Abstract 7470: Extensive genome sequencing on tissue vs large ctDNA panel: what clinical impact?

Abstract Background: Molecular profiling is critical for personalizing cancer treatments, with approaches spanning from tissue DNA sequencing to liquid biopsy analysis of circulating tumor DNA (ctDNA). While both techniques provide valuable insights, the comparative clinical impact of tissue-based genomic profiling versus ctDNA-based profiling in tailoring treatments remains insufficiently explored. Methods: We are investigating the comparison between wide genomic sequencing of tissue and ctDNA profiling with a large panel to evaluate their ability to guide treatment decisions in cancer patients. At Gustave Roussy, Comprehensive genomic profiling (CGP) on ctDNA is routinely used to guide treatment selection for patients with advanced metastatic cancers, in therapy failure after 1st line. In the same patient population, Extensive Genome Sequencing (EGS: WGS, WES, WTS) can also be proposed, from fresh frozen material. To assess the relevance of these approaches, we identified a cohort of patients from Gustave Roussy with prescription of both EGS on fresh frozen tumor tissue and CGP on ctDNA, (Foundation One Liquid CDx Assay, 324 genes, tumor mutational burden [TMB], microsatellite instability) and were discussed in Gustave Roussy’s molecular tumor board. This study will evaluate and compare the capacity of these methods to tailor treatment strategies in this population Results: Between April 2021 and Oct 2024, 202 patients with both EGS and CGP were identified. Failure rate of EGS on tissue was 18.8% (due to lack of sufficient tissue for 36 patients and non-contributive for 2 patients). Conversely, failure rate of CGP on ctDNA was 8.4% (non-contributive for 17 patients). Out of the 147 evaluable patients, main tumor types were HNSCC (n=32, 22%), endocrine tumors (n=26, 18%), gynecological tumors (n=16, 11%), sarcoma (n=13, 9%) and pancreatic tumors (n=14, 9%). The median turnaround time between reception of the sample and results from the molecular analysis was 10 [5:37] days for CGP versus 95 [25:724] days for EGS. We compared the therapeutic recommendations provided with both analyses, after discussion during a molecular tumor board. Independently of the time between tissue sampling and liquid biopsy (median: 111 days), treatment recommendations were concordant in 83% of cases. For 13 cases (8.8%), alterations were identified only on tissue (deletion (n=4), mutation (n=6), genomic signature (n=3)). Conclusion: Our analysis on a small cohort of patient shows that EGS and CGP have a high concordance rate in terms of therapeutic recommendations when both are contributive. Given organizational barriers of EGS on tissue (cost, turnaround time, difficulty to obtain tumor material of sufficient quality), a sequential strategy could be interesting. Citation Format: Marie Morfouace, Etienne Rouleau, Marc Deloger, Ludovic Lacroix, Voreak Suybeng, Sofiane Taleb, Claudio Nicotra, Maud Ngo Camus, Fabrice Barlesi, Fabrice André, Antoine Italiano, Benjamin Besse, Arnaud Bayle. Extensive genome sequencing on tissue vs large ctDNA panel: what clinical impact [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 7470.