Hemithoracic radiation therapy after extrapleural pneumonectomy for malignant pleural mesothelioma: Toxicity and outcomes at an Australian institution

Our plain-English summary of Hemithoracic radiation therapy after extrapleural pneumonectomy for malignant pleural mesothelioma: Toxicity and outcomes at an Australian institution, by A. Bece, M.M. Tin, D. Martin, et al (Journal of Medical Imaging and Radiation Oncology, 2015).

The study

• Authors: A. Bece, M.M. Tin, D. Martin, R. Lin, J. McLean, B. McCaughan
• Journal: Journal of Medical Imaging and Radiation Oncology
• Published: 2015;59(3):355-62
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: We aim to report the outcome of patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy (EPP) and adjuvant hemithoracic radiotherapy with or without chemotherapy at a single Australian institution.

Method: Between July 2004 and March 2013, 53 patients were referred for radiation treatment following EPP, of whom 49 were suitable for adjuvant treatment. Radiation treatment initially involved a 3D conformal, mixed electron/photon technique, delivering 45-50.4 Gy in 25-28 fractions (31 patients) and subsequently a nine-field intensity-modulated radiotherapy technique, delivering 50.4-54 Gy in 28-30 fractions (18 patients). Fifty-five per cent of patients also received pre-operative chemotherapy. We assessed toxicity, disease-specific and overall survival in patients who commenced radiation treatment.

Results: Forty-one patients (84%) completed treatment as prescribed. Six patients stopped prematurely due to toxicity, and two with disease progression. Most patients discontinuing due to toxicity received over 90% of the prescribed dose. Common acute toxicities included nausea, fatigue, anorexia and dermatitis. Severe early toxicities were rare. Late toxicities were uncommon, with the exception of a persistent elevation in liver enzymes in those with right-sided disease. Neither clinical hepatitis nor radiation pneumonitis was documented. With a median follow up of 18.7 months, median disease-free and overall survival were 21.6 and 30.5 months, respectively, and 2-year overall survival was 57.3%.

Conclusion: Hemithoracic radiotherapy following EPP, although associated with significant early toxicity, is well tolerated. Most patients complete the prescribed treatment, and clinically significant late toxicities are rare.

© 2015 The Royal Australian and New Zealand College of Radiologists.

In plain English

This report covered 49 people with malignant pleural mesothelioma treated at Royal Prince Alfred Hospital, Camperdown, Australia, from July 2004 to March 2013. All had surgery removing the lung and its lining on the affected side (extrapleural pneumonectomy). They then began radiotherapy to that side of the chest, by a mixed electron/photon technique (31 patients) or intensity-modulated radiotherapy (18 patients). The article does not discuss asbestos exposure. Forty-one patients (84%) completed treatment as prescribed; six stopped because of side effects and two because the disease progressed. Severe early side effects were uncommon, and no patient developed radiation pneumonitis (lung inflammation). Nine of 26 patients treated on the right side had liver enzymes above 2.5 times the upper limit of normal; none developed clinical hepatitis. Nine patients (18.4%) had cancer return in the treated side of the chest, and 23 (46.9%) had spread elsewhere. Median overall survival was 30.5 months, and 57.3% were alive at 2 years. The authors concluded the treatment was reasonably well tolerated despite significant early side effects, cautioning that their patients were highly selected.

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: single-institution case series (review of all patients who received radiotherapy after surgery)
• Who was studied: 53 patients with malignant pleural mesothelioma referred for radiotherapy after extrapleural pneumonectomy at Royal Prince Alfred Hospital (Camperdown, New South Wales, Australia), July 2004 to March 2013. 49 began radiotherapy (88% male, aged 33 to 76, 84% epithelioid histology).
• Exposure: No asbestos exposure is reported. The study examined a treatment: radiotherapy to one side of the chest after extrapleural pneumonectomy. The mixed electron/photon technique prescribed 45 to 50.4 Gy in 25 to 28 fractions (31 patients). Intensity-modulated radiotherapy prescribed 50.4 to 54 Gy in 28 to 30 fractions (18 patients).
• Main results:
  • Of 49 patients who began radiotherapy, 41 (84%) completed treatment as prescribed. Six stopped early because of toxicity, five of whom had received more than 90% of the prescribed dose. Two stopped because of disease progression.
  • Severe (grade 3) early skin toxicity occurred in 8% of patients, nausea in 6% and oesophagitis in 2%
  • No patient developed radiation pneumonitis
  • Of 26 patients treated for right-sided disease, 9 (35%) developed elevations of the liver enzymes ALP or GGT greater than 2.5 times the upper limit of normal (grade 2 or higher). No patient developed clinical hepatitis.
  • Grade 2 to 3 liver toxicity was more common with the conventional technique (50%) than with intensity-modulated radiotherapy (10%)
  • One patient required removal of the right kidney (nephrectomy) 15 months after radiotherapy because of fibrosis around the kidney and obstruction where the kidney joins the ureter
  • One patient with left-sided disease developed constrictive pericarditis 3 months after radiation. This patient died of right heart failure 12 months later, without evidence of recurrence.
  • Nine patients (18.4%) had a local recurrence, at a median of 7 months (range 1 to 34 months) after radiation treatment
  • 23 patients (46.9%) developed distant metastases, 15 of them in the abdomen
  • Median follow-up was 18.7 months
  • Disease-free survival at 2 years was 46.1%, and median disease-free survival was 21.6 months
  • Overall survival was 83.7% at 1 year, 57.3% at 2 years and 42.2% at 3 years. Median survival was 30.5 months.
  • Seven patients (14%) were alive beyond 5 years
  • Median disease-free survival was 26.6 months in node-negative patients versus 10.8 months in node-positive patients. This difference did not reach statistical significance (log-rank P = 0.07).
  • Pathological stage was the only statistically significant predictor of outcome
• The authors' conclusion: The authors concluded that radiotherapy to one side of the chest after extrapleural pneumonectomy, although associated with significant early toxicity, is reasonably well tolerated. They also concluded that most patients complete the prescribed course and that clinically significant late toxicities are rare.
• Limitations the authors state:
  • The authors state that selection bias affects the survival and recurrence results, because patients were selected and referred for radiotherapy after surgery
  • The authors state that local recurrences were likely under-reported because chest CT was not routine at first

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: Extrapleural Pneumonectomy (EPP), Pleural Mesothelioma, Chemotherapy, Intensity-Modulated Radiation Therapy (IMRT), Overall Survival, Disease Progression, Pneumonitis.

Related studies

• 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)
• Impact of induction therapy on postoperative outcome after extrapleural pneumonectomy for malignant pleural mesothelioma: does induction-accelerated hemithoracic radiation increase the surgical risk? — P. Mordant, K. McRae, et al. (2016)
• Hemithoracic intensity-modulated radiotherapy using helical tomotherapy for patients after extrapleural pneumonectomy for malignant pleural mesothelioma — T. Ebara, H. Kawamura, et al. (2012)
• Clinical experience of volumetric modulated arc therapy for malignant pleural mesothelioma after extrapleural pneumonectomy — T. Kimura, Y. Doi, et al. (2015)
• Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma — M. de Perrot, R. Feld, 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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