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The prognostic impact of PD-L1 and CD8 expression in anal cancer patients treated with chemoradiotherapy

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression has been shown to be prognostic in many cancer types and used in consideration of checkpoint inhibitor immunotherapy. However, there are very limited and conflicting data on the prognostic impact of PD-L1 in patients with anal squamous cell ca...

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Autores principales: Chan, Angela MY., Roldan Urgoiti, Gloria, Jiang, Will, Lee, Sandra, Kornaga, Elizabeth, Mathen, Peter, Yeung, Rosanna, Enwere, Emeka K., Box, Alan, Konno, Mie, Koebel, Martin, Joseph, Kurian, Doll, Corinne M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585228/
https://www.ncbi.nlm.nih.gov/pubmed/36276142
http://dx.doi.org/10.3389/fonc.2022.1000263
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author Chan, Angela MY.
Roldan Urgoiti, Gloria
Jiang, Will
Lee, Sandra
Kornaga, Elizabeth
Mathen, Peter
Yeung, Rosanna
Enwere, Emeka K.
Box, Alan
Konno, Mie
Koebel, Martin
Joseph, Kurian
Doll, Corinne M.
author_facet Chan, Angela MY.
Roldan Urgoiti, Gloria
Jiang, Will
Lee, Sandra
Kornaga, Elizabeth
Mathen, Peter
Yeung, Rosanna
Enwere, Emeka K.
Box, Alan
Konno, Mie
Koebel, Martin
Joseph, Kurian
Doll, Corinne M.
author_sort Chan, Angela MY.
collection PubMed
description BACKGROUND: Programmed death-ligand 1 (PD-L1) expression has been shown to be prognostic in many cancer types and used in consideration of checkpoint inhibitor immunotherapy. However, there are very limited and conflicting data on the prognostic impact of PD-L1 in patients with anal squamous cell carcinoma (ASCC). The objectives of this study were to measure the expression of PD-L1 and CD8 in patients with ASCC treated with radical chemoradiotherapy (CRT) and to correlate tumor expression with progression-free survival (PFS) and overall survival (OS). METHODS: Ninety-nine patients with ASCC treated with primary CRT at two tertiary care cancer centers between 2000 and 2013, with available pre-treatment tumors, were included. Tissue microarrays (TMAs) from pre-treatment tumor specimens were stained for PD-L1 and CD8. PD-L1 expression in the tumor and stroma was quantified using HALO image analysis software, and results were interpreted using quantitative methods. The density of CD8 cells within the tumor was interpreted by a trained pathologist semi-quantitatively, using a 0-4 scoring system. Kaplan-Meier analysis with log-rank was used to determine the significance in the association of tumor markers with PFS and OS. Cox multivariate analysis was used to explore independent predictors of PFS and OS. RESULTS: Of the 99 patients, 63 (64%) had sufficient tumor samples available for full analysis. CD8 high status was documented in 32 of 63 (50.8%) % of cases. PD-L1 expression was positive in 88.9% of cases. Approximately half the patients had tumor PD-L1 ≥ 5%. Patients with tumor PD-L1 ≥ 5% had better OS vs those with lower expression, HR=0.32 (95% CI 0.11-0.87), p=0.027; 10 years OS: 84% for tumor PD-L1 ≥ 5% vs 49% for PD-L1 < 5%. PD-L1 expression was not associated with PFS. On multivariate analysis, tumor PD-L1 ≥ 5% showed a trend to statistical significance for better OS, HR=0.55 (95% CI 0.12- 1.00), p=0.052. CONCLUSIONS: Tumor PD-L1≥5% is associated with OS in patients with ASCC treated with CRT. PD-L1 expression status using this unique cut-point warrants further validation for prognostication in patients with this disease. Future studies are required to determine the benefit of alternative treatment strategies based on PD-L1 status.
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spelling pubmed-95852282022-10-22 The prognostic impact of PD-L1 and CD8 expression in anal cancer patients treated with chemoradiotherapy Chan, Angela MY. Roldan Urgoiti, Gloria Jiang, Will Lee, Sandra Kornaga, Elizabeth Mathen, Peter Yeung, Rosanna Enwere, Emeka K. Box, Alan Konno, Mie Koebel, Martin Joseph, Kurian Doll, Corinne M. Front Oncol Oncology BACKGROUND: Programmed death-ligand 1 (PD-L1) expression has been shown to be prognostic in many cancer types and used in consideration of checkpoint inhibitor immunotherapy. However, there are very limited and conflicting data on the prognostic impact of PD-L1 in patients with anal squamous cell carcinoma (ASCC). The objectives of this study were to measure the expression of PD-L1 and CD8 in patients with ASCC treated with radical chemoradiotherapy (CRT) and to correlate tumor expression with progression-free survival (PFS) and overall survival (OS). METHODS: Ninety-nine patients with ASCC treated with primary CRT at two tertiary care cancer centers between 2000 and 2013, with available pre-treatment tumors, were included. Tissue microarrays (TMAs) from pre-treatment tumor specimens were stained for PD-L1 and CD8. PD-L1 expression in the tumor and stroma was quantified using HALO image analysis software, and results were interpreted using quantitative methods. The density of CD8 cells within the tumor was interpreted by a trained pathologist semi-quantitatively, using a 0-4 scoring system. Kaplan-Meier analysis with log-rank was used to determine the significance in the association of tumor markers with PFS and OS. Cox multivariate analysis was used to explore independent predictors of PFS and OS. RESULTS: Of the 99 patients, 63 (64%) had sufficient tumor samples available for full analysis. CD8 high status was documented in 32 of 63 (50.8%) % of cases. PD-L1 expression was positive in 88.9% of cases. Approximately half the patients had tumor PD-L1 ≥ 5%. Patients with tumor PD-L1 ≥ 5% had better OS vs those with lower expression, HR=0.32 (95% CI 0.11-0.87), p=0.027; 10 years OS: 84% for tumor PD-L1 ≥ 5% vs 49% for PD-L1 < 5%. PD-L1 expression was not associated with PFS. On multivariate analysis, tumor PD-L1 ≥ 5% showed a trend to statistical significance for better OS, HR=0.55 (95% CI 0.12- 1.00), p=0.052. CONCLUSIONS: Tumor PD-L1≥5% is associated with OS in patients with ASCC treated with CRT. PD-L1 expression status using this unique cut-point warrants further validation for prognostication in patients with this disease. Future studies are required to determine the benefit of alternative treatment strategies based on PD-L1 status. Frontiers Media S.A. 2022-10-07 /pmc/articles/PMC9585228/ /pubmed/36276142 http://dx.doi.org/10.3389/fonc.2022.1000263 Text en Copyright © 2022 Chan, Roldan Urgoiti, Jiang, Lee, Kornaga, Mathen, Yeung, Enwere, Box, Konno, Koebel, Joseph and Doll https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Chan, Angela MY.
Roldan Urgoiti, Gloria
Jiang, Will
Lee, Sandra
Kornaga, Elizabeth
Mathen, Peter
Yeung, Rosanna
Enwere, Emeka K.
Box, Alan
Konno, Mie
Koebel, Martin
Joseph, Kurian
Doll, Corinne M.
The prognostic impact of PD-L1 and CD8 expression in anal cancer patients treated with chemoradiotherapy
title The prognostic impact of PD-L1 and CD8 expression in anal cancer patients treated with chemoradiotherapy
title_full The prognostic impact of PD-L1 and CD8 expression in anal cancer patients treated with chemoradiotherapy
title_fullStr The prognostic impact of PD-L1 and CD8 expression in anal cancer patients treated with chemoradiotherapy
title_full_unstemmed The prognostic impact of PD-L1 and CD8 expression in anal cancer patients treated with chemoradiotherapy
title_short The prognostic impact of PD-L1 and CD8 expression in anal cancer patients treated with chemoradiotherapy
title_sort prognostic impact of pd-l1 and cd8 expression in anal cancer patients treated with chemoradiotherapy
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585228/
https://www.ncbi.nlm.nih.gov/pubmed/36276142
http://dx.doi.org/10.3389/fonc.2022.1000263
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