Multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage III non-small cell lung cancer Journal Article
| Authors: | Alessi, J. V.; Price, A.; Richards, A. L.; Ricciuti, B.; Wang, X.; Elkrief, A.; Pecci, F.; Di Federico, A.; Gandhi, M. M.; Lebow, E. S.; Santos, P. M. G.; Thor, M.; Rimner, A.; Schoenfeld, A. J.; Chaft, J. E.; Johnson, B. E.; Gomez, D. R.; Awad, M. M.; Shaverdian, N. |
| Article Title: | Multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage III non-small cell lung cancer |
| 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. © 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. |
| Keywords: | genetics; carcinoma, non-small-cell lung; lung neoplasms; lung tumor; aneuploidy; non-small cell lung cancer; programmed death 1 receptor; non small cell lung cancer; tumor microenvironment; tumor biomarkers; humans; human; programmed cell death 1 receptor; durvalumab; immune checkpoint inhibitors |
| Journal Title: | Journal for ImmunoTherapy of Cancer |
| Volume: | 11 |
| Issue: | 11 |
| ISSN: | 2051-1426 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2023-11-01 |
| Start Page: | e007618 |
| Language: | English |
| DOI: | 10.1136/jitc-2023-007618 |
| PUBMED: | 37914383 |
| PROVIDER: | scopus |
| PMCID: | PMC10626762 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Narek Shaverdian -- Source: Scopus |
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