This single-center cohort study evaluated primary tumor genomic features (via MSK-IMPACT targeted sequencing) associated with disease-free survival (DFS) and patterns of metastatic spread (hematogenous, peritoneal, lymphatic) in 377 patients with stages I–III gastric adenocarcinoma who underwent curative-intent, margin-negative resection between 2010 and 2024.
KRAS alterations (HR 1.54; 95% CI 1.04–2.28) and PIK3CA alterations (HR 2.15; 95% CI 1.25–3.69) were independently linked to worse DFS. Hematogenous recurrence tumors showed higher chromosomal instability (fraction genome altered 0.11 vs. 0.03), more whole-genome duplication (47% vs. 15%), and more cell-cycle gene alterations (39% vs. 6%) than peritoneal recurrence tumors. Bone metastases arose from more genomically stable tumors and more frequently Lauren diffuse-type histology (36% vs. 3%).
Single-center design at an academic quaternary referral center limits generalizability. Only primary tumor tissue was sequenced — no matched metastatic samples to confirm clonal evolution. Patients with fewer than 2 years of follow-up and no recurrence were excluded, which may introduce selection bias.
Clinicians should consider KRAS and PIK3CA alterations as genomic risk flags when planning postoperative surveillance intensity and perioperative treatment for resected gastric cancer. Lauren diffuse histology combined with a genomically stable primary tumor profile may warrant heightened vigilance for bone metastasis.
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