tbuckley/cabot-search huggingface dataset:
MDB-31. THE CLINICAL SIGNIFICANCE OF SUB-TOTAL SURGICAL RESECTION IN CHILDHOOD MEDULLOBLASTOMA: A MULTI-COHORT ANALYSIS OF 1100 PATIENTS
Authors: Claire Keeling, Simon Davies, Jack Goddard, Vijay Ramaswamy, Edward C Schwalbe, Simon Bailey, Debbie Hicks, Steven C Clifford
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Medulloblastoma patients with sub-total surgical resection (STR; &amp;gt;1.5 cm2 primary tumour residuum) typically receive intensified treatment. However, the association of STR with poor outcomes has not been observed consistently, questioning the validity of STR as a high-risk disease feature. METHODS We collected extent of resection (EOR) data from 1110 patients (UK CCLG centres (n=416), published cohorts (n=694)), the largest cohort with clinico-molecular annotation assembled to specifically assess the significance of EOR to date. We performed association and survival analyses, assessing overall survival (OS) cohort-wide with reference to the consensus medulloblastoma molecular groups and clinico-molecular features. RESULTS STR was reported in 20% (226/1110) of the cohort and was enriched in patients (i) &amp;lt;5 years at diagnosis (p=0.021), (ii) with metastatic disease (p&amp;lt;0.0001) or (iii) with non-WNT tumours (p=0.047). In cohort-wide analysis, STR was associated with worse survival in univariable analysis (p&amp;lt;0.0001), though, outcomes for patients with STR as their only risk-feature were as per standard-risk disease. Examination of specific disease contexts showed STR was prognostic in univariate analysis for patients (i) receiving cranio-spinal irradiation (CSI) and chemotherapy (p=0.016) and (ii) with Group 3 tumours receiving CSI (p=0.039). In non-metastatic CSI treated patients, STR was not prognostic, independent of CSI dose. Crucially, STR was not independently prognostic in multivariable analyses when considered alongside established clinico-molecular high-risk features. CONCLUSIONS In a cohort of 1100 molecularly characterised medulloblastoma patients, STR (n=226) predicted significantly lower OS in univariable analysis, but was not an independent prognostic factor. Our data suggest that maximal safe resection can continue to be carried out for patients with medulloblastoma and suggest STR should not inform patient management when observed as a sole, isolated risk feature. These findings provide necessary evidence to inform the selection criteria for forthcoming risk-adapted medulloblastoma clinical trials.
QOL-07. EFFICIENT NEUROPSYCHOLOGICAL ASSESSMENT IN PATIENTS WITH BRAIN TUMORS AND ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Ivana Kreft Hausmeister, Sandra Klašnja Hafner, Katarina Uršič, David Gosar, Lidija Kitanovski
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Children treated for cancer may experience a decline in performance for a variety of reasons, one of which is the impact of treatment. Children treated for leukemias and brain tumours are at the highest risk of developing neurocognitive sequale (Daly and Brown, 2015). METHODS In our study we used Bayesian regression to identify assessment tools that would best predict the sequale of brain tumors (BT) and acute lymphoblastic leukemia (ALL) in children and adolescents. Using data from 15 patients with BT, 15 patients with (ALL) and 9 siblings controls we compared the predictive validity of the Wechsler Intelligence Scales for Children (WISC-V), Delis-Kaplan Executive Function System (D-KEFS), Continuous Performance Test (CPT-3), the Developmental Neuropsychological Assessment (NEPSY-II) and the parent and teacher report forms of the Achenbach Assessment System (ASEBA). RESULTS We found that the best predictors of ALL were d’ scores on the CPT (BF = 20.69, pd =.05) and CPT ommission scores (BF = 17.50, pd =.05), while the best predictor a BT was the WISC-IV Coding subtest (BF = 21.17, pd =.05) in addition to CPT omission scores (BF = 12.00, pd =.08) and HRT SD scores (BF = 11.91, pd =.08). CPT d’s scores were also predictive of Methotrexate treatment (MTX) (BF = 32.61, pd = 0.03), as were WISC-V Symbol Search scores (BF = 32.61, pd = 0.03) and the NEPSY-II Auditory Attention subtest (BF = 26.06, pd = 0.04). We also noted differential sensitivity of the ASEBA teacher report form for detecting deficits identified during the neuropsychological assessment. CONCLUSIONS We feel our findings will, together with previous meta-analyses, contribute to more efficient neuropsychological assessment in patients with BT and ALL. Neuropsychological asseessment is vital for identifying potential sequale of disease and treament in pediatric oncology.
MDB-30. ZOLPIDEM, A PROMISING DRUG TO IMPROVE POSTOPERATIVE CEREBELLAR MUTISM SYNDROME (CMS): RETROSPECTIVE STUDY OF 19 PEDIATRIC PATIENTS WITH POSTERIOR FOSSA TUMORS
Authors: Diannet Quintero-Garcia, Juan Añon, Felisa Vazquez-Gomez, Jose Luis Moreno-Carrasco, Marta Perez-Somarriba, Serafin Castellano, Hyaissa Ippolito, Belen Rivero, Begoña Arce, Carmen De Caceres-Velasco, Susana Cartas, Borja Esteso, Sebastian Galas, Isis Alonso-Garcia, Roser Mingarro, Veronica Cantarín, Alvaro Lassaletta
Journal: Neuro-Oncology (2024)

Abstract INTRODUCTION Postoperative Cerebellar Mutism Syndrome (CMS) affects up to 25% of patients undergoing surgeries for posterior fossa (PF) tumors. There is no established treatment for CMS, although zolpidem has become widespread after reporting remarkable responses in some cases. However, there is very limited scientific evidence, prompting us to document our experience with zolpidem. OBJECTIVES To evaluate the efficacy and safety of zolpidem in patients with postoperative CMS in PF tumors. METHODS Observational, descriptive, retrospective study conducted at our institution. Patients &amp;lt;21 years diagnosed with CMS following PF tumor surgery between 2011-2023 and treated with zolpidem were included. Demographic and clinical data, therapies, CMS scales, and outcomes were collected. RESULTS Nineteen patients met the criteria, 84% males, median age 8 years (range, 9 months-19 years), and median follow-up time 30 months (range, 2-126). Diagnoses included 58% medulloblastoma, 21% pilocytic astrocytoma, 10.5% ependymoma, 10.5% others. CMS mutism scale was rated mild, moderate and severe in 5%, 21% and 74%, respectively. Median zolpidem administration was 31 days (range, 2-241) and median maximum dose was 0.25 mg/kg/day (range, 0.10-0.90). Mutism scores improved in 37% (7/19), 53% (8/15) and 64% (9/14) of patients that received zolpidem for at least 48h, 7 and 14 days, respectively. Subjective improvement in communication and interaction was observed in 74% (14/19). Only three patients with mild somnolence and one with initial irritability and insomnia were reported. CONCLUSIONS To our knowledge, this is the largest study of patients treated with zolpidem for CMS. A considerable proportion of children improved their language abilities within the first 24-48h, but some patients may even benefit from more prolonged treatment. Most children showed an adequate tolerance with very few side effects. Further studies are urgently needed, preferably within a randomized clinical trial, to find the real efficacy, appropriate dosage, and duration of zolpidem.
QOL-15. PAEDIATRIC LOW-GRADE GLIOMA (PLGG): A LIFELONG DISEASE THAT BEGINS IN CHILDHOOD. EVALUATION AND PROGNOSTICATION OF LONG-TERM PLGG SURVIVOR FUNCTIONAL AND QUALITY OF LIFE OUTCOMES
Authors: Katie L Green, Tom J Stone, Thomas S Jacques, Jessica C Pickles, Deborah Ridout, Kristian Aquilina, Kim Phipps, Richard Bowman, Jenny Gains, Brownwen Aldridge, Hoong-Wei Gan, Mette Jorgensen, Patricia O’Hare, Olga Slater, Sarita Depani, Elwira Syzchot, Yen Chang, Deirdre Leyden, Myra Bluebond-Langner, Darren Hargrave
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND For many patients, PLGG has a chronic disease course with potential for multiple and significant functional deficits and decreased Quality-of-Life (QOL). However, there have been limited large-cohort evaluations or prognostication studies of QOL &amp; functional outcomes. AIMS 1. Large-cohort analysis of long-term PLGG survivor functional &amp; QOL outcomes: combining clinical follow-up assessment with survivor-reported QOL &amp; function. 2. Evaluation of prognostic associations between PLGG variables &amp; functional/QOL outcomes. METHODS Demographic, tumour &amp; treatment factors of PLGG patients diagnosed 1980-2021 at Great Ormond Street Hospital, UK, were retrospectively collected &amp; evaluated prognostically with functional outcomes from last clinical follow-up.Cohort long-term survivors completed prospective QOL(PedsQl Core) &amp; function(PESAT-PT) questionnaires.PedsQL scores were evaluated prognostically with patient/tumour/treatment factors using multivariate logistic regression.PedsQL scores were compared with healthy (N=649) &amp; chronically-ill (N=137) reference populations. RESULTS PLGG cohort (N=814) OS was 94.3%,PFS 76% &amp; median treatments 1 (0-21) at median follow-up 8 years. 42% had 1 functional deficit at last clinical follow-up. Diagnostic age, tumour location, surgical resection, &amp; receipt chemo/radiotherapy were independently associated with functional outcomes. 122 long-term survivors completed prospective questionnaires at median follow-up 21 years. 87% reported dysfunction: physical 60%,visual 50%,neurocognitive 49%,social 25%, endocrine 23%,travel 21%,employment 18%,&amp; hearing 11%. Mean PedsQl scores:Physical 82(0-100), Psychosocial 73(13-100), Total 76(9-100). PLGG survivors had significantly lower mean Total, Physical &amp; Psychosocial PedsQl scores than healthy controls (p0.0001,p0.0003,p0.0001), but comparable to people with chronic illness (p0.60,p0.14,p0.21). No correlation identified between PedsQl scores &amp; number of impaired functional domains. Favourable Total PedsQl scores were associated with surgical resection(OR-5.94,p0.02) &amp; fewer treatment interventions on multivariate analysis(OR-2.8,p0.0005). Adverse PedsQl scores were associated with NF1 (OR-11.82,p0.04), BRAF-V600E mutation(OR-18.55,p0.04), OPGs(OR-12.1,p0.01), &amp; seizures(OR-18.93,p&amp;lt;0.0001). CONCLUSIONS Prognostication of heterogeneous PLGG survivor functional and QOL outcomes is complex but possible, without clear correlation between QOL and functional outcomes. For many, PLGG is a lifelong disease that begins in childhood.
QOL-12. LESSONS LEARNED FROM LONGITUDINAL CARE IN POSTERIOR FOSSA SYNDROME
Authors: Vera Tsetlina, Deborah Cassidy, Amy Lynn Tenaglia, Jared Levin, Elaine Tsao, Katarzyna Ibanez
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Posterior fossa syndrome (PFS) is a constellation of neurobehavioral symptoms occurring in 8–24% of children following surgical resection of posterior fossa tumors. Symptoms may include a combination of mutism or reduced verbal output, emotional lability, hypotonia, dysphagia, ataxia and weakness. Direct surgical injury to the dentato-thalamo-cortical pathway has been the proposed pathological mechanism. The trajectory of recovery and the functional outcomes of PFS are not well described. Khan et al. published a prospective study on children after medulloblastoma resection where they divided PFS into type 1 (complete mutism) and type 2 (diminished speech). They showed that PFS type 1 patients had a worse prognosis and a delayed recovery with 44.4% of children being non-ambulatory at one year. Ricci et al. recently published a more detailed severity grading algorithm which over time will hopefully help with data collection and analysis leading to improved prognostication regarding functional recovery. METHODS We present a unique longitudinal look (range 12 months to 19 years) at 5 pediatric patients with posterior fossa tumors who developed PFS following their tumor resections. RESULTS Tumor diagnoses included ependymoma and medulloblastoma. Rehabilitation interventions consisted of acute inpatient rehabilitation where they received intensive physical, occupational, speech and feeding therapy. Most patients benefited from early utilization of trunk and lower extremity bracing as well as a variety of assistive devices and durable medical equipment. Patients continued their rehabilitation for months to years in an outpatient and school setting. All patients demonstrated significant neurological and functional gains however, none of them had a complete resolution of symptoms. We discuss the anatomy, the time to symptom onset, the trajectory of our patients’ recoveries and the rationale behind the applied rehabilitation strategies. CONCLUSIONS This work gives insights on long term sequalae of PFS and demonstrates current rehabilitation approach for children with this complex condition.
QOL-10. PHYSICAL ACTIVITY LEVELS AND PATTERNS IN SURVIVORS OF CHILDHOOD CENTRAL NERVOUS SYSTEM TUMOURS
Authors: Rachael Keating, Sarah Curry, Juliette Hussey
Journal: Neuro-Oncology (2024)

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.
QOL-16. IMPACT OF LESION LOCATION ON MOTOR AND COGNITIVE OUTCOMES IN PEDIATRIC CEREBELLAR TUMORS
Authors: Karin Walsh, Catherine Stoodley, Johanna Nielsen, Alex Kaufman, Brooks Baucom, Aly Muir, Maneli Pakhejad, Rebecca Tegiacchi
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Children with cerebellar damage are at increased risk for various adverse outcomes, including higher rates of autism and long term neurocognitive challenges. Traditionally considered a motor structure, extensive evidence links the cerebellum to a range of behaviors and atypical cerebellar structure and function have been reported in multiple neurodevelopmental and psychiatric conditions. A key feature of cerebellar neuroanatomy are the functional subregions that support sensorimotor and non-motor functions, leading to the hypothesis that motor, cognitive and behavioral outcomes should be predicted by the cerebellar lesion location.We aimed to determine how lesion location relates to outcomes in pediatric cerebellar patients. We predicted that lesions of the anterior lobe would disrupt motor performance, posterolateral lesions would impact cognitive functions, and behavioral dysregulation would be associated with posterior midline damage. METHODS We conducted lesion-symptom mapping in 30 children with a history of cerebellar tumor resection (sex: 19 male, 11 female; age at diagnosis, mean 6.8 years [SD 4.2]). Clinical MRI scans and neuropsychological data were used to evaluate the impact of lesion location on motor (pegboard), cognitive (verbal comprehension, verbal fluency, working memory, processing speed) and behavioral control measures (BRIEF). We mapped individual lesions using T1-weighted MRIs and normalized the lesion maps into standard template space for group analyses. RESULTS Behavioral scores ranged from impaired to above average. Lesion overlap maps were used to assess the lesion patterns associated with performance. As predicted, anterior and medial lesions disrupted motor performance and processing speed; posterolateral lesions were associated with impaired cognitive scores. CONCLUSIONS These preliminary analyses indicate that long-term outcomes are associated with disruption of specific cerebellar subregions. This could aid in prognosis and management of pediatric cerebellar tumor patients. Future work will address age of surgery, longitudinal changes in performance, and the developmental impact of early cerebellar disruption on supratentorial structures.
QOL-13. RETURNING TO SCHOOL TO REDUCE LATE COGNITIVE SIDE EFFECTS IN SURVIVING CHILDREN WITH BRAIN TUMORS AFTER RADIOTHERAPY
Authors: Yangqiong Zhang, Huajun Yang, Yuliang Xiang, Danlei Wang, Lihan He, Linbo Cai
Journal: Neuro-Oncology (2024)

Abstract OBJECTIVE To investigate whether returning to school can reduce advanced cognitive impairment related to chemo-radiotherapy in children with brain tumors. METHOD From 2013 to 2018, 132 children with brain tumors aged 3-14 who received chemo-radiotherapy for brain tumors were retrospectively analyzed for gender, tumor type, age of radiotherapy, education level, place of residence, and return to school. The Wechsler Intelligence Test was conducted before and 5-10 years after radiotherapy and chemotherapy, and they were divided into a return to school regular class group, a return to school family/community education group, and a non return to school no education group. RESULT 78 cases were in the group of returning to school for regular classes, 30 cases were in the group of returning to school for family/community education, and 24 cases were in the group of not returning to school without teaching. The verbal intelligence, operational intelligence, and overall intelligence of the group returning to school and attending regular classes were significantly higher than the other two groups. The return to school situation of urban children is better than that of rural children (p=0.028&amp;lt;0.05). Children with germ cell tumors had the best return to school, while those with glioma had the worst return to school (p&amp;lt;0.05). The quality of life score of returning to school children was significantly higher than that of out of school children (p&amp;lt;0.05). CONCLUSION Children returning to school are significantly better than those of out of school children in terms of physiological, emotional, social, and school functions. After 5 years of radiotherapy, the cognitive level of the returning children significantly improved, and the overall quality of life was relatively high.
QOL-09. EQUI AND HIPPO: A STUDY ASSESSING THE FEASIBILITY AND ACCEPTABILITY OF HORSE THERAPY FOR CHILDREN, ADOLESCENTS AND YOUNG ADULTS IN REMISSION FROM A MEDULLOBLASTOMA
Authors: Anne Isabelle BERTOZZI, Morgan DEJEAN, Malory BEAUDA, Eloïse BAUDOU
Journal: Neuro-Oncology (2024)

Abstract INTRODUCTION Psycho-social and motor disorders are common long-term sequalae in patients treated for a medulloblastoma during childhood. They often require long-term, multidisciplinary rehabilitation and post-therapeutic care that can be difficult to maintain over time. To address this common problem, we hypothesized that a horse therapy can re-engage children in their rehabilitation. The expected benefits of the horse therapy involve both psycho-social skills thought animal mediation (equitherapy) and motor skills using the horse’s three-dimensional movement (hippotherapy). MATERIALS AND METHODS We conducted a single-center prospective interventional trial including patients treated for medulloblastoma during childhood, aged 10 to 26, in complete remission. The intervention consisted on weekly 2-hours sessions of equitherapy and hippotherapy with a specialized physiotherapist and psychologist over a 4-month period (16 sessions per patient) in groups of 2 participants. The primary objective was to determine the feasibility of a rehabilitation program combining equitherapy and hippotherapy. The secondary objective was to assess changes in motor skills, balance, emotional feelings, self-esteem and quality of life at the end of the sessions, at 4 months and at 6 months using questionnaires and standardized and validated measurements. RESULTS The study began in April 2023 and is still ongoing. Six participants were included and four ended the intervention period. On this preliminary cohort, the recruitment rate was excellent with 100% of patients offered the program agree to take part. Three participants completed the program with a 100% adherence rate. All participants were very satisfied with their participation in the program. Analysis of second objective will be presented in the form of case reports. CONCLUSION The expected outcome of this study is to define a framework for the application of this practice, enabling a model of this rehabilitative management, and then to lead to dissemination and recognition of this activity, enabling larger-scale studies.
QOL-14. EPILEPTIC SEIZURES, ANTI-SEIZURE MEDICATIONS, AND NEUROCOGNITION IN SURVIVORS OF PEDIATRIC BRAIN TUMORS
Authors: Edvard Fine de Licht, Tova Ideland, Gunnar Sigurdsson, Stavroula Anastasopoulou, Ingrid Tonning Olsson
Journal: Neuro-Oncology (2024)

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.