After identifying independent risk factors for the failure of plaque brachytherapy, this study's investigators developed a predictive scoring system that could help quantify risk and guide discussions between physicians and patients regarding treatment options for posterior uveal melanoma.
Study design
This single-center, retrospective cohort study reviewed records of patients who received plaque brachytherapy for posterior (choroidal and/or ciliary body) uveal melanoma in order to develop a prognostic scoring system for the incidence of treatment failure. Iris melanomas were excluded. Eligible patients received plaque brachytherapy with Ruthenium-106 (Ru-106) or Iodine-125 (I-125) from 1995 through 2019. Treatment failure was defined as the need for secondary transpupillary thermotherapy, plaque brachytherapy, or enucleation due to local tumor recurrence, lack of regression, scleral necrosis, uncontrollable uveitis, severe radiation retinopathy/optic neuropathy, or blind painful eye. Patients were randomized 1:1 for training and validation cohorts to create and validate a predictive model using Cox regression analysis.
Outcomes
Of 1636 included patients, 248 experienced plaque brachytherapy failure, most frequently due to tumor recurrence (87%) or lack of regression (6%). Most failures were managed with secondary enucleation (65%) or secondary plaque brachytherapy (34%). Predictors of treatment failure on multivariate analysis included worse presenting visual acuity (LogMAR ≥0.30, HR 1.32), shorter distance from tumor to optic disc (≤2 mm, HR 1.45), greater presenting American Joint Committee on Cancer stage (HR 1.22), and greater maximal tumor thickness (>4 mm for Ru-106 or >9 mm for I-125, HR 1.45). A prognostic scale quantified the risk of failure by assigning 1 point for each of the 3 most significant risk factors: poor presenting visual acuity (LogMAR >0.20), ≤2 mm proximity to optic disc, and large tumor thickness (>4 mm for Ru-106 or >9 mm for I-125). Low- (≤1 point), medium- (2 points), and high-risk (3 points) scores correlated with increasing 10-year cumulative risk for plaque brachytherapy failure (19, 28, and 35%, respectively).
Limitations
These study outcomes should be interpreted with caution. Due to the single-center, retrospective design, results might not be generalizable to other centers. Furthermore, the study included patients treated over a 25-year period, during which time surgical techniques and physician experience could have evolved. Additionally, patients were treated in a nonuniform fashion with the use of both Ru-106 and I-125 isotopes. The choice of primary radiotherapy over other options, such as primary enucleation, varied based on the judgement of the treating ocular oncologist, which also could have biased the study cohort.
Clinical significance
Knowing the potential risk factors associated with increased risk of treatment failure after plaque brachytherapy for posterior uveal melanoma—and that most treatment failures were related to tumor recurrence or failure to regress—could guide patient discussions regarding the optimal choice of primary treatment based on the level of acceptable risk.
Financial disclosures: Dr. Lauren Dalvin discloses financial relationships with Leonard and Mary Lou Hoeft Career Development Award Fund, National Cancer Institute, and National Center for Advancing Translational Science (Grant Support).