Determining pattern of recurrence following pancreaticoduodenectomy and adjuvant 5-flurouracil-based chemoradiation therapy: Effect of number of metastatic lymph nodes and lymph node ratio

Background: There are limited data on patterns of recurrence and factors associated with local recurrence following pancreaticoduodenectomy for pancreatic adenocarcinoma and adjuvant 5-flurouracil-based chemoradiation therapy. Methods and Materials: Between 1995 and 2005, 905 patients underwent pancreaticoduodenectomy for pancreatic adenocarcinoma; 154 patients had complete pattern of recurrence data available. Results: At median follow-up of 20.2 months, 103 (66.9%) patients recurred with median time to recurrence of 16.2 months. Most patients recurred with distant disease only (68.9%), while 21.4% patients recurred with local disease only; ten (9.7%) patients recurred with local and distant disease. Several factors were associated with local recurrence: poor tumor differentiation (hazards ration [HR] 2.39) and presence of metastatic lymph nodes (HR 1.89, both p∈<∈0.05). Among N1 patients, poor tumor differentiation (HR 3.92), >5 metastatic LN (HR 3.75), and lymph node ratio (LNR) >0.4 (HR 2.96) had the highest risk of local recurrence (all p∈<∈0.05). Increasing LNR was associated with an incremental increased risk of local recurrence (LNR <0.2, 21.3% versus LNR 0.2 to 0.4, 25.2% versus LNR >0.4, 40.4%; p∈<∈0.05). Conclusions: Although most patients who receive standard 5-flurouracil-based chemoradiation therapy will ultimately succumb to distant disease, about 30% recur locally. Poor tumor differentiation, a high number of metastatic LN (>5), and LNR >0.4 are associated with the highest risk of local failure. In these patients, radiation dose escalation and/or a combination of radiation with novel chemotherapeutic agents may be necessary to improve outcomes.