bluuebunny/crossref_metadata_2025 huggingface dataset:
QOL-25. Neurocognitive assessment of pediatric medulloblastoma treated by MBMET_MEYER trial. Censullo M.L1, Bertoluzzo G2, Fonte C1, Pavone R1, Guidi M1, Enrico G1, Gori C.G1, Martin R2, Teodori C2, Sardi I1 1Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children’s University Hospital, Florence, Italy2Psychology Unit, Meyer Children’s University Hospital, Florence, Italy
Authors: Censullo Maria Luigia , Bertoluzzo Giulia , Fonte Carla , Pavone Rossana , Guidi Milena , Giorgia Enrico , Gori Carlotta Gemma , Martin Rosanna , Teodori Caterina , Sardi Iacopo
Published: June 2022

The MBMET_MEYER is an interventistic monocentric trial of Meyer Children’s Hospital. The goal of this protocol is to reduce toxicity by use of protontherapy and reducing chemo-induced neurotoxicity by limited use of high dose chemotherapy. To date, a neurocognitive assessment is the standard in medulloblastomas but it is very difficult an assessment at baseline for clinical problems such as age, intracranial hypertension and immediate intervention. 10 neurocognitive assessments were reviewed in patients with medulloblastoma treated by MBMET_MEYER protocol: 3 anaplastic medulloblastoma M0 and 7 classic (2 M0, 1 M1, 1 M2, 3 M3). The median age was 10 years (range 5-18). All the patients were treated with surgery (gross total removal), 2 received chemotherapy and conventional radiotherapy, 8 chemotherapy and protontherapy and only 1 received autologos-hemotopoietic stem cell transplant for progression disease after induction chemotherapy. As for protocol, the neurocognitive assessment was defined by Weschler Intelligence Scales, fonemic and semantic fluency, immediate and deferred memory, tests for working memory, attention and visuo-spatial tests at baseline, after treatment and at the end of follow-up. For 3 patients it was not possible a baseline assessment for bad clinic conditions, 8 are still in treatment. From interviews and assessments emerged that 80% of patients had neurocognitive deficits: at baseline 5 had speed elaboration difficulties, 1 of these also presented verbal deficit, 1 showed problems in recalling verbal material and 1 in working memory; after two years from chemotherapy and radiotherapy 2 presented speed processig and working memory deficit. In conclusion, an assessment at baseline is very difficult for post-surgical problems but necessary to perform as soon. In this way, it is possible to evaluate the impact of the treatment on neurocognitive impairment. Further investigations are necessary to well understand the appropriate schedule of neurocognitive assessment of pediatric medulloblastoma.
QOL-28. Clinico-molecular correlates of quality of survival and neurocognitive outcomes in medulloblastoma; a meta-analysis of the SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 trials
Authors: Chevignard* Mathilde , Bull* Kim S , Holt James , Harrington Bertie , Castle Jemma , Heng Marie-Amelie , Kennedy Colin , Doz Francois , Lannering Birgitta , Rutkowski Stefan , Massimino Maura , Bailey Simon , Oyefiade Adeoye , Mabbott Donald , Clifford† Steven C , Hicks† Debbie
Published: June 2022

Determinants of survivorship outcomes are emerging from limited studies of medulloblastoma (MB) survivors. We undertook an integrated analysis of biological (tumour group, host genetics) and clinico-demographic features in patients treated on the SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 clinical trials with available quality of survival (QoS) data (n=218), to determine key correlates of survivorship, and their clinical potential. Treatment/demographic factors and molecular subgroup (MBWNT, MBSHH, MBGrp3, MBGrp4) were assessed against health status, behavioural functioning, and health-related quality of life (HrQoL). In DNA from HIT-SIOP-PNET4 (n=74), 39 candidate SNPs with known modifying effects on neurocognitive outcomes (e.g., involved in oxidative stress/inflammation) were genotyped and assessed against Wechsler Intelligence Scale (WISC) scores. As expected, MBSHH was associated with improved HrQoL, but subgroup did not associate further with QoS outcomes. SIOP-UKCCSG-PNET3 patients receiving chemotherapy before craniospinal irradiation (CSI) had significantly lower health status (p=0.021) and behavioural functioning (p<0.016) compared to patients treated with CSI alone, and those treated on both arms (maintenance chemotherapy and hyperfractionated (36Gy) or standard (23.4Gy) CSI) of HIT-SIOP-PNET4. SIOP-UKCCSG-PNET3 patients receiving CSI-only had better HrQoL scores than those who received pre-CSI chemotherapy and both HIT-SIOP-PNET4 arms (p=0.004). Females reported worse HrQoL/behavioural functioning across both trials (p<0.04). In HIT-SIOP-PNET4, longer intervals from diagnosis to CSI predicted worse HrQoL/health status (p<0.05). Neither molecular group nor clinico-demographic features tested were associated with neurocognition. In contrast, 6 SNPs significantly associated with ≥1 WISC domain; 4/6 showed multiple associations and were independently prognostic; further associations were apparent at the gene/pathway level. This large, integrated and multi-disciplinary analysis of two independent trials cohorts has revealed multiple factors predictive of medulloblastoma survivorship including treatment (chemotherapy, time to CSI), tumour (molecular group) and host genetic factors. Assessment in further prospective series are required to determine their potential as a basis for modifications to disease management.
QOL-33. Adaptive behaviour of patients treated for malignant brain tumor in the first three years of life
Authors: Giaquinta Simonetta , Tremolada Marta , Rossi Bartolomeo , Biffi Alessandra , Viscardi Elisabetta
Published: June 2022

BACKGROUND: Adaptive behavior is defined as the effectiveness and degree to which an individual meets social/cultural standards of personal independence and social responsibility. Patients treated for brain tumor are at risk of alteration of adaptive behaviour that, with a reduced intellectual function, makes diagnosis of mental retard. OBJECTIVE: The aim of this study was to evaluate the adaptive behaviour of patients treated for malignant brain tumor in the first three years of life and the variables that may correlate with its alteration. PATIENTS AND METHODS: Twelve survivors of brain tumor diagnosed in the first three years of life followed in the Pediatric Hematology and Oncology Department of Padua between January 2000 and December 2020 were enrolled in this study. We defined the level of the adaptive behaviour by evaluation adaptive behavior questionnaire (ABAS II) completed by the parents. RESULTS: None of the patients shows a high level of adaptive behavior. Preliminary evidences suggest that, the level of adaptive behavior may be influenced by the sex, irradiation and time from the end of treatment. In details, females show a higher level of performance than males, patients not treated with radiotherapy performed better than patients irradiated and longer-term survivors have a better level of adaptive behaviour. CONCLUSIONS: This study confirms that patients treated for brain tumor show a lower level of adaptive behaviour than peers. The future objective is to assess adaptive behaviour at many times to recognize the problem early.
QOL-34. The relationship between Psychological Flexibility, Quality-of-Life and psychological health in young people who have experienced a brain tumour
Authors: Airdrie Jac , Geagan Chloe , Davies Nicholas , Powers Katie , Wright Ingram , Borrill Heather , Gibson Faith , Clifford Steve , Lowis Stephen , Bailey Simon , Limond Jennifer , Owen Ray , Grundy Richard , Lemon James , Hayes Louise , Malins Sam , Thomas Sophie
Published: June 2022

Despite increasing survival rates in young people who have experienced a brain tumour, this patient group have the poorest reported quality-of-life (QoL) of all cancer survivors. QoL is defined as an individual’s perception of their position in life in relation to their goals, expectations and standards. QoL can be influenced by physical functioning but one of its strongest predictors is psychological health. A concept that has a large impact on psychological health is Psychological Flexibility (PF). PF refers to the ability to recognise and adapt to situations, shift cognitive and behavioural repertoires which are impacting negatively on personal and social functioning and commit to behaviours that are in line with strongly held values. Studies have demonstrated a relationship between PF and QoL in other patient populations such as chronic pain and breast cancer survivors. In this study we explored the relationship between PF and QoL at baseline in a sample of young people enrolled in a randomised controlled trial of Acceptance and Commitment Therapy (ACT) for young people who have experienced a brain tumour. We found that higher PF was associated with higher QoL in both 11-15 year olds (R2 = .69, p < .05) and 16 – 24 year olds (R2 = .29, p < .01). We also found higher PF was associated with lower levels of mental health difficulties (R2s ≥ .24, ps < .01) which was also associated with higher levels of QoL (R2 = .49 , p < .01). The results suggest assessing and providing support to increase PF is important for young people who have experienced a brain tumour. It highlights that interventions found to increase PF, such as ACT, could be helpful in improving psychological health in this population.
QOL-35. School reentry of children and adolescents with a brain tumor: can we improve family-school-hospital cooperation? An analysis of supportive and inhibiting factors as a result of a pilot project
Authors: Leiss Ulrike , Krottendorfer Kerstin , Pletschko Thomas , Peyrl Andreas , Azizi Amedeo , Wekerle Karoline , Schneider Fee , Rosenmayr Verena , Sanin Lisa , Weiler-Wichtl Liesa Josephine , Kutschera Andrea
Published: June 2022

OBJECTIVE: School reentry support focusing on providing information to schools and communication between patient/family-hospital-school is defined as a psychosocial standard of care in pediatric oncology (Thompson et al., 2015). This is critical for students with brain tumors (BT) - although it is not yet universally implemented - especially during follow-up, as they are a risk group for late effects. Due to long distances between family-hospital-school, limited personnel capacities and since 2020 Covid-19 restrictions, an online-event (OE) for teachers from external schools was designed, with the aim of: (1) strengthening cooperation, (2) breaking down barriers and (3) increasing level of knowledge.

METHODS: 54 teachers participated in each of two OEs. Content was presented by an interdisciplinary team (clinician, clinical/neuropsychologist, social worker, teacher), followed by time for sharing experience. Two months after event 2, participants were asked to complete an evaluation in an anonymous online survey. Supportive and inhibiting factors for successful school reintegration were included in the survey and statistically analyzed.

RESULTS: 54% of 23 respondents (70% teaching > 10 years) felt that their training before the event did not prepare them adequately for a teaching setting with seriously ill children (1-3 points on a 10-point Likert-scale). 92% rated their knowledge greater after the event. All interdisciplinary inputs were rated very useful and practical (79-88%: 8-10 points). 38% felt relieved to got to know contact persons. 33% rated teaching a student with BT as fundamentally challenging and felt more confident after the event.

CONCLUSION: The results of this pilot project indicate that an online-information-event can increase knowledge and cooperation. Resulting promoting and inhibiting factors for school reintegration will be incorporated into future concept improvement. The findings further highlight the great importance of ongoing support in the form of a reintegration teacher and interdisciplinary input for schools to appropriately support students with BT.
SURG-03. Durability of an Early Management Strategy Facilitating Endoscopic Removal of Recurrent Choroid Plexus Carcinoma
Authors: Guadix Sergio , Garman Tyler , Pisapia David , Souweidane Mark
Published: June 2022

BACKGROUND: Choroid plexus carcinoma (CPC) is a rare, primarily intraventricular neoplasm with a dismal prognosis. Extent of surgical removal is correlated with improved outcomes but is frequently limited due to tumor vascularity and size. Information related to surgical management and molecular drivers of tumor recurrence is currently limited. Here we characterize a case of multiply recurrent CPC treated solely with sequential endoscopic tumor removals over a 10-year period and highlight its genomic properties. METHODS: We performed a retrospective review of a 16-year-old female treated for CPC with local and distal recurrences undergoing repeat excision with minimally invasive neuro-endoscopy. We describe technical nuances associated with neuro-endoscopic intervention, mean hospital stay, complications, and perioperative MRI. Whole exome sequencing (WES), targeted sequencing, and methylation profiling results over time are reviewed. RESULTS: Five years after standard treatment, the patient was evaluated for a distant intraventricular recurrence. A total endoscopic resection was performed given the local, non-disseminated recurrence pattern. WES results included NF1, PER1, and GLI3 mutations as well as FGFR3 gain, and was negative for TP53 alterations. Repeat sequencing on a recurrence 4 years later showed persistent NF1 and FGFR3 alterations. Methylation profiling was consistent with “plexus tumor, subclass pediatric B”. Overall, short-term surveillance neuroimaging detected four isolated recurrences, all treated with complete endoscopic resections at 5 years, 6.5 years, 9 years, and 10 years after initial CPC diagnosis. Mean hospital stay for all recurrences was 1 day with no complications from treatment. CONCLUSION: We describe a patient with 4 isolated recurrences of CPC over a decade, each treated with complete endoscopic removal, and identify an unusual set of molecular alterations that persisted over time. These outcomes support a strategy encompassing frequent neuroimaging surveillance to facilitate a minimally invasive endoscopic surgical approach at early detection and relatively low tumor mutagenicity.
SURG-06. Management outcome (5years or more) of paediatric vertebral haemangiomas presenting with myelopathy
Authors: Singh Pankaj , Chandra Sarat , Kale Shashank
Published: June 2022

INTRODUCTION: Vertebral hemangiomas are very rare in pediatric age group. In this study we analysed the outcomes of patient treated at department of neurosurgery , All india institute of medical sciences New Delhi since may 2010 to January 2022 with at least 5 year follow up. MATERIALS AND METHOD: All patients up to 18 years age of vertebral haemangioma treated at our hospital from may 2010 to january 2022 with at least 5 year follow up. All had features of myelopathy.Patients demography, clinical details and follow up and complications were retrieved from hospital records. Functional clinical outcomes were measured using ASIA score. Mean age was 14.21 years with range of 12 years to 18 years. All patients had magnetic resonance imaging and computed tomography of spine in preoperative and postoperative period. Mean follow up was 78 months with range from 60 month to 144 months. RESULTS: There were 6 male and 8 female patients with sex ratio of 3:4. All were located in dorsal spine with single level involvement . Upper dorsal spine involvement was more common (10 cases 71.43%) than lower dorsal spine involvement (4 case 28.57%). All patients had weakness of lower limbs with features of myelopathy, urinary bladder symptoms were present in 6 patients local site pain in 1. D1 involvement was present in 1, D3 in 2, D4 in 2, D5 in 2, D6 in 3 , D8 in 1,D10 in 1,D11 in 1 and D12 in 1. All patients have improvement in power of both lower limbs after surgery. Bladder symptom and pain resolved in all patients. CONCLUSION: Good postoperative results can be achieved in pediatric symptomatic vertebral hemangioma with minimal complications. Individualization of treatment for each patient should be done with avoidance of selecting more blood loss procedures like corpectomies.
SURG-12. Endoscopic evaluation of ventricular dissemination in primary central nervous system (CNS) germ cell tumors (GCTs)
Authors: Yan Rachel , Lin Tong , Carnevale Joseph , Bhatia Aashim , Shaw Dennis , MacDonald Shannon , Murphy Erin , Leary Sarah , Bartels Ute , Khatua Soumen , Fouladi Maryam , Gajjar Amar , Dhall Girish , Fangusaro Jason , Onar-Thomas Arzu , Souweidane Mark
Published: June 2022

INTRODUCTION: Endoscopic third ventriculostomy and endoscopic tumor biopsy have become integral to the surgical management of children with primary CNS GCTs. Observing ependymal tumor dissemination at the time of endoscopic surgery has been anecdotally reported. The incidence and impact of this finding in CNS GCT has not been reported. METHODS: Baseline neurosurgery data capture forms and operative reports from the Children’s Oncology Group (COG) ACNS1123 study were reviewed for ventriculoscopic findings of suspected tumor dissemination. The association between these findings and relapse was determined using Fisher’s exact test for each stratum and the Cochran-Mantel-Haenszel test for the entire cohort. Progression-free survival (PFS) was defined as time from enrollment to relapse, progression, death, or last follow-up; and survival probabilities were estimated using the Kaplan-Meier method with log-rank tests for outcome comparisons. RESULTS: 110/244 patients (45.1%) underwent endoscopic neurosurgery. Twelve patients (10.9%) had a documented observation suggestive of metastatic disease within the ventricular compartment. Ten were in the third ventricle and two were in the lateral ventricle. Nine of 12 were nongerminomatous germ cell tumors (NGGCTs) and three were germinoma. Ventriculoscopic findings of metastatic tumor were not significantly associated with relapse in NGGCT (p=0.4091), germinoma (p=0.1832), or overall (p=0.1540); odds ratio 2.57 (95%CI:0.66–10.11). PFS was not influenced in NGGCT (Log-rank test, p=0.1953) but was negatively impacted in germinoma (p=0.0250) when tumor dissemination was found during ventriculoscopy. CONCLUSIONS: Ventriculoscopic observation of tumor dissemination was reported in 10.9% of cases. This may negatively influence outcomes in children with germinoma, though due to the small number of relapses, more data is needed to verify these findings. Ventriculoscopic observation of tumor dissemination may contribute toward more accurate staging and influence future therapy, but a larger sample size is needed. Prospective studies should routinely integrate documentation of endoscopic observation in the study protocol.
SURG-13. The COMBAT Project - Core post operative morbidity set for paediatric brain tumours
Authors: Trichinopoly Krishna Sandhya , Millward Christopher , Mallucci Conor , Gamble Carrol , Jenkinson Michael , Pizer Barry
Published: June 2022

BACKGROUND: Brain tumours are associated with high morbidity both from the tumour and the medical and surgical interventions used to treat them. Post operative morbidity reporting following surgery for paediatric brain tumours is poor due to the lack of a common language when reporting harms. One solution is to develop a core adverse outcome set to stipulate the minimum post operative harms that should be reported. The COMBAT (Core post operative morbidity set for paediatric brain tumours) Project will develop a core adverse outcome set that can be applied to post operative paediatric brain tumour patients to harmonise how harms are measured and reported, enabling comparison between different trials, studies and clinical services. We aim to generate interest in the COMBAT Project and invite collaboration with healthcare professionals and researchers experienced in paediatric neuro oncology surgery. METHODS AND ANALYSIS : A systematic review will identify harms reported in post operative paediatric brain tumour patients and how they are measured. We will engage with national and international stakeholders including healthcare professionals, researchers, patients and their carers. Qualitative interviews with patients and carers will identify any important harms not extracted in the systematic review. A Delphi survey will be created from the harms identified. An international consensus meeting will be held to finalise the core adverse outcomes set. The final core adverse outcome set will be published and disseminated to encourage uptake. DISCUSSION: There is a clear need for a common language to harmonise measurement and reporting of harms following surgery for paediatric brain tumour patients. The core adverse outcome set will be developed with collaboration with key stakeholder groups to ensure it is representative. It will be used to standardise surgical morbidity outcome measurement and reporting in trials, studies and clinical practice and will inform future research in this field.
SURG-15. A Case Series of Pediatric Patients with Brain Tumors and Perioperative COVID-19 Infection
Authors: Emmanuel Torio John , Baticulon Ronnie , Alcasabas Anna Patricia
Published: June 2022

INTRODUCTION: Surgery in patients diagnosed with COVID-19 is associated with increased risk of morbidity and mortality, especially within 6 weeks of SARS-CoV-2 infection. Furthermore, most studies have focused on adults, and little is known about perioperative outcomes in children with COVID-19. METHODS: We reviewed the operative census of the Division of Neurosurgery of Philippine General Hospital from March 2020 until December 2021. We identified all pediatric patients with brain tumors and confirmed COVID-19 infection within two weeks of their neuro-oncologic surgery. Their clinical course and outcomes are described herein. RESULTS: Four patients were included in this case series: three had tumors in the cerebellum, one in the pineal region. All of them were boys, with ages ranging from 4 months to 13 years. All tumors were malignant, and two were confirmed to be medulloblastoma after tumor resection. COVID-19 infection was diagnosed by the presence of SARS-CoV-2 RNA through a nasopharyngeal swab. Three patients acquired the virus post-operatively, likely from nosocomial transmission. In the remaining patient, it was community-acquired. All the patients had chest radiographs consistent with pneumonia but none had marked elevation of serum inflammatory markers. No patient received remdesivir or tocilizumab. At the time of their presentation, either the COVID-19 vaccine was not yet available in the country, or the patient was not yet eligible for vaccination. One patient died because of brain herniation from tumor progression, two were discharged and eventually underwent adjuvant therapy, and one remained in-hospital as of this writing. DISCUSSION: COVID-19 infection resulted in delays in the management of patients with pediatric CNS tumors. Given the high risk of these patients for potential complications, consensus guidelines must be established to achieve good outcomes and prolong survival.
SURG-17. Impact of introduction of sagittal dimensions to predictive model of post-operative cerebellar mutism (CMS): A report of the Nottingham CMS Workshop
Authors: Walker David , Liu Jo-Fen , Dineen Rob A , Thomale Ulrich-Wilhelm , Driever Pablo Hernáiz
Published: June 2022

BACKGROUND: The Nottingham-Liverpool risk stratification tool for predicting post-operative cerebellar mutism syndrome (CMS) requires further refinement. Previous smaller studies identified tumours arising in cerebellar hemispheres (CH+ve) as very low risk and proposed that larger sagittal dimensions may be associated with a higher CMS risk. METHODS: An international multi-centre workshop assembled clinical, imaging and surgical data from 242 posterior fossa tumour patients from 9 centres (age 2-23.8, mean 8.23 years; histology 122 medulloblastoma, 75 pilocytic astrocytoma, 25 ependymoma, 18 other tumour types, 2 not known). Post-operative CMS developed in 0/66 CH+ve and 40/176 CH-ve patients (23%, range 13-33%) and. Tumour measurements in the sagittal plane were incorporated into the predictive model. RESULTS: In CH-ve tumours, CMS was associated higher D-Sag (CMS+ve 3.91±1.08 vs CMS-ve 3.01±1.56 cm p=0.001), d-Sag (CMS+ve 0.63±0.27 vs CMS-ve 0.44±0.31 cm p=0.001) and D-Sag*d-Sag (CMS+ve 2.60±1.36 vs CMS-ve 1.65±1.45 cm2 p=0.001). The Rotterdam model identified CMS rates for CH-ve tumours for low, intermediate and high risk groups as: 4% (2/45), 20% (16/79) and 42% (22/52), respectively. CONCLUSIONS: Incorporating D-sag and d-Sag estimates of tumour size, proposed, and adopted by the Beijing and Rotterdam groups, respectively, enhanced the objectivity and supports the model’s CMS predictive capacity for the purposes of consent and future trials. Higher CMS risk, associated with larger sagittal dimensions, may account for variability in CMS rates between cohorts and, as a new finding, may have broader clinical implications around the timing of diagnosis.
NURS-01. Development and Implementation of a MEK Inhibitor Targeted Therapy Standardized Educational Curriculum for Pediatric Oncology Patients, Caregivers, and Clinical Staff
Authors: Rangan Kasey , Bira Kimberly , Bryant Lauren , Waters Kaaren
Published: June 2022

Molecular targeted therapies have become a fundamental treatment regimen within pediatric oncology practice, yet these medications are not without side effects, which often require interruption, dose reduction, or early discontinuation of treatment. Existing chemotherapy education curriculums focus on the side effect profile of traditional chemotherapy regimens and do not include standardized instruction on toxicities related to targeted therapies, resulting in a knowledge gap for caregivers and the clinical team. The purpose of this project was to development and implement a standardized teaching curriculum to educate patients, caregivers and clinical staff on common toxicities related to MEK inhibitors including anticipated side effects, symptom management, and toxicity surveillance. The education was presented to patients and families by a neuro-oncology nurse or nurse practitioner at the initiation of MEK inhibitor therapy. The cohort consisted of 11 patients over a 12-month period with a diagnosis of plexiform neurofibromas and neurofibromatosis type 1. Additionally, the education curriculum was presented to clinical staff during an in-service and included a pre-post intervention survey to assess effectiveness of the education curriculum. The results demonstrated that increasing patient and family knowledge at initiation of MEK inhibitor therapy likely leads to fewer dose reductions, drug interruptions, and early therapy discontinuations. Greater than 90% of the patient cohort were able to complete the treatment regimen without early termination due to toxicity, with only 18% requiring dose reduction and 9% requiring interruption of therapy. Surveys evaluating the effectiveness of the staff educational curriculum demonstrated an increased knowledge in the identification and treatment of MEK inhibitor side effects with a 26% improvement in survey results post-intervention. This project is a feasible educational approach for preventing and treating toxicities associated with MEK inhibitors and can be initiated at pediatric oncology practices to standardize MEK inhibitor education to clinicians, patients, and caregivers.
OTHR-11. The effects of the COVID-19 Pandemic on the time to diagnosis in pediatric patients with Primary central nervous system tumors
Authors: Canova Tyler , McNinch Neil , Judd Alexis , Rush Sarah , Wright Erin
Published: June 2022

Primary central nervous system (CNS) tumors are a leading cause of death and disability amongst pediatric cancer patients. The early identification of symptom onset is critical in preventing diagnostic delays. In 2018, Akron Children’s Hospital published data on our response time to brain tumor diagnosis and launched educational programs in an effort to decrease diagnostic delays. The goal was to reduce the total diagnostic interval (TDI) in our patient population and reduce tumor- and treatment-related morbidities for these patients. Our post intervention group (2018-2021) was drastically affected by the numerous hospital changes secondary to the COVID-19 pandemic. We sought to examine the impact of COVID-19 related changes on TDI and attempted to identify groups at potential increased risk for diagnostic delays due to the unique pandemic constraints. A retrospective chart review was performed on patients at Akron Children’s Hospital to evaluate both for pre- (diagnosed Jan 1, 2018-February 29, 2020) and post-COVID-19 (diagnosed Mar 1, 2020-June 8, 2021) groups. Both subsets were evaluated statistically and were similar in all respects including demographics, symptomatology, tumor location, tumor type, and survival. The pre-COVID-19 group demonstrated a median TDI of 43.5 days, while the post-COVID-19 group demonstrated a 30-day median. The TDI for low-grade lesions increased from 32 to 59 days and for high-grade lesions decreased from 60 to 27.5 days in the post-pandemic cohort. Overall, this demonstrates a maintained average time to diagnosis for patients despite the pandemic restrictions in place. In addition, the differences in low vs. high-grade lesions suggest that tumors with a more subtle onset of symptoms were disproportionately affected, and highlight a population for intervention during the continued pandemic.
OTHR-13. Effectivity and toxicity of off-label treatment with Trametinib monotherapy or in combination with Dabrafenib in children with relapsed or refractory brain tumor
Authors: Bregonje S (Selena) , de Vos-Kerkhof E (Evelien) , Engels F K (Frederike) , van Veelen M L C (Marie-Lise) , van der Lugt J (Jasper)
Published: June 2022

INTRODUCTION: Most pediatric low grade gliomas, and a substantial part of PXAs, have a BRAF alteration/activated MAPK pathway. This group often requires several lines of therapy, which coincides with significant morbidity. There is growing evidence that molecular targeted treatment may be beneficial for this population. Here we report the toxicity and efficacy of patients treated off-trial with either trametinib monotherapy or in combination with dabrafenib. METHODS: We performed a single-center retrospective chart review of all neuro-oncological patients who received trametinib monotherapy or in combination with dabrafenib (compassionate-use) in the Princes Maxima Center between April 1st, 2018 and December 31st, 2021. RESULTS: 22 patients (ages 1-21 years) were included of whom 14 received trametinib monotherapy (BRAF-KIAA fusion, n=10) and eight received trametinib/dabrafenib combination therapy (BRAFV600 mutation, n=8). All patients on trametinib monotherapy (n=14) developed skin problems such as rash (100%), dry skin (86%), paronychia (71%) and eczema (64%). Eight patients (57%) had at least one adverse event (AE) ≥grade 3. Patients on trametinib and dabrafenib showed similar toxicity, although with lower prevalence and no paronychia. One patient (13%) had an AE ≥grade 3. Median treatment time of trametinib was 514 days (IQR 455) and for trametinib and dabrafenib 360 days (IQR 512). Five patients (36%) on trametinib are still on treatment and nine patients (64%) stopped treatment due to e.g. tumor progression or toxicity. All patients on trametinib and dabrafenib are still on treatment. Best overall response of trametinib monotherapy (n=14 evaluated) was observed as partial response (50%), stable disease (33%) and progressive disease (17%). Combination therapy (n=7 evaluated) brought 100% partial response. CONCLUSION: Dermatological toxicities are mostly seen in trametinib monotherapy or in combination with dabrafenib. Despite moderate toxicity patients seem to benefit from treatment. Results suggest that combination therapy has a more favorable toxicity profile than monotherapy.
OTHR-14. Responding to the COVID Challenge: evaluating a new method of adverse event recording in response to remote working.
Authors: Reiners Stephanie , Barnwell Alison , Murray Lisa , Abdelbaki Mohamed , Jones Sally , Lluka Brunilda , Roemerman Heather
Published: June 2022

BACKGROUND: The SARS-COV2 pandemic had huge impact on how clinical research is conducted when clinical research coordinators (CRC) transitioned to working remotely. An urgent transition of paper documentation into electronic formats had to occur without compromising participant safety or data integrity. Adverse event (AE) reporting had previously been captured in various paper formats with wet signature. AEs, attribution, severity, and clinical significance had to be changed into being electronically captured and incorporated into the medical record that captures the events in real time. METHOD: We assessed the satisfaction of the new method of AE recording amongst pediatric hematology oncology physicians and staff in a large academic institution during the COVID pandemic through a REDCap survey. The survey assessed the time, effort, perceived efficacy and overall acceptability of the paper-based and electronic methods of AE documentation. RESULTS: Seventy-one staff members were surveyed. Fifty (65%) responded, including 6 participants who were not involved in the AE reporting process and did not complete the survey. Of the remaining 44 participants, 43 (98%) preferred an electronic documentation method. Secondary results and further analysis will be presented at the meeting. CONCLUSIONS: The COVID pandemic has changed how CRC report AEs and electronic documentation seems to be the preferred method of documentation.
PATH-01. Infant-Type Hemispheric Glioma: New Molecular Alterations and Precision-Medicine Treatment
Authors: Hu Wanming , Yuan Li , Zeng Jing
Published: June 2022

BACKGROUND: Infant-type hemispheric glioma, harboring alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET, is a new subtype of Pediatric-type diffuse high-grade gliomas in the 2021 WHO classification of CNS tumors. It has important clinical therapeutic value with specialized therapeutic drugs. Here, we presented 3 cases of infant-type hemispheric glioma. Patient1 with EML4-ALK fusion which often appeared in lung cancer, the other 2 patients have new molecular alterations which has not been reported before (Patient2 has both NTRK1-TP53/TP53-NTRK1 fusions and p53 protein showed characteristic cytoplasm positive; Patient3 presented a brand-new ALK-QKI fusion combined with ALK mutation and focal SMARCB1 deletion. All these 3 cases received corresponding targeted therapy and have a good recovery and normal neurologic function till now.

METHOD: Immunohistochemistry, fluorescent in situ hybridization and whole-transcriptome sequencing. RESULTS: Case 18 months, male, right semiovale center occupation. Histopathology: High-grade neuroepithelial neoplasm. IHC: GFAP(only few cells+), Olig2(-), S100(+), CD56(+), Syn(-), NSE(focal+), NeuN(-), CD34(-), INI-1(+), Ki67(10%+). Characteristic Molecular Information: EML4-ALK fusion. Follow-up: 15 months, alive. Case 2: 3 years, female, insular lobe occupation.Histopathology: Gliosarcoma. IHC: GFAP(partly+), Olig2(partly+), Vimentin(+), P53(cytoplasm+), pan-TRK(+), Ki67(25%+). Reticular fiber staining showed biphasic tissue pattern with reticulin-rich sarcomatous and reticulin-free gliomatous elements. Characteristic Molecular Information: NTRK1-TP53 and TP53-NRTK1 fusion. Follow-up: 27 months, alive. Case 3: 3 years, male, left parietal occipital lobe occupation. Histopathology: GBM and AT/RT. IHC: GFAP(partly+), Olig2(partly+), INI-1(partly-), BRG1(+), SYN(-), CD34(-), BRAF(-), S100(-), CK(-), H3K27M(-), IDH1(-), P53(40%+), ATRX(+), pan-TRK(-), ALK(+), Ki67(30%+). Characteristic Molecular Information: ALK mutation, ALK-QKI fusion, RAD51C mutation and focal SMARCB1(INI-1) deletion. Follow-up: 14 months, alive. CONCLUSION: Infant-type hemispheric glioma is a special kind of glioma, which is particularly suitable for precision-medicine treatment approaches. Their overall survival is good compared with other three pHGG subtype.
PATH-08. DNA methylation profiling improves routine diagnostics of paediatric CNS tumours: a prospective population-based study
Authors: Schepke Elizabeth , Löfgren Maja , Pietsch Torsten , Bontell Thomas Olsson , Kling Teresia , Wenger Anna , Vega Sandra Ferreyra , Danielsson Anna , Dosa Sandor , Holm Stefan , Öberg Anders , Nyman Per , Eliasson-Hofvander Marie , Sandström Per-Erik , Pfister Stefan M , Lannering Birgitta , Sabel Magnus , Carén Helena
Published: June 2022

AIMS: Paediatric brain tumours are rare and establishing a precise diagnosis can be challenging. Analysis of DNA methylation profiles has been shown to be a reliable method to classify central nervous system (CNS) tumours with high accuracy. We aimed to prospectively analyse CNS tumours diagnosed in Sweden, to assess the clinical impact of adding DNA methylation-based classification to standard paediatric brain tumour diagnostics in an unselected cohort. Methods: All CNS tumours diagnosed in children (0-18 years) during 2017-2020 were eligible for inclusion provided sufficient tumour material was available. Tumours were analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier. The initial histopathological diagnosis was compared to the DNA methylation-based classification. For incongruent results, a blinded re-evaluation was performed by an experienced neuropathologist. Results: 240 tumours with a histopathology-based diagnosis were profiled. A high-confidence methylation score of 0.84 or more was reached in 78% of the cases. In 69%, the histopathological diagnosis was confirmed and for some of these also refined, 6% were incongruent and the re-evaluation favoured the methylation-based classification. In the remaining 3% of cases, the methylation class was non-contributory or could not be predicted. The change in diagnosis would have had a direct impact on the clinical management in 5% of all patients.Conclusions: Integrating DNA methylation-based tumour classification into routine clinical analysis improves diagnostics and molecular information important for treatment decisions. The results from methylation profiling should be interpreted in the context of clinical and histopathological information.
PATH-14. Alteration of histopathological diagnoses by molecular profiling
Authors: Knirsch Stephanie , Milde Till , Pfister Stefan M , Blattmann Claudia
Published: June 2022

Here, we present a 4.5 year old patient presented with disturbed vision (double vision) and nausea over 2 weeks. Cerebral MRI revealed a tumor mass (6.5 x 6 x 5cm) located in the left temporal lobe. A macroscopical complete resection was achieved in May 2020. Conventional histopathology diagnosed a glioblastoma multiforme WHO IV° locally as well upon central review. A pleomorphic xanthoastrocytoma was considered to be unlikley due to the lack of eosinophile granular corpuscules, CD34-positive cells and dense reticulin fibres. The patient received treatment according to the SIOP HGG protocol with a postsurgical radiotherapy (total dosage of 54 Gy) accompanied by oral chemotherapy with temozolomide and valproic acid. After completion of radiotherapy, another 12 cycles of oral temozolomide were applied resulting in 1 year of consolidation treatment. In parallel, the tumor tissue was examined molecularly through the INFORM precision oncology platform (INdividualized Therapy FOr Relapsed Malignancies in Childhood). The results revealed an NTRK1-fusion as possible treatment target. Furthermore, methylation profiling of the tumor classified it as a pleomorphic xanthoastocytoma. The molecular results were completed during treatment of the patient and were discussed interdisciplinary. Finally, the diagnosis was changed integrating histopathology and molecular results, but the treatment was completed. In about 10% of the brain tumor cases within molecular diagnostic studies such as INFORM or PTT, the histopathological diagnosis differs from the molecular results leading to reconsideration of the initial diagnosis and potential impact on clinical management. These results demonstrate the importance of molecular profiling in brain tumors (and sarcomas) to complement conventional histopathology and select appropriate risk adapted treatment, especially in young patients.
PATH-15. Molecular and clinical landscape of CNS tumors arising among adolescents and young adults (AYA) at Memorial Sloan Kettering Cancer Center (MSKCC): a single-institutional experience
Authors: Li Bryan K , Miller Alexandra , Bouvier Nancy , Hill Katherine , Berger Michael F , Sait Sameer Farouk , Karajannis Matthias
Published: June 2022

BACKGROUND: The management of CNS tumors arising among AYA represents an unmet challenge. Treatment may be split between pediatric and adult centers, often with conflicting approaches. Biology also appears to be distinct compared to younger/older age groups but has yet to be fully characterized. Such features would have important implications for prognostication and informing vulnerabilities for targeted therapies.METHODS: To establish the clinical and molecular landscape of these tumors, we analyzed all cases in patients aged 15-39 years old who were treated at MSKCC between 2018-2021. RESULTS: 302 patients with accompanying MSK-IMPACT targeted sequencing, copy number analysis, Archer fusion panel, and clinical data were found. 239/302 cases (79%) were gliomas, with the remaining consisting mainly of neuro-epithelial tumors (n=15; 5%), meningiomas (9; 3%), ependymomas (10; 3%), and embryonal tumors (7; 2%). Among gliomas, 163/239 (68%) had IDH1/2 mutations, which were significantly more enriched for TP53 (121/163; 74%) and ATRX (90/163; 55%) co-mutations compared to IDH-wild type (IDH-WT) (q<0.0001). In comparison, IDH-WT gliomas (n=76) were enriched for alterations in BRAF (16/76 with SNV, 9/76 fusion; q<0.0001), H3F3A (14/76; q<0.0001), PTEN (10/76; q=0.038), and CDKN2A (16/76; q=0.038). Among 113 patients with high-grade gliomas (WHO grade 3/4), those with IDH-WT tumors (n=34) had a poorer prognosis that those with IDH-mutant tumors (n=79) (1 and 5-year OS of 68% and 28% vs. 97% and 76%, respectively) (p<0.0001). Further, a lower frequency of alterations in TERT (26/113; 23%), EGFR (6/113; 5%), and PDGFRA (4/113; 4%) were observed compared to previous studies for adult-only cohorts (~50-70%, 40%, and 10%, respectively). CONCLUSIONS: IDH-mutant gliomas were the most common tumor type seen in this AYA cohort. However, some alterations characteristic of adult high-grade gliomas (TERT, EGFR, PDGFRA) were not as frequently observed. Additional identification of molecular features that predict response to conventional and targeted therapies is underway.
LINC-07. Challenges in management of paediatric CNS tumors in low- and middle-income countries: experience from a tertiary center in Pakistan.
Authors: Zia Nida , Kaleem Bushra , Hamid Ahmer , Moreira Daniel
Published: June 2022

BACKGROUND: The cure rate of children with central nervous system (CNS) tumors in low- and middle-income countries (LMICs) is lower than high-income countries due to under diagnosis, treatment abandonment, lack of appropriate radiological, histopathologic, neurosurgical, radiotherapeutic, and pediatric oncologic services. The present study aimed to evaluate the treatment challenges observed in a tertiary center in Pakistan. MATERIALS AND METHODS: Patients younger than 17 years-of-age with CNS tumors either diagnosed at or referred to Indus Hospital from January 2015 to December 2021 were included. RESULTS: A total of 235 patients were included with a median age of 10.0 years and male preponderance (60.8%). The three most frequent CNS malignancies observed were glioma (105; 44.3%), medulloblastoma (63;26.6%), and ependymoma (34;14.3%). Of 235 patients, 45(19%) received palliative treatment upfront, 37(15.6%) were referred to other institutions for care, and 33 (13.9%) abandoned prior to treatment initiation. Of the 120 (51.0%) patients who started curative treatment, 74(61.6%) completed treatment, 22(18.3%) continue on treatment, 19(15.8%) abandoned treatment, and 5(4.2%) died during treatment . Overall survival in patients on curative treatment at the time of analysis was close to 80%. CONCLUSION: This study describes the outlook of care for children with CNS tumors in a tertiary center of Pakistan.It is observed that high rate of patients with upfront palliation and abandonment lead to poor outcomes. Stigma cancer, financial toxicity, delayed referral and burden of neurosurgeries in government sectors could be contributing to these outcomes. Further work must be done to clarify the barriers to quality care. Futhermore, a conscious effort to increase integrated care for these patients is of utmost importance.
LINC-12. Encouraging early outcomes with image guided pencil beam proton therapy for cranio-spinal irradiation and unique considerations for paediatric population – First report from India
Authors: Gaikwad Utpal , Sudarsan Rishan Thimma , Noufal M P , Jacinthlyn Sylvia , Reddy Ashok K , Panda Pankaj Kumar , Chilukuri Srinivas , Sharma Dayananda , Jalali Rakesh
Published: June 2022

BACKGROUND: To report our experience with image guided pencil beam proton beam therapy (PBT) for craniospinal irradiation (CSI). MATERIALS AND METHODS: Between January 2019 to Dec 2021, we carried out a detailed audit of the first forty patients treated with PBT. All patients were carefully selected after approval from our institutional multidisciplinary tumour and proton board meetings. Median age of the patient cohort was 8 years, and histologies include 20 medulloblastoma, 7 recurrent ependymoma, 3 pineoblastoma, 3 were germ cell tumors and remaining 7 constituted other diagnoses. Forty percent patients received concurrent chemotherapy. We had recorded acute toxicities on a prospectively maintained database. We also report early outcomes in this cohort and discuss limitations of current contouring guidelines during CSI PBT planning. RESULTS: Median CSI dose was 23.4 GyE (Gray Equivalent; range 21.6 - 35). Thirty-five patients (87.5%) completed their CSI without interruption as an outpatient procedure. Five patients required hospital admission during treatment, while one developed grade 3 mucosal toxicity, requiring plan adaptation and treatment break. No patient had grade 2 or more weight loss during the treatment. Forty-five percent (18) developed grade 1 hematological toxicities and 20% (8) developed grade 2 or 3 toxicities; none had grade 4 toxicities. At median follow up of 12 months, 90 % patients are alive of whom 88.9 % are having local control. Special consideration with modification in standard contouring used at our institute helped in limiting acute toxicities in paediatric CSI patients. CONCLUSION: Our preliminary experience with modern contemporary PBT using pencil beam technology and daily image guidance in a range of tumours suitable for CSI is encouraging. Patients tolerated the treatment well with acceptable acute toxicity and expected short-term survival outcome. In paediatric CSI patients, modification in standard contouring guidelines required to achieve better results with PBT