title: Risk of second cancer after treatment of aggressive non-Hodgkin's lymphoma; an EORTC cohort study.
abstract: OBJECTIVE
  Second cancer has been associated with non-Hodgkin's Lymphoma (NHL) treatment, but few studies have addressed this issue considering specific treatments.
  
  
  METHODS
  We estimated risk by standardized incidence ratios (SIR) and absolute excess risk (AER) based on general population rates (European Network of Cancer Registries) in 748 patients (aged 15-82 years) treated for aggressive NHL in four successive EORTC (European Organization for Research on Treatment of Cancer) trials.
  
  
  RESULTS
  All patients received fully-dosed CHOP-like chemotherapy, 65% received involved-field radiotherapy and 14% high-dose treatment. Half of the patients needed salvage treatment and 37% were followed for more than 10 years. The cause of death was NHL in 79% of the patients; 4% died of second cancer (median survival 8.9 (0.8- 20.5) years). Cumulative incidences (death from any cause being a competing event) were 5% and 11% for solid cancer and 1% and 3% for acute myeloid leukemia/myelodysplastic syndrome at 10 and 15 years, respectively. Cancer risk appeared age-related: in young patients high risks were observed for leukemia (SIR 16.7,95% CI 1.4-93.1,AER 5.0), Hodgkin's lymphoma (SIR 60.1,95% CI 12.4-175.2, AER 15.7), colorectal cancer (SIR 12.5, 95% CI 2.6-36.5, AER 14.7) and lung cancer (SIR 15.4; 95% CI 4.2-39.4, AER 19.8), while risk in patients older than 45 years matched than that in the normal population. The risk of cancer was significantly raised by smoking and salvage treatment.
  
  
  CONCLUSIONS
  Half of the patients die of aggressive NHL before living long enough to experience second cancer. Only young patients have a high risk of second cancer during follow-up beyond 10 years.
authors.affiliation: EORTC Data Centre, Brussels, Belgium. e.c.moser@lumc.nl
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Moser
authors.forename: Evert M
authors.initials: EM
authors.lastname: Noordijk
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
authors.forename: Joke W
authors.initials: JW
authors.lastname: Baars
authors.forename: José
authors.initials: J
authors.lastname: Thomas
authors.forename: Patrice
authors.initials: P
authors.lastname: Carde
authors.forename: Jacobus H
authors.initials: JH
authors.lastname: Meerwaldt
authors.forename: Martine
authors.initials: M
authors.lastname: van Glabbeke
authors.forename: Hanneke C
authors.initials: HC
authors.lastname: Kluin-Nelemans
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000453:epidemiology*; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone