Abstract 4637: National multidisciplinary tumor board improves diagnostic stratification and therapeutic management in cancers of unknown primary

Abstract Introduction: With the increasing complexity of current diagnostic investigations, the integration of clinical, pathological and genomic characteristics is crucial for the management of patients (pts) with cancers of unknown primary (CUP). A national multidisciplinary tumor board (NatCUPMTB) was created in July 2020 in France to discuss the diagnostic and therapeutic management of CUP pts. The objective of this study was to evaluate the diagnostic, prognostic and therapeutic impact of this NatCUPMTB after 39 months of activity. Methods: This was a multicenter retrospective study with prospective follow-up. All pts discussed at least once in the NatCUPMTB between July 2020 and October 2023 were included. Pts and tumors characteristics, pathological and genomic analyses including WGS, WES and transcriptome analysis performed on the two PFMG2025 (French Genomic Medecine Plan 2025) national sequencing laboratories, multidisciplinary tumor board (MTB) conclusions, and follow-up after MTB were collected. Results: 244 pts were included. The median age at diagnosis was 60 yo, 53% were female, and the majority of patients had an OMS status <2. The median number of metastatic sites at diagnosis was 2, with a majority located in the lymph nodes (62%). The median time between diagnosis and first MTB presentation was 3 months (1-20). At the time of analysis, NatCUPMTB conclusions were available for 129 pts with a second MTB presentation. MTB investigations enabled to identify a likely primary origin in 89/129 (69%) pts, the most frequent being breast carcinoma (N=15), renal carcinoma (N=13) and lung carcinoma (N=13). The most frequently molecular alterations found were in TP53 (37%), KRAS (19%), CDKN2A (18%), NF2 (12%), KMT2C (10%), CDKN2B (9%), PBRM1 (9%) genes. MTB diagnoses were based on the combination of clinical, pathological and genomic investigations in 51/89 (59%) of pts. Importantly, a personalized therapeutic strategy was recommended by NatCUPMTB in 91/129 (71%) of pts. Among these recommendations, 72/91 (79%) were based on the diagnosis of tissue of origin (TOO), 9/91 (10%) on an actionable molecular alteration validated in the TOO indication, 8/91 (9%) on an actionable molecular alteration not validated in the TOO indication and 2/91 (2%) based on a druggable alteration only independently from the TOO. After a median follow-up of 1.5 months, the median overall survival (OS) was 17.7 months from the 2nd MTB presentation. Conclusion: NatCUPMTB provides significant diagnostic in 69% of pts with CUP and a therapeutic strategy recommendation for 71% of pts. Citation Format: Célia Dupain, Nicolas Jacquin, Isabelle Guillou, Etienne Rouleau, Julien Masliah Planchon, Isabelle Soubeyran, Christelle De La Fouchardière, Camille Tlemsani, Hélène Blons, Laëtitia Marisa, Anna Patrikidou, Fabienne Escande, Pierre Blanc, Jennifer Wong, Pierre Saintigny, Sandrine Boyault, Adrien Buisson, Yves Allory, Anne Vincent-Salomon, Vincent Cockenpot, Janick Selves, Ivan Bièche, Maud Kamal, Christophe Le Tourneau, Sarah Watson. National multidisciplinary tumor board improves diagnostic stratification and therapeutic management in cancers of unknown primary [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 4637.