Long-term outcomes of intensity-modulated radiotherapy following extra-pleural pneumonectomy for malignant pleural mesothelioma

Our plain-English summary of Long-term outcomes of intensity-modulated radiotherapy following extra-pleural pneumonectomy for malignant pleural mesothelioma, by Y. Matsuo, K. Shibuya, K. Okubo, et al (Acta Oncologica, 2017).

The study

• Authors: Y. Matsuo, K. Shibuya, K. Okubo, N. Ueki, A. Aoyama, M. Sonobe, M. Nakamura, T. Mizowaki, H. Date, M. Hiraoka
• Journal: Acta Oncologica
• Published: 2017;56(7):957-962
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: The purpose was to evaluate safety and efficacy of intensity-modulated radiotherapy (IMRT) following extra-pleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM).

Material And Methods: Patients with MPM of clinical stage I-III, which were macroscopic completely resected with EPP were eligible for this prospective study. The ipsilateral hemithorax was irradiated with a prescribed dose of 50.4 Gy. When the high-risk surgical margins or FDG-avid regions were identified, simultaneous integrated boost (SIB) with 56.0 Gy or 61.6 Gy was applied.

Results: Twenty-one patients were enrolled. SIB was applied to five patients. The planned IMRT fractions were completed in all, but four patients who suffered from severe fatigue or radiation pneumonitis. With a potential median follow-up of 6.3 years, overall survival was 37.5% at 3 years since the IMRT. The median survival time was 17.5 and 27.0 months since the IMRT and the initial treatment, respectively. Three patients have survived for more than 5 years. Distant metastasis was observed in 15 patients. Local recurrence was also observed in 2 of the 15 patients. Acute toxicities of Grade 3 or worse were observed in 15 patients, including 9 with hematological, 3 with pneumonitis and 6 with fatigue, nausea or vomiting. Five patients developed Grade 3 or worse late toxicities associated with IMRT, consisting of one with persistent Grade 4 thrombocytopenia, one with brain infarction and congestive liver dysfunction, and three with elevation of serum transaminase or biliary enzyme. No Grade 5 toxicity was observed. Patients with N2 showed significantly worse survival than those with N0-1 (18.2% vs. 60.0% at 3 years, p = .014).

Conclusion: IMRT following EPP achieved excellent local control for MPM, that might lead to the long-term survival in selected patients. However, treatment burden including acute and late toxicities should be considered in this treatment approach.

In plain English

This prospective Japanese study followed 21 malignant pleural mesothelioma patients enrolled in 2006–2013. All had had extra-pleural pneumonectomy (removal of the lung and pleura) with chemotherapy. They received intensity-modulated radiotherapy (IMRT), a targeted radiation technique, to that side of the chest, planned at 50.4 Gy (50 Gy for the first patient), with boosts in five; 17 completed treatment as planned. The article does not discuss asbestos exposure. Median survival from the start of IMRT was 17.5 months (95% CI 9.0–48.3); 3-year survival was 37.5% (95% CI 17.7–57.4%). Three patients survived over 5 years. Cancer spread to distant sites in 15 patients; 2 of these also recurred in the chest. Serious (Grade 3 or worse) side effects occurred early in 15 of 21 patients and late in 5 of 18 surviving 6 months or more; none were fatal. Patients with N2 lymph node involvement had worse 3-year survival than those with N0–1 (18.2% vs 60.0%). The authors concluded that IMRT after surgery achieved excellent local control, possibly leading to long-term survival in selected patients, but that toxicities should be considered. They noted possible selection bias.

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: Prospective single-group clinical trial of radiotherapy after surgery
• Who was studied: 21 patients with malignant pleural mesothelioma who had extra-pleural pneumonectomy with chemotherapy before or after surgery, enrolled November 2006 to June 2013 at Kyoto University, Japan. There were 19 men and 2 women with a median age of 61 (range 48–73). Histology was epithelioid in 17, sarcomatoid in 2 and biphasic in 2.
• Exposure: The study does not examine asbestos exposure. It studied a treatment: IMRT to the affected side of the chest, planned at 50.4 Gy in 28 fractions (50 Gy for the first patient). Boosts of 56.0 Gy to close surgical margins or 61.6 Gy to FDG-avid regions were given in 5 patients.
• Main results:
  • Among all 21 patients, median survival from the start of IMRT was 17.5 months (95% CI 9.0–48.3). Overall survival was 61.9%, 47.6% and 37.5% at 1, 2 and 3 years (95% CI 38.1–78.8, 25.7–66.7 and 17.7–57.4%).
  • Median survival from the initial treatment was 27.0 months (95% CI 17.1–53.2 months).
  • Three patients survived more than 5 years after IMRT.
  • Disease progression occurred in 15 patients, all with distant metastasis, and 2 of those 15 also had local recurrence. The 3-year incidence of local recurrence was 12.3% (95% CI 3.2–41.2%).
  • The planned IMRT fractions were completed in 17 of 21 patients. In one patient the delivered dose was reduced to 44 Gy because of Grade 3 fatigue. Three patients developed radiation pneumonitis during the course.
  • Acute toxicities of Grade 3 or worse occurred in 15 of the 21 patients.
  • Of the 18 patients who survived 6 months or more, 5 developed Grade 3 or worse late toxicities. These included one patient with persistent Grade 4 thrombocytopenia. Another, with left-sided disease, had a brain infarction and congestive liver dysfunction, which were considered likely related to heart irradiation. No Grade 5 (fatal) toxicity was observed.
  • Patients with N2 nodal status had significantly worse 3-year overall survival than those with N0–1: 18.2% vs 60.0% (p = .014).
  • The survival difference between epithelioid and non-epithelioid histology was not statistically significant. Three-year survival was 34.3% for epithelioid and 50.0% for non-epithelioid (p = .286).
• The authors' conclusion: The authors concluded that IMRT following extra-pleural pneumonectomy achieved excellent local control for malignant pleural mesothelioma, which might lead to long-term survival in selected patients. They added that acute and late toxicities should be considered, and that the approach should be limited to selected patients at low risk of distant metastasis.
• Limitations the authors state:
  • Selection bias: only patients who were treated with IMRT were evaluated, not all patients with malignant pleural mesothelioma.
  • There were no data on how many patients did not go on to receive IMRT before registration.

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: Intensity-Modulated Radiation Therapy (IMRT), Pneumonectomy, Pleural Mesothelioma, Hemithorax, Pneumonitis, Overall Survival, Median Survival, Metastasis.

Related studies

• Extra-pleural pneumonectomy in the era of image-guided intensity-modulated radiotherapy — M. Trovo, D. Franceschini, et al. (2019)
• Patterns of failure, toxicity, and survival after extrapleural pneumonectomy and hemithoracic intensity-modulated radiation therapy for malignant pleural mesothelioma — D.R. Gomez, D.S. Hong, et al. (2013)
• Intensity modulated radiation therapy after extra-pleural pneumonectomy for malignant pleural mesothelioma is feasible without fatal pulmonary toxicity and provides good survival — S. Jhavar, J. Pruszynski, et al. (2018)
• Intensity-modulated radiotherapy after extrapleural pneumonectomy in the combined-modality treatment of malignant pleural mesothelioma — A. Chi, Z. Liao, et al. (2011)
• Optimal gross tumor volume definition in lung-sparing intensity modulated radiotherapy for pleural mesothelioma: an in silico study — A. Botticella, G. Defraene, et al. (2016)
• High-dose-rate surface brachytherapy to boost elongated, curvilinear incisional scars after extrapleural pneumonectomy for malignant pleural mesothelioma treated with adjuvant intensity-modulated radiation therapy — L.A. Doyle, T.N. Showalter, et al. (2010)

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