Impact of induction therapy on postoperative outcome after extrapleural pneumonectomy for malignant pleural mesothelioma: does induction-accelerated hemithoracic radiation increase the surgical risk?

Our plain-English summary of Impact of induction therapy on postoperative outcome after extrapleural pneumonectomy for malignant pleural mesothelioma: does induction-accelerated hemithoracic radiation increase the surgical risk?, by P. Mordant, K. McRae, J. Cho, et al (European Journal of Cardio-thoracic Surgery, 2016).

The study

• Authors: P. Mordant, K. McRae, J. Cho, S. Keshavjee, T.K. Waddell, R. Feld, M. de Perrot
• Journal: European Journal of Cardio-thoracic Surgery
• Published: 2016;50(3):433-8
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: Patients with malignant pleural mesothelioma (MPM) eligible for extrapleural pneumonectomy (EPP) may benefit from induction chemotherapy (CT) as historically described, or from induction-accelerated hemithoracic intensity-modulated radiation therapy (IMRT) as a potential alternative. However, the impact of the type of induction therapy on postoperative morbidity and mortality remains unknown.

Methods: We performed a retrospective study including every patient who underwent EPP for MPM in our institution between January 2001 and December 2014. Patients without induction treatment (n = 7) or undergoing both induction CT and IMRT (n = 2) were then excluded. The remaining patients (study group) were divided according to the type of induction treatment in Group 1-CT and Group 2-IMRT. Major complications were defined by complications of Grade 3 or higher according to the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 guidelines. Red blood cell (RBC) transfusion was analysed as a number of packs, and dichotomized as <3 vs ≥3 packs. Plasma and platelet transfusion were analysed as a number of units, and dichotomized as no transfusion versus any plasma or platelet transfusion.

Results: Altogether, 126 patients (mean age 61.3 ± 8.1 years, males 82.5%, right side 60.3%, 90-day mortality rate 4.8%) accounted for the study group. Sixty-four patients were included in Group 1-CT and 62 patients were included in Group 2-IMRT. When compared with Group 1-CT, Group 2-IMRT was characterized by older patients (59.3 ± 9.2 vs 63.3 ± 8.3 years, P = 0.012), more right-sided resections (46.8 vs 74.1%, P = 0.003), more advanced disease (pathological stage IV: 28.1 vs 53.2%, P = 0.007), less RBC transfusions (5.1 ± 3.0 vs 3.0 ± 2.4 packs, P < 0.001), less plasma or platelet transfusions (31.2 vs 9.6%, P = 0.005) and similar rate of major complications (29.6 vs 35.4%, P = 0.614). The 90-day mortality rate was 6.2% in Group 1-CT (n = 4) and 3.2% in Group 2-RT (n = 2, P = 0.680). Induction with IMRT was significantly associated with a decreased risk of transfusion with RBCs [odds ratio (OR) = 0.10, 95% confidence interval (CI) 0.04-0.23, P < 0.001] as well as plasma and platelets (OR = 0.25, 95% CI 0.086-0.67, P = 0.008).

Conclusions: In this large single-centre series of EPP for MPM, the implementation of induction IMRT was not associated with any significant increase in the surgical risks above and beyond induction CT. The switch from induction CT to induction IMRT was associated with resection in older patients with more advanced tumours, less transfusion requirements, comparable postoperative morbidity and 90-day mortality.

© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

In plain English

This retrospective study from Toronto General Hospital, Canada, reviewed patients who had extrapleural pneumonectomy for malignant pleural mesothelioma between January 2001 and December 2014. In this operation the lung, outer chest lining, diaphragm and heart sac on one side are removed together. The study compared 126 patients: 64 given chemotherapy and 62 given a short, high-dose course of radiation to that side of the chest (IMRT), each before surgery. It did not examine asbestos exposure. The radiation group was older and had more right-sided operations and more pathological stage IV disease, staged from the removed tissue. It needed fewer red blood cell transfusions (mean 3.0 versus 5.1 packs) and fewer plasma or platelet transfusions (9.7% versus 31.2% of patients). Major complications occurred in 35.5% of the radiation group and 29.7% of the chemotherapy group, not a statistically significant difference. Deaths within 90 days were 2 (3.2%) and 4 (6.3%). The authors concluded that induction radiation was not associated with a significant increase in surgical risk compared with chemotherapy. They noted the single-centre, retrospective design and possible bias from changes in care over time.

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 single-centre study of prospectively collected records, comparing two types of induction (pre-surgery) treatment
• Who was studied: Of 135 patients who had extrapleural pneumonectomy for malignant pleural mesothelioma at Toronto General Hospital, Canada, from January 2001 to December 2014, 126 were studied after 9 were excluded. Of these, 64 had induction chemotherapy (Group 1-CT) and 62 had induction IMRT (Group 2-IMRT). There were 104 males (82.5%) and the mean age was 61.3 years.
• Exposure: Type of induction treatment before surgery: chemotherapy (CT) or a short accelerated course of high-dose hemithoracic intensity-modulated radiation therapy (IMRT). The study does not report asbestos exposure or fiber types.
• Main results:
  • Compared with Group 1-CT, Group 2-IMRT patients were older (mean 63.3 versus 59.3 years, P = 0.012) and had more right-sided tumours (74.2% versus 46.9%, P = 0.003). They also had more pathological stage IV disease (53.2% versus 28.1%, P = 0.007), staged on the resected specimen.
  • The mean number of red blood cell packs transfused was 3.0 in Group 2-IMRT versus 5.1 in Group 1-CT (P less than 0.001).
  • Three or more red blood cell packs were needed by 33.8% of Group 2-IMRT and 82.8% of Group 1-CT (P = 0.004).
  • Any plasma or platelet transfusion was needed by 9.7% of Group 2-IMRT and 31.2% of Group 1-CT (P = 0.005).
  • Major complications (Grade 3 or higher) occurred in 19 of 64 patients (29.7%) in Group 1-CT and 22 of 62 (35.5%) in Group 2-IMRT. This difference was not statistically significant (P = 0.614).
  • Deaths within 90 days were 4 (6.3%) in Group 1-CT and 2 (3.2%) in Group 2-IMRT. This difference was not statistically significant (P = 0.680).
  • Induction IMRT was the only factor associated with a decreased risk of transfusion. The odds ratio was 0.08 (95% CI 0.03 to 0.21) for three or more red blood cell packs and 0.20 (95% CI 0.06 to 0.57) for plasma or platelets.
  • Right-sided resection was the only factor associated with an increased risk of major complications, with an odds ratio of 2.31 (95% CI 1.04 to 5.37, P = 0.043).
  • No preoperative factor was significantly associated with postoperative death. The authors did not show these data.
• The authors' conclusion: The authors concluded that, in their series, switching to induction IMRT was not associated with any significant increase in surgical risk compared with induction chemotherapy. They also found the switch was associated with surgery in older patients with more advanced tumours. It was also associated with fewer transfusions, and with comparable complications and 90-day mortality.
• Limitations the authors state:
  • The study was conducted at a single centre and was retrospective.
  • No one calculated in advance whether the sample size was large enough.
  • There was a risk of chronological bias, because the switch to IMRT may have coincided with other improvements in care over time.
  • The authors stated that the findings should be confirmed by a prospective study, a large multicentre study or a national registry study.

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), Odds Ratio, confidence interval.

Related studies

• Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma — M. de Perrot, R. Feld, et al. (2016)
• Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial) — S. Hasegawa, M. Okada, et al. (2016)
• Hemithoracic radiation therapy after extrapleural pneumonectomy for malignant pleural mesothelioma: Toxicity and outcomes at an Australian institution — A. Bece, M.M. Tin, et al. (2015)
• 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)
• Extrapleural pneumonectomy after induction chemotherapy: perioperative outcome in 251 mesothelioma patients from three high-volume institutions — O. Lauk, M.A. Hoda, et al. (2014)
• Induction chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy for malignant pleural mesothelioma: experience of Guy's and St Thomas' hospitals — A. Bille, E. Belcher, et al. (2012)

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