title: Risk of subsequent gastrointestinal cancer among childhood cancer survivors: A systematic review.
abstract: BACKGROUND
  Childhood cancer survivors (CCS) are at increased risk of developing subsequent malignant neoplasms, including gastrointestinal (GI) cancer. We performed a systematic review to summarize all available literature on the risk of, risk factors for, and outcome after subsequent GI cancer among CCS.
  
  
  METHODS
  A systematic search of the literature databases Medline/PubMed (1945-2014) and Embase (1947-2014) was performed to identify studies that consisted of ⩾1000 CCS and assessed incidence of or mortality from subsequent GI cancer as an outcome.
  
  
  RESULTS
  A total of 45 studies were included. Studies that reported risk measures for subsequent GI cancer compared to the general population showed a 3.2 to 9.7-fold elevated risk in cohort studies including all childhood cancer types. Abdominal radiotherapy was associated with an increased risk of subsequent GI cancer in all four studies that assessed this risk. Survivors who had received procarbazine and platinum agents were also suggested to be at increased risk.
  
  
  CONCLUSIONS
  Abdominal radiotherapy is a risk factor for developing a subsequent GI cancer. Few studies examined detailed treatment-related risk factors and most studies had small number of GI cancer cases. Therefore, no conclusions could be drawn on the effect of time since childhood cancer on GI cancer risk and on outcome after a subsequent GI cancer. Additional research is necessary to further explore risk factors for and outcome after a subsequent GI cancer, and to systematically evaluate the harms and benefits of GI screening among high-risk survivors in order to give sound screening recommendations.
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. Electronic address: j.c.teepen@amc.uva.nl.
authors.forename: Jop C
authors.initials: JC
authors.lastname: Teepen
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: de Vroom
authors.affiliation: Department of Epidemiology, The Netherlands Cancer Institute, P.O. Box 90203, 1066 CX Amsterdam, The Netherlands.
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
authors.affiliation: Department of Pediatric Oncology and Hematology, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Wim J
authors.initials: WJ
authors.lastname: Tissing
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands.
authors.forename: Leontien C
authors.initials: LC
authors.lastname: Kremer
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands.
authors.forename: Cécile M
authors.initials: CM
authors.lastname: Ronckers
mesh_terms: D000005:Abdomen / Q000528:radiation effects*; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D002648:Child; D055088:Early Detection of Cancer; D005770:Gastrointestinal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D006801:Humans; D015994:Incidence; D010984:Platinum / Q000494:pharmacology*; D011344:Procarbazine / Q000494:pharmacology*; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods; D018570:Risk Assessment; D012307:Risk Factors; D017741:Survivors / Q000706:statistics & numerical data*
chemical_list: D000970:Antineoplastic Agents; D011344:Procarbazine; D010984:Platinum
keywords: Abdominal radiotherapy; Childhood cancer survivors; Subsequent gastrointestinal cancer; Systematic review