Retrospective and prospective analysis of treatment modalities and neurological and neurocognitive outcomes of pediatric patients with central nervous system malignacies

Pediatric tumors of the central nervous system (CNS) are the most common group of solid neoplasms and the first cause of cancer mortality in children. Despite significant advancements in diagnostic and treatment techniques have improved survival rates over the last years, long term effects experienced by survivors still represent a challenge. Since childhood represents a moment of heightened brain sensitivity, during which crucial developmental milestones occur, toxicities correlated with both the tumour and its treatments can have strong consequences on brain development. Several neurological, neurocognitive and neuropsychological late effects have been reported in children with CNS tumors and these effects significantly impact their overall quality of life. For this reason neuropsychological monitoring is considered an important part of CNS tumors’ diagnostic process. These tests allow an earlier detection of adverse medical effects and an earlier intervention that could moderate subsequent disability coming from them. Neuropsychological evaluations should be performed immediately after diagnosis and then repeated at predetermined intervals. The study has been designed as a bidirectional cohort study. The primary aim is to describe neurological and neurocognitive deficits in a group of children diagnosed with brain tumors in the Pediatric Oncology Unit of Azienda Ospedaliero Universitaria Policlinico di Modena from the Year 2015 until 1st January 2021. Additionally the study aims to longitudinally follow a cohort of newly diagnosed patients from 31st August 2021, with a program of prospective evaluations at specific timepoints, in order to analyze the progression of these deficits over time. The secondary objective is to identify risk factors for neurological and neurocognitive impairments. Our evaluations included the review of patients’ medical records, such as clinical and neurological examinations. Neuroimaging studies were interpreted by a neuroradiologist experienced in pediatric neuro-oncology. Neuropsychological assessments were administered by an expert clinical psychologist. These evaluations were conducted at the time of diagnosis (when allowed by the patient’s clinical condition), after surgery and during follow-up. To assess the neuropsychological status, we used Wechsler Intelligence Scale for Children (WISC-IV), Wechsler Preschool and Primary Scale of Intelligence (WPPSI III), Griffiths Scales of Mental Development (GMDS) and NEPSY II. At the time of data analysis, a total of 36 patients were enrolled in the study (9 retrospectively, 27 prospectively). Neuropsychological assessment still needs to be administered for 3 patients due to the critical condition of the children upon admission. The population of patients was representative of data reported in literature in terms of prevalence of different tumor subtypes. This study confirmed several important literature findings. First, in literature it is established that patients who undergo a combination of surgery, radiotherapy and chemotherapy are at higher risk for severe sequelae. Our study also confirmed, as recent study suggested, that LGGs, even though they are considered indolent lesions often treated with surgery only, are at risk of causing long-term neurocognitive impairment. Another literature finding confirmed in our sample is the importance to assess global cognitive functioning but specific domains too. Our study confirmed that core cognitive functions and developmental domains are more affected than global intelligence. Although full-scale IQ remains an important measure, it may fail to fully represent underlying cognitive deficits. In our sample, according to the literature, children diagnosed under the age of 5 years have the worst outcomes in terms of neurological and neurocognitive sequelae.