare, it may be difficult to set a safe dose threshold for each lung dose measure.
  • The value of PET/CT for surveillance still needs confirmation in prospective clinical trials.

Topics

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

Medical terms in this study, explained in our Lexicon: Intensity-Modulated Radiation Therapy (IMRT), Extrapleural Pneumonectomy (EPP), Pleural Mesothelioma, Trimodality Therapy, Chemotherapy, Systematic Review.

Related studies

• 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)
• Long-term outcomes of intensity-modulated radiotherapy following extra-pleural pneumonectomy for malignant pleural mesothelioma — Y. Matsuo, K. Shibuya, et al. (2017)
• Extra-pleural pneumonectomy in the era of image-guided intensity-modulated radiotherapy — M. Trovo, D. Franceschini, et al. (2019)
• Hemithoracic intensity-modulated radiotherapy using helical tomotherapy for patients after extrapleural pneumonectomy for malignant pleural mesothelioma — T. Ebara, H. Kawamura, et al. (2012)
• Clinical experience of volumetric modulated arc therapy for malignant pleural mesothelioma after extrapleural pneumonectomy — T. Kimura, Y. Doi, et al. (2015)
• 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)

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