How does the timing of chemotherapy affect outcome following radical surgery for malignant pleural mesothelioma?

Our plain-English summary of How does the timing of chemotherapy affect outcome following radical surgery for malignant pleural mesothelioma?, by A.J. Sharkey, K.J. O'Byrne, A. Nakas, et al (Lung Cancer, 2016).

The study

• Authors: A.J. Sharkey, K.J. O'Byrne, A. Nakas, S. Tenconi, D.A. Fennell, D.A. Waller
• Journal: Lung Cancer
• Published: 2016;100:5-13
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: There is little evidence regarding the use of chemotherapy as part of multimodality treatment of malignant pleural mesothelioma (MPM). We aimed to determine whether, in those patients fit for chemotherapy, a delay in this treatment affected survival.

Materials And Methods: We analysed postoperative variables of 229 patients undergoing either extrapleural pneumonectomy (EPP) (81 patients) or extended pleurectomy-decortication (EPD) (197 patients) for MPM at a single centre. There was no standard protocol for additional chemotherapy and varied with referral centre. Outcome was compared between 4 chemotherapy strategies: true adjuvant therapy, neo-adjuvant therapy, therapy reserved until evidence of disease progression in those otherwise fit in the post-operative setting, and those unfit for chemotherapy.

Results: There was no effect of the timing of chemotherapy on overall or progression free survival in patients fit enough for treatment (p=0.39 and p=0.33 respectively). However delaying chemotherapy until evidence of disease progression in patients with non-epithelioid disease had a detrimental effect on overall survival (OS), and on progression free survival (PFS) in lymph node positive patients (15.6 vs. 8.2 months p=0.001, and 14.9 vs. 6.0 months p=0.016). Further analysis of 169 patients receiving platinum/pemetrexed as first line treatment, showed similar results; there was no effect of the timing of chemotherapy on OS or PFS (p=0.80 and p=0.53 respectively) and an improved OS in patients with non-epithelioid disease, and improved PFS in those with lymph node metastases, if chemotherapy was given in the immediate adjuvant setting (p=0.001 and 0.038) when therapy was not delayed until disease progression.

Conclusion: Our results suggest that the timing of additional chemotherapy may be important in those with a poorer prognosis on the basis of cell type and nodal stage. In these patients additional postoperative chemotherapy should not be delayed.

Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

In plain English

This retrospective study examined 294 consecutive patients having radical surgery for malignant pleural mesothelioma at one UK centre, 2000 to 2014; 229 were analysed. Without a set protocol, referring centres gave chemotherapy as adjuvant (within 3 months after surgery), neo-adjuvant (before surgery), or expectant (held until progression in fit patients); a fourth group was judged unfit for adjuvant chemotherapy. Among fit patients, timing had no statistically significant effect on overall or progression-free survival. Patients unfit for adjuvant chemotherapy had a significantly shorter median survival, 7.7 months. In non-epithelioid patients, median survival was 15.6 months for 19 given adjuvant chemotherapy versus 8.2 months for 11 managed expectantly, though a table gives 10.5 months for the latter. In lymph-node-positive patients, median progression-free survival was 14.9 months with adjuvant chemotherapy (56 patients) versus 6.0 months with expectant management (20 patients). A separate 169-patient platinum/pemetrexed analysis showed similar patterns. The authors concluded that cell type and nodal stage should influence timing, suggesting immediate post-operative chemotherapy may benefit these poorer-prognosis patients. They noted the study was non-randomised with small subgroups, so results may reflect chance.

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 study of consecutive patients drawn from a prospectively updated institutional database (non-randomised comparison of chemotherapy timing strategies)
• Who was studied: 294 consecutive patients who had radical surgery (extrapleural pneumonectomy or extended pleurectomy-decortication) for malignant pleural mesothelioma at a single surgical centre from 2000 to 2014. Patients were referred from 28 cancer centres across the United Kingdom. 65 were excluded, leaving 229 for analysis: 197 (86.0%) male, median age 60 years (range 14 to 80). 148 had extended pleurectomy-decortication and 81 had extrapleural pneumonectomy.
• Exposure: Timing of chemotherapy around surgery, in four groups. Adjuvant: started within 3 months of surgery, after a CT scan showing no progression. Neo-adjuvant: given before surgery. Expectant: fit patients in whom chemotherapy was reserved until disease progression. Unfit: patients judged unfit for chemotherapy in the adjuvant setting. Most patients received platinum and pemetrexed. Others received platinum plus gemcitabine or vinorelbine, vinorelbine alone, or mitomycin, vinblastine and cisplatin. The article does not report asbestos exposure.
• Main results:
  • Among patients fit for chemotherapy, the timing of chemotherapy had no statistically significant effect on overall survival (p = 0.39) or progression-free survival (p = 0.33).
  • Patients in group 4, unfit for adjuvant chemotherapy, had a significantly shorter median overall survival than the other three groups: 7.7 months (p less than 0.001).
  • Among the 51 patients with non-epithelioid histology, the text reports median overall survival of 15.6 months with true adjuvant chemotherapy (group 1) versus 8.2 months with expectant management (group 3), p = 0.001.
  • Table 4 shows that this non-epithelioid comparison involved 19 adjuvant (group 1) and 11 expectant (group 3) patients. The table gives median overall survival of 15.6 months for group 1 and 10.5 months for group 3, not the 8.2 months stated in the text.
  • In the 178 patients with epithelioid histology, adjuvant chemotherapy gave no significant survival benefit (22.2 vs. 28.5 months, p = 0.43).
  • In lymph-node-positive patients (n = 113), overall survival did not differ significantly between groups 1 and 3 (21.7 vs. 13.5 months, p = 0.105).
  • In lymph-node-positive patients, median progression-free survival was significantly longer with adjuvant chemotherapy (group 1, 56 patients in Table 5) than with delayed chemotherapy (group 3, 20 patients in Table 5): 14.9 vs. 6.0 months, p = 0.016.
  • In the 169-patient analysis focused on platinum/pemetrexed, which also included expectant and unfit groups, timing had no significant effect on overall survival (p = 0.80) or progression-free survival (p = 0.53) among fit patients.
  • In the platinum/pemetrexed analysis, among the 41 non-epithelioid patients, median overall survival was 28.9 months with adjuvant chemotherapy (group 1) versus 10.5 months without it (group 3), p = 0.001.
  • In the platinum/pemetrexed analysis, among the 81 lymph-node-positive patients, median progression-free survival was 28.3 months with adjuvant chemotherapy versus 7.4 months when it was delayed, p = 0.038.
• The authors' conclusion: The authors concluded that no strategy showed an outstanding benefit over the others, but that the timing of chemotherapy should be influenced by cell type and nodal stage. In patients with non-epithelioid cell type and/or positive lymph nodes, they suggested that chemotherapy given immediately after surgery may be beneficial.
• Limitations the authors state:
  • The study was retrospective and non-randomised.
  • The non-epithelioid and node-positive groups were small, and the non-epithelioid group was mostly biphasic tumours.
  • The results may be due to chance given the small numbers of patients.
  • The subgroup benefit findings must be used with caution.
  • The practice volume of the oncology centre may be a confounding factor that the study did not examine.

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: Chemotherapy, Pleural Mesothelioma, Extrapleural Pneumonectomy (EPP), Pleurectomy/Decortication (P/D), Adjuvant Therapy, Disease Progression, Non-epithelioid, Overall Survival.

Related studies

• The management of the diaphragm during radical surgery for malignant pleural mesothelioma — A.J. Sharkey, R. Bilancia, et al. (2016)
• Surgery as part of radical treatment for malignant pleural mesothelioma — D.A. Waller, S. Tenconi (2017)
• Predictors of long-term survival following radical surgery for malignant pleural mesothelioma — A. Nakas, D. Waller (2014)
• The new case for cervical mediastinoscopy in selection for radical surgery for malignant pleural mesothelioma — A. Nakas, D. Waller, et al. (2012)
• Long-term Survival and Propensity Score Matched Outcomes of Bilateral vs. Unilateral Diaphragm Interventions in Cytoreductive Surgery plus Intra-peritoneal Chemotherapy — B. Singh, G. Singh, et al. (2018)
• Multimodal therapy of malignant pleural mesothelioma: is the replacement of radical surgery imminent? — J. Lindenmann, V. Matzi, et al. (2013)

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