How does TP53 mutation status influence radiotherapy decisions?

• A. TP53 carriers should always receive higher doses of radiotherapy.
• B. TP53 carriers may have increased sensitivity to radiation and risk of radiation-induced malignancies; clinicians may avoid or limit radiotherapy when alternatives exist.
• C. TP53 status has no impact on radiotherapy decisions.
• D. TP53 carriers are not allowed any radiotherapy.

Answer: (B)

Mutations in TP53 disrupt the p53-mediated DNA damage response, which is crucial for deciding how a cell repairs damage from radiation. In carriers of germline TP53 mutations (as in Li-Fraumeni syndrome), there is an increased risk that radiation will not only damage normal tissues more readily but also provoke secondary cancers over a person’s lifetime. Because of these true risks, clinicians often avoid radiotherapy or limit its use when there are effective alternatives (such as surgery or systemic therapy) or when treatment goals can be achieved with less risk. If radiotherapy is used, they aim to minimize exposure and dose to reduce potential harm. This balance—recognizing heightened radiation sensitivity and cancer risk, and opting for non-radiation options when possible—explains why this choice is considered the best.