bluuebunny/crossref_metadata_2025_split huggingface dataset:
SDPS-44 RAPID DETECTION OF MUTATIONS IN CSF-CFTNA WITH THE GENEXUS INTEGRATED SEQUENCER
Authors: Arjuna Srividya , Shah Mauli , Dono Antonio , Pichardo Pavel , Nunez-Rubiano Luis , Zhu Jay-Jiguang , Riascos-Castaneda Roy F , Luthra Rajyalakshmi , Roy-Chowdhuri Sinchita , Duose Dzifa , Lang Frederick F , Esquenazi Yoshua , Ballester Leomar Y 
Published: August 2023

Abstract
Brain metastases commonly arise in patients with lung and breast carcinomas and pose distinctive clinical challenges. Genomic alterations are fundamental for diagnosis and therapy selection in cancer patients. However, the turn-around-time (TAT) of standard next generation sequencing (NGS) assays is a limiting factor in the timely delivery of genomic information for clinical decision making. The GenexusTM Sequencer automates the NGS workflow delivering results in less than 24hrs. The Oncomine Precision Assay (OPA) evaluates somatic mutations, copy number variations and fusions in hot-spot regions of 50 cancer-related genes. In this study, we evaluated genomic alterations in 46 cerebrospinal fluid (CSF) samples from 33 patients with metastatic lung cancer (mLC) (N=32) and metastatic breast cancer (mBC) (N=14) to the brain. Cell-free total nucleic acids, (cfTNA) were extracted using QIAamp Circulating Nucleic Acid kit with cfDNA concentrations ranging from 0.1-11.2(ng/ul) and 0.5-6.6 (ng/ul) for mLC and mBC samples, respectively. Median base coverage was 37,913X and 33,576.5X for mLC and mBC samples, respectively, with cfDNA input ranging from 2-20ng. Mutations were detected in 15/32 (46.8%) mLC and 8/14 (57.1%) mBC CSF samples. Among the samples with no mutations detected, 18/23 (78.2%) had suboptimal DNA input (&lt;20ng). The EGFR exon 19 deletion was detected in 4 samples from one patient, with increasing mutant allele fraction in CSF over time, highlighting the potential of CSF-cfTNA analysis for monitoring patients. Moreover, the EGFR T790M mutation was detected in a patient with prior EGFR inhibitor treatment. In addition, ESR1 D538G and ESR1::CCDC170 alterations, associated with endocrine therapy resistance, were detected in 2 mBC patients. The average TAT from cfTNA-to-results was ~16hrs. In summary, our results indicate that CSF-cfTNA analysis with the OPA in the Genexus instrument can provide clinically relevant information in patients with brain metastases with a short TAT.
SPCR-07 REDEFINING BOUNDARIES: STEREOTACTIC RADIOSURGERY FOR ENHANCED QUALITY OF LIFE AND SURVIVAL IN PATIENTS WITH 5-20 BRAIN METASTASES
Authors: Cialdella Fia , van Grinsven Eva , van der Boog Arthur , Nagtegaal Steven , Smid Ernst , Claes An , Kleynen Karin , Seravalli Enrica , Philippens Marielle , van Zandvoort Martine , Verhoeff Joost 
Published: August 2023

Abstract

INTRODUCTION
Brain metastases (BMs) occur in 10-30% of adult patients with cancer. The therapeutic approach for BMs depends on several factors including lesion number, location and size, primary cancer type, and the patient’s overall health. ASCO-SNO-ASTRO guidelines conditionally recommend stereotactic radiosurgery (SRS) for 1-10 BMs. The aim of this study was to investigate the outcomes of radiotherapy in patients with 5 or more BMs using SRS.

METHODS
We implemented the prospective Cohort for patient-reported Outcomes, Imaging and trial inclusion in Metastatic BRAin disease (COIMBRA) to examine all patients with BM(s) who underwent radiotherapy. In this sub-study we investigated overall survival (OS) and health related quality of life (HRQoL) for 47 patients with 5 to 20 BMs. We evaluated patients’ HRQoL using the EQ5D-VAS, at baseline and at 3 monthly intervals after radiotherapy.

RESULTS
Median OS was 21.3 months for patients with 5-10 BMs (n=38) and 12.5 months for patients with &gt;10 BMs (n=9). Questionnaires at both baseline and 6 months after radiotherapy showed stability or improvement on the EQ5D-VAS after radiotherapy in 58.1%. Additionally, independence in self-care was not limited before or after SRS. Also, the proportion of patients (66.7%) reporting no limitation on their ability to do daily activities remained stable after radiotherapy. Fewer patients reported pain or other discomfort after SRS compared to before (25% vs 40%).

CONCLUSION
Our findings suggest that radiotherapy may improve QoL in patients with 5-20 BMs. Furthermore, compared to the literature, we observed a prolonged OS in this prospective cohort, suggesting that SRS should be considered as the treatment option for these patients. These results highlight the need for further investigation of the role of SRS instead of Whole Brain Radiotherapy (WBRT) in the management of patients with multiple BMs.
SPCR-08 ACADEMIC READINESS AMONG CHILDREN TREATED FOR BRAIN TUMORS IN INFANCY
Authors: Silverman Melanie , Ashford Jason , Swain Michelle , Harder Lana , Carlson-Green Bonnie , Wallace Joanna , Kaner Ryan , Billups Catherine , Onar-Thomas Arzu , Merchant Thomas , Gajjar Amar , Conklin Heather 
Published: August 2023

Abstract

BACKGROUND
Children treated for brain tumors are more likely to have academic difficulties, receive special education services, and experience lower educational attainment than peers. Infants receiving treatment are at highest risk due to increased vulnerability of the developing brain and missed early developmental opportunities. The current study is the first to examine the emergence of academic readiness in children treated for brain tumors in infancy.

METHODS
Children were treated on a prospective, longitudinal multisite study with chemotherapy, with or without focal proton or photon radiation therapy (SJYC07). Academic readiness was monitored with the Bracken School Readiness Composite (SRC), and once age-appropriate, academic skills were assessed with the Woodcock Johnson III (WJII) word reading and applied math subtests. A subset of patients (n=70; median age at treatment 1.7 years; 67% male; 79% White) who completed the SRC during at least 2 timepoints were included.

RESULTS
Linear mixed models revealed SRC scores decreased significantly over time (p=0.033). There was a main effect of socioeconomic status (SES) such that lower SES predicted lower SRC scores, irrespective of time since treatment (p&lt;0.0001). Other demographic and clinical factors were not predictive (i.e., age at diagnosis, disease risk, resection extent, number of surgeries, chemotherapy vs photon irradiation vs proton irradiation, shunt status, tumor location; ps&gt;0.05). At the most distal assessment timepoint (median time since treatment 5.96 years), 28.8% and 20.3% scored below average (less than one standard deviation) on WJIII word reading and applied math, respectively; the former was significantly greater than normative expectations (16%, p=0.007).

CONCLUSIONS
Treatment for brain tumors in infancy appears to slow development of academic readiness skills, with SES predictive of risk and a disproportionate number of long-term survivors performing below age expectations in reading. These findings suggest the need for monitoring and interventions targeting early academic skills in this population.
SYST-18 BELZUTIFAN TREATMENT FOR PATIENTS WITH VON HIPPEL-LINDAU DISEASE–ASSOCIATED CENTRAL NERVOUS SYSTEM HEMANGIOBLASTOMAS ENROLLED IN THE PHASE 2 LITESPARK-004 STUDY
Authors: Narayan Vivek , Iliopoulos Othon , Iversen Ane B , Maughan Benjamin L , Beckermann Kathryn E , Oudard Stephane , Else Tobias , Maranchie Jodi K , Fu Wei , Perini Rodolfo F , Liu Yanfang , Linehan W Marston , Srinivasan Ramaprasad , Jonasch Eric 
Published: August 2023

Abstract
Previous results of the ongoing single-arm, phase 2 LITESPARK-004 (NCT03401788) study showed clinically meaningful antitumor activity with the HIF-2α inhibitor belzutifan for von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC), CNS hemangioblastomas, and other neoplasms. Adults with VHL disease diagnosis based on germline VHL alteration, ≥1 measurable RCC tumor, and no prior systemic anticancer treatment received belzutifan 120 mg orally once daily. End points included ORR, DOR, and PFS per RECIST v1.1; linear growth rate (LGR); and safety. CNS hemangioblastomas were assessed with measurable (≥1 cm) and/or nonmeasurable disease at baseline, which included associated cysts if present, or with measurable disease at baseline excluding associated cysts. Of enrolled patients, 50/61 (82%) had ≥1 CNS hemangioblastoma evaluable at baseline; 22/50 patients (44%) underwent ≥1 CNS-related surgery within 4 years before starting belzutifan treatment. Median follow-up for patients with CNS hemangioblastomas was 38.0 months (range, 36.1-46.1). ORR was 44% and DCR was 90%. Median DOR was not reached (NR; range, 3.7+ to 38.7+ months). Median PFS was NR (95% CI, 38 months-NR). After initiating belzutifan, median LGR for all evaluable patients was –1.6 mm/year (range, –7.0 to 3.1). A total of 25/50 patients (50%) had ≥1 measurable CNS hemangioblastomas, excluding any associated cysts. For these patients, ORR was 76% and DCR was 96%. Median DOR was NR (range, 3.7+ to 38.7+ months). Median PFS was NR (95% CI, 36 months-NR). After initiating belzutifan, median LGR was –1.1 mm/year (range, –3.9 to –0.1). Of all patients, 1/50 (2%) underwent a CNS-related surgery after starting belzutifan. Two patients (3%) discontinued treatment due to treatment-related adverse events. In summary, consistent and durable antitumor activity was observed in patients with CNS hemangioblastomas. Our data demonstrated that belzutifan induced the shrinkage of VHL disease-related CNS hemangioblastomas with or without the presence of associated cysts.
SYST-32 A NOVEL APPROACH TO TARGET TREG-MEDIATED IMMUNOSUPPRESSION IN GBM
Authors: Pant Ayush , Jain Aanchal , Jackson Christopher , Lim Michael 
Published: August 2023

Abstract
Macrophage inflammatory protein-3, or MIP-3α, is a chemokine that is highly expressed in gliomas, with expression progressively increasing with tumor grade. It is one of the top expressed genes in pseudopalisading and perinecrotic zones of glioblastoma (GBM) and as a chemokine, can greatly influence tumor-immune interactions. The receptor for MIP-3α, CCR6, is found on a variety of GBM-infiltrating immune subsets such as γδ T cells, conventional CD4 T cells and most notably, Tregs, which is disproportionately increased in GBM patients. Patients with lower CCR6-MIP3α gene signatures in tumors have improved overall survival and disease-free progression. We have found that circulating MIP-3α is also increased in the presence of intracranial glioma in mice, and can be normalized with immunotherapy. We note that ablation of CCR6 remarkably improves response of glioma-bearing mice to anti-PD-1 therapy. Mechanistically, we observed a reduction in regulatory T cell immunosuppressive phenotype with CCR6 ablation, which improves CD8 T cell effector function against tumor cells. Specifically, we found that CCR6 expression marks highly glycolytic Tregs, which is a known mechanism of immunosuppression of CD8 T cells, and that ablation of CCR6 from Tregs reduces their glycolytic capacity and immunosuppressivity. Targeting the CCR6:MIP-3α axis can therefore be a promising approach to alleviate CD8 T cell immunosuppression in GBM and to improve anti-tumor response.
TIPS-04 A RANDOMIZED, MULTI-INSTITUTIONAL PILOT STUDY TO EVALUATE THE MOLECULAR AND CELLULAR RESPONSE TO TREATMENT WITH NIVOLUMAB WITH EITHER ADJUVANT IPILIMUMAB OR RELATLIMAB IN ADULT PATIENTS WITH SURGICALLY RESECTABLE MELANOMA BRAIN METASTASES: ONGOING TRIAL
Authors: Pina Yolanda , Chen Ann , Tran Nam , Etame Arnold , Liu James , Furlan Andre Beer , Mokhtari Sepideh , Peguero Edwin , Li Jiannong , Law Vincent , Khushalani Nikhil , Smalley Inna , Vogelbaum Michael , Yu Michael , Arrington John , Macaulay Robert , Tawbi Hussein , Smalley Keiran , Forsyth Peter 
Published: August 2023

Abstract

BACKGROUND
Melanoma brain metastases (MBM) is a major cause of morbidity and mortality. The way melanoma malignant cells interact with the microenvironment in distal sites including the brain, plays a major role in tumorigenesis, metastasis, and tumor survival. Data supports the tumor microenvironment (TME) in MBM is different at the molecular/cellular level than the TME in other metastatic sites. Objectives: (1) to determine the safety and feasibility of presurgical administration of Nivolumab (Nivo) in combination with Ipilimumab (Ipi) or Opdualag (Nivo + Relatlimab [Rela]); and (2) to investigate the TME and estimate the immune cell population difference between the different treatment groups.

METHODS
We are carrying a randomized open label pilot study with adult patients (n=24) with MBM with surgically resectable brain tumors, who have not received treatment with immune-checkpoint inhibitors for six months or with BRAF/MEK inhibitors for 1 month, and on ≤3 mg/day dexamethasone or equivalent/day. Patients will be treated with either Nivo+Ipi, Opdualag, or no treatment pre-surgery (NCT05704933). Following treatment, all subjects will undergo surgical resection of their brain tumors and systemic disease biopsy, if clinically indicated. Post-surgery, all subjects will receive stereotactic radiosurgery (SRS) or fractionated SRS (fSRS), followed by Nivo+Ipi x4 dosages and adjuvant Nivo for 1 year or until disease progression and/or intolerable adverse events. All subjects will be on levetiracetam 500 mg twice a day or equivalent medication throughout the duration of the study. A lumbar puncture for CSF collection will be performed if clinically indicated and CSF and blood collected at different time points. Collected tissue will be send for sc RNA-seq, TCR/BCR seq. A one-way ANOVA will be used to compare the cellular population differences between treatment arms. CNS clinical response will be defined using RANO-BM and i-RANO. Trial is open and actively recruiting.
TIPS-11 EFFICACY AND SAFETY OF STUPP REGIMEN WITH OR WITHOUT ANLOTINIB FOR NEWLY DIAGNOSED GLIOBLASTOMA: INTERIM RESULTS OF A MULTICENTER, DOUBLEBLIND, RANDOMIZED PHASE II TRIAL
Authors: Chen Yuanyuan , Liu Guihong , Li Meihua , Wang Liang , Sun Pengfei , Chen Zhongping 
Published: August 2023

Abstract

BACKGROUND
Postoperative radiotherapy with concomitant temozolomide (TMZ) followed by ≤ six cycles of adjuvant TMZ chemotherapy (STUPP regimen) is the standard treatment for newly diagnosed glioblastoma (GBM) with limited effectiveness. Anlotinib inhibits both tumor angiogenesis and tumor cell proliferation by targeting multiple kinases, and showing promising results in preclinical GBM models and phase I clinical trials. We designed a phase II trial to verify the efficacy and safety of the STUPP regimen plus anlotinib (NCT 04959500).

METHODS
This is a multicenter, double-blind, randomized, placebo-controlled trial with an expected 150 patients randomly assigned 1:1 ratio to receive TMZ-based radiochemotherapy with anlotinib or placebo. Major eligibility criteria include histologically confirmed newly diagnosed GBM and an ECOG performance score ≤2. Other criteria for inclusion include age ≥18 years and lack of significant comorbidity. The primary endpoint is the median progression-free survival (PFS). Secondary endpoints include 1-year overall survival rate, PFS at 6 months, overall response rate, duration of response, disease control rate, quality of life, and toxicity.

RESULTS
From July 2021 to February 8th 2023, 147 patients were enrolled. The results in this abstract were all obtained without exposing the blind state. The median PFS was 9.9 months (95% CI, 9.5-11.9) in the overall patient population, while the predicted mPFS of placebo group was 7 months according to the results of STUPP and AVAGlio trials. Grade 1 (72.82%) and grade 2 (24.27%) adverse events (AEs) were mainly observed, while grade 3 or worse AEs accounted for 2.9% among all AEs. The most frequent TRAEs were lymphocytopenia, decreased platelet count, decreased white blood cell count, decreased neutrophil count and hypertension. Two death cases occurred due to COVID-19 and severe pneumonia.

CONCLUSIONS
Under the condition of data blinding, these interim results suggest that the STUPP regimen with anlotinib demonstrate potential promising efficacy and a tolerable safety.
TIPS-15 NEUROCOGNITIVE FUNCTION AND NEUROCOGNITIVE CONCERNS IN AN ONGOING PHASE III TRIAL OF PRE-OPERATIVE SRS VERSUS POST-OPERATIVE SRS FOR BRAIN METASTASES
Authors: Wefel Jeffrey , Noll Kyle , Rao Ganesh , Ferguson Sherise , Tawbi Hussein , Huse Jason , Johnson Jason , Court Laurence , O'Brien Barbara , Lang Frederick , Ejezie Lynette , Sullaway Catherine , Thomas Ashley , Suki Dima , Yeboa D Nana 
Published: August 2023

Abstract
In our ongoing phase III randomized trial (NCT03741673) evaluating risk of leptomeningeal disease (LMD) in patients with brain metastasis, patients are stratified by tumor size, location, and histology, and randomized to pre-operative SRS versus post-operative SRS. The primary endpoint is 1-year LMD-free rate, and exploratory endpoints include neurocognitive function (NCF). NCF is assessed prior to treatment and longitudinally (1.5, 6, and 12 months from the start of treatment) with the HVLT-R, TMT, and COWA yielding the Clinical Trial Battery Composite score (CTB COMP). Patients also complete the MDASI-BT, which includes a Cognitive Factor measuring patient reported cognitive concerns. Currently, 41 patients completed pre-treatment NCF baseline. Characteristics of patients with pre-treatment NCF baseline include mean (SD): age 60.0+/-11.7 years, 2.6+/-2.2 metastases, 15.2+/-10.1 cc brain metastases volume, median KPS 90 (range: 70-100), 83% white, 52% male, and 50% received AEDs at time of surgery. The most common primary cancers among this cohort were: 31% NSCLC, 19% RCC, 14% melanoma, 7% breast, 2% thyroid, and 26% other. Mean (SD) NCF z-scores ranged from z= -0.09 (1.08) to -3.09 (6.13), CTB COMP z=-1.13 (1.65), and the mean (SD) MDASI-BT Cognitive Factor score was 1.1 (1.3). Using multivariable linear regression including CTB COMP, MDASI-BT Cognitive and Affective Factor, KPS, number of and intracranial volume of metastases, only intracranial volume of metastases was statistically significantly associated with CTB COMP (B=-.058, p=.034) and only the MDASI-BT Affective Factor was statistically significantly associated with the MDASI-BT Cognitive Factor (B=.305, p=&lt;.001). At baseline, disease factors such as tumor burden appear to be the primary driver of objectively measured neurocognitive dysfunction and mood factors appear to be the primary driver of subjective patient reported neurocognitive concerns. This has important implications for interpretation of these different clinical outcome assessments in clinical trials measuring objective neurocognitive function and subjective neurocognitive concerns.
TIPS-22 A TWO-PART, PHASE 1 STUDY OF RHENIUM (186RE) OBISBEMEDA (186RNL) DELIVERED BY CONVECTION ENHANCED DELIVERY (CED) FOR RECURRENT, REFRACTORY, OR PROGRESSIVE CHILDHOOD EPENDYMOMA AND HIGH-GRADE GLIOMA (HGG)
Authors: Plant Ashley , DeCuypere Michael , Lam Sandi , Quijano Carla , Bao Ande , Moore Melissa , LaFrance Norman , Hedrick Marc , Brenner Andrew , Michalek Joel 
Published: August 2023

Abstract
INTRODUCTION: Childhood ependymoma and HGG are difficult tumors to treat. Recurrent ependymoma is treated with re-resection and multiple rounds of EBRT. HGG is treated with chemoradiation followed by clinical trials, if available. While EBRT remains a central component of management, it is limited by tolerance of the surrounding normal brain tissue. 186RNL permits the selective delivery of beta-emitting radiation with excellent tumor retention. In an adult Phase 1/2 trial for recurrent glioblastoma (NCT01906385), the mean absorbed dose to the tumor was ~300-500 Gy, markedly higher than absorbed doses typically delivered by EBRT. Despite this, no dose-limiting toxicity was observed, and no treatment-related serious adverse events have occurred. Here, we describe the first pediatric trial using a two-part, Phase 1 dose-finding study followed by expansion cohorts to explore efficacy. Enrolling subjects will be 6 to 21 years of age with a diagnosis of recurrent ependymoma or HGG. Subjects will be allowed to enroll either if they have exhausted standard of care options or if they are clinically stable and surgical resection can be deferred by 4 weeks. Part 1 will enroll up to 24 subjects to determine the maximum feasible dose (MFD) of 186RNL administered by CED. Tumor size and concentration of infusate will be escalated in each cohort (A-D) to a maximum tumor diameter of 6 cm (114.1 mL) and a concentration of 2mCi/ml. Up to 4 CED catheters will be used. Part 2 will independently evaluate 186RNL in 2 different expansion cohorts: Cohort 2A: recurrent ependymoma; Cohort B: recurrent HGG. The primary endpoint for Cohort 2A is overall response rate (ORR) by Radiographic Assessment in Pediatric Neuro-Oncology (RAPNO) criteria and the primary endpoint for Cohort 2B is progression free survival. Planned enrollment will begin in early 2023.
TIPS-23 SAFETY AND FEASIBILITY RESULTS FROM A PHASE 1/2 CLINICAL TRIAL OF RHENIUM (186RE) OBISBEMEDA (186RNL) IN RECURRENT GLIOMA: THE RESPECT-GBM TRIAL
Authors: Brenner Andrew , Patel Toral , Youssef Michael , Bao Ande , Phillips William , Hedrick Marc , Moore Melissa , LaFrance Norman , Weinberg Jeffrey , Floyd John , Michalek Joel 
Published: August 2023

Abstract

OBJECTIVES
186RNL is BMEDA-chelated 186Re encapsulated in nanoliposomes. 186Re’s ~2 mm beta emission path length provides direct delivery of radiation therapy while sparing surrounding healthy tissue. 186RNL is delivered via convection enhanced delivery (CED) to achieve durable, localized tumor retention with high absorbed radiation doses. We present results from our ongoing ReSPECT-GBM trials (NCT01906385).

METHODS
ReSPECT-GBM is a multi-center, sequential cohort, open-label, dose escalation, Phase 1/2 clinical trial in adults with recurrent glioma to evaluate the safety, tolerability, and activity of a single dose of 186RNL administered by CED. Following computer-assisted MRI guidance treatment planning for CED catheter placement, patients received a single administration of 186RNL before whole body planar and SPECT/CT imaging for dosimetry and distribution. Patients were followed for safety, progression, and survival.

RESULTS
25 patients across 8 dosing cohorts including 23 with recurrent GBM were treated with a single dose of 186RNL ranging from 1.0-41.5mCi. Average absorbed radiation dose (AARD) to the tumor was ~300 Gy over a wide range. Exposure outside the brain was negligible. A single dose of 186RNL was well-tolerated, with no dose limiting toxicities. No patient had treatment-related death or withdrawals and most AEs mild or moderate (Grade 1 or 2) and non-serious. 5 patients remain alive. mOS for all patients was &gt;12 months, with an OS30 of 25% overall and 50% for those receiving &gt;100Gy. Cox Proportional Hazards Ratio and Accelerated Failure Time modeling both demonstrate absorbed dose and percent tumor treated to significantly correlate with overall survival (p&lt;0.003-0.0001). Five patients have subsequently enrolled in Phase 2 and all are alive.

CONCLUSION
A single dose of 186RNL in recurrent glioma patients achieves high absorbed doses without significant toxicity, is well tolerated, and shows favorable OS. Cohort 8 and Phase 2 continue enrolling. Development progress and data will be reported.
Nursing Education as a Key Strategy to Combat Ageism: Preparing Nurses to Proactively Dismantle Their Own Ageist Views as Well as Ageist Practices Within Health Care Settings
Authors: Tweedie Jeanine 
Published: August 2023

Abstract
The prevalence of ageism in health care prevents nurses from providing the best care to older adults. Nursing education can prepare nurses to proactively dismantle their own ageist views as well as ageist practices within health care settings. Active learning strategies, such as role-play and case studies, can be used to teach nurses how to become anti-ageism advocates and improve the quality of health care for older adults.