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
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 >or=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.
Asiyanbola
Bolanle
B
Department of Surgery, Johns Hopkins Hospital, 600 North Wolfe Street, Halsted 614, Baltimore, MD 22187-6681, USA.
Gleisner
Ana
A
Herman
Joseph M
JM
Choti
Michael A
MA
Wolfgang
Christopher L
CL
Swartz
Michael
M
Edil
Barish H
BH
Schulick
Richard D
RD
Cameron
John L
JL
Pawlik
Timothy M
TM
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery*; D016577:Pancreaticoduodenectomy; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil