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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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2023
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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. |
format | Online Article Text |
id | pubmed-10626762 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
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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