The implications of genetic testing on radiation therapy decisions: A guide for radiation oncologists Review


Authors: Bergom, C.; West, C. M.; Higginson, D. S.; Abazeed, M. E.; Arun, B.; Bentzen, S. M.; Bernstein, J. L.; Evans, J. D.; Gerber, N. K.; Kerns, S. L.; Keen, J.; Litton, J. K.; Reiner, A. S.; Riaz, N.; Rosenstein, B. S.; Sawakuchi, G. O.; Shaitelman, S. F.; Powell, S. N.; Woodward, W. A.
Review Title: The implications of genetic testing on radiation therapy decisions: A guide for radiation oncologists
Abstract: The advent of affordable and rapid next-generation DNA sequencing technology, along with the US Supreme Court ruling invalidating gene patents, has led to a deluge of germline and tumor genetic variant tests that are being rapidly incorporated into clinical cancer decision-making. A major concern for clinicians is whether the presence of germline mutations may increase the risk of radiation toxicity or secondary malignancies. Because scarce clinical data exist to inform decisions at this time, the American Society for Radiation Oncology convened a group of radiation science experts and clinicians to summarize potential issues, review relevant data, and provide guidance for adult patients and their care teams regarding the impact, if any, that genetic testing should have on radiation therapy recommendations. During the American Society for Radiation Oncology workshop, several main points emerged, which are discussed in this manuscript: (1) variants of uncertain significance should be considered nondeleterious until functional genomic data emerge to demonstrate otherwise; (2) possession of germline alterations in a single copy of a gene critical for radiation damage responses does not necessarily equate to increased risk of radiation-induced toxicity; (3) deleterious ataxia-telangiesctasia gene mutations may modestly increase second cancer risk after radiation therapy, and thus follow-up for these patients after indicated radiation therapy should include second cancer screening; (4) conveying to patients the difference between relative and absolute risk is critical to decision-making; and (5) more work is needed to assess the impact of tumor somatic alterations on the probability of response to radiation therapy and the potential for individualization of radiation doses. Data on radiosensitivity related to specific genetic mutations is also briefly discussed. © 2019 Elsevier Inc.
Keywords: radiotherapy; oncology; risk assessment; tumors; radiation oncology; diagnosis; toxicity; decision making; diseases; gene encoding; functional genomics; radiation oncologists; dna sequences; radiation toxicity; radiation damage; genetic mutations; provide guidances; facsimile; next-generation dna sequencing; radiation-induced toxicity
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 105
Issue: 4
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 2019-11-15
Start Page: 698
End Page: 712
Language: English
DOI: 10.1016/j.ijrobp.2019.07.026
PUBMED: 31381960
PROVIDER: scopus
DOI/URL:
Notes: Source: Scopus
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  1. Anne S Reiner
    248 Reiner
  2. Simon Nicholas Powell
    331 Powell
  3. Nadeem Riaz
    415 Riaz
  4. Jonine L Bernstein
    142 Bernstein