bluuebunny/crossref_metadata_2025 huggingface dataset:
MDB-96. CEREBROSPINAL FLUID LEVELS OF THE MIR216B-5P AS A MINIMALLY INVASIVE MONITORING TOOL FOR MEDULLOBLASTOMA
Authors: Koptyra Mateusz P , Coyle Anne , Hollawell Madison , Rathi Komal , Arif Shehbeel , Diamond Maura , Diarra Noni , Naqvi Ammar , Madsen Peter , Storm Phillip B , Foster Jessica B , Resnick Adam C
Published: June 2024

BACKGROUND

Current management of pediatric brain tumor patients relies on imaging as the only non-invasive tool available for monitoring therapeutic response and tumor progression. Results are often inconclusive and unable to capture biologically relevant changes that presage progression on imaging. Circulating miRNA provides an attractive non-invasive biomarker because miRNA has an essential role in regulating gene expression, stability in bio-fluids, selective over-expression in tumors, and is actively released from tumors into the extracellular environment. We aimed to establish the diagnostic and monitoring value of miRNA biomarkers for pediatric brain tumors in cerebrospinal fluid (CSF).

METHODS

We performed HTG EdgeSeq miRNA panel profiling (2100 targets) of CSF (n=33) samples across pediatric brain tumors from 5 histologies (low grade glioma, ependymoma, germ cell tumor, medulloblastoma, high-grade glioma). We utilized unsupervised consensus clustering, differential expression analysis, and machine learning approaches to investigate miRNA biomarkers. Results were validated using qPCR and ddPCR methods.

RESULTS

CSF miRNA signatures revealed a correlation with leptomeningeal disease and higher disease burden (p<0.05). Differentially expressed miRNA revealed histology-specific signatures for low grade glioma, medulloblastoma, and germinoma (p<0.05). miR216 expression was significantly elevated in medulloblastoma patients with active disease, indicating a potential novel biomarker for tumor monitoring. The miR216b-5p expression in CSF was confirmed using qPCR and ddPCR. The analysis of independent tumor tissue-based dataset confirmed miR216b-5p and its coding gene MIR217HG expression upregulated in medulloblastoma. MiR-216b-5p expression was also confirmed in patient-derived medulloblastoma cell lines and detected in cell free-media composition indicating extracellular release of miR216b-5p.

CONCLUSIONS

These results support the use of circulating miRNA in CSF as a potential biomarker for diagnosis and clinical monitoring of medulloblastoma. Further utilization of this approach provides a unique platform to inform liquid biopsy-based management in the clinical setting.
MDB-101. TARGETING CTPS1 AND NUCLEOTIDE BIOSYNTHESIS PATHWAYS AS A NOVEL THERAPEUTIC APPROACH IN MYC-AMPLIFIED MEDULLOBLASTOMA
Authors: Hathaway Matthew , Jagana Hawa , Terrones Isabella , Miyaki Aya , Hemenway John , Meechan Michael , Gadek Kate , Slusher Barbara , II Myron Evans
Published: June 2024

Although leukemia is the leading pediatric oncology diagnosis, brain tumors are the leading cause of pediatric cancer-related death. Medulloblastoma (MB) is the most common pediatric brain tumor, representing approximately 20% of all diagnoses. MYC-amplified Group 3 medulloblastoma (G3 MB) tumors are the deadliest, with a < 50% 5-year overall survival rate. High risk patients receive large doses of chemo- and radio- therapy (CT/RT) with most survivors experiencing debilitating neurological and cognitive sequelae making the identification of novel targets of the utmost importance. Utilizing whole-genome CRISPR screening, we identified the enzyme CTPS1 as a strong G3 MB-specific vulnerability. Further analysis revealed dependencies on other enzymes in the de novo pyrimidine synthesis pathway, which is corroborated by recent metabolic studies. Targeted knockdown of CTPS1 restricts sphere formation and reduces proliferation of G3 MB tumor lines. Treatment with a specific CTPS1 inhibitor reduced proliferation but did not induce cell death, suggesting a cytostatic mechanism. Previous work has shown that triggering an imbalance in pyrimidine and purine levels leads to replication stress and activation of the ATR/CHK1 pathway. Both genetic and pharmacologic inhibition of CTPS1 leads to CHK phosphorylation, allowing for cell survival despite lack of dNTPs. Previously, the CHK1 inhibitor, prexasertib, demonstrated robust brain accumulation and targeting of G3 MB in pre-clinical models. Dual inhibition of CHK1 and CTPS1 synergizes to significantly reduce cell viability in vitro and tumor growth in vivo. We further demonstrated robust synergy of CHK1 inhibition with either glutamine antagonists or other inhibitors of the de novo pyrimidine synthesis pathway, prolonging in vivo survival in an orthotopic xenograft G3 MB model. The results of this investigation confirm CTPS1 as a novel target in G3 MB, pinpoint a dependency on de novo pyrimidine rather than purine biosynthesis, and identifies a novel rational combination for treatment in MYC-amplified MB patients.
MDB-110. A NOVEL TRANSGENIC MOUSE MODEL FOR GLI2-AMPLIFIED MEDULLOBLASTOMA
Authors: Murad Najiba , Xu Zhenhua , Liu Xiao , Rivero-Hinojosa Samuel , Ramawickrama Prathibhani Gamachchige , Pei Yanxin
Published: June 2024

BACKGROUND

Medulloblastoma (MB) is one of the most common malignant childhood brain tumors. The sonic hedgehog (SHH) subgroup represents 30% of MBs and can arise from granule neuron progenitors (GNPs). SHH-MB is a diverse subgroup of tumors which often exhibit loss-of function mutations in PTCH1 or SUFU, activating mutations in the receptor SMO and amplification of the transcription factor GLI2. Of note, SHH-MBs harboring GLI2-amplification and associated with P53 mutations have extremely poor prognosis with a 5-year survival rate less than 30%. These tumors are non-responsive to SMO inhibitors, which are the only targeted treatment currently available for SHH-MB. Therefore, the development of novel effective therapies for this disease is urgent. Although GLI2 amplification is detected in SHH-MBs, it is not yet known if GLI2 can drive oncogenic activity in this disease.

METHOD

To elucidate the mechanisms underlying tumorigenesis, our group has developed a novel transgenic model of GLI2-driven MB by expressing a constitutively active form of GLI2 (GLI2A) in Atoh1+ cells in the developing mouse cerebellum to form tumors. To accomplish this, we crossed R26;Gli2A mice with Atoh1-Cre.

RESULTS

The resulting tumors faithfully recapitulate human GLI2-amplified MB at the cellular and molecular levels. Inactivation of GLI2A resulted in tumor regression, indicating that GLI2 is not only critical for tumorigenesis, but also required for tumor maintenance, suggesting that targeting GLI2 itself or its downstream targets may be effective to inhibit growth of GLI2-driven MB. Interestingly, activation of GLI2A expression in the neonatal cerebellum was not sufficient to drive tumorigenesis, indicating that GLI2-driven MB arises from more primitive cells in the developing cerebellum.

CONCLUSION

Taken together, our studies demonstrate for the first time the role of GLI2 as an oncogenic driver of MB and introduce a novel mouse model which can be used to develop targeted therapies for this disease.
NFS-10. ROLE OF CDKN2A CO-DELETION IN DRIVING TUMOR INVASIVENESS IN NF1 MUTANT GLIOMA
Authors: Chong Wai Chin , Subramaniam Bavani , Tomasso Federica , Roy Debasish , Yadavilli Sridevi , Bornhorst Miriam , Packer Roger , Nazarian Javad
Published: June 2024

BACKGROUND

Neurofibromatosis type 1, caused by mutations in the NF1 gene, is a common autosomal dominant genetic disorder associated with an increased risk of glioma tumor development. A high occurrence of CDKN2a codeletion in NF1-mutant high-grade gliomas (HGG) compared to low-grade gliomas (LGG) implies a potential role of CDKN2a loss in the transformation of NF1-mutant LGG to HGG. In our study, we aimed to elucidate the role of NF1 and CDKN2a in tumor transformation using a panel of glioma cell line models with varying NF1 and CDKN2a expression.

METHOD

A diverse panel of glioma cell lines, encompassing LGG (1667-ON, RES259, RES186, JHH-NF1-PA1) and HGG (GBM511, GBM110, SF8628, U87-MG, TM-31, 7316-2189, 7316-3058, 7316-4917), was cultured. Their growth rates and invasiveness were further evaluated using cell proliferation and Boyden chamber invasiveness assays.

RESULTS

LGG cell lines exhibited relatively lower growth rates and invasiveness compared to their high-grade counterparts. Intriguingly, RES259, a LGG cell line harboring both NF1 and CDKN2a variants, demonstrated the highest growth rate and invasiveness among LGG cell lines, surpassing even those with intact NF1 and CDKN2a, such as JHH-NF1-PA1 and RES186. To further elucidate the roles of NF1 and CDKN2a, CRISPR-Cas9 technology was employed to knockout these genes individually and in various combinations in RES186. Our findings unveiled that sole NF1 knockout had negligible impact on RES186. Conversely, CDKN2a knockout increased both growth rate and invasiveness. Strikingly, the codeletion of NF1 and CDKN2a in RES186 significantly exacerbated its growth rate and invasiveness. These results underscore the intricate interplay of NF1 and CDKN2a in governing the growth and invasiveness dynamics of glioma cells.

CONCLUSION

In conclusion, our preliminary study suggests that the concurrent loss of NF1 and CDKN2a promotes enhanced growth and invasiveness in gliomas, shedding light on the collaborative role of these genetic alterations in tumor transformation.
NFS-19. ATYPICAL PRESENTATION OF GLIOMAS IN ADOLESCENTS WITH NEUROFIBROMATOSIS TYPE 1 (NF1): A CASE SERIES
Authors: Rocco Abbey , Beck Mary , McHugh Michele , Lampe Ashley , Meyer Ashley , Ogle Andrea , Cluster Andrew , Shatara Margaret , Abdelbaki Mohamed S , Brossier Nicole M
Published: June 2024

BACKGROUND

Patients with NF1 are at risk for developing gliomas, usually low-grade in childhood but may be high-grade in adults. In children, the most common sites of disease are the optic pathway and brainstem; tumors in these regions often arise in young children and display histological features characteristic of pilocytic astrocytoma (PA) when biopsied. Typical MRI findings include T2 hyperintense, T1 hypointense lesions with minimal contrast enhancement and no diffusion restriction. Due to the well-established pattern of low-grade tumor formation in children with NF1, as well as the surgically challenging areas in which these tumors develop, low-grade glioma (LGG) therapy is often initiated without histologic confirmation of the diagnosis in classic cases. In cases with atypical disease location, older age at presentation or imaging appearance, a biopsy may be considered to exclude higher-grade lesions.

METHODS

Retrospective chart review, case series

RESULTS

Four adolescent patients with NF1 presented with atypical suspected gliomas. All four patients underwent surgical biopsy/resection. Case 1 was a left temporal lesion in the previous radiation field for optic pathway glioma; biopsy confirmed LGG with MAP2K1 mutation and increased focal proliferation index (28%), but methylation did not match with any established classification. The patient progressed through multiple rounds of therapy and succumbed to her tumor. Case 2 was a left occipital lesion; biopsy confirmed PA with CDKN2A deletion. The tumor displayed rapid regrowth, but subsequently stabilized. Case 3 was a right frontal lesion; confirmed PA. The tumor demonstrated some regrowth but then stabilized. Case 4 was a basal ganglia lesion; confirmed PA. The patient has demonstrated stable MRI findings and has not required further intervention.

CONCLUSIONS

Biopsy yielded helpful prognostic information (additional mutations, proliferation rate) in half of these atypical cases. Biopsy should be carefully considered for NF1 patients with atypical presentation or a history of radiation.
NFS-28. CLINICAL CHARACTERISTICS AND THERAPEUTIC INTERVENTIONS IN A CASE SERIES OF PEDIATRIC PATIENTS WITH VESTIBULAR SCHWANNOMAS AND NEUROFIBROMATOSIS TYPE 2
Authors: Stitzlein Lea M , Sun Yusha Y , Munir Faryal , McCutcheon Ian E , Slopis John M , Zaky Wafik
Published: June 2024

BACKGROUND

Pediatric neurofibromatosis type 2 (NF2) is an understudied genetic disorder with high incidence of tumors including vestibular schwannomas (VS) and meningiomas. Although predominately recognized as an adult disease, there is a shortage of comprehensive studies in pediatric NF2. This case series describes a large cohort of pediatric NF2 patients with VS and their disease management.

METHODS

Our study included 24 patients with initial symptoms of NF2 before age 19. The patients were treated at the Neurofibromatosis Clinic of The University of Texas MD Anderson Cancer Center between 1/1/2005-12/31/2023. Our analysis incorporated data from clinic notes, surgical reports, audiology reports, electromyography reports, pathology reports, and imaging studies.

RESULTS

Patients presented with NF2 at an age range from 18 months to 18 years (mean age 8.1 ± 5.2 years). Among the patients, 67% underwent surgical interventions, including auditory brainstem implants, cochlear implants, ventriculoperitoneal shunts, and/or craniotomies for tumor resection. Additionally, treatment in 21% of cases involved radiotherapy, employing stereotactic radiosurgery, intensity-modulated radiotherapy, and proton beam irradiation. Targeted therapies, including bevacizumab, lapatinib, everolimus, temsirolimus, brigatinib, or a combination thereof, were administered to eleven patients. The best exhibited response by most patients was stable disease for a median duration of 10 months, and clinical improvement/stabilization of the hearing loss. Most reported toxicities related to bevacizumab or temsirolimus. Overall, limited clinical improvement was observed within this cohort after interventions.

CONCLUSION

This study discusses the clinical presentation of pediatric NF2 with VS and highlights the need for effective therapeutic options to manage tumors and symptoms in this patient population. A notable research gap exists in pediatric NF2, compounded by the lack of preclinical models to study the disease. The absence of approved drugs underscores the necessity for more comprehensive studies to guide therapeutic strategies. Combination therapies may advance treatment approaches and achieve improved outcomes.
QOL-03. BONE HEALTH IN CHILDREN WITH SUPRASELLAR AND THALAMIC LOW GRADE GLIOMA; AN UNDERSTUDIED PROBLEM
Authors: van Roessel IMAA , Gorter J E , Bakker B , van den Heuvel-Eibrink M M , Lequin M H , van der Lugt J , Meijer L , van Meeteren A Y N Schouten- , van Santen H M
Published: June 2024

BACKGROUND

Children with a supratentorial midline Low Grade Glioma (LGG) may be at risk for impaired bone health due to hypothalamic-pituitary dysfunction, obesity, exposure to multiple treatment modalities, and/or decreased mobility. The presence of impaired bone health and/or its severity in this population has been understudied. We aimed to identify the prevalence and risk factors for bone problems in children with supratentorial midline LGG.

METHODS

A retrospective study was performed in children with supratentorial midline (suprasellar or thalamic) LGG between 1-1-2003 and 1-1-2022, visiting the Princess Máxima Center for Pediatric Oncology. Impaired bone health was defined as presence of vertebral fractures or collapse, any fractures not related to (the intensity of) trauma, treatment with bisphosphonates, and/or very low bone mineral density (BMD).

RESULTS

In total, 161 children were included, with a median age at tumor diagnosis of 4.7 years (range 0.1 – 17.9) and a median follow-up of 6.1 years (range 0.1 – 19.9). ‘Any’ bone problem occurred in 22.4% (36/161) and nontraumatic fractures in 3.7%. Impaired visual capacity was associated with bone problems in multivariate analysis (OR 3.56 95% CI 1.30 – 9.76, p = 0.014).

CONCLUSIONS

In this retrospective evaluation, bone problems and decreased BMD were prevalent in 36.1% of children with supratentorial midline LGG. Risk to develop bone problems appears to be multifactorial, but visual capacity seems highly relevant. Surveillance of bone health must be an aspect for awareness in the care and follow-up of children with a supratentorial midline LGG.
QOL-06. RECURRENCE PATTERNS AND SURVEILLANCE IMAGING IN PEDIATRIC BRAIN TUMOR SURVIVORS
Authors: Cacciotti Chantel , Lenzen Alicia , Self Chelsea , Pillay-Smiley Natasha
Published: June 2024

BACKGROUND

Surveillance magnetic resonance imaging (MRI) is routinely used to detect recurrence in pediatric central nervous system (CNS) tumors. Frequency of neuroimaging varies with no standardized approach.

METHODS

A single institution retrospective cohort study evaluated frequency and pattern of recurrences. Pediatric patients (birth to age 21 years) diagnosed with a primary CNS tumor between 1988 and 2011 treated at Lurie Children’s Hospital were included.

RESULTS

This study included 476 patients; the majority diagnosed with a low-grade glioma (LGG) (n=138; 29%), high grade glioma (HGG) (n=77; 16%), ependymoma (n=70; 15%) or medulloblastoma (n=61; 13%). LGG, HGG and ependymoma patients more commonly had multiply recurrent disease (p=0.08), with ependymoma patients demonstrating ≥2 relapses in 47% of cases. Recurrent disease was identified by imaging more often than clinical symptoms (65% vs 32%; p=<0.01). Treatment at relapse included surgical managment more often than non-surgical approach (59% vs. 41%; p=0.0016) in patients, leading to pathology confirmation of recurrence. Mean time to first relapse for the entire cohort was 2.5 years (range 1 day-24.8 years). Patients diagnosed with meningioma demonstrated the longest mean time to first relapse (74.7 months) whereas those with Atypical Teratoid Rhabdoid Tumor and Choroid plexus carcinoma tended to have the shortest time to relapse (8.9 months and 9 months, respectively). Overall, 22 patients sustained first relapse >10 years from initial diagnosis, including those diagnosed with LGG, medulloblastoma, pineoblastoma, craniopharyngioma, GCT, and meningioma.

CONCLUSION

With a higher percentage of tumor recurrence/progression seen on neuroimaging before development of symptoms, surveillance imaging is necessary in routine follow up of pediatric CNS tumor survivors. While the study is limited since we did not look at overall survival, earlier detection of recurrence would lead to earlier initiation of treatment and implementation of salvage treatment regimens which can impact survival and quality of life.
QOL-20. A REVIEW OF THE LITERATURE ON THE REHABILITATION OF PATIENTS WITH POSTERIOR FOSSA SYNDROME
Authors: Levin Jared , Rosenberg Nathan , Tsao Elaine
Published: June 2024

BACKGROUND

Posterior fossa syndrome (also recently described as pediatric postoperative cerebellar mutism syndrome) is a well described phenomenon, in which a patient develops a spectrum of speech and motor/coordination deficits generally in the acute stage after posterior fossa tumor resection. While most patients recover well, some patients evidence significant deficits years after diagnosis, and there is some evidence that minor long-term deficits may remain. While its frequency of occurrence is relatively low, and efforts have been made to identify strategies to decrease the rate of Posterior Fossa Syndrome, the fundamental interventions for functional optimization and rehabilitation of patients are still being discussed and researched.

METHODS

Along with reviewing the most up-to-date literature on the rehabilitation management of patients with posterior fossa syndrome, we will discuss current a survey based study designed by a group of representatives from the American Academy of Physical Medicine and Rehabilitation (AAPM&R) Pediatric Cancer Rehabilitation subcommittee, to better understand the standards of how the syndrome is managed by physiatrists in the US. This survey distributed via email, posting on an AAPM&R online community, as well as social media sites.

RESULTS

While literature is limited, there is evidence for the practice of therapy services, bracing, and in admission for acute inpatient rehabilitation to guide treatment for patients with posterior fossa syndrome. Results from the above survey study will be discussed, which preliminarily shows a consistent reliance on therapy services and a broader heterogeneity to frequency and treatment preferences among physicians in the US.

CONCLUSION

Posterior Fossa Syndrome can be a challenging and debilitating disorder for pediatric brain tumor patients. Further research into treatment options and outcomes is necessary to guide future management.
QOL-21. FUNCTION-BASED OUTCOME MEASURES AND HOW THEY CAN BE APPLIED IN PATIENTS WITH PEDIATRIC BRAIN TUMOR FOR TRACKING RECOVERY AND RESEARCH
Authors: Tsao Elaine , Tsetlina Vera , Levin Jared
Published: June 2024

BACKGROUND

Currently an estimated 15,000 children are diagnosed with cancer annually in the United States. Among pediatric patients, central nerve system tumors make up the highest percentage of solid tumor malignancies. Tumors of the peripheral nervous system also occur, most commonly in syndromes such as neurofibromatosis. Tumor growth and tumor treatments can result in developmental and functional impacts on patients. As survival rates continue to improve through the years with advancement of pediatric cancer treatment, an increasing focus is being placed on improving function and quality of life both during and after treatment. This presentation aims to introduce a variety of validated outcome measures that assess a patient’s strength and function, to discuss how they can be applied to patient monitoring, and to propose future studies in the pediatric neuro-oncology population.

METHODS

This presentation will review the currently validated and commonly used outcome measures used by physicians and therapists for assessing a patient’s strength, endurance, and function. Emphasis will be placed on how these tools can be used in assessing and monitoring patients with conditions such as chemotherapy induced peripheral neuropathy, posterior fossa syndrome, and cachexia.

RESULTS AND CONCLUSIONS

This presentation aims to educate attendees on the current tools and outcome measures available to track a patient’s function and progress during and after treatment of neuro-oncologic conditions. It aims to highlight how these tools can be used in clinic for patient monitoring, and for future possible prospective research.
QOL-24. TREATMENT- AND TIME-RELATED IMPACT ON LONG-TERM NEUROCOGNITIVE OUTCOMES IN ADULT SURVIVORS OF A PEDIATRIC BRAIN TUMOR
Authors: Bullens Kristien , Blommaert Jeroen , Sleurs Charlotte , Laic Rebeca Alejandra Gavrila , Lemiere Jurgen , Jacobs Sandra
Published: June 2024

Treatment for pediatric brain tumors has been associated with the risk of developing long-term neurocognitive impairment. However, it is not well understood which neurocognitive profiles exist within this population. We investigated neurocognitive functioning (NF) in survivors in early adulthood and aimed to assess the impact of radiotherapy dose (RTD) and time since treatment (TxT) on NF. Forty-six survivors of pediatric brain tumors (mean age 23.99±4.71, mean age at diagnosis 9.29±4.54) performed an extensive neurocognitive test battery resulting in intelligence (n=5), memory (n=2), and language (n=3) scores. NF in long-term survivors was compared to sex-, age-, and education-matched controls, and between the different treatment strategies (surgery-only n=19, chemotherapy n=8, radiotherapy n=11, or chemo-radiotherapy n=8). Furthermore, relation between max-RTD (range 40.28 – 61.61 Gy) as well as TxT and NF was assessed. Three ANCOVA models were tested, and false discovery rate (FDR) was applied. For all scales and domain scores, survivors scored lower compared to controls. Scores were significant lower on full scale intelligence (pfdr< 0.001), verbal comprehension (pfdr< 0.001), working memory (pfdr= 0.003), perceptual reasoning (pfdr< 0.001), processing speed (pfdr< 0.001), spoken word comprehension (pfdr= 0.001), and semantic word generation (pfdr= 0.036) compared to controls. NF was not significantly different between the different treatments, nor did the association with max-RTD reach significance. TxT was associated with verbal comprehension and spoken word comprehension; albeit significance was not retained after FDR correction. In this study, the overall survivor cohort scored lower on multiple cognitive outcomes. More detailed analysis of various risk factors might further elucidate the different neurocognitive profiles for this population. Furthermore, more detailed analysis of RTD distributions and affected brain structures may provide greater insight on the impact of radiotherapy on NF.
QOL-28. NEUROCOGNITIVE DEFICITS, EMOTIONAL DISTURBANCES, PSYCHOSOMATIC COMPLAINS – ADDITIONAL SYMPTOMS OR COMORBID DIAGNOSIS IN CNS GERMINOMA? OVERVIEW OF GROUP AND CASE STUDIES
Authors: Korzeniewska Justyna
Published: June 2024

BACKGROUND

CNS Germinoma cases are associated with good medical prognosis, low risk for neurological deficits and high cognitive functioning. Deeper psychological and neuropsychological examination and longitudinal observation shows also neurocognitive problems and emotional disturbances. The purpose of the study was to assess patients with CNS Germinoma (during and after anticancer treatment), expressed specific psychological and physical symptoms and to find the reason for this.

METHODS

Since 1998 all patients treated at our center are under psychological control and care. From these group 78 patients with CNS Germinoma with additional significant symptoms, seriously affected their quality of life and everyday activity, were selected for psychological and neuropsychological assessment. Age at psychological intervention ranged from 6 5/12 to 34 8/12 yrs. The patients have no pre-diagnosis history of neurological, developmental or psychiatric disorder. They were examined using a battery of standardized psychological and neuropsychological methods.

RESULTS

In our sample FIQ (full-scale intelligence quotient) score ranged from 59 to 139. The most patients presented average level of intelligence. However, cognitive functioning was often reduced due to emotional disturbances and psychosomatic complains. 2 patients showed memory disorders, one of them TGA (transient global amnesia) at the time of diagnosis. All patients struggled with emotional disturbances at different grades, especially internalizing type of problems (immaturity, depression, anxiety, instability, inhibition, negative attitude) or were considered to be at risk for psychological adjustment difficulties and tendency to somatization. Analyzed group of patients showed also social competences deficits. They may exhibit deficit in age-appropriate social competence and peers relations.

CONCLUSIONS

Although CNS Germinoma patients shows similar behavioral and emotional phenotype, there are significant differences between them in terms of cognitive functions. The range of results is wide, from high levels to neurocognitive disorders. Therefore, risk factors, diagnostic criteria and effective neuropsychological intervention, will also be presented and discussed.
QOL-30. NEUROPSYCHOLOGICAL FUNCTIONING AFTER WHOLE VENTRICULAR OR CRANIOSPINAL PROTON RADIATION FOR PEDIATRIC INTRACRANIAL GERM CELL TUMORS
Authors: Paltin Iris , O’Brien Meghan K
Published: June 2024

BACKGROUND

In Western countries, intracranial germ cell tumors (ICGT) represent 3-5% of central nervous system tumors, with peak incidence in the second decade of life. Compared to those receiving photon radiation therapy, pediatric patients receiving proton radiation therapy demonstrate stronger neurocognitive outcomes, particularly in verbal and visual reasoning. Ongoing treatment advances aim to reduce morbidity, such as neurocognitive late effects. This study characterizes memory functioning for patients with intracranial germinoma treated with either whole ventricular (WV) or craniospinal (CSI) proton radiation therapy.

METHODS

29 patients received proton radiation therapy (17 WV, 12 CSI) for an ICGT (20 germinoma, 8 NGGCT, 1 mixed GCT; 3 disseminated at diagnosis). Age at diagnosis was 5-21 years (M=14.14; SD=3.91) with age at neuropsychological evaluation 8-25 years (M=17.66, SD=4.11). Evaluations occurred 0.71-7.85 years after diagnosis (M=3.52; SD=2.02). Patients (82.8% male, 65.5% white, 44.8% Very High Childhood Opportunity Index [COI]) had multiple additional interventions (surgeries, chemotherapy) prior to neuropsychological evaluation.

RESULTS

Patients in the WV group did not differ from patients in the CSI group on sex, COI, race, or ethnicity. Mean performance was stronger in the WV group than the CSI group for Full Scale IQ (FSIQ; t(27)=2.50, p=.019, Cohen’s d =0.94), Verbal Reasoning (VCI; t(24)=2.52, p=.019, d=1.0), Visual Memory (WRAML-2 Picture Memory Recognition; t(14)=2.51, p=.025, d=1.26), and Verbal Memory [(WRAML-2 Story Memory Delay, t(15.32)=2.82, p=.013, d=1.25); (WRAML-2 Story Memory Recognition, t(20)=2.34, p=.03, d=1.0)], all with large effect sizes.

CONCLUSIONS

Within this small ICGT sample with various medical treatments and comorbidities, demographic factors did not differ between groups, and WV proton radiation therapy appears to have less negative impact on aspects of reasoning and memory abilities compared to CSI proton radiation therapy.
QOL-42. ANALYSIS OF LATE EVENTS AFTER RADIATION THERAPY FOR PRIMARY PEDIATRIC BRAIN TUMORS
Authors: Trkova Katerina , Vicha Ales , Krskova Lenka , Koblizek Miroslav , Ondrova Barbora , Kopecka Marie , Landova Lucie , III Vladimir Benes , Zapotocky Michal , Sumerauer David
Published: June 2024

BACKGROUND

Late events after radiation therapy for primary brain tumors consist of secondary malignant neoplasms (SMN) and tumor recurrences. The incidence and biology of late events are not very well described. Therefore, we aimed to identify late events in our institutional cohort and describe their biology.

METHODS

A retrospective chart review of all irradiated pediatric brain tumor patients treated between 2000 and 2015 at our institution was performed to obtain demographics and clinical data of late events. Late events were defined as intracranial intraaxial SMN or tumor recurrence occurring later than 3 years after radiation therapy. A whole-genome methylation array was employed to identify the methylation class of the late event.

RESULTS

In the observed period, 267 patients received some form of cranial radiotherapy for primary brain tumor; high-grade glioma (HGG, n=66), medulloblastoma (n=74), ependymoma (n=50), germ-cell tumors (GCT, n=22), low-grade glioma (LGG, n=24), and other diagnoses (n=31). Out of the 174 patients who were alive and without an event after 3 years from the radiation therapy, 30 developed late events (16.8%), and 27 of them were histologically verified. Verified late events consisted of 8 SMNs (29.6%) and 19 primary tumor recurrences. SMNs were mainly radiation-induced gliomas (RIG, n=7) and one atypical teratoid/rhabdoid tumor (ATRT) after craniopharyngioma. All RIG tumors clustered with the “pediatricHGG_RTK1” methylation class. Tumor recurrences consisted of medulloblastomas (Group 4 and Wnt), ependymomas (PFA and ST_ZFTA), GCTs, gliomas (one NF1-associated HGG, one H3-altered thalamic glioma, one diffuse astrocytoma with BRAF-V600E mutation), and craniopharyngiomas. The overall survival rate 5 years after a late event was 39.7%, with a worse survival rate for SMN patients (14.3%) compared to those with recurrences (44.9%) (p=0.05).

CONCLUSIONS

Late events affected 16.8% of long-term survivors. Strikingly, SMNs represented almost 30% of late events and were associated with a very poor prognosis.
QOL-49. BOOKS4BRAINS: PILOTING A COMMUNITY CIRCLE BOOK CLUB TO IMPROVE SELF EXPRESSION
Authors: Knight Kelsey M , Appel Susan , Coven Scott L
Published: June 2024

BACKGROUND

Children with brain or spinal cord tumors often have limited interactions with their primary care providers who focus on developmentally appropriate recommendations, including the assessment of literacy. Additionally, we know that children with brain or spinal cord tumors have neurocognitive disruptions secondary to their diagnosis. Due to their disease process, these children are at high-risk for learning difficulties. We want to assist in building their self-confidence and acceptance. The objective was to provide a monthly virtual experience that utilized books, creative writing, and illustration to build a community centered on trust, shared experiences, and discussions of social emotional tools.

METHODS

We aimed to enroll 40 total participants diagnosed with a brain or spinal cord tumor who were followed by the Pediatric Neuro-Oncology Program at Riley Hospital for Children. These participants were divided amongst two groups: 1st-3rd grade and 6th-8th grade. After final enrollment, we had a total of 30 participants that received the following supplies: a copy of each months book, an audio recording of each book, and creative writing and craft supplies for each session.

RESULTS

We held three monthly hour-long virtual sessions for each group on Saturday mornings. Ten total children were available to meet consistently over the two groups. Positive feedback we received included, “we loved it,” “everyone felt included in book time,” and “[it] was so helpful that the books were read out loud and it was amazing to have the read along aspect with it for her visual impairment.” We even heard from one caregiver that “[they] noticed that she has some more tools in her toolbox when she is facing a difficult day.”

CONCLUSIONS

A pilot community book club is feasible through community partnerships. We plan to build on this experience by focusing on improving consistent attendance in future sessions.
QOL-51. FEASIBILITY AND EASE OF USE OF A REMOTE ONLINE COGNITIVE BATTERY AMONG PEDIATRIC BRAIN TUMOR SURVIVORS
Authors: Lee Kristin M , Yu Joan , Stancel Heather , Okcu M Fatih , Chintagumpala Murali , Kahalley Lisa , Raghubar Kimberly P
Published: June 2024

BACKGROUND

Pediatric brain tumor survivors are at risk for cognitive deficits, including inattention, poor memory, and slow processing speed. Due to technology advances, computerized neuropsychological batteries were developed that can be completed via internet in the home. The primary aim of this study was to evaluate the rate of successful completion and ease of use of the Penn Computerized Neuropsychological Battery (CNB) among pediatric brain tumor survivors.

METHODS

Forty-eight pediatric brain tumor survivors completed the online remote administration version of the Penn CNB (10 subtests) assessing complex cognition, memory, executive control, processing speed, and motor speed. Participants were provided with an electronic link to the online cognitive battery as well as paper and electronic copies of an instruction guide and post-completion surveys to return via mail/email.

RESULTS

Patients (56.3% female) were diagnosed and treated for a brain tumor (54.2% received radiotherapy). All participants were at least 8 years of age (M=13.71, SD=3.82) and at least one-year post-diagnosis (M=4.76, SD=2.58 years). Eighty-eight percent of participants beginning the CNB completed all subtests. Sixty percent of participants completed and returned the post-assessment survey. Participants who returned post-assessment surveys were similar to those who did not on demographic and medical factors (all p-values >.05). Mean ratings suggest that survivors were “very interested” in the tasks and they were “somewhat easy” to complete. Younger children were more likely to have trouble understanding task instructions (r=.56, p <.01) and ask for help answering specific questions (r=.46, p <.05).

CONCLUSIONS

Remote administration of computerized batteries are feasible among pediatric brain tumor survivors and may assist with advancing both research and patient care. From a research standpoint, remote batteries may allow for participation and engagement in research with minimal survivor burden. Clinically, such batteries may offer alternatives for screening patients who will benefit from comprehensive services.
SURG-01. ULTRA-FAST DEEP-LEARNED CNS TUMOR CLASSIFICATION USING STURGEON; THE IMPACT ON STRATEGY FOR THE PEDIATRIC NEUROSURGEON
Authors: Hoving Eelco , Rooda Oscar Eelkman , Sie Mariska , Vermeulen Carlo , Pages-Gallego Marc , Kester Lennart , Kranendonk Mariette , Wesseling Pieter , van der Lugt Jasper , Tops Bastiaan , de Ridder Jeroen
Published: June 2024

INTRODUCTION

Central nervous system tumors still represent one of the most challenging fields to create curation in pediatric oncology. The primary treatment always starts with a neurosurgical intervention to obtain tumor tissue for diagnosis. In most cases this intervention is a maximal safe resection of the tumor. The oncological prognostic value of extent of resection is determined by the precise molecular diagnosis and per-operative ultra-fast molecular classification of central nervous tissue provides the neurosurgeon relevant information for choosing the right strategy. This per-operative molecular diagnosis determines the balance between the need of radicality versus the prevention of neurological morbidity in the individual patient. We shall report on our neurosurgical experiences with the per-operative use of Sturgeon in our national practice of pediatric neuro-oncology in the Netherlands.

METHODS

The ultra-fast AI-based nanopore sequencing method, Sturgeon, has been implemented as per-operative diagnostic in most neurosurgical tumor resections in our center (1). An overview of our nanopore sequencing pipe- and timeline will be presented and its impact on neurosurgical strategies will be shared.

RESULTS

Reliable and accurate diagnoses can be obtained within 40 minutes after starting sequencing in 45 out of 50 retrospectively sequenced samples (while abstaining from diagnosis of the other 5 samples). The implementation in real time surgery results in a turnaround time between taking out sample material to diagnosis in less than 90 minutes. The most important result is that there is a high sensitivity and virtually no false positives since it is refraining from diagnosis when there is too much uncertainty. Several illustrative cases with impact on the neurosurgical strategy have been collected.

CONCLUSION

Ultra-fast deep-learning CNS tumor classification using Sturgeon is feasible. Results of per-operative implementation illustrate the impact on neurosurgical strategy. 1. Ultra-fast deep-learned CNS tumour classification during surgery. Vermeulen C et al. Nature. 2023 Oct;622(7984):842-849.
SURG-02. INTRAOPERATIVE APPLICATION OF A POLYMER-BASED HYDROGEL AGAINST MEDULLOBLASTOMA GROUP 3 AND ATYPICAL TERATOID/RHABDOID TUMOURS
Authors: Moloney Cara , ElSherbeny Amr , McCrorie Phoebe , Porter Harry , Bastiancich Chiara , Bayraktutan Hulya , Oz Umut Can , Grundy Richard G , Nilsson Karin Forsberg , Brem Henry , Alexander Cameron , Tyler Betty , Smith Stuart J , Rahman Ruman
Published: June 2024

BACKGROUND

Local drug delivery systems (LDDSs) applied during neurosurgery offer a means of overcoming poor blood brain barrier (BBB) permeability and have been extensively investigated for the treatment of adult gliomas. To the best of our knowledge, they have not been investigated for the treatment of paediatric cerebellar tumours, including medulloblastoma group 3 (MB3) and atypical teratoid/rhabdoid tumours (ATRT), both of which are associated with poor prognoses.

METHODS

We prepared and characterised an injectable and biodegradable poly(ethyleneglycol)-poly(caprolactone)-poly(ethyleneglycol) (PECE) hydrogel, which has been investigated broadly throughout the literature with an array of therapeutic agents against numerous cancer types. Here, we loaded the PECE hydrogel with chemotherapeutics previously identified as being effective against primary MB3 and ATRT in vitro, but which do not cross the BBB in vivo, namely CHIR99021, ribavirin and PG545. Biocompatibility and cytotoxicity of drug loaded hydrogels was assessed in vitro. LDDSs safety and efficacy was evaluated using patient derived MB3 and ATRT intracranial xenograft resection models.

RESULTS

The hydrogel was both biocompatible and effected cytotoxicity following drug release. In vivo efficacy experiments against MB3 indicated a comparable median survival in treatment arms receiving radiotherapy or CHIR99021 and PG545 loaded LDDS. However, combined radiotherapy and LDDS conferred a significant survival enhancement including long-term survivors. Against ATRT, the median survival of arms receiving radiotherapy was comparable to that of the CHIR99021 and ribavirin loaded LDDS, with long-term survivors observed only in the latter arm.

CONCLUSIONS

The application of LDDSs against cerebellar brain tumours offers a promising novel therapeutic alternative. For MB3, the combination of radiotherapy and a LDDS significantly enhances survival compared to radiotherapy alone. For ATRT, the comparable survival of the LDDS and radiotherapy alone is encouraging and indicates the possibility of circumventing radiation-induced adverse effects for young children impacted by this disease.
SURG-04. COMPARABLE SAFETY OF INTRATHECAL CHEMOTHERAPY GIVEN VIA LUMBAR PUNCTURE OR INTRAVENTRICULAR RESERVOIRS FOR PEDIATRIC CENTRAL NERVOUS SYSTEM (CNS) TUMORS: A SINGLE-INSTITUTION EXPERIENCE
Authors: Richmond Caleb , Zimmerman Mary Ann , Chordas Christine , Helt Jessica , Fitzgerald Caroline , Matson Kathryn , Wright Karen D , Yeo Kee Kiat , Chi Susan N , Rosenberg Tom
Published: June 2024

BACKGROUND

Intrathecal (IT) delivery of chemotherapy is utilized for the treatment of pediatric cancers, particularly leukemia and CNS tumors, either via lumbar puncture (LP) or intraventricular reservoir (IR). While the latter allows easier administration and more frequent IT dosing, data are lacking on the comparative safety and efficacy between these administration routes. We now present the IT chemotherapy experience from a single high-volume pediatric neuro-oncology center.

METHODS

We performed a retrospective chart review of patients with primary CNS tumors treated with IT chemotherapy between the years 2004-2022 at Dana-Farber/Boston Children’s Hospital. We collected demographic, clinical and outcome data. Safety evaluation included review of immediate (procedural) and short-term post-procedural assessments.

RESULTS

We identified 74 patients who received a total of 1,211 IT chemotherapy administrations. Excluding patients with insufficient data, we report on 38 patients who received 717 administrations (LP, n=207; IR, n=510). Median age was 26.5 months (range, 0.1-14.5), and diagnoses included medulloblastoma (n=14), ATRT (n=14) and others (n=10). Immediate events were reported in 11 (0.2%) IR and 1 (0.4%) LP administrations, i.e technical (n=5), high ICP (n=3), and immediate adverse side effects (n=3). Short-term events were reported in 16 (3%) IR and 12 (5.8%) LP administrations, i.e. fever (n=6), seizures (n=6), arachnoiditis (n=4), and others (n=10). No grade 4-5 adverse events were reported. No statistically significant difference was found between routes of administration and the rate of immediate or short-term events. Of note, 14/18 (78%) patients with CSF-positive disease achieved CSF clearance, with median time to response of 57 days (range, 27-446).

CONCLUSIONS

IT chemotherapy shows an excellent safety profile in children with malignant CNS tumors, with no differences between IR and LP administration. IT delivery can be efficacious in CFS clearance for patients with metastatic disease, lending support to inclusion of IT chemotherapy in current treatment regimens.
SURG-06. FRAMELESS STEREOTACTIC INTRACRANIAL CATHETER PLACEMENT FOR DELIVERY OF INTRATUMORAL CELLULAR THERAPIES
Authors: Murugesan Rakesh A , Tucker Alexander , Kline Cassie , Foster Jessica , Madsen Peter
Published: June 2024

BACKGROUND

As the leading disease-related cause of death in children, pediatric brain tumors, and in particular diffuse midline glioma, require novel treatment approaches. Cellular-based therapies offer promise, but challenges still exist in defining their optimal delivery route. Emerging data from our group suggest there may be a role for intratumoral injection in treatment algorithms. We here describe a surgical workflow for intratumoral injection of cellular therapies that utilizes existing and widely used neurosurgical technologies that can be incorporated into future clinical trials.

METHODS

Infusion target and catheter trajectory was planned using standard pre-operative MRI. Components from an FDA-approved frameless stereotactic intracranial biopsy system were chosen such that they would accept and guide an FDA-approved rigid intracranial catheter system intended for MR-guided procedures. Following catheter insertion, an intraoperative CT was used to determine accuracy of catheter placement by merging the image with the pre-operative MRI.

RESULTS

The proposed system was tested in a simulated fashion using a phantom cranial model registered to an accompanying brain MRI. The stereotactic biopsy mount was affixed to the skull at the planned entry site for a posterior fossa approach to the pons. Catheter insertion depth was determined using the stereotactic system and the catheter was inserted to this depth through the biopsy mount. Intraoperative CT confirmed the catheter tip location which correlated with the planned infusion target with sub-millimetric accuracy.

CONCLUSION

Our proposed intratumoral delivery method using frameless stereotaxy shows promise for use in future clinical trials that require intratumoral delivery of cellular therapies. Utilizing FDA-approved devices allows for quick integration into protocols and their wide-spread use makes the approach generalizable. This approach also eliminates the need for MR-guided procedures which can increase cost and require significant hospital resources to perform. Future work will be aimed at streamlining the intraoperative workflow.
NURS-02. THE DEVELOPMENT AND IMPLEMENTATION OF SKINCARE TREATMENT PLANS AND PRODUCT KITS FOR PEDIATRIC PATIENTS RECEIVING TARGETED THERAPIES THAT CAUSE SKIN TOXICITY
Authors: Meyer Ashley S , Ogle Andrea , Mchugh Michele , Beck Mary , Lampe Ashley , Cluster Andrew , Brossier Nicole M , Shatara Margaret , Rocco Abbey , Abdelbaki Mohamed S , Coughlin Carrie C
Published: June 2024

BACKGROUND

Mitogen-activated protein kinase (MAPK) pathway inhibitors are incorporated into the treatment regimens for several pediatric cancers. However, they commonly trigger dermatologic side effects, which can be challenging to manage and may have a significant impact on the quality of life.

METHODS

We previously performed a prospective study looking at the satisfaction and utilization of skincare kits and patient education regarding basic skincare practices. Based on these data, we developed revised skincare product kits and treatment plans that can be individualized for patients who are at risk of developing dermatologic side effects from targeted therapies.

RESULTS

Based on our prior study, 77% of patients thought the skincare kits and instructions were helpful. Seventy-seven percent of patients also recommended that they be distributed at the initiation of therapy. Through this study, we discovered that the patient reported medical history questions were inconsistent when compared with medical chart reviews. The most common discrepancies included information regarding patient’s diagnosis, prescribed medications, skin-related problems, and past medical history. From this data, we have developed a new skincare product kit and patient skincare plans which we distribute to every patient prior to starting their targeted therapy. The skincare kits consist of a cleanser, emollient, oral care products, sunscreen, pyrithione zinc containing shampoo, and facial moisturizers for adolescent patients. Our patient skincare plans consist of patient-specific information including diagnosis, medications, and their targeted agent. The plan provides details on how and when to use each product, application time, and order in which to apply products and topical medications.

CONCLUSION

Our project has highlighted the importance of patient education regarding dermatologic side effects in those starting targeted therapies. We have successfully implemented this by providing our patients with both skincare products and patient-specific care plans.