Li-Fraumeni syndrome is defined as a germ-lime mutation in the p53 tumor suppressor gene. Patients with this syndrome are at high risk for multiple malignancies occurring early in life. Brain tumors, both primary and metastatic are common in this cohort of patients. While much data exists regarding the risk of second malignancies after treatment, very little is known about the inherent radiosensitivity of Li-Fraumeni related cancers. 

     Our objective was to study radiosensitivity and toxicity of Gamma Knife radiosurgery in this cohort of patients

     Family 1 had 4 members treated for brain tumors: 1 with anaplastic meningioma; 1 with metastatic lung cancer; 2 with metastatic breast cancer. Family 2 had 2 members with metastatic leiomyosarcoma. Family 3 had 2 members with metastatic breast cancer.

      Patients had 1-3 lesions treated. The patient with anaplastic meningioma had undergone previous resection followed by fractionated radiotherapy to 60 Gy and then recurred. Radiation dose was based on maximal diameter per RTOG 90-05. Median dose was 22 Gy with median diameter 1.8 cm. Local control with a median follow-up of 1.4 years was 87.5% with the only failure being the patient with anaplastic meningioma. There were no incidences of radiation necrosis and no clear second malignancies associated with treatment, although 3 patients did develop disseminated CNS metastases requiring whole brain radiation.

     In vitro, it has been documented that p53 mutations are associated with chemo- and radio-resistance. Our observations on these 8 patients would suggest that this may not be true with ablative doses of radiation given as a single fraction. 

     This is a retrospective study.

     Although follow up is relatively short due to the overall poor prognosis of these patients, treatment related toxicities or second malignancies were not seen.

     Radiation sensitivity studies can be important in certain populations.