title: Revised staging classification improves outcome prediction for small intestinal neuroendocrine tumors.
abstract: OBJECTIVE
  Small intestinal (SI) neuroendocrine tumors (NETs) have heterogeneous outcomes. The NET societies have recently proposed a TNM staging classification. In this study, we used population-based data to assess the validity of the staging system.
  
  
  METHODS
  We identified patients with SI-NETS diagnosed between 1988 and 2009 from the Surveillance, Epidemiology, and End Results registry. We used Kaplan-Meier analysis to assess disease-specific survival according to TNM status. Cox models were constructed to evaluate differences in prognosis after controlling for potential confounders.
  
  
  RESULTS
  We identified 6,792 patients with SI-NET. Although the current staging system was predictive of prognosis, there was overlap among some groups (stage I/IIA, P = .36; stage IIB/IIIB, P = .70). Additionally, stage IIIB patients had better survival than stage IIIA patients (P < .001). Adjusted analyses showed similar outcomes for T1 versus T2 disease (hazard ratio [HR], 1.02; 95% CI, 0.63 to 1.66). Patients with T3 (HR, 3.60; 95% CI, 2.28 to 5.69) and T4 (HR, 5.50; 95% CI, 3.42 to 8.86) tumors had significantly worse survival than patients with T1 disease. N1 involvement conferred worse survival in T1 (HR, 3.08; 95% CI, 1.75 to 5.44) and T2 disease (HR, 2.73; 95% CI, 1.84 to 4.07) but not in T3 (HR, 0.99; 95% CI, 0.76 to 1.30) or T4 (HR, 0.98; 95% CI, 0.71 to 1.35) disease. A revised classification showed no overlap in survival across groups.
  
  
  CONCLUSIONS
  Progressively more advanced T status is associated with worse SI-NET prognosis. Regional lymph node involvement is a marker of worse survival only among patients with T1 or T2 status. These results suggest that revisions to the current staging classification may be helpful.
authors.affiliation: All authors: Mount Sinai School of Medicine, New York, NY.
authors.forename: Michelle Kang
authors.initials: MK
authors.lastname: Kim
authors.forename: Richard R P
authors.initials: RR
authors.lastname: Warner
authors.forename: Sasan
authors.initials: S
authors.lastname: Roayaie
authors.forename: Noam
authors.initials: N
authors.lastname: Harpaz
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Ward
authors.forename: Steven
authors.initials: S
authors.lastname: Itzkowitz
authors.forename: Juan P
authors.initials: JP
authors.lastname: Wisnivesky
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000401:mortality / Q000473:pathology*; D007421:Intestine, Small; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000401:mortality / Q000473:pathology*; D016017:Odds Ratio; D011379:Prognosis
references.citation: J Clin Oncol. 2008 Jun 20;26(18):3063-72
references.pmid: 18565894
references.citation: Am J Gastroenterol. 1994 May;89(5):699-701
references.pmid: 8172140
references.citation: Pancreas. 2010 Aug;39(6):753-66
references.pmid: 20664473
references.citation: J Clin Oncol. 2011 Aug 1;29(22):3044-9
references.pmid: 21709192
references.citation: Cancer. 2011 Aug 1;117(15):3332-41
references.pmid: 21246527
references.citation: J Clin Oncol. 2013 Feb 1;31(4):420-5
references.pmid: 23248248
references.citation: Ann Surg. 2012 Aug;256(2):321-5
references.pmid: 22415420
references.citation: Clin Cancer Res. 2008 Dec 1;14(23):7798-803
references.pmid: 19047107
references.citation: J Natl Cancer Inst. 2012 May 16;104(10):764-77
references.pmid: 22525418
references.citation: Virchows Arch. 2006 Oct;449(4):395-401
references.pmid: 16967267
references.citation: Endocrinol Metab Clin North Am. 2011 Mar;40(1):1-18, vii
references.pmid: 21349409
references.citation: Hum Pathol. 2009 Jan;40(1):30-40
references.pmid: 18715612
references.citation: Br J Surg. 2008 May;95(5):627-35
references.pmid: 18306152
references.citation: Int J Epidemiol. 1996 Aug;25(4):722-8
references.pmid: 8921448
references.citation: Virchows Arch. 2007 Oct;451(4):757-62
references.pmid: 17674042
references.citation: Am J Surg. 2008 Dec;196(6):896-903; discussion 903
references.pmid: 19095106
references.citation: Virchows Arch. 1995;425(6):547-60
references.pmid: 7697211
references.citation: Cancer. 2008 Jul 15;113(2):256-65
references.pmid: 18506737