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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.[1] The specific risks of radiation therapy for LFS patients include radiosusceptibility, radiosensitivity, and radioresistance.[1] However, radiosensitivity in germline TP53 variant carriers seems similar to that in the general population.[1]
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.[1] 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.[1]
Recent studies have shown that the risk of radiation-induced secondary malignancies in LFS breast cancer patients may be lower than previously reported.[2] 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.[2] It is recommended that radiation therapy should be considered as part of the treatment algorithm when clinically indicated and after multidisciplinary discussion.[3]


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.