Descriptive Statistics for Patients with Glioblastoma Associated with Germline Mismatch Repair Gene Mutation

Abstract

<h3>Purpose/Objective(s)</h3> Hereditary Nonpolyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, is a genetic mismatch repair mutation associated with increased risk for development of glioblastoma (GBM). There is a paucity of data describing the clinical outcomes of GBM patients with HNPCC. We aim to describe tumor characteristics, treatment patterns, and outcomes. <h3>Materials/Methods</h3> IRB approved retrospective review of consecutive patients with a diagnosis of both HNPCC and GBM at a single institution. <h3>Results</h3> Nine patients with a diagnosis of HNPCC and GBM were treated at a single institution from 2001-2022. Six patients were male. Median age at GBM diagnosis was 61 (range 21-84). Median follow up from the time of GBM diagnosis was 7.83 months. Eight patients had prior malignancies: n=7 with colon adenocarcinoma, n=1 with Burkitt lymphoma. Two patients had active synchronous cancers with GBM. The most common presenting symptoms were facial droop (n=3) and cognitive changes (n=2). Others include headache, gait change, visual field defect, and seizures with n=1 each. All patients underwent surgery: n=2 gross total resection, n=4 subtotal resection, and n=3 biopsy alone. There were 3 temporal lobe, 3 parietal lobe, 2 frontal lobe, and 1 frontoparietal lobe tumors. Two patients had multifocal disease at diagnosis. One patient had a giant cell variant GBM. Seven patients had MSH6 mutations and 2 had MSH2 mutations. Two patients progressed rapidly after surgery and were unable to receive RT. Seven patients received adjuvant radiation therapy (RT): n=5 received concurrent TMZ- 1 with concurrent bevacizumab, 5-fluorouracil, and leucovorin due to synchronous metastatic colon cancer, 1 received no chemotherapy. The most common dose and fractionation schedules were 60 Gy in 30 fractions (fx) (n=3), 40.05 Gy in 15 fx (n=3), and n=1 received 30 Gy in 10 fx due to poor performance status and large tumor volume. One patient received proton therapy for active MS, n=8 received IMRT. Two patients initiated tumor treating fields following RT completion. The median time to progression after RT was 3.35 months, and all progressed within the radiation field. Median survival from diagnosis was 6.5 months (range 1.2-15.5). No patients received immune checkpoint inhibitors. One patient was alive at the time of data collection. Seven died due to GBM progression, and n=1 died from progression of a synchronous malignancy. <h3>Conclusion</h3> In this small series, patients with mismatch repair mutation associated glioblastoma had especially poor outcomes and a rapidly progressive disease course.