Ki67 (MIB-1) as a Prognostic Marker for Clinical Decision Making Before Extended Pleurectomy Decortication in Malignant Pleural Mesothelioma

Our plain-English summary of Ki67 (MIB-1) as a Prognostic Marker for Clinical Decision Making Before Extended Pleurectomy Decortication in Malignant Pleural Mesothelioma, by R.A. Belderbos, A.P.W.M. Maat, S.J. Baart, et al (JTO Clinical and Research Reports, 2021).

The study

• Authors: R.A. Belderbos, A.P.W.M. Maat, S.J. Baart, E.V.E. Madsen, A.J.J.C. Bogers, R. Cornelissen, J.G.J.V. Aerts, E.A.F. Mahtab, J.H. von der Thüsen
• Journal: JTO Clinical and Research Reports
• Published: 2021;2(4):100155
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: The role of surgery for early stage malignant pleural mesothelioma (MPM) remains controversial. Current expert opinion is only to treat patients surgically as part of multimodality therapy. It is still challenging to identify patients who will not benefit from surgery. We specifically evaluated tumor-related parameters in combination with clinical parameters to identify prognostic markers for survival.

Methods: Clinical data of 27 consecutive patients with MPM treated with extended pleurectomy and decortication within a multimodality approach were collected and analyzed. Several tumor (immuno-)histopathologic characteristics were determined on resected tumor material, among which MTAP and Ki67 (MIB-1). Univariable and multivariable analyses served to correlate clinical and tumor-related parameters to overall survival (OS) and progression-free survival (PFS).

Results: The median PFS (mPFS) was 15.3, and the median OS (mOS) was 26.5 months. Patients with a Ki67 score greater than 10% had a significantly shorter PFS (mPFS = 8.81 versus 25.35 mo, p = 0.001) and OS (mOS 19.7 versus 44.5 mo, p = 0.002) than those with a Ki67 score less than or equal to 10. Receiver operating characteristic curve analysis for Ki67 revealed an area under the curve of 0.756 with a sensitivity of 90% and specificity of 71% for a cutoff of 10% for Ki67. Patients with loss of MTAP had a significantly shorter mPFS (9 versus 21.1 mo, p = 0.014) and mOS (19.7 versus 42.6 mo, p = 0.047) than those without MTAP loss.

Conclusions: In our study, Ki67 was prognostic for OS and PFS in patients with MPM treated with extended pleurectomy/decortication in a multimodality approach. Determination of Ki67 before surgery combined with specific clinical parameters could assist in clinical decision making by identifying patients, with high Ki67, who are unlikely to benefit from surgery.

© 2021 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.

In plain English

This retrospective study from the Erasmus University Medical Center in Rotterdam, the Netherlands, looked at 27 patients with malignant pleural mesothelioma. Between May 2010 and May 2019 they had extended pleurectomy/decortication surgery combined with chemotherapy or radiotherapy. The study did not examine asbestos exposure. The authors measured features of the removed tumor, including Ki67 (a marker of dividing cells) and loss of a protein called MTAP. Median follow-up was 60.7 months, and median overall survival after surgery was 26.5 months. Patients whose tumors had Ki67 above 10% had shorter median overall survival than those at or below 10% (19.7 versus 44.5 months; hazard ratio 6.594, 95% CI 1.998–21.754). Ki67 stayed significant in separate two-factor models, one with sex and one with MTAP loss. MTAP loss was linked to shorter progression-free survival (9 versus 21.1 months). Its link with overall survival was not statistically significant in the Cox model (p 0.055). The authors concluded that Ki67 was prognostic and that testing it before surgery could help identify patients unlikely to benefit. They noted the small number of patients and the lack of a control group.

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-center study of consecutive surgically treated patients, analyzing tumor and clinical factors against survival
• Who was studied: 27 patients with malignant pleural mesothelioma (22 male, median age 60, 20 epithelioid) treated with extended pleurectomy/decortication at Erasmus University Medical Center, Rotterdam, the Netherlands, May 2010 to May 2019
• Exposure: Asbestos exposure was not studied. The factors examined were tumor markers measured on resected tumor and clinical factors. Tumor markers were Ki67 (percentage of positive tumor cells), BAP1 and MTAP (present or absent), histology, mitoses, necrosis and nuclear grade. Patients were treated with eP/D plus chemotherapy (platinum-based and pemetrexed) or radiotherapy.
• Main results:
  • Whole cohort: at a median follow-up of 60.7 months, 21 of 27 patients had progressed and 17 had died. Median overall survival was 26.5 months (95% CI 22.0 to not applicable) and median progression-free survival 15.3 months (95% CI 9.6–31.5).
  • Ki67 above 10% (13 of 27 patients) versus 10% or less: median progression-free survival 8.81 versus 25.35 months (HR 6.301, 95% CI 2.200–18.047, p = 0.001); median overall survival 19.7 versus 44.5 months (HR 6.594, 95% CI 1.998–21.754, p = 0.002)
  • Only two coefficients could be estimated per model, so Ki67 was tested in separate two-factor models, one with sex and one with MTAP loss. In each, only Ki67 kept its prognostic value.
  • MTAP loss versus MTAP expression: median progression-free survival 9 versus 21.1 months (HR 0.313, 95% CI 0.124–0.788, p = 0.014); median overall survival 19.7 versus 42.6 months (log-rank p = 0.047, but Cox HR 0.373, 95% CI 0.136–1.021, p = 0.055)
  • For predicting death before the median overall survival of 26.5 months, Ki67 had an area under the curve of 0.756. A cutoff of 12.5% (or 10%) gave sensitivity 90% and specificity 71%. A 20% cutoff gave sensitivity 100% and specificity 47%.
  • Men had shorter progression-free survival than women (male median 11 months; women's median not reached; HR 8.389, 95% CI 1.113–63.258, p = 0.039). The overall survival difference by sex was not significant in the Cox model (HR 7.105, 95% CI 0.930–55.86, p = 0.062).
  • Ki67 measured on small 2-mm tumor areas, mimicking needle biopsies, put 19 of 24 patients in the same high or low category as the whole-specimen score. 199 of 229 sub-analyses (87%) agreed.
  • No in-hospital deaths or deaths within 90 days of surgery were reported
• The authors' conclusion: The authors concluded that Ki67 is prognostic for progression-free and overall survival in these patients and is likely to be reliably assessable from needle biopsies. They said measuring it before surgery, together with clinical factors, could help identify patients with high Ki67 (above 10%) who are unlikely to benefit from surgery. They added that a definitive cutoff still has to be validated.
• Limitations the authors state:
  • Small number of patients
  • Few events, so a multivariable analysis of all parameters was not possible and the analyses had low power
  • There was no control group, so whether Ki67 predicts benefit from surgery could not be assessed
  • Ki67 may have been higher before chemotherapy in patients given neoadjuvant chemotherapy, and the analysis did not correct for this
  • No consensus on the Ki67 cutoff in the literature; the cutoff needs validation

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Multimodal Therapy, MTAP, Overall Survival, Progression-Free Survival, Pleurectomy/Decortication (P/D).

Related studies

• Prolonged survival and novel prognostic factors in women with pleural mesothelioma treated with extended pleurectomy decortication — M. Lapidot, E. Mazzola, et al. (2024)
• A randomised phase II study of extended pleurectomy/decortication preceded or followed by chemotherapy in patients with early-stage pleural mesothelioma: EORTC 1205 — J. Raskin, V. Surmont, et al. (2024)
• Gender Differences in the Use of ChatGPT as Generative Artificial Intelligence for Clinical Research and Decision-Making in Occupational Medicine — P. Mashburn, F.A. Weuthen, et al. (2025)
• Understanding clinical decision-making in mesothelioma care: a mixed methods study — C. Henshall, P. Dawson, et al. (2022)
• Extended Pleurectomy-Decortication-Based Treatment for Advanced Stage Epithelial Mesothelioma Yielding a Median Survival of Nearly Three Years — J.S. Friedberg, C.B. Simone, et al. (2017)
• Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma — E. Lim, L. Darlison, et al. (2020)

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