KRAS mutational status in patients with unresectable liver metastases from colorectal cancer predicts a worse response to hepatic arterial infusion (HAI) pump chemotherapy, according to research presented by Kolbeinsson et al at the Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care (Abstract 39).
The KRAS gene provides instructions for making the KRAS protein, which relays signals from outside the cell to the cell's nucleus. These signals instruct the cell to grow and divide or to mature and take on specialized functions.
KRAS mutation predicts negative outcomes following resection of colorectal liver metastases and adjuvant HAI pump chemotherapy. Less is known about the effects of KRAS mutation on tumor response in patients with unresectable colorectal liver metastases treated with HAI chemotherapy.
Review and Results
To examine this, a research team designed a retrospective review investigating the effects of KRAS mutation on tumor response in patients with unresectable colorectal liver metastases treated with HAI pump chemotherapy. Maximal tumor response and objective response rate was assessed with computed tomography imaging; objective response rate was defined as cross-sectional decrease in target lesions by greater than 50%.
Researchers reviewed cases from 25 patients with unresectable liver metastases from colorectal cancer who were treated with HAI chemotherapy between August 2017 and May 2019. Median age was 59 years (range = 35–77) and 13 (52%) were male. Median number of liver lesions was 12 (range = 1–59), and almost all patients (n = 24) had prior chemotherapy before starting HAI therapy. Median number of cycles administered via HAI chemotherapy pump was six (range = 3–12).
The team observed an overall decrease in liver tumor burden of 63.5%, with an objective response rate of 80% and 40% of patients converting to resectable status. Eleven (44%) patients had a KRAS mutation. When compared to wild-type, KRAS mutation–positive tumors had a lower rate (7 of 11 [64%] vs 13 of 13 [100%]; P = .03) and magnitude of response (median = 58% vs 70%, P = .04). Fewer patients with KRAS mutation–positive tumors converted to resectable status during HAI therapy (2 of 11 vs 8 of 13, P = .05).
