Induction chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy for malignant pleural mesothelioma: experience of Guy's and St Thomas' hospitals

Our plain-English summary of Induction chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy for malignant pleural mesothelioma: experience of Guy's and St Thomas' hospitals, by A. Bille, E. Belcher, H. Raubenheimer, et al (General Thoracic and Cardiovascular Surgery, 2012).

The study

• Authors: A. Bille, E. Belcher, H. Raubenheimer, D. Landau, P. Cane, J. Spicer, L. Lang-Lazdunski
• Journal: General Thoracic and Cardiovascular Surgery
• Published: 2012;60(5):289-96
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: The treatment of malignant pleural mesothelioma (MPM) remains controversial. We present a prospective study of patients treated at our institution with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP), and radical radiotherapy.

Methods: Patients with MPM who were eligible for EPP and multimodality therapy were included in this study. Staging was through computed tomography and positron emission tomography and computed tomography (PET/CT) scanning, video-assisted thoracoscopic surgery (VATS), and mediastinoscopy. Our protocol involved three cycles of cisplatin-based neoadjuvant chemotherapy followed by extrapleural pneumonectomy and adjuvant radiotherapy (54 Gy). All patients were followed up every 3-6 months until death.

Results: From March 2004 through October 2008, 25 patients were referred for EPP following neoadjuvant chemotherapy. EPP was performed in all but three patients, who were found to have T4 disease at surgery. Surgical complications included arrhythmias (28%), bronchopleural fistulas (12 %), reoperations for bleeding (8%), acute respiratory distress syndrome (4%), pneumonia (4%), septicemia (4%), vocal cord palsy (4%), and Horner's syndrome (4%). The 30-day mortality was 4%. Adjuvant radiotherapy was administered to 81% of patients after EPP. Radiotherapy toxicities included thrombocytopenia, radiation pneumonitis, pulmonary embolus, radiation hepatitis, herpes zoster, transverse myelitis, and late constrictive pericarditis. Median survival from diagnosis was 12.8 months (95% confidence interval 7.8-17.7 months). One-year survival was 54.5%; 2-year survival was 18.2%. Disease progression occurred in 77.3% of patients. Nodal status (N0 disease versus N1-N2) or histology (epithelioid versus biphasic) had no significant impact on survival.

Conclusion: Despite recent advances in chemotherapy, surgery, and radiotherapy, survival rates remain low for patients with MPM completing multimodality therapy including EPP.

In plain English

This prospective study from Guy's and St Thomas' hospitals in London followed 25 patients with malignant pleural mesothelioma (23 men and 2 women, median age 62) who agreed to extrapleural pneumonectomy after cisplatin-based chemotherapy. The study did not examine asbestos exposure. In three patients the operation was abandoned because the tumor had spread too far. Of the 22 who had the operation, one died during surgery, and the authors counted 4 of 22 deaths (18.2%) as treatment-related. Seventeen patients (81% of the 21 who survived surgery) went on to radiotherapy. Among patients completing the operation, median survival from diagnosis was 12.8 months (95% confidence interval 7.8 to 17.7). At one year 54.5% were alive, at two years 18.2%, and at three years 13.6%. Differences in survival by lymph node status (p = 0.42) or tumor cell type (p = 0.25) were not statistically significant. The authors said this was probably because the study was small. The authors concluded that the combined treatment gave limited survival benefit and believed it should be given only within a controlled trial.

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-institution analysis (case series) of patients treated with chemotherapy, extrapleural pneumonectomy and radiotherapy
• Who was studied: 25 patients with malignant pleural mesothelioma (23 men, 2 women, median age 62, range 52 to 68) referred to Guy's and St Thomas' hospitals, London, 2004 to 2008, who consented to extrapleural pneumonectomy
• Exposure: No asbestos exposure data were reported. The treatment studied was three cycles of chemotherapy: cisplatin with gemcitabine before 2007, or cisplatin with pemetrexed after that date. This was followed by extrapleural pneumonectomy and adjuvant radiotherapy.
• Main results:
  • The operation was abandoned in 3 of the 25 patients because of the extent of disease found at surgery.
  • One patient died during surgery, giving a 30-day mortality rate of 4.5% in the article text.
  • Treatment-related deaths: 4 of 22 patients (18.2%).
  • The most common complication of the operation was irregular heart rhythm (arrhythmia), in 7 patients (28%).
  • 17 patients (81% of the 21 who survived the operation) received adjuvant radiotherapy.
  • Among patients completing the operation, median survival from diagnosis was 12.8 months (95% confidence interval 7.8 to 17.7).
  • Survival rates were 54.5% at 1 year, 18.2% at 2 years and 13.6% at 3 years.
  • Survival did not differ significantly by lymph node status (p = 0.42). Two-year survival was 25% in patients with N0 disease and 10% in those with N1-N2 disease.
  • Survival did not differ significantly between epithelioid and biphasic histology (p = 0.25). Two-year survival was 28.6% for epithelioid and 0% for biphasic.
  • 17 patients (81%) developed recurrence inside the chest. Death was attributed to disease progression.
• The authors' conclusion: The authors concluded that, in their experience, trimodality therapy including extrapleural pneumonectomy provided limited survival benefit. They said they believe patients should receive it only within a controlled trial.
• Limitations the authors state:
  • The authors attributed the lack of significant survival differences by histology and nodal status probably to the limited number of patients.
  • 36% of patients were found to have N2 lymph node disease after surgery despite mediastinoscopy and PET-CT. The authors said this influenced survival and that mediastinoscopy is not an adequate staging method.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Chemotherapy, Extrapleural Pneumonectomy (EPP), Pleural Mesothelioma, Neoadjuvant Chemotherapy, Multimodal Therapy, Staging, Video-Assisted Thoracoscopic Surgery (VATS), Mediastinoscopy.

Related studies

• What is the optimum strategy for thromboembolic prophylaxis following extrapleural pneumonectomy in patients with malignant pleural mesothelioma? — A. Billè, L. Okiror, et al. (2012)
• Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma — M. de Perrot, R. Feld, et al. (2016)
• 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)
• Adjuvant radiotherapy after extrapleural pneumonectomy for mesothelioma. Prospective analysis of a multi-institutional series — S. Tonoli, P. Vitali, et al. (2011)
• Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine followed by adjuvant chemotherapy in patients with malignant pleural mesothelioma — L. Lang-Lazdunski, A. Bille, et al. (2011)
• Staging of patients after extrapleural pneumonectomy for malignant pleural mesothelioma--institutional review and current update — C. Cao, S.K. Krog Andvik, et al. (2011)

Browse more research in General Thoracic and Cardiovascular Surgery, or return to medical research.