Carabenciov, Ivan D.

Introduction: Glioblastoma is a uniformly lethal primary central nervous system neoplasm. Despite the increased understanding of its pathophysiology and treatment advancements, median overall survival for patients with glioblastoma, IDH-wild type remains 14 to 21 months from diagnosis. Case Report: We present the case of a 48-year-old female who presented with a focal seizure and was found to have a right frontal lobe mass on the brain magnetic resonance imaging. She underwent gross total resection and received a histological diagnosis of glioblastoma. She received radiotherapy and 6 cycles of carmustine (BCNU). Seventeen months later, she developed left hemiparesis. Imaging was concerning for tumor progression, and she was treated with 1 cycle of mechlorethamine, vincristine (oncovin), procarbazine, and prednisone (MOPP). Subsequent surveillance imaging demonstrated a therapeutic response. Twenty-seven years after her glioblastoma diagnosis, she developed status epilepticus and died from respiratory failure. Neuropathology on autopsy demonstrated extensive treatment-related changes but no evidence of recurrent glioblastoma. Genomic testing performed over 30 years after her original diagnosis revealed a profile diagnostic of glioblastoma, IDH-wild type per 2021 World Health Organization criteria. Conclusions: This patient is one of the longest-known survivors of glioblastoma, IDH-wild type, with pathologic confirmation of glioblastoma at the time of her resection and no evidence of residual disease 26 years after her last treatment. She presented with multiple factors associated with long-term glioblastoma survivorship, including female sex, young age, high Karnofsky score, and multimodal therapy. This case shows that long-term survival after glioblastoma diagnosis is possible and likely mediated through a combination of individual, tumor, and treatment factors.

Abstract BACKGROUND Hypercoagulability is a well-described paraneoplastic phenomenon associated with strokes in cancer patients, but whether driver mutations or antineoplastic treatments contribute in a significant way to recurrent stroke risk are not well understood. METHODS As part of a larger study focusing on lung cancer and stroke, we retrospectively identified 103 patients with tissue-confirmed adenocarcinoma and prior diagnosis of stroke treated at the Mayo Clinic between 2000-2022. We collected data regarding demographics, performance status, cerebrovascular risk factors, antithrombotic use, chemotherapy, radiation, and genetic testing data, which were assessed for impact on recurrent stroke risk. RESULTS 71.8% of patients had recurrent strokes (74/103). No class of chemotherapeutics was significantly associated with increased risk for recurrent strokes, including immune checkpoint inhibitors and thrombogenic chemotherapeutics (Gemcitabine, Cisplatin, Carboplatin, anti-VEGF therapies). 78 patients had genetic testing data available. Driver mutations in KRAS, EGFR, MET, and BRAF were not associated with increased risk for recurrent stroke. There was a signal towards increased risk for stroke recurrence in patients with ALK mutations (OR 2.647, p=0.4056). There was a trend towards increased risk for stroke recurrence in patients with advanced staging (Stage III/IV) at diagnosis (OR 2.125, p=0.09). Stroke recurrence risk was higher in patients treated with single antiplatelet agents compared to anticoagulation or dual antiplatelet therapy (OR 3.385, p=0.0061) though risk of hemorrhagic complications was similar (OR 1.559, p=0.3376). Patients with recurrent stroke had longer overall survival compared to those without (Median OS 43.2 months vs 26.3 months, Mantel-Haenszel HR 0.5202, p=0.0367). CONCLUSIONS In patients with lung adenocarcinoma who experienced ischemic stroke, prolonged survival and single antiplatelet therapy compared to dual antiplatelet therapy or anticoagulation were associated with increased recurrent stroke risk. ALK mutations and higher stage at initial diagnosis trended towards higher risk for stroke recurrence. Larger retrospective analyses are under way to confirm these findings.

Abstract Li-Fraumeni Syndrome (LFS) is a rare autosomal dominant disorder characterized by a germline mutation in the TP53 gene that confers an increased risk of developing cancers, including brain tumors. There is continued need to understand how LFS diagnosis impacts clinical management and outcomes of gliomas. We report the clinical course of two patients from our Neuro-Oncology. Patient 1 is a male who was diagnosed with a low-grade astrocytoma, IDH1 mutant at age 20 status post gross total resection. Given radiographic concern for tumor progression, he underwent re-resection 8 years later. Pathology showed gliosis with TP53-mutant cells. Next-generation sequencing (NGS) was positive a germline TP53 mutation, consistent with LFS. He is currently in surveillance 12 years after diagnosis without need for radiation or chemotherapy. Patient 2 is a female who was diagnosed with glioblastoma, IDH wildtype, MGMT promoter unmethylated at age 40. She was asymptomatic at the time of diagnosis as the tumor was found during routine screening. She underwent gross total resection, radiation with concurrent and adjuvant temozolomide. She is now 5 years from last treatment without recurrence. These cases illustrate the clinical spectrum of glioma in LFS. Both patients have had prolonged periods of survival without progression, even accounting for respective tumor type. Patient 1 was only diagnosed with LFS after radiographic concerns for progression. Using NGS to diagnosis LFS was clinically important, as previous reports have shown greater propensity for malignant transformation of low-grade glioma in LFS. Patient 2 was diagnosed with glioblastoma during screening and has had no recurrence. This highlights the value of early diagnosis and treatment of gliomas in patients with LFS, even if asymptomatic at discovery. Further research is needed to understand the clinical spectrum of glioma in LFS and to optimize the care of this unique patient population.