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CXCR4 positivity linked to liver recurrence, poor survival after PAC resection

Results from a recent study indicated associations between CXCR4 positivity and reduced survival time and early liver recurrence in patients who underwent resection for pancreatic adenocarcinoma.

Researchers analyzed the CXCR4 expression of 97 patients with pancreatic adenocarcinoma (PAC) who underwent R0 tumor resection between 1995 and 2006 in Taiwan. Overall and liver recurrence-free survival were measured to ascertain the potential impact of CXCR4 expression.

CXCR4 positivity and liver recurrence was determined in 45.4% and 43.3% of patients, respectively. Death due to cancer recurrence was observed in 63.9% of patients, and 15.9% died from non-PAC causes. Common causes of mortality included cardiovascular disease, postoperative complications, gastrointestinal bleeding and infection. Surviving patients were monitored for a median of 26.3 months. The median survival time among patients with liver recurrence was 3.9 months.

Patients who were CXCR4-positive experienced shorter overall survival (median 10.2 months vs. 22.3 months; P<.001) and liver recurrence-free survival periods (median 8.7 months compared with 39.7 months; P=.004) than CXCR4-negative patients. Overall survival also was longer among CXCR4-negative patients with stage 2a compared with CXCR4-positive patients with stage 2a (27.4 months vs. 9.7 months; P=.002). Survival length was similar between CXCR4-positive patients with stage 2a and those with stage 2b.

Investigators observed a significant association between liver recurrence and CXCR4 positivity (adjusted HR=2.22, 1.15-4.30) via multivariate analysis. CXCR4 positivity was associated with poor overall survival (HR=1.78, 1.02-3.09). Models including CXCR4 status, tumor extent, lymph node metastasis and pathologic grade predicted a 35% reduction in overall survival and a 46% reduction in liver recurrence-free survival related to CXCR4 positivity (acceleration factor of positivity=1.85, 1.10-3.10 for recurrence-free survival and 1.54, 1.08-2.19 for overall survival) (95% CI for all).

“This study indicates that CXCR4 positivity is an independent predictor of early liver recurrence and poor overall survival after resection of PAC,” the researchers wrote. “These findings reaffirm the notion that CXCL12/CXCR4 signaling has crucial roles in live metastasis of PAC, and CXCR4 status should be evaluated to optimize risk stratification and treatment selection. Future studies are needed to investigate the optimal treatment strategies … and to explore the therapeutic potential of CXCR4 antagonists.”