title: Pancreatic neuroendocrine tumors with involved surgical margins: prognostic factors and the role of adjuvant radiotherapy.
abstract: OBJECTIVE
  Pancreatic neuroendocrine tumors (pNET) are rare neoplasms associated with poor outcomes without resection, and involved surgical margins are associated with a worse prognosis. The role of adjuvant radiotherapy (RT) in these patients has not been characterized.
  
  
  METHODS
  We retrospectively evaluated 46 consecutive patients with positive or close (<1 mm) margins after pNET resection, treated from 1983 to 2010, 16 of whom received adjuvant RT. Median RT dose was 50.4 Gy in 1.8-Gy fractions; half the patients received concurrent chemotherapy with 5-fluorouracil or capecitabine. No patients received adjuvant chemotherapy. Cox multivariate analysis (MVA) was used to analyze factors associated with overall survival (OS).
  
  
  RESULTS
  Median age at diagnosis was 56 years, and 52% of patients were female. Median tumor size was 38 mm, 57% of patients were node-positive, and 11% had a resected solitary liver metastasis. Patients who received RT were more likely to have larger tumors (median, 54 mm vs. 30 mm, respectively, p = 0.002) and node positivity (81% vs. 33%, respectively, p = 0.002) than those not receiving RT. Median follow-up was 39 months. Actuarial 5-year OS was 62% (95% confidence interval [CI], 41%-77%). In the group that did not receive RT, 3 patients (10%) experienced local recurrence (LR) and 5 patients (18%) developed new distant metastases, while in the RT group, 1 patient (6%) experienced LR and 5 patients (38%) developed distant metastases. Of all recurrences, 29% were LR. On MVA, male gender (adjusted hazard ratio [AHR] = 3.81; 95% CI, 1.21-11.92; p = 0.02) and increasing tumor size (AHR = 1.02; 95% CI, 1.01-1.04; p = 0.007) were associated with decreased OS.
  
  
  CONCLUSIONS
  Long-term survival is common among patients with involved-margin pNET. Despite significantly worse pathologic features among patients receiving adjuvant RT, rates of LR between groups were similar, suggesting that RT might aid local control, and merits further evaluation.
authors.affiliation: Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA, USA.
authors.forename: Nils D
authors.initials: ND
authors.lastname: Arvold
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Willett
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez-del Castillo
authors.forename: David P
authors.initials: DP
authors.lastname: Ryan
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Ferrone
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Clark
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Blaszkowsky
authors.forename: Vikram
authors.initials: V
authors.lastname: Deshpande
authors.forename: Andrzej
authors.initials: A
authors.lastname: Niemierko
authors.forename: Jill N
authors.initials: JN
authors.lastname: Allen
authors.forename: Eunice L
authors.initials: EL
authors.lastname: Kwak
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Wadlow
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Warshaw
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Hong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000069287:Capecitabine; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality; D018365:Neoplasm, Residual; D018358:Neuroendocrine Tumors / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000379:methods / Q000401:mortality; D012189:Retrospective Studies; D012737:Sex Factors; D047368:Tumor Burden
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil