Tumour cell PD-L1 expression is prognostic in patients with malignant pleural effusion: the impact of C-reactive protein and immune-checkpoint inhibition

Our plain-English summary of Tumour cell PD-L1 expression is prognostic in patients with malignant pleural effusion: the impact of C-reactive protein and immune-checkpoint inhibition, by B. Ghanim, A. Rosenmayr, P. Stockhammer, et al (Scientific Reports, 2020).

The study

• Authors: B. Ghanim, A. Rosenmayr, P. Stockhammer, M. Vogl, A. Celik, A. Bas, I.C. Kurul, N. Akyurek, A. Varga, T. Plönes, A. Bankfalvi, T. Hager, M. Schuler, K. Hackner, P. Errhalt, A. Scheed, G. Seebacher, B. Hegedus, E. Stubenberger, C. Aigner
• Journal: Scientific Reports
• Published: 2020;10(1):5784
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural effusion (MPE) confers dismal prognosis and has limited treatment options. While immune-checkpoint inhibition (ICI) proved clinical efficacy in a variety of malignancies, data on the prognostic role of PD-L1 in MPE is scarce. We retrospectively studied PD-L1 tumour proportion score and Ki-67 index in pleural biopsies or cytologies from 123 patients (69 lung cancer, 25 mesothelioma, and 29 extrathoracic primary malignancies). Additionally, the impact of C-reactive protein (CRP) and platelet count was also analysed. Median overall survival (OS) after MPE diagnosis was 9 months. Patients with PD-L1 positive tumours (≥1%) had significantly shorter OS than patients with negative PD-L1 status (p = 0.031). CRP and Ki-67 index were also prognostic and remained independent prognosticators after multivariate analysis. Interestingly, Ki-67 index and CRP influenced the prognostic power of PD-L1. Finally, patients receiving ICI tended to have a longer median OS and CRP - but not PD-L1 - was a significant prognosticator in this subgroup. In summary, histological and circulating biomarkers should also be taken into account as potential biomarkers in ICI therapy and they may have an impact on the prognostic power of PD-L1. Our findings might help personalizing immune-checkpoint inhibition for patients with MPE and warrant further prospective validation.

In plain English

This was a retrospective study of 123 patients with malignant pleural effusion (cancer-related fluid around the lungs) at hospitals in Austria, Germany and Turkey. Of these, 69 had lung cancer, 25 had mesothelioma and 29 had cancers that began outside the chest. The article did not study asbestos exposure. The authors measured two markers in pleural tissue or fluid samples: PD-L1, a tumour protein targeted by immune-checkpoint drugs, and Ki-67, a sign of tumour cell growth. They also measured C-reactive protein (CRP), a blood marker of inflammation, and platelet counts. Median survival after diagnosis was 9 months. Patients with PD-L1 positive tumours (1% or more of tumour cells) had shorter survival (hazard ratio 1.581, CI 1.043–2.396), and this held in a combined analysis. High CRP and high Ki-67 were also linked to shorter survival. PD-L1 was linked to survival only in the high-CRP group. The 20 patients given immune-checkpoint drugs had a median survival of 12 months, compared with 7 months for those not given them. The authors described this as a trend. They noted the small treated group and the retrospective design, and called for prospective studies.

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 international multicentre study
• Who was studied: 123 patients with malignant pleural effusion (69 lung cancer, 25 mesothelioma, 29 pleural metastases of extrathoracic primary tumours) from University Hospital Krems, Austria (58 patients, 01/2015 to 09/2017), University Medicine Essen – Ruhrlandklinik, Germany (42 patients, 08/2016 to 05/2018) and Gazi University, Ankara, Turkey (23 patients, 04/2013 to 11/2018)
• Exposure: Not an asbestos exposure study; no fiber exposure was assessed. The factors examined were tumour PD-L1 expression, Ki-67 index, blood CRP and platelet count, and immune-checkpoint inhibitor treatment after diagnosis
• Main results:
  • Median overall survival after malignant pleural effusion diagnosis was 9 months for the whole cohort
  • Patients with PD-L1 positive tumours (1% or more) had worse survival than PD-L1 negative patients: HR 1.581, CI 1.043–2.396, p = 0.031
  • In multivariate analysis, PD-L1 positivity (1% or more) remained an independent prognostic marker: HR 1.637, CI 1.004–2.674, p = 0.048
  • High CRP (3.8 mg/dL or more) was associated with worse survival: HR 2.288, CI 1.505–3.478, p less than 0.001
  • High Ki-67 (35% or more) was associated with shorter survival: HR 2.465, CI 1.513–4.016, p less than 0.001
  • PD-L1 was a significant prognostic factor only in the high-CRP group (p = 0.003) and not in the low-CRP group (p = 0.9)
  • Patients receiving immune-checkpoint inhibitors had a median overall survival of 12 months, compared with 7 months for those without (Mantel-Cox p = 0.309, Gehan-Breslow-Wilcoxon p = 0.051)
  • In the subgroup treated with immune-checkpoint inhibitors, PD-L1 and Ki-67 were not significant prognosticators (p = 0.634 and p = 0.81)
  • In that same treated subgroup, high CRP remained a significant prognostic factor (p = 0.047)
• The authors' conclusion: The authors concluded that they showed, for the first time, an independent prognostic role of Ki-67 index and tumour cell PD-L1 expression in malignant pleural effusion. They also concluded that CRP, Ki-67 and PD-L1 might affect the outcome of immune-checkpoint therapy, which warrants further investigation.
• Limitations the authors state:
  • The limited amount of tissue available meant that variation in PD-L1 expression within a tumour could not be addressed
  • The retrospective design brings inherent limitations
  • Immune-checkpoint treatment was given at the physician's choice, probably influenced by the patient's clinical status
  • Relatively few patients (n = 20) received immune-checkpoint inhibitors after diagnosis
  • Because some specimens were cytology preparations, immune-cell-specific or combined PD-L1 scores could not be used

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: PD-L1, Pleural Effusion, Prognosis, Ki-67, Lung Cancer, Mesothelioma, Median Overall Survival, Multivariate Analysis.

Related studies

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• Characterizing soluble immune checkpoint molecules and TGF-β1,2,3 in pleural effusion of malignant pleural mesothelioma — R. Okita, T. Senoo, et al. (2024)
• The C-Reactive Protein/Albumin Ratio is a Novel Significant Prognostic Factor in Patients with Malignant Pleural Mesothelioma: A Retrospective Multi-institutional Study — S. Takamori, G. Toyokawa, 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)
• Determination of PD-L1 expression in effusions from mesothelioma by immuno-cytochemical staining — M.S.I. Mansour, T. Seidal, et al. (2017)
• Immune checkpoint inhibitors in non-small cell lung cancer (NSCLC): Approaches on special subgroups and unresolved burning questions — J. Remon, N. Vilariño, et al. (2018)

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