Risk factors for neovascular glaucoma after proton beam therapy of uveal melanoma: a detailed analysis of tumor and dose-volume parameters

Int J Radiat Oncol Biol Phys. 2013 Oct 1;87(2):330-6. doi: 10.1016/j.ijrobp.2013.05.051. Epub 2013 Jul 23.

Abstract

Purpose: To determine neovascular glaucoma (NVG) incidence and identify contributing tumor and dosing factors in uveal melanoma patients treated with proton beam radiation therapy (PBRT).

Methods and materials: A total of 704 PBRT patients treated by a single surgeon (DHC) for uveal melanoma (1996-2010) were reviewed for NVG in our prospectively maintained database. All patients received 56 GyE in 4 fractions. Median follow-up was 58.3 months. Analyses included the Kaplan-Meier method to estimate NVG distributions, univariate log-rank tests, and Cox's proportional hazards multivariate analysis using likelihood ratio tests to identify independent risk factors of NVG among patient, tumor, and dose-volume histogram parameters.

Results: The 5-year PBRT NVG rate was 12.7% (95% confidence interval [CI] 10.2%-15.9%). The 5-year rate of enucleation due to NVG was 4.9% (95% CI 3.4%-7.2%). Univariately, the NVG rate increased significantly with larger tumor diameter (P<.0001), greater height (P<.0001), higher T stage (P<.0001), and closer proximity to the disc (P=.002). Dose-volume histogram analysis revealed that if >30% of the lens or ciliary body received ≥50% dose (≥28 GyE), there was a higher probability of NVG (P<.0001 for both). Furthermore, if 100% of the disc or macula received ≥28 GyE, the NVG rate was higher (P<.0001 and P=.03, respectively). If both anterior and posterior doses were above specified cut points, NVG risk was highest (P<.0001). Multivariate analysis confirmed significant independent risk factors to include tumor height (P<.0001), age (P<.0001), %disc treated to ≥50% Dose (<100% vs 100%) (P=.0007), larger tumor diameter (P=.01), %lens treated to ≥90% Dose (0 vs >0%-30% vs >30%) (P=.01), and optic nerve length treated to ≥90% Dose (≤1 mm vs >1 mm) (P=.02).

Conclusions: Our current PBRT patients experience a low rate of NVG and resultant enucleation compared with historical data. The present analysis shows that tumor height, diameter, and anterior as well as posterior critical structure dose-volume parameters may be used to predict NVG risk.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Female
  • Glaucoma, Neovascular / etiology*
  • Humans
  • Incidence
  • Macula Lutea
  • Male
  • Melanoma / epidemiology
  • Melanoma / etiology
  • Melanoma / pathology
  • Melanoma / radiotherapy*
  • Middle Aged
  • Neoplasm Staging
  • Optic Disk
  • Organ Sparing Treatments / methods
  • Organs at Risk / radiation effects
  • Proton Therapy / adverse effects*
  • Radiotherapy Dosage
  • Risk Factors
  • Tumor Burden
  • Uveal Neoplasms / epidemiology
  • Uveal Neoplasms / etiology
  • Uveal Neoplasms / pathology
  • Uveal Neoplasms / radiotherapy*
  • Young Adult

Supplementary concepts

  • Uveal melanoma