tbuckley/cabot-search huggingface dataset:
QOL-11. LATE MORBIDITY AND MORTALITY IN SURVIVORS OF CHILDHOOD EPENDYMOMA: A REPORT FROM THE CHILDHOOD CANCER SURVIVOR STUDY (CCSS)
Authors: Katharine R Lange, Peter deBlank, Mengqi Xing, Sedigheh Mirzaei, Deo Kumar Srivastava, Kevin Oeffinger, Joseph Neglia, Kevin Krull, Paul Nathan, Rebecca Howell, Kirsten K Ness, Lucie Turcotte, Wendy Leisenring, Gregory T Armstrong, Tara Brinkman, Daniel C Bowers, M Fatih Okcu
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Between the 1970s and 1990s, therapy for childhood ependymoma evolved to include chemotherapy and focal rather than whole-brain radiation. The impact of these changes on health outcomes is unknown. METHODS 404 five-year survivors of ependymoma (52.5% male, median 6 [range 0-20] years old at diagnosis, 22 [5-49] years from diagnosis) were evaluated for cumulative incidence of late mortality, subsequent neoplasms, and chronic health conditions (CHC). Outcomes were analyzed by diagnosis decade and brain radiation and chemotherapy exposures. Fine-Gray’s test compared cumulative incidence curves. Relative Risks (RRs) with 95% CIs estimated outcomes using multivariable piecewise exponential models. RESULTS Throughout the three decades whole brain radiation exposure decreased (32.7% to 2.3%) while focal brain radiation increased (16.4% to 59.2%), and chemotherapy use increased (23.6% to 47.9%). Fifteen-year all-cause late mortality (incidence, 95% CI) estimates were similar across treatment eras: 1970s (9.3%, 3.4-18.8%), 1980s (14.7%, 9.4-21.2%), 1990s (10.3%, 6.7-14.9%), (p=0.9). Mortality was higher with whole brain radiation (22.5%, 11.2-36.5%) compared to focal radiation (11.4%, 7.5-16.1%) or no brain radiation (3.5%, 0.9-9.1%), (p &amp;lt;0.001). Mortality was also higher with chemotherapy (14.4%, 9.6-20.0%) compared to no chemotherapy (6.8%, 3.8-11.0%) (p=0.004). Differences in mortality were due to recurrence/progression of the primary cancer and health-related causes. Compared to no brain radiation, there were increased risks (RR, 95% CI) of any grade 3-4 CHCs for focal (2.6, 1.3-5.4) and whole brain radiation (3.5, 1.5-8.1) and &amp;gt;1 Grade 3-4 CHCs for whole brain radiation (6.5, 1.3-31.6). There were no differences in CHCs or subsequent neoplasms by chemotherapy exposure. CONCLUSIONS Despite the treatment changes over the 1970s to 1990s, late morbidity and mortality in pediatric ependymoma remained unchanged. Whole and focal brain radiation were associated with increased risk of grade 3-4 CHCs compared to no radiation. Future therapies for childhood ependymoma should target reductions in late morbidity and mortality.
LMIC-21. SERIES OF 9 CASES OF SPINAL CORD COMPRESSION IN CHILDREN: A SINGLE EXPERIENCE FROM THE PEDIATRIC NEURO-ONCOLOGY GROUP, IN A MIDDLE INCOME COUNTRIES
Authors: Karina Amélia Morikawa, Mariana Massue Komatsu, Felipe Hada Sanders, Leandro Tavares Lucato, Helena Baraldi, Yuri Reis Casal, Juliana Silveira Barreto, Lilian Cristófani, Vicente Odone Filho, Eduardo Weltman, Alessandra Prandini de Azambuja
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Spinal cord compression secondary to pediatric neoplasms is a rare but serious event that can result in irreversible neurological sequelae, with paralysis, sensory losses and sphincter dysfunction. This retrospective study aims to describe the main causes, treatments and outcomes of a series of cases of spinal cord compression in patients admitted to the Childhood Cancer Treatment Institute- ITACI, University of São Paulo, Brazil. METHODS Based on data collected from the pediatric neuro oncology group, we analyzed nine cases of spinal cord compression in patients under 18 years, admitted from 2020 to 2023. RESULTS In our case series, 7 of the 9 children were female, with an average age of 104 months, the youngest being 3 months. Of the cases described, 77.7% had extradural spinal cord compression. Ewing’s sarcoma was the main neoplasm associated with extradural compression, representing 44.4%. Neuroblastoma, giant cell tumor and B acute lymphoblastic leukemia accounted for 11.1% of cases each. Cases of intradural compression were represented by low-grade glioma with cervical compression and germ cell tumor from with thoracolumbar lesion. Spinal cord compression was the first manifestation of malignancy in 8 of the 9 patients, who presented loss of motricity and sensitivity. All patients were treated with corticosteroid, therapy due to its benefits in reducing vasogenic edema caused by spinal cord compression. Additionally, 8 patients underwent surgical spinal decompression. A patient with Ewing sarcoma received cytoreductive chemotherapy and achieved complete motor recovery. CONCLUSIONS Spinal cord compression is associated with serious neurological sequelae when not treated appropriately. However, neurological recovery is possible with early diagnosis and adequate decompression treatment. We increased the importance of specialized services with a pediatric neuro-oncology group, in which several professionals work together to provide individualized care, even in developing countries, as demonstrated by the patients treated at our institution.
LGG-04. TRAMETINIB COMBINED WITH CHEMOTHERAPY FOR INFANT BRAF-FUSED CHIASMATIC GLIOMA
Authors: Helen Toledano, Orli Michaeli, Walid Kaadan, Shlomi Caduri, Rivka Friedland, Gad Dotan, Osnat Konen
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Infant chiasmatic gliomas present a major therapeutic challenge due to large size, threat to vision and progressive nature. Infants &amp;lt;1 year respond poorly to Vincristine/Carboplatinum chemotherapy (SIOP-LGG2). BRAF fusion is common, so MEK inhibitors have been used second line in older children, but time to response is slow (median ~20 months). Data on the use of these drugs in infants is limited as is data on the safety and efficacy of combining chemotherapy with MEK inhibitors. METHODS We report two infants treated successfully for BRAF fused chiasmatic glioma - both presented age 5 months with nystagmus and diencephalic syndrome. Both had significant tumor progression within 6 weeks of starting Vincristine/ Carboplatin which responded rapidly to the addition of Trametinib. RESULTS Case 1 required tumor debulking at week 6 of chemotherapy due to progressive hyponatremia, hydrocephalus and brainstem compression. Surgery caused diabetes insipidus, hemianopia and hemiparesis. Tumor growth continued despite reinstating chemotherapy. Addition of trametinib caused tumor shrinkage by 75% within 12 weeks and 90% by 1 year. Minirin doses were reduced by 80% on Trametinib. After 1.3 years, chemotherapy was stopped &amp; Trametinib continued alone. Case 2 - tumor growth and severe hyponatremia by week 6 of chemotherapy prompted addition of Trametinib without surgery. There was tumor reduction of 50% over 6 months and improvement of severe failure to thrive. Hyponatremia, requiring sodium and urea supplementation, stabilized. Bilateral vision and age-appropriate development are maintained. Hypertension developed early, but resolved completely after stopping and then gradually reintroducing Trametinib. Recurrent diarrhea required dose reduction. CONCLUSIONS We show the safety and efficacy of combined treatment with chemotherapy and MEK inhibition in infants and postulate that both the combination and the young age at initiation of therapy may have contributed to the excellent outcome. We urge for clinical trials of combination therapy in this age group.
MDB-65. RESULTS FROM THE SJ-ELIOT PHASE 1 CLINICAL TRIAL EVALUATING PREXASERTIB (LY2606368) IN COMBINATION WITH CYCLOPHOSPHAMIDE OR GEMCITABINE FOR CHILDREN AND ADOLESCENTS WITH REFRACTORY OR RECURRENT MEDULLOBLASTOMA
Authors: Nicholas G Gottardo, Raelene Endersby, Catherine Billups, Brent Orr, Jordan R Hansford, Tim Hassall, David S Zielgler, Clinton Stewart, Arzu Onar-Thomas, Molly Clarke, Martine F Roussel, Amar Gajjar, Giles W Robinson
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND SJ-ELIOT (NCT04023669) was a phase 1 trial that explored the combination of the checkpoint kinase inhibitor, prexasertib with the DNA-damaging agents, cyclophosphamide and gemcitabine, in recurrent or refractory medulloblastoma. METHODS Participants ≥ 1 year and &amp;lt; 25 years were stratified to one of two treatment strata: stratum A prexasertib and cyclophosphamide and stratum B prexasertib and gemcitabine. Patients with Group 3/4 medulloblastoma were assigned to either stratum A or B, whereas patients with SHH medulloblastoma were assigned to stratum A. A Rolling-6 design was used. RESULTS Fifteen patients were enrolled on stratum A and six patients on stratum B. The study was closed early due to drug supply issues. In stratum A, three patients were escalated to dose level (DL) 3 and none had dose limiting toxicity (DLT). For stratum B, of the first three patients enrolled on DL1, two had DLTs (grade 3 hypotension) related to drug reactions. Consequently, stratum B was amended to add hydrocortisone prophylaxis. A further three patients were enrolled. One patient had a grade 3 DLT (ALT increase). The remaining two patients electively stopped therapy within the first two courses. One patient on stratum A, with SHH TP53 mutant, MYCN amplified medulloblastoma, achieved a complete sustained response, received 12 cycles, and electively stopped treatment after 408 days. They progressed nine months later. The remaining 14 patients on stratum A progressed. There were no objective responses on stratum B. Median PFS were 1.9 and 2.1 months for stratum A and B respectively. CONCLUSIONS The MTD/RP2D was not established for either arm. In stratum A, DL3 was tolerated, whereas DL1 for Stratum B was not tolerated. Despite robust preclinical data, no efficacy signal was observed. Intriguingly, one patient with a highly aggressive tumor (SHH TP53 mutant, MYCN amplified) appeared to derive a sustained benefit from the combination of prexasertib and cyclophosphamide.
QOL-19. THE SIBLING TOOLKIT: DEVELOPMENT OF A PSYCHOLOGICALLY-INFORMED TOOLKIT TO SUPPORT SIBLINGS OF CHILDHOOD CNS TUMOUR PATIENTS WITH LIMITED ACCESS TO FORMAL SERVICES
Authors: Sarah J Verity, Claire Adey, Tracy Dyson, Kate Fifield, Natalie Holman, Philippa Lewington, Kirsty Marshall, Meghan Owens, Amandeep Samrai, Jeni Tregay, Kimberley Davies, Phil Martinez, Deborah Mitchell
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND There is a recognised gap in service provision addressing the psychological and social needs of siblings of children with a diagnosis of brain tumour. In the absence of funding to provide direct psychological service provision for siblings, a project development group was established to identify and advance alternative methods of delivering support. METHODS Funding for a two year sibling-needs project was sourced from UK child brain tumour charity Tom’s Trust and led by the Neuro-Oncology psychology service at the Great North Children’s Hospital (Newcastle, UK). A development group was established of clinical psychologists and neuropsychologists representing nine UK hospital Trusts and one former school teacher. Following a comprehensive priorities exercise a toolkit was developed to support siblings of children with brain tumours. Significant further stakeholder involvement, including input from the regional Young People’s Advisory Group, resulted in positive revision to the initial draft. RESULTS A 39 page toolkit was produced for the use of any adult involved in the sibling’s life. This psychologically-informed toolkit provides guidance and support for a caring but potentially uninformed adult, such as a teacher, community leader, or member of the wider family, to be able to offer support to siblings. Guidance is included to help the adult talk about cancer, know what common issues siblings face, and to think about how to safely and appropriately undertake supportive work with this age group. The kit is associated with a website link, allowing toolkit users to download worksheets and resources for use with the sibling. CONCLUSIONS Early feedback on the published toolkit is highly positive, suggesting that the toolkit is considered ‘comprehensive’, ‘accessible’, and ‘practical’. We believe that this toolkit offers the potential to bridge some of the gap in service provision to siblings of a child with brain tumour.
QOL-17. LIFE AFTER PAEDIATRIC LOW-GRADE GLIOMA: THE SURVIVOR NARRATIVE. QUALITATIVE INTERVIEWS OF ADULT PLGG SURVIVORS
Authors: Katie L Green, Deirdre Leyden, Darren Hargrave, Myra Bluebond-Langner
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Most patients with PLGG will survive, but long-lasting functional &amp; Quality of Life (QOL) impairments can occur. No PLGG survivorship research has yet included individual survivor narratives. The true impact of the tumour &amp; its treatment on lived experiences from the survivor perspective remains to be explored. AIMS To evaluate PLGG survivor narratives across a heterogeneous group of adult survivors atleast 5 years from PLGG treatment. METHODS An interview guide was created comprising topics around survivors’ past and present experiences and hopes for the future. Open-ended semi-structured interviews were completed with adult survivors diagnosed with PLGG at Great Ormond Street Hospital, UK, 1980-2005. Video interviews were completed on zoom with the same interviewer, and recordings dictated verbatim to transcripts for Framework Analysis(FA). The codebook for analysis was created according to prior literature &amp; themes emerging within and across the transcripts. RESULTS 10 of 26 (38%) eligible survivors (median age 21.5yrs) completed interviews 28-73 minutes long. Median duration 12 years from diagnosis (9-18yrs). FA comprised 18 codes categorised into 4 major themes: The Self, The Social World, Experiences Of A PLGG, &amp; Survivorship. Interviews allowed novel identification that seizures universally contributed long-lasting trauma and mental health disturbance. They also demonstrated that personality, adaptation to a new normal, and both the social &amp; practical support received significantly influenced the impact of objective functional deficits on perceived QOL.All 10 survivors directly reported considering themselves to continue to be functionally affected by their PLGG as an adult. CONCLUSIONS We provide novel first-hand accounts of adult PLGG survivors, representing an important first-attempt at incorporating the survivor narrative and lived experiences as a core component of the evaluation of PLGG survivor outcomes. The narrative accounts allowed us to gain a more in-depth understanding of life for PLGG survivors; and allowed identification of new themes and topics not identified by PedsQl or similar quantitative QOL instruments.
LGG-05. REPORT ON PEDIATRIC BRAIN TUMOR CONSORTIUM (PBTC)-029B, A PROSPECTIVE PHASE 2 CLINICAL TRIAL OF SELUMETINIB IN TREATING YOUNG PATIENTS WITH RECURRENT/PROGRESSIVE LOW-GRADE GLIOMA: NEW RESULTS ON STRATA 2, 5, AND 6 WITH UPDATED LONG-TERM SURVIVAL OUTCOMES ON STRATA 1, 3, AND 4
Authors: Jason Fangusaro, Arzu Onar-Thomas, Tina Young Poussaint, Shelly Lensing, Azra H Ligon, Neal Lindeman, Anuradha Banerjee, Lindsay Kilburn, Alicia Lenzen, Natasha Pillay-Smiley, Ian F Pollack, Nathan Robison, Sonia Partap, Ibrahim Qaddoumi, Daniel Landi, David T W Jones, Clinton F Stewart, Maryam Fouladi, Ira J Dunkel
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND PBTC-029B was a phase 2 trial evaluating efficacy of selumetinib (up to 26 courses) in children with recurrent/progressive low-grade glioma. We report new results on strata 2, 5, and 6 as well as update long-term survival outcomes on strata 1, 3, and 4. METHODS Stratum 2 enrolled children with pilocytic astrocytoma (PA) whose tumor screened negative for the BRAF-KIAA1549 fusion and the BRAFV600E mutation. Stratum 5 enrolled children with non-PA whose tumor screened positive for one of these two BRAF aberrations. Stratum 6 enrolled children who consented to tissue screening, but there was an assay failure. Responses were based on T2/FLAIR. RESULTS Stratum 2: among 14 patients, there was 1 partial response (PR), 7 stable disease (SD) and 6 progressive disease (PD) with overall response rate (ORR) of 7.1%. Two-year progression-free survival (PFS)/overall survival (OS) were 57.1/100%, respectively. Stratum 5: among 23 patients, there was 1 complete response, 4 PR, 12 SD and 6 PD with ORR of 21.7%. Two-year PFS/OS were 74.8%/100%, respectively. Stratum 6: among 26 patients, there were 7 PR, 14 SD and 5 PD with ORR of 26.9%. Two-year PFS/OS were 72.0%/100%, respectively. Long-term outcomes have now been evaluated in strata 1, 3, and 4. Stratum 1 enrolled patients with PA whose tumor screened positive for one of the two BRAF aberrations; stratum 3 enrolled patients with neurofibromatosis type-1 (NF1) associated pLGG; and stratum 4 enrolled non-NF1 optic pathway/hypothalamic tumors. Among strata 1, 3, and 4, the current median follow-up for patients without events are 60.4, 60.4, and 58.1 months, respectively. Five-year PFS/OS are 30.8%/88.9%, 54.2%/100%, and 51.0%/100%, respectively. CONCLUSIONS These data demonstrate that selumetinib provides tumor stability and responses among diverse pLGG tumors as well as show that many patients will achieve long-term disease control even several years after stopping treatment.
QOL-20. A REVIEW OF THE LITERATURE ON THE REHABILITATION OF PATIENTS WITH POSTERIOR FOSSA SYNDROME
Authors: Jared Levin, Nathan Rosenberg, Elaine Tsao
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Posterior fossa syndrome (also recently described as pediatric postoperative cerebellar mutism syndrome) is a well described phenomenon, in which a patient develops a spectrum of speech and motor/coordination deficits generally in the acute stage after posterior fossa tumor resection. While most patients recover well, some patients evidence significant deficits years after diagnosis, and there is some evidence that minor long-term deficits may remain. While its frequency of occurrence is relatively low, and efforts have been made to identify strategies to decrease the rate of Posterior Fossa Syndrome, the fundamental interventions for functional optimization and rehabilitation of patients are still being discussed and researched. METHODS Along with reviewing the most up-to-date literature on the rehabilitation management of patients with posterior fossa syndrome, we will discuss current a survey based study designed by a group of representatives from the American Academy of Physical Medicine and Rehabilitation (AAPM&amp;R) Pediatric Cancer Rehabilitation subcommittee, to better understand the standards of how the syndrome is managed by physiatrists in the US. This survey distributed via email, posting on an AAPM&amp;R online community, as well as social media sites. RESULTS While literature is limited, there is evidence for the practice of therapy services, bracing, and in admission for acute inpatient rehabilitation to guide treatment for patients with posterior fossa syndrome. Results from the above survey study will be discussed, which preliminarily shows a consistent reliance on therapy services and a broader heterogeneity to frequency and treatment preferences among physicians in the US. CONCLUSION Posterior Fossa Syndrome can be a challenging and debilitating disorder for pediatric brain tumor patients. Further research into treatment options and outcomes is necessary to guide future management.
QOL-18. THE MODERATING ROLE OF SOCIAL VULNERABILITY IN THE RELATIONSHIP OF MATERNAL CAREGIVER CONDITION MANAGEMENT ABILITY AND TRANSITION READINESS OF THEIR YOUNG ADULT SURVIVORS OF PEDIATRIC BRAIN TUMORS
Authors: Ashley Anil, Shannon N Hammer, Wendy L Hobbie, Brian P Daly, Janet A Deatrick, Lamia P Barakat
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The transition into adulthood is a particularly vulnerable time for young adult survivors of pediatric brain tumors (YAS) due to tumor/treatment-related late effects. Reduced supportive resource access and social determinants of health (SDH) can exacerbate challenges, impacting caregiver condition management ability (CMA) and YAS transition readiness. This study’s aim was to evaluate the relationship between YAS cognitive late effects, caregiver CMA, and YAS transition readiness, and the moderating role of SDH for YAS and caregivers with condition-focused family management. METHODS Fifty-three maternal caregivers (93% white, 98% non-Hispanic) of YAS (Mage=22) reporting low CMA completed the Transition Readiness Assessment Questionnaire (TRAQ; 5 subdomains) and rated YAS cognitive late effect severity. Medical experts scored 1) cognitive medical sequelae (0-6 scale), and 2) the Pediatric Neuro-Oncology Rating of Treatment Intensity. Social Vulnerability Index (SVI) measured cumulative SDH using 16 factors across US Census residential zip code data. Pearson correlations and moderated mediation analyses in Process Macro were used. RESULTS Caregiver ratings were associated with overall transition readiness (r=-.38, p=.005), cognitive medical sequelae (r=.53, p&amp;lt;.001), and treatment intensity (r=.28, p=.039). Expert ratings were not related to transition readiness (ps&amp;gt;.05); therefore, only caregiver ratings were used in moderated mediation models. For overall transition readiness, managing medications, appointment keeping, talking with providers, and managing daily activities, the direct effects of caregiver ratings (ps&amp;gt;.05) and indexes of moderated mediation via CMA (ps&amp;gt;.05) were not significant. For tracking health issues, the direct effect of caregiver ratings (p=.085) was not significant, but the index of moderated mediation was significant (95%CI=.026;.315). CONCLUSIONS Only caregiver cognitive late effect ratings were helpful in explaining YAS overall transition readiness. The role of social vulnerability in CMA and transition readiness warrants further exploration. Empirically based transition readiness YAS programs targeting access to resources for families with more social vulnerability are needed.