ROLE OF KRAS MUTATIONS IN HEPATIC PFS FOR UNRESECTABLE CRLM RECEIVING HAI THERAPY
Alexis Andrea Webber1, Caio Max S. Rocha Lima1, Michael McCormack1, Ravi Paluri1, Perry Shen11. Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, NC, United States.
Background:
About 25% of patients with colorectal cancer present with liver metastases (CRLM). Hepatic arterial infusion (HAI) chemotherapy improves hepatic response and conversion-to-resection rates in high-volume centers, but outcomes"”particularly by tumor molecular features"”remain unclear. We evaluated progression patterns in patients with unresectable CRLM treated with HAI at a single academic center.
Methods:
We performed a retrospective single-institution case series including adults who underwent HAI pump placement for unresectable CRLM from Jan 2020-Aug 2025. Patients receiving adjuvant HAI were excluded. Clinical, molecular, and treatment data were extracted. The primary outcome was hepatic progression-free survival (hPFS) by mutation status (KRAS vs. other: PI3K, BRAF).
Results:
Twenty patients were included (median age 55 years). Primary tumors were right colon (40%), left colon (45%), and rectum (15%). Median preoperative CEA was 8.1 ng/mL (1.3-197.7). KRAS mutations were most common (55%), followed by PI3K (30%) and BRAF (10%). Eleven patients (55%) underwent simultaneous resection with HAI placement, 7 (35%) had prior resection, 1 had no resection, and 1 underwent resection after HAI. Median estimated blood loss was 113 mL for HAI alone, 300 mL with hepatectomy/ablation, and 165 mL with primary tumor resection. Three patients (15%) were readmitted within 30 days. Pump-related complications occurred in 5 patients (25%). All patients received FUDR (median 28 days to initiation; 5 cycles), and systemic chemotherapy most commonly included FOLFOX (55%, median 42 days to initiation; 4 cycles).Median hPFS was 6.7 months [4.3-NR]. Stratified by RAS status, median hPFS was 7.8 months [4.3-NR] for RAS-mutated vs. 14.2 months [9.3-NR] for wild-type (p = 0.16). Because median hPFS 95% CI was not reached, restricted mean survival time (RMST) analysis truncated at 18 months was performed. RMST was 7.9 months for KRAS-mutated vs. 13.3 months for wild-type (difference -5.46 months, 95% CI -10.54 to -0.38, p = 0.035), with greater restricted mean time lost in KRAS-mutated patients.
Conclusion:
In this exploratory analysis, KRAS mutations were associated with shorter hepatic progression-free survival by RMST. These findings suggest tumor genetics may influence outcomes and support larger studies to guide patient selection for HAI therapy. Additionally, our observation of shorter hepatic PFS under HAI in patients with KRAS-mutated tumors is consistent with this adverse biology and suggests that the addition of liver-directed therapy may only partially mitigate the inherent propensity of RAS-mutant tumors to progress within the liver.
Hepatic Progression Free Survival Stratified by RAS mutant vs. wildtypeIMAGE CAPTION: Hepatic Progression Free Survival Stratified by RAS mutant vs. wildtype
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