Effects of plaque brachytherapy and proton beam radiotherapy on prognostic testing: a comparison of uveal melanoma genotyped by microsatellite analysis

Br J Ophthalmol. 2020 Oct;104(10):1462-1466. doi: 10.1136/bjophthalmol-2019-315363. Epub 2020 Feb 5.

Abstract

Background/aims: Proton beam radiotherapy and plaque brachytherapy are commonly applied in primary uveal melanoma (UM); however, their effect on chromosome 3 classification of UM by microsatellite analysis (MSA) for prognostication purposes is unknown, where the tumour is sampled post-irradiation. This study examined the prognostic accuracy of genotyping UM biopsied before or after administration of radiotherapy, by MSA.

Methods: 407 UM patients treated at the Liverpool Ocular Oncology Centre between January 2011 to December 2017, were genotyped for chromosome 3 by MSA; 172 and 176 primary UM were sampled prior to and post irradiation, respectively.

Results: Genotyping by MSA was successful in 396/407 (97%) of UM samples (196 males, 211 females; median age of 61 years (range 12 to 93) at primary treatment). There was no demonstrable association between a failure of MSA to produce a chromosome 3 classification and whether radiation was performed pre-biopsy or post-biopsy with an OR of 0.96 (95% CI 0.30 to 3.00, p=0.94). There was no evidence of association (measured as HRs) between risk of metastatic death and sampling of a primary UM before administration of radiotherapy (HR 1.1 (0.49 to 2.50), p=0.81). Monosomy 3 (HR 12.0 (4.1 to 35.0), p<0.001) was significantly associated with increased risk of metastatic death.

Conclusions and relevance: This study revealed that successful genotyping of UM using MSA is possible, irrespective of irradiation status. Moreover, we found no evidence that biopsy prior to radiotherapy increases metastatic mortality.

Keywords: diagnostic tests/investigation; eye (globe); genetics; iris; neoplasia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Brachytherapy*
  • Child
  • Chromosomes, Human, Pair 3 / genetics*
  • DNA, Neoplasm / genetics
  • Female
  • Follow-Up Studies
  • Genotype
  • Genotyping Techniques
  • Humans
  • Male
  • Melanoma / genetics
  • Melanoma / radiotherapy*
  • Microsatellite Repeats / genetics*
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Proton Therapy*
  • Uveal Neoplasms / genetics
  • Uveal Neoplasms / radiotherapy*

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm

Supplementary concepts

  • Uveal melanoma