Patient Age, Melanoma Location, Affect Risk for Radio-Induced Complications

TO GO WITH AFP STORY BY CHRISTINE COURCOL – A medical staff member shows the head frame screwed into the skull of a patient for immobilization, getting ready for a Gamma Knife surgery on May 2, 2011 at the Pitie-Salpetriere hospital in Paris. The Gamma Knife sugery is a minimally invasive treatment that can destroy deep-seated blood vessel malformations in the head and brain tumors once considered inoperable. It can also eliminate pain conditions and certain movement disorders, as well as silence malfunctioning areas of the brain, reduce Parkison’s diseases effects, epilepsy including certain eye conditions such as ocular melanoma (Uveal melanomas). AFP PHOTO BERTRAND LANGLOIS (Photo credit should read BERTRAND LANGLOIS/AFP via Getty Images)
Posterior uveal melanoma had greater risk for radiation retinopathy and papillopathy.

Clinicians performing the advanced technique of gamma knife radiosurgery (GKR) achieved local tumor control in 94% of eyes in one of the largest GKR-treated uveal melanoma cohorts to date, according to a longitudinal study published in Acta Ophthalmologica. This retrospective review analyzed data of 194 patients, treated at the Ocular Oncology Service, San Raffaele Scientific Institute in Milan, Italy, from June 1994 to November 2018.

With radiation treatment, there is a known risk for side effects. Researchers explored factors that may be associated with greater chance for radio-induced complications. Previous work has focused on short-term follow-up, but this investigation took place across the long term, with median follow-up time of 57 months. Post-GKR visits took place after 1 day, 7 days, 1 month, and every 6 months until year 3. Patients then returned for yearly examinations.

The study population ranged from 27 to 89 years old at the time of treatment. Investigators found that participants with plateau-shaped tumors were younger (mean age 45 years) than those with dome-configured tumors (mean 62.3 years). Those with mushroom-shaped tumors averaged 66 years old. 

Radio-induced complications affected 152 eyes, 78% of the study population. Notably, cataract developed in 87 eyes, 45% of the cohort. Another principal complication was radiation retinopathy (RR), arising in 67 eyes, 35% of participants. The predominant risk factor found for RR was a tumor positioned at the macula (P =.006). Being older was protective (P =.02), confirmed by logistic regression, with best cut-off value at 55 years of age, according to researchers. Neovascular glaucoma (NVG) occurred in 53 eyes, 27% of the population. Risk factors for NVG proved to be peripapillary-located lesion (P =.002) and tumor thickness (P <.001), with cut-off value at 7.4 mm.

Radiation papillopathy (RP) developed in 35 eyes, 18% of the cohort. Macular tumor location (P =.02) or peripapillary site (P <.001) were connected to elevated risk, as well as peripheral radiation dose (P =.001). Peripapillary tumors, close to the optic nerve, were 3 times more likely to develop RP, similar to results in previous studies. Older age was protective here as well (P =.001), with 68 years of age as best cut-off value. 

Researchers suggest that being older may decrease risk because younger individuals are potentially more sensitive to radiation, or genes that repair DNA could be expressed differently. Alternately, due to a long follow-up period, higher risk may be coincidental, as the younger patients received longer follow-up according to their lifespan.

The sample was Caucasian, 51% men, and all participants’ melanoma was unilateral. A limitation of this analysis was non-standardized imaging — the imaging mode was chosen based on clinical judgment. Also, systemic conditions such as diabetes and treatments including chemotherapy were not taken into account when adjusting for complication risk. However, one of this study’s strengths was the use of logistic regression analysis to confirm risk probability.

“Understanding factors predictive for radiation-related complications in patients undergoing GKR might help for better counseling and treatment planning,” the investigators added.


Cicinelli MV, Di Nicola M, Gigliotti CR, et al. Predictive factors of radio-induced complications in 194 eyes undergoing gamma knife radiosurgery for uveal melanoma, Acta Ophthalmol. Published online February 26, 2021. doi:10.1111/aos.14814