This abstract seems to show some support for HAI (Hepatic arterial
infusion) improving survival TIME (months) of patients with elevated
Thymidylate synthase levels. Article is from MSK, one of the few
institutions having data showing HAI can impact survival.

KEY SENTENCE: Treatment with HAI+SYS significantly improved the
survival profile of TS+ patients

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J Clin Oncol 2003 Feb 1;21(3):406-12
Thymidylate synthase expression in hepatic tumors is a predictor of
survival and progression in patients with resectable metastatic
colorectal cancer.

Gonen M, Hummer A, Zervoudakis A, Sullivan D, Fong Y, Banerjee D,
Klimstra D, Cordon-Cardo C, Bertino J, Kemeny N.

Departments of Epidemiology and Biostatistics, Medicine, Surgery, and
Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.

Purpose: To investigate the role of thymidylate synthase (TS),p53,
and epidermal growth factor receptor (EGF-R) expressions in hepatic
tumors in predicting overall survival (OS), progression-free survival
(PFS), and hepatic progression-free survival (HPFS) in patients with
resectable metastatic colorectal cancer who were randomly assigned to
receive either systemic chemotherapy (SYS) alone or systemic and
hepatic arterial infusion (HAI+SYS) chemotherapy following liver
surgery.

Patients and Methods: Tissues from metastatic tumors were
collected during liver resection from 156 patients, and marker
expressions were determined using immunohistochemistry on frozen
samples. Univariate associations between marker expressions and
baseline variables with OS, PFS, and HPFS were examined. Independent
predictors of outcome were determined using a multivariate Cox model.

Results: In multivariate analyses, TSoverexpression was found to be
an independent factor of poor prognosis in OS (P <.01), PFS (P =.06),
and HPFS (P <.01). In addition, resection margin was a significant
independent factor for all three outcomes. Patients who received
HAI+SYS experienced delayed progression in general, and in the liver,
specifically. Increased levels of serum alkaline phosphatase
correlated with hepatic progression. We also found a significant TS-
treatment interaction for OS (P =.01) in multivariate analysis. In
particular, TS+ patients receiving HAI+SYS had significantly higher
survival than those receiving SYS (64 monthsv 21 months; P =.01).

Conclusion: TSlevels in hepatic tumors and resection margin are
independent predictors of survival and progression in patients with
metastatic colorectal cancer, whereasp53and EGFRare not independent
predictors. Treatment with HAI+SYS significantly improved the
survival profile of TS+ patients.

PMID: 12560427