bluuebunny/crossref_metadata_2025 huggingface dataset:
QOL-38. PSYCHOSOCIAL OUTCOMES OF CHILDREN WITH DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) AND HIGH-GRADE GLIOMA (HGG) –PROSPECTIVE, LONGITUDINAL PROMIS ASSESSMENTS OF PATIENTS ENROLLED ON CONNECT PHASE I CLINICAL TRIALS
Authors: Wright-Nadkarni Mariah L , Moscato Emily L , Stanek Joseph R , Schaefer Megan R , Gerhardt Cynthia A , Ashley David M , Baxter Patricia A , Chi Susan N , Dorris Kathleen , Fisher Michael J , Hummel Trent R , Hwang Eugene I , Gass David , Leary Sarah E S , Pillay-Smiley Natasha , Plant Ashley S , Murala Mythili , Mikael Leonie , Fouladi Maryam , Lazow Margot A
Published: June 2024

INTRODUCTION

Given poor prognoses, children with DIPG/HGG may experience psychosocial sequelae throughout their illness journey, negatively impacting quality of life (QOL). We prospectively assessed caregiver-proxy and patient-reported psychosocial outcomes of children with DIPG/HGG enrolled on two early-phase CONNECT trials.

METHODS

Patient-Reported Outcomes Measurement Information System (PROMIS) short forms were administered monthly to patients ≥8 years and caregivers of patients aged 5-17 years while enrolled on two phase I clinical trials for newly-diagnosed DIPG/HGG involving upfront radiotherapy (RT) and concurrent and/or adjuvant oral agents. T-scores (M=50, SD=10) were calculated relative to the general population for emotional distress (Anxiety and Depression) and relationship quality (Peer Relationships and Family Relationships). Linear mixed modeling compared scores at pre-RT, post-RT, 1 month pre-progression, and end of therapy (EOT). Spearman’s correlations were calculated.

RESULTS

Twenty-eight patients (median age=10 years; DIPG [n=23]; HGG [n=17]) and 40 caregivers participated. Patient and caregiver-proxy reports demonstrated comparable levels of emotional distress and relationship quality to norms and were stable over time. The proportion of patients endorsing mild or greater impairment in emotional distress (T-score >55) was relatively comparable at pre-RT (Anxiety & Depression=26%), post-RT (Anxiety=36%, Depression=23%), and 1 month pre-progression (Anxiety=23%, Depression=36%), with more patients endorsing impairment (Anxiety=58%, Depression=67%) at EOT, often corresponding to disease progression; though differences were not statistically significant. Caregiver-proxy and patient-reported scores were similar across all timepoints and domains, with a pattern of higher caregiver-reported versus patient-reported emotional distress (Spearman’s Rho range: 0.62-0.67;p<0.0001).

CONCLUSIONS

Children with DIPG/HGG and their caregivers reported comparable emotional functioning and relationship quality to the general population. Caregivers slightly overestimated psychological distress compared to youth self-reports. Findings may reflect resilience of this population when faced with adversity, while highlighting benefit of psychosocial supports and low therapy toxicity on QOL. Future analyses will compare psychosocial, physical, and functional symptoms.
QOL-41. FEASIBILITY OF PREOPERATIVE NEUROPSYCHOLOGICAL EVALUATION IN PEDIATRIC BRAIN TUMOR PATIENTS: IS IT POSSIBLE TO ASSESS BEFORE SURGERY?
Authors: Esteso-Orduña Borja , Vázquez-Gómez Felisa , Moreno-Carrasco José Luis , Pérez-Somarriba Marta , Castellano Serafín , Cartas-Carrión Susana , Cantarín Verónica , Cámara-Barrio Silvia , Galas Sebastián , Mingarro-Mezquita Roser Mingarro Mezquita , Alonso-García Isis , Castillo Concepción Fournier-Del , Lassaletta Álvaro
Published: June 2024

BACKGROUND

We aim to evaluate the feasibility of pre-surgical neuropsychological assessment in pediatric brain tumor patients and to examine the impact of various factors on cognitive changes during follow-up.

METHODS

Between 2021 and 2023, we analyzed the timing of pre-surgery neuropsychological evaluations, completion rates, referral sources, non-referral rates, as well as general cognitive ability, executive and socioemotional functioning in relation to clinical variables.

RESULTS

There were 11 preoperative evaluations (mean referral time=2.45 days) and 12 postoperative but pre-oncologic evaluations, reflecting the timing of referrals (M=13.92 days). Referrals came mainly from oncology (17 patients) and rehabilitation (6 patients) teams. Ten patients lacked preoperative or pretreatment neuropsychological referral, 7 discontinued follow-up, and 7 died. 10 patients showed full cooperation, 4 families didn’t complete questionnaires, 3 assessments were adapted due to clinical conditions, 1 patient did not cooperate and 7 were developmental assessments. Six patients’ IQ or Development Quotient (DQ) was below normal at preoperative assessment, despite a group mean of z=0.22. Only three patients had a developmental delay diagnosed at time of presurgery evaluation, 2 of whom had comorbid AED. The remaining patients had no previous diagnosis. At post-treatment evaluation, 15 patients experienced a significant decline in IQ/DQ (t=5.157; p=0.000) and worsened in executive functioning (t=-2.462; p=0.042), while 8 patients improved IQ/DQ scores (t=3.672; p=0.008) with no significant changes in executive (t=1.462; p=0.203) or socioemotional (t=-0.218; p=0.836) functioning.

CONCLUSIONS

Early neuropsychological assessment is paramount in pediatric patients with a brain tumor. However, it is not always feasible and presents significant challenges: requiring adaptation to the patient’s clinical status, coordination across departments, and managing the family’s emotional response to potential diagnoses. Incorporating preoperative neuropsychological assessment into care protocols is essential to analyze premorbid cognitive and behavioral functioning and to improve patient management and guide targeted interventions.
SURG-07. A PHASE I STUDY EXAMINING THE FEASIBILITY OF INTERMITTENT CONVECTION-ENHANCED DELIVERY (CED) OF MTX110 FOR THE TREATMENT OF CHILDREN WITH NEWLY DIAGNOSED DIFFUSE MIDLINE GLIOMAS
Authors: Szalontay Luca , CreveCoeur Travis , Neira Justin , Englander Zachary , Spinazzi Eleonora , Canoll Peter , Garvin James , Fino Jessica , Zamoryakhin Dmitry , Maddocks Alexis , Feldstein Neil , Bruce Jeffrey , Wu Cheng-Chia , Zacharoulis Stergios
Published: June 2024

BACKGROUND

Histone deacetylase inhibitors have been found preclinically to be among the most active agents against Diffuse Midline Gliomas (DMGs), however, they are clinically ineffective with systemic delivery due to low blood brain barrier penetration and systemic toxicity. Using an implantable subcutaneous pump connected with a catheter directly implanted into the pons we have conducted a phase I, 3 + 3 dose escalation study to investigate the safety and feasibility of repeated infusions of MTX110 (Biodexa Ltd), a water-soluble formulation of panobinostat, via CED.

METHODS

Eligible patents were between 3 and 18 years of age with newly diagnosed DMG following radiation therapy, without evidence of hemorrhage or cyst in the tumor, and having normal organ function. First, patients underwent tumor biopsy and device implantation, then received two 48-hour-infusion pulses 7 days apart. Three dose levels of MTX110 infusions (30, 60, 90 mcM) were studied. The infusion pump was prefilled with MTX110 (and gadolinium for co-infusion as a contrast agent), which was then administered using the wireless N’Vision clinical programmer at a rate of 0.2 mL/hr.

RESULTS

Nine patients were treated in the study (30 mcM group, n=3; 60 mcM group, n=4; 90 mcM group, n=2). All patients had an H3K27M mutated tumor. All but one patient had adequate tumor coverage with the infusate. One patient suffered a severe adverse event related to the infusion and tumor anatomy. Four patients had Grade 2 transient neurological deficits related to biopsy (n=1) or infusion (n=3). We observed one objective response. Median PFS was 10 months from diagnosis (range 8 to 20 months) while median OS was 16.5 months (range 12 to 35 months).

CONCLUSIONS

The study has demonstrated safety and feasibility of repeated infusions of MTX110 via CED in DMG patients with a favorable trend in overall survival warranting further trials with higher number of infusion pulses.
NURS-06. MUSIC THERAPY: AN INTEGRAL PART OF REHABILITATION FOR CEREBELLAR MUTISM SYNDROME
Authors: Matson Kathryn , Corr Gwendolyn
Published: June 2024

BACKGROUND

Cerebellar mutism syndrome (CMS) also known as posterior fossa syndrome (PFS), can occur in up to 25% of pediatric patients following surgical resection of posterior fossa brain tumors, particularly medulloblastoma. It is well recognized that intensive rehabilitation with physical therapy, occupational therapy and speech therapy are essential to recovery. Music therapy can be immensely helpful during rehabilitation to stimulate brain functions involved in movement, cognition, speech, emotions, and sensory perceptions. This case-based review aims at analyzing the available evidence to support our recommendation to include music therapy in the rehabilitation plan for all patients.

METHODS

We report on the case of a 4-year-old male with medulloblastoma and cerebellar mutism syndrome who began talking after just a few sessions with music therapy. We include an extensive review of the literature where multiple papers were found describing the positive effects of music therapy for management of neurologic diseases.

RESULTS

The pathophysiology of CMS is still poorly understood however, the most likely mechanism is injury along proximal components of the efferent cerebellar pathway. Intensive inpatient rehabilitation remains the standard of care. Music therapy uses and activates many different parts of the brain at the same time, promoting neuron repair and regeneration. Some of the advantages of music therapy are: it promotes plasticity in the brain and facilitates processing of sensory information and motor function; improves stress and helps patients adapt to stressful environments; facilitates more normative speech production for patients with dysarthria.

CONCLUSIONS

Despite efforts to identify preventative measures for CMS, it still occurs. Intensive rehabilitation remains the cornerstone of treatment. The case study as well as the review of the literature support our recommendation to include music therapy in the rehabilitation plan for patients with CMS. More studies are necessary to explore the therapeutic efficacy of music on patients with CMS.
NURS-07. A NEEDS ASSESSMENT OF THE BRAIN TUMOR EDUCATION AND THERAPY (BEAT) GROUP AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS
Authors: McHugh Michele , Meyer Ashley , Ogle Andrea , Beck Mary , Lampe Ashley , Brossier Nicole M , Cluster Andrew , Rocco Abbey , Shatara Margaret , Abdelbaki Mohamed
Published: June 2024

BACKGROUND

The Brain Tumor Education and Therapy (BEAT) group extends support to patients and families with pediatric brain tumor diagnoses. Social Work and healthcare providers typically meet with families quarterly to provide psychosocial support and address their educational needs. To better understand the factors that may impact participation and engagement, we sought to evaluate the opinions of current patients and their families.

METHODS

Both caregivers and adolescent patients, aged 16 years or older, were invited to participate in a 25-question survey. The survey assessed current sources of support, preferred meeting format, as well as educational and psychosocial needs. Additionally, the survey included questions about the patient’s diagnosis, treatment, and side effects experienced.

RESULTS

Over six weeks, 28 surveys were completed. Almost all respondents reported receiving support from family (93%) and friends (78%), while a smaller percentage (21%) sought support from families with similar diagnoses. Nearly half (46%) of respondents follow online or social media groups. When it comes to receiving support, 47% preferred online sessions (social media or virtual meetings), compared to in-person meetings (16%) or a combination of online and in-person (24%). Most respondents (85%) reported educational needs related to the late effects of therapy, while 69% cited concerns about friendships and socialization, and 57% on transitioning to young adulthood. Sixty-two percent request resources for emotional and psychosocial support. Respondents prefer (87%) healthcare professional-led sessions.

CONCLUSION

Our findings highlight an ongoing demand for healthcare professionals to provide psychosocial support and education to families of brain tumor patients. However, the preference is shifting towards virtual attendance of these meetings. In response, we intend to introduce a virtual support group and educational sessions, complemented by informative videos and handouts available on our hospital website or social media platforms. Subsequent studies will focus on family satisfaction with changes to the program.
NURS-08. CLINICAL MANAGEMENT OF PATIENTS RECEIVING CAR T CELL THERAPY FOR CNS TUMORS: FIVE YEAR UPDATE
Authors: Holtzclaw, ARNP Susan , Hoeppner, ARNP Cory
Published: June 2024

BACKGROUND

Chimeric antigen receptor (CAR) T cells are an innovative new therapy with proven efficacy in some pediatric cancers such as leukemia and lymphoma, but there has been less experience in solid tumors, especially tumors of the central nervous system (CNS). Seattle Children’s Hospital (SCH) has opened a total of four phase 1 CAR T cell studies for recurrent/refractory CNS tumors and DIPG. These include BrainChild-01; targeting HER2, BrainChild-02; targeting EGFR, BrainChild-03; targeting B7-H3, and BrainChild-04; targeting B7H3, EGFR, HER2, and IL13-zetakine (QUAD). As of February 2024, 105 patients have been treated at SCH with CAR T cells infused on a weekly to bi-weekly schedule through indwelling catheters into the tumor resection cavity or ventricular system. APPs provide much of the day-to-day care of these patients and have learned best management practices for these patients.

METHOD

Given the scrutiny of clinical care needed for Phase 1 studies, we are now able to report detailed clinical information around management of patients receiving CNS immunotherapy that we have learned during the treatment of these patients over the past five years.

RESULTS

Clinical care includes the judicious use of steroids, clinical support of each patient’s symptoms, and management of Ommaya catheters and reservoirs. Additionally, providing psychosocial support is essential for families who travel long distances to receive this therapy compounded by the many emotional components of being enrolled on any Phase 1 trial.

CONCLUSION

Case studies will be provided and discussed to provide the most up-to-date management of patients receiving CNS Immunotherapy. With now over 550 CAR T cell infusions completed, our discussion will provide recommendations for management of side effects from CAR T cell therapy and discuss clinical standard around accessing Ommaya catheters and shunt reservoirs for immunotherapy infusions.
NURS-14. DEVELOPMENT OF A CLINICAL PRACTICE INTERVENTION TO SUPPORT NURSES CARING FOR PATIENTS WITH DIABETES INSIPIDUS (DI) DURING CHEMOTHERAPY HYDRATION
Authors: Schmus Cynthia , DiDomenico Concetta , McWhorter Jessica
Published: June 2024

BACKGROUND

Pediatric neuro-oncology patients with germ cell tumors (GCT) and diabetes insipidus (DI) often require management with vasopressin (DDAVP). Fluid and sodium balance, ordinarily managed successfully with DDAVP, can be disrupted during chemotherapy and associated hydration. Patients with an intact thirst mechanism may be able to self-regulate fluid and salt balance under the right conditions, whereas patients without an intact thirst may experience sodium fluctuations if intravenous hydration exceeds the amount they drink independently. Patients may be unable to maintain adequate hydration and sodium levels due to nausea and/or sedating antiemetics. These factors create a unique clinical challenge for nurses. Nurses sought guidance in understanding DI and its impact on hydration during chemotherapy.

METHODS

Two nursing education sessions were held and focused on DI management. Nurses were surveyed pre and post education. The goals of the intervention were that the oncology nurse will be to describe the pathophysiology of diabetes insipidus, the role of desmopressin, the ability to differentiate between management of patients with and without an intact thirst mechanism, and the special care of a DI patient receiving chemotherapy.

RESULTS

Nurses reported an increased awareness post education of the need to closely assess patients and manage their DI in collaboration with clinicians. Routine chemotherapy management does not apply to this population, because drastic fluctuations in sodium and water balance put them at risk of other complications. Nurses identified the need to closely manage hydration, DDAVP, recording strict intake/output, monitoring sodium levels, assessing for nausea/vomiting and the degree of sedation from antiemetics.

CONCLUSION

Outcomes from this educational intervention were that nurses had an increased understanding of DI management in patients with GCT receiving chemotherapy. Future goals would be to implement a standard approach to hydration, DDAVP administration, and monitoring sodium levels in patients with GCT and DI.
OTHR-05. ROLES OF GEMCITABINE-OXALIPLATIN (GEMOX) ADD-ON THERAPY IN INFANT-TYPE BRAIN TUMORS: A SINGLE CENTER EXPERIENCE
Authors: Castelli Barbara , Fonte Carla , Guidi MIlena , Nicola Marco Di , Giunti Laura , Buccoliero Anna Maria , Caporalini Chiara , Giordano Flavio , Scagnet Mirko , Tintori Veronica , D’Incerti Ludovico , Genitori Lorenzo , Tellini Marco , Sardi Iacopo
Published: June 2024

BACKGROUND

Combined gemcitabine and oxaliplatin (GemOx) was evaluated in recurrent pediatric solid tumors, showing safety but limited activity. In neuro-oncological infant patients, chemotherapy intensified to high doses (HDC) represents the cornerstone, avoiding radiotherapy toxicities. We describe the roles of GemOx towards autologous transplantation in infant-type brain tumors.

METHODS

From May 2017 to January 2024, at the Meyer Children’s Hospital IRCCS in Florence, six children (median age 19 months, sex equally distributed, three high-grade gliomas, a metastatic medulloblastoma MM, a pineoblastoma, a choroid plexus carcinoma CPC) completed GemOx after induction chemotherapy delivered according to Italian program for malignant brain tumors under 3 years. GemOx was administered to achieve clinical and neuroradiological permissiveness to HDC and to raise the possibility of second look neurosurgery.

RESULTS

Gemcitabine 1000 mg/m2 and Oxaliplatin 100 mg/m2 were given every 14-28 days for 1-6 cycles. At re-assessment, maximum every four cycles, disease control was optimal (five stable diseases and one partial response according to RECIST criteria). After GemOx, one patient was also subjected to further neurosurgery. The treatment was overall well tolerated, except for Common Terminology Criteria for Adverse Events (CTCAE) grade 4 platelet toxicity in two patients (one of whom also developed hydrocephalus CTCAE 3 and hyponatremia CTCAE 4 during treatment). All patients were safely exposed to HDC (1-2 courses). MM and CPC patients progressed respectively 4 ad 19 months after the end of GemOx. The latter underwent second look neurosurgery, and a radiotherapy course was delivered to both, considering the achievement of permissive age. To date all patients are alive.

CONCLUSIONS

In brain infant-type malignant tumors strategies are limited due to the extremely vulnerable age. GemOx treatment should be considered a reasonable and safe option waiting for intensified treatment, especially in radiotherapy delaying programs, and it should result incisive in the therapeutic or palliative choice.
OTHR-09. HEALTHCARE PROVIDERS’ PERSPECTIVES ON MALAYSIA-SINGAPORE VIRTUAL PEDIATRIC NEURO-ONCOLOGY TUMOR BOARD MEETING
Authors: Rajagopal Revathi , Foo Jen Chun , Teo Jillian Chui Lin , Sawal Rafikah , Jawin Vida , Alcasabas Ana Patricia , Ho Thi Kim Nguyen , Loh C-Khai , Bansal Shweta , Teh Kok Hoi , Low Sharon , Ganesan Dharmendra , Chang Kenneth , Soh Shui Yen , Abdelbaki Mohamed S , Bouffet Eric , Gottardo Nicholas G , Tan Enrica
Published: June 2024

BACKGROUND

Virtual pediatric neuro-oncology tumor board meetings have been reported to be highly beneficial in improving the delivery of high-quality care for childhood central nervous system (CNS) tumors. However, such meetings are lacking in the Asia Pacific region. Hence, we initiated the first pediatric neuro-oncology online platform in the Asia Pacific region in January 2019, and we aimed to describe the participants’ perception of the virtual tumor board meetings.

METHODS

We retrospectively reviewed all cases from January 2019 to December 2023 and conducted a web-based survey to all participants in December 2023. Centers that presented more than five cases were invited to assess the impact of virtual meetings.

RESULTS

Fifty-four meetings have been conducted over five years. A total of 160 cases were presented by 20 institutions from six Asian countries, which include Malaysia, Singapore, Philippines, Vietnam, India, and Taiwan. Thirty participants responded to the survey. Majority of them attended the meetings to enhance their knowledge in pediatric neuro-oncology (96.7%), to learn evidence-based management (83.3%), and to build connections with regional colleagues and international experts (53.3%). Almost all concluded that tumor board meetings improved treatment decisions, addressed challenges of complex CNS tumor cases, and promoted continuity of care with appropriate post-surgical chemotherapy administration and surveillance investigations after completion of treatment. The main reason for case discussion was diagnostic difficulties followed by multimodal treatment advice (85.7%). More than 25% of management changes were observed in pathological diagnosis and treatment approaches. All the hospitals reported that the online case discussions improved pediatric neuro-oncology service delivery capacity and increased local team competence.

CONCLUSION

Virtual pediatric neuro-oncology tumor board meetings facilitated improvement in pathological diagnosis and multimodal treatment approach. The establishment of virtual CNS tumor board meetings is an effective way to seek international expert advice and promote pediatric neuro-oncology education in our region.
OTHR-11. TITLE: ELECTROGRAPHIC SEIZURES AND EEG BACKGROUND FEATURES IN PEDIATRIC NEURO-ONCOLOGY PATIENTS ADMITTED TO THE PEDIATRIC INTENSIVE CARE UNIT
Authors: Pickup Elizabeth E S , Keenan Julia S , Packer Roger J , Wells Elizabeth M , Conley Caroline , Staso Katelyn , Harrar Dana B , Sansevere Arnold J
Published: June 2024

BACKGROUND

Electrographic seizures (ES) are common in critically ill children with the incidence of ES ranging from 10-50%. Continuous EEG (cEEG) is frequently obtained in children with brain tumors due to encephalopathy or concern for seizures. Despite this, little is known about the incidence of ES, EEG background features, or the impact of EEG on clinical management in this population.

METHODS

This is a prospective single center study of critically ill children with brain tumors admitted to the pediatric intensive care unit (PICU) from July 2021 to July 2023. Patients with new or known primary brain tumors and cEEG completed during their admission were included. We excluded patients with planned admissions for EEG. Clinical variables included age, sex, oncologic diagnosis, tumor grade and location, indication for EEG, EEG features, and changes in management.

RESULTS

Thirty-six patients were identified who met the inclusion criteria. 21 patients were female. The median age was 11.0 years (IQR 6.6– 15.4 years). The most common indication for EEG was encephalopathy in 42% followed by clinical seizure in 31%. ES were captured in 19% (7/36) with the majority being subclinical; in patients with acute encephalopathy, ES were captured in 20% (3/15). The EEG background was abnormal in 97% of cases. The most common EEG background was slow disorganized with background asymmetry seen in in 74%. EEG background features met criteria for the ictal-interictal continuum in 14%. A higher rate of ES was seen in patients with disseminated tumors (p=0.03) and severe encephalopathy on EEG (p=0.006). EEG led to a change in management in 31% of patients.

CONCLUSIONS

ES are common in critically ill children with brain tumors and would go undetected without cEEG. EEG findings often led to a change in clinical management and is a vital tool for the evaluation of this population.
PALC-03. MEDICAL AID IN DYING: EXPERIENCE IN THE CENTER FOR CANCER AND BLOOD DISORDERS AT CHILDREN’S HOSPITAL COLORADO
Authors: Winzent-Oonk Shelby , Vallejos Chelsea , Hemenway Molly , Lindsay Holly B , Green Adam L
Published: June 2024

BACKGROUND

Medical Aid in Dying (MAiD) is now legal in 10 US states and Washington, DC, allowing terminally ill patients to self-administer medications to peacefully end their life. There is little published on pediatric hospitals’ approach to young adult patients requesting MAiD.

METHODS

We review the two patients who have participated in MAiD at the Center for Cancer and Blood Disorders at Children’s Hospital Colorado (CHCO). We also explore publicly available Colorado MAiD statistics.

RESULTS

Between 2017 and 2022, there have been 1,090 prescriptions written for MAiD medication in Colorado, 5 of which were for patients aged 18-34 (0.5%). Two of these patients were treated at CHCO. Patient A was a 26 year old male with a CNS non-germinomatous germ cell tumor whose treatment was complicated by mucormycosis and severe engraftment syndrome. He relapsed 23 months after completing therapy. He had neurologic decline including ataxia and blindness, at which time he requested MAiD. Patient B was a 24 year old male with multiply recurrent IDH-mutant medullary high grade glioma. With metastatic progression, he had many tumor-related symptoms including dysphagia, dysarthria, and weakness impacting his activities of daily living, so he requested MAiD. Both patients had multidisciplinary care conferences with neuro-oncology, social work, ethics, psychology, and palliative care. After completing psychological evaluation and all steps required by law, they were prescribed DDAMP2 (digoxin 50 mg, diazepam 1 gram, morphine 15 grams, and propranolol 2 grams). Both patients took the medications and died peacefully. Barriers encountered included infrequency of MAiD requests leading to unclear policies and processes.

CONCLUSIONS

Young adults represent a small but important subset of those seeking MAiD prescriptions. Despite challenges, patients were able to receive MAiD without delay in a compassionate manner. Our experience may be applicable to other pediatric hospitals facing these requests.
PATH-14. A CLINICAL CONUNDRUM - INFANTILE POSTERIOR FOSSA EPENDYMOMA WITH YAP1:MAML FUSION?
Authors: Govender Dinisha , Goetti Robert , Kim Young-Jun , Graf Nicole
Published: June 2024

BACKGROUND

Ependymomas of infancy (0-18months) have been reported to comprise distinct clinical, pathological and genetic entities. Young age is typically associated with posterior fossa group A (PF-A) tumours and therefore a poor prognosis. Treatment of these infants is challenging with limited therapeutic options that have significant long-term sequelae.

METHOD

We report a single case of a 4-month old baby girl who presented with obstructive hydrocephalus and a presumed posterior fossa mass.

RESULTS

Imaging demonstrated a large fairly well-defined solid lesion with multiple T1 high and corresponding T2 intermediate signal intensity foci scattered throughout the lesion and marked mass effect on the cerebellum and fourth ventricle. The lesion was inseparable from the pineal gland, habenula and tectum and only mild diffusion restriction. Whilst initially considered to be a posterior fossa tumour, the presence of a claw sign with the tectal plate, favoured a tectal origin. Histological appearances, together with immunohistochemistry findings (GFAP positive and EMA patchy perinuclear dot expression) were consistent with classic ependymoma. Grading was difficult as mitotic activity was relatively low, although focal areas of high ki67 proliferation index were noted suggesting at least focal grade 3 areas. Retained expression of tumour cells for H3K27me3 on immunohistochemistry suggested the likely posterior fossa group B (PF-B) ependymoma. Local SNP chromosome microarray found no acquired clonal abnormality; with no detection of gain chromosome 1q; loss/LOH 6q; Loss/LOH 9p21.3 [CDKN2A, CDKN2B], chromothripsis 11q [ZFTA::RELA], Loss/LOH 17p13 [TP53] or Loss/LOH 22q [NF2]. Additional NGS sequencing identified a YAP1::MAML2 fusion (confirmed with targeted RT-PCR followed by subsequent Sanger sequencing).

CONCLUSION

This case highlights the challenges with overlapping clinical, pathological and radiological features in an infant with ependymoma, necessitating a molecular diagnosis. After 21months, the patient remains in complete remission following surgery alone.
LMIC-03. BRAINSTEM RADIATION NECROSIS IN A PATIENT WITH RECURRENT MEDULLOBLASTOMA. SUCCESFULL TREATMENT OF A HIGHLY FEARED COMPLICATION
Authors: Leal-Cavazos Carlos A , Arenas-Ruiz Jose A , Piñeiro-Retif Rafael , Vidal-Gutierrez Oscar
Published: June 2024

BACKGROUND

Medulloblastoma is the most common malignant brain tumor in pediatric population. Standard treatment combines surgery, risk-adapted craniospinal irradiation and chemotherapy. Given the well-known cognitive sequelae in young children associated to radiation, strategies in infants try to avoid upfront radiation. A significant number of patients treated during infancy will ultimately relapse. Re-irradition in relapse setting has proven to be effective in disease control (survival depending on several factors) although there is a concern in exceeding radiation tolerance and risk of toxicity.

METHODS

Herein, we describe the case of male patient that presented at 1 year of age with a non-metastatic anaplastic medulloblastoma that was completely resected. He received 3 cycles of adjuvant chemotherapy (as per Head Start II), local relapse was detected in tumor bed during evaluation and was completely resected, afterwards he received myeloablative chemotherapy with stem cell rescue and posterior fossa radiation therapy (54 Gy). At 8 months off therapy patient developed spinal relapse in imaging with negative cytology, then treated with spinal irradiation 36Gy without adjuvant chemotherapy. He remained disease free during 12 months, then tumor recur at the right cerebellopontine angle, surgery was complete and there was no evidence of distant disease. Patient received adjuvant local radiation with 30.6Gy followed by chemotherapy (bi weekly bevacizumab + irinotecan). Cumulative maximal dose to brainstem was 84Gy. 2 months after radiation patient presented with extreme sleepiness and imaging findings compatible with brainstem radiation necrosis, symptoms resolved promptly after scheduled bevacizumab. Patient is currently 6-year-old and remains free of disease after 3 years off therapy.

CONCLUSION

Medulloblastoma treatment in infants is challenging because survival is not the only goal. Future clinical trials will help to better tailored treatment based on molecular biology. Re-irradiation in medulloblastoma has been described as well tolerated but clinician should be aware of its complications and management.
LMIC-05. THE ROLE OF CENTRALIZATION IN PEDIATRIC NEURO-ONCOLOGY: EVIDENCE FROM A DEVELOPING COUNTRY
Authors: Hoveyan Julieta , Asatryan Eduard , Hovhannisyan Saten , Papyan Ruzanna , Lazaryan Armine , Mkhitharyan Armen , Matinyan Narek , Arzumanyan Niko , Minasyan Mariam , Melnichenko Irina , Minasyan Elya , Salman Zeena , Qaddoumi Ibrahim , Iskanyan Samvel , Hakobyan Lusine , Sargsyan Lilit , Danielyan Samvel , Tamamyan Gevorg , Bardakhchyan Samvel , Bailey Simon , Amayiri Nisreen
Published: June 2024

BACKGROUND

Several studies from developed countries showed that centralization of pediatric cancer care is associated with survival benefits. The role of centralization might be crucial in pediatric neuro-oncology where multidisciplinary approach is essential. The aim of this study is to evaluate the impact of centralization in neuro-oncology in a developing country.

METHODS

In 2019, the consolidation of three pre-existing pediatric oncology units in Armenia resulted in the centralization of pediatric cancer care. After 2019 all patients undergo chemotherapy and follow up at the Pediatric Cancer and Blood Disorders Center of Armenia. This analysis compares demographic data, tumor characteristics and management of 54 patients diagnosed before centralization (2009-2018) and 66 patients diagnosed after centralization (2019-2023).

RESULTS

After centralization the incidence of recorded newly diagnosed CNS tumors in Armenia has dramatically increased (2.4 times). Six cases of CNS tumors diagnosed before 2019 were first registered after centralization. Assessment for metastatic status in embryonal tumors after centralization improved (20% vs 93.75%, p=0.0001). In addition, increased molecular testing was achieved (5.56% vs 31.8%, p=0.001). The number of patients getting access to multidisciplinary care and discussions via teleconference increased dramatically (5.56% versus 86.4%, p=0.0001). A trend toward a shorter median time from first symptoms to diagnosis was found (1.75-month vs 1-month, p=0.85). In addition, significant changes in the underlying pathology were recorded. Before and after centralization embryonal tumors, low-grade gliomas and high-grade gliomas accounted 37% vs 24.25%, 22.2% vs 31.8% and 11.1% vs 15.15% of CNS tumors, respectively. The availability of follow-up information marginally increased after centralization (83.3% vs 87.8%, p=0.48).

CONCLUSIONS

CNS tumors especially low-grade gliomas were frequently not registered before centralization. The current study proves that centralization helps to improve CNS tumors registration, diagnosis, and evaluation as well as facilitating multidisciplinary care. Further research is needed for evaluating the survival benefits of centralization.
LMIC-26. DEVELOPMENT OF THE ST. JUDE GLOBAL VIRTUAL PEDIATRIC NEURO-ONCOLOGY FELLOWSHIP (VPNOF): INCREASING PEDIATRIC NEURO-ONCOLOGY CAPACITY IN LOW- AND MIDDLE- INCOME COUNTRIES (LMIC)
Authors: Salman Zeena , Moreira Daniel , Resendiz Alma Benito , Hoveyan Julieta , Rahmartani Ludi , Ain Rahat Ul , Zhang Anan , Amayiri Nisreen , Bailey Simon , Bouffet Eric , Chan Godfrey Chi-Fung , Liu Anthony P Y , La Madrid Andres Morales , Mushtaq Naureen , Tsui Karen , Bhat Vasudeva , Cirt Ramona , Ngcana Thandeka , Salazar Mauricio Sanchez , Somathilaka Mahendra , Yang Peiyi , Chinnaswamy Girish , Dhall Girish , Gupta Tejpal , Jalali Rakesh , Lassaletta Alvaro , Osorio Diana S , Shatara Margaret , Upadhyaya Santhosh , Uppuluri Ramya , Rodriguez-Galindo Carlos , Qaddoumi Ibrahim
Published: June 2024

BACKGROUND

Most children with central nervous system (CNS) tumors reside in LMICs, yet their complex management is limited by the availability of trained pediatric neuro-oncologists (PNO). The St. Jude Global VPNOF was designed to train pediatric oncologists (PO) in LMICs as CNS tumor experts while remaining in their home countries.

METHODS

The VPNOF structure was initially developed through semi-structured interviews of physicians who had served as global mentors or mentees in pediatric oncology. Employing a modified Delphi method, we identified the key components necessary to virtually train POs in LMICs to become PNOs.

RESULTS

A two-year fellowship program was designed with a curriculum tailored for POs in LMICs. Two main components were identified as critical to the objective of building PNO capacity: mentorship and clinical training. Mentorship involves a triad with one global and one loco-regional mentor per fellow, aiding in the fellow’s career and institutional goal setting to advance PNO care. Clinical training includes regularly scheduled virtual tumor boards and didactics, and ad-hoc case discussions with mentors while managing patients at their home institution. Additionally, fellows travel to their mentors’ institution twice for a four-week clinical rotation. In 2022, five fellows from Armenia, China, Indonesia, Mexico, and Pakistan were selected. In 2023, an additional six fellows were selected from China, Costa Rica, India, Romania, South Africa, and Sri Lanka. To date, 18 months of the two-year fellowship have resulted in the establishment of multi-disciplinary approaches, increased patient volume, increased evidence-based practices, and publication by the first cohort of 21 abstracts and two journal publications to date.

CONCLUSIONS

The VPNOF is an innovative approach to leveraging global mentorship to train PO in resource-limited settings to become PNOs. Virtual mentorship and training have led to implementation of new practices aimed at improving quality of care for children with CNS tumors in LMICs.
MODL-01. IN VITRO MODELING OF AND AUTOMATED DRUG SCREENING IN EMBRYONAL BRAIN TUMORS USING TUMOR-BRAIN ORGANOIDS
Authors: Riedel Nicole C , Walter Carolin , Aust Paula , de Faria Flavia , Altendorf Lea , Göbel Carolin , Verma Archana , Roy Rajanya , Thomas Christian , Schüller Ulrich , Bruder Jan M , Kerl Kornelius
Published: June 2024

BACKGROUND

Embryonal brain tumors (EBTs) such as medulloblastoma, atypical teratoid rhabdoid tumor (AT/RT), and embryonal tumor with multilayered rosettes (ETMR) uniquely arise in the developing brain. Traditional 2D models often fall short in capturing the tumoral microenvironment (TME) and intratumoral heterogeneity, which may limit their translational potential.

METHODS

To address this, we co-aggregated EBT cells from AT/RT (Chla02 and SHH310) and ETMR (BT183 and murine GEMM cells) with forebrain organoids derived from human induced pluripotent stem cells and developed an automated, screening-ready in vitro model (EBT-FBO). We used immunohistochemistry, whole-mount immunostaining, and single-cell RNA sequencing to characterize our model and compared it with a developmental forebrain atlas. We further used our model for cell type-specific drug screening and validated the results in vivo.

RESULTS

Our EBT-FBO model mimicked the differentiation states of a mid-gestational fetal forebrain, providing a natural immature neuronal environment for supratentorial EBT cells. This environment allowed the EBT cells from both AT/RT and ETMR to mimic in vivo tumor cell states and avoided the cycling cell selection common in other models. We screened over 160 drugs in ETMR-FBO and identified antracyclines and Triptolide as having anti-tumor, yet non-neurotoxic effects. Our in-depth transcriptomic analysis identified new therapeutic targets, including PDGFR-signaling for ETMR. Building on this insight, we disrupted tumor-TME interactions and observed significant anti-tumor effects both in vitro and in vivo.

CONCLUSIONS

EBT-FBO provide embryonal brain tumors like ETMR or AT/RT with their intrinsic, immature neuronal microenvironment essential for recapitulating natural tumor heterogeneity. This marks a significant advancement towards targeted therapy and patient-specific models in precision medicine.
MODL-03. THERAPEUTIC EFFICACY OF IMIPIRIDONES IN LYNCH SYNDROME-ASSOCIATED GLIOMAS
Authors: Chong Wai Chin , Putnam Ethan , Subramaniam Bavani , Woldegerima Ayda , Mizoguchi Sean , Cerna Steve , Yadavilli Sridevi , Bornhorst Miriam , Packer Roger , Nazarian Javad
Published: June 2024

INTRODUCTION

Lynch Syndrome, a hereditary cancer syndrome linked to DNA mismatch repair gene mutations (MMRD), predisposes individuals to various cancers, including high grade gliomas (Lynch-HGG). Effective treatments for Lynch-HGGs are scarce, and suitable pre-clinical models are needed to identify novel therapeutic combinations.

METHODS

In this study, we generated patient-derived cell line models of Lynch-HGGs (n=3), characterized them through Western blot analysis for MMRD gene markers, and conducted genome and transcriptomic analyses. Murine models were then generated via intracranial injection of cultured cells expressing mCherry-luciferase reporter genes. Drug screening based on transcriptomic analysis was performed to identify potential therapeutic agents.

RESULTS

Our findings showed loss of MMRD protein consistent with the primary mutation, and a constant loss of P53, a tumor suppressor protein. One cell line, 7316-3058, exhibited an absence of NF1 expression, another critical tumor suppressor protein. Transcriptomic analysis unveiled upregulation in cell cycle processes and SUMOylation of DNA damage response and repair proteins. In vitro treatment with imipiridone compounds (ONC201 and ONC206) demonstrated varying degrees of drug response, with 7316-3058 displaying high sensitivity to the targeted inhibitor. Unfortunately, this therapeutic efficacy did not translate to the in vivo murine model, suggesting underlying mechanisms that impede drug efficiency.

CONCLUSION

In summary, we developed effective pre-clinical models of Lynch-HGG that can be used to screen different drug combinations targeted to treat these tumors. Furthermore, despite promising in-vitro data, we demonstrated the limited efficacy of imipiridones in treating Lynch-HGG in vivo, emphasizing the challenges in translating in vitro findings to in vivo contexts. This study contributes valuable insights to the development of effective therapeutic strategies for Lynch Syndrome-associated gliomas.
RADT-10. LITHIUM TREATMENT PROTECTS MICROGLIA AND NEWLY GENERATED NEURONAL POPULATIONS IN A MOUSE MODEL OF CRANIAL RADIOTHERAPY
Authors: Rodrigues Carlos F D , Preka Efthalia , Lastra-Romero Alejandro , Zisiadis Georgios Alkis , Ruchiy Yana , Fragkopoulou Adamantia , Blomgren Klas
Published: June 2024

BACKGROUND

Radiotherapy remains a cornerstone of the treatment of high-grade brain tumors. However, while lifesaving, it results in long-term complications in 50-96 % of the treated individuals, where cognitive deficits are particularly debilitating. Currently, no treatments or preventive strategies are available to avert these deficits. Lithium (Li), long used to treat bipolar affective disorder, has been shown to reduce radiation-induced cognitive deficits in rodent models by preventing apoptosis of the neuronal stem and progenitor cells in the hippocampus and stimulating their proliferation. This work aimed to further elucidate the mechanisms behind the protective and pro-regenerative actions of Li in the irradiated young brain.

METHODS

Postnatal day (PD) 21, C57BL6/J mice were injected intraperitoneally with Li chloride (4 mmol/kg) and kept on a Li carbonate-containing diet for 4 weeks. Control animals were injected with saline and administered an equivalent control diet. On PD 25, the animals were administered a single-dose whole-brain radiation of 8 Gy and were subsequently sacrificed at different time points, spanning from 2 weeks to 1 year. At sacrifice, the hippocampi were harvested for single-cell RNA sequencing using a novel, 2-step protocol to harvest viable cells of all types, including neurons.

RESULTS

The results showed that radiation triggered the expression of senescence-related genes in the hippocampal microglia (e.g., Cdkn1a, Ccl12), which Li has prevented through the activation of the Bcl2 family of genes. Moreover, they corroborate the protective effect of Li on newly generated hippocampal neurons, which undergo remodeling over time, leading to the emergence of new subpopulations.

CONCLUSIONS

This work represents another advancement towards understanding the action of Li in the irradiated brain and confirms its potential to become the first pharmacological treatment for radiation-induced complications.
Long-term Outcomes of Adjunctive Lung Resection for Nontuberculous Mycobacteria Pulmonary Disease
Authors: Kang Noeul , Jhun Byung Woo
Published: June 2024

Background

Adjunctive lung resection is recommended for select patients with nontuberculous mycobacteria (NTM) pulmonary disease (PD). However, data are limited on long-term recurrence rates in patients infected with major pathogens, including Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MABC).

Methods

In this prospective observational study, we retrospectively analyzed data from 125 patients with MAC-PD (n = 90) or MABC-PD (n = 35) who underwent adjunctive lung resection. We evaluated microbiological response, postoperative complications, recurrence, and all-cause mortality over a median 80-month follow-up.

Results

Persistent culture positivity (64%) was the most common indication for surgery, followed by hemoptysis, recurrent pneumonia, or radiologic deterioration. Postoperative complications occurred in 18 (14%) patients, with no surgery-related deaths. Treatment outcomes did not significantly differ between the MAC- and MABC-PD groups. Cure with culture conversion was achieved in 112 (90%) patients. Recurrence occurred in 37 (33%) of 112 patients, of which 18 (49%) cases were attributed to reinfection by different NTM species or subspecies. The MAC group had higher recurrence rates than the MABC group (Kaplan-Meier curve, log-rank test, P = .043) and was significantly associated with recurrence in the multivariable analysis (adjusted hazard ratio, 2.71; 95% CI, 1.23–5.99). However, mortality was higher in the MABC-PD group than the MAC-PD group (7/35 vs 4/90, P = .006).

Conclusions

Adjunctive lung resection with antibiotics helps to reduce bacterial burden and manage symptoms in patients with NTM-PD. However, it does not prevent recurrence, which is mostly caused by reinfection.
Incidence of checkpoint inhibitor-associated inflammatory arthritis, immunomodulation and mortality in cancer patients on immunotherapy: a retrospective cohort study
Authors: Bass Anne R , Xie Fenglong , Jannat-Khah Deanna , Ghosh Nilasha , Chan Karmela K , Saxena Ashish , Curtis Jeffrey R
Published: June 2024

Objectives

Immune checkpoint inhibitor (ICI)-associated inflammatory arthritis (ICI-IA) occurs in 4–6% of ICI-treated patients based on one observational study. We identified cases of ICI-IA using administrative claims to study its incidence and characteristics at the population level.

Methods

We used the Medicare 5% sample to identify patients initiating ICIs. Cancer patients were identified by having ≥2 ICD-9/10-CM diagnosis codes from an oncologist for lung cancer, melanoma or renal/urothelial cancer. ICI-IA was defined as having two Medicare claims ≥30 days apart with combinations of ICD-9/10-CM diagnosis codes that favoured specificity. ICI-IA was identified in patients with a musculoskeletal diagnosis after ICI initiation, who had (i) no inflammatory arthritis or inflammatory rheumatic disease before ICI initiation ever, and (ii) no musculoskeletal complaint in the one year prior to ICI. We examined DMARD utilization and visits to rheumatology in patients with ICI-IA. Landmark analysis and a time varying Cox proportional hazards model for overall survival were constructed.

Results

The incidence of ICI-IA was 7.2 (6.1–8.4) per 100 patient years. Patients with ICI-IA had a mean (s.d.) age of 73.5 (7.0) years, 48% were women and 91% were white. Median (IQR) time from ICI initiation to first ICI-IA diagnosis was 124 (56, 252) days. Only 24 (16%) received care from a rheumatologist, and 24 (16%) were prescribed a DMARD (46% by a rheumatologist). The HR for mortality in patients with ICI-IA was 0.86 (95% CI 0.59–1.26, P = 0.45).

Conclusions

The incidence of ICI-IA identified in claims data is similar to that reported in observational studies; however, few patients are treated with a DMARD or are referred to rheumatologist. There was no difference in overall survival between ICI-treated patients with and without ICI-IA.