A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the "SMART" approach for resectable malignant pleural mesothelioma

Our plain-English summary of A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the "SMART" approach for resectable malignant pleural mesothelioma, by B.C. Cho, R. Feld, N. Leighl, et al (Journal of Thoracic Oncology, 2014).

The study

• Authors: B.C. Cho, R. Feld, N. Leighl, I. Opitz, M. Anraku, M.S. Tsao, D.M. Hwang, A. Hope, M. de Perrot
• Journal: Journal of Thoracic Oncology
• Published: 2014;9(3):397-402
• Cited by: 102 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: We developed an innovative approach for malignant pleural mesothelioma (MPM) with a short accelerated course of high-dose hemithoracic intensity-modulated radiation therapy (IMRT) followed by extrapleural pneumonectomy (EPP). This phase I/II study assessed the feasibility of Surgery for Mesothelioma After Radiation Therapy (SMART).

Methods: All resectable clinical T1-3N0M0 histologically proven, previously untreated MPMs were eligible. Patients received 25 Gy in five daily fractions during 1 week to the entire ipsilateral hemithorax with concomitant 5 Gy boost to areas at risk followed by EPP within 1 week of completing neoadjuvant IMRT. Adjuvant chemotherapy was offered to ypN2 patients on final pathologic findings. The primary end point was treatment-related mortality and secondary end points were overall survival, disease-free survival, treatment-related morbidity, and patterns of failure.

Results: Targeted accrual of 25 patients was completed between November 2008 and October 2012. All patients completed SMART. IMRT was well tolerated with no grade 3+ toxicities. EPP was performed 6 ± 2 days after completing IMRT without any perioperative mortality. Thirteen patients developed grade 3+ surgical complications. One patient (4%) died from treatment-related toxicity (empyema) during follow-up. All but one patient had stage III or IV disease on final pathologic findings. Five of 13 ypN2 patients received adjuvant chemotherapy. After a median follow-up of 23 months (range, 6-51), the cumulative 3-year survival reached 84% in epithelial subtypes compared with 13% in biphasic subtypes (p = 0.0002).

Conclusions: SMART is feasible in resectable MPM patients. This innovative protocol presents encouraging results and supports future studies looking at long-term outcome in patients with epithelial subtypes.

In plain English

This phase I/II feasibility study came from Princess Margaret Cancer Centre and Toronto General Hospital, Canada. It tested a treatment, SMART, for surgically removable malignant pleural mesothelioma. It did not study asbestos exposure. From November 2008 to October 2012, 25 previously untreated patients received about a week of high-dose radiation to the affected side of the chest. The dose was 25 Gy in five daily doses, with a 5 Gy boost to visible tumor. Surgery then removed the lung, pleural lining and nearby tissues (extrapleural pneumonectomy). All 25 completed both steps; the radiation caused no grade 3 or higher side effects. Thirteen patients (52%) had grade 3 or higher surgical complications; the most common was atrial fibrillation, in five patients. No one died within 30 days of surgery. One patient (4%) died of an empyema at 88 days. After a median follow-up of 23 months, 3-year overall survival was 58%. It was 84% in the epithelial subtype and 13% in the biphasic subtype. The authors concluded SMART is feasible, noting the study was nonrandomized and needed more patients and longer follow-up.

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, nonrandomized, single-cohort phase I/II clinical feasibility study of a treatment protocol
• Who was studied: 25 patients with previously untreated, resectable malignant pleural mesothelioma (clinical stage T1-3N0M0), treated at Princess Margaret Cancer Centre and Toronto General Hospital, Toronto, Canada, between November 2008 and October 2012. There were 19 men and 6 women; final histology was 16 epithelial and 9 biphasic. Of 138 patients seen in the same period, 82% were not eligible.
• Exposure: No asbestos exposure was studied. The study examined a treatment: hemithoracic intensity-modulated radiation therapy, 25 Gy in five daily fractions over about 1 week with a concomitant 5 Gy boost to visible tumor and tract sites. This was followed within 1 week by extrapleural pneumonectomy. Patients with mediastinal lymph node involvement (ypN2) were offered adjuvant chemotherapy.
• Main results:
  • All 25 patients completed radiation and surgery; the radiation caused no grade 3 to 5 toxicities.
  • 13 of 25 patients (52%) developed grade 3 or higher complications after surgery. The most common was atrial fibrillation, in five patients.
  • No patient died within 30 days of surgery or during the hospital stay.
  • One patient (4%) died of a treatment-related complication (empyema) at 88 days.
  • Age was the only factor possibly linked to more grade 3 or higher complications (mean 66 versus 60 years in patients without such complications), but this was not statistically significant (p = 0.06).
  • On final pathology, all but one patient had stage III (11) or stage IV (13) disease.
  • 5 of the 13 patients with ypN2 disease (38%) received adjuvant chemotherapy.
  • After a median follow-up of 23 months (range 6 to 51), cumulative 3-year overall survival for all 25 patients was 58%.
  • In patients with the epithelial subtype, 3-year cumulative survival was 84% and disease-free survival was 65%.
  • In patients with the biphasic subtype, 3-year survival was 13%; the difference from the epithelial subtype had p = 0.0002.
  • All patients with epithelial, ypT3 or ypT4, N2-negative disease were alive at last follow-up; only one of them had a recurrence.
  • 11 patients had a recurrence (7 biphasic, 4 epithelial). In 6 of these 11 (55%), the recurrence was at distant sites only.
• The authors' conclusion: The authors concluded that SMART is feasible in patients with resectable malignant pleural mesothelioma. They said it may potentially improve survival in selected patients with epithelial mesothelioma, but that larger numbers and longer follow-up are required.
• Limitations the authors state:
  • The study was nonrandomized and had a single cohort, so patient selection is a potential confounding factor.
  • Longer follow-up and more patients are needed before definitive conclusions can be drawn about long-term effects.
  • The protocol needs close coordination between radiation oncology and thoracic surgery, which may hamper its use in some centers.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma, Intensity-Modulated Radiation Therapy (IMRT), Extrapleural Pneumonectomy (EPP), Hemithorax, Chemotherapy, Overall Survival, Disease-Free Survival.

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)
• Tomotherapy after pleurectomy/decortication or biopsy for malignant pleural mesothelioma allows the delivery of high dose of radiation in patients with intact lung — E. Minatel, M. Trovo, et al. (2012)
• Surgery for malignant pleural mesothelioma after radiotherapy (SMART): final results from a single-centre, phase 2 trial — B.C.J. Cho, L. Donahoe, et al. (2021)
• Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma — M. de Perrot, R. Feld, et al. (2016)
• Improved Outcomes with Modern Lung-Sparing Trimodality Therapy in Patients with Malignant Pleural Mesothelioma — F. Shaikh, M.G. Zauderer, et al. (2017)
• 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)

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