ESTRO 2025 - Abstract Book

S1324

Clinical - Lung

ESTRO 2025

1556

Poster Discussion Effect of SABR on circulating tumor DNA detection in early-stage lung cancer: Interim results from a prospective, multi-center trial Sympascho Young 1 , Saurav Verma 2 , Thomas Kennedy 3 , Morgan Black 2 , Britney Messam 2 , Andrew Warner 1 , Emma Churchman 2 , Joanna M Laba 1 , George B Rodrigues 1 , Yee Ung 4 , May Tsao 4 , Chris Goodman 1 , Melody Qu 1 , Pencilla Lang 1 , Brian Yaremko 1 , Ruoying Yu 5 , Wanxiangfu Tang 5 , Alexander V Louie 4 , David A Palma 1 , Daniel Breadner 2 1 Radiation Oncology, London Health Sciences Centre, London, Canada. 2 Medical Oncology, London Health Sciences Centre, London, Canada. 3 Radiation Oncology, BC Cancer Agency, Kelowna, Canada. 4 Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada. 5 Nanjing, Geneseeq Technology Inc., Nanjing, China Purpose/Objective: SABR is a standard of care treatment for inoperable patients with early-stage lung cancer. Patients with high risk of biopsies are sometimes treated without a tissue diagnosis, based on a high clinical likelihood of malignancy. The use of blood-based circulating tumor DNA (ctDNA) liquid biopsies in this setting may allow pathological confirmation and further molecular testing. However, detection rates in early-stage lung cancer are typically low. We hypothesize that liquid biopsies may have higher ctDNA detection rates after initiation of SABR. Material/Methods: We report interim results from a multi-institutional, prospective study (SABR-DETECT NCT05921474). We enrolled two cohorts of patients: Cohort 1: suspected stage I/IIA non-small cell lung cancer (NSCLC) based on a pretreatment likelihood of malignancy of ≥60% using validated models (n=45); cohort 2: biopsy-proven NSCLC patients (n=45). Plasma was collected for ctDNA analysis prior to SABR and 24-72 hours after the first fraction of SABR (range: 7.5-18 Gy). ctDNA was analyzed using SHIELDING™ ULTRA MRD panel of hotspot regions in 2365 cancer-related genes. Results: Paired plasma samples (pre- and post-SABR) were tested for 56 patients, and 106 total samples were analyzable and included in this interim analysis. The median patient age was 80 years (range: 58-89) and 59% (n=33) were male. This cohort comprised of 23% current and 73% former smokers, with a median of 40 pack years (interquartile range [IQR]: 30-50). Baseline and post-SABR samples had a median total ctDNA of 19.9 ng (IQR: 12.4-32.6) and 21.8 ng (IQR: 15.8-28.6), respectively. The total yield of ctDNA extraction was proportional to the number of unique DNA molecules (R 2 =0.91), which correlated positively with detection rates. Detectable ctDNA post-treatment was present pre-SABR in 28% (n=15) patients. After a single fraction of SABR, 15% (n=8) additional patients had detectable ctDNA, while 4% (n=2) patients no longer had detectable ctDNA. The rest of the samples remained undetectable (53%, n=30). Pre-SABR rate of detection was 32% versus 43% post-SABR, whereas 47% of patients had detectable ctDNA either before or after SABR. In cohort 2, 24 patients had tissue confirmed diagnosis; of these, 54% (n=13) were adenocarcinoma, 42% (n=10) were squamous cell carcinoma (SCC), and 4% (n=1) was large cell. SCC had higher detection rates of ctDNA (44% pre-SABR; 56% post-SABR) compared with adenocarcinoma (15% pre-SABR; 39% post-SABR). Conclusion: In this interim analysis, detection rates of ctDNA in early-stage NSCLC patients increased when collected within 24 72 hours after a single fraction of SABR.

Keywords: ctDNA, SABR/SBRT, liquid biopsy