Abstract 3386: Clinicogenomic comparison of patients with liver-avid/lung-adverse and lung-avid/liver-adverse patterns of metastases highlights commonalities across cancer types

Abstract Background: The analysis of metastatic trajectories and their association with genomic features can provide valuable insights to improve patient stratification and prognostication. We analyzed real-world data from a large multi-cancer cohort of patients who developed metastasis to either the liver but not the lung or the lung but not the liver, and we compared their clinical and molecular profiles. Methods: We queried a pan-cancer database of more than 85,000 patients treated at Memorial Sloan Kettering Cancer Center. All patients were profiled using MSK-IMPACT, a targeted sequencing panel that identifies somatic alterations in 341-505 genes using matched tumor and blood. Liver-avid/lung-adverse (“LiverA”) patients were defined as having developed liver metastasis but not lung metastasis, while lung-avid/liver-adverse (“LungA”) patients were defined conversely. We identified 4 cancer subtypes with at least 100 patients in each metastatic cohort: pancreatic adenocarcinoma (PAAD, n=1247, 968 LiverA/ 279 LungA), microsatellite stable colon adenocarcinoma (MSS COAD, n=905, 653/252), esophageal adenocarcinoma (ESCA, n=344,193/151), and HR+/HER2− ductal breast adenocarcinoma (HR+/HER2− BRCA, n=298,156/142). Overall survival (OS) was measured from the time of diagnosis. Results: LiverA patients had shorter OS: MSS COAD (median 53 vs. 106 months, p<0.0001), ESCA (median 21 vs. 41 months, p<0.0001), HR+/HER2− BRCA (percentage surviving after 9 years, 22% for LiverA vs. 69% for LungA patients, p<0.0001), and PAAD (median 16 vs. 33 months, p<0.0001). LiverA patients were diagnosed at a significantly younger age in 4 cancer types: HR+/HER2− BRCA (median 54 vs. 61 years, p<0.0001), ESCA (median 63 vs. 68 years, p<0.0001), PAAD(median 67 vs. 71 years, p<0.0001), and MSS COAD (median 59 vs. 61.5 years, p=0.017). Genomic analyses of primary tumors identified significantly higher chromosomal instability in the LiverA patients quantified as the fraction of genome altered (FGA) by copy number changes in 3 cancer types: ESCA (median 0.69 vs. 0.59, p=.036), HR+/HER2− BRCA (median 0.64 vs. 0.43, p=0.001), and PAAD (median 0.28 vs. 0.18, p=1.1e-5). Among HR+/HER2− BRCA patients, LiverA patients had higher rates of 11q13 (36% vs. 11%, q=0.002), MYC (14% vs. 2%, q=0.02) and FGFR1 (21% vs. 9%, q=0.06) amplifications. TP53 alterations were more frequent in LiverA patients within PAAD cohorts (84% vs. 59%, q<0.0001). MSS COAD patients in the LiverA group had higher rates of SMAD4 (19% vs. 9%, q=0.02) and lower rates of KRAS alterations (44% vs. 56%, q=0.05). Conclusions: Our data demonstrate distinct outcomes and clinicogenomic features associated with LiverA and LungA patients consistent across several cancer types, suggesting potential commonalities in underlying tumor biology that could be exploited to improve patient stratification. Citation Format: ohn Nguyen, Walid K. Chatila, Paolo Manca, Henry Walch, Subhiksha Nandakumar, Pedram Razavi, Eileen M. O'Reilly, Yelena Y. Janjigian, Rona Yaeger, Karuna Ganesh, Michael F. Berger, Nikolaus Schultz, Francisco Sanchez-Vega. Clinicogenomic comparison of patients with liver-avid/lung-adverse and lung-avid/liver-adverse patterns of metastases highlights commonalities across cancer types [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 3386.