Tumor Survivors Research Articles

P-372 Reproductive ability in survivors of childhood, adolescent, and young adult testicular tumors

Abstract Study question There is little comprehensive fertility evaluation in testicular tumors. Summary answer Our study provides evidence that sexual dysfunction and infertility represent the major persisting side effects with testicular tumor patients. What is known already Testicular cancer, although accounting for 1% of all cancers, is the most common cancer in men of reproductive potential with a peak incidence in men between the ages of 15-35, with more than 95% of the patients being cured.There are many researches on semen quality in testicular cancer. Study design, size, duration We performed a retrospective study by collecting 126 records of testicular cancer patients who attempted sperm banking in the Human Sperm Bank, West China Second University Hospital, Sichuan University between 2011 and 2022. Participants/materials, setting, methods Semen samples were collected by masturbation after 2–7 days of sexual abstinence. While a few of the patients had a longer period of sexual abstinence than one week, due to emergency treatment (data not shown). All samples were allowed to liquefy at 37 °C for 60 min and were then assessed according to World Health Organization protocols (WHO, 1999, 2010). Main results and the role of chance Semen quality and hormone levels before chemotherapy/radiotherapy In our study, we compare semen samples before and after orchiectomy, no differences in semen analysis were observed between pre-and post-orchiectomy groups. Semen quality after cancer treatment: type of treatment Total sperm number worsened significantly at T3(T6, 6 months after the end of treatment), T6 compared to baseline (T0, before beginning cancer treatment) and returned to near-baseline values at T24 in Carboplatin 2 cycles and EP/BEP 2-4 cycles groups. Moreover, Serum LH and FSH was increased at T3, T6 compared at T0. Sexual Functioning The BFSI (Brief Male Sexual Function Inventory) is a validated self-report measure of sexual functioning. We compared BSFI scores before and after orchiectomy, no differences were observed in sexual drive, sexual erection, sexual ejaculation, DEE (drive, erection, ejaculation) problems and sexual satisfaction between pre-and post-orchiectomy groups. Chemotherapy/radiation group significantly fewer sexual satisfaction problems compared with untreatment/surgery group. Fertility outcome Fertility data were available for 88 patients. 65 (73.9%) had no children, for various reasons (young age, financial reasons, marital status), 6 (6.8%) already had at least one child prior to their cancer diagnosis. Seventeen patients (19.3%) wanted children, but only 11 of these succeeded in achieving fatherhood, through natural fertility (8 patients) or ART (3 patients). Limitations, reasons for caution Small sample size, and the follow-up was not long enough. Wider implications of the findings We analyzed semen parameters, hormone levels, sexual functioning, fertility outcome for testicular cancer patient, both before diagnosis and after treatment, with the aim to provide practical recommendations. Trial registration number not applicable’

Motor and sensory impairment in survivors of childhood central nervous system (CNS) tumors in the St. Jude Lifetime Cohort (SJLIFE).

Survivors of childhood central nervous system (CNS) tumors can develop motor and sensory impairment from their cancer and treatment history. We estimated the prevalence of motor and sensory impairment in survivors compared with controls through clinical assessment and identified associated treatment exposures and functional, quality of life (QOL), and social outcomes. Survivors of childhood CNS tumors from the St. Jude Lifetime Cohort (n = 378, median [range] age 24.0 [18.0-53.0] years, 43.4% female) ≥5 years from diagnosis and controls (n = 445, median [range] age 34.0 [18.0-70.0] years, 55.7% female) completed in-person evaluation for motor and sensory impairment using the modified Total Neuropathy Score. Impairment was graded by modified Common Terminology Criteria for Adverse Events. Multivariable models estimated associations between grade ≥2 motor/sensory impairment, individual/treatment characteristics, and secondary outcomes (function by Physical Performance Test, fitness by physiologic cost index, QOL by Medical Outcomes Survey Short Form-36 physical/mental summary scores, social attainment). Grade ≥2 motor or sensory impairment was more prevalent in survivors (24.1%, 95% Confidence Interval [CI] 19.8%-29.4%) than controls (2.9%, CI 1.4-4.5%). Among survivors, in multivariable models, motor impairment was associated with vinca exposure <15 mg/m2 versus none (OR 4.38, CI 1.06-18.08) and etoposide exposure >2036 mg/m2 versus none (OR 12.61, CI 2.19-72.72). Sensory impairment was associated with older age at diagnosis (OR 1.09, CI 1.01-1.16) and craniospinal irradiation versus none (OR 4.39, CI 1.68-11.50). There were lower odds of motor/sensory impairment in survivors treated in the year 2000 or later versus before 1990 (Motor: OR 0.29, CI 0.10-0.84, Sensory: OR 0.35, CI 0.13-0.96). Motor impairment was associated with impaired physical QOL (OR 2.64, CI 1.22-5.72). In survivors of childhood CNS tumors, motor and sensory impairment is prevalent by clinical assessment, especially after exposure to etoposide, vinca, or craniospinal radiation. Treating motor impairment may improve survivors' QOL.

Exploring Memory Systems After Pediatric Posterior Fossa Tumor: From Memory Profile Comparisons in Nonirradiated Versus Irradiated Patients to Episodic Memory Tests Capable of Detecting Radiation-induced Hippocampal Damage

AimsPediatric posterior fossa tumor (PFT) survivors experience long-term cognitive sequelae, including memory disorders, for which irradiation is one of the main risk factors. The aims of the present study were to (1) explore the profile of impairment in episodic, semantic, working and procedural memory systems in irradiated versus nonirradiated PFT survivors, and (2) test whether an autobiographical questionnaire and a two-phase ecological test (Epireal) assessing episodic memory are more sensitive to radiation-induced hippocampal damage than commonly used tests. Materials and methodsA total of 60 participants (22 irradiated PFT survivors, 17 nonirradiated PFT survivors, and 21 controls) were included in the prospective IMPALA study. They all underwent a broad battery of tests assessing the different memory systems in two 2-day sessions 3 weeks apart. We performed between-groups comparisons and analyzed impairment profiles, using -1.65 SDs as a cut-off. For irradiated patients, correlations were calculated between mean radiation doses to key brain structures involved in memory (hippocampus, cerebellum, and striatum) and corresponding memory scores. ResultsPBT survivors performed significantly more poorly than controls (p < 0.001) on conventional tests of episodic, semantic and working memory: 64% of irradiated patients and 35% of nonirradiated patients had a deficit in at least two memory systems, with episodic memory impairment being more specific to the irradiated group. Epireal had a larger effect size than the other episodic memory tests, allowing us to detect deficits in a further 18% of irradiated patients. These deficits were correlated with the mean radiation dose to the left hippocampus. ConclusionMemory impairment is a frequent long-term cognitive sequela in PFT survivors, especially after radiation therapy. New ecological tests of episodic memory that are more sensitive to radiation-induced deficits than conventional tests could yield specific markers of the toxicity of medial temporal lobe irradiation.

QOL-10. PHYSICAL ACTIVITY LEVELS AND PATTERNS IN SURVIVORS OF CHILDHOOD CENTRAL NERVOUS SYSTEM TUMOURS

Abstract BACKGROUND Engaging in regular physical activity (PA) has multiple positive health benefits and for survivors of childhood cancer can additionally result in reduced severity of late-effects. There is a lack of objectively measured PA data in survivors of childhood central nervous system (CNS) tumours. The aims of this study were to objectively measure PA levels and patterns in survivors of childhood CNS tumours and to determine whether survivors were meeting the World Health Organisation (WHO) recommended PA guidelines of 60 minutes of moderate to vigorous intensity physical activity (MVPA) daily. METHODS Survivors of childhood CNS tumours aged between 6-17 years, between 3 months and 5 years post treatment, were provided with Actigraph GT3X accelerometers to assess their PA patterns over a seven day recording period. RESULTS Twenty-six participants were recruited with a mean age of 12.75 (SD 3.29) years. Participants met the WHO PA guidelines for a mean of 3.18 (SD 2.56) days during the assessment week. Participants spent a mean daily time of 591.77 (SD 146.91) minutes in sedentary behaviour and 129.45 (SD 54.14) minutes in light intensity PA. A significant association was found between PA and age (p&amp;lt;0.001, CI[-8.48, -3.05]), child participants engaged in significantly less sedentary time and significantly more MVPA daily than adolescent participants. No significant differences in PA patterns were identified between participants in early survivorship versus those in late survivorship (≥ 2 years post treatment), (p=0.095 – p=0.513). CONCLUSIONS The majority of survivors of childhood CNS tumours do not meet the WHO recommended daily PA guidelines and lead significantly sedentary lives. PA patterns differed significantly between child and adolescent participants. Further research is required on interventions to support engagement in PA particularly for adolescent survivors of CNS tumours, with a focus on how this can be implemented into clinical practice.

NURS-05. CATALYZING AND INFORMING THE DEVELOPMENT OF MORE COMPREHENSIVE AND ACCESSIBLE PROGRAMS FOR CAREGIVERS OF YOUNG ADULT SURVIVORS OF CHILDHOOD BRAIN TUMORS

Abstract BACKGROUND The chronic and intensive care needs of young adult survivors of childhood brain tumors are most often addressed by their maternal caregivers with limited, specific psychosocial or other programs to reduce caregiving demands and enhance their family management. Using a social ecological perspective, the purpose of this study was to catalyze and inform the development of more comprehensive and accessible programs for caregivers of young adult survivors of childhood brain tumors. METHODS Semi-structured interviews were conducted with 21 maternal caregivers, 6 post baccalaureate students/professional coaches for a problem-solving intervention for maternal caregivers, and 16 neuro-oncology clinical experts using interview guides tailored to their roles and constructed based on the Consolidated Framework for Implementation Science. Qualitative. Interview data were analyzed using content analysis. RESULTS Barriers included: need for internet connected devices (microsystem level); lack of care matched to their identified needs (mesosystem); poor tracking of long-term survivors and lack of survivorship psychosocial services (macrosystem); and lack of supportive health care policies and funding mechanisms for individuals and organizations (exosystem). Facilitators included: web-based platform accessible to the individuals and population (microsystem); widespread acknowledgement regarding gaps in survivorship psychosocial care (mesosystem); partnerships with survivors of childhood brain tumors, caregivers, and organizations that treat them (macrosystem); and dissemination among childhood brain tumor treatment/survivorship programs, healthcare systems, and community organization and endorsement from them (exosystem). CONCLUSIONS Multilevel approaches that address barriers and facilitators for improving health equity for maternal caregivers of young adult survivors of childhood brain tumors incorporate the design and dissemination of accessible, web-based programs designed in partnership with survivors, caregivers, and organizations to build care matched to need, as well as organizational, political, and community advocacy.

NURS-03. NEED FOR PROGRAMS FOCUSING ON CAREGIVERS FOR YOUNG ADULT SURVIVORS OF CHILDHOOD BRAIN TUMORS

Abstract BACKGROUND The physical, emotional, social, developmental, and economic risk experienced by survivors of childhood brain tumors and their families is well documented, as is the acceleration of those risks as survivors transition into young adulthood. Further, the impact of the lack of services in the community is compounded by insufficient investigation of interventions to support survivor functioning and their caregiver’s management of their medical and psychosocial needs.The purpose of this study was to describe maternal caregivers’ perspectives about key components of potential interventions to support maternal caregivers of young adult survivors of childhood brain tumors. METHODS Data were obtained from 21 at-risk maternal caregivers (based on the Family Management Style Measure) of young adult survivors aged 18-29 years old who were not partnered, were presently living at home, and who participated in a pilot randomized trial Training in Problem Solving (TIPS) for Caregiver of Young Adult Survivors of Childhood Brain Tumors. Caregivers were interviewed using a semi-structured qualitative interview guide constructed using the Consolidated Framework for Implementation Science. Codes, categories, then themes were identified by means of directed content analysis. RESULTS All caregivers agreed these services were absent and the most effective timing would be at the transition to survivorship with ongoing follow-up. Key components of potential interventions identified by maternal caregivers were skill-building, motivational interviewing to increase readiness to change long-standing patterns of family management, use of validation of their efforts as parents and caregivers to build confidence in trying new approaches and shifting their perspectives on ongoing caregiving for a childhood brain tumor survivor to find hope in even small changes. CONCLUSIONS Caregivers endorsed the importance of targeted psychosocial support throughout survivorship for caregivers within the context of their family, facilitating their roles as both parents and caregivers to young adult childhood brain tumor survivors.

QOL-33. CANCER WORRY AND PSYCHOPATHOLOGICAL SYMPTOMS IN ADOLESCENTS AND YOUNG ADULTS SURVIVORS OF PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Adolescent and young adult (AYA) survivors of pediatric brain tumors may experience cancer-related worries, defined as concerns about relapse and late effects of treatment. Late psychological effects include psychological distress, depression, immaturity, and poor development of social skills. Furthermore, pediatric brain tumor survivors (PBTS) are more vulnerable to developing long-term neurocognitive and psychosocial consequences compared both to the general population and survivors of other types of childhood cancer. The purpose of the study was to identify the presence of cancer worry and psychopathological symptoms in AYA survivors of pediatric brain tumors. METHODS AYA survivors were assessed using the Cancer Worry Scale and Child Behavior Checklist questionnaires. Neurocognitive evaluation was performed using the age-appropriate Wechsler Scale. RESULTS Among 22 AYA survivors (M =14; F=8), the diagnosed tumor types were: germ cell tumor (10/22), low-grade glioma (4/22), embryonal tumor (3/22), high-grade glioma (2/22), craniopharyngioma (2/22), and mesenchymal tumor of the meninges (1/22). Survivors received the assessment at a median age of 20.2 years (range 13.6-28.7), with a median of 92 months after diagnosis. Cancer worry was reported in 50% of patients. The psychological evaluation showed clinical levels of internalizing problems in 17% and externalizing problems in 8%. Depressive and anxiety problems were reported in 25% of our cohort. Neurocognitive assessment demonstrated an average tIQ of 104. CONCLUSIONS As reported in the literature, cancer worry can influence the psychosocial adjustment process, alter self-image, and influence lifestyle decisions in PBTS. These concerns can affect their life prospects and their ability to successfully complete developmental tasks. Therefore, these issues must be early identified to prevent, through targeted psychosocial interventions, the onset of troubles in having romantic relationships, finishing school, entering the job market, and obtaining a good quality of life.

QOL-31. NEUROPSYCHOLOGICAL FUNCTIONING AND QUALITY OF LIFE IN INFANT AT/RT SURVIVORS: FOCUS ON FLUID INTELLIGENCE AND VISUAL PROCESSING

Abstract BACKGROUND Understanding the long-term cognitive sequelae in infant brain tumor survivors remains incomplete, particularly regarding the impact of tumor type, multimodal treatment, and other patient-related factors. This retrospective analysis explores neuropsychological and quality of survival (QoS) outcomes in survivors of atypical teratoid/rhabdoid tumors (AT/RT) and extracranial malignant rhabdoid tumors of soft tissues (eMRT) and kidneys (RTK), all treated within the same framework. Neuropsychological data from children with AT/RT were compared to data from children with non-irradiated low-grade glioma (LGG). METHODS Patients (0 - 36 months at diagnosis) underwent various treatments, including radio-chemotherapy for AT/RT (n = 13) and eMRT/RTK (n = 7), chemotherapy only for LGG (n = 4) and eMRT/RTK (n = 1), or observation for LGG (n = 11). Neuropsychological evaluations were conducted at a median of 6.8 years (AT/RT), 6.6 years (eMRT/RTK), and 5.2 years (LGG) post-diagnosis. RESULTS Impairments were observed for all tumour types. Patients with AT/RT exhibited impairments in fluid intelligence (p =.041; d = 1.11) and visual processing (p =.001; d = 2.09) when compared to LGG-patients. Both groups demonstrated deficits in psychomotor speed and attention abilities (p &amp;lt;.001–.019; d = 0.79–1.90). Diagnosis significantly predicted cognitive outcomes, whereas gender and age-related variables did not. QoS outcomes for all rhabdoid patients indicated lower scores in psychosocial functioning (p =.023; d = 0.78) and quality of life (p =.006; d = 0.79) compared to healthy controls. CONCLUSIONS Infant rhabdoid tumor survivors experience cognitive and quality-of-life sequelae. Patients with AT/RT are especially vulnerable to impairments in fluid intelligence and visual processing, while infant LGG-patients without radiotherapy demonstrated comparable deficits in psychomotor and attention abilities. Close monitoring of neuropsychological and quality of life outcomes is crucial for early onset and multimodal treatment.

QOL-34. POST-TRAUMATIC GROWTH AND COPING STRATEGIES AMONG ADOLESCENTS AND YOUNG ADULTS SURVIVORS OF PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Pediatric brain tumor survivors (PBTS) often report late psychosocial effects following the disease and the treatments. Recent studies have shown that PBTS can experience growth in their personal and interpersonal dimensions and develop coping strategies that allow them to deal with the stress caused by cancer diagnosis and subsequent therapies. This study aimed to describe post-traumatic growth (PTG) experiences and coping strategies among adolescents and young adults (AYA) survivors of pediatric brain tumors. METHODS AYA survivors were assessed using Post-Traumatic Growth Inventory (PTGI) and Coping Inventory for Stressful Situations (CISS) questionnaires. They received evaluation at a median age of 20.2 years (range 13.6-28.7), with a median of 92 months from diagnosis. RESULTS Among 22 AYA survivors (M =14; F=8), the diagnosed tumor types were: germ cell tumor (10/22), low-grade glioma (4/22), embryonal tumor (3/22), high-grade glioma (2/22), craniopharyngioma (2/22), and mesenchymal tumor of the meninges (1/22).The domains of PTG in which positive changes were most frequently reported were Personal Strength (25%), Appreciation for Life (25%), and New Possibilities (23%). The less impacted domain was Spiritual Growth (9%). As regards the most adopted coping style, 38% showed higher values in the Distraction scale, 31% in the Task-Oriented scale, 15% in the Avoidance scale, and 15% in the Social Diversion scale. CONCLUSIONS PTG and coping are important indicators of psychosocial adaptation to difficult or stressful events. To develop specific interventions that enhance PTG, it is essential to understand which factors influence growth in PBTS. Our preliminary data show that all AYA survivors report PTG after treatments, at least in some domains. Further analysis is needed to identify which coping styles may influence the development of PTG.

QOL-14. EPILEPTIC SEIZURES, ANTI-SEIZURE MEDICATIONS, AND NEUROCOGNITION IN SURVIVORS OF PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Younger age at diagnosis and cranial radiation therapy are associated with neurocognitive late complications in survivors of pediatric brain tumors (PBT). Less is known about the association between neurocognition and epileptic seizures, with the latter affecting 27% of 5-year survivors. This study aimed to explore whether epileptic seizures exacerbate neurocognitive late complications beyond treatment and demographic factors. METHODS Fifty-nine survivors of PBT who had experienced at least one epileptic seizure, and a control group of survivors matched on sex, age at diagnosis, and cancer treatment, all diagnosed at Skåne University Hospital, were included in the study. Demographic and clinical variables, along with neurocognitive measures of verbal and non-verbal reasoning, cognitive processing speed, working memory, and cognitive flexibility were collected from medical records. Neuropsychological scores, assessed on average 3.68 years after diagnosis, were transformed into z-scores employing age-adjusted norms (m=0, sd=1). Generalized linear models, controlling for increased intracranial pressure at diagnosis and tumor localization, were used to analyze the association between epileptic seizures, cumulative use of anti-seizure medications (ASM), and neurocognition. RESULTS Experiencing any type of epileptic seizures was associated with reduced processing speed (β = -0.91z, p&amp;lt;0.01) and cognitive flexibility (β =-1.05z, p&amp;lt;0.01). Treatment with one ASM was associated with reduced cognitive processing speed (β =-0.81z, p=0.03), and treatment with two or more ASM was associated with lower scores on measures of non-verbal reasoning (β =-0.81z, p&amp;lt;0.01), working memory (β =-0.77z, p=0.01), processing speed (β=-1.26z, p&amp;lt;0.01), and flexibility (β =-1.54z, p&amp;lt;0.01). CONCLUSIONS Epileptic seizures and treatment with ASM were both associated with neurocognitive late complications. Optimal seizure management presents a potential modifiable factor for reducing cognitive burden in survivors of PBT.

QOL-24. TREATMENT- AND TIME-RELATED IMPACT ON LONG-TERM NEUROCOGNITIVE OUTCOMES IN ADULT SURVIVORS OF A PEDIATRIC BRAIN TUMOR

Abstract Treatment for pediatric brain tumors has been associated with the risk of developing long-term neurocognitive impairment. However, it is not well understood which neurocognitive profiles exist within this population. We investigated neurocognitive functioning (NF) in survivors in early adulthood and aimed to assess the impact of radiotherapy dose (RTD) and time since treatment (TxT) on NF. Forty-six survivors of pediatric brain tumors (mean age 23.99±4.71, mean age at diagnosis 9.29±4.54) performed an extensive neurocognitive test battery resulting in intelligence (n=5), memory (n=2), and language (n=3) scores. NF in long-term survivors was compared to sex-, age-, and education-matched controls, and between the different treatment strategies (surgery-only n=19, chemotherapy n=8, radiotherapy n=11, or chemo-radiotherapy n=8). Furthermore, relation between max-RTD (range 40.28 – 61.61 Gy) as well as TxT and NF was assessed. Three ANCOVA models were tested, and false discovery rate (FDR) was applied. For all scales and domain scores, survivors scored lower compared to controls. Scores were significant lower on full scale intelligence (pfdr&amp;lt; 0.001), verbal comprehension (pfdr&amp;lt; 0.001), working memory (pfdr= 0.003), perceptual reasoning (pfdr&amp;lt; 0.001), processing speed (pfdr&amp;lt; 0.001), spoken word comprehension (pfdr= 0.001), and semantic word generation (pfdr= 0.036) compared to controls. NF was not significantly different between the different treatments, nor did the association with max-RTD reach significance. TxT was associated with verbal comprehension and spoken word comprehension; albeit significance was not retained after FDR correction. In this study, the overall survivor cohort scored lower on multiple cognitive outcomes. More detailed analysis of various risk factors might further elucidate the different neurocognitive profiles for this population. Furthermore, more detailed analysis of RTD distributions and affected brain structures may provide greater insight on the impact of radiotherapy on NF.

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&amp;lt;.001), and treatment intensity (r=.28, p=.039). Expert ratings were not related to transition readiness (ps&amp;gt;.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&amp;gt;.05) and indexes of moderated mediation via CMA (ps&amp;gt;.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.

QOL-51. FEASIBILITY AND EASE OF USE OF A REMOTE ONLINE COGNITIVE BATTERY AMONG PEDIATRIC BRAIN TUMOR SURVIVORS

Abstract BACKGROUND Pediatric brain tumor survivors are at risk for cognitive deficits, including inattention, poor memory, and slow processing speed. Due to technology advances, computerized neuropsychological batteries were developed that can be completed via internet in the home. The primary aim of this study was to evaluate the rate of successful completion and ease of use of the Penn Computerized Neuropsychological Battery (CNB) among pediatric brain tumor survivors. METHODS Forty-eight pediatric brain tumor survivors completed the online remote administration version of the Penn CNB (10 subtests) assessing complex cognition, memory, executive control, processing speed, and motor speed. Participants were provided with an electronic link to the online cognitive battery as well as paper and electronic copies of an instruction guide and post-completion surveys to return via mail/email. RESULTS Patients (56.3% female) were diagnosed and treated for a brain tumor (54.2% received radiotherapy). All participants were at least 8 years of age (M=13.71, SD=3.82) and at least one-year post-diagnosis (M=4.76, SD=2.58 years). Eighty-eight percent of participants beginning the CNB completed all subtests. Sixty percent of participants completed and returned the post-assessment survey. Participants who returned post-assessment surveys were similar to those who did not on demographic and medical factors (all p-values &amp;gt;.05). Mean ratings suggest that survivors were “very interested” in the tasks and they were “somewhat easy” to complete. Younger children were more likely to have trouble understanding task instructions (r=.56, p &amp;lt;.01) and ask for help answering specific questions (r=.46, p &amp;lt;.05). CONCLUSIONS Remote administration of computerized batteries are feasible among pediatric brain tumor survivors and may assist with advancing both research and patient care. From a research standpoint, remote batteries may allow for participation and engagement in research with minimal survivor burden. Clinically, such batteries may offer alternatives for screening patients who will benefit from comprehensive services.

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&amp;gt;.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&amp;gt;.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.

MDB-39. HOW DO TUMOUR DERIVED EXTRACELLULAR VESICLES INTERACT WITH THE DEVELOPING NERVOUS SYSTEM AND LEAD TO ALTERED PAIN PROCESSING IN CANCER SURVIVORS?

Abstract BACKGROUND Childhood cancer-related pain and its treatment lack sufficient clinical attention due to limited understanding of the underlying mechanisms. While chemotherapy-induced peripheral neuropathic pain (CIPN) mechanisms in adults have been extensively studied, those in early life remain unexplored. In the CIPN literature there is a growing body of evidence for tumour derived factors altering pain processing. Our study aims to understand how tumour derived extracellular vesicles (EVs) interact with the developing nervous system and impact pain processing in childhood brain tumour survivors. METHODS We determined dose-response curves and IC50 values for several medulloblastoma (MB) cell lines using standard-of-care chemotherapy drugs: vincristine, etoposide, cisplatin, and lomustine. EVs were isolated via size exclusion chromatography and characterised through western blotting, flow cytometry and electron microscopy. We quantified the effects of chemotherapy on EV release using ZetaView analysis. We then tested whether EVs from relevant MB cell lines could influence axon development in primary mouse embryonic day 16.5 dorsal root ganglion (DRG) neurons in vitro after pre-treatment with chemotherapy-treated EVs. RESULTS EVs from chemotherapy-treated and untreated cells exhibited similar size and shape. However, a combination of vincristine, etoposide, and cisplatin at low concentrations significantly increased EV secretion by MB cell lines. Moreover, 24-hours following treatment with chemotherapeutic exposed EVs there was complete cell death of embryonic DRG neurons compared to the PBS or control EV treated neurons. CONCLUSION Standard chemotherapy drugs substantially enhanced EV release from MB cells, and co-culture of embryonic DRG neurons with chemotherapy exposed EVs resulted in neuronal death. Our next step is to investigate whether administering these selected EVs in healthy animals alters pain responses and pain maturation. We also aim to study the biodistribution of these EVs within the nervous system and body, after infusion into the cerebrospinal fluid as well as how EV cargo is altered by chemotherapeutics.

QOL-06. RECURRENCE PATTERNS AND SURVEILLANCE IMAGING IN PEDIATRIC BRAIN TUMOR SURVIVORS

Abstract BACKGROUND Surveillance magnetic resonance imaging (MRI) is routinely used to detect recurrence in pediatric central nervous system (CNS) tumors. Frequency of neuroimaging varies with no standardized approach. METHODS A single institution retrospective cohort study evaluated frequency and pattern of recurrences. Pediatric patients (birth to age 21 years) diagnosed with a primary CNS tumor between 1988 and 2011 treated at Lurie Children’s Hospital were included. RESULTS This study included 476 patients; the majority diagnosed with a low-grade glioma (LGG) (n=138; 29%), high grade glioma (HGG) (n=77; 16%), ependymoma (n=70; 15%) or medulloblastoma (n=61; 13%). LGG, HGG and ependymoma patients more commonly had multiply recurrent disease (p=0.08), with ependymoma patients demonstrating ≥2 relapses in 47% of cases. Recurrent disease was identified by imaging more often than clinical symptoms (65% vs 32%; p=&amp;lt;0.01). Treatment at relapse included surgical managment more often than non-surgical approach (59% vs. 41%; p=0.0016) in patients, leading to pathology confirmation of recurrence. Mean time to first relapse for the entire cohort was 2.5 years (range 1 day-24.8 years). Patients diagnosed with meningioma demonstrated the longest mean time to first relapse (74.7 months) whereas those with Atypical Teratoid Rhabdoid Tumor and Choroid plexus carcinoma tended to have the shortest time to relapse (8.9 months and 9 months, respectively). Overall, 22 patients sustained first relapse &amp;gt;10 years from initial diagnosis, including those diagnosed with LGG, medulloblastoma, pineoblastoma, craniopharyngioma, GCT, and meningioma. CONCLUSION With a higher percentage of tumor recurrence/progression seen on neuroimaging before development of symptoms, surveillance imaging is necessary in routine follow up of pediatric CNS tumor survivors. While the study is limited since we did not look at overall survival, earlier detection of recurrence would lead to earlier initiation of treatment and implementation of salvage treatment regimens which can impact survival and quality of life.

QOL-53. EXPLORING HEADACHES IN PEDIATRIC NEURO-ONCOLOGY PATIENTS: A SINGLE INSTITUTION RETROSPECTIVE CHART REVIEW

Abstract BACKGROUND Despite the high prevalence of headaches in pediatric patients with brain tumors, very little research has been done to characterize their traits and to assess current management practices. Effective and efficient treatment of these headaches is critical to the optimization of brain tumor survivors’ quality of life. Foundational knowledge of any clinical associations likely would be beneficial to develop rational management strategies. METHODS A retrospective single-institution chart review of pediatric patients seen in the Children’s Hospital Colorado (CHCO) Neuro-oncology clinic from 1/1/22-12/31/22 is underway. Information is being collected via manual chart review including basic demographic information, oncologic diagnosis and tumor location, surgical interventions, and tumor-directed treatments. Headache characteristics, including timing of onset, associated symptoms, severity and frequency, referral to CHCO Neurology Headache Clinic and any headache therapies attempted will be sought. Additional information will include the number of emergency department visits and unplanned MRIs obtained as part of headache management. RESULTS 384 patients (53% male; median age 12 years, range 2-24 years) received care in the CHCO Neuro-oncology clinic in 2022. The majority of these patients were Caucasian/Non-Hispanic (61.7%), followed by Caucasian/Hispanic (13.8%) and African American/Non-Hispanic (4.2%). In this cohort, the preferred language for 93% was English and for 6% was Spanish. The majority (55%) of patients had a low-grade glioma/ glioneuronal tumor as their oncologic diagnosis. Patients with referrals to CHCO Headache clinic made up 13% of this cohort. Data collection and analysis are ongoing. CONCLUSIONS This data set will help to characterize the prevalence and features of headaches in pediatric patients with CNS tumors. This information will serve as the foundation for planned prospective studies that will collect more comprehensive and consistent data related to headaches in the pediatric neuro-oncology population and to formalize processes that will identify appropriate patients for referral to specialized headache providers.

QOL-39. FATIGUE AS A RISK FACTOR FOR REDUCED SOCIAL CONNECTEDNESS IN PEDIATRIC BRAIN TUMOR SURVIVORS

Abstract BACKGROUND Pediatric brain tumor survivors (PBTS) experience reduced social connectedness, including fewer friendships, less social acceptance, and greater isolation. Identifying modifiable factors contributing to social issues would yield treatment opportunities. Fatigue is common among PBTS and may relate to social challenges. This study evaluated fatigue among PBTS and its associations with various indices of social connectedness. METHODS Survivors (N = 34) of three types of brain tumors—medulloblastoma (N = 11), pilocytic astrocytoma (N = 15), and craniopharyngioma (N = 8)—completed self-reported measures of fatigue and social connectedness. Laboratory studies assessed thyroid function and growth hormone status. Caregivers completed measures of social functioning. Descriptive statistics summarized fatigue and endorsement of fatigue items. ANOVAs, t-tests, and Pearson correlations evaluated fatigue according to various medical factors, and Pearson correlations evaluated associations between self-reported fatigue and indices of social connectedness. RESULTS Over 20% of survivors reported elevated fatigue, with 53% and 35% indicating fatigue interfering with attention and socialization, respectively. We did not detect associations between self-reported fatigue and diagnosis, current age or age at diagnosis, time since end of treatment, or history of chemotherapy or cranial radiation therapy. We did not detect an association between BMI Z-score and collected hormones. Mean T scores on the self-reported peer relationships measure were below the reference mean (M = 45.8, SD = 11.9), with 22% of survivors endorsing concerns. Higher self-reported fatigue was significantly correlated with poorer self-reported peer relationships (r = -.62, p &amp;lt; 0.001) and more parent-reported social impairments (r =.61, p &amp;lt; 0.001). CONCLUSIONS Fatigue is common among PBTS and may interfere with peer relationships. Clinicians should screen for fatigue as a risk factor for reduced social connectedness. Further research is needed to identify predictors of fatigue and social difficulties and determine temporal associations between fatigue and social connectedness.

IMG-04. ASSOCIATION BETWEEN MICROSTRUCTURAL INTEGRITY OF BRAIN SUBSTRUCTURES AND NEUROCOGNITIVE OUTCOMES: A MULTI-TRAJECTORY ANALYSIS IN CHILDHOOD BRAIN TUMOR SURVIVORS

Abstract BACKGROUND The relationship between the brain’s microstructural integrity and neurocognitive outcomes is not well characterized in childhood brain tumor survivors. In healthy children, mean diffusivity (MD) generally decreases and fractional anisotropy (FA) increases with age as the brain progressively myelinates and develops. Increasing MD and decreasing FA is suggestive of microstructural injury. We investigate the association between longitudinal neurocognitive outcomes and change in MD and FA in childhood brain tumor survivors. METHODS Patients diagnosed with a brain tumor at &amp;lt; 20 years of age with ≥ 2 neurocognitive assessments and paired DTI at each neurocognitive timepoint were retrospectively identified and eligible for inclusion. Multi-trajectory modeling was applied to cluster patients into distinct neurocognitive trajectories based on intelligent quotient, processing speed and working memory. Linear mixed models were used to determine whether the clusters were associated with change in MD and FA over time. RESULTS A total of 61 patients were eligible with 151 neurocognitive assessments paired with DTI. Mean follow-up was 4.8 years. Multi-trajectory modeling identified two clusters of patients with distinct neurocognitive trajectories. Compared to the low-performance group, the high-performance group (45.5%) had higher baseline neurocognitive scores with less decline in all neurocognitive outcomes. The high-performance group was also associated with a greater decrease in MD and greater increase in FA of the hippocampus and several white matter tracts such as the corpus callosum, pontine crossing tract, anterior limb of the internal capsule and inferior cerebellar peduncle, after adjusting for age and sex (all p&amp;lt;0.05). Additionally, the high-performance group was associated with a greater increase in FA in the superior, middle and inferior frontal gyri (all p&amp;lt;0.05). CONCLUSIONS The high-performance neurocognitive group was associated with greater microstructural integrity over time in multiple brain substructures compared to the low-performance group, as measured by change in fractional anisotropy and mean diffusivity.

NURS-13. NEUROCOGNITIVE SIDE EFFECTS OF PEDIATRIC BRAIN TUMORS: A CONTINUING CHALLENGE

Abstract BACKGROUND Pediatric brain tumors pose a considerable challenge in clinical oncology, necessitating multimodal treatment approaches. Many of these have the potential to impact cognition on vulnerable, young brains. While advancements in therapies have improved survival rates, neurocognitive outcomes continue to be one of the most challenging late effects that affect quality of life for pediatric brain tumor survivors. METHODS We conducted a literature review to identify 1) current treatment approaches for pediatric brain tumors, 2) the neurocognitive effects that survivors of pediatric brain tumors experience, and 3) appropriate interventions that can be implemented to mitigate those neurocognitive effects. RESULTS Novel chemotherapeutic agents, such as molecularly targeted therapies, are increasingly implemented in a personalized approach to treatment. New approaches to radiation therapy, particularly proton therapy, have shown promise in minimizing cognitive decline compared to traditional photon therapy. Advances in neuroimaging techniques have enabled a more detailed understanding of structural and functional brain changes associated with treatment. While these newer treatment modalities are promising, their long-term side effects are mostly unknown and bear close monitoring over time. Because neurocognitive side effects continue to underscore the impact of pediatric brain tumor treatments, recent studies often specifically evaluate the cognitive side effects as well as attempt to personalize treatments to reduce cognitive damage. CONCLUSIONS Recent research findings reinforce the enduring concern of neurocognitive side effects in pediatric brain tumor survivors. The integration of advanced therapeutic modalities and targeted supportive care interventions may hold the key to optimizing treatment outcomes while minimizing cognitive morbidity. Continued research efforts are essential for refining treatment protocols and developing personalized strategies to safeguard neurocognitive function in this vulnerable population. Additionally, studies exploring the role of supportive care interventions, such as cognitive rehabilitation and neuroprotective strategies, demonstrate potential avenues for mitigating cognitive sequelae but require ongoing research.