bluuebunny/crossref_metadata_2025 huggingface dataset:
QOL-37. THE CREATION OF A PLAY PREPARATION CLINIC FOR CHILDREN WITH CENTRAL NERVOUS SYSTEM TUMOURS TO REGAIN CONTROL ONCE MORE
Authors: Ryles * J , Ternent * L , Arif T , Halliday G , Hill R M , Bailey S
Published: June 2024

Targeted therapies are becoming more readily available for children with Central Nervous System (CNS) tumours, not only for early phase but also late phase trials. With this knowledge, we have created a play preparation clinic whereby all children with a CNS tumour diagnosis are invited to attend. Initially the play preparation clinic was solely a programme to train children to take tablets using a technique created at The Great North Children’s Hospital called ‘Kidzmeds’. On average children are successful in achieving the ‘Kidzmeds’ technique within ten minutes so we were able to expand the programme and incorporate two other areas of play preparation. Firstly, we have been able to include play preparation for children undergoing procedures without sedation or general anaesthesia such as MRI scans and lumbar punctures. Secondly, we have been able to use play preparation to teach children how to achieve cannulation or blood taking using a specific technique we have called the ‘GNCH way’. Our aim is that children leave our hospital having a positive experience and regain control and choice in how procedures take place, feeling they have ownership of their bodies. There is an added incentive of cost saving for our hospital, for example converting medication from liquid to tablet form. Forty-eight children have took part in the clinic so far. Every child has been able to achieve two of the play preparation techniques we offer and eighty-three percent of children have been successful in achieving all three. The youngest child in achieving all three play preparation techniques has been four years old. All forty-eight children continue to be successful in their achievements. Within our service, the feedback from children and families have been overwhelmingly positive and our hope is that other hospitals across the world can benefit from our experience.
QOL-39. FATIGUE AS A RISK FACTOR FOR REDUCED SOCIAL CONNECTEDNESS IN PEDIATRIC BRAIN TUMOR SURVIVORS
Authors: Fantozzi Peter , Fisher Michael J , Herrington John D , Li Yimei , McCormack Shana E , Parish-Morris Julia , Hocking Matthew C
Published: June 2024

BACKGROUND

Pediatric brain tumor survivors (PBTS) experience reduced social connectedness, including fewer friendships, less social acceptance, and greater isolation. Identifying modifiable factors contributing to social issues would yield treatment opportunities. Fatigue is common among PBTS and may relate to social challenges. This study evaluated fatigue among PBTS and its associations with various indices of social connectedness.

METHODS

Survivors (N = 34) of three types of brain tumors—medulloblastoma (N = 11), pilocytic astrocytoma (N = 15), and craniopharyngioma (N = 8)—completed self-reported measures of fatigue and social connectedness. Laboratory studies assessed thyroid function and growth hormone status. Caregivers completed measures of social functioning. Descriptive statistics summarized fatigue and endorsement of fatigue items. ANOVAs, t-tests, and Pearson correlations evaluated fatigue according to various medical factors, and Pearson correlations evaluated associations between self-reported fatigue and indices of social connectedness.

RESULTS

Over 20% of survivors reported elevated fatigue, with 53% and 35% indicating fatigue interfering with attention and socialization, respectively. We did not detect associations between self-reported fatigue and diagnosis, current age or age at diagnosis, time since end of treatment, or history of chemotherapy or cranial radiation therapy. We did not detect an association between BMI Z-score and collected hormones. Mean T scores on the self-reported peer relationships measure were below the reference mean (M = 45.8, SD = 11.9), with 22% of survivors endorsing concerns. Higher self-reported fatigue was significantly correlated with poorer self-reported peer relationships (r = -.62, p < 0.001) and more parent-reported social impairments (r =.61, p < 0.001).

CONCLUSIONS

Fatigue is common among PBTS and may interfere with peer relationships. Clinicians should screen for fatigue as a risk factor for reduced social connectedness. Further research is needed to identify predictors of fatigue and social difficulties and determine temporal associations between fatigue and social connectedness.
QOL-50. THE ROLE OF TUMOR SIZE IN COGNITIVE FUNCTIONING AMONG SURVIVORS TREATED FOR MEDULLOBLASTOMA
Authors: Raghubar Kimberly P , Christopher Krystal , Kim Se-Kang , Mash Lisa , Stancel Heather , Parsons Kelley , Feuerbach Natasha , Rizvi Maheen , Paulino Arnold , Grosshans David , Okcu M Fatih , Kahalley Lisa S , Chintagumpala Murali
Published: June 2024

BACKGROUND

Medical and treatment variables, including presence of post-operative cerebellar mutism syndrome (CMS), shunt placement, craniospinal radiation, and total radiotherapy (RT) dose, have been evaluated as potential risk factors for adverse cognitive effects among pediatric patients diagnosed and treated for medulloblastoma. Larger brain tumor size is associated with increased risk of medical complications, but cognitive risk of larger tumor size remains unknown.

METHODS

Cognitive scores were examined for 40 participants diagnosed and treated for medulloblastoma. The age-appropriate Wechsler Intelligence Scale was administered at the start of RT and up to 10 years post-RT (M=4.96, SD=3.78). A total of 162 evaluations were examined across participants. Linear mixed models examined change in Wechsler Index scores over time since RT based on tumor size, which was dichotomized at the median diameter (small ≤4.6cm versus large >4.6cm), covarying for maternal education, total RT dose, and presence of CMS.

RESULTS

Patients (72.5% male) were diagnosed with medulloblastoma and began RT at a mean age of 8.89 years. Groups did not differ on demographic or medical variables with the exception of presence/absence of CMS, with a higher proportion of patients diagnosed with CMS having large-size tumors (40%) versus small-size tumors (5%). Tumor size did not predict change in IQ, working memory, or processing speed performance over time since RT after accounting for covariates. CMS was associated with significant decline in processing speed (p<.001) and IQ over time (p<.05); RT dose was associated with significant working memory and IQ decline (both p<.05); and maternal education was associated with decline in processing speed, working memory, and IQ (all p<.05).

CONCLUSIONS

While tumor size may be associated with treatment intensity and other medical risk factors, CMS and RT dose significantly increase cognitive risk, independent of tumor size. Lower socioeconomic status also increases cognitive risk post-RT, which may illuminate pathways for prevention and intervention efforts.
QOL-53. EXPLORING HEADACHES IN PEDIATRIC NEURO-ONCOLOGY PATIENTS: A SINGLE INSTITUTION RETROSPECTIVE CHART REVIEW
Authors: DeMarsh Samantha J , Ackley Elizabeth R , Staley Alyse , Dorris Kathleen M
Published: June 2024

BACKGROUND

Despite the high prevalence of headaches in pediatric patients with brain tumors, very little research has been done to characterize their traits and to assess current management practices. Effective and efficient treatment of these headaches is critical to the optimization of brain tumor survivors’ quality of life. Foundational knowledge of any clinical associations likely would be beneficial to develop rational management strategies.

METHODS

A retrospective single-institution chart review of pediatric patients seen in the Children’s Hospital Colorado (CHCO) Neuro-oncology clinic from 1/1/22-12/31/22 is underway. Information is being collected via manual chart review including basic demographic information, oncologic diagnosis and tumor location, surgical interventions, and tumor-directed treatments. Headache characteristics, including timing of onset, associated symptoms, severity and frequency, referral to CHCO Neurology Headache Clinic and any headache therapies attempted will be sought. Additional information will include the number of emergency department visits and unplanned MRIs obtained as part of headache management.

RESULTS

384 patients (53% male; median age 12 years, range 2-24 years) received care in the CHCO Neuro-oncology clinic in 2022. The majority of these patients were Caucasian/Non-Hispanic (61.7%), followed by Caucasian/Hispanic (13.8%) and African American/Non-Hispanic (4.2%). In this cohort, the preferred language for 93% was English and for 6% was Spanish. The majority (55%) of patients had a low-grade glioma/ glioneuronal tumor as their oncologic diagnosis. Patients with referrals to CHCO Headache clinic made up 13% of this cohort. Data collection and analysis are ongoing.

CONCLUSIONS

This data set will help to characterize the prevalence and features of headaches in pediatric patients with CNS tumors. This information will serve as the foundation for planned prospective studies that will collect more comprehensive and consistent data related to headaches in the pediatric neuro-oncology population and to formalize processes that will identify appropriate patients for referral to specialized headache providers.
SURG-05. INTRA-ARTERIAL CHEMOTHERAPY FOR NEWLY DIAGNOSED, RESIDUAL, OR RECURRENT ATYPICAL CHOROID PLEXUS PAPILLOMA AND CHOROID PLEXUS CARCINOMA PRIOR TO SECOND-LOOK SURGERY
Authors: Larsen Alexandra M Giantini , Rangaraj Rashi , Sanders Colleen , Garton Andrew , Gobin Y Pierre , Knopman Jared , Tsiouris Apostolos John , Pisapia David , Souweidane Mark
Published: June 2024

BACKGROUND

Atypical choroid plexus papilloma (ACPP) and choroid plexus carcinoma (CPC) are rare malignant tumors of the central nervous system. Complete resection, the most important prognostic variable for long-term survival, is often limited by tumor vascularity and voluminous size in children. While systemic chemotherapy is known to reduce tumor volume and intra-operative blood loss, children often experience dose-limiting side effects. We hypothesize the use of intra-arterial (IA) chemotherapy for newly diagnosed, recurrent, or residual CPC/ACPP would increase likelihood of achieving complete resection in a safer manner.

OBJECTIVE

To assess the safety, feasibility, and effect of pre-operative IA chemotherapy for CPC/ACPP.

METHOD

The patient was treated according to phase I clinical trial protocol (NCT04994977) which consists of a single IA chemotherapy administration of melphalan, topotecan, and carboplatin followed by MRI-based response assessment to determine eligibility for second-look surgery. Primary endpoints are serious adverse events, and secondary endpoints include angiographic procedural success, tumor volume reduction on MRI, extent of resection and caclulated blood loss (CBL), and pathologic correlates of vascularity and tumor viability.

RESULT

7-year-old male with Li-Fraumeni syndrome was enrolled for residual CPC (4.8 x 4.6 cm) after three prior resection attempts were limited by significant blood loss. Pre-operative IA chemotherapy was delivered to two targets without complication: the right posterolateral and anterior choroidal arteries. Five weeks later, MRI confirmed tumor volume reduction of 6.3%. On angiographic evaluation for administration of pre-surgical embolization, a significant reduction in angiographic hypervascularity was found, and liquid embolic embolization was not pursued. Craniotomy resulted in gross total resection without transfusion requirement and minimal CBL. Pathology demonstrated reduced proliferative index (Ki67 4% versus 10% in prior tissue).

CONCLUSION

Early phase results indicate pre-operative IA chemotherapy for residual CPC/ACPP may serve as safer bridge to second look surgery by decreasing tumor volume and vascularity.
NURS-11. NEURO-ONCOLOGIC EMERGENCY MANAGEMENT
Authors: Fitzgerald Caroline , Phelan Alison
Published: June 2024

BACKGROUND

Due to disease location, neuro-oncology patients experience emergencies that are infrequently encountered in general oncology and require unique interventions. Paramount among these emergencies is vasogenic cerebral edema (CE). Urgent and accurate interventions are needed to decrease associated morbidity and mortality. In an educational institution, access to knowledge of next steps is crucial. This prompted further inquiry of best practice into recognition of increasing intracranial pressure (ICP) and management of cerebral edema using a literature review and reflection on institutional experience.

METHODS

A literature review was conducted using pubmed to identify articles through January 2014. The Key words used in the search included “neuro-ongologic emergencies” “brain herniation management” “cerebral edema.

RESULTS

The searched yielded 3237 results. Of these, 3236 were excluded. Ten full text articles were relevant and included in the review. In combination with the literature and institutional experience of neuro-oncological emergencies, interventions and outcomes were evaluated to provide recommendations for treatment in the event of an emergency.

CONCLUSION

CE is not an uncommon finding with malignant brain tumors given disrupted blood brain barrier. This subsequently increases ICP and left unmanaged, can lead to brain herniation. Signs and symptoms can vary depending on tumor location and extent of edema. Most common exam findings to be aware of include headache, nausea, vomiting, altered pupil exam, abnormal eye movements, and altered consciousness. Ultimately surgical intervention may be the definitive treatment, non-surgical management is important. Literature review supported the use of both high dose dexamethasone and hyperosmolar solutions are temporizing measures to decrease CE. Additional measures such as positioning, treatment of pain or fever, are also recommended. Prompt recognition and intervention of CE are crucial to improved patient outcomes. An educational poster with recommendations for best practice when encountering neuro-oncological emergencies will be created. Dissemination of findings will be done at local, national and international levels.
OTHR-02. ONE-YEAR FOLLOW-UP OF THE NEW ERN PAEDCAN CNS TUMOR BOARD: LESSONS LEARNT AND FUTURE PROSPECTS
Authors: Sönksen Marthe , Bison Brigitte , Bußenius Lisa , Rascon Jelena , Obrecht-Sturm Denise , Pizer Barry , Scheinemann Katrin , Schalling Martin , Ladenstein Ruth , Mynarek Martin , Rutkowski Stefan
Published: June 2024

BACKGROUND

European Reference Networks (ERN) are collaborative networks connecting healthcare professionals across Europe. A virtual tumor board for pediatric patients with central nervous system (CNS) tumors was established within the ERN for pediatric oncology (ERN PaedCan) in September 2022. We report the feasibility, the implementation of recommendations and satisfaction of the participants.

METHODS

A web-based questionnaire was distributed to physicians presenting cases between November 2022 and November 2023. Questions addressed the implementation of recommendations, satisfaction and basic information about the local institution. Basic data of the presented cases were taken from anonymized tumor board protocols.

RESULTS

In the first year, 19 patients from 11 institutions located in nine European countries were discussed in 21 tumor boards. Median age at diagnosis was 10 (1-17) years. Demonstration of MRI findings by the German national reference center for neuroradiology was conducted in 19/21 conferences. 18/21 questionnaires (86%) were answered by physicians from eight countries. Main reason to request the discussion were questions about therapy (78%, n=14/18). Inquiring institutions treated a median of 10 (5-150) neuro-oncological pediatric patients per year. All hospitals conducted own institutional tumor boards. National central review was available in 3/8 countries (38%). Recommendations were followed, at least partly, in all cases except for one patient experiencing unexpected clinical deterioration. Recommendations were deemed helpful in 89%. All participants would recommend the tumor board to colleagues. Technical issues regarding data provision were reported as the main obstacle in 50 %.

CONCLUSIONS

A European virtual tumor board for pediatric patients with CNS tumors is feasible and perceived as useful by the participating institutions. Recommendations were followed frequently. Optimization of privacy-compliant data exchange is crucial for continuance of the format. This project has been supported by ERN PaedCan, which is funded by the European Union within the EU4Health Program 2021-2027. Funded by EU-grant 101085543.
OTHR-06. A NEW INTERNATIONAL, MULTIDISCIPLINARY ACCELERATOR PROGRAMME FOR NOVEL BRAIN TUMOUR THERAPIES
Authors: Aitken Charlotte , Huskens Nicky , Bushby Katie , Noble Karen , Hamerlik Petra , Kaye Edward , Kobayashi Dione , Matthew Ryan , McCall John , Nazarian Javad , Plummer Ruth , Rahman Ruman , Lopez Juanita , Nagaraju Kanneboyina
Published: June 2024

BACKGROUND

Developing a comprehensive translational programme for brain tumours involves navigating numerous challenges, including robustness of preclinical studies, safety, clinical trial design, regulatory issues, and commercialisation. Recognising this journey can be difficult, the Brain Tumour Research Novel Therapeutics Accelerator (BTR-NTA) was launched. The BTR-NTA is an accelerator programme that provides independent guidance to de-risk drug or device development through systematic evaluation. The international, multidisciplinary BTR-NTA Committee spans the entire therapeutic development pathway to avoid a siloed approach to therapeutic development. Thanks to Brain Tumour Research funding, the BTR-NTA is free for academics and available at nominal cost for industry.

METHODS

Researchers at any stage of therapeutic development are invited to apply to BTR-NTA, and, if accepted, their application proceeds as follows: 1. The Applicant completes an application form covering work to date and future plans under a confidentiality agreement that protects the Applicant’s intellectual property; 2. The Applicant’s therapeutic is reviewed by the BTR-NTA Committee 3. The Applicant and BTR-NTA Committee meet in-person to discuss the Applicant’s work; and 4. The Applicant receives a comprehensive report with feedback on strengths, identification of potential risks, and guidance on next steps. The BTR-NTA Committee dedicates half a day to reviewing the Applicant’s work in-person, and extensive time pre- and post-meeting.

RESULTS

Following the launch of BTR-NTA in 2023 and review of the first therapies, we will report on impact to date, early learnings, and how we hope to grow BTR-NTA to accelerate novel brain tumour therapies globally.

CONCLUSIONS

The ultimate goal of BTR-NTA is to enable researchers with a potential therapy for brain tumours to navigate the development journey and successfully reach the clinic in an efficient way. It is hoped this programme will strengthen international collaboration and support the development of novel therapies to improve outcomes for brain tumour patients.
OTHR-15. POSTMORTEM TISSUE BIOBANKING AND COLLABORATIVE EFFORTS: A SINGLE INSTITUTION REPORT
Authors: Peck Sydney N , Lebert Brittany , Hegert Julia , Wright Avery , Zapata Claudia , Pitts Blaine , Bonilla Ana Aguilar- , Smith Amy A
Published: June 2024

BACKGROUND

Post-mortem tissue donation holds significant value to researchers, clinicians and bereaved families however it is an underutilized tool. Initiatives in pediatric neuro-oncology allow new insights into tumors such as DIPG and is becoming more widespread. Barriers include treating physicians lack of knowledge, lack of resources, religious beliefs and more. Postmortem tissue gives insight into the evolving biology of cancer and failed treatments. Postmortem tissue donation offers some understanding to families and empower them to help others. Surgical tissue collection used for diagnosis, leaves limited amounts for research.

METHODS

Since 2012, we have contributed to pediatric cancer research by offering postmortem donation to 48 patients. We have consented and facilitated 35 autopsies. In 2020, Arnold Palmer Hospital for Children became a lead institution for the COG’s Project:EveryChild. In 2021, we became a Center of Excellence for Gift From A Child. Our local Translational Protocol, IRB-approved, allowing us to collect and store our surgical and postmortem samples. To date, we have collected over 839 postmortem samples from 35 patients. In our Translational Laboratory, we have access to 207 postmortem samples from 13 patients. Through collaborative research initiatives, we have successfully sent over 368 samples from 11 patients and 14 parents to GFAC. Through Project:EveryChild we have shared 218 samples from 7 patients.

RESULTS

To explore the quality of postmortem tissues, we tested the integrity of our samples through DNA and RNA sequencing. The DNA quality is excellent across specimens and equivalent to surgical specimens however the RNA quality from autopsy specimens has degraded 7.5% RINe factor > 8 (excellent) and 38% RINe factor > 6 (mildly degraded) compared to surgical specimens, 85% with RINe factor > 8, 14.3% RINe factor > 6.

CONCLUSION

The platform of postmortem tissue donation can lead to further advancements in understanding the evolution and resistance of cancer.
OTHR-17. FACILITATING THE POSTMORTEM DONATION OF WHOLE BRAIN AND SPINAL CORD IN PEDIATRIC PATIENTS WITH CENTRAL NERVOUS SYSTEM CANCERS
Authors: Kopsidas Caroline A , Morinigo Denise , Nourmohammadi Niku , Eze Augustine , Debasish Roy , Bornhorst Miriam , Yadavilli Sridevi , Packer Roger , Nazarian Javad
Published: June 2024

BACKGROUND

Postmortem tissue donation is often presented to families during end-of-life discussions. The sensitive nature requires every step to be handled with care, leading with empathy and delicately balancing scientific research and humanity. The Children’s National Hospital Postmortem Tissue Donation Workflow (The Workflow) provides a step-by-step guide for coordinating a successful donation. It outlines the order in which clinical research teams communicate with patient care teams, families and collaborators to make the donation possible. This program, established in 2010, aims to acquire more pediatric brain and spinal cord tumor specimens to further understand the disease biology.

OBJECTIVE

This paper aims to provide a template for coordinating a successful postmortem tissue donation. Ultimately, to broaden the network of tissue donation across all hospitals and institutions, thus furthering scientific research.

METHOD

In order to create The Workflow, Clinical Research Coordinators from Children’s National Hospital conducted numerous postmortem donations and noted the failures and successes of each case. This information was compiled into a stepwise workflow including email templates and checklists. It begins with contacting the care team, and the following hours to days are spent obtaining a pathologist for tissue procurement, and facilitating the shipment of samples. While these steps must be completed in a timely manner for sample integrity, we also prioritize the wishes of the family and act with compassion at the forefront.

RESULTS/DISCUSSION

Children’s National Hospital was designated as a Center of Excellence for postmortem coordination by the Swifty Foundation in 2018. Our team has since established and standardized a workflow for the donation process. The Children’s National Hospital Postmortem Workflow allows our research team to study brain tumors including DMGs, High and Low Grade Gliomas, and Medulloblastomas. The generosity of the families and hard work of each collaborator allows us to expand our knowledge of tumor biology.
OTHR-24. CLINICAL COURSE OF ISOLATED PITUITARY STALK THICKENING IN PEDIATRIC PATIENTS AND RISK FACTOR FOR NEOPLASTIC ETIOLOGY: A SINGLE INSTITUTIONAL EXPERIENCE
Authors: Miller Hannah K , Rajan Vikram P , Gorsi Hamza S
Published: June 2024

BACKGROUND

The incidence of pituitary stalk thickening (PST) has increased in recent years due to the increased utilization of diagnostic MRI of the brain. The etiology of PST includes germ cell tumors, Langerhans cell histiocytosis (LCH), and lymphocytic hypophysitis, among others. The clinical significance of PST, appropriate diagnostic workup, and clinical course for these patients is not well documented. We report our institutional experience with patients presenting with PST.

METHODS

After IRB approval, we reviewed lists of patients discussed in pediatric tumor boards from 2003-2023 to identify patients with PST. We excluded patients with other significant intracranial masses from our analysis. We followed the clinical course of these patients to collect applicable data.

RESULTS

A total of 20 patients were identified with PST, five patients were excluded due to additional MRI findings. The median age of diagnosis with PST was 14 years; 60% of cases were female. Seven patients had diabetes insipidus (DI), and five patients had other endocrinological abnormalities. Initial diagnostic workup included serum and CSF tumor markers (AFP, B-HCG), skeletal survey, CBC, and CMP. With this initial workup, no patients were diagnosed with neoplasm. All patients were followed with serial MRIs. Four patients (26.6%) displayed progression of PST, warranting biopsy. The median time from diagnosis to biopsy was seven months (range 4-26 months). Among four patients with biopsy, two had LCH, one had germinoma, and one inconclusive result. Among those diagnosed with neoplasm, 100% of them had DI. Three patients had complete resolution of PST during the follow-up period. Eight patients had stable PST during the median follow-up period of 19.5 months (Range 3-59 months).

CONCLUSIONS

Most isolated PST among pediatric patients remained stable during the follow-up period. The risk for neoplastic process was high among patients with increasing thickening of pituitary stalk and DI.
OTHR-25. ANAPLASTIC TRANSFORMATION OF DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMORS: TWO PEDIATRIC CASES
Authors: Aguilera Dolly , Janss Anna , Schniederjan Matthew , Goldman-Yassen Adam , Velazquez Jose , Mazewski Claire , Gray Rachel , MacDonald Tobey , Fangusaro Jason , Castellino Robert Craig
Published: June 2024

BACKGROUND

Diffuse Leptomeningeal Glioneuronal Tumors (DLGT) typically have a clinical course with slow progression; however, there have been cases of anaplastic transformation. We describe the clinical presentation, radiographic features, and molecular characteristics in 2 pediatric DLGT cases that underwent aggressive transformation.

METHODS

Patient 1: A 20 y/o male with DLGT with BRAF-KIAA1549 fusion and loss of 1p who was first diagnosed at 2.5 y/o. Over the course of 17 years, he was treated with numerous therapies due to multiple progressions, including temozolomide, carboplatin/vincristine, selumetinib, and vinblastine. At age 17, he developed significant growth of a posterior fossa mass with solid and cystic characteristics. Resection revealed new anaplastic pathologic features. Patient 2: He was diagnosed with DLGT at age 2 y/o. Imaging demonstrated intramedullary spinal nodules at T4 and T5 with abnormal thickening and enhancement over the cerebral leptomeningeal space. A biopsy revealed DLGT with a BRAF-KIAA1549 fusion, 1p loss and Ki67 5%. He received multiple therapies including carboplatin/vincristine, vinblastine, and selumetinib.

RESULTS

Patient 1: Molecular characterization revealed new ATRX mutation, and CDKN2A/B homozygous deletion. Over the following 2 years, he had multiple treatments, progressions, and surgeries. Final pathology revealed significant anaplasia with Ki67 90%, ATRX loss, and mutation of PPM1D and ARID1A. He rapidly declined. Patient 2: Approximately 2.5 years after diagnosis, he developed rapid progression in the 4th and lateral ventricles. Pathology confirmed recurrent DLGT, but with high-grade transformation, H3K27M (-), H3k27m3 loss, ATRX (+), Ki67 40%. He was treated with focal irradiation followed by temozolomide/CCNU.

CONCLUSION

In rare cases, DLGT can undergo anaplastic transformation. Once this occurs, it behaves clinically like a high-grade glioma. Understanding the molecular underpinnings and prognostic features that lead to this transformation are important for future study.
PALC-02. PALLIATIVE RADIOTHERAPY FOR HAEMOSTASIS IN CHILDREN WITH CEREBRAL METASTATIC HAEMORRHAGE
Authors: Coassin Elisa , Vitullo Angelo , Pilotto Chiara , Liguoro Ilaria , Toniutti Maristella , Tuniz Francesco , Vindigni Marco , Pegolo Enrico , Cogo Paola Elisa , Mascarin Maurizio
Published: June 2024

BACKGROUND

Among children, bleeding from brain metastases is rare. Bleeding could be caused by: cancer, treatments and chemotherapy/other drugs such as Bevacizumab, NSAIDs and anticoagulants. We report a case of brain RT after metastases bleeding.

METHODS

A 14-years-old boy with a negative previous medical history presented to the Emergency Department with seizures and loss of consciousness. Full-body CT scan revealed brain and renal haemorrhages and a right testicular lesion. Serum βhCG was 223,773 mIU/mL. Neurosurgical bleeding control and right orchiectomy were performed: the histopathology revealed a metastatic mixed non-seminomatous germ cell neoplasia of the testis. First-line chemotherapy (4 cycles of Cisplatin/Etoposide/Ifosfamide) and second-line treatments (Paclitaxel/Ifosfamide/Cisplatin and Gemcitabine/Paclitaxel/Oxaliplatin) were performed. Suddenly, he presented with left-sided hyposthenia and partial left hemibody seizure. CT scan revealed 2 haemorrhagic brain lesions, one in each hemisphere. Surgery was not feasible. We started anti-oedema and anti-epileptic therapy, and whole brain RT (WBRT, 36 Gy/12 fx, BEDα/β= 10 Gy= 46.8 Gy). After 5 days from the start, RT had a 7-day stop because of acute oedema and clinical deterioration. Fourth-line chemotherapy was administered with CarboPEB (1st of further 4 cycles), and then WBRT was restarted. At the end of WBRT a stereotactic RT boost to both the haemorrhagic lesions was delivered (20 Gy/10 fx, BEDα/β= 10 Gy= 24.0 Gy). As of today, eight months after the end of therapy, the patient is free from disease and βhCG is negative.

CONCLUSION

Palliative RT in children is a non-conventional indication, but potentially effective at providing rapid haemostasis, especially in selected cases (surgery not feasible/contraindicated, adult-type histologies, …) and it is ensuring a good tumor control and low-grade acute toxicities. Hypofractionation is suggested to balance patient comfort and treatment effectiveness, especially when life expectancy is short. The optimal RT schedule, dose and fractionations need to be further investigated.
PATH-11. FEASIBILITY OF BRAIN TUMOR CLASSIFICATION BY ENZYMATIC DNA METHYLATION SEQUENCING ANALYSIS OF CELL-FREE DNA OBTAINED FROM CEREBROSPINAL FLUID
Authors: Taylor Aaron Michael , Lombardi Jody T , Patel Areeba , Martin Jonathan , Bookland Markus J , Hersh David S , Cantor Evan , Song Xianyuan , Sahm Felix , Ng Patrick Kwok-Shing , Gell Joanna J , Lau Ching C
Published: June 2024

BACKGROUND

Array-based DNA methylation profiling is the gold standard for molecular classification of brain tumors. However, it relies on significant amount of input DNA extracted from surgical tissue, thus limiting its use for tumors where biopsy is challenging or limited in quantity. Cell-free tumor DNA (cfDNA) in cerebrospinal fluid (CSF) presents alternative opportunities for brain tumor diagnosis and disease monitoring following treatment. Novel enzymatic DNA methylation sequencing (EM-seq) methods may allow us to overcome input DNA limitations and accurately quantify methylation from cfDNA.

METHODS

We performed methylation sequencing using the NEBNext EM-seq kit on cfDNA from archival CSF samples collected from three brain tumor patients with confirmed histopathological diagnoses. Variable amounts of input cfDNA (0.1ng-10ng) were tested. We utilized the methylseq pipeline for data processing. For tumor classification, data was limited to CpG sites overlapping the MethylationEPIC array before analysis using MNP-Flex, a modified platform-agnostic version of the Heidelberg methylation classifier

RESULTS

Using the EM-seq method, genomic coverage for 10 and 1ng input DNA samples (average: 46x and 26x, respectively) was sufficient for generating global methylation profiles. Samples with 0.1ng input showed an average coverage of only 5.32x due to high levels of read duplication. However, methylation levels for CpG sites with at least 5x coverage were highly correlated across varying input DNA amounts, suggesting that lower input cfDNA could still be used for tumor classification based on relevant CpG sites.

CONCLUSIONS

Using the MNP-Flex classifier, which was originally trained with methylation array data from tumor tissue, we successfully predicted brain tumor types (both high-grade glioma and medulloblastoma) with cfDNA methylation data down to only 0.1ng of input cfDNA, matching diagnosis based on tissue methylation and histopathology in this pilot study. Further classification of additional tumor types using CSF cfDNA is required to confirm the clinical utility of this platform.
LMIC-15. OUTCOMES OF PEDIATRIC MEDULLOBLASTOMA IN LOW- AND MIDDLE-INCOME COUNTRIES: A REPORT OF 330 PATIENTS FROM 8 COUNTRIES
Authors: Diaz-Coronado Rosdali , Hernandez-Broncano Eddy , Negreiros-Chinchihuara Tatiana , Casavilca-Zambrano Sandro , Campos Danny A , Baticulon Ronny E , Alcasabas Ana Patricia A , Khu Kathleen , Hamid Ahmer , Zia Nida , Syed Yumna , Yousuf Bisma , Omran Nuha , Sharafeldin Hend A , Seddik Khaled , Fadel Shady , Pineda Estuardo , Polanco Ana , Foo Jen Chun , Rajagopal Revathi , Ganesan Dharmendra , Campo Regina Navarro-Martin del , Arredondo-Navarro Luis , Escamilla Gabriela , Ruvalcaba Rafael , García Beatriz , Amarillo Paloma , Villegas Cesar A , Job Godwin , Faughnan Lane , Devidas Meenakshi , Qaddoumi Ibrahim , Moreira Daniel C
Published: June 2024

BACKGROUND AND AIMS

Reports from low-and middle-income countries (LMICs) indicate lower survival in medulloblastoma (MB), though these studies are mainly from single institutions. This multi-institutional, retrospective study aimed to analyze the outcomes for MB in 9 centers in 8 LMICs.

METHODS

Patients <18 years old with newly diagnosed MB, treated from January 2014 to December 2018 in Egypt, El Salvador, Malaysia, Mexico, Pakistan, Peru, Philippines, and Uruguay were included. Data on demographics, clinical presentation, treatment and biological characteristics were collected. Factors associated with patient outcomes were analyzed.

RESULTS

The study included 330 patients with a median age of 7.7 years. Of these, 49 patients (15%) were <3 years old and 212 (64%) were male. Eighty-eight patients (26%) had experienced symptoms for >3 months at diagnosis. Gross total resection was achieved in 153 (47%) patients. Sixty-three patients (19%) experienced post-operative infections. Eighty-four patients (24%) had metastatic disease at diagnosis. The histologic subtype was not specified in 98 cases (30%), and 25 patients (7%) had molecular subgroups identified. Radiotherapy was administered to 216 patients (64%). The median number of chemotherapy cycles was 8 (range 0-14). There were 64 patients (19%) who abandoned treatment, and 24 patients (7%) died due to treatment-related toxicity. The 5-year event-free survival (EFS) was 44±4%, while the 5-year overall survival was 58±4%. The 5-year EFS for patients <3 years was 42±9%, while 44±4% for older patients (p=0.49). The 5-year EFS for patients with metastasis was 38±7%, while it was 46±4% for patients without metastasis (p=0.13).

CONCLUSIONS

This large, multinational cohort of MB in LMICs describes poor outcomes, which may be attributed to delays in care, high abandonment rate, surgical complications, treatment-related mortality and a low fraction of patients receiving radiotherapy. Interventions to build care capacity can be prioritized based on these data.
RADT-03. IDENTIFYING BRAIN STRUCTURES LINKED TO RADIATION-INDUCED ENDOCRINE AND COGNITIVE SEQUELAE: A MULTI-CENTRE VOXEL-BASED ANALYSIS
Authors: Davey Angela , Wilson Lydia J , Osorio Eliana Vasquez , Green Andrew , Vaughan Kate , Clayton Peter , Albutt Lesley , van Herk Marcel , Merchant Thomas E , McCabe Martin G , Aznar Marianne C
Published: June 2024

BACKGROUND

Radiotherapy (RT) is a common treatment for paediatric brain tumours. Despite advancements in techniques to mitigate RT-induced toxicity, almost two-thirds of patients develop long-lasting endocrine and cognitive sequalae. Image-based data mining (IBDM) is a voxel-based analysis tool that can identify dose-sensitive regions, supporting development of tailored radiation treatments for future patients that avoids these regions. We present the first IBDM study localising endocrine and cognitive effects in paediatric brain tumour patients.

METHODS

Imaging (MRI and CT) and clinical data were available for 261 children (146 medulloblastoma patients in centre A, 115 patients with mixed diagnoses in centre B). Outcomes were reported as Growth Hormone Deficiency (GHD, presence/absence, both centres) and processing speed (PS, continuous slope derived from a linear mixed-effects model, centre A). IBDM evaluated where dose was associated with outcome (p-value<0.01). Mean dose to this region was included in multivariable analysis adjusting for age, risk status, hydrocephalus status/management, and chemotherapy.

RESULTS

GHD was associated with dose to a region overlapping the pituitary and brainstem. In centre A, multivariable analysis revealed a 13(2-27)% average increase in GHD odds per 1Gy increase in dose, with an inverse effect for age. Center B showed a 8(4-13)% average increase for every 1Gy, with no other predictors. For PS, a central frontal region from the medial frontal lobes to the hypothalamus was identified (139 patients in centre A). Every 1Gy increase led to a -0.08(-0.20 – 0.04) PS change, with age and hydrocephalus management as contributing factors.

CONCLUSION

We identified a region (encompassing the pituitary and brainstem) associated with increased risk of GHD, that was consistent in two independent cohort analyses. Furthermore, PS decline was linked to dose to a frontal region. Minimising dose to these regions for future patients could reduce the risk of cognitive and endocrine sequelae.
RADT-08. BASAL GANGLIA TOXICITY FOLLOWING PROTON THERAPY OF THE PINEAL REGION WITH BILATERAL ACTION-INDUCED MYOCLONUS
Authors: Soike Michael H , Warren Emily , Gonçalves Fabrício G , Cardenas Agustin , Littrell Mary E , Metrock Laura K , Alva Elizabeth , Thompson Marla , Gantz Emily , Rocque Brandon , Murdaugh Donna , Dhall Girish
Published: June 2024

INTRODUCTION

We sought to evaluate the toxicity profile for children receiving 54Gy to the pineal region with a significant dose delivered to posterior thalamus and basal ganglia.

METHODS

We performed a retrospective review of patients treated at a single institution with intensity modulated proton therapy (IMPT) receiving 54Gy to the pineal region. Multiple beam angles were utilized for planning. Patient characteristics and dosimetric data were correlated with late-toxicity and imaging.

RESULTS

From 2021-2023, six children were treated, and at a median follow-up of 13 months [9-26], all patients remain disease-free. Three patients had non-germinomatous germ cell tumors, 1 low-grade glioma, 1 atypical teratoid rhabdoid tumor (ATRT), and 1 embryonal tumor with multilayered rosettes. Age range was 2.4 to 16.8 years. All patients received chemotherapy prior to IMPT. Neuropsychological evaluation indicated range of intellectual functioning (mean = 98.3 [83-118]). One patient, a 4-year-old female with ATRT, developed T2 changes within the globus pallidus and thalamus on 3 month follow-up. At 5 months, she developed bilateral action-induced myoclonus with corresponding enhancing lesions in the globus pallidus bilaterally. Neuropsychological evaluation at 5 months post-treatment indicated memory impairments. She was treated with dexamethasone without improvement. Between 912 months post-treatment, tremors improved with physical therapy and imaging showed near complete resolution of enhancement within globus pallidus.

CONCLUSION

One of six children developed grade 3 toxicity manifesting as bilateral action-induced myoclonus with imaging changes in the globus pallidus bilaterally following IMPT and exhibited related neuropsychological deficits. While brainstem toxicity from IMPT is well documented, globus pallidus toxicity is not well characterized. Given the contiguous neuronal tracts with the brainstem, it is logical to apply similar treatment planning techniques, i.e. minimizing hotspots within the globus pallidus and thalamic “core” structures, and being cognizant of LET/RBE effects for treatment involving the pineal region in young children.
STEM-03. A NOVEL MOUSE MODEL OF CHOROID PLEXUS CARCINOMA UNRAVELS SEQUENTIAL DEDIFFERENTIATION OF HINDBRAIN CHOROID PLEXUS TISSUE AND REVEALS NEW THERAPEUTIC PROSPECTS
Authors: Peter Levke-Sophie , Altendorf Lea , Hack Karoline , Thaden Vanessa , Göbel Carolin , Krebs Christian F , Jauch-Speer Saskia-Larissa , Kordes Uwe R , Obrecht-Sturm Denise , Thomas Christian , Schüller Ulrich , Schoof Melanie
Published: June 2024

BACKGROUND

Choroid Plexus tumors constitute 10-20% of brain tumors in the first year of life. Among those, Choroid Plexus Carcinomas (CPC) pose a significant challenge due to their aggressiveness, resulting in poor survival rates and long-term adverse effects stemming from intense therapeutic approaches. Although loss of p53 and Sonic hedgehog signaling have been implicated in CPC development, a deeper biological understanding is needed to expand mechanistic insights and advance targeted therapies.

METHODS

We generated a novel mouse model with a simultaneous loss of TP53 and overexpression of MYCN and Gli2 in central nervous system precursors (hGFAP-cre::P53Fl/Fl::lsl-MYCN::lsl-Gli2). Resulting tumors were histologically characterized and compared to human CPC. Moreover, spatial transcriptomic data were generated for molecular characterization. Finally, mouse tumor-derived cell lines were employed for differentiation analysis and therapeutic testing.

RESULTS

Examinations at different developmental stages revealed brain tumors in the choroid plexus as well as smaller lesions in the subcallosal cortex with a penetrance of 80% within 18 days. We observed a gradual dedifferentiation of hindbrain CP tissue from day 5 onwards, indicating a continuous developmental sequence corresponding with expanding tumor growth. The mouse model recapitulates early tumor development, aggressive and metastatic growth along with histological features of human tumors. Spatial transcriptomic analysis highlighted chromosomal aberrations as well as other features known from human CPCs and emphasized the disturbance of ciliary pathways in tumor development. In vitro studies revealed rapidly growing tumor cells with stem cell-like differentiation potential and high sensitivity to targeted therapies.

CONCLUSION

Through in-depth analysis, including multiple data types, we show that our novel CPC mouse model closely resembles human tumors. Our tumors reveal a strict pattern of dedifferentiation implying similar mechanisms in humans. Additionally, primary mouse tumor cells in culture facilitate further in vitro analysis, and newly generated spatial transcriptomic data enables further insights into tumor biology.
Entinostat in patients with relapsed or refractory abdominal neuroendocrine tumors
Authors: Jamison Jacob K , Zhou Mengxi , Gelmann Edward P , Luk Lyndon , Bates Susan E , Califano Andrea , Fojo Tito
Published: June 2024

Background

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms with an increasing annual incidence and prevalence. Many are metastatic at presentation or recur following surgical resection and require systemic therapy, for which somatostatin analogs such as octreotide or lanreotide comprise typical first-line therapies. Nonetheless, treatment options remain limited. Epigenetic processes such as histone modifications have been implicated in malignant transformation and progression. In this study, we evaluated the anti-proliferative effects of a histone deacetylase (HDAC) inhibitor, entinostat, which was computationally predicted to show anti-cancer activity, as confirmed in in vitro and in vivo models of GEP-NETs.

Methods

This was a phase II study to evaluate the efficacy and safety of entinostat in patients with relapsed or refractory abdominal NETs. The primary objective was to estimate the objective response rate to entinostat. Additionally, with each patient as his/her own control we estimated the rates of tumor growth prior to enrollment on study and while receiving entinostat. Patients received 5 mg entinostat weekly until disease progression or intolerable toxicity. The dose could be changed to 10 mg biweekly for patients who did not experience grade ≥ 2 treatment-related adverse events (AEs) in cycle 1, but was primarily administered at the starting 5 mg weekly dose.

Results

The study enrolled only 5 patients due to early termination by the drug sponsor. The first patient that enrolled had advanced disease and died within days of enrollment before follow-up imaging due to a grade 5 AE unrelated to study treatment and was considered non-evaluable. Best RECIST response for the remaining 4 patients was stable disease (SD) with time on study of 154+, 243, 574, and 741 days. With each patient as his/her own control, rates of tumor growth on entinostat were markedly reduced with rates 17%, 20%, 33%, and 68% of the rates prior to enrollment on study. Toxicities possibly or definitely related to entinostat included grade 2/3 neutrophil count decrease [2/4 (50%)/ 2/4 (50%)], grade 3 hypophosphatemia [1/4, (25%)], grade 1/2 fatigue [1/4 (25%)/ 2/4 (50%)], and other self-limiting grade 1/2 AEs.

Conclusion

In the treatment of relapsed or refractory abdominal NETs, entinostat 5 mg weekly led to prolonged SD and reduced the rate of tumor growth by 32% to 83% with an acceptable safety profile (ClinicalTrials.gov Identifier: NCT03211988).
A diagnostic challenge of KIT p.V559D and BRAF p.G469A mutations in a paragastric mass
Authors: Habringer Stefan , Ihlow Jana , Kleo Karsten , Klostermann Anna , Schmidt Max , Chai Lidan , Knödler Maren , Leyvraz Serge , Sigler Christian , Sinn Bruno , Maschmeyer Georg , Jegodka Yvette , Benary Manuela , Ott Claus-Eric , Tinhofer Ingeborg , Schäfer Reinhold , Möbs Markus , Keller Ulrich , Keilholz Ulrich , Rieke Damian T
Published: June 2024

A patient with gastrointestinal stroma tumor (GIST) and KIT p.V559D and BRAF p.G469A alterations was referred to our institutional molecular tumor board (MTB) to discuss therapeutic implications. The patient had been diagnosed with B-cell chronic lymphocytic leukemia (CLL) years prior to the MTB presentation. GIST had been diagnosed 1 month earlier. After structured clinical annotation of the molecular alterations and interdisciplinary discussion, we considered BRAF/KIT co-mutation unlikely in a treatment-naïve GIST. Discordant variant allele frequencies furthermore suggested a second malignancy. NGS of a CLL sample revealed the identical class 2 BRAF alteration, thus supporting admixture of CLL cells in the paragastric mass, leading to the detection of 2 alterations. Following the MTB recommendation, the patient received imatinib and had a radiographic response. Structured annotation and interdisciplinary discussion in specialized tumor boards facilitate the clinical management of complex molecular findings. Coexisting malignancies and clonal hematopoiesis warrant consideration in case of complex and uncommon molecular findings.