Abstract 1097: Tumor purity (TP) as a predictive biomarker for adjuvant radiotherapy (ART) in stage IIIAN2 non-small cell lung cancer (NSCLC): An ancillary analysis of Lung ART-IFCT 0503
Authors: Wael Salem Zrafi, Victor Albarrán-Artahona, Maria-Rosa Ghigna, Nicolas Signolle, Nathalie Cozic, Filippo Gustavo Dall’Olio, Julien Adam, Ludovic Lacroix, Cécile Le Pechoux, Antonin Levy, Daniel Gautheret, Benjamin Besse
Journal: Cancer Research (2025)

Abstract BACKGROUND: TP is defined as the proportion of cancer cells in the tumor tissue and serves as a key characteristic of the tumor microenvironment .ESTIMATE algorithm infers TP on samples using gene expression. Its association with the effects of radiotherapy has not yet been explored. METHODS: In the Lung ART trial (NCT00410683), 501 patients (pts) with completely resected stage IIIN2 NSCLC (AJCC 7th), were randomized to ART or observation (Obs). (Neo)adjuvant chemotherapy was permitted. RNA libraries were successfully extracted from 285 FFPE surgical primary, captured using SureSelect XT HS2 RNA Agilent kit, paired-end sequencing was conducted. Molecular barcode (MBC) was preprocessed using AGeNT tools and quantification was achieved using Kallisto. Gene level TPM quantification was used for TP estimation, then assessed as a prognostic and predictive biomarker using uni and multivariable Cox and Kaplan-Meier analyses. RESULTS: Among the 285 pts, 141 (49.5%) received ART. Clinical baseline characteristics were well balanced between ART and Obs arms, 61 years as a median age, 30-31% female, 77-83% of non-squamous histology respectively. TP was higher in the ART arm (0.65) Vs (0.63) in Obs p=0.006. TP was positively associated with cancer cell percentage assessed by pathologist on Hematoxylin and Eosin (HE) slides (rho 0.23, p 7.2e-5). Higher TP was significantly associated with lower T cells infiltrate, CD3+ and CD8+ cell density on IHC (rho -0.52, -0.45 respectively p &amp;lt; 2e-16, p 1.1e-14). Higher TP was associated with higher necrosis percentage if not exceeding 50% of the slide (rho 0.3 p 4.2e-6). No significant drop in TP was found after neoadjuvant treatment. Patients with high TP, according to the median value in each arm, had worse overall survival (OS) and disease-free survival (DFS) with a median OS of 48.5 vs. 106.5 months (m) for low TP patients (p=0.0008) and median DFS of 18.4 Vs 48 m (p=0.017). The predictive role of TP was amplified in the ART arm, with median OS of 38.9 m (high TP) vs not reached (low TP; p=0.0017) and median DFS of 24 (high TP) vs 58.7 m (low TP; p=0.044). A multivariable cox model showed a significant interaction between TP and ART (HR 71.3 for OS p=0.04 and 33 for DFS p=0.07). CONCLUSIONS: Our results show that higher TP is significantly associated with poorer outcomes in Stage IIIAN2 NSCLC. ART may have better efficacy in tumors with lower TP. TP is a potential new predictive biomarker for ART. Confirmatory studies are needed. Citation Format: Wael Salem Zrafi, Victor Albarrán-Artahona, Maria-Rosa Ghigna, Nicolas Signolle, Nathalie Cozic, Filippo Gustavo Dall’Olio, Julien Adam, Ludovic Lacroix, Cécile Le Pechoux, Antonin Levy, Daniel Gautheret, Benjamin Besse. Tumor purity (TP) as a predictive biomarker for adjuvant radiotherapy (ART) in stage IIIAN2 non-small cell lung cancer (NSCLC): An ancillary analysis of Lung ART-IFCT 0503 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1097.