Prospective validation and extension of the Multimodality Prognostic Score for the treatment allocation of pleural mesothelioma patients

Our plain-English summary of Prospective validation and extension of the Multimodality Prognostic Score for the treatment allocation of pleural mesothelioma patients, by D. Greb, M. Hebeisen, A. Matter, et al (European Journal of Cardio-thoracic Surgery, 2022).

The study

• Authors: D. Greb, M. Hebeisen, A. Matter, I. Opitz, O. Lauk
• Journal: European Journal of Cardio-thoracic Surgery
• Published: 2022;62(2)
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: Patient allocation to multimodality treatment in patients with malignant pleural mesothelioma remains a challenge. The aim of this study was to validate our previously established Multimodality Prognostic Score (MMPS) (tumour volume before chemotherapy, histological subtype, C-reactive protein before chemotherapy and tumour progression after chemotherapy) and to extend the score with additional blood parameters for better patient outcome.

Methods: Patients with histologically proven malignant pleural mesothelioma and curative intended therapy with clinical stage T1-T3 N0-N2 M0 were eligible. The existing MMPS was validated and further additional blood markers (erythrocytes, neutrophils, monocytes, albumin, gamma-glutamyl transferase and alkaline phosphatase) were evaluated for potential incorporation.

Results: For the validation of the existing MMPS, as the first part of this analysis, 117 patients treated as of September 2011 were included. A total of 88 patients were treated with macroscopic complete resection, whereas 29 patients were treated with palliative or no surgery. Patients treated with macroscopic complete resection and a high MMPS showed statistically significant lower overall survival. In the second part, the extension of the MMPS with additional blood parameters was analysed. Albumin, the only parameter showing evidence for having influence on overall survival, was further added to the extended MMPS. When comparing the performance measures Area under the curve (AUC) and Brier score, the extended score performed better (higher AUC, lower Brier score) than the original MMPS.

Conclusions: The extended score with albumin showed improved performance in comparison to the original score. The extended MMPS also may help allocating patients to surgery.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.

In plain English

This single-centre Zurich study tested the group's Multimodality Prognostic Score (MMPS) for choosing patients with malignant pleural mesothelioma for surgery after induction chemotherapy. It gives one point each for tumour volume over 500 ml, non-epithelioid type in the diagnostic biopsy and C-reactive protein over 30 mg/l, all before chemotherapy, and for progression afterwards. Of 117 patients treated from September 2011, 88 had macroscopic complete resection and 29 palliative or no surgery. In resected patients, median survival was 30 months (95% CI 21–45) for a score of 0, 18 (14–29) for 1 and 13 (9 to more than 23) for 2. Of six blood markers, only albumin showed marginal evidence of an effect on survival. In 61 resected patients with an albumin result (53 deaths), its hazard ratio was 1.727 (95% CI 0.987 to 3.020, P 0.06). It became a fifth item. The extended score had a higher area under the curve and lower Brier score. Albumin was often missing, and imputation made results less clear. The authors concluded the extended score performed better and called for further prospective study.

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: Single-centre validation and extension of a previously developed prognostic score, using prospectively collected patient data
• Who was studied: Patients with histologically proven malignant pleural mesothelioma, clinical stage T1–T3 N0–N2 M0, treated with curative intent at University Hospital Zurich, Switzerland. The validation cohort was 117 patients treated from September 2011 onward: 88 had macroscopic complete resection and 29 had palliative or no surgery. Some analyses also included earlier patients treated from May 1999 (170 resected patients in total).
• Exposure: Not a study of asbestos exposure. It studied prognostic factors: the four MMPS items, each scored as 1 point. These were tumour volume before chemotherapy over 500 ml, non-epithelioid histological subtype in the diagnostic biopsy before chemotherapy, C-reactive protein over 30 mg/l before chemotherapy, and progressive disease after chemotherapy. Six blood markers were also tested: erythrocytes, neutrophils, monocytes, albumin, gamma-glutamyl transferase and alkaline phosphatase. Treatment was induction chemotherapy followed by extrapleural pneumonectomy or (extended) pleurectomy/decortication, or by palliative or no surgery. A history of asbestos exposure was recorded as 'yes' for 94 (55.6%) of the 170 resected patients.
• Main results:
  • In the resected group treated from September 2011 onward, median overall survival was 30 months (95% CI 21–45) for MMPS 0, 18 months (95% CI 14–29) for MMPS 1 and 13 months (95% CI 9 to more than 23) for MMPS 2.
  • In the group with palliative or no surgery, median overall survival was 26 months (95% CI 11 to more than 39) for MMPS 0, 12 months (95% CI 10 to more than 45) for MMPS 1 and 10 months (95% CI 8 to more than 16) for MMPS 2.
  • In resected patients (n = 114, 98 events), each MMPS item had a hazard ratio for death slightly above 2: CRP over 30 mg/l 2.307 (95% CI 1.470–3.620); tumour volume over 500 ml 2.048 (1.098–3.819); non-epithelioid subtype 2.600 (1.490–4.537); progressive disease 2.012 (1.112–3.643). The score as a single linear variable had a hazard ratio of 2.299 (95% CI 1.719–3.074).
  • For resected patients with an MMPS above 2 versus 2 or less, the hazard ratio was 35.977 (95% CI 6.862–188.632). The authors cautioned that this estimate may be unreliable because only 2 patients had a score above 2.
  • Of the six blood markers, albumin performed best as a single predictor of overall survival in resected patients. In the 61 resected patients with an albumin value (53 events), its hazard ratio was 1.727 (95% CI 0.987–3.020, P 0.06), and its AUC at 6 months was 0.84. The authors described albumin's effect as reaching only marginal statistical significance. The other five markers had P-values from 0.11 to 0.47. Albumin below 40 g/l was added as a fifth point.
  • The original 4-item MMPS had a hazard ratio of 1.725 (95% CI 1.123–2.649, P 0.01). The extended 5-item score had a hazard ratio of 1.563 (95% CI 1.132–2.158, P 0.0067), with a higher AUC and a lower Brier score. The likelihood ratio test P-value was less than 0.0001. The authors described the comparison overall as giving ambiguous results.
  • When the models were refitted using multiple imputation for missing data, results were similar, but the ability of albumin and of the extended score to distinguish survival was reduced.
• The authors' conclusion: The authors concluded that albumin was the blood marker with the largest influence on overall survival and that adding it improved the score's performance. They also concluded that further prospective, ideally randomized, analysis including patients without complete resection is needed.
• Limitations the authors state:
  • Because the score was already being used to select patients, very few resected patients had an MMPS above 2, so the sample for that group was small.
  • Some patients fell on the other side of the cut-off from the treatment they received; the authors said treatment decisions should not rest on the score alone.
  • Many values were missing, especially albumin (62.6% missing), and the data may not have been missing at random, which makes imputation difficult.
  • The authors stated that more data are needed.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Chemotherapy, Histological Subtype, Palliative Care, Overall Survival.

Related studies

• A New Prognostic Score Supporting Treatment Allocation for Multimodality Therapy for Malignant Pleural Mesothelioma: A Review of 12 Years' Experience — I. Opitz, M. Friess, et al. (2015)
• Phase II study of first-line bortezomib and cisplatin in malignant pleural mesothelioma and prospective validation of progression free survival rate as a primary end-point for mesothelioma clinical trials (European Organisation for Research and Treatment of Cancer 08052) — M.E. O'Brien, R.M. Gaafar, et al. (2013)
• The Mesothelioma Systemic Inflammation Score Is Independently Associated with Overall Survival and Predicts Benefit of Multimodality Treatment in Pleural Mesothelioma — B. Mosleh, K. Sinn, et al. (2025)
• Prognostic Score of Long-Term Survival After Surgery for Malignant Pleural Mesothelioma: A Multicenter Analysis — G. Leuzzi, F. Rea, et al. (2015)
• External validation of prognostic indices for overall survival of malignant pleural mesothelioma — Y. Kataoka, Y. Yamamoto, et al. (2017)
• Relapse pattern and second-line treatment following multimodality treatment for malignant pleural mesothelioma — A. Kostron, M. Friess, et al. (2016)

Browse more research in European Journal of Cardio-thoracic Surgery, or return to medical research.