HGG-28. THE IMPACT OF CMMRD IN HIGH-GRADE GLIOMA PATIENTS, A RETROSPECTIVE ANALYSIS OF 7 YEARS IN LMIC; AN IRRDC STUDY

Abstract

Abstract BACKGROUND Constitutional mismatch repair (MMR) deficiency (CMMRD) is a genetic cancer predisposition syndrome presenting among children and young adults. This study is the first to evaluate CMMRD prevalence among high-grade glioma patients in Pakistan, a country with high consanguinity rates. METHODS We reviewed data of patients younger than 18 diagnosed with pediatric high-grade glioma, anaplastic astrocytoma, and diffuse midline glioma with CMMRD testing between 2016 and 2023. Tumor slides of all included cases were prepared and sent to Sick Kids Toronto to review the MMR protein stains via multi-gene panels. RESULTS Forty-five patients were identified (62.3% females); median age of 11. Headache (88.9%) was the most common symptom, followed by vomiting (60%) and seizures (37.8%); median duration of symptoms was two months. Histopathology revealed 73.3% pediatric high-grade glioma, 22.2% Anaplastic Astrocytoma, and 4.4% Diffuse Midline Glioma. Thirty-six patients (80%) had a cerebral tumor, 13.3%, and 6.7% had a posterior fossa and midline tumor, respectively. CMMRD was positive in 15 of 45 patients (33.3%). Eight patients (53.4%) had CMMRD with loss of PMS 2, two (13.3%) had loss of PMS 2 and MLH 1, two (13.3%) had loss of MSH 2, two (13.3%) had loss of MSH 6, and only one patient had loss of MSH 6 and MSH 2. Consanguinity correlated with CMMRD (P=0.045), but family history of malignancy was not significant (P=0.202). One-year overall survival of all patients, with a median follow-up of 4.8 months, was 44.4 %, whereas 1-year overall survival compared to CMMRD was 33.3%, with a median follow-up of 7.2 months (P=0.616) CONCLUSION We found high prevalence of CMMRD among pediatric high-grade glioma patients and patients with consanguinity. The findings of our study emphasize the importance of genetic testing and counseling. Timely accurate diagnosis is essential as decreased response to conventional treatment regimens may increase disease burden.