title: Risk of second cancers according to radiation therapy technique and modality in prostate cancer survivors.
abstract: OBJECTIVE
  Radiation therapy (RT) techniques for prostate cancer are evolving rapidly, but the impact of these changes on risk of second cancers, which are an uncommon but serious consequence of RT, are uncertain. We conducted a comprehensive assessment of risks of second cancer according to RT technique (>10 MV vs ≤10 MV and 3-dimensional [3D] vs 2D RT) and modality (external beam RT, brachytherapy, and combined modes) in a large cohort of prostate cancer patients.
  
  
  METHODS
  The cohort was constructed using the Surveillance Epidemiology and End Results-Medicare database. We included cases of prostate cancer diagnosed in patients 66 to 84 years of age from 1992 to 2004 and followed through 2009. We used Poisson regression analysis to compare rates of second cancer across RT groups with adjustment for age, follow-up, chemotherapy, hormone therapy, and comorbidities. Analyses of second solid cancers were based on the number of 5-year survivors (n=38,733), and analyses of leukemia were based on number of 2-year survivors (n=52,515) to account for the minimum latency period for radiation-related cancer.
  
  
  RESULTS
  During an average of 4.4 years' follow-up among 5-year prostate cancer survivors (2DRT = 5.5 years; 3DRT = 3.9 years; and brachytherapy = 2.7 years), 2933 second solid cancers were diagnosed. There were no significant differences in second solid cancer rates overall between 3DRT and 2DRT patients (relative risk [RR] = 1.00, 95% confidence interval [CI]: 0.91-1.09), but second rectal cancer rates were significantly lower after 3DRT (RR = 0.59, 95% CI: 0.40-0.88). Rates of second solid cancers for higher- and lower-energy RT were similar overall (RR = 0.97, 95% CI: 0.89-1.06), as were rates for site-specific cancers. There were significant reductions in colon cancer and leukemia rates in the first decade after brachytherapy compared to those after external beam RT.
  
  
  CONCLUSIONS
  Advanced treatment planning may have reduced rectal cancer risks in prostate cancer survivors by approximately 3 cases per 1000 after 15 years. Despite concerns about the neutron doses, we did not find evidence that higher energy therapy was associated with increased second cancer risks.
authors: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: berringtona@mail.nih.gov.
authors: Amy
authors: A
authors: Berrington de Gonzalez
authors: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors: Jeannette
authors: J
authors: Wong
authors: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors: Ruth
authors: R
authors: Kleinerman
authors: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors: Clara
authors: C
authors: Kim
authors: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors: Lindsay
authors: L
authors: Morton
authors: Department of Radiation Oncology, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Justin E
authors: JE
authors: Bekelman
mesh_terms: D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000706:statistics & numerical data*; D015984:Causality; D015331:Cohort Studies; D015897:Comorbidity; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D015994:Incidence; D008297:Male; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology* / Q000517:prevention & control; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000706:statistics & numerical data*; D012004:Rectal Neoplasms / Q000453:epidemiology* / Q000517:prevention & control; D012307:Risk Factors; D017741:Survivors / Q000706:statistics & numerical data; D014481:United States / Q000453:epidemiology
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