bluuebunny/crossref_metadata_2025 huggingface dataset:
PATH-07. QUALITY ASSURANCE IN CEREBROSPINAL FLUID CYTOLOGY ASSESSMENT FOR MEDULLOBLASTOMA STAGING LEADS TO POTENTIAL IMPROVED RISK-GROUP ASSESSMENT IN THE PROSPECTIVE MULTICENTER HIT-2000 TRIAL
Authors: Hagel Christian , Sloman Veronika , Mynarek Martin , Petrasch Katharina , Obrecht Denise , Deinlein Frank , Schmid Renate , von Bueren André O , Friedrich Carsten , Juhnke B Ole , Gerber Nicolas U , Kwiecien Robert , Girschick Hermann , Höller Alexandra , Zapf Antonia , von Hoff Katja , Rutkowski Stefan
Published: December 2020

BACKGROUND

Cerebrospinal fluid (CSF) dissemination of medulloblastoma (M1 stage) is a high-risk prognostic factor. However, because diagnostic criteria for M1 staging are missing we specified process-related and cytomorphological parameters influencing the predictive value of the CSF status.

PATIENTS AND METHODS

CSF samples and cytology reports from 405 medulloblastoma patients of the prospective multicenter trial HIT-2000 were reviewed and related to 5-year progression free survival (5y-PFS).

RESULTS

Tumor cells were detected in 237/1073 CSF cytospins. M1-patients and M2/3 patients with radiologically detected metastases showed a worse 5y-PFS than M0 patients (54% and 52% vs. 76%; p=0.01 and p<0.001). Lumbar sampling was more sensitive than ventricular sampling. M0 diagnosed specimens containing >50% lytic cells and/or less than 10 nucleated cells showed a decreased 5y-PFS (61%). Further investigation of cytological parameters revealed a poor outcome for cases harboring > 3 tumor cell clusters and individual tumor cells (5y-PFS 33%) vs. cases with ≥ 2 individual tumor cells but no clusters (5y-PFS 61%). In bi-variable Cox-regression, ≥ 2 vs. 0 or 1 tumor cells were associated with a Hazard Ratio (HR) of 0.52 (95%-Confidence Interval (CI): 0.12, 2.30; p=0.39), whereas > 3 vs. no tumor cell clusters were associated with a HR of 8.94 (95%-CI: 1.66, 48.22; p=0.01).

CONCLUSIONS

CSF staging in medulloblastoma should comprise lumbar specimens with <50% lytic cells and a minimum of 10 nucleated cells. The predictive value of CSF cytology in M1 cases may predominantly depend on tumor cell clusters. The latter finding needs to be confirmed in prospective trials.
PATH-08. THE IMPORTANCE OF RE-DIAGNOSIS OF TUMORS PREVIOUSLY CLASSIFIED AS CENTRAL NERVOUS SYSTEM PRIMITIVE NEUROECTODERMAL TUMORS
Authors: Fujita Naohide , Akiyama Osamu , Kondo Akihide
Published: December 2020

BACKGROUND

The recent molecular analyses have revealed that central nervous system primitive neuroectodermal tumors (CNS PNETs) those having clusters of small round tumor cells are genetically different tumors. However, the concepts of CNS PNET are complicated, and it is difficult to diagnose them appropriately in clinical field. To overcome this difficulty, we reviewed previous studies associated with CNS PNETs, and carried out several approaches, those are relatively easy access to use in clinics, for our 8 samples of embryonal brain tumors diagnosed CNS PNETs in our institution, initially.

METHODS

We used in combination with immunohistochemistry (IHC), Sanger sequence, Pyrosequence, polymerase chain reaction (PCR), real time PCR and copy number analysis referring recent reports.

RESULTS

In terms of the diagnosis three out of 8 cases were changed based on the results in this study from previous diagnoses.

CONCLUSION

In this review, it seemed that either the histopathological evaluation or molecular analyses would be not enough to make accurate diagnosis of CNS embryonal brain tumors, and it is essential to combine both of them including recent comprehensive analysis methods.
PATH-11. PROSPECTIVE (EPI-)GENETIC CLASSIFICATION OF > 1,000 PEDIATRIC CNS TUMORS—THE MNP 2.0 STUDY
Authors: Sturm Dominik , Sahm Felix , Andreiuolo Felipe , Capper David , Gessi Marco , Rode Agata , Bison Brigitte , Hirsch Steffen , Gerber Nicolas U , Gottardo Nicholas G , Kramm Christof M , Rutkowski Stefan , von Deimling Andreas , Pietsch Torsten , Pfister Stefan M , Jones David T W
Published: December 2020

The large variety of CNS tumor entities affecting children and adolescents, some of which are exceedingly rare, results in very diverging patient outcomes and renders accurate diagnosis challenging. To assess the diagnostic utility of routine DNA methylation-based CNS tumor classification and gene panel sequencing, the Molecular Neuropathology 2.0 study prospectively integrated these (epi-)genetic analyses with reference neuropathological diagnostics as an international trial for newly-diagnosed pediatric patients. In a four-year period, 1,215 patients with sufficient tissue were enrolled from 65 centers, receiving a reference neuropathological diagnosis according to the WHO classification in >97%. Using 10 FFPE sections as input, DNA methylation analysis was successfully performed in 95% of cases, of which 78% with sufficient tumor cell content were assigned to a distinct epigenetic tumor class. The remaining 22% did not match any of 82 represented classes, indicating novel rare tumor entities. Targeted gene panel sequencing of >130 genes performed for 96% of patients with matched blood samples detected diagnostically, prognostically, or therapeutically relevant somatic alterations in 48%. Germline DNA sequencing data indicated potential predisposition syndromes in ~10% of patients. Discrepant results by neuropathological and epigenetic classification (29%) were enriched in histological high-grade gliomas and implicated clinical relevance in 5% of all cases. Clinical follow-up suggests improved survival for some patients with high-grade glioma histology and lower-grade molecular profiles. Routine (epi-)genetic profiling at the time of primary diagnosis adds a valuable layer of information to neuropathological diagnostics and will improve clinical management of CNS tumors.
PATH-15. PROTEOMIC SIGNATURES PREDICT GRADE IN PEDIATRIC AND YOUNG ADULT INFILTRATIVE ASTROCYTOMAS
Authors: Graham Richard T , Sells Blake E , Fleming Jessica , McElroy Joseph P , Bell Erica H , Haque S Jaharul , Becker Aline P , Boué Daniel R , Finlay Jonathan L , Chakravarti Arnab
Published: December 2020

BACKGROUND

Infiltrative astrocytomas in children and young adults pose a treatment challenge due to the difficulty of achieving gross total resection and tumor resistance to irradiation and chemotherapy. Histopathologic grade is an essential part of determining prognosis and treatment, but it is subjective and provides limited understanding of the molecular mechanisms underlying tumor development and progression.

METHODS

We performed liquid chromatography/mass spectrometry (LC/MS-MS) on 28 FFPE samples of primary infiltrative astrocytomas (10 grade II, 8 grade III and 10 grade IV – WHO classification) from Nationwide Children’s Hospital (NCH). Initial unsupervised clustering was performed. Lasso regression yielded a protein signature separating low- and high-grade tumors which was validated using a similar cohort of pediatric and young adult infiltrative astrocytomas from the Proteomic Data Commons (PDC) (n=28) of the National Cancer Institute.

RESULTS

Unsupervised clustering of NCH samples essentially recapitulated grade and lasso regression yielded a 10-protein signature that distinguished grade II from grade III/IV tumors. This 10-protein signature when applied to the PDC validation dataset, accurately predicted grade for 89.3% of the tumors (p=0.00014).

CONCLUSIONS

We identified a quantitative protein signature that can reliably distinguish between low- and high-grade infiltrative astrocytomas from FFPE tissue. Further validation will enable the development an objective prognostic proteomic clinical test that complements and may outperform current histopathological strategies. Additionally, proteomic profiling of tumors will clarify the molecular mechanisms contributing to treatment resistance and tumor progression and help identify novel treatment targets. Independent functional validation and characterization of proteins is ongoing.
PATH-16. CORRELATION OF PATHOLOGICAL AND RADIOGRAPHICAL DIAGNOSES FOR CHILDREN WITH BRAIN TUMORS AT TWO MAJOR HOSPITAL IN KENYA
Authors: Okemwa Dr Minda , Omouk Dr Simon , Mwangombe Prof Nimrod , Macharia Dr Benson
Published: December 2020

BACKGROUND

Central nervous system (CNS) tumors are the leading solid tumors in the childhood population but vastly underreported in the African population. There’s limited data on childhood brain tumors as well as the histopathological distribution in Kenya. Our study aimed at assessing the spectrum as well as the level of correlation with imaging in diagnosis of brain tumors within two major hospital settings. DESIGN: This was a cross-sectional retrospective descriptive study conducted at the two major hospitals in Kenya: Kenyatta National Hospital (KNH) and Moi Teaching and Referral Hospital (MTRH). Children who underwent treatment for brain tumors between 2015 and 2017 and whose tissue biopsies were available at the laboratory archives were included.

RESULTS

87 cases were available for review, and the majority of the affected population were of ages 5–9 years. The most affected site was infratentorial compartment (48.3%) with gliomas and medulloblastoma being equally distributed. Majority of the gliomas were low grade (69%) with pilocytic astrocytoma being the most common subtype (42.9%). The overall sensitivity for the diagnosis of brain tumors through radiology was 69.4%. The level of correlation of histopathological to radiological diagnosis was statistically insignificant with P and kappa values of 0.814 and -0.024 respectively.

CONCLUSION

Gliomas and medulloblastomas were the commonest tumors at both centers. Histopathological diagnoses have a high concordance of agreement among various morphologists. The level of correlation between histopathological and radiological diagnosis was high. Next steps include standardizing clinical, radiological and pathological details within Kenya.
PATH-21. TELOMERE LENGTH ANALYSIS OF CNS TUMORS IN THE PEDIATRIC BRAIN TUMOR ATLAS
Authors: Rokita Jo Lynn , Gaonkar Krutika , Ijaz Heba , Miller Daniel , Karras Tasso , Santi Mariarita , Martinez Daniel , Koptyra Mateusz , De Raedt Thomas , Mason Jennifer , Appert Elizabeth , Lilly Jena , Zhu Yakun , Waanders Angela , Resnick Adam , Storm Jay , Cole Kristina
Published: December 2020

Subsets of pediatric cancers, including high grade glioma (pHGG), have high rates of uniquely long telomeres, associated with ATRX gene mutations and alternative lengthening of telomeres (ALT). Ultimately, these cancers may benefit from a therapy stratification approach. In order to identify and further characterize pediatric brain tumors with telomere lengthening (TL), we determined the intratelomeric content in silico from paired WGS of 918 tumors from CBTTC Pediatric Brain Tumor Atlas (PBTA). The results were highly concordant with experimental assays to determine ALT in a subset of 45 pHGG tumors from the set. Overall, 13% of the PBTA cohort had telomere lengthening. We confirmed the highest rate of TL (37%) in the pHGG cohort (37/100 tumors; 30/82 patients). There was no statistical difference in age, gender or survival in subset analysis. As expected, the patient pHGG tumors with telomere lengthening were enriched for ATRX mutations (60%, q= 1.76e-3). However, 6 tumors without ATRX mutation also had normal protein expression, suggesting a different mechanism of inactivation or TL. The pHGG tumors with telomere lengthening had increased mutational burden (q=8.98e-3) and included all known pHGG cases (n=6) in the cohort with replication repair deficiencies. Of interest, the second highest rate of telomere lengthening was 9 subjects (24%) in the craniopharyngioma cohort. None of the craniopharyngioma tumors had ATRX mutations or low ATRX expression, and 55% of those with TL had CTNNB1 mutations. Finally, lower rates of telomere lengthening were found in medulloblastoma (10%), ependymoma (10%), low grade astrocytoma (8%) and ganglioglioma (7/47, 15%).
QOL-01. LONGITUDINAL COMPARISON OF NEUROCOGNITIVE TRAJECTORIES IN PEDIATRIC MEDULLOBLASTOMA PATIENTS TREATED WITH PROTON VERSUS PHOTON RADIOTHERAPY
Authors: Kahalley Lisa , Peterson Rachel , Ris M Douglas , Janzen Laura , Okcu M Fatih , Grosshans David , Ramaswamy Vijay , Paulino Arnold , Hodgson David , Mahajan Anita , Tsang Derek , Laperriere Normand , Whitehead William , Dauser Robert , Taylor Michael , Conklin Heather , Bouffet Eric , Chintagumpala Murali , Mabbott Donald
Published: December 2020

PURPOSE

By reducing dose to normal brain tissue, proton radiotherapy (PRT) may lessen neurocognitive risk traditionally associated with photon radiotherapy (XRT). We examined change in neurocognitive scores over time in pediatric medulloblastoma patients treated with PRT versus XRT.

METHODS

Neurocognitive scores from 79 patients (37 PRT, 42 XRT) were examined. Patients were treated between 2007–2018 on the same treatment protocols that differed only by craniospinal modality (PRT versus XRT). Change in scores over time since diagnosis were compared between groups.

RESULTS

Groups were similar on most demographic/clinical variables: sex (67.1% male), age at diagnosis (mean 8.6 years), CSI dose (median 23.4 Gy), length of follow-up (mean 4.3 years), and parental education (mean 14.3 years). Boost dose (p<0.001) and margin (p=0.001) differed between groups. Adjusting for covariates, the PRT group exhibited superior outcomes in global IQ, perceptual reasoning, and working memory versus the XRT group (all p<0.05). The XRT group exhibited significant decline in global IQ, working memory, and processing speed (all p<0.05). The PRT group exhibited stable scores in all domains except processing speed (p=0.003). Posterior fossa syndrome imparted risk independent of modality.

CONCLUSION

This is the first study comparing neurocognitive trajectories between pediatric patients treated for medulloblastoma with PRT versus XRT on comparable, contemporary protocols. PRT was associated with more favorable neurocognitive outcomes in most domains compared to XRT, although processing speed emerged as vulnerable in both groups. This is the strongest evidence to date of an intellectual sparing advantage with PRT in the treatment of pediatric medulloblastoma.
QOL-06. QUALITY OF LIFE IN MEDULLOBLASTOMA SURVIVORS IN WESTERN MEXICO
Authors: del Campo Regina M Navarro-Martin , Macias-Toscano Jorge L , Toral-Casillas Erika , Sánchez-Zubieta Fernando , Orozco-Alvarado Ana L
Published: December 2020

BACKGROUND

Treatment of children with medulloblastoma (MB) can lead survivors to lidiate with long term sequelae and affect their quality of life (QoL). This study evaluates QoL in long term MB survivors. DESIGN/

METHODS

Clinical files of MB survivors from 1997 to 2016 were retrospectively analyzed. QoL was defined by Schipper Criteria in a five dimensional evaluation: clinical data, physic effects of treatment, academic develop, functional state and self welfare report.

RESULTS

Clinical data: Twenty eight survivors were identified, mean age at review was 18 years, median follow up was 106 months. Functional state: Last visit Karfnosky/lansky were 90 to 80% in 25% of patients. Physic effects of treatment: Cerebellar Mutism or ataxia were present in 25% of cases. Two patients required external dispositives. Audiometry detected an auditive tonal decrease in 25% of cases. An endocrine disfunction was present in 46% of cases, 32% required hormone replacement and 28% having short size. Renal damage without dialysis was detected in 7% and 10% had a transient tubulopaty. One case had bilateral amaurosis and 14% uses glasses. Three patients had a life partner. One female has offspring and two males had azoospermia. Academic development: While 90% attends to school, 35.7% complained of learning difficulties and 18% needed special education. Self welfare report: Difficulties in social environment were described in 21% and 14% still feeling sick during years.

CONCLUSIONS

Survivors of MB had adverse physical effects, followed by academic development, functional state and self welfare report and all this has a negative impact in their QoL.
QOL-13. NEUROCOGNITIVE OUTCOMES ACCORDING TO RISK-ADAPTED TREATMENT REGIMENS FOR CHILDREN OLDER THAN 4 WITH MEDULLOBLASTOMA AND POSTERIOR FOSSA EPENDYMOMA – RESULTS OF THE HIT2000 TRIAL
Authors: Mynarek Martin , Neumann-Holbeck Anne , Resch Anika , Ottensmeier Holger , von Hoff Katja , Traunwieser Thomas , Kortmann Rolf-Dieter , Obrecht Denise , Warmuth-Metz Monika , Bison Brigitte , Pietsch Torsten , Pfister Stefan M , Sill Martin , Kool Marcel , Sturm Dominik , Jones David , von Deimling Andreas , Sahm Felix , Tischler Tanja , Rutkowski Stefan
Published: December 2020

OBJECTIVES

Reduced neuropsychological outcomes are a major concern in pediatric patients with malignant brain tumors. We aimed to estimate decline in cognitive function according to treatment regimens.

METHODS

Cross-sectional analysis of cognitive functions tested with the Neuropsychological Basic Diagnostic tool (NBD) in 279 patients >4 years at diagnosis (median: 8.66; range: 4.01–18.98) with medulloblastoma (n=110, 23.7–25.0Gy CSI; n=131, >30Gy CSI) or posterior fossa ependymoma (n=38 local radiotherapy) who participated in the HIT-2000 trial. Multivariable regression analysis was conducted to adjust for postoperative cerebellar mutism syndrome, preoperative hydrocephalus, postoperative shunt placement, the interval between diagnosis and assessment, sex and age.

RESULTS

Mean time from diagnosis to assessment was 5.1 years. Increasing CSI-dose was significantly associated with a deterioration in performance of most subtests, particularly in areas of fluid intelligence (mean z-values per test for no CSI/23.4Gy/>30Gy respectively: matrix reasoning:-0.40/-0.52/-0.98, p<.001), short-term memory (number recall: -0.07/-0.58/-0.64, p=.002), visuo-spatial skills (visual-motor integration:-0.49/-0.68/-1.12, p<.001) and fine motor skills (dominant-hand:-1.09/-1.80/-2.12, p=.008; non-dominant-hand:-1.47/-2.59/-2.82, p=.003; bimanual coordination:-1.33/-2.68/-2.76, p=.001). These differences were retained after adjustment for confounding variables. Within medulloblastoma patients treated with >30Gy CSI, selective attention, but no other function was reduced in patients treated with pre-radiotherapy chemotherapy including intraventricular MTX (selective attention (with chemotherapy/without chemotherapy mean z-values: -0.66/0.00, p=.006)). Patients with SHH-activated medulloblastoma did significantly better than WNT or Group3/Group4 medulloblastoma patients in fluid intelligence and fine motor skills.

CONCLUSION

CSI dose among other highly relevant factors had significant effects on neuropsychological outcome. Pre-radiotherapy intraventricular MTX had only minor effects. Patients with SHH-activated medulloblastomas showed a more favorable outcome when compared to patients in the other subgroups.
QOL-14. A BIOPSYCHOSOCIAL APPROACH TO BRAIN INJURY REHABILITATION FOLLOWING TREATMENT FOR PAEDIATRIC BRAIN TUMOURS: CAN PHARMACOTHERAPY AID NEUROPSYCHOLOGICAL OUTCOME?
Authors: Phillips Jo , Brougham Mark
Published: December 2020

Long term survival following paediatric brain tumours has vastly improved in recent decades. Consequently there is a drive towards improved quality of survivorship. Brain tumours, surgical resection and adjuvant therapies represent mechanisms for brain injury and can therefore negatively impact a child’s neuropsychological trajectory; affecting cognition, behaviour, emotional and adaptive functioning and educational/occupational outcomes. A biopsychosocial approach to rehabilitation should target each of these domains through supported remediation, environmental modification and psychoeducation for young people and the key systems around them (e.g. families, education). There is a growing evidence base for the role of concordant psychopharmacologies to improve neuropsychological outcome. Since 2015 children treated at RHSC Edinburgh for brain tumours have been offered pharmacotherapy alongside usual rehabilitation approaches if they demonstrate significant difficulties with Attention, Processing Speed and/or Executive Function on formal neuropsychological assessment. Patients are referred to a Consultant Psychiatrist or Paediatrician (as per local protocol) for medication selection, titration and monitoring. A short case series (N=14) is presented outlining brain tumour pathologies, treatment modalities, neuropsychological profile and rationale for recommending pharmacotherapy. Approximately 50% of patients took up the offer. The treatment/s offered and self or parents reported outcomes is summarised. Pharmacotherapy was broadly effective; “it’s been like night and day”, although for one case (N=1) the side effects outweighed any benefit; “she became even more emotional”. Findings indicate that pharmacotherapy should be considered alongside conventional neurorehabilitation techniques for CYP with specific cognitive difficulties following treatment for paediatric brain tumours.
QOL-15. NEURAL NETWORK INTEGRITY FOR FACIAL AFFECT RECOGNITION IN SURVIVORS OF MEDULLOBLASTOMA
Authors: Brinkman Tara , Krull Kevin , Scoggins Matthew , Li Zhenghong , Glass John , Zou Ping , Ness Kirsten , Sabin Noah , Gajjar Amar , Armstrong Gregory , Robison Leslie , Hudson Melissa , Reddick Wilburn
Published: December 2020

BACKGROUND

Medulloblastoma survivors are at risk for social deficits, yet underlying mechanisms are poorly understood.

METHODS

Facial affect recognition was assessed in 50 medulloblastoma survivors treated with craniospinal radiation (median[range] 21.4[12.5–30.9] years old, 11.0[5.7–22.6] years since diagnosis) and 56 non-cancer age-, sex-, and race-matched controls. Brain activation and connectivity in core regions/nodes of the face perception network (fusiform gyri, occipital gyri, superior temporal sulcus) were examined using structural and functional neuroimaging. Structural networks were constructed from diffusion tensor imaging (DTI) data and individual node strength and efficiency were assessed. Functional MRI (fMRI) was conducted using a 1-back facial affect recognition task with assessment of regional differences in task-related cerebral blood flow (BOLD). Standardized neurocognitive testing was completed with 24 hours of brain imaging.

RESULTS

Medulloblastoma survivors performed worse on a behavioral measure of facial affect recognition (P=0.003) compared to matched controls. During the facial affect recognition task, controls demonstrated greater BOLD activation of the left and right fusiform gyri and the left and right middle occipital gyri compared to survivors (P’s<0.05, corrected for multiple comparisons). DTI indicated weaker core node strength in survivors in the right lateral occipital gyri (P=0.02) and efficiency was lower in the left (P=0.01) and right (P=0.03) occipital gyri compared to controls.

CONCLUSIONS

Medulloblastoma survivors have deficits in facial affect recognition and reduced activation and efficiency in brain regions comprising the face perception network compared to matched controls. Interventions targeting this specific skill and neural network may improve social functioning in survivors.
QOL-21. DEVELOPMENT AND UTILISATION OF A NEURO-ONCOLOGY REHABILITATION TEAM: 2018–2019 UPDATE
Authors: Paisley Helen , Hartley Helen , Kearney Anna , Hagan Alex , Owen Joanne , Pizer Barry , Holman Natalie , Kumar Ram
Published: December 2020

INTRODUCTION

A multi-disciplinary Neuro-Oncology Rehabilitation Team (NORT) was established at our institution in 2014. We reviewed NORT inputs, processes and outputs in 2018 to 2019 compared to our previously presented data from 2015, soon after service inception.

METHODS

Retrospective analysis of patients who received NORT input June 2018 - May 2019 compared to 2015 data. Descriptive analysis of changes to NORT operational processes and structure. Complexity of rehabilitation needs was measured using the Rehabilitation Complexity Scale-Extended V13 (RCS).

RESULTS

54 children received NORT input in 2018–2019 (10 children in 2015) with total of 129 outputs. NORT input was highest in children with high grade glioma (median reviews: 3; median RCS: 5) and ependymoma (median reviews: 3; median RCS: 5). Pilocytic astrocytoma formed the largest tumour group (n = 11; median reviews: 2; median RCS: 7). 11% patients were referred to neurologist (9% already known); 17% referred to community services (44% already known); 31% referred to neuropsychology. In 2015, outputs were predominantly referral to occupational therapy and physiotherapy. 6 patients (11% of 54) were discharged in 2018–2019 (40% of 10 patients in 2015). 4 patients died. Between 2015 and 2019, developments included: clarifying referral and discharge pathways, use of screening measures, neuropsychology integration, therapy-led drop-in clinics, use of RCS-E. DISCUSSION: There has been a clear increase in utilisation and scope of work of NORT over last 4 years. The strength of this team is multidisciplinary working and expertise. Further developments planned: multidisciplinary rehabilitation interventions and NORT outcome tools.
QOL-22. MACHINE-LEARNING INFERENCE MAY PREDICT QUALITY OF LIFE SUBGROUPS OF ADAMANTINOMATOUS CRANIOPHARYNGIOMA
Authors: Hengartner Astrid C , Prince Eric , Staulcup Susan , Vijmasi Trinka , Souweidane Mark , Jackson Eric M , Johnston James M , Anderson Richard C E , Naftel Robert P , Grant Gerald , Niazi Toba N , Dudley Roy , Limbrick David D , Ginn Kevin , Smith Amy , Kilburn Lindsay , Jallo George , Wilkening Greta , Hankinson Todd
Published: December 2020

BACKGROUND

Due to disease and/or treatment-related injury, such as hypothalamic, visual, and endocrine damage, quality of life (QoL) scores after childhood-onset Adamantinomatous Craniopharyngioma (ACP) are among the lowest of all pediatric brain tumors. Decision-making regarding management would be aided by more complete understanding of a patients likely QoL trajectory following intervention.

METHODS

We retrospectively analyzed caregiver and patient-reported QoL-instruments from the first 50 patients (ages 1–17 years at diagnosis) enrolled in the international Advancing Treatment for Pediatric Craniopharyngioma (ATPC) consortium. Surveys included 205 pediatric-relevant questions and were completed at diagnosis, and 1- and 12-months following diagnosis. Using Multiple Correspondence Analysis (MCA), these categorical QoL surveys were interrogated to identify time-dependent patient subgroups. Additionally, custom deep learning classifiers were developed using Google’s TensorFlow framework.

RESULTS

By representing QoL data in the reduced dimensionality of MCA-space, we identified QoL subgroups that either improved or declined over time. We assessed differential trends in QoL responses to identify variables that were subgroup specific (Kolmogorov-Smirnov p-value < 0.1; n=20). Additionally, our optimized deep learning classifier achieved a mean 5-fold cross-validation area under precision-recall curve score > 0.99 when classifying QoL subgroups at 12 month follow-up, using only baseline data.

CONCLUSIONs

This work demonstrates the existence of time-dependent QoL-based ACP subgroups that can be inferred at time-of-diagnosis via machine learning analyses of baseline survey responses. The ability to predict an ACP patient’s QoL trajectory affords caregivers valuable information that can be leveraged to maximize that patient’s psychosocial state and therefore improve overall therapy.
QOL-23. ASSESSING THE IMPACT OF METHYLPHENIDATE ON LATE COGNITIVE EFFECTS IN PAEDIATRIC BRAIN TUMOUR SURVIVORS: A SERVICE-BASED EVALUATION
Authors: Verity Sarah , Hill Rebecca , Halliday Gail , Ryles Jade , Bailey Simon
Published: December 2020

OBJECTIVE

One of the most disabling side effects of treatment in survivors of brain tumours is the resultant reduction in level of processing speed and attention. This study aimed to evaluate intellectual and psychological benefit of short-acting methylphenidate to survivors of brain tumour.

METHODS

Paediatric BT patients attending a UK specialist treatment centre received assessment of cognitive performance. All patients identified with attentional difficulties were screened for contraindications to methylphenidate. Participants (N=23), mean age 11.09 years, completed a 6-month trial of methylphenidate. Measures of attention (Test of Everyday Attention for Children 2; SNAP-IV), side-effects (Stimulant Side-Effects Rating Scale), Health-Related Quality of Life (PEDS-QL), and experience of methylphenidate questionnaire (purpose-developed semi-structured questionnaire) were administered prior to medication and after six months.

RESULTS

Participants showed improvement in selective attention (t(18)=-5.4, p=<.001, d=.93) and processing speed (t(16)=-3.0, p=.01) at follow up. Family ratings of attention were significant (t(17)=14.46, p<.001, d=-1.19). Change in subjective measures of Health-Related Quality of Life (HRQoL) was also statistically significant as reported by children (t(16)=3.91, p=.001, d=-.99), and on a parental-report measure of child HRQoL (t(15)=-8.19, p<.001, d=-1.09). HRQoL measures show improvement to physical, academic, and emotional domains as reported by participants.

CONCLUSIONS

Paediatric BT survivors showed benefit from provision of methylphenidate in terms of reduced attentional and processing deficit, and in terms of emotional wellbeing. Treatment was well tolerated. Continued follow-up of the current participants in a longitudinal study aims to evidence longer-term benefit to participants.
QOL-24. DIFFERENTIAL IMPACT OF TUMOR LOCATION, LOCAL AND CRANIOSPINAL IRRADIATION ON NEUROPSYCHOLOGICAL LONG-TERM OUTCOME IN CHILDREN WITH MEDULLOBLASTOMA, EPENDYMOMA AND SUPRATENTORIAL PNET: A LONGITUDINAL MULTICENTER OUTCOME ASSESSMENT OF CHILDREN FROM THE HIT-2000 AND HIT-REZ TRIALS
Authors: Ottensmeier Holger , Schlegel Paul G , Eyrich Matthias , Zimolong Bernhard , Mynarek Martin , von Hoff Katja , Frahsek Stefanie , Schmidt Rene , Faldum Andreas , Wolff Johannes , Fleischhack Gudrun , Warmuth-Metz Monika , Krauss Jürgen , Kortmann Rolf-Dieter , Galley Niels , Kühl Joachim , Rutkowski Stefan
Published: December 2020

Neurocognitive deficits are frequent in childhood brain tumor survivors and affect mental intelligence, psychomotor and executive abilities. The differential impact of factors such as disease (location, histology) or treatment (local (LI) vs. craniospinal irradiation (CSI)) on these parameters is not fully understood. Between 2007–2011 and 2013–2017 300 testings were performed on-site by one neuropsychologist. Of these, 274 tests from n=208 children with medulloblastoma (MB), ependymoma (EP) and supratentorial embryonal tumors (SET) <4 years at diagnosis are currently included into the analysis. Applied tests included the Bayley II, WUEP-KD, K-ABC, tapping speed (TS), CPT_Hits/CPT_DT, and, as a new score, CPT_Power which integrates the latter. Treatment consisted of surgery and chemotherapy ± LI/CSI. All children receiving CSI and MB children with LI showed substantial deficits in general intelligence scores. In contrast, children with MB or SET without CSI/LI and those with EP receiving LI performed surprisingly well after 2 and 5 years follow-up. Motor function (TS) was reduced in all children except those with SET without irradiation. Of note, mental processing speed (as measured in CPT_Power) was not essentially reduced in MB and EP patients, indicating that mental processing is less affected than motor speed (TS) in children with infratentorial tumors. In conclusion, our data show that besides the established detrimental effects of CSI on general intelligence, infratentorial tumor location is a main risk factor for motor dysfunction irrespective of irradiation. Appropriate sensitive testing tools are warranted to assess cognitive function without the interfering influence of motor dysfunction.
QOL-28. NEUROCOGNITIVE PROFILE OF PEDIATRIC MEDULLOBLASTOMA PATIENTS PRIOR TO RADIATION THERAPY
Authors: Baig Muhammad , Osthoorn Ineke , McGovern Susan , Grosshans David , McAleer Mary , Woodhouse Kristina , Paulino Arnold , Yang Grace , Stavinoha Peter , Zaky Wafik
Published: December 2020

Neurocognitive late effects are unfortunately common following treatment for pediatric medulloblastoma. While radiation therapy is an essential component of treatment for most pediatric medulloblastoma patients, it is associated with neurocognitive compromise. Effects include deficits in cognitive speed and performance efficiency, aspects of attention, as well as working memory. Yet long after treatment it is difficult to tease apart relative contributions of other risk factors to neurocognitive functioning beyond radiation. We examined neurocognitive functioning in a sample of pediatric medulloblastoma patients prior to radiation therapy, including investigation of neurocognitive risk factors such as hydrocephalus, presence of posterior fossa syndrome, and duration of neurological symptoms prior to diagnosis. Results indicated that the sample functioned in the average range in terms of overall IQ (n=34, X̅=103). Patients also functioned in the normal range in terms of language-based ability (X̅=106), nonverbal ability (X̅=104), and working memory (X̅=103). However, the sample performed statistically significantly lower than the general population in terms of cognitive speed and efficiency (z=-2.026, p=.043). The sample was also rated by parents as exhibiting more attention problems relative to the general population (z=1.988, p=.047). There was no specific association with hydrocephalus, duration of symptoms, or history of posterior fossa syndrome. Results suggest weaknesses in attention and processing speed may exist in some pediatric medulloblastoma patients prior to radiation therapy secondary to tumor and related complications. Implications for future research are presented, along with difficulties inherent to “baseline” assessment with pediatric brain tumor survivors.
QOL-32. THE PROMOTE STUDY: HEALTH-RELATED QUALITY OF LIFE COMMUNICATION NEEDS OF CHILDREN, ADOLESCENTS, AND THEIR FAMILIES ATTENDING OUTPATIENT CONSULTATIONS AFTER TREATMENT FOR A BRAIN TUMOUR
Authors: Stubley Shelly , Freeman Anita , Liossi Christina , Darlington Anne-Sophie , Grootenhuis Martha , Hargrave Darren , Morris Christopher , Walker David , Kennedy Colin , Bull Kim
Published: December 2020

BACKGROUND

Childhood brain tumours and their treatment can reduce health-related quality of life (HRQoL) and cause anxiety and depression, withdrawal, and social isolation. Improved communication within outpatient consultations may allow early identification and treatment of these issues. We explored family communication needs in survivors of childhood brain tumours receiving six-monthly follow-up outpatient review within the English NHS.

METHODS

Semi-structured interviews were conducted with 18 families whose child aged 8–17 years had finished treatment for a brain tumour within the preceding five years. Thematic analysis used the Framework Method.

RESULTS

Adjusting to change and finding a “new normal” was the overarching theme to emerge. HRQoL issues included fatigue, coping with physical changes, challenges at school, isolation, and adjusting to changes in abilities. Survivors described a need for greater knowledge about and more support with changes in cognitive functioning. Parents spoke about the impact on the wider family and their changed role in supporting the child’s HRQoL. Communication barriers included short-term memory loss, shyness, and the need to suppress or regulate emotions evoked by these issues. Communication needs included more information regarding recovery and rehabilitation and/or help managing anxiety or emotional health.

CONCLUSION

The above communication needs and barriers should be addressed. Having a digital record to document and monitor this information systematically could improve service planning and provide patients and their families with the resources to reach their full potential and experience a better HRQoL.
QOL-34. CAREER FAIR AND RESOURCE EXPO: ADVOCATING FOR THE LONG TERM SUCCESS OF BRAIN TUMOR SURVIVORS
Authors: Hoerig Clay , Allen Karlie , Noskoff Kara , Frediani Jamie , Pathare Jody , Koerner Casey , DeRosa Veronica , Madrid Nina , Miller Kristin , Mucci Grace , Abongwa Chenue , Plant Ashley
Published: December 2020

Pediatric cancer survivors have increased unemployment and lower educational attainment rates. This is most significant in brain tumor survivors who show five-fold relative odds increase in unemployment over other pediatric cancer survivors. The long-term effects of brain tumor treatment potentiate the difficulty with work and school reintegration seen in the broader Adolescent and Young Adult (AYA) population. To address this, our team designed an annual job fair for AYA Neuro-Oncology survivors. Vendors were invited representing disability advocacy groups, legal services, scholarship organizations, and employers with strong disability services, several who offered on-site interviews. Additionally, brain tumor survivors served as inspirational speakers for the event. Between thirty to forty survivors have attended each event. Pre- and post-surveys, as well as 3- and 6- month follow up was obtained. Universally, the day was engaging and motivating, both for survivors and staff, and stimulated conversation for pursuing career or academic success within families and the care team. While all the patients took applications, none of the patients completed the on-site interviews, finding them overwhelming. Even at the 3- and 6-month follow-ups following the first event, the survivors continued to be at varying levels of application completion; no one who was previously unemployed attained new employment. This improved after pre-event meetings were held with survivors to participate in resume building and interview preparation. Currently, two survivors obtained employment and are still employed at 1 year and five survivors were able to advocate for their disabilities services in college with help of a non-profit legal assistant.
QOL-46. LATE EFFECTS CARE FOR CHILDHOOD BRAIN TUMOUR SURVIVORS: A QUALITY IMPROVEMENT PROJECT
Authors: Cacciotti Chantel , Fleming Adam , Duckworth JoAnn , Tseitlin Hanna , Anderson Loretta , Marjerrison Stacey
Published: December 2020

BACKGROUND

Childhood and adolescent brain tumor survivors are at risk for considerable late morbidity and mortality from their disease and the treatment they receive. Surgery, chemotherapy, radiation therapy and tumor location all have the potential to impact the physical, psychological, functional and social health of these survivors. Comprehensive late effects care may mitigate these risks, but the necessary elements of this care model is unclear. We describe a quality-improvement initiative to improve the long-term follow-up (LTFU) care provided to brain tumour survivors at the McMaster Children’s Hospital.

METHODS

An anonymous needs assessment circulated to health providers was used to evaluate the LTFU practices. Utilizing this feedback as well as the LTFU guidelines from the Children’s Oncology Group a care plan was made for these survivors.

RESULTS

17 of 33 (52%) health care staff responded to the survey, this included 70% physicians or nurse practitioners, and 30% nurses and allied health staff. Improvements suggested included consistent inclusion of additional care providers (i.e. social work, dietitians, endocrinology) reported by 76%, as well as a need for improved patient education and surveillance for late effects of therapy.

CONCLUSION

Treatment summaries with surveillance care plans and LTFU resources were created for all survivors of childhood brain tumours at risk of treatment-related complications. Late effects counselling with distribution of these materials is ongoing as part of this quality improvement initiative. To provide comprehensive management, a neuro-oncology specific late effects programs with multi-disciplinary support is essential for the care of brain tumour survivors.
QOL-49. THE IMPACT OF OTOTOXICITY AND VISUAL IMPAIRMENT ON EDUCATION IN CHILDREN TREATED FOR CNS TUMOURS
Authors: Dulson Harriet , McAndrew Rachel , Brougham Mark
Published: December 2020

INTRODUCTION

Children treated for CNS tumours experience a very high burden of adverse effects. Platinum-based chemotherapy and cranial radiotherapy can cause ototoxicity, which may be particularly problematic in patients who have impaired vision and cognition as a result of their tumour and associated treatment. This study assessed the prevalence of impaired hearing and vision and how this may impact upon education.

METHODS

53 patients diagnosed with solid tumours in Edinburgh, UK between August 2013–2018 were included in the study. Patients were split into three groups according to treatment received: Group 1 – cisplatin-based chemotherapy and cranial radiotherapy; Group 2 - platinum-based chemotherapy, no cranial radiotherapy; Group 3 – benign brain tumours treated with surgery only. Data was collected retrospectively from patient notes.

RESULTS

Overall 69.5% of those treated with platinum-based chemotherapy experienced ototoxicity as assessed by Brock grading and 5.9% of patients had reduced visual acuity. Patients in Group 1 had the highest prevalence of both. 44.4% of patients in Group 1 needed increased educational support following treatment, either with extra support in the classroom or being unable to continue in mainstream school. 12.5% of Group 2 patients required such support and 31.3% in Group 3.

CONCLUSIONS

Children with CNS tumours frequently require support for future education but those treated with both platinum-based chemotherapy and cranial radiotherapy are at particular risk, which may be compounded by co-existent ototoxicity and visual impairment. It is essential to provide appropriate support for this patient cohort in order to maximise their educational potential.
QOL-51. LISTENING BEFORE WE SPEAK: A PATIENT-CENTERED APPROACH TO DEVELOPING RESOURCES FOR PEDIATRIC BRAIN TUMOR SURVIVORS AND THEIR FAMILIES
Authors: Riley Kathy
Published: December 2020

In the United States, more than 28,000 children and teenagers live with the diagnosis of a primary brain tumor (Porter, McCarthy, Freels, Kim, & Davis, 2010). In 2017, an estimated 4,820 new cases of childhood primary brain and other central nervous system tumors were expected to be diagnosed in children ages 0 – 19 in the United States (Central Brain Tumor Registry of the United States, 2017). Survivors suffer from lifelong side effects caused by their illness or by various treatments. Commonly identified late effects of treatment include a decline in intellectual functioning and processing speed, performance IQ deficits, memory deficits, psychological difficulties, deficits in adaptive functioning (daily life skills), and an overall decrease in health-related quality of life (Castellino, Ullrich, Whelen, & Lange, 2014). To address the ongoing challenges these survivors and their families face, the Pediatric Brain Tumor Foundation (PBTF) met extensively with working groups comprised of survivors and caregivers to develop the outline for a comprehensive Survivorship Resource Guidebook. In 2019, the PBTF published the guidebook which categorizes survivor and caregiver needs into three primary areas: physical and mental health, quality of life, and working the system. Expert authors included survivors and caregivers themselves in addition to medical and mental health professionals. Key outcomes discovered during the creation and production of this resource highlight how caregivers, survivors and professionals can collaborate to provide needed information and practical help to one segment of the pediatric cancer population who experience profound morbidities as a result of their diagnosis and treatment.
RARE-02.RE-IRRADIATION FOR RECURRENT CRANIOPHARYNGIOMA
Authors: Foran Sarah , Laperriere Normand , Edelstein Kim , Janzen Laura , Ramaswamy Vijay , Shultz David , Gentili Fred , Bouffet Eric , Tsang Derek
Published: December 2020

PURPOSE

Patients with recurrent craniopharyngioma after radiotherapy (RT) have few treatment options. At our institution, re-irradiation has been offered to selected individuals with recurrent craniopharyngioma not suitable for further surgery, intracystic therapy or targeted agents.

METHODS

A retrospective study was performed of patients with craniopharyngioma treated with two courses of fractionated RT. First RT (RT1) prescriptions ranged from 50–54 Gy in 25–30 fractions; re-irradiation (RT2) prescriptions were 54 Gy in 30 fractions with full, in-field overlap of dose. The maximum dose to organs-at-risk (brainstem, optic structures) were maintained at or below the prescription dose. There was no cumulative dose limit to any structure.

RESULTS

We identified four patients. Median RT1-to-RT2 interval was 5.8 years (range, 4.7–20.4). Cumulative maximum doses to optic chiasma and nerves were >100 Gy in all four patients. With a median follow-up of 33 months after RT2, three patients had disease control and are alive at 9, 23 and 42 months from RT2; one patient developed progressive disease and died 33 months after RT2. In three evaluable patients, vision remained stable or improved after RT2; the remaining one patient had no light perception prior to re-irradiation. Two patients had neuropsychological testing before and after RT2; neurocognitive domains were generally stable in one patient but working memory declined in the second patient.

CONCLUSIONS

Despite exceeding usual tolerances for optic chiasm and nerves, visual outcomes were stable in all living patients. Re-irradiation should be discussed as a treatment option for patients with recurrent craniopharyngioma but without other therapeutic options.
RARE-03. AGGRESSIVE RESECTION FOR PEDIATRIC CRANIOPHARYNGIOMAS VIA ENDOSCOPIC ENDONASAL APPROACH
Authors: Morisako Hiroki , Goto Takeo , Ohata Hiroki , Sakamoto Hiroaki , Ohata Kenji
Published: December 2020

OBJECTIVE

In recent years, the endoscopic endonasal approach (EEA) has been increasingly used for pediatric craniopharyngiomas. We here present our experience and the outcomes of the EEA resection of pediatric craniopharyngiomas.

MATERIALS AND METHODS

Between April 2014 and December 2019, 16 cases of pediatric craniopharyngiomas were operated at the Osaka city university (OCU) hospital. Eight patients were diagnosed with primary craniopharyngiomas while 8 had a recurrent tumor. There were 5 males and 11 females, with a mean age of 10.7 years (3–17 years). EEA was selected in all patients and a case of large muti-lobulated tumor was resected by combination of microscopic transcranial approach.

RESULTS

Gross total resection was achieved in 14 patients and near total resection in other 2. Post-op CSF leak occurred in 3 patients, which was treated with re-exploration. Pituitary stalk was preserved intraoperatively in 4 cases, and 15 patients developed diabetes insipidus and anterior hormonal replacement therapy was required in 15 patients at last follow-up. Visual improvement was noted in 4 patients while vision remained unchanged in the rest. Neuropsychological function status was preserved in all patients, and there was no new-onset obesity postoperatively. The mean follow-up duration was 35.1 months (2 – 69 months) and 4 of 8 recurrent cases had re-recurrence during this period, however there was no recurrent in 8 primary cases.

CONCLUSIONS

EEA should be the surgical modality of choice for treating pediatric craniopharyngiomas. It results in better visual and cognitive outcomes with a significantly increased extent of resection.