The implications of genetic testing on radiotherapy decisions: a guide for radiation oncologists. - PubMed - NCBI

The implications of genetic testing on radiotherapy decisions: a guide for radiation oncologists. - PubMed - NCBI

Int J Radiat Oncol Biol Phys. 2019 Aug 2. pii: S0360-3016(19)33530-8. doi: 10.1016/j.ijrobp.2019.07.026. [Epub ahead of print]

The implications of genetic testing on radiotherapy decisions: a guide for radiation oncologists.

Bergom C1, West CM2, Higginson DS3, Abazeed ME4, Arun B5, Bentzen SM6, Bernstein JL7, Evans JD8, Gerber NK9, Kerns SL10, Keen J11, Litton JK5, Reiner AS7, Riaz N3, Rosenstein BS12, Sawakuchi GO13, Shaitelman SF14, Powell SN3, Woodward WA15.

Author information

1

Department of Radiation Oncology, Medical College of Wisconsin, 9200 West Wisconsin Ave., Milwaukee, WI, 53226, USA.

2

Division of Cancer Sciences, NIHR Manchester Biomedical Research Centre, University of Manchester, The Christie NHS Foundation Trust Hospital, Manchester, M20 4BX, UK.

3

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA.

4

Department of Radiation Oncology, 10201 Carnegie Ave/CA-60, Cleveland Clinic, Cleveland, OH, 44195; Department of Translational Hematology Oncology Research, 12111 East 96th St/NE6-258, Cleveland Clinic, Cleveland, OH, 44195, USA.

5

Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center. 1515 Holcombe Boulevard Unit 1354, Houston, Texas 77030, USA.

6

Department of Epidemiology and Public Health, University of Maryland School of Medicine, 660 W. Baltimore Street, Howard Hall 109D, Baltimore, MD 21201, USA.

7

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA.

8

Department of Radiation Oncology, Mayo Clinic, 200 First St. SW, Rochester, MN 55901; Department of Radiation Oncology and Precision Genomics, Intermountain Healthcare, 4401 Harrison Blvd., Ogden, UT 84403, USA.

9

Department of Radiation Oncology, NYU Langone Health, 160 E. 34th Street New York, NY, 10075, USA.

10

Department of Radiation Oncology, University of Rochester, 601 Elmwood Avenue, Rochester, New York, 14642, USA.

11

Scientific Affairs, American Society for Radiation Oncology, 251 18th Street South, 8th Floor, Arlington, VA 22202, USA.

12

Department of Radiation Oncology and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.

13

Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 1420, Houston, TX, 77030, USA.

14

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 1202, Houston, TX, 77030, USA.

15

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 1202, Houston, TX, 77030, USA. Electronic address: wwoodward@mdanderson.org.

Abstract

PURPOSE AND METHODS:

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. Since minimal clinical data exist to inform decisions at this time, the American Society for Radiation Oncology (ASTRO) 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.

RESULTS AND CONCLUSIONS:

During the ASTRO Workshop, several main points emerged, which are discussed in this manuscript: 1) Variants of uncertain significance should be considered non-deleterious until functional genomic data emerges 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 ATM mutations may modestly increase second cancer risk after radiotherapy, thus follow-up for these patients after indicated radiotherapy 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 radiotherapy and the potential for individualization of radiation doses. Data on radiosensitivity related to specific genetic mutations is also briefly discussed.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS:

ATM; BRCA; genetic screening; mutations; radiation; radiation resistance; radiation toxicity; single nucleotide polymorphisms

PMID:

 

31381960

 

DOI:

 

10.1016/j.ijrobp.2019.07.026