title: Pancreatic cancer risk after treatment of Hodgkin lymphoma.
abstract: BACKGROUND
  Although elevated risks of pancreatic cancer have been observed in long-term survivors of Hodgkin lymphoma (HL), no prior study has assessed the risk of second pancreatic cancer in relation to radiation dose and specific chemotherapeutic agents.
  
  
  METHODS
  We conducted an international case-control study within a cohort of 19 882 HL survivors diagnosed from 1953 to 2003 including 36 cases and 70 matched controls.
  
  
  RESULTS
  Median ages at HL and pancreatic cancer diagnoses were 47 and 60.5 years, respectively; median time to pancreatic cancer was 19 years. Pancreatic cancer risk increased with increasing radiation dose to the pancreatic tumor location (Ptrend = 0.005) and increasing number of alkylating agent (AA)-containing cycles of chemotherapy (Ptrend = 0.008). The odds ratio (OR) for patients treated with both subdiaphragmatic radiation (≥10 Gy) and ≥6 AA-containing chemotherapy cycles (13 cases, 6 controls) compared with patients with neither treatment was 17.9 (95% confidence interval 3.5-158). The joint effect of these two treatments was significantly greater than additive (P = 0.041) and nonsignificantly greater than multiplicative (P = 0.29). Especially high risks were observed among patients receiving ≥8400 mg/m(2) of procarbazine with nitrogen mustard or ≥3900 mg/m(2) of cyclophosphamide.
  
  
  CONCLUSIONS
  Our study demonstrates for the first time that both radiotherapy and chemotherapy substantially increase pancreatic cancer risks among HL survivors treated in the past. These findings extend the range of nonhematologic cancers associated with chemotherapy and add to the evidence that the combination of radiotherapy and chemotherapy can lead to especially large risks.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda; Department of Veterans Affairs Medical Center, Oklahoma City, USA. Electronic address: doresg@mail.nih.gov.
authors.forename: G M
authors.initials: GM
authors.lastname: Dores
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda.
authors.forename: R E
authors.initials: RE
authors.lastname: Curtis
authors.affiliation: Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: F E
authors.initials: FE
authors.lastname: van Leeuwen
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston,USA.
authors.forename: M
authors.initials: M
authors.lastname: Stovall
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Hall
authors.affiliation: Department of Epidemiology, University of Iowa, Iowa City, USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Lynch
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston,USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Smith
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston,USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Weathers
authors.affiliation: Cancer Prevention and Documentation, Danish Cancer Society, Copenhagen, Denmark.
authors.forename: H H
authors.initials: HH
authors.lastname: Storm
authors.affiliation: Department of Radiation Oncology, University of Toronto, Toronto,Canada.
authors.forename: D C
authors.initials: DC
authors.lastname: Hodgson
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda.
authors.forename: R A
authors.initials: RA
authors.lastname: Kleinerman
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Joensuu
authors.affiliation: Cancer Registry of Norway, Oslo, Norway.
authors.forename: T B
authors.initials: TB
authors.lastname: Johannesen
authors.affiliation: Department of Oncology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Andersson
authors.affiliation: Dalla Lana School of Public Health, University of Toronto, Toronto,Canada.
authors.forename: E J
authors.initials: EJ
authors.lastname: Holowaty
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Kaijser
authors.affiliation: Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki and School of Health Sciences, University of Tampere, Tampere, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Pukkala
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Vaalavirta
authors.affiliation: Department of Oncology, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: S D
authors.initials: SD
authors.lastname: Fossa
authors.affiliation: Cancer Registry of Norway, Oslo, Norway.
authors.forename: F
authors.initials: F
authors.lastname: Langmark
authors.affiliation: Department of Radiation Oncology, University of Rochester Medical Center, Rochester,USA.
authors.forename: L B
authors.initials: LB
authors.lastname: Travis
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda.
authors.forename: J F
authors.initials: JF
authors.lastname: Fraumeni
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: B M
authors.initials: BM
authors.lastname: Aleman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda.
authors.forename: L M
authors.initials: LM
authors.lastname: Morton
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda.
authors.forename: E S
authors.initials: ES
authors.lastname: Gilbert
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006689:Hodgkin Disease / Q000150:complications* / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000209:etiology*; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors
keywords: Hodgkin lymphoma; chemotherapy; pancreatic cancer; radiotherapy; second cancer