Assessment of Isocitrate Dehydrogenase Markers, Clinical Presentation and Imaging Characteristics in Patients Under Management of Glial Neoplasms at Kenyatta National Hospital

Abstract

Tumors of the central nervous system are caused by mutations in genes that regulate cell growth. Improved molecular techniques have enabled scientist to investigate this mutation in detail and even correlate them with prognosis. Isocitrate dehydrogenase mutations are the most important prognosticating factors in patients with glial tumors. This has led to changes in the classification of glial tumors in the new 2016 World Health Organization classification of Tumors of the central Nervous system. Study Broad Objective To characterize the IDH-1 status and clinical characteristics of glial tumors managed surgically at the Kenyatta National Hospital Study Design and Site This was a cross sectional observational study involving all patients with glial tumors managed at the Kenyatta National Hospital. The study was conducted in the Kenyatta National Hospital, outpatient department, trauma and main theatres, neurosurgical ward(4c) and intensive care unit. The lab work was done in the university of Nairobi histopathology labs. Participants/Materials and Methods The cases were accrued over a period of 18 months and included six months of retrospective data review and 1year prospective accrual of patients. Patients who had surgery within the last 6 months, had their records traced in the surgical operations book and files in the records department. Patients were contacted using the contacts given in the files and seen in the clinic. New patients were recruited during routine neurosurgical clinics. Participants included all patients with new onset glial tumors as determined by histology, those on follow-up for confirmed glial tumors managed within 6 months of the start of the study, and patients with recurrent tumors. All patients received routine standard of care and clinical data collected. Tumors were examined after extirpation by the pathology department and glial tumors identified. Immunohistochemistry was done for oligodendrogliomas, Astrocytomas and Glioblastomas. Grade I tumors and ependymomas were excluded from IDH-1 characterization as it is not prognostic in these tumors. Once sample size was achieved the tumor blocks were processed and tested for isocitrate dehydrogenase mutation. The IDH-1 staining was done xii using Anti-IDH1 R132H antibody clone H09 (Heidelberg 2009) Patients were followed up for 3 months to detect any early postoperative morbidity or mortalities. Results A total of 33 glioma patients were operated and managed within an 18-month period. Twenty- three cases were prospective and 10 retrospectives. Twenty two cases were eligible for IDH-1 characterization (Astrocytomas, Oligodendrogliomas and Glioblastomas). Five (24%) of tumors had IDH-1 mutation compared to 16(76%) of tumors with the wild type genotype. The Male to female ratio 1:1.6 with mean age of patients 43.5 years(SD±20.62) with a range of 18-70 years. Most patients came from counties that bordered Nairobi county where the hospital is based. Fourteen patients (63%) of the patients presented with headache as the primary symptom followed by 4 patients(18%) who presented with seizures. Thirteen patients (59%) of the patients presented within 2 weeks and 3 months of onset of the symptoms. Of patients who thought a delay had occurred, physician delay at 22.73% was the commonest cause. Fifteen patients (68%) of the patients had a karnofsky performance score of 70 and above. Twenty-one patients (95 %) had CT scan as an initial evaluation with sixteen patients (72%) having MRI for surgical planning. Nine patients (45%) had tumors in the frontal lobe followed by 5 patients (23%) with tumours in the parietal lobe. Sixteen patients (76%) of the tumours had well defined margins. Seventeen patients (85%) of the tumours had surrounding oedema. In 3-month, post-operative follow-up, ten patients (45%) of the patients were alive compared to 8 (38.1%) of patients who had died. Three patients(14.2%) of patients were lost to follow-up. Tumour grade was a predictor of early postoperative mortality with a diagnosis of low-grade glioma having a 6 times protective effect on odds ratio. Whilst Absence of oedema and IDH-1 mutation were also significantly protective from early post-operative mortality.