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

Authors :
Biagio Ricciuti
Joao V Alessi
Mark M Awad
Arielle Elkrief
Jamie E Chaft
Bruce E Johnson
Xinan Wang
Allison L Richards
Federica Pecci
Alessandro Di Federico
Adam J Schoenfeld
Malini M Gandhi
Adam Price
Emily S Lebow
Patricia Mae G Santos
Maria Thor
Andreas Rimner
Daniel R Gomez
Narek Shaverdian
Source :
Journal for ImmunoTherapy of Cancer, Vol 11, Iss 11 (2023)
Publication Year :
2023
Publisher :
BMJ Publishing Group, 2023.

Abstract

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.

Details

Language :
English
ISSN :
20511426
Volume :
11
Issue :
11
Database :
Directory of Open Access Journals
Journal :
Journal for ImmunoTherapy of Cancer
Publication Type :
Academic Journal
Accession number :
edsdoj.13b34cc4df014ca0bde4aed8a337931d
Document Type :
article
Full Text :
https://doi.org/10.1136/jitc-2023-007618