bluuebunny/crossref_metadata_2025_split huggingface dataset:
INNV-33. NEURO-ONCOLOGY VISITS AT HOME (NOVAH): A PILOT PROGRAM TO IMPROVE CARE FOR PATIENTS WITH BRAIN CANCER
Authors: Eichler April , Merker Vanessa , Von Imhof Liesel , Pavlovich Renee , Forst Deborah , Plotkin Scott R 
Published: November 2023

Abstract
Informational and care needs of brain cancer patients change rapidly and often outstrip the capacity of clinical encounters at key time points, including transitions from inpatient to home and times of high emotional and psychological needs (e.g., new diagnosis, disease progression). The existing care-model leaves little time for illness understanding and advance care planning (ACP) work. We piloted a home visit program (NoVaH) to assess feasibility and acceptability of specialty-level clinical support in the home at times of increased care needs. METHODS: Eligible patients were treated in the neuro-oncology practice of a single academic medical center, resided within 15 miles of the hospital, and were referred by clinic staff. Home visits were conducted by a neuro-oncologist one half-day per week and scheduled longitudinally according to need, in parallel with primary outpatient visits. 9 family caregiver interviews were conducted virtually and analyzed by a qualitative researcher using rapid analysis methods to synthesize findings across predetermined, deductive categories. RESULTS: 18 patients referred from outpatient (61%) or inpatient service (39%) completed ≥ 1 home visit. Most patients had glioblastoma (78%). 59 home visits took place over 12 months (median per patient 2, range 1-8). A first life-sustaining treatment order form was completed by 10/18 patients (56%). Among 10 patients who died, place of death was home (50%), skilled nursing facility (20%), inpatient hospice (20%), or hospital (10%); 90% were enrolled in hospice at time of death. Caregivers voiced specific benefits such as ability to receive care patients would have otherwise forgone, improved communication about illness understanding and ACP, and enhanced sense of control and ability to digest prognostic information compared with office setting. CONCLUSIONS: Neuro-oncology home visits are feasible and acceptable to patients with brain cancer and represent an innovative way to provide patient-centered cancer care at times of transition and complex decision-making.
INNV-36. ULTRA-FAST DEEP-LEARNED CNS TUMOR CLASSIFICATION USING NANOPORE-SEQUENCING DURING SURGERY
Authors: Wesseling Pieter , Vermeulen Carlo , Pages-Gallego Marc , Kester Lennart , Kranendonk Mariëtte , Verburg Niels , Hamer Philip de Witt , Kooi Evert-Jan , Dankmeijer Luuk , van der Lugt Jasper , Van Baarsen Kirsten , Hoving Eelco , Tops Bastiaan , De Ridder Jeroen 
Published: November 2023

Abstract

BACKGROUND
Preoperative imaging and intraoperative histological analysis provide important guidance during CNS tumor surgery but are not always precise enough. Also, the diagnosis of CNS tumors increasingly requires a combination of morphological and molecular analysis. Illumina DNA methylation array analysis provides information on hundreds of thousands of methylation sites genome-wide but is relatively time-consuming and expensive. Nanopore sequencing enables real-time generation of an increasingly precise methylation profile. AIM: To exploit the potential of nanopore sequencing as a tool for intraoperative molecular diagnostics of CNS tumors.

METHODS
We developed Sturgeon, a patient-agnostic, transfer-learned neural network approach. Sturgeon leverages publicly available Illumina 450K DNA methylation profiles to simulate millions of nanopore sequencing experiments, which were used to train and validate classifier models. Subsequently, snap-frozen archival samples of 50 CNS tumors were analyzed, as well as fresh tumor samples of an additional 25 CNS tumors intraoperatively.

RESULTS
Sturgeon delivers models capable of classifying 81 different CNS tumor types based on relatively sparse, randomly distributed nanopore sequencing data. Sturgeon was able to suggest within 40 minutes after the start of sequencing the correct diagnosis with high confidence in 45 out of 50 archival CNS tumor samples; in the remaining cases Sturgeon abstained from a diagnosis. In the real-life scenario, in 18 out of 25 cases (72%) the suggested diagnosis was correct, and in 7 cases the required confidence threshold was not reached (mostly because of low tumor cell percentage). Importantly, the Sturgeon models are portable, work across patients and sequence depths, and require less than a minute of computation on a laptop CPU.

CONCLUSIONS
Intraoperative nanopore sequencing can assist neurosurgical decision making and opens avenues for starting tumor-specific therapy already during operation. Furthermore, this diagnostic approach has the potential to reduce the costs of methylation profiling analysis and speed-up the multidisciplinary decision-making process.
INNV-42. INTRA-ARTERIAL MELPHALAN FOR HISTIOCYTIC NEOPLASMS INVOLVING NEUROLOGIC, OCULAR, AND HEAD AND NECK STRUCTURES
Authors: Diamond Eli , Ramos Alexander , Knopman Jared , Reilly Julia , Canestaro Julia , Hatzoglou Vaios , Pierre Gobin Y , Garton Andrew , Abramson David , Francis Jasmine 
Published: November 2023

Abstract

BACKGROUND
Histiocytic neoplasms are clonal hematopoietic disorders of myeloid lineage. Involvement of neurologic structures by histiocytic infiltration or disease-associated neurodegeneration (ND) represents a severe disease phenotype associated with morbidity and mortality. Despite recent advances with BRAF and MEK inhibitors, patients with neurohistiocytic involvement continue to demonstrate suboptimal outcomes. Intra-arterial chemotherapy (IAC) may represent an effective therapy for this disease manifestation.

METHODS
Patients with biopsy-proven histiocytic neoplasms involving neurologic, ocular, or head and neck structures were treated with intra-arterial melphalan delivered via selective catheterization of tumor arterial vasculature. Patients treated had refractory/persistent tumorous disease or progressive functional decline despite BRAF/MEK inhibition, or had limited disease appropriate for local therapy. Patients were evaluated for radiologic (PET or CT/MRI) response and functional neurologic response with quantified ataxia and dysarthria scales, or change in visual acuity (VA), as appropriate. Procedure-related adverse events as well as clinical and laboratory toxicities were captured.

RESULTS
74 IAC treatments were administered to 17 patients, 12 with tumorous disease (6 Rosai-Dorfman disease; 3 xanthogranuloma; 3 Langerhans cell histiocytosis[LCH]; 1 Erdheim-Chester disease [ECD]), 5 with ND-LCH/ECD, and ten with disease-related impairment of VA. Patients received a range of 2-12 IAC doses. 9/12 (75%) patients with tumorous disease had complete or partial radiologic response. 4/5 patients with ND had measurable improvement in dysarthria and 2/5 had measurable improvement in ataxia. 4/10 patients had improved VA. Of all patients with clinical or radiologic response, three have experienced disease recurrence since IAC in long-term follow-up. No procedural adverse events were observed, 1 patient had neutropenia and 1 patient melphalan hypersensitivity.

CONCLUSIONS
IA melphalan is a safe and robustly effective treatment option for tumorous and ND histiocytic neoplasms of neurologic, ocular, and head and neck structures.
PATH-14. MSI GENETIC FINDINGS IN FAMILIAL TURCOT SYNDROME 1 ASSOCIATED TO REPRODUCTION FAILURE
Authors: Abdelmoula Nouha Bouayed , Abdelmoula Balkiss 
Published: November 2023

Abstract
The aim of this study was to report MSI genetic findings in a three-generation Tunisian pedigree of Turcot syndrome 1 (TS1), characterized by an uncommon association with infertility and child mortality. Microsatellite instability testing and genetic counseling were offered to affected members and their young relatives, to provide optimal clinical and preventive care. The index case of our Tunisian pedigree was a 38-year-old female, in whom histologic assessment of endoscopic specimens through a colorectal adenoma resection during screening colonoscopy, showed a tubular adenoma of the lower rectum with low-grade intraepithelial neoplasia. The screening procedure was conducted because her two brothers, 58 and 60 years old, harbored respectively glioblastoma multiforme and colon adenocarcinoma. The first brother exhibited an intracranial hypertension syndrome and a left hemiplegia leading to the diagnosis of a brain tumor. Whereas the second brother manifested diarrhea and intestinal colic that were investigated by colonoscopy. Histologic assessment of endoscopic specimens through a right preangular budding formation showed a well-differentiated liberkhunian adenocarcinoma that was treated by a right hemicolectomy. Genetic assessment at the germinal and somatic levels was conducted for the three affected patients using conventional microsatellite instability (MSI) testing methods. Molecular analysis determined MSI status of the tumors and classified them into stable types (MSS) without any mutation or aberrant expression of MLH1, MSH2, MSH6, and PMS2 genes. Familial history revealed, at the first generation, a consanguineous couple who lost several children at a young age. This couple gave birth to eight children, three of whom were infertile, three affected by MMS TS1 and two healthy. The third generation consists of 15 children, so far, without any tumors. Genetic counselling for TS remains difficult because of the rarity of the condition, its shifting definition over the years, and its genetic and phenotypic heterogeneity.
PATH-15. GLIOBLASTOMA, IDH-WILDTYPE WITHOUT KEY MOLECULAR FEATURES.
Authors: Saito Ryuta , Motomura Kazuya , Ohka Fumiharu , Yamaguchi Junya , Maeda Sachi , Nishikawa Tomohide , Mizutani Kosuke , Kibe Yuji , Shimizu Hiroki , Takido Yuhei 
Published: November 2023

Abstract
Molecular alterations that predict aggressive behavior of astrocytic tumors include EGFR amplification, TERT promoter (pTERT) mutations, gain of chromosome 7 and loss of chromosome 10. During January 2020 and February 2023, we encountered 21 cases of pathologically diagnosed glioblastoma, IDH-wildtype without the above-mentioned molecular characteristics. In this study, we tried to characterize these tumors. For all cases, genomic DNA was extracted from fresh frozen tissue. Using extracted DNA, to analyze the status of IDH mutation, 1p/19q codeletion, pTERT mutation, EGFR gene amplification, combined gain of entire chromosome 7, and loss of entire chromosome 10 (+7/− 10), whole exome sequencing, Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) was performed. In addition, gene panel testing was performed for suspected familial cases. Among 21 cases, 2 harbored histone G34 mutation and was diagnosed as diffuse hemispheric gliomas, H3 G34-mutant. Among the rest 19 patients, CDKN2A/B homozygous deletions were detected in 7. Three of the rest 12 patients were diagnosed as patients with Li Fraumeni syndrome. Glioblastoma IDH-wildtype CNS WHO grade 4 typically presents necrosis and/or microvascular proliferation. Molecular alterations including EGFR amplification, pTERT mutations, gain of chromosome 7 and loss of chromosome 10 are key features that characterize GBM IDH-wildtype. However, some of the pathologically diagnosed GBM, do not carry these gene alterations. Among those, there existed cases harboring CDKN2A/B homozygous deletions or H3 G34 mutations, and cases suffering Li Fraumeni syndrome.
PATH-16. SURVIVAL ANALYSIS OF ADULT MIDLINE-LOCATED GLIOMAS: DOES THE H3K27 ALTERATION IN ADULT MIDLINE-LOCATED GLIOMAS ACTUALLY INDICATE A POOR PROGNOSIS?
Authors: Chang Jong Hee , Jung In-Ho , Yoo Jihwan , Park Hun Ho , Lim Jaejoon , Moon Ju Hyung , Kim Eui-Hyun , Kang Seok-Gu , Yoon Hong In , Kim Se Hoon 
Published: November 2023

Abstract

OBJECTIVE
Although pediatric midline-located gliomas (MGs) with H3K27 alteration have been widely known to have a poor prognosis, few researchers have assessed adult MGs with H3K27 alteration. We aimed to determine the effect of H3K27 alteration on the prognosis of adult MGs. And we tried to identify the factors affecting the prognosis of diffuse midline glioma (DMG). This is the first study to investigate the prognosis of adult DMGs according to histological grade and is the largest study to investigate the survival of adult patients with DMGs.

METHODS
We reviewed the charts of adult patients diagnosed with MG after undergoing resection or biopsy at our institution between 2010 and 2020. The Gehan–Breslow–Wilcoxon test was used for univariate survival analysis, and the Cox regression proportional hazard model was used for multivariate survival analysis.

RESULTS
Among the 125 adult MGs identified, 45 (36.0%) showed H3K27 alterations. Surprisingly, the H3K27 alteration group showed significantly better median survival than the wildtype group in patients of all ages (23.1 vs. 15.9 months, p=0.040). However, after adjusting for age, the difference in survival between the H3K27-alteration and wildtype groups was not significant (p=0.121). In the survival analysis of 45 patients with DMG, low histological grade, KPS ≥ 80, total resection, and concurrent chemoradiation therapy were associated with significantly better survival.

CONCLUSION
Adult MGs did not show a poor prognosis due to H3K27 alterations, unlike pediatric cases. The prognosis of adult DMGs is based on the histological grade, KPS, adjuvant treatment, and extent of tumor resection.
PATH-17. PILOCYTIC ASTROCYTOMA EXHIBITING DIFFUSE LEPTOMENINGEAL DISSEMINATION: EXTREMELY RARE FORM OF LOW-GRADE GLIOMA WITH DICHOTOMOUS (CHILDREN VERSUS ADULTS) AND UNCHARACTERISTICALLY AGGRESSIVE BEHAVIOR
Authors: Brown Nolan , Kuo Cathleen , Mehkri Yusuf , Gendreau Julian 
Published: November 2023

Abstract

OBJECTIVE
To identify all prior reports of pilocytic astrocytoma (PA) exhibiting diffuse leptomeningeal dissemination (LMD) (WHO Grade I) in an effort to comprehensively characterize this anomalous, predominantly pediatric pathology.

METHODS
A systematic review of the literature was performed using the PubMed, Scopus, and Web of Science databases.

RESULTS
Twenty-nine studies featuring 60 patients (54 pediatric,6 adult) were identified.The mean age at initial diagnosis was 10.2 ± 10.6 years (range, 0.3 to 55 years), and most of the patients were male (n=39,65.0%). The most common primary tumor locations were the hypothalamus (n=18,30.0%), cerebellum (n=16,26.7%), and optic chiasm (n=8,13.3%). Signs/symptoms at presentation included paralysis, cerebellar findings, and symptomatic, obstructive hydrocephalus. Most patients underwent surgery alone (n=26,43.4%) or in combination with radiotherapy (n=10,16.7%) or chemotherapy (n=8,13.3%). Of 43 patients who underwent surgery, subtotal resection (STR) was achieved in 26. STR appeared to be a risk factor for future LMD and poor prognosis. Additionally, adjuvant therapy did not seem to reduce the odds of subsequent LMD. Twenty-two patients (36.7%) were found to have LMD at presentation. Time to dissemination for the remaining patients ranged from between 3.6 - 206 months. Among all the included patients, 24 (40%) exhibited LMD within the brain only, 22 (36.7%) within the spine only, and 14 (23.3%) within both locations. Multi-agent chemotherapy alone (n=20, 33.3%) was the most commonly utilized treatment modality, followed by radiotherapy alone (n=13,21.7%), surgery with radiotherapy (n=10,16.7%), and surgery alone (n=5,8.3%). The mean follow-up duration was 44.2 ± 47.7 months (range, 0 to 221 months). Mortality occurred in 18 out of the 58 patients who had follow-up information available, with a mean time from LMD diagnosis to death of 19.9 ± 23.6 months.

CONCLUSION
Given its truly anomalous behavior, future concerted efforts to analyze the genetic profile of all identified tissue samples of PA with LMD is warranted.
PATH-19. PROGNOSTIC FACTORS, RESPONSE TO TREATMENT, AND OUTCOME OF PATIENTS WITH ISOCITRATE DEHYDROGENASE (IDH)-MUTANT ASTROCYTOMA, CNS WHO GRADE 4
Authors: Weller Michael , Felsberg Jörg , Hentschel Bettina , Gramatzki Dorothee , Kubon Nadezhda , Wolter Marietta , Roth Patrick , Krex Dietmar , Herrlinger Ulrich , Westphal Manfred , Tonn Joerg-Christian , Regli Luca , Maurage Claude-Alain , von Deimling Andreas , Pietsch Torsten , Rhun Emilie Le , Reifenberger Guido 
Published: November 2023

Abstract

PURPOSE
To study disease characteristics, prognostic markers and outcome in patients with isocitrate dehydrogenase (IDH)-mutant astrocytoma by CNS WHO grade.

EXPERIMENTAL DESIGN
We determined molecular biomarkers and assembled clinical and outcome data in a cohort of 258 patients with IDH-mutant astrocytomas (114 CNS WHO grade 2, 73 CNS WHO grade 3, 71 CNS WHO grade 4) confirmed by central pathology review.

RESULTS
The median age for astrocytoma, IDH mutant, CNS WHO grade 4, was 37 (range: 23-79 years) and similar to patients with CNS WHO grade 2 or 3 tumors. Karnofsky performance status at diagnosis inversely correlated with CNS WHO grade (p&lt; 0.001). Despite more intensive treatment upfront with higher grade, CNS WHO grade was strongly prognostic: median overall survival was 22.2 years (95% n.a.) for grade 2, 8.1 years (95% 5.4-10.8) for grade 3 and 4.7 years (95% 3.4-6.0) for grade 4. Among patients with CNS WHO grade 4 astrocytoma, median overall survival was 5.5 years (95% 4.3-6.7) without (n=58) versus 1.8 years (95% 0-4.1) with (n=12) homozygous CDKN2A homozygous deletion. Reduced global DNA methylation as indicated by LINE-1 methylation levels was strongly associated with CNS WHO grade 4 (p&lt; 0.001) and poor outcome among IDH-mutant astrocytoma patients. MGMT promoter methylation status was not prognostic for overall survival.

CONCLUSIONS
The CNS WHO grade is prognostic in patients with IDH-mutant astrocytoma. CDKN2A homozygous deletion and reduced LINE-1 methylation levels are linked to CNS WHO grade 4 and associate with shorter survival. These data serve to inform on clinical trial designs, e.g., using IDH inhibitors, in this patient population.
PATH-30. GLIOMAS WITH FGFR ONCOGENIC ALTERATIONS: CLINICO-PATHOLOGICAL FEATURES, MANAGEMENT AND OUTCOMES IN PEDIATRIC, ADOLESCENT AND YOUNG ADULT PATIENTS.
Authors: Vanan Magimairajan Issai , Kakumanu Saranya , Pitz Marshall , Harlos Craig , Kazina Colin , McDonald Patrick , Drapeau Annie , Kaufmann Anthony , O'Carroll Aoife , Xu Qi , Drimes Tina , Bourne Cathy , Streilein Jessica , Sinha Namita 
Published: November 2023

Abstract

INTRODUCTION
Fibroblast growth factor receptor (FGFR1-4) pathway alterations are rare in pediatric cancers (1-3%) but are enriched in certain specific subtypes of difficult to treat pediatric and AYA brain tumors. Some of the common oncogenic alterations include structural variants (fusions, duplications), mutations and amplifications.

METHODS
We describe here the clinico-pathological features and therapeutic outcomes of pediatric and AYA patients (ages 0-39yrs) with FGFR pathway altered gliomas diagnosed in the past 10yrs (2013-2023). Data was collected from review of patient charts.

RESULTS
We identified 13 patients with gliomas harboring an oncogenic FGFR alteration. Median age at diagnosis was 16yrs (range, 6-30yrs) and was more common in males (M: F-3:1). Seizures were the most common presenting symptom (N=5/13, 38%); all of these patients had cortical tumors, which were resected and seizures were adequately controlled. A biopsy only approach was done in more than half (N=7/13, 54%) of the patients. Pathological diagnosis included low grade glio-neuronal tumors in all but one of the patients, who had a high-grade glioma (Pilocytic astrocytoma N=6, Diffuse astrocytoma N=2, glio-neuronal tumors N=2, PLNTY N=2). FGFR alterations included oncogenic fusions (FGFR1-TACC1=1, FGFR2-TACC1=1, FGFR2-CTNNA3=2, FGFR3-TACC3=1), tandem duplications (FGFR1-TKD-ITD=3) and mutations (FGFR1- N546K=2, K654E=1, K656E=2). Co-occurring mutations were seen in 4 patients (H3.3-K27M=1, PIK3CA-E545K=1, PTPN11-G503V=1, PTPN11-E69K=1). Patients with symptomatic residual tumors (N=6, 46%) were treated with targeted therapies (Erdafitinib=3, Trametinib=1, Ponatinib / Everolimus=1, Dasatinib=1) and two patients received Radiation therapy. Erdafitinib was discontinued in one patient due to intra-tumoral bleed. Rest of the patients are tolerating the targeted therapy well and all of the patients are alive.

CONCLUSION
In summary, cortical tumors bearing FGFR alterations present with refractory seizures and are eminently treatable with surgical resection. Targeted therapy with FGFR specific inhibitors is tolerated well and updated response assessment of our patients will be presented in the meeting.
PATH-35. SHIFTS IN GLIOMA PROGNOSTIC MOLECULAR FEATURES ACROSS THE LIFESPAN
Authors: Patel Ruchit , Ghosh Hia , Antonio Chiocca E , Reardon David , Wen Patrick , Santagata Sandro , Ligon Keith , Beroukhim Rameen , Bi Wenya Linda 
Published: November 2023

Abstract

INTRODUCTION
Epidemiological studies examining glioma prognostic features have consistently identified older age as a negative predictor of survival. Accumulation and co-occurrence of favorable or deleterious molecular alterations across the lifespan likely plays a role in the age-dependent variability seen in glioma patient outcomes.

METHODS
We assembled 4,297 molecularly and clinically annotated glioma patients from multi-institutional datasets and TCGA, with IDH1/2-mutation, MGMT-methylation, and chromosome 1p19q codeletion status assayed. Patient age was stratified: pediatric (&lt; 20 years), young adult (20-39 years), middle aged (40-64 years), and older adults ( &gt;65 years). Pairwise proportions were tested to study distribution of alterations across age as well as variability in assaying for MGMT-methylation.

RESULTS
4,297 patients with glioma were identified with molecular annotation of IDH1/2-mutation status (40.1% IDH1/2-mutant). Of assayed gliomas, 44.3% were MGMT-methylated and 13.9% had chromosome 1p19q codeletion. IDH1/2-mutation incidence decreased with age across all gliomas (85% in young adults, 35% middle aged, and 8% older adults) and in grade 4 gliomas (64% IDH1/2-mutation in young adults, 9% middle aged, and 2% older adults). 1p19q codeletion also decreased in incidence with increasing age (young adult 22%, middle aged 15%, older adults 6%). MGMT-methylation remained consistent across adult patients, between 43-50% across all gliomas. Interestingly, amongst the few patients &gt;65 years old with IDH1/2-mutation or 1p19q codeletion, 87% possessed co-occurring MGMT-methylation, significantly greater than young adults (54%, p&lt; 0.001). Consistent with this, 82% of patients &gt;65yrs with grade 4 IDH1/2-mutant gliomas had co-occurring MGMT-methylation. Despite the treatment response implication of MGMT-methylation, 72.2% of low-grade gliomas were not assayed for MGMT.

CONCLUSIONS
There is an age-dependent pattern of molecular alterations in gliomas, with the incidence of certain favorable prognostic signatures decreasing over time. Given the stability of MGMT-methylation across the age spectrum and grade, more widespread MGMT profiling may be beneficial to guide treatment decisions.