Nomogram for predicting radiation maculopathy in patients treated with Ruthenium-106 plaque brachytherapy for uveal melanoma

Abstract

Purpose: To develop a predictive model and nomogram for maculopathy occurrence at 3 years after ¹⁰⁶Ru/¹⁰⁶Rh plaque brachytherapy in uveal melanoma.

Material and methods: Clinical records of patients affected by choroidal melanoma and treated with ¹⁰⁶Ru/¹⁰⁶Rh plaque from December 2006 to December 2014 were retrospectively reviewed. Inclusion criteria were: dome-shaped melanoma, distance to the fovea > 1.5 mm, tumor thickness > 2 mm, and follow-up > 4 months. The delivered dose to the tumor apex was 100 Gy. Primary endpoint of this investigation was the occurrence of radiation maculopathy at 3 years. Analyzed factors were as follows: gender, age, diabetes, tumor size (volume, area, largest basal diameter and apical height), type of plaque, distance to the fovea, presence of exudative detachment, drusen, orange pigment, radiation dose to the fovea and sclera. Univariate and multivariate Cox proportional hazards analyses were used to define the impact of baseline patient factors on the occurrence of maculopathy. Kaplan-Meier curves were used to estimate freedom from the occurrence of the maculopathy. The model performance was evaluated through internal validation using area under the ROC curve (AUC), and calibration with Gronnesby and Borgan tests.

Results: One hundred ninety-seven patients were considered for the final analysis. Radiation-related maculopathy at 3 years was observed in 41 patients. The proposed nomogram can predict maculopathy at 3 years with an AUC of 0.75. Distance to fovea appeared to be the main prognostic factor of the predictive model (hazard ratio of 0.83 [0.76-0.90], p < 0.01). Diabetes (hazard radio of 2.92 [1.38-6.20], p < 0.01), and tumor volume (hazard radio of 21.6 [1.66-281.14], p = 0.02) were significantly predictive for maculopathy occurrence. The calibration showed no statistical difference between actual and predicted maculopathy (p = 1).

Conclusions: Our predictive model, together with its nomogram, could be a useful tool to predict the occurrence of radiation maculopathy at 3 years after the treatment.

Keywords: brachytherapy; maculopathy; nomogram; radiotherapy; ruthenium plaque; uveal melanoma.

Fig. 1

Comparison of dose distribution for ¹⁰⁶Ru/¹⁰⁶Rh (A) and ¹²⁵I plaques (B). Dose normalized to apex of the tumor and expressed in percentage

Fig. 2

Kaplan-Meier curve of maculopathy (solid line) with confidence interval (dashed line)

Fig. 3

A) Receiver operating characteristic (ROC) curve of the multivariate Cox proportional hazard model based on dataset population. Area under the curve (AUC) is 0.75 (CI = 0.67-0.83). B) Internal validation: calibration plot estimating the observed probabilities of the outcome Maculopathy = TRUE (y-axis) in relation to the predicted probabilities (x-axis). Dotted line indicates perfect prediction. Round black dots show subjects grouped by similar probabilities (quantiles) of dataset population, the brackets show 95% CI of the prediction, and the points are joint by straight lines. No statistically significant difference was observed between actual and predicted maculopathy (p = 1)

Fig. 4

Nomogram using example 1: a woman with a tumor volume of 0.2 ml, tumor distance to fovea of 10 mm, and not affected by diabetes, would have 68 total points (13 + 55 + 0), corresponding to a 19% probability of developing maculopathy at 3 years after the treatment

Fig. 5

Nomogram using example 2: patient extracted from the database of the photodynamic therapy (PDT) experience. This patient had diabetes, a tumor thickness of 2.79 mm, tumor volume of 0.22 ml, and tumor distance to fovea of 3.83 mm before neoadjuvant PDT. After PDT, a reduction of tumor thickness (from 2.79 mm to 2.25 mm) and volume (from 0.22 ml to 0.12 ml) were observed. The nomogram shows a probability decrease to develop maculopathy from 86% to 74% in the patient in exam. Patient’s characteristics before PDT are indicated with solid line and after PDT with dashed line