A New Prognostic Score Supporting Treatment Allocation for Multimodality Therapy for Malignant Pleural Mesothelioma: A Review of 12 Years' Experience

Our plain-English summary of A New Prognostic Score Supporting Treatment Allocation for Multimodality Therapy for Malignant Pleural Mesothelioma: A Review of 12 Years' Experience, by I. Opitz, M. Friess, P. Kestenholz, et al (Journal of Thoracic Oncology, 2015).

The study

• Authors: I. Opitz, M. Friess, P. Kestenholz, D. Schneiter, T. Frauenfelder, T.D. Nguyen-Kim, B. Seifert, M.A. Hoda, W. Klepetko, R.A. Stahel, W. Weder
• Journal: Journal of Thoracic Oncology
• Published: 2015;10(11):1634-41
• Type of article: Review
• Cited by: 60 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Treatment of malignant pleural mesothelioma (MPM) remains a clinical challenge. The aim of this study was to identify selection factors for allocation of MPM patients to multimodal therapy based on survival data from 12 years of experience.

Methods: Eligible patients had MPM of all histological subtypes with clinical stage T1-3 N0-2 M0. Induction chemotherapy consisted of cisplatin/gemcitabine (cis/gem) or cisplatin/pemetrexed (cis/pem), followed by extrapleural pneumonectomy (EPP). Multivariate analysis was performed to assess independent prognosticators for overall survival (OS). A Multimodality Prognostic Score was developed based on clinical variables available before surgery.

Results: From May 1999 to August 2011, 186 MPM patients were intended to be treated with induction chemotherapy followed by EPP. Hematologic toxicity was significantly less frequent after cis/pem compared to cis/gem, but there was no difference in response or OS between the regimens. One hundred and twenty-eight patients underwent EPP with a 30-day mortality of 4.7%. Fifty-two percent of the patients received adjuvant radiotherapy. The median OS of patients undergoing EPP was significantly longer with 22 months (95% confidence interval: 20-24) when compared to 11 months (9-12) for patients treated without EPP. A prognostic score was defined considering tumor volume, histology, C-reactive protein level, and response to chemotherapy that identified patient groups not benefitting from multimodality treatment which was confirmed in an independent cohort.

Conclusion: Patients receiving induction chemotherapy followed by EPP for MPM of all histological subtypes and irrespective of nodal status showed a median survival of 22 months. A prognostic score is proposed to help patient allocation for surgery after validation in an independent cohort.

In plain English

Despite its title, this was not a review but an analysis of malignant pleural mesothelioma patients treated in Zurich, 1999 to 2011. Of 323 patients, 186 were eligible and agreed to chemotherapy followed by extrapleural pneumonectomy (removal of lung and pleura): 63 received cisplatin-gemcitabine, 122 cisplatin-pemetrexed and one cisplatin-vinorelbine. Severe blood toxicity was significantly rarer with pemetrexed. Of 128 who had the pneumonectomy, 101 (79%) had recorded asbestos exposure and 6 (4.7%) died within 30 days. Counted from first chemotherapy, their median survival was 22 months (95% CI 20 to 24), versus 10 months (9 to 12) without that operation; the authors said this might reflect surgery and patient selection. The authors' score combined tumor volume, subtype, C-reactive protein and chemotherapy response. Pneumonectomy patients scoring above 2 survived a median 4 months (95% CI 3 to 5), versus 21 months (15 to 28) for 2 or less. The authors concluded it can identify patients unlikely to benefit. They noted the study was retrospective and non-randomized, and the score not yet qualified as a selection test (area under the curve 69%).

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 consecutive patients at one hospital. The authors developed a prognostic score and then tested it in patients from the same group who did not have extrapleural pneumonectomy and in a separate cohort from Vienna. It is not a literature review, despite the title.
• Who was studied: 186 of 323 malignant pleural mesothelioma patients at the Division of Thoracic Surgery, University Hospital Zurich, Switzerland, treated from May 1999 to August 2011. Of these, 128 underwent extrapleural pneumonectomy. The score was also tested in 37 patients from the same group who did not have extrapleural pneumonectomy, and in 22 patients treated the same way at University Hospital Vienna.
• Exposure: This is a treatment study. Patients received three cycles of induction chemotherapy: cisplatin plus gemcitabine (63 patients), from March 2003 cisplatin plus pemetrexed (122 patients), and cisplatin plus vinorelbine (one patient). This was followed by extrapleural pneumonectomy and, in 67 patients (52%), adjuvant radiotherapy. Asbestos exposure was recorded only as a patient characteristic; no fiber types were reported.
• Main results:
  • Grade III/IV blood (hematological) toxicity at day 8 was significantly less frequent after cisplatin/pemetrexed than after cisplatin/gemcitabine (p less than 0.0005).
  • Response to chemotherapy did not differ significantly between the two regimens.
  • Median overall survival for all 186 patients intended for treatment was 19 months (95% CI 15 to 23).
  • Patients whose disease progressed on chemotherapy (n = 33) had a median survival of 14 months (95% CI 9 to 18). Patients with partial response or stable disease (n = 95) had a median survival of 22 months (95% CI 17 to 26). The difference was significant (p = 0.02).
  • Asbestos exposure was recorded in 101 of the 128 patients who underwent extrapleural pneumonectomy (79%).
  • 128 patients underwent extrapleural pneumonectomy. Six died within 30 days after the operation (30-day mortality 4.7%), and major postoperative complications occurred in 47 cases (37%).
  • Survival time was measured from the first cycle of chemotherapy.
  • Median survival for the 128 patients who had extrapleural pneumonectomy was 22 months (95% CI 20 to 24). This differed significantly from patients who did not have extrapleural pneumonectomy, whom the results section describes as treated with chemotherapy alone (p less than 0.0005). The authors said the difference might be attributed to surgery and to patient selection.
  • The Figure 2 legend gives a median survival of 10 months (95% CI 9 to 12) for patients who did not have extrapleural pneumonectomy.
  • Among patients who had extrapleural pneumonectomy, those with a Multimodality Prognostic Score above 2 had a median survival of 4 months (95% CI 3 to 5). Those with a score of 2 or less had a median survival of 21 months (95% CI 15 to 28). The difference was significant (p less than 0.0005).
  • In multivariate analysis, a score above 2 compared with 2 or less had a hazard ratio for death of 14.1 (95% CI 4.0 to 85.1).
  • In the 37 Zurich patients who did not receive extrapleural pneumonectomy and in the 22 Vienna patients, those with a score of 0 had significantly longer survival. Median survival could not be calculated for every score in the Vienna cohort.
  • At 2 years, the new score (three- and four-variable versions) showed better predictive power for survival than the existing EORTC score.
• The authors' conclusion: The authors concluded that the new score allows identification of mesothelioma patients who would not get relevant benefit from intensified therapy. They noted that it is built from clinical information available before surgery and was validated in an independent cohort, and they stated it will be further evaluated prospectively.
• Limitations the authors state:
  • The analysis was retrospective, so not all data were available for every patient.
  • The score's area under the curve of 69% does not by itself qualify it as a predictive test for patient selection.
  • The series was not randomized.
  • The survival advantage of patients who had extrapleural pneumonectomy over those who did not may partly reflect patient selection.
  • Eligibility criteria were wide and became less stringent over time. The authors linked this to overall survival levelling off at nearly 2 years.

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: Multimodal Therapy, Pleural Mesothelioma, Histological Subtype, Chemotherapy, Cisplatin, Gemcitabine, Pemetrexed (Alimta), Extrapleural Pneumonectomy (EPP).

Related studies

• Induction Therapy for Mesothelioma — I. Opitz, W. Weder (2015)
• Updated patterns of failure after multimodality therapy for malignant pleural mesothelioma — E.H. Baldini, W.G. Richards, et al. (2015)
• 18F-FDG PET/CT in the management of patients with malignant pleural mesothelioma being considered for multimodality therapy: experience of a tertiary referral center — H.S. Elliott, U. Metser, et al. (2018)
• Pretreatment serum C-reactive protein levels predict benefit from multimodality treatment including radical surgery in malignant pleural mesothelioma: a retrospective multicenter analysis — B. Ghanim, M.A. Hoda, et al. (2012)
• Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma — D.J. Sugarbaker, G.M. Strauss, et al. (1993)
• Relapse pattern and second-line treatment following multimodality treatment for malignant pleural mesothelioma — A. Kostron, M. Friess, et al. (2016)

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