Medulloblastoma and familial adenomatous polyposis: Good prognosis and good quality of life in the long-term?

INTRODUCTION: Mutations of the APC (adenomatous polyposis coli) gene correlate mainly with familial adenomatous polyposis (FAP), but can occasionally be pathogenic for medulloblastoma (MBL) wingless-related integration site (WNT) subtype, the course of which has only recently been described. METHODS: We retrieved all patients with documented germline APC mutations and a diagnosis of MBL to examine their outcome, late effects of treatment, and further oncological events. RESULTS: Between 2007 and 2016, we treated six patients, all with a pathogenic APC variant mutation and all with MBL, classic histotype. None had metastatic disease. All patients were in complete remission a median 65 months after treatment with craniospinal irradiation at 23.4 Gy, plus a boost on the posterior fossa/tumor bed up to 54 Gy, followed by cisplatin/carboplatin, lomustine, and vincristine for a maximum of eight courses. Five of six diagnostic revised MRI were suggestive of the WNT molecular subgroup typical aspects. Methylation profile score (in two cases) and copy number variation analysis (chromosome 6 deletion in two cases) performed on four of six retrieved samples confirmed WNT molecular subgroup. Four out of six patients had a positive family history of FAP, while gastrointestinal symptoms prompted its identification in the other two cases. Four patients developed other tumors (desmoid, MELTUMP, melanoma, pancreatoblastoma, thyroid Tir3) from 5 to 7 years after MBL. DISCUSSION: Our data confirm a good prognosis for patients with MBL associated with FAP. Patients' secondary tumors may or may not be related to their syndrome or treatment, but warrant adequate attention when planning shared guidelines for these patients.

Early neuropsychological profile of children diagnosed with a brain tumor predicts later academic difficulties at school age.

PURPOSE: Children diagnosed with a brain tumor (BT) in the first years of their life are at high risk of cognitive and neuropsychological problems, more school difficulties, and an increased need for educational support. To improve this condition, it will be beneficial to be able to identify the neuropsychological variables that are early predictors of school competences at later ages. METHODS: We longitudinally assessed 30 school-age BT children with a diagnosis before the age of 5 who were administered cognitive and neuropsychological evaluations before entering school or in the first 2 school years and who were followed up for academic performance at least one year after the first evaluation. A discriminant function analysis was conducted to detect the early neuropsychological profile that best predicted those children who turned out to need school support or not; we tested 5 block multiple regression models, one for each academic variable entering as predictors the neuropsychological variables that significantly discriminated the two groups. RESULTS: A total of 93.3% of the cases were correctly classified according to the discriminant function in "with vs. without" educational support. Visual attention abilities were highly correlated with resulting school problems, both for reading (accuracy and speed) and math (operations) at school age. CONCLUSIONS: Analysis provided evidence that the early neuropsychological profile may predict academic difficulties for both reading and math at school age and that visual attention seems to play an important role in both these academic abilities, allowing clinicians to identify children with major difficulties in/from early years and to intervene beforehand.

Effectiveness of Computerized Cognitive Training Programs (CCTP) with Game-like Features in Children with or without Neuropsychological Disorders: a Meta-Analytic Investigation.

Computerized cognitive training programs (CCTP) are based on the assumption that cognitive abilities may be boosted by repetitively performing challenging tasks. The integration of game-like features in these programs, associated with the goal of amusing or rewarding participants, may contribute to generate cognitive benefits. Indeed, reinforcement contingencies have been reported to produce positive effects on performance and motivation, especially in children. This meta-analysis was aimed at providing a quantitative summary of the effectiveness of CCTP with game-like features in school-aged children with typical and atypical development. A total of 24 studies, with the cognitive and behavioral outcome data of 1547 participants, were selected for inclusion in the meta-analysis. Subgroup analyses were performed to identify the sources of the observed methodological heterogeneity. A robust variance estimation model, after removal of study outliers, yielded a small-to-moderate significant effect size. Final results pointed out smaller but more precise estimate effect sizes according to methodological aspects related to cognitive domain of outcomes, standardization of measures and type of control applied. Alongside supporting the use of CCTP for rehabilitating cognitive functions, the present results shed light on how different methodological choices are able to shape research findings in the field of children's cognitive rehabilitation.

Cerebellar Damage Affects Contextual Priors for Action Prediction in Patients with Childhood Brain Tumor.

Predictive coding accounts of action perception sustain that kinematics information is compared with contextual top-down predictions (i.e., priors) to understand actions in conditions of perceptual ambiguity. It has been previously shown that the cerebellum contributes to motor simulation of observed actions. Here, we tested the hypothesis that a specific contribution of the cerebellum to action perception is to provide contextual priors that guide the sampling of perceptual kinematic information. To this aim, we compared the performance of 42 patients with childhood brain tumor affecting infratentorial (ITT) or supratentorial (STT) areas with that of peers with typical development in an action prediction task. First, participants were exposed to videos depicting a child performing different reaching-to-grasp actions, which were associated with contextual cues in a probabilistic fashion. Then, they were presented with shortened versions of the same videos and asked to infer the action outcome; since kinematics was ambiguous, we expected their responses would be biased toward the previously learned contextual priors. We found that patients with brain tumor were impaired in predicting actions when compared to healthy controls. However, STT patients presented a reliable probabilistic effect, while ITT patients, who had cerebellar damage, did not rely on contextual priors in predicting actions. Furthermore, we found an association between the use of contextual priors and the ability to infer others' mental states as assessed by a standardized test. These results suggest that the cerebellum provides contextual priors to understand others' actions and this predictive function might underlie complex social cognition abilities.

Effects of supratentorial and infratentorial tumor location on cognitive functioning of children with brain tumor.

PURPOSE: Effects of tumor location on cognitive performance of patients with brain tumor are controversial: some studies reported higher risks related to supratentorial locations, some to infratentorial locations, and still others did not find any differences. We aimed to address this issue by comparing school-aged children with supratentorial or infratentorial tumor with respect not only to cognitive outcomes but also to the associations between core cognitive domains and academic abilities. METHODS: 32 children with infratentorial tumor and 22 with supratentorial tumor participated in the study. To detect relationships among cognitive domains, we tested which neuropsychological variable(s) predicted academic skills, controlling for the effects of radiotherapy and time since diagnosis. RESULTS: Radiotherapy and time since diagnosis, but not tumor location, predicted cognitive outcomes. Radiotherapy negatively influenced attention and executive functioning, as well as reading speed and arithmetic operations accuracy. Unexpectedly, longer time since diagnosis was associated with improvement in attention and reading speed. Tumor location showed an effect on the relationships between core cognitive domains and academic skills: verbal and visual-spatial memory influenced reading and mathematical performance in supratentorial patients; in infratentorial patients, an only effect of visual-spatial memory on mathematical performance was detected. CONCLUSIONS: Tumor location seems not to influence cognitive performance, while radiotherapy constitutes a key risk factor for cognitive impairment. Attentional and reading abilities may improve over time, possibly due to the weakening of cancer care effects. Different patterns of cognitive associations seem to characterize supratentorial and infratentorial patients, probably associated with different neuroplastic reorganization processes after tumor occurrence.

Application of the Scale for the Assessment and Rating of Ataxia (SARA) in pediatric oncology patients: A multicenter study.

Posterior cranial fossa (PCF) tumors in childhood are often associated with ataxia as well as other motor, neurobehavioral and linguistic impairment. The use of a reliable outcome measure is mandatory to evaluate the severity of impairment and monitor rehabilitation effectiveness. The aim of this work is to explore the validity of the Scale for the Assessment and Rating of Ataxia (SARA) in pediatric subjects with ataxia secondary to PCF tumor resection and evaluate the influence of age and comorbidities. Seventy eight patients (3-18 years) were recruited in 5 centers from 2016 to 2018. The age effect on SARA was analyzed by correlating total SARA scores and item scores with age and gradually excluding youngest subjects. The comorbidity effect was evaluated by comparing the ataxia-only group vs a group of subjects with ataxia + dysfunction of cranial nerves or cerebellar mutism (CM) and a group of patients with ataxia + hemiparesis. Several negative correlations between SARA scores and age were found under age 9. Differences between ataxia-only group and the other two groups were closely associated with specific comorbidities (e.g. speech disturbance in cranial nerves or CM group (p value < 0.001) and gait, stance, sitting and finger chase in the hemiparetic group (mean p value 0.022)).

Pediatric intracranial ependymoma: correlating signs and symptoms at recurrence with outcome in the second prospective AIEOP protocol follow-up.

PURPOSE: The aims of patients' radiological surveillance are to: ascertain relapse; apply second-line therapy; accrue patients in phase 1/2 protocols if second-line therapy is not standardized/curative; and assess/treat iatrogenic effects. To lessen the emotional and socioeconomic burdens for patients and families, we ideally need to establish whether scheduled radiological surveillance gives patients a better outcome than waiting for symptoms and signs to appear. METHODS: We analyzed a prospective series of 160 newly-diagnosed and treated pediatric/adolescent patients with intracranial ependymoma, comparing patients with recurrent disease identified on scheduled MRI (the RECPT group; 34 cases) with those showing signs/symptoms of recurrent disease (the SYMPPT group; 16 cases). The median follow-up was 67 months. RESULTS: No significant differences emerged between the two groups in terms of gender, age, tumor grade/site, shunting, residual disease, or type of relapse (local, distant, or concomitant). The time to relapse (median 19 months; range 5-104) and the MRI follow-up intervals did not differ between the SYMPPT and RECPT groups. The presence of signs/symptoms was an unfavorable factor for overall survival (OS) after recurrence (5-year OS: 8% vs. 37%, p = 0.001). On multivariable analysis, an adjusted model confirmed a significantly worse OS in the SYMPPT than in the RECPT patients. CONCLUSIONS: Symptomatic relapses carried a significantly worse survival for ependymoma patients than recurrences detected by MRI alone. It would therefore be desirable to identify recurrences before symptoms develop. Radiological follow-up should be retained in ependymoma patient surveillance because there is a chance of salvage treatment for relapses found on MRI.

Cognitive functioning of pediatric patients with brain tumor: an investigation of the role of gender.

PURPOSE: The female gender has been considered a risk factor for cognitive impairment in pediatric brain tumor survivors. However, it is still unknown which specific cognitive domains are at greater risk of impairment in females. The aim of this study was to explore differences between male and female children in distinct domains of cognitive functioning, in order to deepen knowledge on the topic. METHODS: The cognitive performance of 100 males and 71 females aged 6-16 years was assessed by Wechsler Intelligence Scales for Children-Third Edition (WISC-III). Differences between males and females were tested not only on intellectual quotients, but also on WISC-III subtests, which allow the evaluation of different cognitive domains. Analyses were performed in the whole sample and dividing children based on the supratentorial vs. infratentorial location of the tumor. RESULTS: Gender was the only predictor of VIQ in the whole group and in children with supratentorial tumor. Female children with supratentorial tumor performed significantly worse than males in four out of six verbal subtests. However, even among children with infratentorial tumor, females performed worse than males on two verbal subtests. CONCLUSIONS: Overall, findings of this study suggest that females may have more difficulties than males at manipulating verbal oral material. A possible explanation of these findings could be that females present a greater vulnerability to white matter damage due to the illness and post-adjuvant therapies, in line with reports of the literature on female children with lymphoblastic leukemia.

Long-term safety of growth hormone replacement therapy after childhood medulloblastoma and PNET: it is time to set aside old concerns.

To assess the long-term safety of administering growth hormone (GH) in patients with GH deficiency due to treatment for childhood medulloblastoma and primitive neuroectodermal tumor (PNET). Data were retrospectively retrieved on children receiving GH supplementation, assessing their disease-free and overall survival outcomes and risk of secondary malignancies using Kaplan-Meier and Cox models. Overall 65 children were consecutively collected from May 1981 to April 2013. All patients had undergone craniospinal irradiation (total dose 18-39 Gy), and subsequently received GH for a median (interquartile range, IQR) of 81 (50.6-114.9) months. At a median (IQR) of 122.4 months (74.4-149.5) after the end of their adjuvant cancer treatment, two patients (3 %) experienced recurrent disease and 8 (12.3 %) developed secondary malignancies, all but one of them (an osteosarcoma) related to radiation exposure and occurring within the radiation fields. There was no apparent correlation between the administration of GH replacement therapy (or its duration) and primary tumor relapse or the onset of secondary malignancies [HR: 1.01 (95 % CI: 0.98, 1.03) for every additional 12 months of GH supplementation; p = 0.36). At univariate analysis, the large cell or anaplastic medulloblastoma subtype, metastases and myeloablative chemotherapy correlated with a higher risk of secondary malignancies (p < 0.1), but multivariate analysis failed to identify any factors independently associated with this risk. Our data supports once more the safety of long-term GH replacement therapy in children treated for medulloblastoma/PNET, previously reported in larger data sets. The neurooncology community now need to warrant large-scale meta-analyses or international prospective trials in order to consolidate our knowledge of factors other than GH, such as genetic predisposition, high-grade/metastatic disease, high-dose chemotherapy and era of treatment, in promoting the occurrence of secondary malignancies.

Evolving of therapeutic strategies for CNS-PNET.

BACKGROUND: A protocol for the intensive treatment of non-cerebellar PNET (CNS-PNET) combining chemotherapy and radiotherapy was launched in 2000. Efforts were subsequently made to improve the prognosis and to de-escalate the treatment for selected patient groups. PROCEDURE: Twenty-eight consecutive patients were enrolled for a high-dose drug schedule (methotrexate, etoposide, cyclophosphamide, and carboplatin ± vincristine), followed by hyperfractionated accelerated CSI (HART-CSI) at total doses of 31-39 Gy, depending on the patient's age, with two high-dose thiotepa courses following CSI. After the first 15 patients had been treated, craniospinal irradiation (CSI) was replaced with focal radiotherapy (RT) for selected cases (non-metastatic and not progressing during induction chemotherapy). Eight of the 28 children received the same chemotherapy but conventionally fractionated focal RT at 54 Gy. RESULTS: The 5-year progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) rates were 62%, 53%, and 52%, respectively, for the whole series, and 70%, 70%, and 87% for the eight focally irradiated children. Residual disease and metastases were not prognostically significant. In children with residual disease, response to RT was significant (5-year PFS 59% vs. 20%, P = 0.01), while the total dose of CSI was not. There were three treatment-related toxic events. Relapses were local in seven cases (including two of the eight focally irradiated patients), and both local and disseminated in 2. CONCLUSIONS: This intensive schedule enabled treatment stratification for the purposes of radiation, thereby sparing some children full-dose CSI. Local control is the main goal of treatment for CNS-PNET.

Psychological and adjustment problems due to acquired brain lesions in pre-school-aged patients.

OBJECTIVE: To describe and compare psychological, behavioural and adjustment problems in pre-school patients with acquired brain lesions of different aetiology. METHODS: Three groups of patients with acquired brain lesions (14 patients post-TBI, 18 brain tumour survivors and 23 patients with vascular or infectious brain lesions), ranging in age between 24-47 months, received a psychological evaluation, including the Child Behavior Checklist for Ages 2-3 (CBCL) and the Vineland Adaptive Behavior Scales (VABS). RESULTS: About half of the total sample (47.2%) showed psychological and behavioural problems. Difficulties vary according to the aetiology of the brain lesions. Brain tumour survivors showed more marked internalizing problems, whereas children with vascular or infectious brain lesions scored higher on the CBCL externalizing scales. Children with traumatic brain injury reported intermediate scores on most of the CBCL scales. CONCLUSIONS: Psychological and behavioural difficulties are very common, not only among school-aged children and adolescents, but also among pre-schoolers with acquired brain lesions. The relevance and the impact of these difficulties must necessarily be considered when developing psychological treatment and rehabilitation plans and planning for social re-entry.

Randomized clinical trial on the effects of a computerized cognitive training for pediatric patients with acquired brain injury or congenital malformation.

Both acquired injuries and congenital malformations often cause lifelong disabilities in children, with a significant impact on cognitive abilities. Remote computerized cognitive training (CCT) may be delivered in ecological settings to favour rehabilitation continuity. This randomized clinical trial (RCT) evaluated the efficacy of an 8-week multi-domain, home-based CCT in a sample of patients aged 11-16 years with non-progressive acquired brain injury (ABI), brain tumor (BT) and congenital brain malformation (CBM). Following a stepped-wedge research design, patients were randomized into two groups: Training-first group, which started the CCT immediately after baseline assessment and Waiting-first group, which started the CCT after a period of time comparable to that required by the training (8 weeks). Post-training and long-term (6 months) changes were assessed. Both groups improved on visual-spatial working memory after the CCT, with benefits maintained after 6 months, while no other changes in cognitive or psychological measures were found. These findings suggest that a multi-domain CCT can generate benefits in visual-spatial working memory, in accordance with data from extant literature reporting that computer games heavily engage visuo-spatial abilities. We speculate that is tapping on the same cognitive ability with a prolonged training that may generate the greatest change after a CCT.

Long-term results of combined preradiation chemotherapy and age-tailored radiotherapy doses for childhood medulloblastoma.

To reduce the sequelae of craniospinal irradiation (CSI) in children under 10 (≥3) years old and to improve the prognosis for high-risk medulloblastoma in adolescents, we adjusted postoperative chemotherapy and CSI doses to patients' stage and age. From 1986 to 1995, 73 patients entered the study. Children under 10 and adolescents with metastases, residual disease (RD) or stage >T3 received postoperative IV vincristine and high-dose (HD) ± intrathecal (IT) methotrexate, while standard-risk adolescents were given IV vincristine and IT methotrexate. Chemotherapy was followed by CSI (19.8 Gy for children <10; 36 Gy for adolescents), with a 54-Gy posterior fossa boost. Maintenance chemotherapy with lomustine and vincristine was administered for a year afterwards. A total of 39 children were under 10 of whom 20 had metastases. Response to chemotherapy was recorded in 70%, but 5-year EFS and OS were only 48 and 56%, respectively. Results were significantly worse for metastatic cases, patients under 10, those with RD, and those staged without MRI (unavailable early in the study). Efforts to preserve survivors' quality of life did not pay off, and most patients over 30 still depended on their parents' income and had severe cognitive/endocrine disabilities. In conclusion, despite a very high response rate with this preradiation HD methotrexate schedule, the outcome for high-risk medulloblastoma patients did not improve (especially when lower CSI doses were used) and patients still developed severe morbidities.

Parent-child communication and psychological adjustment in children with a brain tumor.

BACKGROUND: Internalizing problems, anxiety, depression, withdrawal, and consequent social problems are frequently observed in children with brain tumors. The objective of this work is to describe the relationship between these psychological problems and the type of parent-child communication established about the disease. PROCEDURES: A group of 64 children surviving a brain tumor (aged 4-18 years) underwent psychological assessment by means of parent reports on the Child Behavior Checklist (CBCL) and the Vineland Adaptive Behavior Scales (VABS). A semi-structured interview with each child and their parents enabled us to classify the method of communication regarding the disease as "avoidance," "ineffective," and "effective." Demographic, clinical, and functional data relating to the disease were also collected. RESULTS: A significant relationship between the onset of Internalizing problems, withdrawal, anxiety-depression, and social problems and the presence of avoidance or ineffective communication about the disease was observed (P = 0.001, P = 0.001, P = 0.001, and P = 0.01, respectively). These psychological problems did not prove to be associated to demographic or clinical variables; however, they were found to be related to the children's residual functional problems. By contrast, the method of communication proved to be unrelated to clinical or functional variables, but it was associated to demographic variables such as sex and age at assessment. CONCLUSIONS: Effective (complete, truthful, consistent, comprehensible, gradual and continuous, and tailored) communication to the child about his/her condition proved to be associated with a better psychological outcome.

Visual Feedback and Virtual Reality in Gait Rehabilitation of Hemiparetic Children and Teenagers after Acquired Brain Injury: A Pilot Study.

Hemiparesis as a term refers to a neurological disorder that can be extremely variable, especially with regard to walking abilities. Few works have assessed the use of virtual reality and biofeedback in children and adolescents with hemiparesis. The aim of this study is to provide insights about the rehabilitation of hemiparetic children and teenagers with visual biofeedback in a virtual reality environment. Six hemiparetic subjects (mean age 13.13 years, age range (7-18), 4 males) received 20 personalized rehabilitation GRAIL (Gait Real-time Analysis Interactive Lab) sessions plus 20 sessions of traditional physiotherapy. After an initial evaluation of rehabilitation needs, training focused on gait pattern correction (GP), walking endurance (WE), or gross motor functions (GMFs). All subjects were assessed for their gait analysis by GRAIL, the Gross Motor Function Measure (GMFM), and the 6-Minute Walking Test (6MWT) before and after rehabilitation. All subjects reached their rehabilitation goals, save for one who showed reduced collaboration. In addition, 4 subjects reached a better GP, 3 subjects reported improvements in WE, and 2 subjects improved in GMF. This personalized training with visual biofeedback delivered in a VR setting appears to be effective in modifying motor control and improving gait pattern, in addition to resistance and functional activities, in subjects with hemiparesis.

The Influence of Socioeconomic Status (SES) and Processing Speed on the Psychological Adjustment and Wellbeing of Pediatric Brain Tumor Survivors.

(1) Background: The relationship between processing speed (PS) and psychological adjustment in the healthy population is well established, as is that between low socio-economic status (SES) and psychological distress. While PS is one of the most impaired functions in pediatric brain tumor survivors (PBTSs), previous research has demonstrated that low SES may be a predictor of increased psychosocial risk in PBTSs. Given the psychological adjustment difficulties observed in PBTS, in the current study we aimed to explore the relationship between SES and psychological functioning, considering the contribution of PS as a mediator. (2) Methods: demographic and clinical data of 80 children (age range: 4-17 y.o.) were retrospectively collected. Psychological measures were the parent-compiled versions of the Child Behavioral Checklist (CBCL) and the Strengths and Difficulties Questionnaire (SDQ). Mediation analysis models were performed on psychological measures with and without the inclusion of covariates. (3) Results: The influence of SES on the CBCL total index was mediated by PS. Furthermore, PS was found to have a mediating effect on the relationship between SES and internalizing problems but not on the relationship between SES and externalizing problems. (4) Conclusions: The results suggest that PS may be a rehabilitation target for the prevention of psychological distress and should be addressed especially for PBTSs who live in a disadvantaged situation.

The Use of Psychotropic Medication in Pediatric Oncology for Acute Psychological and Psychiatric Problems: Balancing Risks and Benefits.

Severe acute behavioral and emotional problems represent one of the most serious treatment-related adverse effects for children and adolescents who have cancer. The critical and severe nature of these symptoms often makes necessary the use of psychotropic drugs. A working group composed of experts in multiple disciplines had the task of creating an agreement regarding a management plan for severe acute behavioral and emotional problems (SABEPs) in children and adolescents treated for cancer. To obtain global information on the use of psychotropic drugs in pediatric oncology, the working group first developed and mailed a 15-item questionnaire to many Italian pediatric oncology centers. Overall, an evident lack of knowledge and education regarding the use of psychotropic medications for the treatment of SABEPs was found. Thus, by referring to an adapted version of the Delphi method of consensus and standard methods for the elaboration of clinical questions (PICOs), the working group elaborated evidence-based recommendations for psychotropic drugs in the pediatric oncology setting. Furthermore, based on a thorough multivariate analysis of needs and difficulties, a comprehensive management flow was developed to optimize therapeutic interventions, which allows more accurate and efficient matching of the acute needs of patients while guiding treatment options.

Feasibility and Acceptability of a Real-Time Telerehabilitation Intervention for Children and Young Adults with Acquired Brain Injury During the COVID-19 Pandemic: An Experience Report.

This study examined the feasibility and acceptability of a telerehabilitation intervention during the COVID-19 pandemic in a sample of children and young adults with Acquired Brain Injury (ABI). Thirteen patients and/or their families agreed to participate in the speech and neuropsychological telerehabilitation sessions. The treatment was synchronous, patient centered and aimed at improving specific abilities. Sessions were held twice a week over a 10-week period. Two questionnaires were completed both by parents and therapists to assess feasibility and acceptability. Neither technical issues nor clinical obstacles were found. The quality of the therapeutic relationship played a key role in the intervention. Synchronous telerehabilitation provided several advantages both for patients and therapists. Moreover, the patient centered intervention eased the burden of the caregivers at a time of high stress. The real-time telerehabilitation treatments were deemed suitable for children and young adults with ABI. Further studies are needed to support the use of telerehabilitation as an integral part of their standard care.

Processing Speed and Time since Diagnosis Predict Adaptive Functioning Measured with WeeFIM in Pediatric Brain Tumor Survivors.

(1) Background: Brain tumor (BT) survivors show difficulties in the acquisition of developmental milestones, related to academic achievement, vocational employment, social relationships, and autonomy. The skills underlying adaptive functioning (AF) are usually damaged in BT survivors due to the presence of the brain tumor, treatment-related factors, and other neurological sequelae. In this study, we aimed to explore the contribution of different cognitive factors in children with BT to AF, considering diagnosis-related variables. (2) Methods: Standardized cognitive assessment was undertaken and clinical information was collected from a retrospective cohort of 78 children with a BT, aged between 6 and 18 year old at the time of the assessment. Regression models were computed to investigate the influence of the selected variables on daily functional skills as measured by the Functional Independence Measure for Children (WeeFIM). (3) Results: The analyses showed that the main explanatory variables are processing speed and time since diagnosis. Other clinical variables, such as age at diagnosis and hydrocephalus, differentially influence functional skills according to distinct domains (i.e., self-care, mobility, and cognition). (4) Conclusions: The main explanatory variables of AF that emerged in our models point to a potential target of improving AF management in pediatric BT survivors.