Cognitive Late Effects Research Articles

Screening Cognition, Sleep, and Physical Activity in Pediatric Oncology Long-Term Follow-Up Care.

Children treated for pediatric cancer are at risk for cognitive late effects, as well as impairments in sleep and physical activity. The aim of the present study was to examine the psychometric properties of clinical screening of child- and caregiver-reported cognitive functioning, sleep, and physical activity and the relationship between cognitive functioning and health behaviors within a pediatric oncology long-term follow-up clinic. The study included a retrospective chart review of 99 caregivers and 80 children (8-17years old) who completed the Conners Short Form (parent only) and PROMIS cognitive functioning, sleep-related impairment, sleep disturbance, and physical activity scales at the child's annual long-term follow-up visit. Test statistics and T-tests were used to assess psychometrics of the PROMIS scales. Bivariate correlations were used to examine the relationship between cognitive function and health behaviors. The child- and parent-report, short-version PROMIS cognitive functioning, sleep, and physical activity scales demonstrated high internal consistency and inter-rater reliability. High convergent validity was observed between PROMIS cognitive functioning and Conners Short Form. Caregiver- and child-reported cognitive functioning and health behaviors were significantly related (p ≤ 0.042). The PROMIS short-version scales are reliable and valid measures for screening cognitive function and health behaviors in pediatric oncology long-term follow-up care. Further research examining the predictive validity and longitudinal utility of the PROMIS scales in survivors is warranted. There was a positive association between cognitive functioning and health behaviors in survivors, warranting further investigation to inform potential targets of intervention in long-term follow-up care.

Effect of Physical Activity on Physical and Mental Health in Young Cancer Patients and Survivors: A Systematic Review of RCTs and CCTs

Introduction Young cancer patients (YCP) face high risks of acute and long-term physical and mental health effects resulting from their malignancy and its treatment (Benzing et al., 2022; Siegwart et al., 2020). Physical activity (PA) is increasingly recognized as a strategy to address physical, mental, cognitive, and social challenges faced by YCP and survivors (Braam et al., 2016). This systematic review aimed to summarize findings from randomized controlled trials (RCTs) and clinical control trials (CCTs) evaluating the impact of PA interventions on physical and mental health outcomes in YCP and survivors. Methods A systematic search was conducted in APA PsycINFO, PubMed, SPORTDiscus, Web of Science, Embase, and Scopus. We examined RCTs and CCTs investigating PA interventions in children and adolescents with cancer, during or after treatment, that reported outcomes related to physical or mental health and/or quality of life. Two authors independently screened studies for inclusion, extracted data, and assessed the risk of bias. Results Of 1,164 articles screened, 32 RCTs and CCTs met eligibility criteria, involving 1,315 participants aged 4–19 years. Studies included inpatients (18), survivors (11), or both (2). Chronic PA interventions, such as aerobic, resistance, or combined motor-cognitive training, were implemented. All studies reported physical health outcomes, primarily focusing on cardiorespiratory fitness, muscle strength, and fatigue, while 18 studies assessed psychological outcomes, including depression and quality of life. Four studies objectively evaluated cognitive functions. Benefits were most frequently observed (>50%) for strength, fatigue, and self-efficacy, with no negative effects reported. Discussion/Conclusion Despite variability in session durations and intervention lengths, this review highlights the broad benefits of PA for YCP and survivors, with no indication of negative effects. Most studies have focused on physical and mental health outcomes (Braam et al., 2016), with limited attention to cognitive performance and motor ability, despite the high risk of cognitive late effects in this population (Krull et al., 2018). High-quality RCTs are needed to better understand the role of PA in motor and cognitive development among YCP and survivors. References Benzing, V., Siegwart, V., Spitzhüttl, J., Schmid, J., Grotzer, M., Roebers, C. M., Steinlin, M., Leibundgut, K., Everts, R., & Schmidt, M. (2021). Motor ability, physical self‐concept and health‐related quality of life in pediatric cancer survivors. Cancer Medicine, 10, 1860–1871. https://doi.org/10.1002/cam4.3750 Braam, K. I., van der Torre, P., Takken, T., Veening, M. A., van Dulmen‐den Broeder, E., & Kaspers, G. J. L. (2016). Physical exercise training interventions for children and young adults during and after treatment for childhood cancer. Cochrane Database of Systematic Reviews, 3, CD008796. https://doi.org/10.1002/14651858.CD008796.pub3 Krull, K. R., Hardy, K. K., Kahalley, L. S., Schuitema, I., & Kesler, S. R. (2018). Neurocognitive outcomes and interventions in long-term survivors of childhood cancer. Journal of Clinical Oncology, 36(21), 2181-2189. https://doi.org/10.1200/jco.2017.76.4696 Siegwart, V., Benzing, V., Spitzhuettl, J., Schmidt, M., Grotzer, M., Steinlin, M., Leibundgut, K., Roebers, C., & Everts, R. (2020). Cognition, psychosocial functioning, and health-related quality of life among childhood cancer survivors. Neuropsychological Rehabilitation, 32 (6), 922–945. https://doi.org/10.1080/09602011.2020.1844243

A - 145 Cognitive Disengagement Syndrome in ALL Survivor

Abstract Objective Cognitive disengagement syndrome (CDS), previously known as sluggish cognitive tempo (SCT), presents with symptoms like mind-wandering, hypoactivity, and mental fogginess. There is a relatively high prevalence (23.7%) of CDS in survivors of acute lymphoblastic leukemia (ALL), although the neuropathology remains poorly understood, potentially involving autonomic nervous system dysfunction. Cognitive late effects, including slowed speed, inattention and executive dysfunction can occur post-cancer treatment. This case highlights the need for regular assessment of CDS, particularly in the pediatric cancer population. Given the symptom overlap it is important to discuss onset, duration, and variability of symptom presentation to rule-in/out the role of cognitive late effects. Method “Alex,” a 14-year-old, B cell ALL survivor, was struggling academically nine years post-treatment. She and parents reported slowness, fatigue, trouble concentrating, and social withdrawal, despite medical stability. She received two years of psychotherapy for anxiety and depression without improvement. Results Alex had average intellectual and cognitive functioning, with mild executive dysfunction. Despite reported slowness in daily activities, processing speed was average. Parent and self-report forms indicated significant problems with executive functioning, somatic symptoms, and inattention. Parents indicated significant symptoms on the SCT scale. Alex’s cognitive profile suggested ADHD-I with features consistent with CDS. Conclusions Discrepancies between testing scores and daily life challenges were inconsistent with cognitive late effects. Her physical symptoms (e.g., fatigue, social withdrawal) did not improve with mood as expected with depression. Identifying these discrepancies and symptom timeline was crucial in diagnosing CDS and guiding interventions, leading to a sense of relief and direction for Alex and her family.

Dose-dependent cranial irradiation associations with brain structures and neuropsychological outcomes in children with posterior fossa brain tumors.

Posterior fossa irradiation with or without whole brain irradiation results in high doses of radiation to the thalamus, hippocampus, and putamen, structures critical to cognitive functioning. As a result, children with brain tumors treated with cranial irradiation (CRT) may experience significant cognitive late effects. We sought to determine the effect of radiation to those structures on neuropsychological outcome. Forty-seven children with a history of posterior fossa tumor (17 treated with surgery; 11 with surgery and chemotherapy; and 19 with surgery, chemotherapy, and CRT) underwent neuroimaging and neuropsychological assessment at a mean of 4.8 years after treatment, along with 17 healthy sibling controls. The putamen, thalamus, and hippocampus were segmented on each participant's magnetic resonance imaging for diffusion indices and volumes, and in the radiation treatment group, radiation dose to each structure was calculated. Performance on visuoconstruction and spatial learning and memory was lower in patient groups than controls. Volume of the thalamus, when controlling for age, was smaller in the patient group treated with CRT than other groups. Higher radiation doses to the putamen correlated with higher fractional anisotropy in that structure. Higher radiation dose to the hippocampus correlated with lower spatial learning, and higher dose to thalami and putamina to lower verbal and nonverbal reasoning. All children with posterior fossa tumors, regardless of treatment modality, had cognitive deficits compared to their sibling controls. Posterior fossa irradiation may affect thalamic volume and aspects of verbal and nonverbal cognitive functioning.

QOL-05. MEMANTINE FOR PREVENTION OF COGNITIVE LATE EFFECTS IN CHILDREN RECEIVING CRANIAL RADIATION THERAPY FOR FOCAL BRAIN TUMORS: A PILOT STUDY

Abstract BACKGROUND Childhood brain tumor survivors treated with cranial irradiation are at significant risk for cognitive late effects that negatively impact quality of life. Memantine (an NMDA receptor antagonist), taken during radiotherapy for brain metastases in adults, resulted in reduced cognitive declines. This is the first investigation of feasibility, acceptability, and preliminary efficacy of memantine for reducing cognitive late effects in children undergoing radiation therapy. METHODS In a randomized, double-blind, controlled trial (MEMCRT; NCT03194906) children took memantine (20 mg/d) or placebo for 12 weeks. During the medication phase, participants received weekly phone calls to assess adherence using pill counts and monitor side effects using the SAFTEE structured interview. At baseline, 6 weeks (end of radiation therapy), and 12 weeks (end of medication), participants completed a brief battery of cognitive measures. RESULTS 30 patients (age at irradiation=11.93±2.87; 47% male) were included; memantine (n=16) and placebo (n=14) groups did not differ in age, sex, race, socioeconomic status or baseline IQ (ps>.26). Study participation (71% of those approached) and medication adherence (88% completed 12 weeks, with 97% of medication taken) were high. Side effects were minimal (only one CTCAE≥ 3; headache in the placebo group) with no difference between groups in change in side effect severity from baseline to any medication week, across any symptom inquiry (ps>.23). At 12 weeks, Cohen’s d effect sizes (ES) indicate the memantine group had better performance on measures of processing speed (Cogstate Identification ES=.61), academic fluency (Woodcock Johnson-IV Reading Fluency ES=.45; Math Fluency ES=.81), and fatigue (PedsQL Multidimensional Fatigue Scale ES=.72). CONCLUSIONS Study findings indicate memantine used as a neuroprotectant during radiation therapy for children with focal brain tumors is feasible and acceptable, with preliminary evidence for better cognitive outcomes that require validation in a larger, definitive trial.

QOL-18. THE MODERATING ROLE OF SOCIAL VULNERABILITY IN THE RELATIONSHIP OF MATERNAL CAREGIVER CONDITION MANAGEMENT ABILITY AND TRANSITION READINESS OF THEIR YOUNG ADULT SURVIVORS OF PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND The transition into adulthood is a particularly vulnerable time for young adult survivors of pediatric brain tumors (YAS) due to tumor/treatment-related late effects. Reduced supportive resource access and social determinants of health (SDH) can exacerbate challenges, impacting caregiver condition management ability (CMA) and YAS transition readiness. This study’s aim was to evaluate the relationship between YAS cognitive late effects, caregiver CMA, and YAS transition readiness, and the moderating role of SDH for YAS and caregivers with condition-focused family management. METHODS Fifty-three maternal caregivers (93% white, 98% non-Hispanic) of YAS (Mage=22) reporting low CMA completed the Transition Readiness Assessment Questionnaire (TRAQ; 5 subdomains) and rated YAS cognitive late effect severity. Medical experts scored 1) cognitive medical sequelae (0-6 scale), and 2) the Pediatric Neuro-Oncology Rating of Treatment Intensity. Social Vulnerability Index (SVI) measured cumulative SDH using 16 factors across US Census residential zip code data. Pearson correlations and moderated mediation analyses in Process Macro were used. RESULTS Caregiver ratings were associated with overall transition readiness (r=-.38, p=.005), cognitive medical sequelae (r=.53, p<.001), and treatment intensity (r=.28, p=.039). Expert ratings were not related to transition readiness (ps>.05); therefore, only caregiver ratings were used in moderated mediation models. For overall transition readiness, managing medications, appointment keeping, talking with providers, and managing daily activities, the direct effects of caregiver ratings (ps>.05) and indexes of moderated mediation via CMA (ps>.05) were not significant. For tracking health issues, the direct effect of caregiver ratings (p=.085) was not significant, but the index of moderated mediation was significant (95%CI=.026;.315). CONCLUSIONS Only caregiver cognitive late effect ratings were helpful in explaining YAS overall transition readiness. The role of social vulnerability in CMA and transition readiness warrants further exploration. Empirically based transition readiness YAS programs targeting access to resources for families with more social vulnerability are needed.

21 Comparison of the NIH Toolbox Cognition Battery to Established Performance-Based Assessments in a Pediatric Cancer Setting

Objective:This study examines the clinical validity of the NIH Toolbox Cognition Battery measures in patients with oncological diagnoses and tumor predisposition syndromes, including Neurofibromatosis, Type 1 (NF1).Participants and Methods:Participants included 158 patients (61% male, 67% White) ages 3 to 25 years (M = 8.38, SD = 4.32) who underwent neuropsychological evaluation between 2019 and 2022. Patients with brain tumors (n = 50) and leukemias (n = 49) accounted for 2/3 of the sample. The remainder had solid tumors, lymphomas, or cancer predisposition syndrome. Forty-eight had a diagnosis of NF1. Performance-based measures of attention, executive functioning, and processing speed were administered as part of neuropsychological evaluations. Patients were administered between 1 to 4 NIH Toolbox Cognition measures, including Flanker Inhibitory Control and Attention Test (Flanker), Dimensional Change Card Sort Test (DCCS), Pattern Comparison Processing Speed Test (PCCS), and List Sorting Test. Parent-reported measures of attention and EF were also obtained. Z-scores were used to compare performance across measures that assessed equivalent constructs. The rates of weak performance (>1 SD below the mean) using Toolbox measures were compared to rates of weak performance on traditional neuropsychological measures (e.g., Digit Span), and rates of functional impairment (e.g., parent-reported concerns, ADHD diagnosis).Results:FSIQ, Coding, and NEPSY Inhibition correlated with all 4 Toolbox measures, while Digit Span correlated with List Sorting, DCCS, and Flanker. DCCS and PCCS correlated with verbal fluency measures. NF1 patients scored lower than non-NF1 patients on Flanker, F(1,126) = 13.01, p<.001 and DCCS, F(1,150) = 6.85, p = .01. Toolbox performance did not differ significantly by age group. Rates of identified weakness were relatively similar on Toolbox measures, some traditional measures, and parent-reported attention problems. In identifying those with and without weakness, the agreement between Flanker and other measures ranged from 52% (Auditory Attention) to 66% (Coding). Agreement between DCCS and traditional measures ranged from 47% (Letter Fluency) to 80% (Switching). For PCCS, concordance ranged from 45% (Semantic Fluency) to 69% (Switching). List Sorting had 80% agreement with Digit Span and Coding.List Sorting had the highest agreement with parent-reported attention problems (76%), EF problems (72%), and ADHD diagnosis (79%). There was relatively high concurrence between DCCS and ADHD diagnosis (69%) and parent-reported attention problems (60%) and EF problems (65%) and between Flanker and ADHD diagnosis (67%). PCCS had less agreement with functional outcomes, ranging from 49% for EF problems to 58% for attention problems and ADHD diagnosis. In comparison, Digit Span had 64% agreement for EF problems, 70% for attention problems, and 73% for ADHD diagnosis.Conclusions:The NIH Toolbox Cognition Battery can be used to identify neurocognitive weaknesses in pediatric oncology patients and provide clinically meaningful data. Evaluation of the Toolbox measures’ sensitivity to change over time is warranted, as monitoring the progression of cognitive late effects is particularly salient in cancer survivorship.

1 Ototoxicity and Cognitive Outcomes among Children Treated for Brain Tumors in Infancy

Objective:Treatment of childhood central nervous system (CNS) tumors can lead to sensorineural hearing loss (SNHL), with prior research indicating associations between SNHL and cognitive difficulties. Infants (0-3 years) treated for CNS tumors are at particular risk for neurocognitive deficits due to increased vulnerability of the developing brain and missed developmental opportunities secondary to prolonged treatment. This study expands upon existing research by examining the association between treatment-related SNHL and later neurocognitive outcomes among infants.Participants and Methods:Serial audiology and neurocognitive assessments were conducted as part of a prospective, multisite, longitudinal trial (SJYC07). Children with newly diagnosed CNS tumors were treated with chemotherapy, with or without focal proton or photon radiation therapy (RT). SNHL was dichotomized based on hearing in the better ear as present versus not present (Chang grade ≥1a vs. <1a). Neurocognitive assessments included intellectual functioning (IQ), and parent ratings of executive functioning and behavioral functioning. Demographic and clinical variables investigated included: sex, age at diagnosis (years), treatment type (chemotherapy only vs. chemotherapy + RT), risk group (low vs. intermediate vs. high), and socioeconomic status (SES, continuous). Logistic regression models were used to identify factors associated with SNHL. Change point longitudinal models were used to examine the effect of each covariate individually and the potential impact of SNHL on trajectories of neurocognitive outcomes.Results:Of 135 patients (median age at diagnosis= 1.5 years), 67% had mild-to-severe SNHL as defined by Chang grade ≥1a at last follow-up. SNHL occurred early after treatment with a 1-year cumulative incidence 63.0% ±4.3%. SNHL was associated with age at diagnosis (p <.001) but not sex, treatment exposure or study risk arm (p >.10). At pretreatment baseline, IQ was associated with age at diagnosis (older age= higher IQ) and SES (higher SES= higher IQ) with a change in the trajectory of IQ after SNHL (stable prior to SNHL and declined 1.46 points/year after SNHL), which was impacted by tumor location (patients with supratentorial tumors stable prior to SNHL and declined 2.84 points/year after SNHL; whereas, patients with infratentorial tumors increased 1.93 points/year prior to SNHL and were stable after SNHL). At pre-treatment baseline, adaptive functioning was associated with age at diagnosis (older age= higher skills) with a change in adaptive functioning after SNHL that varied by age. There was a change in trajectory of attention problems (stable before SNHL and worsening 1.39 points/year after SNHL). SNHL was not associated with parent report of emerging executive functioning.Conclusions:Children with brain tumors experience SNHL and cognitive difficulties early in treatment that can worsen over time. Younger age at diagnosis is associated with greater risk for SNHL and cognitive difficulties. Analyses of the time course between the emergence of SNHL and cognitive late effects suggests even mild SNHL is associated with a clinically signficant decline in IQ and attention problems. These findings have notable implications with respect to refining monitoring guidelines, informing modifications to treatment, advocating for interventions, and helping educate parents, teachers, and providers about the significant impact of mild SNHL.

B - 09 Neuropsychological Impacts and Cognitive Effects of Pediatric Leukemia Treatment.

The current study seeks to investigate the neuropsychological and cognitive late effects of pediatric Acute Lymphoblastic Leukemia (ALL) treatment. A search for peer-reviewed articles was conducted. Google Scholar was searched using keywords including neuropsychology, neuro-cognitive, neuropsychological effects, neuropsychological battery, neuropsychological impacts, cognitive effects, cognitive impacts, pediatric, pediatric leukemia, acute lymphoblastic leukemia treatment, bone marrow transplant, whole brain radiation, whole-body radiation, chemotherapy, cranial radiotherapy, health psychology, and neuropsychological testing. Articles were included if they discussed neuropsychology and ALL. Articles with non-human subjects and case studies were excluded from the study. Fifty-nine studies were included in the study. Treatments for ALL result in impairments in working memory, reduced processing speed, attention deficits, executive functioning deficits, visual-spatial and visuomotor weakness, fine motor weakness, deficits in delayed memory, an initial decline in performance IQ, and a delayed decline in verbal abilities such as attention and reading. The initial decline in performance abilities following a late decline in verbal abilities seen in patients who have undergone CRT may be due to structural changes in the white and gray matter following CRT treatment. Healthcare providers should attend to patients' cognitive complaints, particularly as they pertain to patients' ability to adhere to treatment recommendations and subsequently to their ability to resume attending school or social roles. As patient and parent complaints of cognitive compromise are associated with psychological distress and functional decline, cognitive complaints could justify further in-depth neuropsychological assessment to mobilize comprehensive supportive care or rehabilitative services.

Impaired neurocognitive functioning 3months following diagnosis of high-risk acute lymphoblastic leukemia: A report from the Children's Oncology Group.

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer diagnosis. Cognitive late effects develop in 20%-40% of ALL survivors, but the course of declines is unclear. The aim of this paper is to characterize cognitive functioning, and its association with patient-reported outcomes, early in treatment. A total of 483 children with high-risk ALL, aged 6-12years at diagnosis, consented to the neurocognitive study embedded in a prospective therapeutic trial, Children's Oncology Group (COG) AALL1131. A computerized neurocognitive battery (Cogstate) was administered 3months post diagnosis assessing reaction time, visual attention, working memory, visual learning, and executive functioning. Parent-reported executive functioning and patient-reported physical symptoms were also collected. Data from 390 participants (mean age at diagnosis=9.2years, 55.4% male) were obtained. Relatively few patients reported pain (16.0%) or nausea (22.6%), but a majority (68.5%) reported feeling at least some fatigue at testing. Mean Cogstate Z-scores were within normal limits across tasks; however, rates of impairment (Z-scores ≤ -1.5) for reaction time, working memory, visual learning, and visual attention were all higher than expected compared to the standardization sample. Patients reporting fatigue were significantly more likely to have impaired reaction time and visual attention compared to those reporting no fatigue. Findings support feasibility of computerized cognitive assessments and suggest higher-than-expected rates of impaired cognitive performance early during treatment for pediatric ALL, notably within 3months of diagnosis, suggesting intervention efforts may be indicated. These results also highlight acute factors that may impact reliability of "baseline" assessments conducted soon after diagnosis.

Processing efficiency in pediatric cancer survivors: A review and operationalization for outcomes research and clinical utility.

Childhood cancer and cancer-related treatments disrupt brain development and maturation, placing survivors at risk for cognitive late effects. Given that assessment tools vary widely across researchers and clinicians, it has been daunting to identify distinct patterns in outcomes across diverse cancer types and to implement systematic neurocognitive screening tools. This review aims to operationalize processing efficiency skill impairment-or inefficient neural processing as measured by working memory and processing speed abilities-as a worthwhile avenue for continued study within the context of childhood cancer. A comprehensive literature review was conducted to examine the existing research on cognitive late effects and biopsychosocial risk factors in order to conceptualize processing efficiency skill trends in childhood cancer survivors. While a frequently reported pattern of neurobiological (white matter) and cognitive (working memory and processing speed) disruption is consistent with processing efficiency skill impairment, these weaknesses have not yet been fully operationalized in this population. We offer a theoretical model that highlights the impacts of a host of biological and environmental factors on the underlying neurobiological substrates of cancer survivors that precede and may even predict long-term cognitive outcomes and functional abilities following treatment. The unified construct of processing efficiency may be useful in assessing and communicating neurocognitive skills in both outcomes research and clinical practice. Deficits in processing efficiency may serve as a possible indicator of cognitive late effects and functional outcomes due to the unique relationship between processing efficiency skills and neurobiological disruption following cancer treatment. Continued research along these lines is crucial for advancing childhood cancer outcomes research and improving quality of life for survivors.

1437P Does subjective cognitive impairment reflect objective cognitive impairment in cervical cancer survivors?

Cancer-related cognitive impairment (CRCI) has severe implications for quality of life and sosio-economic functioning in cervical cancer survivors (CCS). Neurophychological (NP) testing remains the gold standard for assessing cognitive late effects, but data on the association between subjective and objective CRCI in cervical cancer is scarce. This cross-sectional study aimed to examine frequency and severity of objective CRCI in CCS reporting significant subjective cognitive impairment (CI) and explore associations between subjective and objective CRCI.

INSP-07. Improving cognitive outcomes for children treated for cancer: moving beyond the cure

With improved survival rates, increasing numbers of childhood cancer survivors are living with long-term cognitive deficits that negatively impact their ability to attain important life milestones. Our collaborative research program has focused on characterizing cognitive outcomes associated with specific treatment modalities to inform modifications in front-line therapy. This line of investigation has demonstrated the negative cognitive impact of high radiation dose/large treatment volume, posterior fossa syndrome, treatment-related ototoxicity, and lower socioeconomic status (SES). Research-informed, treatment approaches under investigation include proton radiotherapy and hippocampal sparing irradiation, molecularly based risk-adapted therapy, surgical approaches with reduced risk of injury, and on-therapy otoprotectants, as well as identification of modifiable factors that are driving the protective effects of higher SES. Our research also strives to improve specification of cognitive deficits following treatment, at the behavioral and neural systems level, to identify targets for intervention. Study findings have revealed disease- and treatment- related alterations in neural systems supporting attention, working memory, and executive functions, as well as genetic factors that increase risk for cognitive late effects. We are now using sophisticated connectivity brain mapping with enhanced sensitivity to behaviorally-relevant changes in brain organization and sensitivity to intervention-based neuroplasticity to guide cognitive intervention development. A primary research focus moving forward is development of empirically validated interventions that prevent or mitigate cognitive late effects among childhood cancer survivors. Our studies have demonstrated the efficacy of stimulant medications, computerized cognitive training, and aerobic exercise for children treated for cancer, as well as the limitations to these approaches. Current investigations include use of neuroprotectant agents during radiotherapy, combining multiple interventions, interventions tailored to children undergoing treatment in infancy, and the use of virtual reality to increase intervention engagement. Our ultimate benchmark of success is ensuring children are not only cured of cancer but also experience a high quality of life.

ATRT-02. Neuropsychological function in infant atypical teratoid/rhabdoid tumor versus low-grade glioma survivors reflects tumor malignancy and multimodal treatment

BACKGROUND: Therapy of infants with brain tumors predisposes these patients to increased risks for cognitive sequelae, especially following radiotherapy. Neuropsychological outcome gains importance for those 40-60% of patients with an atypical teratoid/rhabdoid tumor (ATRT) who survive beyond 2 years. Still, reports on cognitive late-effects in children with ATRT are scarce compared to other pediatric brain tumor groups. We analyzed neuropsychological outcome for long-term ATRT-survivors registered in EU-RHAB and infant low-grade glioma (LGG) survivors from the SIOP-LGG 2004-study and LGG-registry. PATIENTS+METHODS: Age at diagnosis of both cohorts was 0-36 months. ATRT-patients (n=13) treated with up to 54Gy radiotherapy (median age 22 months (±7.1)) were evaluated with the “ATRT-Neuropsychology” tool based on SIOPE-BTG QoS-Group recommendations at median 6.8 years (±2.8) after diagnosis. LGG-patients (n=15) treated without radiotherapy (4/15 with chemotherapy) were analyzed with the German “Neuropsychological-Basic-Diagnostic” tool 5.2 years (±0.6) post-diagnosis. RESULTS: The ATRT- vs. LGG-cohorts were comparable for median age at diagnosis, sex-ratio and tumor-localization, though they differed slightly in median age at assessment (9.5/7.2 years (±2.5/1.1)). Results of age-appropriate tests showed increased impairments for ATRT-patients in fluid intelligence (FI) (p=.006, d=1.214) and in visual-spatial processing (VSP) (p<.001, d=2.233) compared to LGG-patients. The median for neuropsychological test results of ATRT-patients spanned from considerably below the normal to the lower normal range (median=65-90), while results of LGG-patients were mostly in the lower normal range (median=83-103). Results for psychomotor speed abilities (PMS) were distinctly below the norm for both patient groups (p=.002-.007). CONCLUSION: Infant ATRT- and LGG-patients develop significant impairments in PMS abilities following multimodal treatment. Long-term survivors of ATRT suffer from additional FI and VSP deficits. Our data suggest that high malignancy requiring multimodal treatment determines the inferior cognitive outcome for the ATRT-cohort. Long-term neuropsychological monitoring (and treatment options) should be implemented as standard of care in ATRT- and LGG-trials.

INSP-11. Patient-centered monitoring and care of cognitive late effects in pediatric brain tumor survivors with and without Cerebellar Mutism Syndrome (CMS).

Abstract Risks of cognitive late effects in children with brain tumors is well-established. However, group heterogeneity may limit generalizability and result in inadequate neurocognitive monitoring and care. Children with CMS have unique long-term cognitive risks and current knowledge may not adequately describe their experience or needs. The establishment and implementation of patient-centered, empirically-derived assessment of cognitive change following tumor diagnosis and treatment is a novel, precision-based approach to patient care. METHODS: 30 patients diagnosed with posterior fossa tumor who had at least 2 neuropsychological evaluations were included. Primary outcomes were processing speed (Wechsler PSI) and working memory (WMI). Secondary outcomes were verbal and nonverbal intellect. Reliable change indices (RCIs) were computed (Chelune et al., 1993). Using an 80% CI, 10% would be expected to decline, while 90% would stay stable or improve. RESULTS: Mean age in the full sample was 9.2 (3.32) years at T1 and 13.0 (4.11) years at T2, with an average of 2.7 (2.58) years between assessments. Males made up 56.7% of the sample. Five of the 30 (17%) were CMS+. The CMS+ patients were similar in age to CMS- patients, were predominantly male (80%), and mostly received photon radiation (60%). The full sample showed greater prevalence of declining verbal (21%), spatial (58%) and working memory (29%) functions than the expected (10%). The CMS+ group had higher rates of processing speed (50% v. 7%) and working memory (50% v. 27%) declines than the CMS- group. In contrast, the CMS- group appeared to show more prevalent declines in spatial reasoning than the CMS+ group (67% v. 33%). CONCLUSIONS: There appear to be unique domains impacted in the CMS+ group, which can convey specific long-term outcomes specific to this subgroup of patients. These results highlight the utility of individualized, empirically-driven analysis of change in cognitive functioning in this patient population.

Long-Term Follow-Up of Pediatric CNS Tumor Survivors-A Selection of Relevant Long-Term Issues.

Introduction: Survivors of pediatric central nervous system (CNS) tumors are at high risk for late effects and long-term morbidity. The quality of survival became increasingly important, as advances in diagnostics, multimodal treatment strategies, and supportive care have led to significant increases in long-term survival. Aim: This review aims to provide a global overview of the potential late effects and long-term follow-up care of CNS tumor survivors, directed to trainees and practitioners with less targeted training in pediatric oncology. Late effects in CNS tumor survivors: A specific focus on CNS tumor survivors relies on cognitive and psychosocial late effects, as they may have an impact on education, professional career, independent living, and quality of life. Further important late effects in CNS tumor survivors include endocrine, metabolic, cardiovascular, and cerebrovascular diseases. Conclusions: Comprehensive long-term follow-up care is essential for pediatric CNS tumor survivors to improve their quality of survival and quality of life. An individualized approach, taking all potential late effects into account, and carried out by an interdisciplinary team, is recommended, and should continue into adulthood. Existing recommendations and guidelines on long-term follow-up care guide the multidisciplinary teams.

A-170 Socioeconomic Status as a Predictor of Fine Motor and Graphomotor Outcomes in Patients with Pediatric Brain Tumor

Abstract Objective As the field of neuropsychology strives to provide equitable care among diverse and disadvantaged populations, disparities in treatment and long-term outcomes continue to disproportionately impact individuals of lower socioeconomic status (SES). Motor deficits are common following pediatric brain tumor (PBT) diagnoses. However, while the relationship between SES and cognitive outcomes in this population is well documented, the role of SES in predicting more basic motor outcomes is not yet understood. This retrospective cross-sectional study was designed to determine the impact of SES on fine motor and graphomotor outcomes in PBT patients to ensure appropriate interventions and accommodations for those at higher risk. Method 225 patients with PBT (52.9% male; $ \overset{-}{\textrm{x}} $ age = 12 yrs; SD = 5.3 yrs) underwent neuropsychological evaluation, including assessment of graphomotor speed/coordination, visual-motor integration, and fine motor dexterity. Estimated median household income was used as a proxy for SES ($ \overset{-}{\textrm{x}} $=$71,543; SD = $23,480). Linear regression analyses were used to explore the role of SES in predicting motor outcomes. Results Lower SES predicted poorer graphomotor speed, F(1,96) = 5.205, p = 0.013, graphomotor coordination, F(1,60) = 3.890, p = 0.027, visual-motor integration, F(1,88) = 8.116, p = 0.003, and fine motor dexterity, F(1,166) = 3.755, p = 0.027. All analyses were significant even after implementing false discovery rates. Conclusions Consistent with lower SES predicting poorer cognitive late effects, SES also plays a role in motor-related outcomes of PBT. Unfortunately, lower SES is also associated with barriers in accessing formal evaluations and services required to mitigate such deficits. Therefore, patients with lower SES should be considered higher risk and receive interventions and accommodations even in the absence of formal assessment to prevent delays in care.

Cognitive late effects following allogeneic stem cell transplantation in haematological cancer patients

The objective of this exploratory study was to determine the presence and correlates of self-reported cognition in a sample of haematological cancer patients who had undergone allogeneic stem cell transplantation (SCT). Haematological cancer patients (n=30) who had undergone allogeneic SCT between one and fiveyears previously and age-matched control participants (n=30) completed questionnaires assessing cognition, affect, sleep quality and fatigue and an assessment of premorbid IQ. Patients reported significantly poorer perceived cognitive ability (d=1.12) and greater perceived cognitive impairment (d=0.96) than controls. Lower fatigue was significantly associated with greater perceived cognitive ability (r=0.75 patients and controls) and less perceived cognitive impairment (r=0.80 patients; r=0.57 controls). Interestingly, depression was significantly correlated with perceived cognitive ability in the control group only (r=0.80). Hierarchical multiple regressions showed that fatigue was a significant predictor of perceived cognitive ability in patients, accounting for 56% of the variance. This study established that self-reported cognitive ability and cognitive impairment was significantly poorer in haematological cancer patients than controls. Furthermore, fatigue was significantly associated with perceived cognitive ability in patients. Future research should focus on identifying interventions that target fatigue in allogeneic SCT recipients in order to improve quality of life throughout survivorship.

Cortical Morphometry and Its Relationship with Cognitive Functions in Children after non-CNS Cancer

ABSTRACT Background: Childhood cancer survivors (Ccs) are at risk for cognitive late-effects, which might result from cortical alterations, even if cancer does not affect the brain. The study aimed to examine gray and white matter volume and its relationship to cognition. Methods: Forty-three Ccs of non-central nervous system cancers and 43 healthy controls, aged 7–16 years, were examined. Cognitive functions and fine motor coordination were assessed and T1-weighted images were collected for voxel-based morphometry. Results: Executive functions (p = .024, d = .31) were poorer in Ccs than controls, however still within the normal range. The volume of the amygdala (p = .011, ŋ2 = .117) and the striatum (p = .03, ŋ2 = .102) was reduced in Ccs. No significant structure–function correlations were found, neither in patients nor controls. Conclusion: Non-CNS childhood cancer and its treatment impacts on brain structures relevant to emotion processing.

Cancer Survivors’ Experience of Health-Related Quality of Life Six to Eight Years after Diagnosis—A Qualitative Study

Background: Health-related quality of life (HRQOL) is affected for many years following cancer treatment. With an increasing number of long-term cancer survivors, HRQOL will be a key concern in the future. There is a lack of qualitative studies investigating long-term cancer survivors’ needs and experience of late effects and HRQOL. Objective: The aim of this sub-study is to describe cancer survivors’ own experience of late effects affecting HRQOL six to eight years after diagnosis. Methods: We used a qualitative methodology with semi-structured focus group interviews to gain an in-depth understanding of participants’ experience of their HRQOL. Interviews were audio-recorded, transcribed and analyzed using thematic analysis. Results: All of the participants reported late effects at some point after the treatment. Some of the experienced late effects had improved over the years, while the late effects mentioned in this article were still prominent six to eight years after the diagnosis. They described, among others, late effects such as reduced physical strength, cognitive difficulties, lack of energy and increased sensitivity. The participants described the late effects as bearable, but still affecting their HRQOL by limiting their activity level, their ability to work and their social interactions. Conclusions: Six to eight years post-treatment, cancer survivors still experienced physical and cognitive late effects affecting their HRQOL. The findings indicate that some late effects affect HRQOL for a long time. To prepare cancer survivors for post-treatment life and to optimize their HRQOL, they need information concerning potential late effects before, during and after cancer treatment, as well as support services and follow-up in the municipalities.