Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma

Our plain-English summary of Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma, by M. de Perrot, R. Feld, N.B. Leighl, et al (The Journal of Thoracic and Cardiovascular Surgery, 2016).

The study

• Authors: M. de Perrot, R. Feld, N.B. Leighl, A. Hope, T.K. Waddell, S. Keshavjee, B.C. Cho
• Journal: The Journal of Thoracic and Cardiovascular Surgery
• Published: 2016;151(2):468-73
• Cited by: 101 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: To evaluate a new protocol of accelerated hemithoracic intensity-modulated radiation therapy (IMRT) followed by extrapleural pneumonectomy (EPP) for patients with resectable malignant pleural mesothelioma (MPM).

Methods: A total of 25 Gy of radiation was delivered in 5 daily fractions over 1 week to the entire ipsilateral hemithorax with concomitant boost of 5 Gy to volumes at high risk based on computed tomography and positron emission tomography scan findings. EPP was performed at 6 ± 2 days after the end of radiation therapy. Adjuvant chemotherapy was offered to patients with ypN2 disease.

Results: A total of 62 patients were included between November 2008 and October 2014. One patient died in the hospital 2 months after EPP, for an operative mortality of 1.6%, and 2 died after discharged from the hospital for an overall treatment-related mortality (grade 5 toxicity) of 4.8%. Twenty-four patients (39%) developed grade 3 to 5 (grade 3+) complications. On final pathology, 94% of the patients were stage III or IV, and 52% had ypN2 disease. The median survival for all patients as an intention-to-treat analysis was 36 months. The median overall survival and disease-free survival was 51 and 47 months, respectively, in epithelial subtypes, compared with 10 and 8 months in biphasic subtypes (P = .001). Ipsilateral chest recurrence occurred in 8 patients.

Conclusions: Accelerated hemithoracic IMRT followed by EPP has become our preferred approach for resectable MPM. The results have been encouraging in patients with epithelial subtype.

Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

In plain English

This single-center, single-arm phase II study in Toronto, Canada, tested SMART, a treatment for malignant pleural mesothelioma. It did not study asbestos exposure. Patients received one week of radiation to the whole affected side of the chest (25 Gy in 5 daily doses), with an extra 5 Gy only to visible tumor and biopsy and drainage tract sites. Within 2 weeks the lung and pleura were removed (extrapleural pneumonectomy). Of 256 patients with this disease seen between November 2008 and October 2014, 62 were selected. All 62 completed both treatments. Three (4.8%) died of treatment-related causes. Twenty-four (39%) had grade 3 or higher complications, most often atrial fibrillation. Estimated median survival overall was 36 months. Among 56 previously untreated patients with clinical stage T1-3N0M0 disease (excluding those with chest-wall extension or mediastinal node involvement on scans), median overall survival was 51 months for the epithelial subtype versus 10 months for the biphasic subtype. Thirty had a recurrence. The authors concluded the approach was associated with encouraging survival in epithelial disease. They noted the single-center, single-arm design, need for longer follow-up, and patient selection.

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: Prospective single-center, single-arm phase II expansion study (clinical treatment trial), following an earlier seamless phase I/II safety study of 25 patients
• Who was studied: 62 patients with malignant pleural mesothelioma judged suitable for the protocol, out of 256 patients with the disease seen at the authors' institution (Princess Margaret Cancer Centre and Toronto General Hospital, Toronto, Canada) between November 2008 and October 2014. 52 (84%) were male, median age was 64 years (range 41-75), 44 had epithelial and 18 had biphasic histology.
• Exposure: Asbestos exposure was not studied. The intervention was accelerated intensity-modulated radiation to the whole affected side of the chest (25 Gy in 5 daily fractions over 1 week), with a 5 Gy boost to the gross tumor volume and tract sites only, followed within 2 weeks by extrapleural pneumonectomy. Patients with ypN2 disease were offered adjuvant chemotherapy.
• Main results:
  • All 62 patients completed the planned radiation and surgery.
  • Treatment-related death occurred in 3 of 62 patients (4.8%). One died in hospital 2 months after surgery, and no patient died within 30 days of surgery.
  • 24 patients (39%) had grade 3 or higher complications. The main one was atrial fibrillation, in 12 patients.
  • On final pathology, 57 patients (92%) had stage III (25) or stage IV (32) disease, and 32 (52%) had ypN2 disease.
  • Estimated median survival for all 62 patients (intention-to-treat) was 36 months, with 36 patients alive at last follow-up.
  • Among 56 previously untreated patients with clinical stage T1-3N0M0 disease, median disease-free survival was 47 months and overall survival was 51 months in the epithelial subtype. The comparable figures in the biphasic subtype were 8 and 10 months. Six patients were left out of this analysis: those with tumor extending to the chest wall on pre-treatment CT, those with mediastinal lymph node involvement on PET scan, and those given chemotherapy first.
  • In epithelial-subtype patients, 3-year disease-free survival was 66% for those with ypN0 disease, compared with 48% for those with node-positive (ypN+) disease.
  • 30 patients developed recurrence. Recurrence within the same side of the chest occurred in 8 patients.
• The authors' conclusion: The authors concluded that extrapleural pneumonectomy can be performed after induction hemithoracic radiation. They also concluded that the approach is associated with encouraging overall and disease-free survival in patients with epithelial cT1-3N0M0 mesothelioma.
• Limitations the authors state:
  • The study was a single-center trial with a single treatment arm.
  • Longer follow-up is needed before definitive conclusions can be drawn.
  • In the published meeting discussion, the first author acknowledged that the patients were a selected group.

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), Pleural Mesothelioma, Intensity-Modulated Radiation Therapy (IMRT), Hemithorax, Chemotherapy, Pathology, Median Survival, Median Overall Survival.

Related studies

• Impact of induction therapy on postoperative outcome after extrapleural pneumonectomy for malignant pleural mesothelioma: does induction-accelerated hemithoracic radiation increase the surgical risk? — P. Mordant, K. McRae, et al. (2016)
• Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial) — S. Hasegawa, M. Okada, et al. (2016)
• 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)
• Importance of excision repair cross-complementation group 1 and ribonucleotide reductase M1 as prognostic biomarkers in malignant pleural mesothelioma treated with platinum-based induction chemotherapy followed by surgery — L. Frischknecht, M. Meerang, et al. (2015)
• Induction chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy for malignant pleural mesothelioma: experience of Guy's and St Thomas' hospitals — A. Bille, E. Belcher, et al. (2012)
• 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)

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