No Association Between Polygenic Risk Scores for Cancer and Development of Radiation Therapy Toxicity

Barnett, Gillian C.; Kerns, Sarah L.; Dorling, Leila; Fachal, Laura; Aguado-Barrera, Miguel E; Martínez-Calvo, Laura; Jandu, Harkeran K; Welsh, Ceilidh; Tyrer, Jonathan P.; Coles, Charlotte E.; Haviland, J.S.; Parker, Christopher; Gómez-Caamaño, Antonio; Calvo-Crespo, Patricia; Sosa-Fajardo, Paloma; Burnet, N.G.; Summersgill, Holly; Webb, Adam; Ruysscher, Dirk De; Seibold, Petra; Chang‐Claude, Jenny; Talbot, Christopher J.; Rattay, Tim; Parliament, Matthew; Ruyck, Kim De; Rosenstein, Barry S.; Pharoah, Paul D.P.; Dunning, Alison M.; Vega, Ana; West, Catharine

doi:10.1016/j.ijrobp.2022.06.098

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…The oxidative stress response has been described for a long time as being involved in determining the response to irradiation. Some assays to predict radiation toxicities have focused on the quantification of enzymes involved in DNA repair mechanisms of the base, nucleotide, single DNA, or double DNA strand breaks: one such first study on 38 patients with head and neck cancer showed that the dysfunction of these pathways might be associated with some risk of toxicity depending on the treatment’s outcome [ 136 ].…”

Section: Predictive/prognostic Irs Biomarker Researchmentioning

confidence: 99%

“…Knowledge of the prediction of adverse events after RT has improved in the last years [ 46 , 85 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 120 , 121 , 122 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 ], so much so that some new avenues may be considered in the therapeutic management of patients. Early diagnosis of toxicities is possible when subclinical biological or radiological signs appear and are associated with unusual early or late toxicity events.…”

Section: Practical Consequences Of a Priori Knowledge Of Irs For Prec...mentioning

confidence: 99%

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The Normal, the Radiosensitive, and the Ataxic in the Era of Precision Radiotherapy: A Narrative Review

Pereira

Orlandi

Deneuve

et al. 2022

Cancers

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(1) Background: radiotherapy is a cornerstone of cancer treatment. When delivering a tumoricidal dose, the risk of severe late toxicities is usually kept below 5% using dose-volume constraints. However, individual radiation sensitivity (iRS) is responsible (with other technical factors) for unexpected toxicities after exposure to a dose that induces no toxicity in the general population. Diagnosing iRS before radiotherapy could avoid unnecessary toxicities in patients with a grossly normal phenotype. Thus, we reviewed iRS diagnostic data and their impact on decision-making processes and the RT workflow; (2) Methods: following a description of radiation toxicities, we conducted a critical review of the current state of the knowledge on individual determinants of cellular/tissue radiation; (3) Results: tremendous advances in technology now allow minimally-invasive genomic, epigenetic and functional testing and a better understanding of iRS. Ongoing large translational studies implement various tests and enriched NTCP models designed to improve the prediction of toxicities. iRS testing could better support informed radiotherapy decisions for individuals with a normal phenotype who experience unusual toxicities. Ethics of medical decisions with an accurate prediction of personalized radiotherapy’s risk/benefits and its health economics impact are at stake; (4) Conclusions: iRS testing represents a critical unmet need to design personalized radiotherapy protocols relying on extended NTCP models integrating iRS.

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Section: Predictive/prognostic Irs Biomarker Researchmentioning

confidence: 99%