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Background: Histopathological growth patterns (HGPs) are a prognostic biomarker in colorectal liver metastases (CRLM). Desmoplastic HGP (dHGP) is associated with liver-only recurrence and superior overall survival (OS), while non-dHGP is associated with multi-organ recurrence and inferior OS. This study investigated the predictive value of HGPs for adjuvant hepatic arterial infusion pump (HAIP) chemotherapy in CRLM., Methods: Patients undergoing resection of CRLM and perioperative systemic chemotherapy in two centers were included. Survival outcomes and the predictive value of HAIP versus no HAIP per HGP group were evaluated through Kaplan-Meier and Cox regression methods, respectively., Results: We included 1233 patients. In the dHGP group (n = 291, 24%), HAIP chemotherapy was administered in 75 patients (26%). In the non-dHGP group (n = 942, 76%), HAIP chemotherapy was administered in 247 patients (26%). dHGP was associated with improved overall survival (OS, HR 0.49, 95% CI 0.32-0.73, p < 0.001). HAIP chemotherapy was associated with improved OS (HR 0.61, 95% CI 0.45-0.82, p < 0.001). No interaction could be demonstrated between HGP and HAIP on OS (HR 1.29, 95% CI 0.72-2.32, p = 0.40)., Conclusions: There is no evidence that HGPs of CRLM modify the survival benefit of adjuvant HAIP chemotherapy in patients with resected CRLM., (© 2023. The Author(s).)

Background: After resection of colorectal liver metastases (CRLM), recurrent disease in the liver is a major cause of death but may be reduced with the addition of adjuvant hepatic arterial infusion (HAI) chemotherapy to systemic chemotherapy (SYS)., Objective: This study investigates organ-specific causes of death in patients receiving adjuvant HAI and SYS compared to adjuvant SYS alone., Methods: Between 2000 and 2007, patients undergoing complete CRLM resection were identified from a prospectively maintained liver resection database and categorized as receiving HAI + SYS or SYS only. Using newly constructed definitions, mortality was attributed to specific organs (liver, lung, peritoneum, and brain) or infection. Univariate models and cumulative incidence functions were generated using competing risk methods., Results: Of 361 eligible patients, 208 (57.6%) received HAI + SYS and 153 (42.4%) received SYS. The median follow up among survivors was 142 months (range = 12-217 months). Ten-year overall survival was 50.6% in the HAI + SYS group compared to 30.9% in those receiving SYS (P = .004). The 5-year cumulative incidence of liver-related mortality was 6.8% in the HAI + SYS group compared to 14.3% in the SYS group (P = .007)., Conclusion: The addition of HAI to SYS after CRLM resection is associated with a 50% reduction in liver-related mortality at 5 years., (© 2020 Wiley Periodicals, Inc.)

Background: Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM., Methods: This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 μg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4-12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and a reduction of costs, compared to resection alone., Discussion: If this PUMP trial demonstrates that adjuvant HAIP chemotherapy improves survival in low-risk patients, this treatment approach may be implemented in the standard of care of patients with resected CRLM since adjuvant systemic chemotherapy alone has not improved survival., Trial Registration: The PUMP trial is registered in the Netherlands Trial Register (NTR), number: 7493 . Date of registration September 23, 2018.