Potential clinical impact of normal-tissue intrinsic radiosensitivity testing

Area of Science:

• Radiation oncology
• Radiobiology
• Medical physics

Background:

• Individual normal-tissue sensitivity to radiotherapy varies.
• In vitro colony-forming assays measure surviving fraction at 2 Gy (SF2).
• Predicting radiosensitivity could optimize radiotherapy.

Purpose of the Study:

• To critically appraise the clinical benefit of pre-treatment knowledge of individual normal-tissue radiosensitivity.
• To review strategies for using in vitro radiosensitivity assays in radiotherapy.
• To assess the impact of these strategies on routine clinical practice.

Main Methods:

• Review of three strategies for utilizing in vitro radiosensitivity data: screening for over-reactors, excluding sensitive patients, and individualizing dose prescriptions.
• Analysis of the limitations of current in vitro radiosensitivity assays, including assay noise and biological variation.
• Consideration of theoretical strategies and current clinical applications of radiosensitivity assays.

Main Results:

• Strategies for using normal-tissue radiosensitivity assays have minimal impact on routine radiotherapy.
• Screening for extreme radiosensitivity is limited by low prevalence and assay predictive value.
• Individualized dosing based on radiosensitivity yields small or negative gains in tumor control probability.
• Current promising applications involve guiding complex or high-risk treatment schedules.

Conclusions:

• Predicting normal-tissue radiosensitivity has limited current clinical utility for routine radiotherapy.
• Assay limitations and biological variability restrict the impact of predictive strategies.
• In vitro radiosensitivity assays are most valuable for guiding specialized and high-risk treatments.