bluuebunny/crossref_metadata_2025_split huggingface dataset:
RADT-25. IMPACT OF SAME-DAY MASK CREATION ON GAMMA KNIFE TREATMENT
Authors: Mizrachi Mark , Hartley Benjamin , Hintz Eric , Goenka Anuj , Schulder Michael 
Published: November 2024

Abstract

OBJECTIVE
Technological advances have allowed stereotactic radiosurgery (SRS) to be administered using fixation with a noninvasive mask, rather than with a stereotactic frame. While the use of such masks offers advantages including the ability to hypofractionate SRS and improved patient comfort, there has been criticism that it eliminates the possibility of same-day, “wheels in to wheels out” SRS. Our study examines the feasibility of conducting mask fitting and SRS treatment on the same day versus the conventional different-day approach.

METHODS
Eligible participants had either underwent single-fraction-SRS (SF-SRS) or were in their initial session of hypofractionated-SRS (HF-SRS). 100 patients who underwent SRS from September 2020 to June 2021 were assessed. 52 patients underwent same-day fabrication and treatment, and 48 patients received treatment at least one day following mask fabrication. The Leksell Gamma Knife (LGK) console data was processed, and operator reports from each patient were extracted and analyzed.

RESULTS
The average number of pauses, pause time, and number of gates was greater for same-day patients. There was no significant difference in the number of positioning alarms between the groups. There were no significant differences in percent overestimation of treatment time or number of treatment alarms. Treatment gates occurred on average 19 minutes earlier for same-day patients then different-day patients, which likely corresponds to “mask fatigue,” due to spending 20 minutes longer on the treatment table, while the masks are being fabricated.

CONCLUSION
Mask-based SRS can be done safely and efficiently in a single day, mirroring the approach of frame-based treatments.
RADT-27. REPORT OF 9 CASES OF EMBRYONAL TUMORS OF THE CENTRAL NERVOUS SYSTEM WITH MULTILAYERED ROSETTES (ETMR)
Authors: Ai Ruyu , Li Juan , Lai Mingyao , Cai Linbo 
Published: November 2024

Abstract

OBJECTIVE
Embryonal Tumors of the Central Nervous System with Multilayered Rosettes (ETMR) are rare, and there’s no standard treatment protocol. This article reports on the current treatment status and prognosis of ETMR in our hospital.

METHODS
We retrospectively collected patients with ETMR who received treatment in the Oncology Department of Guangdong sanjiu Brain Hospital from January 2017 to January 2021, analyzed their clinical data.

RESULTS
Among 31 cases of central nervous system embryonic tumors (excluding medulloblastoma and ATRT), 9 (29.03%) were ETMR. The median age at diagnosis was 3 years old (1-15), and the male to female ratio was 4:5. Among them, 5 cases were accompanied by C19MC gene variation. Tumor location:6 was in supratentorial, 1 in the pineal region, 1 in the pons, 1 in the cerebellopontine. Eight patients underwent surgical resection at the first diagnosis, with 6 cases of total resection, 1 case of partial resection, and 1 case of biopsy. One case was misdiagnosed as a germinoma in the pineal region at the initial. After recurrence, surgical resection was performed to confirm the pathology as ETMR. One case was misdiagnosed as glioblastoma during the first surgery. The initial treatment for 4 patients after surgery was radiotherapy combined with concurrent chemotherapy. Recurrence patterns: 2 cases were intracranial dissemination, 2 cases were local recurrence, 1 was spinal cord dissemination. One patient did not receive treatment after surgery and tumor recurrence 3 months later. Survival analysis: The median survival time was 20 months. The 1-year progression-free survival rate (PFS) and overall survival rate (OS) were 22% and 61%, and the 2-year overall survival rate (OS) was 31%.

CONCLUSION
ETMR has a low incidence and poor prognosis. It is easy to misdiagnose and NGS is necessary to assist diagnosis when needed. More effective treatment methods need to be explored.
RADT-36. FUNCTION-ADAPTED RADIOTHERAPY PLANNING IN THE MANAGEMENT OF HIGH-GRADE GLIOMAS: A COMPARING STUDY FOR DOSE SPARING OF SPEECH-ELOQUENT BRAIN AREAS
Authors: Diehl Christian D , Troendle Malin L , Stefanowicz Sarah , Misslbeck Martin , Kram Leonie , Schwendner Maximilian , Ille Sebastian , Meyer Bernhard , Combs Stephanie E , Krieg Sandro M 
Published: November 2024

Abstract

BACKGROUND
Radiotherapy (RT) for brain tumors can induce injury of functional white matter tracts. In neurosurgery navigated transcranial magnetic stimulation (nTMS)- and diffusion tensor imaging (DTI)-based fiber tracts (FT) is an established tool to protect functional FT during tumor resection. We investigated it´s applicability in RT planning with the aim of dose reduction of language-associated fiber tracts.

METHODS
Preoperative, nTMS-generated and DTI-based FT of the functional left hemispheric language network of patients with language-eloquent malignant gliomas (WHO III/IV) were imported into the planning software (ARIA®) according to the DICOM standard and contoured as a risk structure. Brain shift after tumor resection was compensated using elastic fusion (Brainlab®). The treatment plans were optimized or recalculated with the aim of reducing the dose to the fiber tracts outside the planning target volume (PTV). The dosimetric evaluation was performed according to dose volume histogram parameters.

RESULTS
RT plans of 27 patients were retrospectively evaluated in the study. The mean dose (Dmean) to the fiber tracts was 37.3+/-11.8 Gy, with plan optimization dose was 33.6 +/- 12.2 Gy (-10.9% p&lt;0.01), within the 20 Gy isodose the dose reduction to be achieved was on average - 25.0% (range 0-48.5%). The V54Gy and V20Gy were on average 40.2 +/- 23.7% and 72.3 +/- 21.1% compared to 38.2 +/- 23.5% and 58.1 +/- 23.7% (both p&lt;0.01) with optimization. The Dmean of the PTV did not change (59.8 Gy vs. 59.8 Gy (p=0.5)), nor did the dose homogeneity (HI, (D5-D95)/Dp)(p=0.63)). The dose exposure of the organs at risk was within the specified dose constraints.

CONCLUSION
This study showed that (nTMS)- and diffusion tensor imaging (DTI)-based fiber tractography could be used in radiotherapy planning to spare language-eloquent brain areas without having to accept dose reductions within the PTV. Whether the concept of tract-based sparing of language function brings clinical benefits to patients needs to be further investigated in prospective studies.
RADT-38. CLINICAL, MOLECULAR AND IMAGING FEATURES ASSOCIATED WITH LONG TERM SURVIVAL IN GLIOBLASTOMA PATIENTS
Authors: Sharif Muhammad , Andrews Carrie , Shah Sophia , Haldar Nilanjan , Cappelli Louis , Zhan Tingting , Alnahhas Iyad , Shi Wenyin 
Published: November 2024

Abstract

INTRODUCTION
Glioblastoma (GBM) is the most common malignant brain tumor in adults and has poor prognosis despite standard of care treatment. Nevertheless, certain patients surpass survival expectations. This study seeks to identify the clinical, molecular, and imaging characteristics of GBM associated with extended patient survival.

METHODS
In this retrospective cohort study, we examined records of adult GBM patients (WHO 2016 classification) treated at Thomas Jefferson University Hospital from 2010 to 2023. Exclusion criteria included a preoperative Karnofsky Performance Status (KPS) below 60 and treatment with hypo-fractionated radiation therapy. Patients were categorized into two groups: short-term survivors (STS), who survived less than 36 months from diagnosis, and long-term survivors (LTS), who survived more than 36 months. We reviewed patient charts and pathology reports for comprehensive clinical and molecular data. For radiomics analysis, tumor segmentation was performed using CaPTk software on the initial diagnostic MRI (T1 pre and post-contrast, FLAIR and T2 sequences). The relationship between overall survival of more than three years was analyzed with univariable logistic models for potential predictors using R statistical software.

RESULTS
Of the cohort of 210 patients, 37 (17.6%) survived beyond three years. The median age at diagnosis was 55 years (range; 29-79) Twenty-two patients were male and 15 were female. Twenty-two percent had IDH mutation and 65% had MGMT methylation. Factors associated with long-term survival included younger age at diagnosis (p =0.007), MGMT hypermethylation (p =0.019), IDH mutation (p=0.001), absence of TERT mutation (p = 0.002), higher average number of adjuvant temozolomide cycles (10 vs. 5; p = 0.005), and smaller volume of enhancing tumor on T1 post-contrast imaging segmentation (p=0.022). But there was no significant difference in FLAIR abnormality or necrotic core volumes between the groups.

CONCLUSION
In our cohort of GBM patients, patients diagnosed at a younger age, MGMT hypermethylation, IDH mutation, absence of TERT mutation, receiving more cycles of adjuvant temozolomide treatment, and smaller enhancing tumor volume on preoperative T1 post-contrast imaging were associated with longer survival. Future research involving larger cohorts and validation of our findings is needed.
RADT-46. RADIOSURGERY DOSE REDUCTION FOR BRAIN METASTASES ON IMMUNOTHERAPY (RADREMI):A PROSPECTIVE PILOT STUDY
Authors: Curtis Charles , Weisman Michael , McClelland Shearwood , Rhome Ryan , Anthony Paul , Agrawal Namita , Lautenschlaeger Tim , Zellars Richard , Kamer Aaron , Hanna Nasser , Zang Yong , Boyd LaKeisha , Shiue Kevin 
Published: November 2024

Abstract

BACKGROUND
The combination of immunotherapy and single-fraction stereotactic radiosurgery (SRS) for treatment of metastatic brain disease has yielded symptomatic radiation necrosis rates as high as 16%. The aim of this study was to evaluate the toxicity of dose reduced stereotactic radiosurgery (SRS) in patients receiving concurrent immune checkpoint inhibitors (ICI).

METHODS
RADREMI is a prospective, single arm, phase 1 pilot study evaluating adults with 1-10 brain metastases on MRI receiving ICI within 30 days of treatment. SRS was delivered using dose reduction: 18 Gy for lesions 0-2 cm, 14 Gy for lesions 2.1-3 cm, and 12 Gy for lesions 3.1-4 cm. Patients were evaluated at 6-months with regard to symptomatic radiation necrosis, defined as a 6-month rate of clinical symptomatology requiring steroid administration, bevacizumab, and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis.

RESULTS
Between 2019 and 2023, 18 eligible patents were entered with 12 evaluated. All patients were treated within the 18 Gy cohort. The median follow up was 13.82 months. The median number of brain metastases treated was 1.5 (inner quartiles 1, 3) with up to 7 lesions treated. The proportion of patients who experienced symptomatic radiation necrosis by 6 months was calculated with the 95% confidence interval tested against a historical proportion of 16%. The incidence of symptomatic radiation necrosis at 6 months was 1 of 12 (0.083; 95% CI: 0.002, 0.385; p-value 0.234) following SRS.

CONCLUSIONS
Our findings of dose reduced SRS with concurrent ICI unfortunately did not have statistical significance regarding symptomatic radiation necrosis. This was likely due to the small number of evaluable patients. The secondary endpoint of local control is currently under review. Dose reduced SRS with concurrent ICI warrants further studies to evaluate toxicity and local control.
CTIM-02. PIONEERING QUAD-TARGETING CAR T CELL THERAPY IN PEDIATRIC CNS TUMORS – ANALYSIS FROM THE INITIAL PATIENTS TREATED ON THE FIRST-IN-HUMAN PHASE 1 TRIAL BRAINCHILD-04
Authors: Ronsley Rebecca , Seidel Kristy , Narayanaswamy Prabha , Pattabhi Sowmya , Wendler Jason , Ho On , Rawlings-Rhea Stephanie , Gust Juliane , Huang Wenjun , Crotty Erin , Leary Sarah , Runco Daniel , Hauptman Jason , Gardner Rebecca , Park Julie , Annesley Colleen , Jensen Michael , Vitanza Nicholas 
Published: November 2024

Abstract

BACKGROUND
BrainChild-04 is a first-in-human clinical trial of quad-chimeric antigen receptor (CAR) T cell therapy for children and young adults with central nervous system (CNS) tumors. This trial administers repeated locoregional CAR T cells targeting B7-H3, EGFR, HER2, and IL-13Ralpha2 (“quad-CAR T cells”), leveraging multi-antigen targeting to address the tumor heterogeneity of high-grade CNS tumors.

METHODS
The primary endpoints are feasibility and safety, and secondary endpoints are disease response and correlative studies of CAR T cell activity. The trial utilized a Bayesian Optimal Interval (BOIN) statistical design with three planned dose regimens(DR). There are 2 arms with weekly delivery for 3 weeks of a 4-week cycle:(A) –diffuse intrinsic pontine glioma (DIPG), (B) –non-pontine diffuse midline glioma (DMG) or other relapsed CNS tumors.

RESULTS
Enrolled patients include DMG N=6, DIPG N=5, other CNS tumors N=4. Of the 15 enrolled patients, 7 have been infused with 8 awaiting infusions. A total of 33 intracranial CAR T doses have been delivered, including Arm A DR 1 (N=1), Arm B DR 1 (N=3), DR2 (N=3). The most common adverse events have been grade 1-2 fever (7/7 patients), grade 1-3 headache (6/7), and grade 1-2 nausea/vomiting (6/7). There have been no DLTs and no cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity (ICANS). CTCAE and tumor inflammation-associated neurotoxicity are both being captured. All treated patients are alive with median follow up time post-initial infusion of 93(14-198) days. CAR T cells were detected by flow cytometric analysis of CSF post-infusion in 14/24 CSF samples. Radiographic response, CSF circulating tumor DNA, targeted mass spectrometry, and cytokine analysis will be presented.

CONCLUSIONS
Our preliminary experience suggests tolerability of locoregional delivery of quad-CAR T cells at doses currently evaluated. The trial remains ongoing and these data support continued evaluation of this product to better assess anti-tumor activity in patients with CNS tumors, including DIPG/DMG.
CTIM-06. OUTCOME OF PATIENTS WITH RECURRENT MEDULLOBLASTOMA AND EPENDYMOMA TREATED WITH PEMBROLIZUMAB, AN IMMUNE CHECKPOINT INHIBITOR: A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY (PBTC045)
Authors: Hwang Eugene , Kilburn Lindsey , Mitchell Duane , Lin Tong , Poussaint T Y , Robinson Giles , Gajjar Amar , Lenzen Alicia , Dorris Kathleen , Robison Nathan , Fangusaro Jason , Fouladi Maryam , Onar-Thomas Arzu , Dunkel Ira 
Published: November 2024

Abstract

BACKGROUND
Children with recurrent medulloblastoma and ependymoma typically have a dismal prognosis. Immune checkpoint blockade has revolutionized treatment of some resistant cancers. PBTC045 is a safety and preliminary efficacy study of pembrolizumab, a PD-1 inhibitor, in children with recurrent/progressive brain tumors. Here we present the strata that included children with recurrent/progressive ependymoma and medulloblastoma.

METHODS
Eligibility included patients aged 1-21 years old with recurrent/progressive ependymoma or medulloblastoma and with functional scores ≥70, no greater than physiologic steroid usage and standard washout periods, among other eligibility criteria. Pembrolizumab was administered at 2mg/kg IV every three weeks. Tumor tissue (if available) and serum were collected for correlative studies. Primary endpoints included toxicity and response, and two stages were planned requiring objective responses for potential expansion.

RESULTS
Patients with progressive ependymoma (Stratum D, n=13) or medulloblastoma (Stratum E, n=14, one ineligible) were enrolled. The median age at diagnosis was 3.37 years (range, 1-12.7) and 7 years (range, 2.2-13.1), respectively. The median age at study entry was 8.5 years and 11.4 years, respectively. There were no first-stage objective responses in either stratum, and thus the expansion arms were not initiated. Grade 3 or greater treatment-related adverse events included rash (n=1), anemia (n=1) and neutropenia (n=2), with no dose-limiting toxicities. The median progression-free survival (PFS) for ependymoma and medulloblastoma were 1.38 months (range, 1.08-1.51) and 1.41 months (range, 1.22-3.45), respectively. Immune correlative analyses are ongoing.

CONCLUSIONS
Immune checkpoint inhibition holds potential for CNS cancer treatment, and as a single agent, is well tolerated. However, in the current study, checkpoint inhibition monotherapy does not appear to significantly prolong survival or induce radiographic responses in children with recurrent/progressive ependymoma or medulloblastoma. Potential incorporation of checkpoint inhibitors into treatment for these patients will likely require combinatorial approaches that may be informed by the correlative science.
CTIM-08. FIRST IN HUMAN STUDY OF THE MRNA-BASED CANCER VACCINE CVGBM IN PATIENTS (PTS) WITH NEWLY-DIAGNOSED AND SURGICALLY RESECTED MGMT-UNMETHYLATED GLIOBLASTOMA (GBM): FIRST RESULTS FROM THE DOSE ESCALATION PHASE
Authors: Tabatabai Ghazaleh , Freres Pierre , Glas Martin , Hau Peter , von Baumgarten Louisa , van Den Bent Martin , Burger Michael C , Seidel Clemens , Herrlinger Ulrich , Mildenberger Iris , Neyns Bart , Schafer Henning , Wick Antje , Falk Martin , de Chama Laura Leticia Freitas , Kelemen Peter , Schwenke Frauke , Koch Sven D , Roche Paula Romer , Gnad-Vogt Ulrike 
Published: November 2024

Abstract

INTRODUCTION
CVGBM is an investigational therapeutic mRNA-based vaccine encoding 8 epitopes derived from tumor associated antigens with potential relevance in GBM. This is an ongoing, first-in-human study evaluating the safety of CVGBM in pts with newly-diagnosed MGMT-unmethylated GBM.

METHODS
HLA-A*02:01-positive pts with newly-diagnosed MGMT-unmethylated GBM (CNS WHO Grade [Gr] 4) who had a gross total or partial resection and completed radiotherapy ± concomitant temozolomide received CVGBM on Days 1, 8, 15, 29, 43, 57 and 71 + 6 optional doses at 6-week intervals. Primary endpoints are safety, tolerability and dose-limiting toxicities (DLTs). Immunogenicity is an exploratory endpoint.

RESULTS
As of 29/2/2024, 16 pts were enrolled in the dose-escalation part (Part A); 3 each in DL 1 (12 µg), DL 2 (25 µg), and DL 3 (50 µg), and 7 in DL 4 (100 µg). For all cohorts, mean time on study from 1st dose to last visit was 4.5 months (min: 1.5; max: 8). 109 doses were administered (mean: 6.8 doses per pt). All pts completed the 2-week DLT evaluation period without DLTs. Of 156 treatment-emergent adverse events (TEAEs), the majority (73%) were CTCAE Gr 1 (21% Gr 2, 6% Gr 3). The most common related TEAEs were chills (n=13), pyrexia (n=12), headache (n=12), fatigue (n=11) and malaise (n=5), mostly of mild to moderate severity. 7 pts had 9 ≥ Gr 3 AEs assessed as potentially related to CVGBM by the investigators outside the DLT period (cerebral edema [n=2], leukoencephalopathy, pseudoprogression with cerebral edema, structural epilepsy, ataxia, hypertension, malaise and fever [1 of each]), evenly distributed across cohorts. First immunogenicity data are planned to be presented.

CONCLUSIONS
CVGBM was generally well tolerated with an acceptable safety profile. The highest tolerated dose was not reached. Based on all available safety data, the selected dose for trial expansion was 100 µg. Previously presented at ESMO 2024, “FPN (Final Publication Number): 4400, Ghazaleh Tabatabai et al. - Reused with permission.
CTIM-18. HIGH LEVEL OF MUTATIONAL LOAD AND DIVERSITY OF TUMOR INFILTRATING T LYMPHOCYTES ARE FAVORABLE PROGNOSTIC MARKERS FOR CANCER SURVIVAL IN CHILDREN WITH RECURRENT MEDULLOBLASTOMA DURING ADOPTIVE CELLULAR THERAPY
Authors: Yegorov Oleg , Yang Changlin , Stratford Yanina , Mitchell Duane 
Published: November 2024

Abstract

BACKGROUND
Adoptive cellular therapy (ACT) has shown remarkable efficacy in some patients with solid tumors, resulting in durable complete responses. A key mechanism behind this success is the targeting of neoantigens by T cells. There is culminating evidence that tumor-infiltrating lymphocytes (TILs) have a major effect on the clinical attributes of human cancer and can influence the tumor response to various therapy regimens. We have been sequencing RNA isolated from patient’s tumors to evaluate their mutational burden and identify tumor-specific neoantigens. Additionally, we have identified the entire repertoire of tumor-infiltrating lymphocytes in patients with recurrent medulloblastoma.

METHODS
Total tumor RNA was extracted from resected brain tumor specimens and after we applied in-house bulk RNA-Seq and TCR-Seq techniques using rapid amplification of cDNA ends (RACE) technology with the addition of a common adapter at the 5’ end.

RESULTS & CONCLUSIONS
Analysis of the 22 tumor tissues revealed that the frequency of non-synonymous mutations varied dramatically more than 10-fold among patients with recurrent medulloblastoma undergoing adoptive cellular therapy (Re-MATCH protocol, FDA IND BB-14058). Patients with shorter overall survival exhibited non-synonymous mutation frequencies between 0.113 and 0.335 mutations per megabase (Mb). Children with prolonged overall survival had higher mutation frequencies, ranging from 0.6 to 1.1 mutations per Mb. These findings highlight the potential of using mutational burden as a biomarker for patient selection and treatment customization, ultimately aiming to improve outcomes in ACT for recurrent medulloblastoma. Up to 2000 unique TCR clones were found among TIL populations in patients who responded well to ACT. Patients with poor outcomes had significantly lower TCR diversity, with only 10-40 unique TCR clones among TILs. The correlation between TCR diversity among TILs and clinical outcomes in pediatric brain tumors underscores the importance of a diverse T cell repertoire for the success of ACT.
CTIM-20. IDENTIFYING CANDIDATE ANTIGEN TARGETS FOR PEDIATRIC BRAIN TUMOR IMMUNOTHERAPIES THROUGH COMPREHENSIVE IMMUNOGENOMIC ANALYSIS
Authors: Yang Changlin , Trivedi Vrunda , Yegorov Oleg , Mitchell Duane 
Published: November 2024

Abstract

BACKGROUND
Identifying tumor rejection antigens continues to be a significant challenge in the development of effective immunotherapies and their application to pediatric brain tumors.

METHODS
To identify candidate antigen targets for Medulloblastoma (primary MB, n=170; recurrent MB, n=21), Diffuse Intrinsic Pontine Glioma (DIPG, n=10), and Pediatric High-Grade Astrocytoma (HGA, n=12) for adoptive cellular therapy, we conducted a comprehensive immunogenomic analysis of the transcription profiles of the most aggressive pediatric brain tumors and performed in silico antigen prediction across a wide range of antigen classes.

IMPORTANCE OF THE STUDY
Pediatric brain tumors are heterogeneous diseases, and current standard treatments do not adequately address this variability. Newer and safer patient-specific treatment approaches are needed for high-risk patients who do not respond to standard therapies. Cellular immunotherapy could be crucial for improving survival and reducing morbidity. For an effective immune response against these brain tumors, appropriate tumor antigens must be targeted. While subgroup-specific genetic mutations in medulloblastoma patients have been reported, the immunogenicity of these genetic alterations remains unknown. Using a custom antigen prediction pipeline, we identified potential tumor rejection antigens with significant implications for the development of cellular therapies for MB, DIPG, and HGA.

RESULTS
Antigen prediction analysis revealed that most patients express few candidate neoantigen targets that pass all filtering criteria. Overall, the proportion of predicted tumor-associated antigens (TAAs) was higher than that of neoantigens and gene fusions for all molecular subtypes, except for SHH, which exhibited a higher neoantigen burden. Notably, cancer-testis antigens and previously unrecognized neurodevelopmental antigens were found to be expressed in most patients across all medulloblastoma subgroups. Although the absolute immune cell content is predicted to be low, immune gene-signature analysis revealed subgroup-specific differences.