Treatment of malignant pleural mesothelioma with chemotherapy preceding versus after surgical resection

Our plain-English summary of Treatment of malignant pleural mesothelioma with chemotherapy preceding versus after surgical resection, by V. Verma, C.A. Ahern, C.G. Berlind, et al (The Journal of Thoracic and Cardiovascular Surgery, 2019).

The study

• Authors: V. Verma, C.A. Ahern, C.G. Berlind, W.D. Lindsay, S. Grover, J.S. Friedberg, C.B. Simone
• Journal: The Journal of Thoracic and Cardiovascular Surgery
• Published: 2019;157(2):758-766.e1
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: There are 2 main treatment paradigms recognized by the National Comprehensive Cancer Network for resectable malignant pleural mesothelioma (MPM): induction chemotherapy followed by resection (IC/R), and up-front resection with postoperative chemotherapy (R/PC). These paradigms are being compared in an accruing randomized phase II trial. In the absence of such completed trials, in this study we evaluated overall survival (OS) and postoperative outcomes of IC/R and R/PC.

Methods: The National Cancer Database was queried for newly diagnosed epithelioid/biphasic MPM. Metastatic, node-positive, and/or cT4 disease was excluded, along with nondefinitive surgery and lack of chemotherapy. Multivariable logistic regression ascertained factors independently associated with induction chemotherapy delivery. Kaplan-Meier analysis was used to evaluate OS between cohorts; multivariable Cox proportional hazards modeling was used to assess factors associated with OS. Survival was also evaluated between propensity-matched populations. Last, postoperative outcomes were assessed between groups.

Results: Overall, 361 patients (182 IC/R, 179 R/PC) were analyzed. Temporal trends revealed that IC/R is decreasing over time. Survival of the IC/R cohort was similar to that of R/PC patients (20.9 vs 21.7 months; P = .500); this persisted after propensity matching (20.8 vs 22.0 months; P = .270). However, patients who underwent IC/R experienced longer postoperative hospitalization (median 7 days vs 6 days; P = .001) and higher 30-day mortality (3.3% vs 0%; P = .020).

Conclusions: To our knowledge, this is the only comparative investigation of the 2 major management paradigms of operable MPM. IC/R regimens are decreasing over time in the United States. Although associated with survival similar to R/PC, IC/R might be associated with worse postoperative outcomes. Careful induction chemotherapy patient selection is thus highly recommended.

Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

In plain English

Using the US National Cancer Database, the authors compared chemotherapy before versus after surgery for operable malignant pleural mesothelioma. They analyzed 361 patients diagnosed 2004 to 2012 with epithelioid or biphasic tumors without metastases, lymph node spread or T4 disease. Of these, 182 had chemotherapy first and 179 had surgery first. Use of chemotherapy first declined over time. Median overall survival was 20.9 months (95% confidence interval 18.9 to 23.7) with chemotherapy first and 21.7 months (19.3 to 25.3) with surgery first, which was not a statistically significant difference. After the groups were matched on their characteristics, the difference was still not significant: 20.8 months (16.9 to 25.3) vs 22.0 months (19.9 to 32.4). One adjusted model did link chemotherapy first to poorer survival. Patients given chemotherapy first had longer hospital stays after surgery (median 7 vs 6 days) and higher 30-day mortality (3.3% vs 0.0%). Ninety-day mortality and readmissions did not differ significantly. The authors concluded that survival was similar but postoperative outcomes were worse with chemotherapy first, and called the data hypothesis-generating. The database lacked chemotherapy doses and agents. Asbestos exposure was not studied.

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 a national cancer registry (the National Cancer Database), with multivariable regression, Kaplan-Meier survival analysis and propensity matching
• Who was studied: 361 patients in the US National Cancer Database, diagnosed 2004-2012, with newly diagnosed epithelioid or biphasic malignant pleural mesothelioma. All had chemotherapy and definitive surgery (extrapleural pneumonectomy or pleurectomy/decortication). Metastatic, node-positive, clinical T4, sarcomatoid and palliative-care cases were excluded. 182 had induction chemotherapy followed by resection and 179 had resection followed by postoperative chemotherapy.
• Exposure: Not an asbestos exposure study. The comparison was treatment order: chemotherapy started before surgical resection (induction chemotherapy) versus after resection (postoperative chemotherapy).
• Main results:
  • Use of induction chemotherapy followed by resection decreased over the study period.
  • In the full cohort, median overall survival was 20.9 months (95% CI 18.9-23.7) for induction chemotherapy patients and 21.7 months (95% CI 19.3-25.3) for surgery-first patients, P = .500.
  • After propensity matching, median overall survival was 20.8 months (95% CI 16.9-25.3) for induction chemotherapy patients and 22.0 months (95% CI 19.9-32.4) for surgery-first patients, P = .270.
  • In the multivariable Cox model of the unmatched cohort, induction chemotherapy was associated with poorer overall survival (hazard ratio 1.365, 95% CI 1.029-1.810, P = .030). The authors noted this differed from the Kaplan-Meier findings before and after matching.
  • In the extrapleural pneumonectomy subset, there was a nonsignificant trend toward higher overall survival in surgery-first patients (P = .074). In the pleurectomy/decortication subset there was no difference (P = .900).
  • 30-day mortality was 0.0% in the surgery-first group and 3.3% in the induction chemotherapy group (P = .020).
  • 90-day mortality was 7.1% for induction chemotherapy patients and 2.8% for surgery-first patients, reported as statistically similar (P = .104).
  • Postoperative hospital stay was shorter for surgery-first patients (median 6 days, IQR 4-8) than for induction chemotherapy patients (median 7 days, IQR 5-9), P = .001.
  • 30-day readmission rates did not differ: 5.0% for induction chemotherapy patients and 3.8% for surgery-first patients (P = .544).
• The authors' conclusion: The authors concluded that induction chemotherapy followed by resection was associated with survival similar to resection followed by postoperative chemotherapy, but with worse postoperative outcomes. They said careful patient selection is warranted when giving induction chemotherapy.
• Limitations the authors state:
  • The study was retrospective, so it cannot show causation and may be affected by selection biases.
  • The database does not record the number of cycles, doses or agents of chemotherapy.
  • There was no information on extent of resection or tumor response to induction chemotherapy.
  • Only Commission on Cancer-accredited facilities contribute data, and the study population was about 2% of the database, so the findings may not represent the whole US population.
  • Performance status, pulmonary function tests and salvage therapies were not tracked, and these could confound the results.
  • Only induction chemotherapy patients who went on to surgery were included, which may have enriched that group with more favorable patients.
  • The authors described the data as hypothesis-generating, needing prospective confirmation with an intention-to-treat analysis.

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, Chemotherapy, Surgical Resection, Overall Survival, Epithelioid, Biphasic Mesothelioma.

Related studies

• Facility volume and postoperative outcomes for malignant pleural mesothelioma: A National Cancer Data Base analysis — V. Verma, C.A. Ahern, et al. (2018)
• Survival by Histologic Subtype of Malignant Pleural Mesothelioma and the Impact of Surgical Resection on Overall Survival — V. Verma, C.A. Ahern, et al. (2018)
• Clinical indications and results after chest wall resection for recurrent mesothelioma — B.M. Burt, S.O. Ali, et al. (2013)
• Malignant pleural mesothelioma and the Society of Thoracic Surgeons Database: an analysis of surgical morbidity and mortality — B.M. Burt, R.B. Cameron, et al. (2014)
• Types of surgery post-neoadjuvant chemotherapy for pleural mesothelioma — K. Kuribayashi, H. Doi, et al. (2019)
• Is pleurectomy and decortication superior to palliative care in the treatment of malignant pleural mesothelioma? — I. Zahid, S. Sharif, et al. (2011)

Browse more research in The Journal of Thoracic and Cardiovascular Surgery, or return to medical research.