Precision Radiotherapy and Radiation Risk Assessment: How Do We Overcome Radiogenomic Diversity?

Abstract

Precision medicine is a rapidly developing area that aims to deliver targeted therapies based on individual patient characteristics. However, current radiation treatment is not yet personalized; consequently, there is a critical need for specific patient characteristics of both tumor and normal tissues to be fully incorporated into dose prescription. Furthermore, current risk assessment following environmental, occupational, or accidental exposures to radiation is based on population effects, and does not account for individual diversity underpinning radiosensitivity. The lack of personalized approaches in both radiotherapy and radiation risk assessment resulted in the current situation where a population-based model, effective dose, is being used. In this review article, to stimulate scientific discussion for precision medicine in both radiotherapy and radiation risk assessment, we propose a novel radiological concept and metric-the personalized dose and the personalized risk index-that incorporate individual physiological, lifestylerelated and genomic variations and radiosensitivity, outlining the potential clinical application for precision medicine. We also review on recent progress in both genomics and biobanking research, which is promising for providing novel insights into individual radiosensitivity, and for creating a novel conceptual framework of precision radiotherapy and radiation risk assessment.

Sex and Gender Differences in Kidney Cancer: Clinical and Experimental Evidence

“…Despite the limited number of studies, evidence shows that males and females present differences in response to radiotherapy, as demonstrated in oesophageal squamous cell carcinoma [155] and rectal cancer [156], suggesting a possible benefit from personalized therapy [157,158]. However, so far no such difference has been reported in kidney cancer.…”

The Effect of Low Temperatures on Environmental Radiation Damage in Living Systems: Does Hypothermia Show Promise for Space Travel?

“…This dose is calculated using reference phantoms for the purpose of enabling the summation of doses from all radiation exposures for comparisons with limits, constraints, and reference levels (set at the same quantity), and for the optimization of protection. Implicit in its use is the central assumption of a linear non-threshold dose–response relationship between dose and risk; it is a reasonable assumption for protection purposes but has not been proven for low doses [ 84 ]. A single set of tissue-weighting factors is used in the calculation of the effective dose, despite previously recognized differences in the age and sex dependence of the relative contributions of cancer types to the overall detriment and, crucially, in the overall magnitude of cancer detriment.…”

Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer

“…Beside its therapeutic properties against cancer, radiotherapy inevitably involves exposure of normal tissues where late as well as acute adverse effects are dose-limiting factors for the treatment. Numerous attempts have been made to develop an assay that can be used for identifying radiotherapy (RT) patients who will develop severe adverse healthy tissue reactions [1][2][3]. The identification of patients at high risk of developing severe side effects is important as it would allow clinicians to consider a change to the standard available RT protocol and/or combine it with other therapeutic alternatives that reduce the risk of damage to healthy tissues.…”