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

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Clinical science
Effects of plaque brachytherapy and proton beam radiotherapy on prognostic testing: a comparison of uveal melanoma genotyped by microsatellite analysis
  1. Sophie Thornton1,
  2. Sarah E Coupland2,
  3. Heinrich Heimann3,
  4. Rumana Hussain4,
  5. Carl Groenewald5,
  6. Andrzej Kacperek6,
  7. Bertil Damato7,
  8. Azzam Taktak8,
  9. Antonio Eleuteri8,
  10. Helen Kalirai1
  1. 1 Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
  2. 2 Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
  3. 3 Liverpool Ocular Oncology Centre, Royal Liverpool University Hospital, Liverpool, UK
  4. 4 Liverpool Ocular Oncology Centre, Royal Liverpool University Hospital, Liverpool, UK
  5. 5 Liverpool Ocular Oncology Centre, Royal Liverpool University Hospital, Liverpool, UK
  6. 6 Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK
  7. 7 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  8. 8 Department of Medical Physics and Clinical Engineering, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
  1. Correspondence to Dr Sophie Thornton, Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L7 8TX, UK; sophie.thornton{at}liv.ac.uk

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.

  • genetics
  • neoplasia
  • iris
  • eye (globe)
  • diagnostic tests/investigation

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/bjophthalmol-2019-315363

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    Footnotes

    • Contributors ST, SEC, HK: Design of study; ST: Undertaking microsatellite analysis; ST, SEC, AT, AE, HK: Evaluation of laboratory data with clinical data and outcomes; All authors: Interpretation of results; All authors: Manuscript writing; All authors: Critical review of manuscript.

    • Funding This work was supported by the Eye Tumour Research Fund Charitable Funds, Royal Liverpool University Hospital, UK, grant number (A091/CF).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval Approval for the study was obtained from the Health Research Authority South Central - Hampshire B Research Ethics Committee (REC ref 15/SC/0611).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Deidentified participant data is available from the corresponding author upon reasonable request. ORCID ID. 0000-0001-7693-7279, or sophie.thornton@liv.ac.uk. Conditions of reuse dependent upon ethical approval and appropriate data transfer agreement.