Malignant Pleural Mesothelioma: Preliminary Toxicity Results of Adjuvant Radiotherapy Hypofractionation in a Prospective Trial (MESO-RT)

Our plain-English summary of Malignant Pleural Mesothelioma: Preliminary Toxicity Results of Adjuvant Radiotherapy Hypofractionation in a Prospective Trial (MESO-RT), by E. Parisi, D. Arpa, G. Ghigi, et al (Cancers, 2023).

The study

• Authors: E. Parisi, D. Arpa, G. Ghigi, L. Fabbri, F. Foca, L. Tontini, E. Neri, M. Pieri, S. Cima, M.A. Burgio, M.L. Belli, L. Luzzi, A. Romeo
• Journal: Cancers
• Published: 2023;15(4)
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant Pleural Mesothelioma (MPM) is a rare malignancy with an overall poor prognosis. The standard therapeutic strategy in early-stage disease is trimodality therapy. In this publication, we report the preliminary toxicity results of the first 20 patients treated with accelerated hypofractionated radiotherapy. Between July 2017 to June 2019, 20 MPM patients were enrolled and treated with accelerated hypofractionated radiotherapy using helical tomotherapy and intensity-modulated arc therapy. The prescription dose was 30 Gy in five daily fractions, while an inhomogeneous dose escalation to 40 Gy was prescribed based solely upon the presence of gross residual tumor. Only one case of G3 toxicity was reported, which was a bilateral pneumonitis that occurred two years after treatment probably due to superinfection. Median Time to Progression reached 18.2 months while one- and three-year Overall Survival rates were 85% (95% CI:60.4-94.9) and 49.5% (95% CI:26.5-68.9), respectively. Treatment of the intact lung with pleural intensity-modulated arc irradiation is a novel treatment strategy that appears to be safe, feasible, and without a high grade of lung toxicity. Survival rates and Time to Progression are encouraging.

In plain English

This article reported an interim analysis of MESO-RT, a prospective trial at one cancer institute in Meldola, Italy. It tested a short, high-dose-per-session radiotherapy course for malignant pleural mesothelioma in patients whose lung had not been removed. Twenty patients enrolled from July 2017 to June 2019 received 30 Gy in five daily sessions, up to 40 Gy to visible remaining tumor. Fourteen had undergone pleurectomy/decortication surgery and six had a biopsy only. Of the 17 patients whose history was known, 13 (76.5%) had past asbestos exposure. The main goal was measuring side effects. No grade 3 or 4 acute side effects were found; the most common was lung inflammation (pneumonitis), grade 1 in 65.0% and grade 2 in 10%. Median overall survival was 33.1 months (95% CI 14.4 to not estimable), and median time to progression was 18.2 months (95% CI 11.3 to not estimable). Patients who had surgery had longer time to progression than biopsy-only patients (26.9 vs. 11.3 months). The authors concluded the schedule appears safe without a high grade of lung toxicity, and called for larger randomized trials.

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: Interim analysis of a prospective single-institution (mono-institutional) phase II pilot trial
• Who was studied: 20 patients with malignant pleural mesothelioma (16 men, 4 women; 19 epithelioid, 1 sarcomatoid), enrolled between July 2017 and June 2019 at IRST "Dino Amadori", Meldola, Italy. Fourteen had pleurectomy/decortication and six had biopsy only. The trial aims to enroll 30 patients; 29 had been enrolled at the time of writing.
• Exposure: The exposure studied was a treatment: accelerated hypofractionated radiotherapy, 30 Gy in five daily fractions, with inhomogeneous dose escalation to 40 Gy for gross residual tumor (10 patients). Asbestos exposure was recorded only as a patient characteristic: 13 of 17 patients with known history (76.5%). No fiber types are given.
• Main results:
  • Acute toxicity in all 20 patients: no grade 3 or 4 acute toxicity. The most common acute toxicity was pneumonitis, grade 1 in 65.0% and grade 2 in 10%.
  • Late toxicity: no grade 3 or 4 pneumonitis was reported; grade 1 pneumonitis occurred in two patients (10%).
  • Among 17 patients with lung function tests before treatment and at three months, there was a worsening of restrictive ventilatory defect that was not statistically significant (p-value 0.061).
  • Overall survival for all patients: median 33.1 months (95% CI 14.4 to not estimable); 1-year 85% (95% CI 60.4 to 94.9); 3-year 49.5% (95% CI 26.5 to 68.9).
  • 36-month overall survival was 63.5% (95% CI 33.1 to 82.9) in the pleurectomy/decortication group versus 16.7% (95% CI 0.8 to 51.7) in the biopsy-only group (p-value 0.086).
  • Median time to progression for all patients was 18.2 months (95% CI 11.3 to not estimable). It was 26.9 months for patients who had pleurectomy/decortication versus 11.3 months for those who did not have surgery (p = 0.015).
• The authors' conclusion: The authors concluded that 30 Gy in five daily fractions appears safe without a high grade of lung toxicity. They called for multicentric randomized trials with more patients to consolidate this treatment strategy.
• Limitations the authors state:
  • The cohort was not uniform in type and extent of surgery, because patients had surgery at two different centers.
  • Not all patients could have lung function tests on schedule because of the COVID pandemic, which also slowed enrollment.
  • The lung function data must be interpreted with caution because of the small number of patients and because this is an interim analysis of an ongoing protocol.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Trimodality Therapy, Bilateral, Pneumonitis, Overall Survival.

Related studies

• Adjuvant radiotherapy after extrapleural pneumonectomy for mesothelioma. Prospective analysis of a multi-institutional series — S. Tonoli, P. Vitali, et al. (2011)
• Pattern of failure after adjuvant radiotherapy following extrapleural pneumonectomy of pleural mesothelioma in the SAKK 17/04 trial — O. Riesterer, I.F. Ciernik, et al. (2019)
• Protocol for a prospective observational cohort study collecting data on demographics, symptoms and biomarkers in people with mesothelioma (ASSESS-meso) — R.J.H. Conway, J. Symonds, et al. (2022)
• 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)
• Adjuvant intensity-modulated proton therapy in malignant pleural mesothelioma. A comparison with intensity-modulated radiotherapy and a spot size variation assessment — S. Lorentini, M. Amichetti, et al. (2012)
• An association between postoperative radiotherapy for primary breast cancer in 11 National Surgical Adjuvant Breast and Bowel Project (NSABP) studies and the subsequent appearance of pleural mesothelioma — M. Deutsch, S.R. Land, et al. (2007)

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