Patterns of failure, toxicity, and survival after extrapleural pneumonectomy and hemithoracic intensity-modulated radiation therapy for malignant pleural mesothelioma

Our plain-English summary of Patterns of failure, toxicity, and survival after extrapleural pneumonectomy and hemithoracic intensity-modulated radiation therapy for malignant pleural mesothelioma, by D.R. Gomez, D.S. Hong, P.K. Allen, et al (Journal of Thoracic Oncology, 2013).

The study

• Authors: D.R. Gomez, D.S. Hong, P.K. Allen, J.S. Welsh, R.J. Mehran, A.S. Tsao, Z. Liao, S.D. Bilton, R. Komaki, D.C. Rice
• Journal: Journal of Thoracic Oncology
• Published: 2013;8(2):238-45
• Cited by: 97 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: We investigated safety, efficacy, and recurrence after postoperative hemithoracic intensity-modulated radiation therapy (IMRT) in patients with malignant pleural mesothelioma treated with extrapleural pneumonectomy (EPP), during the past decade at a single institution.

Methods: In 2001-2011, 136 consecutive patients with malignant pleural mesothelioma underwent EPP with planned adjuvant IMRT. Eighty-six patients (64%) underwent hemithoracic IMRT; the rest were not eligible because of postoperative complications, disease progression, or poor performance status. We assessed toxicity, survival, and patterns of failure in these 86 patients. Toxicity was scored with the Common Terminology Criteria for Adverse Events version 4.0; survival outcomes were estimated with the Kaplan-Meier method; and locoregional patterns of failure were classified as in-field, marginal, or out-of-field. Risk factors related to survival were identified by univariate and multivariate Cox regression analysis.

Results: Median overall survival time for all 86 patients receiving IMRT was 14.7 months. Toxicity rates of grade of 3 or more were: skin 17%, lung 12%, heart 2.3%, and gastrointestinal toxicity 16%. Five patients experienced grade 5 pulmonary toxicity. Rates of locoregional recurrence-free survival, distant metastasis-free survival, and overall survival (OS) were 88%, 55%, and 55% at 1 year and 71%, 40%, and 32% at 2 years. On multivariate analysis, pretreatment forced expiratory volume in 1 second, nonepithelioid histology, and nodal status were associated with distant metastasis-free survival and OS.

Conclusion: IMRT after EPP is associated with low rates of locoregional recurrence, though some patients experience life-threatening lung toxicity. Tumor histology and nodal status can be helpful in identifying patients for this aggressive treatment.

In plain English

This retrospective study from The University of Texas M.D. Anderson Cancer Center reviewed 136 consecutive patients with malignant pleural mesothelioma. Each had extrapleural pneumonectomy, surgery removing the lung, pleura, part of the pericardium and diaphragm, between January 2001 and April 2011, with radiation planned afterward. Eighty-six (64%) went on to receive hemithoracic intensity-modulated radiation therapy (IMRT). The rest did not, mainly because of poor condition, death, or cancer found spreading or recurring. The study did not examine asbestos exposure. Among the 86, median overall survival was 14.7 months, and 32% were alive at 2 years. Fourteen (16%) had a recurrence in the treated side of the chest and 51 (59%) had distant spread. Severe (grade 3 or higher) toxicity affected the skin in 17.4%, the gut in 16.3%, the lungs in 11.6% and the heart in 2.3%. Five patients had fatal lung toxicity. Non-epithelioid tumor type, N2 lymph node status and lower lung function before treatment were associated with worse survival. The authors concluded that this approach produced high rates of local control, but that distant spread remained a problem.

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: retrospective single-institution case series (review of patients treated at one center)
• Who was studied: 136 consecutive patients who had extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma at M.D. Anderson Cancer Center, Houston, January 2001 to April 2011. Of these, 86 (64%) received hemithoracic IMRT and were the main group analyzed; 50 had EPP alone.
• Exposure: The exposure studied was treatment, not asbestos: extrapleural pneumonectomy followed by hemithoracic IMRT at 45 to 50 Gy in 25 daily fractions. Thirteen patients received a boost of 55 to 60 Gy. Some patients also received chemotherapy.
• Main results:
  • Of the 50 patients who did not receive IMRT, 22 had poor performance status after surgery and 11 died before radiation could be considered. Another 12 had distant metastasis or significant local recurrence found at or before treatment simulation, and 5 refused radiation or were lost to follow-up.
  • Median overall survival for the 86 patients who received IMRT was 14.7 months.
  • Overall survival at 2 years was 32% in the IMRT group.
  • Grade 3 or higher toxicity in the 86 IMRT patients: skin 17.4% (n = 15), gastrointestinal 16.3% (n = 14), heart 2.3% (n = 2), lung 11.6% (n = 10).
  • Five IMRT patients had grade 5 (fatal) toxicity, all pulmonary: 3 radiation pneumonitis and 2 bronchopleural fistulae.
  • Among the 86 IMRT patients, 14 (16%) had locoregional recurrence and 51 (59%) had distant metastasis. Only 2 had locoregional recurrence alone.
  • Of the 14 patients with locoregional recurrence, 8 had multiple recurrences within the high-dose region.
  • On multivariate analysis in the IMRT group, nonepithelioid histology, higher nodal status and lower pretreatment forced expiratory volume in 1 second predicted worse distant metastasis-free survival and overall survival. For overall survival, the hazard ratio for nonepithelioid histology was 3.64 (95% CI 1.47 to 5.70).
  • No variables were associated with locoregional recurrence-free survival, and chemotherapy was not associated with any survival outcome.
  • Median overall survival was 4.5 months for patients who had EPP alone. The authors stated that this comparison is affected by selection: these patients missed IMRT because of poor condition, early failure or death.
• The authors' conclusion: The authors concluded that EPP followed by IMRT produced high rates of locoregional control, with low but non-negligible high-grade cardiopulmonary toxicity. Because patients remained at risk of distant metastasis, they called for further trials of systemic agents.
• Limitations the authors state:
  • Some recurrences were not confirmed by tissue examination and were judged from clinical and imaging records.
  • Small numbers prevented full analysis of the effect of chemotherapy.
  • The comparison of EPP plus IMRT with EPP alone is subject to substantial bias, because the EPP-alone group had factors predicting worse prognosis.
  • Lung-sparing surgery has shown similar outcomes in other trials, and there is no consensus on the best approach.

Topics

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

Medical terms in this study, explained in our Lexicon: Extrapleural Pneumonectomy (EPP), Intensity-Modulated Radiation Therapy (IMRT), Pleural Mesothelioma, Disease Progression, Performance Status, Median Overall Survival, Recurrence-Free Survival, Metastasis.

Related studies

• 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)
• Hemithoracic radiation therapy after extrapleural pneumonectomy for malignant pleural mesothelioma: Toxicity and outcomes at an Australian institution — A. Bece, M.M. Tin, et al. (2015)
• Clinical experience of volumetric modulated arc therapy for malignant pleural mesothelioma after extrapleural pneumonectomy — T. Kimura, Y. Doi, et al. (2015)
• Hemithoracic intensity-modulated radiotherapy using helical tomotherapy for patients after extrapleural pneumonectomy for malignant pleural mesothelioma — T. Ebara, H. Kawamura, et al. (2012)
• High-dose-rate surface brachytherapy to boost elongated, curvilinear incisional scars after extrapleural pneumonectomy for malignant pleural mesothelioma treated with adjuvant intensity-modulated radiation therapy — L.A. Doyle, T.N. Showalter, et al. (2010)
• Long-term outcomes of intensity-modulated radiotherapy following extra-pleural pneumonectomy for malignant pleural mesothelioma — Y. Matsuo, K. Shibuya, et al. (2017)

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