Oligometastatic Mesothelioma Treated with Ablative Radiotherapy (OMAR): A Multicenter Study

Our plain-English summary of Oligometastatic Mesothelioma Treated with Ablative Radiotherapy (OMAR): A Multicenter Study, by D. Franceschini, P. Ghirardelli, P. Frrokaj, et al (Cancers, 2025).

The study

• Authors: D. Franceschini, P. Ghirardelli, P. Frrokaj, N.H. Andratschke, L. Nicosia, E. Parisi, G. Piperno, M. Sepulcri, E. Alì, A.M. Marzo, S. Bendoni, R. Spoto, M. Krengli, P. Ciammella, B.A. Jereczek-Fossa, A. Romeo, R. Mazzola, F. Alongi, M. Guckenberger, G.L. Ceresoli, M. Loi, P. Borghetti, M. Scorsetti
• Journal: Cancers
• Published: 2025;17(17)
• Read it: PubMed · Publisher · Free full text

Abstract

Background/objectives: This multicenter retrospective study aims to evaluate the role of Ablative Radiotherapy (RT) in patients with unresectable pleural mesothelioma (PM) who experienced radiological progression after at least one line of chemotherapy, with a maximum involvement of three pleural or extrapleural sites.

Methods: Adult patients (≥18 years) with PM treated with stereotactic radiotherapy between 2011 and 2022, limited to a maximum of three pleural or extrapleural sites, were included in the analysis. Ablative RT was required to be administered with radical intent. Endpoints were time to further systemic therapy (TFST), local control (LC), progression-free survival (PFS), overall survival (OS), and acute and late radiotherapy-related toxicity.

Results: A total of 56 patients were identified from six Italian and one Swiss radiotherapy center. Treatment was generally well tolerated. Ten patients experienced grade 1 or 2 acute toxicity, while four patients reported persistent chest pain, with one case reaching grade 3 as late toxicity. The median TFST was 18.6 months, with TFST rates of 61.7% and 46.4% at 12 and 24 months, respectively. The median OS was 37.63 months, with 1- and 2-year OS rates of 85.2% and 65.6%. Local control was favorable (79% at 1 year), but most patients experienced disease recurrence outside the SABR treatment volume. The median disease progression-free survival (DPFS) was 8.17 months, with 1- and 2-year DPFS rates of 36% and 19%, respectively. Smoking history correlated with OS and DPFS in univariate analysis, while statistical significance for OS was maintained in multivariate analysis. Additionally, nodal status and PTV volume were associated with OS.

Conclusion: SABR is a safe and effective approach for the treatment of oligorecurrent/oligoprogressive PM. The time to further systemic therapy was extended up to 18 months. At two years, 10% of patients remained disease-free, and more than half were alive at three years, suggesting a potentially indolent biological behavior in oligometastatic PM.

In plain English

This was a retrospective study from six Italian centers and one Swiss center. It looked at 56 adults with pleural mesothelioma that could not be removed by surgery. After at least one line of drug treatment, each patient's disease came back, persisted or grew at no more than three sites, 82 lesions in all. Between 2011 and 2022 these sites were treated with high-dose, precisely targeted radiotherapy (SABR). The study did not examine asbestos exposure. Measured from the start of radiotherapy, the median time to further drug treatment (or, for patients without it, to progression or death) was 18.6 months; median overall survival was 37.6 months. Local control of the treated sites was 79% at 12 months, but 48 patients later had disease grow outside the treated area. No acute side effect was worse than grade 2, and one patient had grade 3 lasting chest wall pain. A history of smoking was linked to shorter survival. The authors concluded that this radiotherapy was well tolerated and offered favorable outcomes. They noted the study was retrospective, patients were well selected, and treatment varied across centers and years.

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: Multicenter retrospective study of patients treated with stereotactic ablative radiotherapy (SABR)
• Who was studied: 56 adult patients with unresectable pleural mesothelioma (82 treated lesions) at six Italian and one Swiss center, treated between 2011 and 2022. All had oligorecurrent, oligopersistent or oligoprogressive disease after at least one line of systemic therapy. 39 were male, median age was 68.5 years, and 50 had epithelioid histology.
• Exposure: Ablative radiotherapy (SABR) to a maximum of three pleural or extrapleural sites. Doses ranged from 36 Gy in six fractions to 55 Gy in five fractions, with a median biologically effective dose of 61.25 Gy. Asbestos exposure was not studied.
• Main results:
  • Median time to further systemic therapy for all 56 patients was 18.6 months (IQR 7.2 to 63.8 months). This was measured from the first day of radiotherapy to the start of further systemic therapy, or, if none was delivered, to disease progression or death. 32 patients (57.1%) started a new systemic therapy during follow-up.
  • Median overall survival, measured from the first day of radiotherapy, was 37.6 months (IQR 17.7 to 61.7 months), with 12- and 24-month overall survival rates of 85.2% and 65.6%. At last follow-up 24 patients (42.8%) were alive and 32 (57.2%) had died due to disease progression.
  • Local relapse within the treated volume occurred in 15 patients (26.8%). Local control rates were 79% at 12 months and 73% at 24 months.
  • 48 patients (reported as 84.2%) had progression outside the radiotherapy field, most often in the pleura (58.3%).
  • Median distant progression-free survival was 8.2 months (IQR 3.4 to 16.9 months), with 12- and 24-month rates of 36% and 19%.
  • Counting both local and distant relapse, median progression-free survival was 6.9 months. Progression-free survival rates were 30% at 12 months and 10% at 24 months.
  • No acute toxicity above grade 2 was seen within three months of radiotherapy. Late toxicity was persistent chest wall pain in four patients: two grade 1, one grade 2 and one grade 3.
  • In univariate analysis, never-smokers had significantly longer overall survival (HR 4.31, CI 1.39 to 13.36, p = 0.011). In multivariate analysis, only smoking history remained significantly associated with overall survival (HR 3.706, CI 1.192 to 11.524, p = 0.024).
  • In univariate analysis, nodal status at diagnosis (HR 2.269, CI 1.018 to 5.062, p = 0.045) and PTV volume (HR 2.496, CI 1.054 to 5.912, p = 0.038) also correlated with overall survival.
• The authors' conclusion: The authors concluded that ablative intent radiotherapy is well tolerated and offers favorable outcomes in oligometastatic pleural mesothelioma. In their view, in selected patients it seems to prolong the time before starting or changing systemic therapy. They called for further studies on optimal doses.
• Limitations the authors state:
  • The study was retrospective and therefore subject to inherent biases.
  • Patients were well selected: most had epithelioid histology, were stage I or II at diagnosis, and were treated early in their disease history.
  • The cohort was heterogeneous. Patients were treated at seven institutions over more than ten years, with differing doses, fractionation, techniques, imaging and systemic therapy.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Unresectable Pleural Mesothelioma, Chemotherapy, Systemic Therapy, Progression-Free Survival, Overall Survival, Disease Progression, Statistical Significance.

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• Recognition of and treatment recommendations for oligometastatic disease in multidisciplinary tumor boards — S.M. Christ, P. Heesen, et al. (2023)
• Long-term results in malignant pleural mesothelioma treated with neoadjuvant chemotherapy, extrapleural pneumonectomy and intensity-modulated radiotherapy — C. Thieke, N.H. Nicolay, et al. (2015)
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• Double cancer comprising malignant pleural mesothelioma and squamous cell carcinoma of the lung treated with radiotherapy: A case report — Y. Negi, K. Kuribayashi, et al. (2018)

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