The telovelar approach for fourth ventricular tumors in children: is removal of the posterior arch of C1 necessary?

PURPOSE: Various surgical nuances of the telovelar approach have been suggested. The necessity of removing the posterior arch of C1 to accomplish optimal tumor exposure is still debated. Therefore, we report on our experience and technical details of the fourth ventricular tumor resection in a modified prone position without systematic removal of the posterior arch of C1. METHODS: A retrospective analysis of all pediatric patients, who underwent a fourth ventricular tumor resection in the modified prone position between 2012 and 2021, was performed. RESULTS: We identified 40 patients with a median age of 6 years and a M:F ratio of 25:15. A telovelar approach was performed in all cases. In 39/40 patients, the posterior arch of C1 was not removed. In the remaining patient, the reason for removing C1 was tumor extension below the level of C2 with ventral extension. Gross or near total resection could be achieved in 34/39 patients, and subtotal resection in 5/39 patients. In none of the patients, a limited exposure, sight of view, or range of motion caused by the posterior arch of C1 was encountered, necessitating an unplanned removal of the posterior arch of C1. Importantly, in none of the cases, the surgeon had the impression of a limited sight of view to the most rostral parts of the fourth ventricle, which necessitated a vermian incision. CONCLUSION: A telovelar approach without the removal of the posterior arch of C1 allows for an optimal exposure of the fourth ventricle provided that critical nuances in patient positioning are considered.

Distribution of Bevacizumab into the Cerebrospinal Fluid of Children and Adolescents with Recurrent Brain Tumors.

BACKGROUND: To date, evidence has been lacking regarding bevacizumab pharmacokinetics in the cerebrospinal fluid (CSF). OBJECTIVE: This study assessed the penetration of bevacizumab, as part of a metronomic antiangiogenic treatment regimen, into the CSF of children, adolescents, and young adults with recurrent brain tumors. PATIENTS AND METHODS: Serum and CSF concentrations, malignant cells, and vascular endothelial growth factor A (VEGF-A) were analyzed in 12 patients (5-27 years) following 10 mg/kg bevacizumab intravenous biweekly administration (EudraCT number 2009-013024-23). A population pharmacokinetic model including body weight, albumin, and tumor type as influential factors was extended to quantify the CSF penetration of bevacizumab. RESULTS: Apart from in serum (minimum concentration/maximum concentration [Cmin/Cmax] 77.0-305/267-612 mg/L, median 144/417 mg/L), bevacizumab could be quantified in the CSF (0.01-2.26 mg/L, median 0.35 mg/L). The CSF/serum ratio was 0.16 and highly variable between patients. Malignant cells could be detected in CSF before initiation of treatment in five of 12 patients; after treatment, the CSF was cleared in all patients. VEGF-A was detected in three patients before treatment (mean ± SD: 20 ± 11 pg/mL), and was still measurable in one of these patients despite treatment (16 pg/mL). CONCLUSIONS: This pharmacokinetic pilot study indicated penetration of bevacizumab into the CSF in a population of children, adolescents, and young adults with recurrent brain tumors.

Feasibility and antitumour activity of the FGFR inhibitor erdafitnib in three paediatric CNS tumour patients.

Alterations of the fibroblast growth factor (FGF) signalling pathway are increasingly recognized as frequent oncogenic drivers of paediatric brain tumours. We report on three patients treated with the selective FGFR1-4 inhibitor erdafitinib. Two patients were diagnosed with a posterior fossa ependymoma group A (PFA EPN) and one with a low-grade glioma (LGG), harbouring FGFR3/FGFR1 overexpression and an FGFR1 internal tandem duplication (ITD), respectively. While both EPN patients did not respond to erdafitinib treatment, the FGFR1-ITD-harbouring tumour showed a significant decrease in tumour volume and contrast enhancement throughout treatment. The tumour remained stable 6 months after treatment discontinuation.

Successfully targeting the cancer system with metronomics for medulloblastoma.

The prognosis of the patients with medulloblastoma who relapse after initial treatment including radiotherapy remains dismal. A recent study by Peyrl et al. in JAMA Oncology suggests that the metronomic multidrug combination used in the medulloblastoma European multitarget metronomic antiangiogenic trial (MEMMAT) given at relapse can improve long-term survival.

Reliability of signal intensity in the basal ganglia on non-contrast T1-weighted MR scans after repetitive application of a gadolinium-based contrast agent in pediatric neuro-oncology patients.

PURPOSE: To evaluate the reliability of signal intensity (SI) changes in the basal ganglia as a supposed indicator of gadolinium deposition in the brain after repetitive application of gadolinium-based contrast agents (GBCAs) in a pediatric neuro-oncological collective. METHODS: One hundred and eight neuropediatric patients (54 male, 54 female, 0-17 years old), with repetitive GBCA-enhanced cranial MRIs between 2003 and 2017, were retrospectively analyzed. Two radiologists measured SI in the nucleus dentatus (ND), globus pallidus (GP), thalamus (T), and the pons (P). The NDP and GPT ratio were calculated. An intraclass correlation coefficient, and multiple linear regressions with subsequent stepwise backward variable selection were performed to evaluate the influence of gender, patient's age at the first MRI, time interval between the first and last MRI, linear or macrocyclic GBCAs, residual pathology, treatments, and magnet field strengths. RESULTS: The inter-reader agreement was good for GPT and NDP in the whole collective (ICC = 0.837 and ICC = 0.793) and for children >2 years of age (ICC = 0.874 and ICC = 0.790), but poor to moderate for children ≤2 years of age (ICC = 0.397 and ICC = 0.748). The intra-reader agreement was good (ICC = 0.910 and ICC = 0.882). An SI increase was only observed for both readers in GPT (p = 0.003, or p < 0.001). None of the considered cofactors showed a consistent effect on SI changes for either readers or regions. CONCLUSION: Measurements of SI changes in the basal ganglia are not a reliable parameter with which to evaluate or estimate gadolinium deposition in the brain or to identify suspicious influential factors after repeated GBCA applications.

The Site of Origin of Medulloblastoma: Surgical Observations Correlated to Molecular Groups.

Developmental gene expression data from medulloblastoma (MB) suggest that WNT-MB originates from the region of the embryonic lower rhombic lip (LRL), whereas SHH-MB and non-WNT/non-SHH MB arise from cerebellar precursor matrix regions. This study aimed to analyze detailed intraoperative data with regard to the site of origin (STO) and compare these findings with the hypothesized regions of origin associated with the molecular group. A review of the institutional database identified 58 out of 72 pediatric patients who were operated for an MB at our department between 1996 and 2020 that had a detailed operative report and a surgical video as well as clinical and genetic classification data available for analysis. The STO was assessed based on intraoperative findings. Using the intraoperatively defined STO, "correct" prediction of molecular groups was feasible in 20% of WNT-MB, 60% of SHH-MB and 71% of non-WNT/non-SHH MB. The positive predictive values of the neurosurgical inspection to detect the molecular group were 0.21 (95% CI 0.08-0.48) for WNT-MB, 0.86 (95% CI 0.49-0.97) for SHH-MB and 0.73 (95% CI 0.57-0.85) for non-WNT/non-SHH MB. The present study demonstrated a limited predictive value of the intraoperatively observed STO for the prediction of the molecular group of MB.

Sustained Survival Benefit in Recurrent Medulloblastoma by a Metronomic Antiangiogenic Regimen: A Nonrandomized Controlled Trial.

Importance: Medulloblastoma recurrence in patients who have previously received irradiation has a dismal prognosis and lacks a standard salvage regimen. Objective: To evaluate the response rate of pediatric patients with medulloblastoma recurrence using an antiangiogenic metronomic combinatorial approach (Medulloblastoma European Multitarget Metronomic Anti-Angiogenic Trial [MEMMAT]). Design, Setting, and Participants: This phase 2, investigator-initiated, multicenter nonrandomized controlled trial assessed 40 patients with relapsed or refractory medulloblastoma without a ventriculoperitoneal shunt who were younger than 20 years at original diagnosis. Patients were enrolled between April 1, 2014, and March 31, 2021. Interventions: Treatment consisted of daily oral thalidomide, fenofibrate, celecoxib, and alternating 21-day cycles of low-dose (metronomic) oral etoposide and cyclophosphamide, supplemented by intravenous bevacizumab and intraventricular therapy consisting of alternating etoposide and cytarabine. Main Outcomes and Measures: The primary end point was response after 6 months of antiangiogenic metronomic therapy. Secondary end points included progression-free survival (PFS), overall survival (OS), and quality of life. Adverse events were monitored to assess safety. Results: Of the 40 patients (median [range] age at treatment start, 10 [4-17] years; 25 [62.5%] male) prospectively enrolled, 23 (57.5%) achieved disease control after 6 months of treatment, with a response detected in 18 patients (45.0%). Median OS was 25.5 months (range, 10.9-40.0 months), and median PFS was 8.5 months (range, 1.7-15.4 months). Mean (SD) PFS at both 3 and 5 years was 24.6% (7.9%), while mean (SD) OS at 3 and 5 years was 43.6% (8.5%) and 22.6% (8.8%), respectively. No significant differences in PFS or OS were evident based on molecular subgroup analysis or the number of prior recurrences. In patients demonstrating a response, mean (SD) overall 5-year PFS was 49.7% (14.3%), and for patients who remained progression free for the first 12 months of treatment, mean (SD) 5-year PFS was 66.7% (16.1%). Treatment was generally well tolerated. Grade 3 to 4 treatment-related adverse events included myelosuppression, infections, seizures, and headaches. One heavily pretreated patient with a third recurrence died of secondary acute myeloid leukemia. Conclusions and Relevance: This feasible and well-tolerated MEMMAT combination regimen demonstrated promising activity in patients with previously irradiated recurrent medulloblastoma. Given these results, this predominantly oral, well-tolerated, and outpatient treatment warrants further evaluation. Trial Registration: ClinicalTrials.gov Identifier: NCT01356290.

Bridging the gap: A quality improvement project to implement psychosocial care standards into clinical practice in pediatric oncology.

BACKGROUND: Psychosocial guidelines and standards systematically describe stressors and resources in particularly challenging situations and hence serve as a basis for interventions to achieve defined psychosocial goals. Despite fundamental principles and guidelines for psychosocial methods, the quality of provided care varies considerably depending on setting, provision, and profession. The purpose of the present protocol is to illustrate the development and evaluation of the standardized psychological intervention "My Logbook", a practical guide accompanying children through all stages of treatment by directly translating current quality standards of psychosocial care into practice. METHODS: In an evidence-based set-up, using face-to-face discussions and telephone conferences, a multi-professional team of local experts decide on critical disease-related issues, structure, content (information and intervention elements) and design of the quality improvement tool. Via delphi surveys an extended expert team is asked to rate the content, method, and design of all booklets which is concluded by a final agreement by the specialist group for quality assurance of the psychosocial working group in the Society for Pediatric Oncology (PSAPOH). The developed tools are piloted in an international multicenter study to evaluate the patient-reported outcome and feasibility and to integrate practical views of patients, as well as psychosocial and interdisciplinary professionals into the further development of the "My Logbook". DISCUSSION: The iterative development of the "My Logbook" including local and international experts as well as the patient and practical perspective allow for the design of a process-oriented, consensus - and evidence-based tool directly translating the S3-Guideline into clinical practice. Feasibility and applicability are fostered through an iterative process of constant evaluation and adaptation of the tool by international experts and through the clinical experience gathered in the multi-centered pilot study. Furthermore, the systematic evaluation of the tool by patients, psychosocial, and interdisciplinary professionals enables the identification of persisting gaps between evidence-based standards and clinical practice, discrepancies between the various stakeholders' perspectives as well as regional differences in feasibility, thereby directly linking practice and research. The preliminary results emphasize that psychological support can be standardized, enabling an evaluation and optimization of psychosocial care which future studies need to assess in multicenter clinical randomized controlled trials.

Proof-of-Concept for Liquid Biopsy Disease Monitoring of MYC-Amplified Group 3 Medulloblastoma by Droplet Digital PCR.

BACKGROUND: Liquid biopsy diagnostic methods are an emerging complementary tool to imaging and pathology techniques across various cancer types. However, there is still no established method for the detection of molecular alterations and disease monitoring in MB, the most common malignant CNS tumor in the pediatric population. In the presented study, we investigated droplet digital polymerase chain reaction (ddPCR) as a highly sensitive method for the detection of MYC amplification in bodily fluids of group 3 MB patients. METHODS: We identified a cohort of five MYC-amplified MBs by methylation array and FISH. Predesigned and wet-lab validated probes for ddPCR were used to establish the detection method and were validated in two MYC-amplified MB cell lines as well as tumor tissue of the MYC-amplified cohort. Finally, a total of 49 longitudinal CSF samples were analyzed at multiple timepoints during the course of the disease. RESULTS: Detection of MYC amplification by ddPCR in CSF showed a sensitivity and specificity of 90% and 100%, respectively. We observed a steep increase in amplification rate (AR) at disease progression in 3/5 cases. ddPCR was proven to be more sensitive than cytology for the detection of residual disease. In contrast to CSF, MYC amplification was not detectable by ddPCR in blood samples. CONCLUSIONS: ddPCR proves to be a sensitive and specific method for the detection of MYC amplification in the CSF of MB patients. These results warrant implementation of liquid biopsy in future prospective clinical trials to validate the potential for improved diagnosis, disease staging and monitoring.

Placement of EVD in pediatric posterior fossa tumors: safe and efficient or old-fashioned? The Vienna experience.

PURPOSE: The perioperative treatment of hydrocephalus in pediatric posterior fossa tumors with an external ventricular drain (EVD) is the treatment of choice in our center. We analyzed our experience in using EVD concerning safety and effectivity. METHODS: This is a single-center retrospective cohort study of 100 consecutive pediatric patients who underwent resection for a newly diagnosed tumor in the posterior fossa between 2011 and 2022. RESULTS: Of the 100 patients with posterior fossa tumors, 80 patients (80%) had radiological signs of hydrocephalus at presentation, 49 patients (49%) of whom underwent placement of an EVD. In 40 patients, the EVD was inserted at a mean of 2.25 days prior to the tumor resection; 9 had the EVD inserted during tumor resection (frontal trajectory in 7 patients, occipital trajectory in 2 patients). Histology revealed pilocytic astrocytoma in 48 patients, medulloblastoma in 32, ependymoma in 11, and other histologic entities in 9 patients. Gross total/near-total resection was achieved in 46 (95.83%) of the 48 pilocytic astrocytomas, 30 (93.75%) of the 32 medulloblastomas, and 11 (100%) of the 11 ependymomas. The mean number of total days with the EVD in place was 8.61 ± 3.82 (range 2-16 days). The mean number of days with an EVD after tumor resection was 6.35 ± 3.8 (range 0-16 days). EVD-associated complications were seen in 6 patients (12.24%) including one infection. None of these resulted in a worse clinical course or any long-term sequelae. Permanent CSF diversion at 6 months after surgery was necessary in 13 patients (13%), including two VP shunt, two SD-shunt, six endoscopic third ventriculostomy (ETV), and three combined VP shunt and ETV procedures. Patients with a medulloblastoma or ependymoma had a higher rate of permanent CSF diversion needed than the group of pilocytic astrocytoma patients (27.9% versus 2.13%, p < 0.001). In patients with metastatic disease, 7 of 17 patients (41.18%) needed a permanent CSF diversion, compared to 6 of 83 patients (7.23%) in the group without metastasis (p = 0.001). CONCLUSION: The treatment of hydrocephalus in pediatric posterior fossa tumors with an EVD as a temporary measure is safe and effective, provided that a multi-professional understanding for its handling is given and there is no need for a long transport of the children.

Initial Evidence for Positive Effects of a Psychological Preparation Program for MRI "iMReady" in Children with Neurofibromatosis Type I and Brain Tumors-How to Meet the Patients' Needs Best.

To provide an effective alternative to sedation during MRI examinations in pediatric cancer and NF1 patients, the aims of the present study were to (1) exploratively evaluate a behavioral MRI training program, to (2) investigate potential moderators, as well as to (3) assess the patients' well-being over the course of the intervention. A total of n = 87 patients of the neuro-oncology unit (mean age: 6.83 years) underwent a two-step MRI preparation program, including training inside the scanner, and were recorded using a process-oriented screening. In addition to the retrospective analysis of all data, a subset of 17 patients were also analyzed prospectively. Overall, 80% of the children receiving MRI preparation underwent the MRI scan without sedation, making the success rate almost five times higher than that of a group of 18 children that opted out of the training program. Memory, attentional difficulties, and hyperactivity were significant neuropsychological moderators for successful scanning. The training was associated with favorable psychological well-being. These findings suggest that our MRI preparation could present an alternative to sedation of young patients undergoing MRI examinations as well as a promising tool for improving patients' treatment-related well-being.

A whole-genome scan for Artemisinin cytotoxicity reveals a novel therapy for human brain tumors.

The natural compound Artemisinin is the most widely used antimalarial drug worldwide. Based on its cytotoxicity, it is also used for anticancer therapy. Artemisinin and its derivates are endoperoxides that damage proteins in eukaryotic cells; their definite mechanism of action and host cell targets, however, have remained largely elusive. Using yeast and haploid stem cell screening, we demonstrate that a single cellular pathway, namely porphyrin (heme) biosynthesis, is required for the cytotoxicity of Artemisinins. Genetic or pharmacological modulation of porphyrin production is sufficient to alter its cytotoxicity in eukaryotic cells. Using multiple model systems of human brain tumor development, such as cerebral glioblastoma organoids, and patient-derived tumor spheroids, we sensitize cancer cells to dihydroartemisinin using the clinically approved porphyrin enhancer and surgical fluorescence marker 5-aminolevulinic acid, 5-ALA. A combination treatment of Artemisinins and 5-ALA markedly and specifically killed brain tumor cells in all model systems tested, including orthotopic patient-derived xenografts in vivo. These data uncover the critical molecular pathway for Artemisinin cytotoxicity and a sensitization strategy to treat different brain tumors, including drug-resistant human glioblastomas.

Sociocultural variables have a major impact on participation in patients treated for paediatric posterior fossa tumours.

BACKGROUND: This study investigates the severeness of participation barriers in patients surviving paediatric posterior fossa tumours (PFT) many years after treatment. In the past, aetiological studies on adverse outcome have primarily focused on pathobiological risk factors. The current analysis aims to investigate the importance of environmental variables. METHODS: On average, 10 years after diagnosis, educational and social difficulties of 42 patients surviving paediatric PFT (mean age 17 years) were inquired using a self-constructed questionnaire following the Psychosocial Resource-Orientated Assessment (PREDI). Educational or social participation barriers were defined by self- and/or proxy-reported difficulties in school or in peer relationships. Accordingly, the children and adolescents were categorized into groups of adequate and limited participation. Subsequently, the study identified potential pathobiological (treatment type, hydrocephalus, tumour relapse, gender, age at diagnosis, seizures and cerebellar mutism) and environmental (parental and maternal education, siblings, main language, discrepancies between personal and environmental values, regular physical activity and private living space) risk factors and investigated whether patients with adequate and limited participation differed in the number of risk factors. RESULTS: Almost one decade after treatment, two thirds of patients experienced educational and/or social difficulties. Patients with limited participation were more frequently associated with environmental factors such as low maternal education degree, siblings, main language other than German, discrepancies between societal and personal values and irregular physical activity, as well as the pathobiological risk factors treatment type, hydrocephalus, tumour relapse, cerebellar mutism and seizures. These variables significantly discriminated between patients with and without limited participation. CONCLUSIONS: Limited participation in patients treated for paediatric PFT is common. Next to pathobiological, also environmental risk factors play a major role in educational and social participation barriers. This highlights the fact that solely considering pathobiology is not sufficient when investigating risk factors for the emergence of late sequelae. Future aetiological studies must adopt a biopsychosocial perspective.

Viral infections in pediatric brain tumor patients treated with targeted therapies.

BACKGROUND: Brain tumors are the most common solid malignancies and the leading cause of cancer-related mortality in children. While numerous studies report on viral infections in children with hematologic malignancies and solid organ transplantation, epidemiologic data on the incidence and outcome of viral infections in pediatric patients with brain tumors treated with targeted therapies are still lacking. OBJECTIVES/STUDY DESIGN: We retrospectively reviewed all children with brain tumors receiving targeted therapies in a primary or recurrent setting at the Medical University of Vienna from 2006 to 2021. Demographic variables, quantitative and qualitative parameters of possible infections, and treatment outcomes were recorded. RESULTS: In our cohort (n = 117), 36% of the patients developed at least one PCR-proven viral infection. Respiratory and gastrointestinal tract infections were most common, with 31% and 25%, respectively. Central nervous system (CNS) infections occurred in approximately 10%, with an almost equal distribution of varicella-zoster virus, John Cunningham virus (JCV), and enterovirus. Two patients tested PCR-positive for SARS-CoV-2 infection, with one virus-related death caused by a SARS-CoV-2-related acute respiratory distress syndrome. Patients receiving bevacizumab or mTOR inhibitors seem to have a greater susceptibility to viral infections. CONCLUSION: Pediatric patients with brain tumors receiving targeted therapies have a higher risk of viral infections when compared to children receiving conventional chemotherapy or the general population, and life-threatening infections can occur. Fast detection and upfront treatment are paramount to prevent life-threatening infections in immunocompromised children suffering from brain tumors receiving targeted therapies.

Improved Long-Term Survival of Patients with Recurrent Medulloblastoma Treated with a "MEMMAT-like" Metronomic Antiangiogenic Approach.

Medulloblastoma (MB) recurrence is usually incurable despite intensive therapy including high-dose chemotherapy. An evolving alternative approach to conventional chemotherapy aims at interfering with tumor angiogenesis at different levels. We report on a novel combinatorial metronomic antiangiogenic approach. The study is a retrospective observational study of 29 consecutive patients with first or multiple recurrences prospectively treated according to the MEMMAT strategy ("MEMMAT-like") before the formal protocol (MEMMAT; ClinicalTrials.gov Identifier: NCT01356290) started. The study period was 11/2006 to 06/2016. Treatment consisted of daily oral thalidomide, fenofibrate, celecoxib, and alternating 21-day cycles of low-dose oral etoposide and cyclophosphamide supplemented by IV bevacizumab and intraventricular therapy consisting of alternating etoposide and liposomal cytarabine. Median overall survival (OS) after recurrence for the whole group was 29.5 months, OS was 48.3 ± 9.3% at three years and 34.5 ± 8.8% at five years, and progression-free survival was 42.0 ± 9.5% at three years and 29.4 ± 9% at five years. As of 07/2022, 9/29 patients are alive 86 to 164 months after the recurrence that prompted the "MEMMAT-like" therapy. Treatment was primarily out-patient and generally well-tolerated. Toxicities did occur but were manageable. In conclusion, antiangiogenic therapy according to the MEMMAT strategy increased median OS of patients with recurrent MB and may lead to long-term survival. Adherence to the protocol, including intraventricular therapy, appears important.

Prospective Evaluation of Kidney Function in Long-Term Survivors of Pediatric CNS Tumors.

Purpose: Numerous acute effects of chemotherapeutics on kidney function are well described. However, data on the long-term effects of chemotherapy in the growing population of childhood central nervous system (CNS) tumor survivors is limited. We aimed to evaluate the kidney function of a cohort of long-term CNS tumor survivors treated with different standard chemotherapeutic regimens. Methods: Patients treated for a CNS tumor were prospectively evaluated up to 12 years after completion of their therapy. Examination of kidney function was performed during routine follow-up visits. Blood pressure and blood and urine parameters were analyzed for kidney function evaluation. Glomerular function was assessed by calculating the estimated glomerular filtration rate (eGFR), tubular functions were analyzed by measuring serum electrolytes, bicarbonate and phosphate reabsorption, and proteinuria was assessed by calculating the protein/creatinine ratio and phosphate reabsorption. Results: None of the 65 patients evaluated suffered from clinically relevant kidney impairment (eGFR < 90 mL/min/L, 73 m2). There was no association between chemotherapy dose and eGFR. Only two patients showed mild signs of tubulopathy and 11 patients were diagnosed with elevated blood pressure. Conclusion: With adequate supportive measures, such as sufficient hydration according to chemotherapy protocol guidelines, as well as avoidance or close monitoring of additional nephrotoxic medication, impaired kidney function is rare in CNS tumor survivors treated with standard chemotherapy. Nonetheless, long-term follow-up is essential for early detection of mild impairment of kidney function.

Evaluating the diagnostic validity of the cerebellar cognitive affective syndrome (CCAS) in pediatric posterior fossa tumor patients.

Background: The aim of this case-control study was to investigate the severity of the cerebellar cognitive affective syndrome (CCAS) in patients treated for pediatric posterior fossa tumors (PFT) and evaluate its diagnostic validity and predictive value for long-term effects. Methods: Using neuropsychological test data from 56 patients with PFT (average age: 14 years), the severity of deficits in the CCAS core areas (executive functions, verbal functions, visuospatial abilities and emotions/behaviour) was examined. Neuropsychological and academic long-term outcomes of patients with CCAS were compared to two control groups of PFT patients (treated with either surgery or surgery followed by radio-/chemotherapy) without the syndrome. Risk factors associated with various deficits were considered. Results: All but one PFT patient suffered from slight to severe impairments in at least one CCAS domain, while complete CCAS occurred in 35.7%. Seven years after tumor diagnosis CCAS patients performed worse in information processing, logical reasoning, verbal functions, visuospatial skills, and executive functioning and required more special educational support compared to the control groups. CCAS patients performed equally poor as patients treated with chemo-/radiotherapy in tasks measuring information processing speed. Risk factors were significantly associated with deficits in information processing speed but not CCAS emergence. Conclusions: Deficits in the core CCAS domains are commonly found in PFT patients, but varying in severity, which suggests the syndrome to be continuous rather than dichotomous. However, the validity of CCAS diagnosis was low and unspecific. The exclusion of relevant functions typically impaired in PFT patients (eg, information processing) resulted in difficulties being overlooked.