bluuebunny/crossref_metadata_2025_split huggingface dataset:
NFS-18. LOWER BODY SURFACE AREA IS ASSOCIATED WITH INCREASED LIKELIHOOD OF PLEXIFORM NEUROFIBROMA RESPONSE TO MEK INHIBITION
Authors: Kotch Chelsea , Dombi Eva , Gross Andrea , Weiss Brian , Mueller Sabine , Reddy Alyssa T , Perreault Sébastien , Alves Mélanie , Brown Symone , Li Yimei , Widemann Brigitte C , Fisher Michael J 
Published: June 2024

Abstract

BACKGROUND
MEK inhibitors (MEKi) are altering the management approach for plexiform neurofibroma (PN), with high rates of treatment response to multiple MEKi. Despite these successes, a subset of PN fail to respond and little is known about the clinical features associated with treatment response.

METHODS
We performed a retrospective cohort study integrating clinical trial data (NCT01362803, NCT02407405, NCT02096471, NCT03231306, NCT03363217) to identify baseline clinical features associated with response of PN to MEKi. Partial response (PR) was defined as ≥20 percent reduction in tumor volume from baseline.

RESULTS
Of 232 eligible participants, adequate clinical trial and imaging data was available for 223 participants. In the primary analysis of 184 participants with central response evaluation, the median age was 15.2 years with a median tumor volume of 488 milliliters at clinical trial enrollment. One hundred and eighteen (64%) participants achieved a PR with median time to PR of 8 cycles. Thirty-five participants (19%) required a dose reduction prior to 6 cycles of therapy due to toxicity. Younger age and lower body surface area (BSA) were significantly associated with PR in univariate analysis while female sex and typical PN appearance (versus nodular) on imaging approached significance. In multivariable analysis, only lower BSA was significantly associated with response while typical PN appearance approached significance. In the multivariable analysis of pediatric participants treated per BSA-based dosing, lower BSA was the only feature significantly associated with PR. In the expanded analysis of all 223 participants, lower BSA and typical PN appearance were significantly associated with PR.

CONCLUSION
Lower BSA and typical appearance of PN were associated with PR to MEK inhibitors. Future studies of MEK inhibitor for PN should integrate tumor pharmacokinetic-pharmacodynamic analyses to prospectively explore the impact of BSA on treatment response.
NFS-21. DEMOGRAPHIC, CLINICAL AND IMAGING CHARACTERISTICS OF NEWLY DIAGNOSED OPTIC PATHWAY GLIOMAS ASSOCIATED WITH NF1: RESULTS FROM THE INTERNATIONAL MULTICENTER NF1-OPG NATURAL HISTORY STUDY
Authors: Fisher Michael J , de Blank Peter , Listernick Robert , Liu Grant , Ferner Rosalie , Gutmann David , Lasky-Zeid Janice , Ullrich Nicole , Heidary Gena , Bornhorst Miriam , Stasheff Steven , Rosser Teena , Borcher March , Arden-Holmes Simone , Flaherty Maree , Hummel Trent , Motley Walker , Bielamowicz Kevin , Phillips Paul , Bouffet Eric , Reginald Arun , Wolf David , Peragallo Jason , El-Dairi Mays , Van Mater David , Sato Aimee , Tarczy-Hornoch Kristina , Klesse Laura , Hogan Nick , Foreman Nicholas , McCourt Emily , Allen Jeffrey , Ranka Milan , Campen Cynthia , Beres Shannon , Moertel Christopher , Areaux Ray , Stearns Duncan , Orge Faruk , Crawford John , O’Halloran Henry , Oattes Julius , Reddy Alyssa , Brodsky Michael , Esbenshade Adam , Donahue Sean , Cutter Gary , Avery Robert 
Published: June 2024

Abstract

BACKGROUND
Treatment and clinical management decisions for children with NF1-OPGs remain challenging as most existing data are retrospective and have not included standardized visual outcomes. In this study, we prospectively enrolled newly diagnosed NF1-OPGs and performed standardized neuro-oncology and ophthalmology assessments in order to develop evidence-based guidelines for monitoring and treatment.

METHODS
Children with NF1-OPG on MRI who were evaluated by both a study ophthalmologist and neuro-oncologist/NF1 expert within 1 month of radiologic diagnosis were eligible for enrollment. All subjects attempted quantitative visual acuity using Teller acuity cards (TAC) as well as ATS-HOTV testing. The neuro-oncologist/NF1 expert provided reasons for obtaining the MRI as well as initiating treatment, if applicable. Descriptive statistics calculated the success rate of acquiring TAC and reasons to obtain the MRI.

RESULTS
Two-hundred fifty subjects from 22 institutions were enrolled and had at least one visit beyond baseline (Median age 3.1 years, range 0.1–16.8; 53% female). TAC was successfully acquired in both eyes (N=195, 78%) and at least one eye in (N=206, 82%). ATS-HOTV was successfully acquired in both eyes (N=97, 39%) and at least one eye in (N=98, 39%). The two most common reasons to obtain an MRI were screening due to a diagnosis of NF1 (N=99, 39%) and ophthalmologic concern (N=81, 32%). At enrollment, continued observation occurred in a majority of subjects (N=221, 88%) while treatment with chemotherapy was initiated in only 11% (N=29). Twenty-nine (11%) subjects initially observed transitioned to treatment after enrollment (range: 2.5–25 months) thus far.

DISCUSSION
We present a prospective multicenter study of children with newly diagnosed NF1-OPGs. The ability to acquire quantitative visual acuity was higher than anticipated. The frequency of NF1-OPGs requiring treatment is lower than previously reported. Regression models of clinical and MRI features that prompted immediate treatment with chemotherapy versus observation will be discussed.
NFS-27. SELUMETINIB FOR SYMPTOMATIC, INOPERABLE PLEXIFORM NEUROFIBROMAS IN NEUROFIBROMATOSIS TYPE 1: A SINGLE-INSTITUTION EXPERIENCE
Authors: Vázquez-Gómez Felisa , Perez-Somarriba Marta , Castellano Serafin , Moreno José Luis , Cartas Susana , Cantarín Verónica , Duat Anna , Borrego Pedro , Solís Inés , Valls Isabel , Hernández Ángela , Torrelo Antonio , Esteso Borja , Tamariz-Martel Amalia , Egea Rosa María , Blasco Luis , Colmenero Isabel , Arce Begoña , Rivero Belén , Madero Luis , Lassaletta Álvaro 
Published: June 2024

Abstract

BACKGROUND
Half of patients with Neurofibromatosis type 1 (NF1) develop plexiform neurofibromas (PNs). PNs may grow during childhood causing significant complications, including pain, functional impairment, and disfigurement. Treatment options are limited, given their tendency to regrow following surgery and their propensity to transform into malignant tumors following radiation. Selumetinib is an oral selective inhibitor of RAS-mitogen activated protein kinase (MAPK) 1 and 2, which has shown efficacy for tumor shrinkage/ stabilisation and symptom improvement.

METHODS
Single-institution retrospective review of patients with NF1 treated with selumetinib for symptomatic PNs between 2020 and 2023. Clinical data were abstracted from medical records. Treatment consisted of selumetinib 25 mg/m2 BID. Patient follow-up included monthly complete physical examination, evaluation of treatment adherence, blood analysis, echocardiogram, ophthalmologic assessment every 3 months, and MRI every 6 months. Response evaluation criteria in solid tumors (RECIST) was used for assessment.

RESULTS
Ten patients were treated with selumetinib during the period indicated. Mean age 13.9 years (range 7-21). Predominant target locations were head and neck (60%), and abdomen-pelvis (30%). The most important comorbidities were disfigurement (50%) and pain (50%). The mean follow-up time was 519 days (range 45–1460). None of the patients presented grade 3-4 toxicities; all of them had associated grade 1-2 skin toxicity. None presented cardiac or ophthalmologic alterations. All the patients with pain had sustained clinical improvement in the first 35–60 days of treatment. At one year of treatment 6/8 patients showed stable disease and 2/8 partial response on MRI. In one patient, treatment was discontinued after 270 days (lack of clear benefit).Another patient has not reached one year of therapy yet.

CONCLUSIONS
In this study we expose that selumetinib for symptomatic, inoperable plexiform neurofibromas in NF1 was associated with clinical and radiological response. Our study also confirms the safety and good tolerance of this drug.
QOL-15. PAEDIATRIC LOW-GRADE GLIOMA (PLGG): A LIFELONG DISEASE THAT BEGINS IN CHILDHOOD. EVALUATION AND PROGNOSTICATION OF LONG-TERM PLGG SURVIVOR FUNCTIONAL AND QUALITY OF LIFE OUTCOMES
Authors: Green Katie L , Stone Tom J , Jacques Thomas S , Pickles Jessica C , Ridout Deborah , Aquilina Kristian , Phipps Kim , Bowman Richard , Gains Jenny , Aldridge Brownwen , Gan Hoong-Wei , Jorgensen Mette , O’Hare Patricia , Slater Olga , Depani Sarita , Syzchot Elwira , Chang Yen , Leyden Deirdre , Bluebond-Langner Myra , Hargrave Darren 
Published: June 2024

Abstract

BACKGROUND
For many patients, PLGG has a chronic disease course with potential for multiple and significant functional deficits and decreased Quality-of-Life (QOL). However, there have been limited large-cohort evaluations or prognostication studies of QOL & functional outcomes.

AIMS
1. Large-cohort analysis of long-term PLGG survivor functional & QOL outcomes: combining clinical follow-up assessment with survivor-reported QOL & function. 2. Evaluation of prognostic associations between PLGG variables & functional/QOL outcomes.

METHODS
Demographic, tumour & treatment factors of PLGG patients diagnosed 1980-2021 at Great Ormond Street Hospital, UK, were retrospectively collected & evaluated prognostically with functional outcomes from last clinical follow-up.Cohort long-term survivors completed prospective QOL(PedsQl Core) & function(PESAT-PT) questionnaires.PedsQL scores were evaluated prognostically with patient/tumour/treatment factors using multivariate logistic regression.PedsQL scores were compared with healthy (N=649) & chronically-ill (N=137) reference populations.

RESULTS
PLGG cohort (N=814) OS was 94.3%,PFS 76% & median treatments 1 (0-21) at median follow-up 8 years. 42% had 1 functional deficit at last clinical follow-up. Diagnostic age, tumour location, surgical resection, & receipt chemo/radiotherapy were independently associated with functional outcomes. 122 long-term survivors completed prospective questionnaires at median follow-up 21 years. 87% reported dysfunction: physical 60%,visual 50%,neurocognitive 49%,social 25%, endocrine 23%,travel 21%,employment 18%,& hearing 11%. Mean PedsQl scores:Physical 82(0-100), Psychosocial 73(13-100), Total 76(9-100). PLGG survivors had significantly lower mean Total, Physical & Psychosocial PedsQl scores than healthy controls (p0.0001,p0.0003,p0.0001), but comparable to people with chronic illness (p0.60,p0.14,p0.21). No correlation identified between PedsQl scores & number of impaired functional domains. Favourable Total PedsQl scores were associated with surgical resection(OR-5.94,p0.02) & fewer treatment interventions on multivariate analysis(OR-2.8,p0.0005). Adverse PedsQl scores were associated with NF1 (OR-11.82,p0.04), BRAF-V600E mutation(OR-18.55,p0.04), OPGs(OR-12.1,p0.01), & seizures(OR-18.93,p&lt;0.0001).

CONCLUSIONS
Prognostication of heterogeneous PLGG survivor functional and QOL outcomes is complex but possible, without clear correlation between QOL and functional outcomes. For many, PLGG is a lifelong disease that begins in childhood.
QOL-45. SOCIAL DETERMINANTS OF HEALTH PREDICT NEUROPSYCHOLOGICAL OUTCOMES IN PEDIATRIC BRAIN TUMOR SURVIVORS
Authors: Gioia Anthony R , Jacobson Lisa A , Acharya Sahaja , Peterson Rachel K 
Published: June 2024

Abstract

BACKGROUND
Pediatric brain tumors and their treatment impact cognition including intellectual functioning (IQ), attention, working memory, and processing speed. Few studies have examined the role of social determinants of health (SDoH) on cognition in pediatric brain tumors. To date, studies have primarily focused on family-related SDoH factors such as insurance status or parental education as predictors of cognition. To our knowledge, no study has examined multiple indicators of SDoH to determine which family-based and community-based predict cognition.

METHODS
Participants included 151 pediatric brain tumor patients (M diagnosis age=8.82) seen for a clinical neuropsychological evaluation (M evaluation age=13.71). IQ, brief attention (WISC/DAS-II Digits Forward), working memory (WISC/DAS-II Digits Backwards), and processing speed (WISC Coding) were obtained from age-appropriate measures (WISC&gt;6 years, DAS-II&lt;6 years). Family-based SDoH indicators include insurance type (public, private) and maternal education (&lt;high school degree, some college, ≥college degree). Community-based SDoH include the Area Deprivation Index (ADI) and Childhood Opportunity Index (COI). Multiple regressions examined variance in IQ, attention, working memory, and processing speed accounted for by the SDoH measures, after controlling for treatment exposures using the Neurological Predictor Scale.

RESULTS
Insurance accounted for 14.9% of the IQ variance [β=-.316, t(151)=-4.18; p&lt;.001]; COI accounted for 18.3% of the IQ variance [β=.202, t(151)=2.70; p=.008]. Insurance accounted for 12% of the variance in attention [β=-.324, t(152)=-4.22; p&lt;.001], and 17.5% of the variance in processing speed [F(2,134)=15.399, p&lt;.001]. In the working memory model, insurance [β=-.179, t(148)=-2.19; p=.03] and ADI [β=-.171, t(148)=-2.11; p=.04], accounted for 5.3% and 7.5% of the variance, respectively.

CONCLUSIONS
Findings highlight the important contribution of both family and community factors on neuropsychological outcomes in pediatric brain tumors. Nuances of the data will be discussed as they relate to clinical care and research.
NURS-01. NOVEL TREATMENTS FOR ACNEIFORM ERUPTIONS CAUSED BY TARGETED THERAPIES IN THE PEDIATRIC POPULATION
Authors: Meyer Ashley S , Cluster Andrew , Ogle Andrea , Brossier Nicole , Beck Mary , Lampe Ashley , Rocco Abbey , Shatara Margaret , Mchugh Michele , Abdelbaki Mohamed , Coughlin Carrie C 
Published: June 2024

Abstract

BACKGROUND
Drugs that target the mitogen-activated protein kinase pathway can cause frequent and severe cutaneous toxicities with acneiform eruptions being one of the most common and challenging to manage. The literature is limited regarding treatment recommendations especially when this rash is refractory to first-line therapies.

METHODS
A single-institution case series regarding the treatment of acneiform eruptions with oral isotretinoin after failure of first-line therapies was performed.

RESULTS
Two female, adolescent patients who developed refractory acneiform eruptions while on trametinib were included. Their acneiform eruption emerged within the first cycle of trametinib requiring treatment with oral doxycycline plus a variety of topical medications. They remained on doxycycline for 6 and 7 months. Both patients then switched to oral isotretinoin after minimal rash response and rebound of the rash when attempting to discontinue doxycycline. The initial isotretinoin doses were 0.2-0.3 mg/kg/day rounded per pill size. Both patients required a dose reduction due to worsening xerosis. Once decreased, isotretinoin was well tolerated. No changes in baseline lipid panels or ALT were seen. No associated neurologic symptoms or pseudotumor cerebri. While on oral isotretinoin, no additional topical therapies were required to treat the acneiform eruption. The first patient’s acneiform rash improved from a CTCAE v5 grade 3 to grade 1 after only 3 weeks of isotretinoin. All locations of the rash responded to therapy. The second patient developed a grade 2 acneiform rash after starting trametinib and became ungradable with only residual pink papules to cheeks after receiving isotretinoin.

CONCLUSIONS
Both patients were successfully treated with isotretinoin after multiple prior therapies including 6 or more months of treatment with oral antibiotics. We recommend further research of treatment therapies in addition to oral antibiotics given concerns on their impact of the microbiome.
NURS-13. NEUROCOGNITIVE SIDE EFFECTS OF PEDIATRIC BRAIN TUMORS: A CONTINUING CHALLENGE
Authors: Rangan Kasey , Briamonte Courtney Baker , Higgins Micah , Hoffman Carly , Holtzclaw Susan , McHugh Michele , Meyer Ashley , Raber Shannon , Schmus Cindy , Seidl Kenny , Strachan Marylynne , Waters Kaaren , Yeh-Nayre Lanipua 
Published: June 2024

Abstract

BACKGROUND
Pediatric brain tumors pose a considerable challenge in clinical oncology, necessitating multimodal treatment approaches. Many of these have the potential to impact cognition on vulnerable, young brains. While advancements in therapies have improved survival rates, neurocognitive outcomes continue to be one of the most challenging late effects that affect quality of life for pediatric brain tumor survivors.

METHODS
We conducted a literature review to identify 1) current treatment approaches for pediatric brain tumors, 2) the neurocognitive effects that survivors of pediatric brain tumors experience, and 3) appropriate interventions that can be implemented to mitigate those neurocognitive effects.

RESULTS
Novel chemotherapeutic agents, such as molecularly targeted therapies, are increasingly implemented in a personalized approach to treatment. New approaches to radiation therapy, particularly proton therapy, have shown promise in minimizing cognitive decline compared to traditional photon therapy. Advances in neuroimaging techniques have enabled a more detailed understanding of structural and functional brain changes associated with treatment. While these newer treatment modalities are promising, their long-term side effects are mostly unknown and bear close monitoring over time. Because neurocognitive side effects continue to underscore the impact of pediatric brain tumor treatments, recent studies often specifically evaluate the cognitive side effects as well as attempt to personalize treatments to reduce cognitive damage.

CONCLUSIONS
Recent research findings reinforce the enduring concern of neurocognitive side effects in pediatric brain tumor survivors. The integration of advanced therapeutic modalities and targeted supportive care interventions may hold the key to optimizing treatment outcomes while minimizing cognitive morbidity. Continued research efforts are essential for refining treatment protocols and developing personalized strategies to safeguard neurocognitive function in this vulnerable population. Additionally, studies exploring the role of supportive care interventions, such as cognitive rehabilitation and neuroprotective strategies, demonstrate potential avenues for mitigating cognitive sequelae but require ongoing research.
NURS-23. THE ROLE OF THE ADVANCED PRACTICE PROVIDER IN THE PAIRED NORMAL SPECIMEN PROCESS AT A TERTIARY CARE CENTER
Authors: Hemenway Molly S , Winzent-Oonk Shelby 
Published: June 2024

Abstract

BACKGROUND
Paired tumor - normal specimen testing is standard of care to improve the timing and knowledge of genetic variations present in the brain tumor cell and germline. A new process was developed to ensure the paired normal specimen (PNS) testing was completed.

METHODS
The Neuro-Oncology Advanced Practice Provider (APP) is integral in the process of ordering and obtaining the PNS.

RESULTS
In the last 15 months, this tertiary care center has performed more than 90 pediatric brain tumor biopsies and/or resections. APPs identify patient surgery dates via the neurosurgery calendar. On the day of surgery a PNS is ordered for the Solid Tumor panel (predetermined by pathology and neuro-oncology) and “Include germline variant resolution information if applicable?” is answered as “No”. The laboratory runs the next generation sequencing (NGS) on PNS and tumor but the findings remain blinded until a second order is placed to “unblind” the specimen. By doing so, the treating physician collaborates with a genetics counselor prior to discussing with the family. Initial difficulty included patient identification, ordering, and collecting PNS. The APPs developed a shared list with patient identifiers, surgery date, order and collection date of PNS which has ensured less than 5% of PNS have been missed. Challenges include weekend surgeries, APPs out of office, and communication to nursing to collect PNS. Updated protocol includes ordering PNS, messaging shift nurse with order explanation and request to collect. Additionally, the pathology team now messages the APPs if a PNS is not submitted and the tumor is undergoing NGS.

CONCLUSIONS
Comprehensive processes ensure that paired normal – tumor testing is completed in a timely manner and during the same admission with surgery to ensure better insurance coverage and less cost to families, as well as earlier results of somatic and germline variants.
PATH-06. AN INTEGRATIVE MULTI-MODAL DIAGNOSTIC APPROACH TO PEDIATRIC CHOROID PLEXUS TUMORS
Authors: Markowitz Alexander L , Suddock Jolee , Castaneda Everardo , Ji Jianling , Margol Ashley , Tamrazi Benita , Bluml Stefan , Cotter Jennifer A 
Published: June 2024

Abstract

BACKGROUND
Choroid plexus tumors (CPTs) consist of a diverse group of neoplasms, more prevalent in children. They include choroid plexus papillomas (CPPs, grade 1), atypical choroid plexus papillomas (aCPPs, grade 2), and choroid plexus carcinomas (CPCs, grade 3). Traditional grading of CPTs relies on histologic assessment, but morphologic criteria for determining tumor grade are subjective. Evidence suggests incorporation of clinical, radiologic, and molecular characteristics may increase diagnostic accuracy. Here, we investigated the multi-modal associations of CPT subtypes to develop a classification system to aid in CPT subtype diagnostics.

METHODS
We aggregated an integrative dataset that consists of digitized whole-slide images, NGS sequencing panels, methylation arrays, and magnetic resonance spectroscopy (MRS) spectra from in-house and publicly available data sources (n=110). We tested for clinically significant associations and established multi-modal profiles of CPT subtypes, as well as a machine-learning classifier to predict multi-modal based CPT subtypes.

RESULTS
CPT subtypes exhibit distinct characteristics across modalities with consistent correlations across anatomy, molecular, and metabolic datasets. Computer-vision models achieved high accuracy (89.7%) in classifying CPT subtypes using H&E images. Ki-67 immunostaining displayed increased reactivity in CPC compared to CPP and aCPP (p = 0.007, ANOVA). Methylation-based classifications confidently predicted CPP and CPC subtypes, while aCPP tumors clustered with either CPP or CPC due to the lack of a defined subtype. Molecular variants (i.e. TP53, MYCN) were significantly associated with CPC (p = 0.007, ANOVA). Metabolites such as inositol (p = 0.031) and choline (p = 0.004) were associated with CPT grade based on MRS-spectra.

CONCLUSION
Multi-modal analysis reliably separates CPTs by grade. The study underscores the significance of integrating multi-modal datasets in refining the accuracy of diagnosis and prognosis of CPTs. Continued research will focus on a multi-modal approach to improve prediction of aggressive behavior and understanding of inherent metabolic heterogeneity of CPT subtypes.