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Prognostic Factors for Pancreatic Neuroendocrine Tumors: Analysis of 5,045 Patients
Karl Y. Bilimoria*1,2, James Tomlinson3, Clifford Y. Ko1,3, Mark S. Talamonti2, David J. Bentrem2
1Cancer Programs, American College of Surgeons, Chicago, IL; 2Department of Surgery, Division of Surgical Oncology, Northwestern University, Chicago, IL; 3Department of Surgery, UCLA, Los Angeles, CA

Background: The influence of tumor size, nodal status, and distant metastases on outcomes for pancreatic neuroendocrine tumors (PNET) remains controversial. The relative rarity of these neoplasms has limited the ability to evaluate prognostic factors. Our objective was to utilize a large national cancer registry to identify factors predicting survival for PNETs.
Methods: From the National Cancer Data Base (1985-2003), 306,078 patients were identified with pancreatic tumors of which 5,045 (1.6%) had PNETs. Overall survival was estimated using the Kaplan-Meier method and compared using log-rank tests. Cox proportional hazards modeling was utilized to assess the impact of patient, tumor, and treatment variables on survival. We performed separate analyses to identify factors predicting survival for all patients, all resected patients, and resected patients without distant metastases.
Results: Of 5,045 patients with PNETs, 4414 (87.5%) were of islet cell origin, and 631 (12.5%) were carcinoid tumors. 2158 (42.8%) underwent surgery: 708 (32.8%) pancreaticoduodenectomy, 445 (20.6%) enucleation, 347 (16.1%) distal pancreatectomy, 196 (9.1%) total pancreatectomy; and 462 (21.4%) pancreatectomy NOS. Of those who underwent resection, 1038 (47.9%) had tumors > 4 cm, 900 (41.7%) were node positive, 112 (5.2%) had liver metastases, and 330 (15.3%) had other distant metastases. R0 resections were done in 2039 (94.5%), R1 resections in 95 (4.4%), and R2 resections in 24 (1.1%). Of resected patients, 224 (10.4%) received adjuvant chemotherapy, and 125 (5.8%) received adjuvant radiation.For all patients, overall survival was 42.3% at 5 years and 26.0% at 10 years. For patients who underwent resection, survival was 69.2% at 5 years and 51.0% at 10 years. On univariate analysis, age <65, tumor size <4cm, absence of nodal or distant metastases, well/moderate differentiation, and surgical resection were associated with improved outcomes (P<.0001). On multivariate analysis, only age <65 years (Hazard Ratio [HR] 0.38, 95% Confidence Interval [CI] 0.27-0.53), distant metastases (HR 0.42, CI 0.29-0.61), and definitive surgical resection (HR 0.60, CI 0.47-0.77) were independent predictors of improved survival.
Conclusions: This is the largest reported study of PNETs. We found that tumor size was not an independent predictor of survival. Patient age, definitive surgical resection, and absence of distant metastases were the most important predictors of outcome.

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