Radiogenomics: Identification of Genomic Predictors for Radiation Toxicity

Rosenstein, Barry S.

doi:10.1016/j.semradonc.2017.04.005

Cited by 51 publications

(46 citation statements)

References 91 publications

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“…As most previous reviews of radiogenomics have focused on normal tissue toxicities [2], a critical area that has not received adequate attention for radiogenomic studies has been the identification of genomic biomarkers associated with the development of a new cancer following radiation therapy. Studies in this area are difficult because of the long time scale for radiation-induced malignancies to appear following the initial irradiation and the need for long-term longitudinal studies.…”

Section: Subsequent Malignancies Following Radiotherapymentioning

confidence: 99%

“…The goal of radiogenomics is to identify genomic factors that are associated with the clinical variability observed in response to radiation therapy [1,2]. A principal aim of research in this field is discovering and validating biomarkers predicting susceptibility to develop adverse effects resulting from exposure to the high doses of radiation used to treat cancer.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, results of clinical studies have demonstrated that patient-related characteristics, including inherited genetic factors, could represent an important basis influencing susceptibility to develop radiation-related toxicities [11]. Substantial progress has been achieved toward the discovery and validation of these genomic biomarkers, primarily single nucleotide polymorphisms (SNPs) [2]. However, only a limited number of SNPs have been validated in multiple cohorts and relatively few mechanistic studies have been conducted.…”

Section: Introductionmentioning

confidence: 99%

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Radiogenomic Predictors of Adverse Effects following Charged Particle Therapy

Morton

Ricks-Santi

West

et al. 2018

International Journal of Particle Therapy

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Radiogenomics is the study of genomic factors that are associated with response to radiation therapy. In recent years, progress has been made toward identifying genetic risk factors linked with late radiation-induced adverse effects. These advances have been underpinned by the establishment of an international Radiogenomics Consortium with collaborative studies that expand cohort sizes to increase statistical power and efforts to improve methodologic approaches for radiogenomic research. Published studies have predominantly reported the results of research involving patients treated with photons using external beam radiation therapy. These studies demonstrate our ability to pool international cohorts to identify common single nucleotide polymorphisms associated with risk for developing normal tissue toxicities. Progress has also been achieved toward the discovery of genetic variants associated with radiation therapy–related subsequent malignancies. With the increasing use of charged particle therapy (CPT), there is a need to establish cohorts for patients treated with these advanced technology forms of radiation therapy and to create biorepositories with linked clinical data. While some genetic variants are likely to impact toxicity and second malignancy risks for both photons and charged particles, it is plausible that others may be specific to the radiation modality due to differences in their biological effects, including the complexity of DNA damage produced. In recognition that the formation of patient cohorts treated with CPT for radiogenomic studies is a high priority, efforts are underway to establish collaborations involving institutions treating cancer patients with protons and/or carbon ions as well as consortia, including the Proton Collaborative Group, the Particle Therapy Cooperative Group, and the Pediatric Proton Consortium Registry. These important radiogenomic CPT initiatives need to be expanded internationally to build on experience gained from the Radiogenomics Consortium and epidemiologists investigating normal tissue toxicities and second cancer risk.

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Section: Subsequent Malignancies Following Radiotherapymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Radiogenomic Predictors of Adverse Effects following Charged Particle Therapy

Morton

Ricks-Santi

West

et al. 2018

International Journal of Particle Therapy

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“…In 2009, the Radiogenomics Consortium was established by the National Cancer Institute and now includes more than 200 investigators at more than 130 institutions, who are focused on developing the large-scale genome-wide association studies necessary to identify genetic factors associated with response to radiation therapy [41–43]. The Radiogenomics Consortium holds that the healthy tissue response across the radiotherapy population is a complex polygenic trait in which many common, single-nucleotide polymorphisms (SNPs) and rare variants, combined, modulate the tissue response to radiation exposures, such as those used clinically.…”

Section: Introductionmentioning

confidence: 99%

Developing Predictive or Prognostic Biomarkers for Charged Particle Radiotherapy

Story

Wang

2018

International Journal of Particle Therapy

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The response to radiotherapy can vary greatly among individuals, even though advances in technology allow for the highly localized placement of therapeutic doses of radiation to a tumor. This variability in patient response to radiation is biologically driven, but the individuality of tumor and healthy tissue biology are not used to create individual treatment plans. Biomarkers of radiosensitivity, whether intrinsic or from hypoxia, would move radiation oncology from precision medicine to precise, personalized medicine. Charged particle radiotherapy allows for even greater dose conformity, but the biological advantages of charged particle radiotherapy have not yet been cultivated. The development of biomarkers that would drive biologically based clinical trials, identify patients for whom charged particles are most appropriate, or aid in particle-selection strategies could be envisioned with appropriate biomarkers. Initially, biomarkers for low-linear energy transfer (LET) radiation responses should be tested against charged particles. Biomarkers of tumor radioresistance to low-LET radiations could be used to identify patients for whom the enhanced relative biological effectiveness (RBE) of charged particles would be more effective compared with low-LET radiations and those for whom specific DNA-repair inhibitors, in combination with charged particles, may also be appropriate. Furthermore, heavy charged particles can overcome the radioresistance of hypoxic tumors when used at the appropriate LET. Biomarkers for hypoxia could identify hypoxic tumors and, in combination with imaging, define hypoxic regions of a tumor for specific ion selection. Moreover, because of the enhanced RBE for charged particles, the risk for adverse healthy tissue effects may be greater, even though charged particles have greater tumor conformality. There are many validated healthy-tissue biomarkers available to test against charged particle exposures. Lastly, newer biological techniques, as well as newer bioinformatic and computational methods, are rapidly changing the landscape for biomarker identification, validation, and clinical trial design.

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“…With the substantial advances in genetics and genomics that have been achieved over the past 30 years, the hypothesis was put forward that genomic alterations could influence susceptibility for the development of adverse effects resulting from radiotherapy [5]. This resulted in creation of the field of radiogenomics whose aim is to identify the genomic factors that account for the range of responses observed in individuals following cancer treatment with radiation.…”

mentioning

confidence: 99%