Genomic predictors of pathologic response to hepatic artery infusion pump chemotherapy in colorectal liver metastases.

BACKGROUND

Preoperative hepatic artery infusion pump chemotherapy (HAIP) in colorectal liver metastases (CRLM) is associated with greater pathologic response (PR). We aimed to identify genomic predictors of PR in initially unresectable (IU)-CRLM treated with preoperative HAIP.

METHODS

Three-hundred-fifty patients treated with HAIP for IU-CRLM from 2000 to 2021 were reviewed retrospectively; 96 underwent resection. Specimens were evaluated for PR and next-generation sequencing was performed. Wilcoxon rank-sum test was used to determine the association between genomic alterations and PR (continuous outcome). PR was categorized as minor (0%-74%), major (75%-99%), and complete (100%). Association between co-mutation TP53-RAS and PR was assessed using multivariable linear regression. Cox regression was used to examine the association between PR and survival.

RESULTS

Median PR was 51% in patients with TP53-RAS; 91% in those without the co-mutation (Others) (P < 0.001). TP53-RAS remained associated with lower PR (β -0.25, P < 0.001) on multivariate analysis. PR was associated with event-free survival (EFS) (HR 0.92, 95% CI: 0.85-0.98; P 0.013), not with overall survival (OS) (HR 0.94, 95% CI: 0.86-1.03).

CONCLUSION

TP53-RAS in IU-CRLM is associated with lower rates of PR to preoperative HAIP than Others. PR was associated with EFS, not with OS.