Sinusoidal obstruction syndrome impairs long-term outcome of colorectal liver metastases treated with resection after neoadjuvant chemotherapy.

BACKGROUND: Chemotherapy-induced liver injury is a considerable problem in patients undergoing surgery for colorectal liver metastases, since an increase in postoperative morbidity and mortality has been observed. We investigated whether liver damage had further implications on long-term outcome in these patients. MATERIALS AND METHODS: Liver specimens from 196 patients resected for colorectal liver metastases were evaluated for chemotherapy-associated hepatic damage in the nontumorous liver. Injury patterns were correlated with recurrence free (RFS) and overall survival (OS). Factors leading to sinusoidal injury were identified. RESULTS: Patients who developed grade 2 or 3 sinusoidal dilatation had a significantly shorter RFS (hazard ratio [HR] 2.05; 95% confidence interval [95% CI] 1.23-3.39, P = .005) and OS (HR 2.90; 95% CI 1.61-6.19, P < .001), compared to patients without this alteration. Those patients also had significantly more intrahepatic recurrences (66.7% vs 30.5%, P = .003). Other patterns of chemotherapy-associated liver damage (nonalcoholic steatohepatitis, fibrosis) were not associated with impaired survival. Factors indicating sinusoidal injury were oxaliplatin-based chemotherapy, tumor size >5 cm, and elevated alkaline phosphatase or gamma glutamyltransferase. CONCLUSIONS: Sinusoidal obstruction syndrome due to oxaliplatin-based chemotherapy may not only compromise perioperative outcome, but can lead to early recurrence and decreased survival in the long term. Strategies to prevent this condition are clearly needed.

Bevacizumab improves pathological response of colorectal cancer liver metastases treated with XELOX/FOLFOX.

BACKGROUND: Histological response of colorectal cancer liver metastases to chemotherapy may be graded based on the extent of tumor regression. The knowledge about the effect of bevacizumab, if given in addition to fluoropyrimidines and oxaliplatin, on tumor regression and its consequences on clinical outcome is limited. MATERIALS AND METHODS: Resected liver metastases from patients of 2 prospective nonrandomized trials (fluoropyrimidines and oxaliplatin +/- bevacizumab) were analyzed retrospectively. Histological response was analyzed according to an established tumor regression grading for colorectal cancer liver metastases. Tumor regression grades (TRGs) were correlated to progression-free and overall survival. RESULTS: Bevacizumab improved tumor regression to chemotherapy significantly. Improvement in histological response was translated into a significant prolongation of progression-free and overall survival. CONCLUSIONS: Classifying histological response based on tumor regression grades qualifies to predict the outcome of patients with colorectal cancer liver metastases. Tumor regression grading provides a standardized pathological response evaluation, against which radiologic response on chemotherapy including biologicals can be prospectively evaluated.