title: Risk factors for neovascular glaucoma after proton beam therapy of uveal melanoma: a detailed analysis of tumor and dose-volume parameters.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, San Francisco, California 94115, USA. kmishra@radonc.ucsf.edu
authors.forename: Kavita K
authors.initials: KK
authors.lastname: Mishra
authors.forename: Inder K
authors.initials: IK
authors.lastname: Daftari
authors.forename: Vivian
authors.initials: V
authors.lastname: Weinberg
authors.forename: Tia
authors.initials: T
authors.lastname: Cole
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Quivey
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Castro
authors.forename: Theodore L
authors.initials: TL
authors.lastname: Phillips
authors.forename: Devron H
authors.initials: DH
authors.lastname: Char
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D005260:Female; D015355:Glaucoma, Neovascular / Q000209:etiology*; D006801:Humans; D015994:Incidence; D008266:Macula Lutea; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000209:etiology / Q000473:pathology / Q000532:radiotherapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D009898:Optic Disk; D059351:Organ Sparing Treatments / Q000379:methods; D058958:Organs at Risk / Q000528:radiation effects; D061766:Proton Therapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D012307:Risk Factors; D047368:Tumor Burden; D014604:Uveal Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000473:pathology / Q000532:radiotherapy*; D055815:Young Adult; D000098943:Uveal Melanoma