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Original Investigation |

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

Rodrigue S. Allodji, PhD1,2,3; Ibrahima Diallo, PhD1,2,3; Chiraz El-Fayech, MD1,2,3; Amar Kahlouche, BS1,2,3; Agnès Dumas, PhD1,2,3; Boris Schwartz, MSc1,2,3; Odile Oberlin, MD1; Mohamed Amine Benadjaoud, PhD1,2,3; Martine Labbé, BS1,2,3; Angela Jackson, MSc1,2,3; Julien Bullet, MD4; Carole Rubino, PhD, MD1,2,3; Nadia Haddy, PhD1,2,3; Florent De Vathaire, PhD1,2,3
[+] Author Affiliations
1Department of Clinical Research, Gustave Roussy, Villejuif, France
2Radiation Epidemiology Team, Centre for Research in Epidemiology and Population Health, Institut National de la Santé et de la Recherche Medicale Unit 1018, Villejuif, France
3Department of Clinical Research, Université Paris XI, Villejuif, France
4Centre Ophtalmologique Montbauron, Versailles, France
JAMA Ophthalmol. 2016;134(4):390-397. doi:10.1001/jamaophthalmol.2015.6088.
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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.

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Figure 1.
Study Flow Diagram

Patients were treated for cancer from January 1, 1945, to December 31, 1985; questionnaires were sent to adult survivors from September 1, 2005, to December 31, 2012.

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Figure 2.
Cumulative Incidence of Cataract

Incidence is given for the entire cohort and stratified by receipt of radiotherapy.

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