title: Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease.
abstract: BACKGROUND
  Lung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described. We quantified the risk of treatment-associated lung cancer, taking into account tobacco use.
  
  
  METHODS
  Within a population-based cohort of 19 046 Hodgkin's disease patients (diagnosed from 1965 through 1994), a case-control study of lung cancer was conducted. The cumulative amount of cytotoxic drugs, the radiation dose to the specific location in the lung where cancer developed, and tobacco use were compared for 222 patients who developed lung cancer and for 444 matched control patients. All statistical tests were two-sided.
  
  
  RESULTS
  Treatment with alkylating agents without radiotherapy was associated with increased lung cancer risk (relative risk [RR] = 4.2; 95% confidence interval [CI] = 2.1 to 8.8), as was radiation dose of 5 Gy or more without alkylating agents (RR = 5.9; 95% CI = 2.7 to 13.5). Risk increased with both increasing number of cycles of alkylating agents and increasing radiation dose (P for trend <.001). Among patients treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), risk increased with cumulative amounts of mechlorethamine and procarbazine (P<.001) when evaluated separately. Statistically significantly elevated risks of lung cancer were apparent within 1-4 years after treatment with alkylating agents, whereas excess risk after radiotherapy began 5 years after treatment and persisted for more than 20 years. Risk after treatment with alkylating agents and radiotherapy together was as expected if individual excess risks were summed. Tobacco use increased lung cancer risk more than 20-fold; risks from smoking appeared to multiply risks from treatment.
  
  
  CONCLUSIONS
  Past treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion. The precise risk estimates, however, should be interpreted cautiously, given the possible residual and enhancing effects of tobacco.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. travisl@epndce.nci.nih.gov
authors.forename: Lois B
authors.initials: LB
authors.lastname: Travis
authors.forename: Mary
authors.initials: M
authors.lastname: Gospodarowicz
authors.forename: Rochelle E
authors.initials: RE
authors.lastname: Curtis
authors.forename: E Aileen
authors.initials: EA
authors.lastname: Clarke
authors.forename: Michael
authors.initials: M
authors.lastname: Andersson
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
authors.forename: Timo
authors.initials: T
authors.lastname: Joensuu
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
authors.forename: Eric
authors.initials: E
authors.lastname: Holowaty
authors.forename: Hans
authors.initials: H
authors.lastname: Storm
authors.forename: Ingrid
authors.initials: I
authors.lastname: Glimelius
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Fraumeni
authors.forename: John D
authors.initials: JD
authors.lastname: Boice
authors.forename: Ethel
authors.initials: E
authors.lastname: Gilbert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects; D016022:Case-Control Studies; D002648:Child; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006689:Hodgkin Disease / Q000150:complications* / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000150:complications* / Q000209:etiology*; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents