title: Dose response for radiation cataractogenesis: a meta-regression of hematopoietic stem cell transplantation regimens.
abstract: OBJECTIVE
  To perform a meta-regression on published data and to model the 5-year probability of cataract development after hematopoietic stem cell transplantation (HSCT) with and without total body irradiation (TBI).
  
  
  METHODS
  Eligible studies reporting cataract incidence after HSCT with TBI were identified by a PubMed search. Seventeen publications provided complete information on radiation dose schedule, fractionation, dose rate, and actuarial cataract incidence. Chemotherapy-only regimens were included as zero radiation dose regimens. Multivariate meta-regression with a weighted generalized linear model was used to model the 5-year cataract incidence and contributory factors.
  
  
  RESULTS
  Data from 1386 patients in 21 series were included for analysis. TBI was administered to a total dose of 0 to 15.75 Gy with single or fractionated schedules with a dose rate of 0.04 to 0.16 Gy/min. Factors significantly associated with 5-year cataract incidence were dose, dose times dose per fraction (D•dpf), pediatric versus adult status, and the absence of an ophthalmologist as an author. Dose rate, graft versus host disease, steroid use, hyperfractionation, and number of fractions were not significant. Five-fold internal cross-validation showed a model validity of 83% ± 8%. Regression diagnostics showed no evidence of lack-of-fit and no patterns in the studentized residuals. The α/β ratio from the linear quadratic model, estimated as the ratio of the coefficients for dose and D•dpf, was 0.76 Gy (95% confidence interval [CI], 0.05-1.55). The odds ratio for pediatric patients was 2.8 (95% CI, 1.7-4.6) relative to adults.
  
  
  CONCLUSIONS
  Dose, D•dpf, pediatric status, and regimented follow-up care by an ophthalmologist were predictive of 5-year cataract incidence after HSCT. The low α/β ratio indicates the importance of fractionation in reducing cataracts. Dose rate effects have been observed in single institution studies but not in the combined data analyzed here. Although data were limited to articles with 5-year actuarial estimates, the development of radiation-induced cataracts extends beyond this time.
authors.affiliation: Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Hall
authors.affiliation: Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California. Electronic address: schultheiss@coh.org.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Schultheiss
authors.affiliation: Division of Biostatistics, City of Hope National Medical Center, Duarte, California.
authors.forename: David D
authors.initials: DD
authors.lastname: Smith
authors.affiliation: Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California; Department of Radiation Oncology, Bayhealth Cancer Center, Dover, Delaware.
authors.forename: Khanh H
authors.initials: KH
authors.lastname: Nguyen
authors.affiliation: Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California.
authors.forename: Jeffrey Y C
authors.initials: JY
authors.lastname: Wong
mesh_terms: D000328:Adult; D000367:Age Factors; D001319:Authorship; D002386:Cataract / Q000453:epidemiology / Q000209:etiology*; D002648:Child; D016001:Confidence Intervals; D019583:Dose Fractionation, Radiation; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D016014:Linear Models; D016017:Odds Ratio; D009885:Ophthalmology; D011336:Probability; D011879:Radiotherapy Dosage; D012044:Regression Analysis; D012307:Risk Factors; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects*