title: Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer.
abstract: OBJECTIVE
  To compare radiotherapy and chemotherapy effects on long-term risks of second malignant neoplasms (SMNs) and cardiovascular diseases (CVDs) in testicular cancer (TC) survivors.
  
  
  METHODS
  In our nationwide cohort comprising 2,707 5-year TC survivors, incidences of SMNs and CVDs were compared with general-population rates by calculating standardized incidence ratios (SIRs) and absolute excess risks (AERs). Treatment effects on risks of SMN and CVD were quantified in multivariable Cox regression and competing risks analyses.
  
  
  RESULTS
  After a median follow-up time of 17.6 years, 270 TC survivors developed SMNs. The SIR of SMN overall was 1.7 (95% CI, 1.5 to 1.9), with an AER of 32.3 excess occurrences per 10,000 person-years. SMN risk was 2.6-fold (95% CI, 1.7- to 4.0-fold) increased after subdiaphragmatic radiotherapy and 2.1-fold (95% CI, 1.4- to 3.1-fold) increased after chemotherapy, compared with surgery only. Subdiaphragmatic radiotherapy increased the risk of a major late complication (SMN or CVD) 1.8-fold (95% CI, 1.3- to 2.4-fold), chemotherapy increased the risk of a major late complication 1.9-fold (95% CI, 1.4- to 2.5-fold), and smoking increased the risk of a major late complication 1.7-fold (95% CI, 1.4- to 2.1-fold), compared with surgery only. The median survival time was 1.4 years after SMN and 4.7 years after CVD.
  
  
  CONCLUSIONS
  Radiotherapy and chemotherapy increased the risk of developing SMN or CVD to a similar extent as smoking. Subdiaphragmatic radiotherapy strongly increases the risk of SMNs but not of CVD, whereas chemotherapy increases the risks of both SMNs and CVDs. Prolonged follow-up after chemotherapy is needed to reliably compare the late complications of radiotherapy and chemotherapy after 20 years.
authors: Department of Epidemiology, the Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors: Alexandra W
authors: AW
authors: van den Belt-Dusebout
authors: Ronald
authors: R
authors: de Wit
authors: Jourik A
authors: JA
authors: Gietema
authors: Simon
authors: S
authors: Horenblas
authors: Marieke W J
authors: MW
authors: Louwman
authors: Jacques G
authors: JG
authors: Ribot
authors: Harald J
authors: HJ
authors: Hoekstra
authors: Gabey M
authors: GM
authors: Ouwens
authors: Berthe M P
authors: BM
authors: Aleman
authors: Flora E
authors: FE
authors: van Leeuwen
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology; D002945:Cisplatin / Q000009:adverse effects*; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000209:etiology; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology; D009426:Netherlands / Q000453:epidemiology; D016016:Proportional Hazards Models; D011878:Radiotherapy / Q000009:adverse effects; D012306:Risk; D017741:Survivors / Q000706:statistics & numerical data; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin