Hepatic arterial infusion pump chemotherapy combined with systemic therapy for patients with advanced colorectal liver metastases: Outcomes in a newly established program

Abstract

Presenter: Brett Walker MD | Oregon Health and Science University Background: Metastatic disease to the liver is a leading cause of morbidity and mortality in patients with colorectal cancer, with the majority of patients presenting with initially unresectable disease. Although hepatic resection offers the best chance of cure for colorectal liver metastases (CRLM), 40% of patients will develop intrahepatic recurrence not amenable to additional hepatic resection. Hepatic arterial infusion (HAI) chemotherapy with floxuridine has been demonstrated to improve survival in patients with resected CRLM and can be integrated with systemic therapy to convert patients with technically unresectable disease to a resectable status. Herein, we describe the experience of a recently established multidisciplinary hepatic arterial infusion program for the treatment of patients with advanced CRLM at an NCI Comprehensive Cancer Center. Methods: Between 2016 and 2018, n=22 consecutive patients had a HAI pump placed as part of their multidisciplinary treatment plan for advanced CRLM. All patients received systemic chemotherapy peri-operatively and concurrently with HAI. A multidisciplinary tumor board reviewed each HAI candidate before pump placement and throughout their therapy. Clinicopathologic data were collected and patient overall (OS) and progression-free (PFS) survival was assessed using the Kaplan-Meier method. Results: Over the 30-month period, 7 patients with resected CRLM and 15 patients with unresectable CRLM had an HAI pump operatively placed at a median of 6 months after diagnosis. The median age was 55 years (range: 32-67) and 59% (n=13) were women. The majority of patients had a high hepatic tumor burden (76% with >10 metastases) and received a median of 8 (range: 4-18) cycles of systemic chemotherapy, mostly commonly FOLFOX, prior to HAI pump placement (Table). Of the 12 patients with an intact primary cancer, 11 had simultaneous HAI pump placement with resection of their primary cancer. Only 1 patient experienced a major complication (Clavien-Dindo ≥ 3) within 30 days of their operation (small bowel obstruction from prior loop ileostomy procedure). 21 patients received at least one HAI cycle of floxuridine and had a median of 5 cycles (range: 1-10) before HAI therapy was discontinued or held after clearance of intrahepatic disease. In total, 32% (n=7) of patients developed pump related complications, with biliary sclerosis being the most common (n=5/21, 24%). Of the 13 patients treated to convert their initially unresectable disease, 3 patients (23%) underwent hepatic resection with curative intent after a median of 7 HAI cycles (range: 4-10) and achieved complete clearance of their hepatic disease. For all patients treated with HAI and systemic therapy, the median OS from diagnosis was 52 months (95%: IQR 43-64 months) and the median PFS from pump placement was 21 months (95%: IQR 17-31 months). Conclusion: HAI pump therapy with floxuridine can be used in combination with modern systemic chemotherapy for patients with advanced CRLM, both in the adjuvant setting and to facilitate conversion of unresectable disease in more than 20% of patients presenting with high liver disease burden. When implemented in a multidisciplinary program, HAI therapy is safe with low of peri-operative morbidity and promising outcomes in patients with limited treatment options.