Salvage radiotherapy for oligo-progressive malignant pleural mesothelioma

Our plain-English summary of Salvage radiotherapy for oligo-progressive malignant pleural mesothelioma, by P. Ghirardelli, D. Franceschini, A. D'Aveni, et al (Lung Cancer, 2021).

The study

• Authors: P. Ghirardelli, D. Franceschini, A. D'Aveni, L. Dominici, A. Ravasio, M. Marzo, E. Villa, V. Di Noia, M. Scorsetti, V. Vavassori, G.L. Ceresoli
• Journal: Lung Cancer
• Published: 2021;152:1-6
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: No standard treatment option is available for patients with unresectable malignant pleural mesothelioma (MPM) progressing after upfront chemotherapy. We aimed to explore the role of focal radiotherapy (FRT) as a treatment modality for oligo-progressive MPM.

Materials And Methods: In this retrospective study, consecutive patients pretreated with ≥1 lines of chemotherapy were included. Oligo-progressive MPM was defined as an unresectable disease with radiological progression at ≤3 sites according to a chest-abdominal contrast-enhanced computed tomography. Patients were treated with either stereotactic body radiotherapy (SBRT, ≥5 Gy per fraction) or hypo-fractionated radiotherapy (hypoRT, <5 Gy per fraction). Time to further systemic therapy (TFST) and local control (LC) after FRT were the primary endpoints. Biologically effective dose (BED) was calculated using three different alpha/beta models (1.5 Gy, 3 Gy and 10 Gy).

Results: From April 2006 to March 2019, 37 patients were treated on 43 pleural lesions; 16/37 (43 %) had undergone upfront multimodality treatment (MMT) including surgery. FRT was given in 22/37 (59.5 %) after one line of chemotherapy. SBRT was delivered for 26/43 lesions (60.5 %), hypoRT for 17/43 (39.5 %). Median TFST was 6 months (95 % CI 4.9-7.1). LC at 6 months and 1 year was 84 % and 76 %, respectively. Median TFST was longer in patients treated after 1 vs >1 line of chemotherapy (9 vs 4 months, p = 0.001) and in patients pretreated with MMT (6 vs 3 months, p = 0.021). Six-month LC was better in patients treated with a BED > 100 using alpha/beta 1.5 and 3. No ≥ G3 acute or late toxicities were reported.

Conclusion: FRT was feasible in selected patients with oligo-progressive MPM, allowing delay of further systemic therapies, with no severe toxicity. FRT was more effective when performed at progression after one line of systemic therapy. Our results suggest a radio-resistant behavior of MPM.

Copyright © 2020 Elsevier B.V. All rights reserved.

In plain English

This retrospective study from two Italian hospitals covered 37 patients whose inoperable malignant pleural mesothelioma had regrown at up to 3 pleural sites after chemotherapy. They received focal radiotherapy to 43 lesions, 26 by stereotactic body radiotherapy and 17 by hypo-fractionated radiotherapy. Local control (no regrowth where treated) was 84% at 6 months and 76% at 1 year. Median time until further drug treatment, or until progression or death for patients who had none, was 6 months (95% CI 4.9 to 7.1). It was longer after one line of chemotherapy than after more (9 vs 4 months). Median overall survival from the start of radiotherapy was 26.9 months (95% CI 18.7 to 35.2). No side effects of grade 3 or worse were recorded. Better local control at biologically effective doses above 100 neared statistical significance under two dose models (alpha/beta 1.5 and 3 Gy) but not the third (10 Gy, p = 0.512). The authors concluded the treatment was feasible and safe in selected patients and could delay further drug treatment. They called the series small and retrospective.

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: Retrospective review of clinical records from two institutions
• Who was studied: 37 patients (20 males, 17 females; median age 67) with unresectable malignant pleural mesothelioma progressing at up to 3 pleural sites after at least one line of chemotherapy, treated at two Italian institutions (Bergamo and Rozzano, Milan) from April 2006 to March 2019; 33 (89%) had epithelioid histology
• Exposure: The study examined treatment, not asbestos exposure. Patients received focal radiotherapy to 43 lesions. This was either stereotactic body radiotherapy (more than 5 Gy per fraction; median total dose 35 Gy) or hypo-fractionated radiotherapy (5 Gy or less per fraction; median total dose 40 Gy). All patients had first received platinum/pemetrexed chemotherapy.
• Main results:
  • In all treated patients, local control (no progression within the treated field) was 84% at 6 months and 76% at 1 year after radiotherapy
  • Median time to further systemic therapy was 6 months (95% CI 4.9 to 7.1), with a median follow-up of 12 months. This endpoint ran to the start of further systemic therapy or, if none was given, to disease progression or death. 8 patients (23% as printed) were free from further systemic therapy at 1 year.
  • In univariate analysis, time to further systemic therapy was longer in patients treated after first-line chemotherapy than after more than one line (9 vs 4 months, p = 0.001)
  • Time to further systemic therapy was also longer in patients who had upfront multimodality treatment including extended surgery (6 vs 3 months, p = 0.021)
  • Median progression-free survival was 5.1 months (95% CI 2.3 to 7.8); 6-month and 1-year progression-free survival were 46% and 18%
  • Median overall survival from the start of radiotherapy was 26.9 months (95% CI 18.7 to 35.2); 1-year and 2-year overall survival were 69% and 54%; 17 patients were still alive at the time of analysis
  • No toxicity of grade 3 or higher was recorded during follow-up
  • Better local control with a biologically effective dose above 100 was close to, but did not reach, statistical significance when doses were calculated with alpha/beta 3 (p = 0.059) and 1.5 (p = 0.08). In Table 4, 6-month local control was 91% (n = 30) vs 50% (n = 7) for alpha/beta 1.5, and 100% (n = 11) vs 75% (n = 26) for alpha/beta 3.
  • With the third model (alpha/beta 10 Gy), Table 4 gives 6-month local control of 100% (n = 2) for BED above 100 vs 83% (n = 35) below 100, with p = 0.512
• The authors' conclusion: The authors concluded that, in selected patients with oligo-progressive malignant pleural mesothelioma, focal radiotherapy was feasible and safe and could delay further systemic therapies. They said it gave disease control at least comparable to currently available second- or third-line treatments. They added that their results suggest a radio-resistant behavior of the disease, with better sensitivity to higher doses per fraction.
• Limitations the authors state:
  • The authors described the study as a small retrospective series
  • The authors said overall survival data should be interpreted with caution because of the limited sample size and the selected clinical characteristics of the patients

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: Pleural Mesothelioma, Unresectable, Chemotherapy, Systemic Therapy.

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• Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine, prophylactic radiotherapy, and systemic chemotherapy in patients with malignant pleural mesothelioma: a 10-year experience — L. Lang-Lazdunski, A. Bille, et al. (2015)
• The Role of Adjuvant Radiotherapy in the Treatment of Pleural Mesothelioma — G.D. Lewis, S.M. Dalwadi, et al. (2019)
• Analysis of the effect of radiotherapy on malignant pleural mesothelioma when given on adjuvant or palliative basis — H.A. El Hossieny, F. Aboulkasem, et al. (2010)
• Radiotherapy to intervention sites in mesothelioma: no more? — G.L. Ceresoli, V. Vavassori (2016)

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