Abstract 7490: Clinical utility of liquid biopsy in early stage lung cancer: A single institution experience
Authors: Beshiri Kristi , Marinello Arianna , Vasseur Damien , Zullo Lodovica , Sanchez Becerra Maria Virginia , Pagliaro Arianna , Cani Massimiliano , Parisi Claudia , Lavaud Pernelle , Frelaut Maxime , Abdayem Pamela , Gazzah Anas , Botticella Angela , Levy Antonin , Pechoux Cecile Le , Mercier Olaf , Ponce Santiago , Barlesi Fabrice , Planchard David , Italiano Antonio , Besse Benjamin , Remon Jordie , Aldea Mihaela 
Published: March 2024

Abstract
INTRODUCTION: Liquid biopsy (LB) proved its clinical utility in advanced non-small cell lung cancer, but its role in early-stage disease is less clear. Here, we investigated the clinical utility of LB for molecular diagnosis in early-stage lung cancer and its correlation with cancer relapse.
METHODS: This retrospective, monocentric study collected results from LB performed in patients (pts) with an early-stage lung cancer between January 2021 and May 2023, within the prospective STING study (NCT04932525). LBs were executed at different time points (before, after curative treatment, or under treatment), by using the Foundation One Liquid Dx panel. All patients had tissue molecular testing for at least EGFR, ALK and KRAS alterations. LB was considered positive (ctDNA+) if ≥ 1cancer-related alteration was identified and negative (ctDNA-) in the absence of somatic alterations or the presence of clonal hematopoiesis (CH) only. Disease-free survival (DFS) was calculated from diagnosis to cancer relapse or last follow-up, and correlated with LB results.
RESULTS: A total of 52 pts were included and 52 LBs were conducted. Pts had a median age of 63 years, 40% (25/52) were females, and 84% (43/51) had a smoking history with a median pack-years of 37.5 [4-100]. Adenocarcinoma was the most common histology (48% 25/52), followed by squamous carcinoma (23% 12/52), undifferentiated (20% 10/52) and other hystologies (9% 5/52). Patients had stage I disease in 10% (5/52), stage II in 11% (6/52) and stage III in 79% (41/52). LB was performed before curative treatment in 35/52 (67%), after curative treatment in 6/52 (11.5%) and during curative treatment in 12/52 (23%). Overall, LB was positive in 57% (30/52) of cases: 63% (26/41) in stage III and 36% (4/11) in stage I/II. Major driver mutations identified in tissue were then found in 61.5% (8/13) of LBs. The concordance between LB and tissue findings was 100% in pts with ctDNA+ (7 KRAS, 4 EGFR, 1 ALK, 1 HER2 ampl). CH was present in 66.7% (20/30) of ctDNA+ LB and 47.8% (11/23) of ctDNA- LB. Median tumor mutational burden (TMB) in ctDNA+ LB was 5.5 mut/Mb, with 4 cases of TMB &gt;16. Median follow-up was 12.6 months (mo). In pts with ctDNA+ versus ctDNA- LB, mDFS was 12.9 mo (95% 6.3-18.6) versus 27.7 mo (95%CI 12.7- NR), p=0.07, in the overall population and 12.9 mo (95%CI 7.8-19.2) versus 27.2 mo (12.7-NR) respectively, p=0.19, in pts with stage III disease.
CONCLUSIONS: LB has informal results for molecular diagnosis in nearly half of pts with an early-stage lung cancer. The high frequency of CH may lead to LB misinterpretation as false positive and requires caution. The potential association of positive LB with earlier relapse requires further investigation in larger cohorts with a longer follow-up. Results will be updated by the time of meeting.
Citation Format: Kristi Beshiri, Arianna Marinello, Damien Vasseur, Lodovica Zullo, Maria Virginia Sanchez Becerra, Arianna Pagliaro, Massimiliano Cani, Claudia Parisi, Pernelle Lavaud, Maxime Frelaut, Pamela Abdayem, Anas Gazzah, Angela Botticella, Antonin Levy, Cecile Le Pechoux, Olaf Mercier, Santiago Ponce, Fabrice Barlesi, David Planchard, Antonio Italiano, Benjamin Besse, Jordie Remon, Mihaela Aldea. Clinical utility of liquid biopsy in early stage lung cancer: A single institution experience [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7490.