MD Anderson Cancer Center Houston, Texas, United States
Background: Li-Fraumeni Syndrome (LFS) predisposes patients for cancer, including gliomas, due to pathogenic TP53 germline variants. Little is known about their treatment course, molecular markers, and prognosis.
Methods: This is a retrospective study of patients with diagnosis of LFS and glioma at MD Anderson Cancer Center from 2013 to 2023. Data collected includes next generation sequencing and treatment history. We analyzed descriptive statistics and Kaplan-Meier method to report their clinical characteristics and median progression-free survival (mPFS), defined as the time from initial diagnosis to first recurrence.
Results: 14 patients with LFS had diagnosis of glioma, with half of them as the first manifestation of cancer. There were 8 IDH-mutant gliomas (all WHO grade 2 astrocytoma), 4 IDH-wildtype WHO grade 4 glioblastoma, and 2 gliomas with no molecular markers (WHO grade 3 astroblastoma and astrocytoma). Only IDH1 mutations were identified: R132H (n=4), R132S (n=2), and R132L (n=2). ATRX status was tested in 12 gliomas, 8 with retained protein expression. ATRX co-mutation in IDH-mutant astrocytoma occurred in 38% of cases. TP53 status was tested in 12 gliomas, with 6 having positive expression on immunostaining. MGMT methylation status (n=8) was detected in 2 IDH-mutant gliomas whereas all glioblastomas were unmethylated. For treatment, 7 patients with low-grade glioma opted for observation after initial diagnosis despite 5 being considered high-risk for recurrence (subtotal resection/ > 40 years of age). The mPFS for low-risk and high-risk low-grade astrocytoma on observation was 29.1 months and 28.5 months respectively. Based on IDH status, the mPFS for glioblastoma and IDH-mutant grade 2 astrocytoma was 6.4 months and 25.5 months respectively.
Conclusions: LFS patients may have glioma with higher incidence of non-canonical IDH1 mutations, lower likelihood of ATRX and IDH1 co-mutations, and less likely to be treated upfront after initial diagnosis despite having high risk profile for low grade glioma.
