NCOG-22. Gliomas associated with Li-Fraumeni Syndrome

Li-Fraumeni syndrome increases the risk for multiple cancer types, including glioma. The behavior of gliomas associated with Li-Fraumeni syndrome is not well characterized in the literature. We performed a retrospective review at MD Anderson Cancer Center using the terms “glioma” and “Li-Fraumeni” from January 2013 through January 2025. Patients were followed until June 2025. A total of 25 patients were included. The median age of diagnosis was 25 years and 52% were females. Tumor type included 44% astrocytomas, 32% glioblastoma, and 8% ependymoma. Less common tumors included anaplastic astroblastoma, diffuse high grade glioma histone 3 wildtype and IDH wildtype, and pleomorphic xanthoastrocytoma, each with one patient. In the astrocytoma group, 50% were graded as WHO grade II and 30% as WHO grade III. In the ependymoma group, one patient was graded as WHO grade II and one patient as WHO grade III. In the glioblastoma group, 87.5% were females, compared to 20% in the astrocytoma group. Initial treatment varied by tumor type, and included a combination of resection, radiation, and chemotherapy. Eleven patients had other primary cancer sites, including multiple tumors with the higher frequency of breast cancer (6 patients), thyroid cancer (2 patients), and sarcoma (2 patients). Median overall survival was not reached given that only 7 patients died. Progression free survival after initial diagnosis to first recurrence was 57 months for the entire group, and was 33.8 months for astrocytomas, and not reached for glioblastoma (p=0.925 comparing astrocytomas and glioblastomas). The spectrum of gliomas among Li-Fraumeni syndrome patients is diverse, favoring high-grade glioma as initial presentation in young adults/pediatric patients. However, survival can be longer to what is expected per tumor type.