title: Incidence of Second Primary Malignancies in Patients with Neuroendocrine Tumours.
abstract: BACKGROUND
  An association between neuroendocrine tumours (NET) and increased risk of developing second primary malignancies (SPM) has been recognised.
  
  
  METHODS
  This was a retrospective review of our institutional prospectively maintained database of NET patients. We identified patients who had been diagnosed with both neuroendocrine and any additional malignancies via examination of patient notes.
  
  
  RESULTS
  Clinical data for 169 patients were analysed. After exclusion of patients known to have hereditary tumour predisposition syndromes, 29 SPM were identified in 26 patients (15.38%), the commonest being colorectal (n = 6), breast and renal carcinomas (both n = 5). SPM were classified as previous, synchronous or subsequent relative to NET diagnosis. Rates of SPM in pancreatic and small-bowel NET patients were comparable (15.7 vs. 19.6%, p = 0.78). A person-year methodology was used to compare observed numbers of SPM against expected values generated from age- and sex-specific incidence tables, with standardised incidence ratios (SIR) and 95% confidence intervals (CI) calculated. SPM incidence was significantly elevated in the synchronous subset (SIR 2.732, CI 1.177-5.382) whilst significantly fewer NET patients had a cancer history compared to the general population (SIR 0.4, CI 0.241-0.624). No overall differences were evident between observed and expected incidences of subsequent SPM (SIR 0.36, CI 0.044-1.051). The incidence of synchronous colorectal cancers was markedly elevated (SIR 13.079, CI 4.238-30.474).
  
  
  CONCLUSIONS
  Our data support the use of colonoscopy in the diagnostic work-up of NET patients in anticipation of a colorectal SPM. The mechanistic underpinnings of this clinical phenomenon require further genetic investigation, and consideration of this knowledge in patient management pathways is warranted.
authors.affiliation: School of Medicine, Imperial College London, London, UK.
authors.forename: Ashley K
authors.initials: AK
authors.lastname: Clift
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Drymousis
authors.forename: Adil
authors.initials: A
authors.lastname: Al-Nahhas
authors.forename: Harpreet
authors.initials: H
authors.lastname: Wasan
authors.forename: John
authors.initials: J
authors.lastname: Martin
authors.forename: Sture
authors.initials: S
authors.lastname: Holm
authors.forename: Andrea
authors.initials: A
authors.lastname: Frilling
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D018358:Neuroendocrine Tumors / Q000453:epidemiology*; D012189:Retrospective Studies; D055815:Young Adult