SMART: logical radiotherapy and surgery beyond MARS

Our plain-English summary of SMART: logical radiotherapy and surgery beyond MARS, by H.I. Pass (The Lancet. Oncology, 2021).

The study

• Author: H.I. Pass
• Journal: The Lancet. Oncology
• Published: 2021;22(2):156-157
• Type of article: Comment
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher

In plain English

This article is a short commentary, not a new study. The author, from NYU Langone Health in New York, discussed the published final results of the SMART trial by Cho and colleagues. In that trial, patients with malignant pleural mesothelioma received hemithoracic radiotherapy followed by extrapleural pneumonectomy. The author contrasted SMART with the earlier MARS trial. SMART reported 30-day mortality of 1% and 90-day mortality of 3%, compared with a surgical 30-day mortality of 15.8% in MARS. The author also compared SMART with the SAKK 17/04 trial. Median overall survival was 24.4 months (95% CI 18.5 to 31.1) among the 96 SMART patients and 15.0 months (95% CI 12.1 to 19.3) among 151 patients in the SAKK intention-to-treat population. The author called these 'supposed differences' and noted that without a randomised trial it is difficult to know whether preoperative radiotherapy actually improves survival. The author suggested that the SMART team's earlier laboratory and mouse studies of radiation and immune responses might explain any difference. The commentary did not discuss asbestos exposure.

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: Commentary (editorial comment) on another group's published clinical trial; not original research
• Who was studied: No patients were studied by the author. The commentary discusses the SMART trial's 96 patients with malignant pleural mesothelioma and compares them with patients in the MARS and SAKK 17/04 trials, including 151 patients in the SAKK intention-to-treat analysis.
• Exposure: Treatment, not asbestos: hemithoracic radiotherapy given before extrapleural pneumonectomy for malignant pleural mesothelioma. Asbestos exposure is not discussed.
• Main results:
  • As reported by the author, the SMART trial showed 30-day mortality of 1% and 90-day mortality of 3% after surgery.
  • As reported by the author, the earlier MARS trial had a surgical 30-day mortality of 15.8%.
  • As reported by the author, in SMART there was 15% grade 4 perioperative morbidity. Only seven patients completed adjuvant chemotherapy, even though 60 (63%) had yPN1 or yPN2 disease.
  • In the author's cross-trial comparison, median overall survival was 24.4 months (95% CI 18.5 to 31.1) for the 96 SMART patients and 15.0 months (95% CI 12.1 to 19.3) for the SAKK 17/04 intention-to-treat population of 151 patients.
  • The SAKK 17/04 trial's part one, cited by the author, included 151 patients with mesothelioma assessed in an intention-to-treat analysis.
  • In the author's comparison, disease-free survival from registration was 12.2 months (95% CI 9.5 to 14.8) in the SAKK phase 2 postoperative radiotherapy group and 18.0 months (12.6 to 21.7) in SMART.
  • The author described earlier mouse studies by the SMART team. In these studies, non-ablative, hypofractionated radiotherapy caused immune activation with upregulation of CD8 T cells in a murine mesothelioma model.
• The authors' conclusion: The author concluded that, in the clinical trial setting for mesothelioma, extrapleural pneumonectomy seems to be efficacious but carries substantial complications. The author suggested the SMART team's work on radiation and immune response may be the most logical explanation for any survival difference.
• Limitations the authors state:
  • The author noted that without a randomised trial it is hard to say whether preoperative radiotherapy and macroscopic complete resection actually improve survival. The author called the survival differences between trials 'supposed'.
  • The author noted that patient selection matters but is not a perfect exercise.

Topics

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

Related studies

• 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)
• Prophylactic radiotherapy for the prevention of procedure-tract metastases after surgical and large-bore pleural procedures in malignant pleural mesothelioma (SMART): a multicentre, open-label, phase 3, randomised controlled trial — A.O. Clive, H. Taylor, et al. (2016)
• A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the "SMART" approach for resectable malignant pleural mesothelioma — B.C. Cho, R. Feld, et al. (2014)
• Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study — T. Treasure, L. Lang-Lazdunski, et al. (2011)
• Surgery in mesothelioma--where do we go after MARS? — B.I. Hiddinga, J.P. van Meerbeeck (2013)
• Surgery for mesothelioma: MARS landing and future missions — T. Treasure (2010)

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