Patients with Li-Fraumeni syndrome (LFS) have an increased risk of developing second malignant neoplasms due to their germline TP53 mutations, which can be exacerbated by genotoxic stresses such as radiation therapy. The specific risks of radiation therapy for LFS patients include radiosusceptibility, radiosensitivity, and radioresistance. However, radiosensitivity in germline TP53 variant carriers seems similar to that in the general population.
The risk of second malignant neoplasms should be assessed during specialized multidisciplinary staff meetings, and radiotherapy should be avoided whenever other similarly curative treatment options are available. In cases where radiotherapy is still required, adaptations such as proton therapy, non-ionizing diagnostic procedures, image guidance, and minimal stray radiation can be employed to minimize the risk of second malignant neoplasms.
Recent studies have shown that the risk of radiation-induced secondary malignancies in LFS breast cancer patients may be lower than previously reported. In some cases, the potential risk for locoregional recurrence without radiotherapy must be weighed against the long-term risk for radiation-induced malignancies when considering adjuvant radiotherapy for LFS breast cancer patients. It is recommended that radiation therapy should be considered as part of the treatment algorithm when clinically indicated and after multidisciplinary discussion.
1.Thariat J, Chevalier F, Orbach D, et al. Avoidance or Adaptation of Radiotherapy in Patients With Cancer With Li-Fraumeni and Heritable TP53-related Cancer Syndromes. The Lancet. Oncology. 2021;22(12):e562-e574. doi:10.1016/S1470-2045(21)00425-3.
2.Le AN, Harton J, Desai H, et al. Frequency of Radiation-Induced Malignancies Post-Adjuvant Radiotherapy for Breast Cancer in Patients With Li-Fraumeni Syndrome. Breast Cancer Research and Treatment. 2020;181(1):181-188. doi:10.1007/s10549-020-05612-7.
3.Hendrickson PG, Luo Y, Kohlmann W, et al. Radiation Therapy and Secondary Malignancy in Li-Fraumeni Syndrome: A Hereditary Cancer Registry Study. Cancer Medicine. 2020;9(21):7954-7963. doi:10.1002/cam4.3427.