tbuckley/cabot-search huggingface dataset:
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: Alexandra M Giantini Larsen, Rashi Rangaraj, Colleen Sanders, Andrew Garton, Y Pierre Gobin, Jared Knopman, Apostolos John Tsiouris, David Pisapia, Mark Souweidane
Journal: Neuro-Oncology (2024)

Abstract 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-03. NEED FOR PROGRAMS FOCUSING ON CAREGIVERS FOR YOUNG ADULT SURVIVORS OF CHILDHOOD BRAIN TUMORS
Authors: Janet A Deatrick, Melanie Joseph, Emily Herchline, Shannon Hammer, Ashley Anil, Nithya Ramaswamy, Wendy Hobbie, Jane E Minturn, Lamia P Barakat
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The physical, emotional, social, developmental, and economic risk experienced by survivors of childhood brain tumors and their families is well documented, as is the acceleration of those risks as survivors transition into young adulthood. Further, the impact of the lack of services in the community is compounded by insufficient investigation of interventions to support survivor functioning and their caregiver’s management of their medical and psychosocial needs.The purpose of this study was to describe maternal caregivers’ perspectives about key components of potential interventions to support maternal caregivers of young adult survivors of childhood brain tumors. METHODS Data were obtained from 21 at-risk maternal caregivers (based on the Family Management Style Measure) of young adult survivors aged 18-29 years old who were not partnered, were presently living at home, and who participated in a pilot randomized trial Training in Problem Solving (TIPS) for Caregiver of Young Adult Survivors of Childhood Brain Tumors. Caregivers were interviewed using a semi-structured qualitative interview guide constructed using the Consolidated Framework for Implementation Science. Codes, categories, then themes were identified by means of directed content analysis. RESULTS All caregivers agreed these services were absent and the most effective timing would be at the transition to survivorship with ongoing follow-up. Key components of potential interventions identified by maternal caregivers were skill-building, motivational interviewing to increase readiness to change long-standing patterns of family management, use of validation of their efforts as parents and caregivers to build confidence in trying new approaches and shifting their perspectives on ongoing caregiving for a childhood brain tumor survivor to find hope in even small changes. CONCLUSIONS Caregivers endorsed the importance of targeted psychosocial support throughout survivorship for caregivers within the context of their family, facilitating their roles as both parents and caregivers to young adult childhood brain tumor survivors.
NURS-08. CLINICAL MANAGEMENT OF PATIENTS RECEIVING CAR T CELL THERAPY FOR CNS TUMORS: FIVE YEAR UPDATE
Authors: Susan Holtzclaw, ARNP, Cory Hoeppner, ARNP
Journal: Neuro-Oncology (2024)

Abstract 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-07. A NEEDS ASSESSMENT OF THE BRAIN TUMOR EDUCATION AND THERAPY (BEAT) GROUP AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS
Authors: Michele McHugh, Ashley Meyer, Andrea Ogle, Mary Beck, Ashley Lampe, Nicole M Brossier, Andrew Cluster, Abbey Rocco, Margaret Shatara, Mohamed Abdelbaki
Journal: Neuro-Oncology (2024)

Abstract 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.
MDB-92. EFFECT OF REDUCED-DOSE CRANIOSPINAL IRRADIATION AND REDUCED-DOSE ADJUVANT CHEMOTHERAPY ON CHILDREN AND ADOLESCENTS WITH WNT MEDULLOBLASTOMA WITHOUT RESIDUAL OR METASTATIC DISEASE: RESULTS FROM THE SJMB12 CLINICAL TRIAL
Authors: Giles W Robinson, Thomas E Merchant, Brent A Orr, Johnnie K Bass, Heather M Conklin, Asim Bag, Sandeep K Dhanda, Soniya Pinto, Angela Delaney, Margit Mikkelsen, Wilburn Reddick, Jie Huang, Jason Ashford, Angela Edwards, Leigh Ann Christy, Eroica Soans, Molly Clarke, Doug Strother, Michael J Fisher, Anne Bendel, Eugene I Hwang, Sibo Zhao, Amy Smith, Nicholas G Gottardo, Timothy E G Hassall, Jennifer Elster, Sebastien Perreault, Vijay Ramaswamy, Sonia Partap, Stephen Laughton, Richard Cohn, Murali Chintagumpala, Geoffrey McCowage, Michael Sullivan, Elias Sayour, Daniel Bowers, Asher Marks, John Lucas, Christopher Tinkle, Noah D Sabin, Paul Klimo, David W Ellison, Paul A Northcott, Arzu Onar-Thomas, Amar Gajjar
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND In response to studies showing medulloblastoma (MB) survival is not only contingent on clinical factors (e.g. metastases, residual disease) but also on molecular factors (e.g. molecular group, gene aberrations), we launched the SJMB12 (NCT01878617) trial to stratify treatment using both clinical and molecular risk factors. Specifically, we sought to evaluate if patients with WNT-group MB, without metastatic (M0) or residual disease (R0), treated with reduced-dose craniospinal irradiation (CSI) and reduced-dose cyclophosphamide-based chemotherapy could maintain a high survival with fewer treatment-related side effects. METHODS Tumors were molecularly stratified via immunohistochemistry and fluorescence in-situ hybridization. Patients with WNT tumors were grouped into 3 strata: W1 (M0, R0, classic histology, monosomy of chromosome 6); W2 (M0, R0, without monosomy 6 or classic histology); W3 [metastatic (M+), residual disease (R+), or MYC/MYCN amplification]. Treatment of W1 consisted of 15-Gy CSI/51-Gy primary site (0.5cm CTV margin) followed by 4 cycles of chemotherapy resulting in cumulative doses of 8 mg/m2 vincristine, 300 mg/m2 cisplatin, 12 gm/m2 cyclophosphamide. Serial audiology, neurocognitive, and endocrine evaluations were conducted over a six-year follow-up period. RESULTS From 2013-2022, 72 patients enrolled onto the W1 stratum: median age was 10.3 years (4.9-22.0); 62.5% female; median time of follow-up was 4.5 years (1.1-10.1). 5-year progression-free survival (PFS) and overall survival were 90.4 ± 5.1% and 98.6 ± 2.1%, respectively. Five patients had PFS events: 4 relapses and 1 accidental death. Relapsed disease was local in 2, distant in 1, and mixed in 1. Time to relapse was &amp;gt; 2 years from enrollment for 3 patients. Severe ototoxicity (SIOP grade ≥ 3) at the end of therapy occurred in 14.4 ± 4.5%. Neurocognitive, endocrine, and detailed molecular data are forthcoming. CONCLUSIONS Patients with low-risk WNT-MB maintained a high PFS (&amp;gt;90%) when treated with reduced-dose CSI and reduced-dose cyclophosphamide-based chemotherapy. Preliminary data suggests fewer treatment-related side effects.
NURS-05. CATALYZING AND INFORMING THE DEVELOPMENT OF MORE COMPREHENSIVE AND ACCESSIBLE PROGRAMS FOR CAREGIVERS OF YOUNG ADULT SURVIVORS OF CHILDHOOD BRAIN TUMORS
Authors: Nithya Ramaswamy, Emily Herchline, Melanie Joseph, Shanon Hammer, Ashley E Anil, Wendy Hobbie, Jane E Minturn, Lamia P Barakat, Janet A Deatrick
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The chronic and intensive care needs of young adult survivors of childhood brain tumors are most often addressed by their maternal caregivers with limited, specific psychosocial or other programs to reduce caregiving demands and enhance their family management. Using a social ecological perspective, the purpose of this study was to catalyze and inform the development of more comprehensive and accessible programs for caregivers of young adult survivors of childhood brain tumors. METHODS Semi-structured interviews were conducted with 21 maternal caregivers, 6 post baccalaureate students/professional coaches for a problem-solving intervention for maternal caregivers, and 16 neuro-oncology clinical experts using interview guides tailored to their roles and constructed based on the Consolidated Framework for Implementation Science. Qualitative. Interview data were analyzed using content analysis. RESULTS Barriers included: need for internet connected devices (microsystem level); lack of care matched to their identified needs (mesosystem); poor tracking of long-term survivors and lack of survivorship psychosocial services (macrosystem); and lack of supportive health care policies and funding mechanisms for individuals and organizations (exosystem). Facilitators included: web-based platform accessible to the individuals and population (microsystem); widespread acknowledgement regarding gaps in survivorship psychosocial care (mesosystem); partnerships with survivors of childhood brain tumors, caregivers, and organizations that treat them (macrosystem); and dissemination among childhood brain tumor treatment/survivorship programs, healthcare systems, and community organization and endorsement from them (exosystem). CONCLUSIONS Multilevel approaches that address barriers and facilitators for improving health equity for maternal caregivers of young adult survivors of childhood brain tumors incorporate the design and dissemination of accessible, web-based programs designed in partnership with survivors, caregivers, and organizations to build care matched to need, as well as organizational, political, and community advocacy.
MDB-91. MEDULLOBLASTOMA – MOLECULAR CHARACTERISTICS AND RADIOLOGICAL ASPECTS OF A BRAZILIAN COHORT FROM A SINGLE CENTER
Authors: Flávia Delgado Martins, Benicio Oton de Lima, Bruna Arrais, Emanoelle Cristina da Silva, Marcio Ferreira Marcelino, Pedro Henrique Pinto, Diogenes Diego Carvalho de Bispo
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Four molecular subgroups of medulloblastoma are distinguished by their genomic, epidemiological, and prognostic characteristics: Wingless (WNT), Sonic hedgehog (SHH), Group 3 and Group 4. Genotypic classification permits individualized therapeutic planning based on risk stratification, thereby improving patient outcome. This study aims to characterize the epidemiological and molecular data of a cohort treated at a single Brazilian center, as well as to correlate the heterogeneous aspects of magnetic resonance imaging (MRI) with the molecular characteristics of this tumor. METHODS The study analyzed 47 medulloblastoma cases, treated at the children’s oncology reference institution of a middle-income country between 2011 and 2021. The medical records, radiological findings and the histological and molecular classification are reviewed. The images were evaluated by an experienced neuroradiologist, blinded to clinical and molecular information. RESULTS Thirty-two out 47 patients met the eligibility criteria and were analyzed. The frequency of molecular groups found was 6.25% Non-SHH/ Non-WNT, 12.50% WNT, 34.38% SHH, 3% Group 3 and 44 % Group 4. The analysis revealed tumor location, presence of hemorrhage/calcification, limits and enhancement patterns are significant for molecular group prediction. SHH shows a significant prevalence in the cerebellar hemisphere, lower presence of hemorrhage/calcification and an ill-defined tumor margins when compared with other subgroups. Group 4 showed significantly less enhancement. CONCLUSIONS In accordance with the frequency observed in studies on childhood medulloblastoma, our series found a significant prevalence of Group 4 and a lack of representativeness of Group 3. Despite the limitations, it was possible to identify radiological tumor characteristics that may predict the molecular subgroup and contribute to a more effective therapeutic approach, thereby reducing the incidence of post-surgical complications.
MDB-45. THE PTBP2 SPLICING FACTOR IS ESSENTIAL IN GROUP 3/4 MEDULLOBLASTOMA
Authors: Veronika Caisova, Samuel Rivero-Hinojosa, Samuele Tardito, Huizhen Zhang, I-An Lu, Navya Chintala, Aaron Mochizuki, Yanxin Pei, Najiba Murad, Chaim Sneiderman, Gary Kohanbash, Jianhua Yang, Brian Rood
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Medulloblastoma (MB) is a common malignant pediatric brain tumor with significant heterogeneity among its four molecular subgroups: WNT, SHH, groups 3 and 4. There is a significant rate of disease recurrence with group 3/4 MB indicating a need for novel therapeutic targets. Since transcriptomic profiling of MB has not identified novel targets, we focused on a proteomic approach. We selected 157 proteins significantly over-expressed in Group 3/4 MB and performed a targeted loss-of-function CRISPR-Cas9 screen in four MB cell lines. We identified 17 essential genes shared by at least 2 of the cell lines. The PTBP2 splicing factor was essential for all cell lines. PTBP2 is an RNA-binding protein involved in splicing regulation that plays an important role during neuronal maturation. We hypothesize that persistent expression of PTBP2 results in a differentiation arrest and preservation of proliferative potential. METHODS We stably knocked-out PTBP2 expression in D556 and MB002 MB cells. We performed bulk RNA-seq and quantitative proteomics of these KO clones along with CLIP-seq to map PTBP2 targeted transcripts. We also performed phenotype assays, qPCR array and single-cell RNA-seq in KO clones to validate proliferation and neuronal differentiation. RESULTS RNA-seq in PTBP2 KO MB cells revealed 2,213 differentially expressed genes predominantly involved in neuronal differentiation. These genes were cross-referenced with quantitative proteomic and eCLIP data. Using RNAseq from clinical samples, splice inclusion analysis based upon PTBP2 bound transcripts neatly segregated Group 3/4 MB from SHH and WNT. PTBP2 KO cells exhibited reduced proliferation and, upon stimulation, increased differentiated morphology compared to controls. This latter observation was further supported by qPCR array and single-cell RNA-seq. CONCLUSIONS The results suggests that the loss of PTBP2 expression stimulates MB differentiation with a subsequent reduction of proliferation activity and nominates PTBP2 and its downstream effectors as potential therapeutic targets in group 3/4 MB.
NURS-04. MUSIC THERAPY WITH CAREGIVERS FOR THOSE WITH PEDIATRIC BRAIN CANCER AND BRAIN TUMORS: A CRITICAL REVIEW OF THE LITERATURE AND RECOMMENDATIONS FOR FUTURE PROGRAMS
Authors: Deborah R Rizzo
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Caregivers for those with pediatric brain cancer and brain tumors face significant challenges. During the course of treatment, pediatric brain cancer and brain tumor patients face not just the physical consequences of treatments, but the neurological effects as well. METHODS This critical review of the literature examines the effects of Music Therapy on Caregivers, Caregivers for cancer patients, and Caregivers for pediatric cancer patients. A literature review was specifically chosen with the intention of making recommendations for future program planning. Subjects explored include the psychological, physical, and financial impacts of caregiving. Additional concepts include personality traits of Caregivers and multicultural considerations in caregiving. The topics of brain cancer and the use of Music Therapy with patients are also explored. Special attention is given to Music Therapy for Caregivers for those with pediatric brain cancer and brain tumors. Main points under this headline also include Caregiver stressors, similarities and differences in multicultural caregiving, and the limited research available to Caregivers. RESULTS At the time the literature review, no research had been conducted in the area of Music Therapy and Caregivers for pediatric brain cancer and primary brain tumors. Music Therapy was proven, however, to be a significant non-pharmaceutical intervention for several areas, including anxiety and pain management. CONCLUSION The conclusion drawn was that more research is needed with Music Therapy and this particular population. Additionally, a basic framework for a Music Therapy program for Caregivers for those with pediatric brain cancer and brain tumors has been provided with recommendations on the expansion of the program.