Adjuvant Hepatic Arterial Infusion Pump Chemotherapy after Resection of Colorectal Liver Metastases; Surgical Complications, Toxicity, and Survival in a Prospective Study in the Netherlands

Abstract

Background: Hepatic arterial infusion pump (HAIP) chemotherapy remains a promising treatment for patients with colorectal liver metastases (CRLM). The aim of this study was to investigate surgical complications, toxicity, and survival outcomes of patients who received adjuvant HAIP chemotherapy for CRLM. Methods: A single arm phase II study was performed in four centers. Patients with resectable CRLM without extrahepatic disease were eligible. An infusion pump was implanted after complete local treatment of CRLM followed by a maximum of 6 cycles of HAIP chemotherapy with floxuridine. Outcomes were 90 days pump-related major complications (Clavien Dindo grade ≥III), intra-arterial chemotherapy-related severe toxicity (CTCAE grade ≥III), and overall survival (OS). Results: Twenty-nine patients were included. Four patients (11.8%) had pump-related major complications, all requiring pump replacement; one for pump dysfunction, two for pump dislocation, and one for pump pocket infection. All patients started with HAIP chemotherapy. The median number of cycles was 5 (IQR 4-6), and the median cumulative dosage was 72% (IQR 55-85%). Ten patients (34%) required intra-arterial steroid treatment for biliary toxicity. Seven patients (24%) developed severe toxicity; five patients required stent-placement (three for biliary sclerosis/hyperbilirubinemia, two for persistent increase in liver enzymes without hyperbilirubinemia), one patient developed hepatic artery thrombosis, one patient required endoscopic extraction of an intrahepatic gallstone. Two-year OS was 93% (95%CI: 85-100%). Conclusion: Adjuvant HAIP chemotherapy for CRLM may result in major complications and severe toxicity; 1 in 7 patients required pump replacement and 1 in 6 patients required stent-placement for biliary sclerosis. Two-year OS was 93%.Tabled 1Patient and surgical characteristicsMedian [IQR] / n (%)Age at resection (years)57 [50-64]Clinical Risk Score (Fong score)2 [1-3]Preoperative systemic CTx9 (30)Major hepatectomy6 (21)Synchronous resection with primary CRC3 (10)Open ablation (with or without resection)11 (45)Surgery time (min)247 [204-300]Blood loss (mL)455 [187-762]Postoperative hospital stay (days)8 (6-9) Open table in a new tab