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Multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage III non-small cell lung cancer

There is a need to identify predictive biomarkers to guide treatment strategies in stage III non-small cell lung cancer (NSCLCs). In this multi-institutional cohort of 197 patients with stage III NSCLC treated with concurrent chemoradiation (cCRT) and durvalumab consolidation, we identify that low t...

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Autores principales: Alessi, Joao V, Price, Adam, Richards, Allison L, Ricciuti, Biagio, Wang, Xinan, Elkrief, Arielle, Pecci, Federica, Di Federico, Alessandro, Gandhi, Malini M, Lebow, Emily S, Santos, Patricia Mae G, Thor, Maria, Rimner, Andreas, Schoenfeld, Adam J, Chaft, Jamie E, Johnson, Bruce E, Gomez, Daniel R, Awad, Mark M, Shaverdian, Narek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10626762/
https://www.ncbi.nlm.nih.gov/pubmed/37914383
http://dx.doi.org/10.1136/jitc-2023-007618
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author Alessi, Joao V
Price, Adam
Richards, Allison L
Ricciuti, Biagio
Wang, Xinan
Elkrief, Arielle
Pecci, Federica
Di Federico, Alessandro
Gandhi, Malini M
Lebow, Emily S
Santos, Patricia Mae G
Thor, Maria
Rimner, Andreas
Schoenfeld, Adam J
Chaft, Jamie E
Johnson, Bruce E
Gomez, Daniel R
Awad, Mark M
Shaverdian, Narek
author_facet Alessi, Joao V
Price, Adam
Richards, Allison L
Ricciuti, Biagio
Wang, Xinan
Elkrief, Arielle
Pecci, Federica
Di Federico, Alessandro
Gandhi, Malini M
Lebow, Emily S
Santos, Patricia Mae G
Thor, Maria
Rimner, Andreas
Schoenfeld, Adam J
Chaft, Jamie E
Johnson, Bruce E
Gomez, Daniel R
Awad, Mark M
Shaverdian, Narek
author_sort Alessi, Joao V
collection PubMed
description There is a need to identify predictive biomarkers to guide treatment strategies in stage III non-small cell lung cancer (NSCLCs). In this multi-institutional cohort of 197 patients with stage III NSCLC treated with concurrent chemoradiation (cCRT) and durvalumab consolidation, we identify that low tumor aneuploidy is independently associated with prolonged progression-free survival (HR 0.63; p=0.03) and overall survival (HR 0.50; p=0.03). Tumors with high aneuploidy had a significantly greater incidence of distant metastasis and shorter median distant-metastasis free survival (p=0.04 and p=0.048, respectively), but aneuploidy level did not associate with local-regional outcomes. Multiplexed immunofluorescence analysis in a cohort of NSCLC found increased intratumoral CD8-positive, PD-1-positive cells, double-positive PD-1 CD8 cells, and FOXP3-positive T-cell in low aneuploid tumors. Additionally, in a cohort of 101 patients treated with cCRT alone, tumor aneuploidy did not associate with disease outcomes. These data support the need for upfront treatment intensification strategies in stage III NSCLC patients with high aneuploid tumors and suggest that tumor aneuploidy is a promising predictive biomarker.
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spelling pubmed-106267622023-11-07 Multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage III non-small cell lung cancer Alessi, Joao V Price, Adam Richards, Allison L Ricciuti, Biagio Wang, Xinan Elkrief, Arielle Pecci, Federica Di Federico, Alessandro Gandhi, Malini M Lebow, Emily S Santos, Patricia Mae G Thor, Maria Rimner, Andreas Schoenfeld, Adam J Chaft, Jamie E Johnson, Bruce E Gomez, Daniel R Awad, Mark M Shaverdian, Narek J Immunother Cancer Immunotherapy Biomarkers There is a need to identify predictive biomarkers to guide treatment strategies in stage III non-small cell lung cancer (NSCLCs). In this multi-institutional cohort of 197 patients with stage III NSCLC treated with concurrent chemoradiation (cCRT) and durvalumab consolidation, we identify that low tumor aneuploidy is independently associated with prolonged progression-free survival (HR 0.63; p=0.03) and overall survival (HR 0.50; p=0.03). Tumors with high aneuploidy had a significantly greater incidence of distant metastasis and shorter median distant-metastasis free survival (p=0.04 and p=0.048, respectively), but aneuploidy level did not associate with local-regional outcomes. Multiplexed immunofluorescence analysis in a cohort of NSCLC found increased intratumoral CD8-positive, PD-1-positive cells, double-positive PD-1 CD8 cells, and FOXP3-positive T-cell in low aneuploid tumors. Additionally, in a cohort of 101 patients treated with cCRT alone, tumor aneuploidy did not associate with disease outcomes. These data support the need for upfront treatment intensification strategies in stage III NSCLC patients with high aneuploid tumors and suggest that tumor aneuploidy is a promising predictive biomarker. BMJ Publishing Group 2023-11-01 /pmc/articles/PMC10626762/ /pubmed/37914383 http://dx.doi.org/10.1136/jitc-2023-007618 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Immunotherapy Biomarkers
Alessi, Joao V
Price, Adam
Richards, Allison L
Ricciuti, Biagio
Wang, Xinan
Elkrief, Arielle
Pecci, Federica
Di Federico, Alessandro
Gandhi, Malini M
Lebow, Emily S
Santos, Patricia Mae G
Thor, Maria
Rimner, Andreas
Schoenfeld, Adam J
Chaft, Jamie E
Johnson, Bruce E
Gomez, Daniel R
Awad, Mark M
Shaverdian, Narek
Multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage III non-small cell lung cancer
title Multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage III non-small cell lung cancer
title_full Multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage III non-small cell lung cancer
title_fullStr Multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage III non-small cell lung cancer
title_full_unstemmed Multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage III non-small cell lung cancer
title_short Multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage III non-small cell lung cancer
title_sort multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage iii non-small cell lung cancer
topic Immunotherapy Biomarkers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10626762/
https://www.ncbi.nlm.nih.gov/pubmed/37914383
http://dx.doi.org/10.1136/jitc-2023-007618
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