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

Author:

Pereira SandrineORCID,Orlandi Ester,Deneuve Sophie,Barcellini AmeliaORCID,Chalaszczyk Agnieszka,Behm-Ansmant IsabelleORCID,Hettal LizaORCID,Rancati TizianaORCID,Vogin GuillaumeORCID,Thariat JulietteORCID

Abstract

(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.

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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