title: Treatment-associated leukemia following testicular cancer.
abstract: BACKGROUND
  Men with testicular cancer are at an increased risk of leukemia, but the relationship to prior treatments is not well characterized. The purpose of our study was to describe the risk of leukemia following radiotherapy and chemotherapy for testicular cancer.
  
  
  METHODS
  Within a population-based cohort of 18 567 patients diagnosed with testicular cancer (from 1970 through 1993), a case-control study of leukemia was undertaken. Radiation dose to active bone marrow and type and cumulative amount of cytotoxic drugs were compared between 36 men who developed leukemia and 106 matched control patients without leukemia. Conditional logistic regression was used to estimate the relative risk of leukemia associated with specific treatments. All P values are two-sided.
  
  
  RESULTS
  Radiotherapy (mean dose to active bone marrow, 12.6 Gy) without chemotherapy was associated with a threefold elevated risk of leukemia. Risk increased with increasing dose of radiation to active bone marrow (P for trend =.02), with patients receiving radiotherapy to the chest as well as to the abdominal/pelvic fields accounting for much of the risk at higher doses. Radiation dose to active bone marrow and the cumulative dose of cisplatin (P for trend =.001) were both predictive of excess leukemia risk in a model adjusted for all treatment variables. The estimated relative risk of leukemia at a cumulative dose of 650 mg cisplatin, which is commonly administered in current testicular cancer treatment regimens, was 3.2 (95% confidence interval = 1.5-8.4); larger doses (1000 mg) were linked with statistically significant sixfold increased risks.
  
  
  CONCLUSIONS
  Past treatments for testicular cancer are associated with an increased risk of leukemia, with evidence for dose-response relationships for both radiotherapy and cisplatin-based chemotherapy. Statistically nonsignificant excesses are estimated for current radiotherapy regimens limited to the abdomen and pelvis: Among 10 000 patients given a treatment dose of 25 Gy and followed for 15 years, an excess of nine leukemias is predicted; cisplatin-based chemotherapy (dose, 650 mg) might result in 16 cases of leukemia. The survival advantage provided by current radiotherapy and chemotherapy regimens for testicular cancer far exceeds the small absolute risk of leukemia.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: L B
authors.initials: LB
authors.lastname: Travis
authors.forename: M
authors.initials: M
authors.lastname: Andersson
authors.forename: M
authors.initials: M
authors.lastname: Gospodarowicz
authors.forename: F E
authors.initials: FE
authors.lastname: van Leeuwen
authors.forename: K
authors.initials: K
authors.lastname: Bergfeldt
authors.forename: C F
authors.initials: CF
authors.lastname: Lynch
authors.forename: R E
authors.initials: RE
authors.lastname: Curtis
authors.forename: B A
authors.initials: BA
authors.lastname: Kohler
authors.forename: T
authors.initials: T
authors.lastname: Wiklund
authors.forename: H
authors.initials: H
authors.lastname: Storm
authors.forename: E
authors.initials: E
authors.lastname: Holowaty
authors.forename: P
authors.initials: P
authors.lastname: Hall
authors.forename: E
authors.initials: E
authors.lastname: Pukkala
authors.forename: D T
authors.initials: DT
authors.lastname: Sleijfer
authors.forename: E A
authors.initials: EA
authors.lastname: Clarke
authors.forename: J D
authors.initials: JD
authors.lastname: Boice
authors.forename: M
authors.initials: M
authors.lastname: Stovall
authors.forename: E
authors.initials: E
authors.lastname: Gilbert
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001853:Bone Marrow / Q000528:radiation effects*; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D005060:Europe / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007953:Leukemia, Radiation-Induced / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology; D009656:North America / Q000453:epidemiology; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012042:Registries; D012306:Risk; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D013997:Time Factors
chemical_list: D018906:Antineoplastic Agents, Alkylating