Association of Radiation Dose to the Eyes With the Risk for Cataract After Nonretinoblastoma Solid Cancers in Childhood

JAMA Ophthalmol. 2016 Apr;134(4):390-7. doi: 10.1001/jamaophthalmol.2015.6088.

Abstract

Importance: Few studies have been published on the association of the radiation dose received to the eyes during radiotherapy (RT) for childhood cancer and the risk for later cataract.

Objective: To investigate the risk for cataract after treatment of nonretinoblastoma solid cancer in childhood.

Design, setting, and participants: The study used data from the Euro2K cohort that includes 4389 5-year survivors of solid tumors treated from January 1, 1945, to December 31, 1985; of these, 3172 patients were treated in France. A self-reported questionnaire was sent to French survivors from September 1, 2005, to December 31, 2012, when follow-up was considered completed for this study. However, 619 patients died before the beginning of the study and 128 patients treated for a retinoblastoma or who underwent enucleation were excluded. Likewise, 429 patients with unknown addresses or who did not return the consent form and 163 nonresponders did not participate. The remaining 1833 patients who completed the questionnaire underwent analysis for this study from June 1, 2014, to December 7, 2015.

Main outcomes and measures: Radiation doses in both eyes for individuals were estimated for all patients who had received RT. The role of the radiation dose in cataract risk was investigated using the Cox proportional hazard regression model and the excess relative or the absolute risk model. The role of ctytotoxic chemotherapy was also investigated.

Results: The 1833 patients (961 men [52.4%]; 872 women [47.6%]; mean [SD] age, 37.0 [8.5]) who returned the questionnaire were included in the analysis. After a mean follow-up of 32 years, 33 patients with unilateral or bilateral cataract were identified, for a total of 47 cataract events. The 47 events were validated by medical record review and by contacting the patients and the corresponding medical physician or ophthalmologist to obtain copies of diagnostic examinations or surgical reports. Overall, in a multivariable Cox proportional hazard regression analysis, patients who received RT had a 4.4-fold (95% CI, 1.5- to 13.0-fold) increased risk for cataract compared with patients who did not receive RT. Exposure to radiation doses of at least 10 Gy to the eyes increased the hazard ratio 39-fold (95% CI, 12.0- to 127.9-fold), relative to no radiation exposure. Although based on few patients, a strong increase in cataract risk (hazard ratio, 26.3; 95% CI, 7.1-96.6) was observed in patients treated with melphalan hydrochloride.

Conclusions and relevance: This study can inform guideline-based recommendations for long-term follow-up for cataract.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Cataract / diagnostic imaging*
  • Cataract / epidemiology
  • Child
  • Child, Preschool
  • Confidence Intervals
  • Databases, Factual
  • Dose-Response Relationship, Radiation
  • Female
  • Humans
  • Incidence
  • Linear Models
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Radionuclide Imaging
  • Radiotherapy Dosage
  • Retinal Neoplasms / diagnosis
  • Retinal Neoplasms / radiotherapy*
  • Retinoblastoma / diagnosis
  • Retinoblastoma / radiotherapy*
  • Retrospective Studies
  • Risk Assessment
  • Sex Factors
  • Surveys and Questionnaires*
  • Survivors
  • United Kingdom
  • Young Adult