Moderately Hypofractionated Helical IMRT, FDG-PET/CT-guided, for Progressive Malignant Pleural Mesothelioma in Patients With Intact Lungs

Our plain-English summary of Moderately Hypofractionated Helical IMRT, FDG-PET/CT-guided, for Progressive Malignant Pleural Mesothelioma in Patients With Intact Lungs, by A. Fodor, S. Broggi, E. Incerti, et al (Clinical Lung Cancer, 2019).

The study

• Authors: A. Fodor, S. Broggi, E. Incerti, I. Dell'Oca, C. Fiorino, A.M. Samanes Gajate, M. Pasetti, M.G. Cattaneo, P. Passoni, L. Gianolli, R. Calandrino, M. Picchio, N. Di Muzio
• Journal: Clinical Lung Cancer
• Published: 2019;20(1):e29-e38
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: The objective of this study was to present the outcomes of moderately hypofractionated helical intensity-modulated radiation therapy (HT) with/without simultaneous integrated boost (SIB) on fluorodeoxyglucose-positron emission tomography (FDG-PET) positive areas (gross tumor volume [GTV]-PET) for patients with progressive malignant pleural mesothelioma (MPM) after previous treatments.

Methods And Materials: From May 2006 to April 2014, 51 patients with a median age of 68.8 years (range, 38.6-82 years) were treated. There were 41 men and 10 women; 43 epithelioid MPM and 8 sarcomatoid, involving the left pleura in 25 patients and the right pleura in 26 patients. The initial stage was: I, 11 patients; II, 14 patients; III, 17 patients; and IV, 9 patients. Chemotherapy was prescribed for 46 patients, for 6 cycles (range, 0-18 cycles). Eighteen patients had pleurectomy/decortication, and 33 had talc pleurodesis. FDG-PET was used for target identification. A median dose of 56 Gy/25 fractions was prescribed to the involved pleura, and SIB to 62.5 Gy to GTV-PET was added in 38 patients.

Results: The median survival from diagnosis was 25.8 months (range, 8.4-99.0 months). One patient, treated with SIB, was alive at the October 2017 follow-up. Two cases of grade 5 radiation pneumonitis were registered. A GTV-PET ≤ 205 cc was predictive of late ≥ grade 2 lung toxicity, but also of better survival in stage III and IV disease: 5.9 versus 11.7 months (P = .04). A GTV-PET ≥ 473 cc was predictive of early death (P = .001).

Conclusions: Moderately hypofractionated, FDG-PET guided salvage HT in patients with progressive MPM after previous treatments showed acceptable toxicity and outcome results similar to adjuvant radiotherapy after pleurectomy/decortication, suggesting that the delay of radiotherapy is not detrimental to survival, and has the associated benefit of postponing inherent toxicity.

Copyright © 2018 Elsevier Inc. All rights reserved.

In plain English

This study from San Raffaele Scientific Institute, Milan, Italy, reviewed 51 patients with malignant pleural mesothelioma that had progressed after earlier treatment, and with both lungs intact. From May 2006 to April 2014 they had helical intensity-modulated radiotherapy to the affected pleura, usually 56 Gy in 25 sessions. In 38, PET-positive areas got a same-session boost, planned to 62.5 Gy in total (60 Gy in one patient). The article did not study asbestos exposure. Median survival was 25.8 months from diagnosis and 10.4 from starting radiotherapy. Ten patients died within 3 months of finishing treatment; two deaths overall were recorded as fatal radiation pneumonitis. A PET-positive volume of 473.3 cc or more was associated with death within 3 months of starting radiotherapy. Among stage III-IV patients, volumes below 204.6 cc were associated with longer survival from radiotherapy start (11.7 versus 5.9 months); the authors link this to patients given the boost. Smaller volumes were also associated with more late lung side effects. The authors concluded that radiotherapy at progression appeared feasible with acceptable toxicity. They noted the study was retrospective and small.

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 analysis of patients at a single institution treated under a radiotherapy protocol developed in an earlier dose-escalation pilot study
• Who was studied: 51 patients with malignant pleural mesothelioma, both lungs intact, with progressive disease after previous treatments, treated at San Raffaele Scientific Institute, Milan, Italy, from May 2006 to April 2014. Median age was 68.8 years (range 38.6-82). There were 41 men and 10 women; 43 had epithelioid and 8 had sarcomatoid disease. 18 had pleurectomy/decortication and 33 had talc pleurodesis.
• Exposure: Not an asbestos-exposure study; asbestos exposure is not reported. The treatment studied was moderately hypofractionated, FDG-PET/CT-guided helical intensity-modulated radiotherapy. A median dose of 56 Gy in 25 fractions went to the involved pleura. In 38 patients, FDG-PET-positive areas (GTV-PET) received a simultaneous integrated boost, prescribed to a total of 62.5 Gy (2.5 Gy per fraction). One patient's prescription was reduced to 54 Gy to the planning target with a 60 Gy boost, to reduce dose to the kidney after earlier irradiation for a seminoma.
• Main results:
  • All 51 patients: median survival from diagnosis was 25.8 months (range 8.4-99.0).
  • All patients: crude median survival from the start of radiotherapy was 10.4 months (range 1.2-78.8). It was 5.9 months in the group without the boost and 10.9 months in the boost group.
  • Ten patients died within 3 months of the end of radiotherapy. Most had evidence of progressive disease or infectious episodes.
  • Two cases of grade 5 (fatal) radiation pneumonitis were recorded. One was acute and one was late; the late case died 6.7 months after the end of radiotherapy.
  • Late toxicity was assessed in 42 patients (9 without the boost, 33 with it). The authors reported grade 3 radiation pneumonitis of 21.2%; in the late-toxicity table this corresponds to 7 of 33 patients in the boost group. They reported grade 3 shortness of breath of 9.1%.
  • The statistical analyses (Cox and logistic regression) were measured from the start of radiotherapy. The worst prognosis was defined as death or cancer death within 3 months from the start of radiotherapy.
  • A GTV-PET cut-off of 473.3 cc predicted the worst prognosis, meaning death within 3 months from the start of radiotherapy: p=0.001, OR=18.9 (3.27-108.63).
  • Stage III-IV patients: overall survival was 11.7 months with GTV-PET below 204.6 cc and 5.9 months with GTV-PET above 204.6 cc (p=0.044; HR 0.47; 0.184-0.977). The results section states this for stage III-IV patients without restricting it to the boost group.
  • In the discussion, the authors describe the longer survival with small GTV-PET as applying to stage III-IV patients treated with the boost.
  • A GTV-PET below 204.6 cc (the median) predicted late lung toxicity (p=0.028; OR=0.089; 0.010-0.775). The authors suggested this was possibly because these patients had more remaining lung function.
  • Mean heart dose was split at the median of 21.2 Gy. Patients above it had a median overall survival of 5.6 months, versus 10.5 months for those below it. Patients above it had a significantly increased risk of dying (p=0.039; HR=2.068; 1.053-7.30).
• The authors' conclusion: The authors concluded that radiotherapy at the time of progression is a feasible option with acceptable toxicity and an alternative to adjuvant radiotherapy at initial diagnosis. They concluded that good survival could be obtained in selected patients based on GTV-PET volume. They said the precise benefit of the timing of radiotherapy should be a subject for future studies.
• Limitations the authors state:
  • The authors stated that the study was retrospective and had a limited number of 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, Intensity-Modulated Radiation Therapy (IMRT), Epithelioid, Sarcomatoid, Pleura, Chemotherapy, Pleurectomy/Decortication (P/D), Talc Pleurodesis.

Related studies

• FDG PET-derived parameters as prognostic tool in progressive malignant pleural mesothelioma treated patients — E. Incerti, S. Broggi, et al. (2018)
• 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)
• PET-guided dose escalation tomotherapy in malignant pleural mesothelioma — A. Fodor, C. Fiorino, et al. (2011)
• Geometric dose prediction model for hemithoracic intensity-modulated radiation therapy in mesothelioma patients with two intact lungs — L. Kuo, E.D. Yorke, et al. (2016)
• Early experience with intensity modulated proton therapy for lung-intact mesothelioma: A case series — H.Y. Pan, S. Jiang, et al. (2015)
• Dosimetric Correlates of Pulmonary Toxicity in Patients with Malignant Pleural Mesothelioma Receiving Radiation Therapy to the Intact Lungs — M.R. Thompson, V.A. Dumane, et al. (2019)

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