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

Abstract

Background/aimsProton 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.Methods407 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.ResultsGenotyping 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 relevanceThis 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.

Targeted Next-Generation Sequencing of 117 Routine Clinical Samples Provides Further Insights into the Molecular Landscape of Uveal Melanoma

“…No diminished quality or ability to genotype these tumors was observed amongst these samples. This is consistent with our findings using MSA/MLPA to genotype irradiated UM [36][37][38].…”

Carbon ion radiotherapy for synchronous choroidal melanoma and lung cancer: A case report

“…Brachytherapy is effective for small-to-medium-sized uveal melanomas with thicknesses of less than 7 mm, whereas PRT is used when the uveal melanoma is larger or closer to the optic disc or fovea, taking advantage of the Bragg peak and biological profile. Newer techniques, such as stereotactic radiosurgery with CyberKnife, achieve similar local control rates with eye retention to PRT but have a poorer post-treatment visual prognosis[ 17 ]. Carbon ion beams have unique physical and biological properties that make high-precision, high linear energy transfer (LET) radiotherapy[ 12 ].…”

Small High-Risk Uveal Melanomas Have a Lower Mortality Rate

“…Tumor DNA extraction, DNA quality assessment and quantification were conducted, as previously described [ 95 , 96 ]. Chromosome 3 aberrations were assessed by either multiplex ligation-dependent probe amplification (MLPA) (MRC-Holland, Amsterdam, The Netherlands) or microsatellite analysis (MSA).…”

“…Chromosome 3 aberrations were assessed by either multiplex ligation-dependent probe amplification (MLPA) (MRC-Holland, Amsterdam, The Netherlands) or microsatellite analysis (MSA). MLPA and MSA methods have been previously described [ 95 , 96 , 97 , 98 , 99 ].…”