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Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer

In locally advanced rectal cancer, radiotherapy (RT) followed by surgery have improved locoregional control, but distant recurrences remain frequent. Although checkpoint inhibitors have demonstrated objective response in several cancers, the clinical benefit of PD-1/PD-L1 blockade remains uncertain...

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Autores principales: Boustani, Jihane, Derangère, Valentin, Bertaut, Aurélie, Adotevi, Olivier, Morgand, Véronique, Charon-Barra, Céline, Ghiringhelli, François, Mirjolet, Céline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563314/
https://www.ncbi.nlm.nih.gov/pubmed/32927784
http://dx.doi.org/10.3390/cells9092071
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author Boustani, Jihane
Derangère, Valentin
Bertaut, Aurélie
Adotevi, Olivier
Morgand, Véronique
Charon-Barra, Céline
Ghiringhelli, François
Mirjolet, Céline
author_facet Boustani, Jihane
Derangère, Valentin
Bertaut, Aurélie
Adotevi, Olivier
Morgand, Véronique
Charon-Barra, Céline
Ghiringhelli, François
Mirjolet, Céline
author_sort Boustani, Jihane
collection PubMed
description In locally advanced rectal cancer, radiotherapy (RT) followed by surgery have improved locoregional control, but distant recurrences remain frequent. Although checkpoint inhibitors have demonstrated objective response in several cancers, the clinical benefit of PD-1/PD-L1 blockade remains uncertain in rectal cancer. We collected data from biopsies and surgical specimens in 74 patients. The main objective was to evaluate the impact of neoadjuvant RT and fractionation on PD-L1 expression. Secondary objectives were to study the relation between PD-L1 expression and tumor regression grade (TRG), progression-free survival (PFS), overall survival (OS), and CD8 TILs infiltration. Median rates of cells expressing PD-L1 pre- and post-RT were 0.15 (range, 0–17) and 0.5 (range, 0–27.5), respectively (p = 0.0005). There was no effect of RT fractionation on PD-L1+ cell rates. We found no relation between CD8+ TILs infiltration and PD-L1 expression and no difference between high-PD-L1 or low-PD-L1 expression and TRG. High-to-high PD-L1 expression profile had none significant higher OS and PFS compared to all other groups (p = 0.06). Median OS and PFS were higher in biopsies with >0.08 PD-L1+ cells. High-to-high PD-L1 profile and ypT0-2 were significantly associated with higher OS and PFS. This study did not show the differential induction of PD-L1 expression according to fractionation.
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spelling pubmed-75633142020-10-27 Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer Boustani, Jihane Derangère, Valentin Bertaut, Aurélie Adotevi, Olivier Morgand, Véronique Charon-Barra, Céline Ghiringhelli, François Mirjolet, Céline Cells Article In locally advanced rectal cancer, radiotherapy (RT) followed by surgery have improved locoregional control, but distant recurrences remain frequent. Although checkpoint inhibitors have demonstrated objective response in several cancers, the clinical benefit of PD-1/PD-L1 blockade remains uncertain in rectal cancer. We collected data from biopsies and surgical specimens in 74 patients. The main objective was to evaluate the impact of neoadjuvant RT and fractionation on PD-L1 expression. Secondary objectives were to study the relation between PD-L1 expression and tumor regression grade (TRG), progression-free survival (PFS), overall survival (OS), and CD8 TILs infiltration. Median rates of cells expressing PD-L1 pre- and post-RT were 0.15 (range, 0–17) and 0.5 (range, 0–27.5), respectively (p = 0.0005). There was no effect of RT fractionation on PD-L1+ cell rates. We found no relation between CD8+ TILs infiltration and PD-L1 expression and no difference between high-PD-L1 or low-PD-L1 expression and TRG. High-to-high PD-L1 expression profile had none significant higher OS and PFS compared to all other groups (p = 0.06). Median OS and PFS were higher in biopsies with >0.08 PD-L1+ cells. High-to-high PD-L1 profile and ypT0-2 were significantly associated with higher OS and PFS. This study did not show the differential induction of PD-L1 expression according to fractionation. MDPI 2020-09-10 /pmc/articles/PMC7563314/ /pubmed/32927784 http://dx.doi.org/10.3390/cells9092071 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Boustani, Jihane
Derangère, Valentin
Bertaut, Aurélie
Adotevi, Olivier
Morgand, Véronique
Charon-Barra, Céline
Ghiringhelli, François
Mirjolet, Céline
Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer
title Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer
title_full Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer
title_fullStr Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer
title_full_unstemmed Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer
title_short Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer
title_sort radiotherapy scheme effect on pd-l1 expression for locally advanced rectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563314/
https://www.ncbi.nlm.nih.gov/pubmed/32927784
http://dx.doi.org/10.3390/cells9092071
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