Effect Of Time To Diagnosis In Children With Malignant Central Nervous System Tumors On Survival Outcomes And Disease-Associated Morbidity: An Institutional Cohort Study

Abstract OBJECTIVE To determine the impact of time to diagnosis on disease related morbidity and mortality. METHODS This is a retrospective review of all diagnoses of malignant CNS tumors in children presenting to BC Children’s Hospital (BCCH) from 2000-2019. Analyses were conducted to assess the relationship between time to diagnosis and overall survival as well as long-term morbidity; stratified by tumor type, age and presence of metastatic disease. RESULTS From 2000-2019, there were 116 children diagnosed with malignant CNS tumors at BCCH (mean age 9.5 years, 67% male). Tumors included medulloblastoma (27, 23.3%), ependymoma (14, 12.1%), high grade gliomas (19, 16.4%), CNS germ cell tumors (40, 34.4%), and other embryonal CNS tumors (16, 13.8%). Median time to diagnosis from first symptom onset was 63 days (IQR 26.5 – 237.5 days). 18% had metastatic disease. Within this cohort, 3-year EFS was 57%, and 5-year overall survival was 78.4%. 64% of patients were alive with no evidence of disease at median follow up from treatment completion of 4.31 years (IQR 1.77 – 6.15 years). Long-term morbidity included panhypopituitarism (20.7%), vision loss(22.4%), hearing loss(30.2%), learning disability(17.2%) and cognitive impairment (19.8%). In a cox proportional hazards model, overall survival was associated with time to diagnosis(estimate 0.0271;SE=1.6500;p=0.028), high grade glioma(estimate 8.3200; SE=0.6650; p=0.001), age at diagnosis(estimate 0.8590; SE=0.0532; p=0.004), relapse (estimate 4.9600; SE=0.6100; p=0.009) and metastatic disease (estimate 9.1700; SE=0.5660; p< 0.001). Vision loss was also significantly correlated with time to diagnosis (estimate 0.542; SE=0.2940; p=0.038). CONCLUSION Median time to diagnosis is associated with overall survival and long-term morbidity in pediatric patients treated for malignant CNS tumors. These data highlight that knowledge translation to the public, primary care and emergency room professionals should be a priority in order to promote early connection with medical care and mitigate morbidity and mortality in those with pediatric CNS tumors.