SBS5 (clock-like) mutational signature flags longer PFS after cisplatin HIPEC in EOC

In a single-center WES biomarker analysis of patients with primary or recurrent epithelial ovarian cancer (EOC) treated with cisplatin HIPEC during optimal cytoreductive surgery (cisplatin 75mg/m², 60 min, 42°C; NCT01970722), SBS5 (unknown etiology; “clock-like”) was enriched in “good responders” defined by PFS ≥18 months (primary) or ≥12 months (recurrent) vs “poor responders” (n=36 tumors; 21 primary/15 recurrent; p=0.017). Clinically, good responders had longer OS vs poor responders (NR vs NR; p=0.02), but this is a retrospective, threshold-defined endpoint rather than randomized HIPEC vs no-HIPEC predictive evidence; in first-line interval-debulking HIPEC trials, median PFS benchmarks have typically been in the mid–teens months range (e.g., ~14 months in the van Driel setting), so the “good responder” cutoffs are directionally consistent with clinically meaningful separation rather than a marginal tweak. Recurrence pattern signal: peritoneal-only recurrence (64%) showed higher SBS15 (MMR-associated) burden than extraperitoneal recurrence (36%) (p=0.048), while median PFS was similar by recurrence site (15.3 vs 14.3 months), suggesting SBS15 may be more about metastatic pattern than overall disease control in this dataset.