bluuebunny/crossref_metadata_2025_split huggingface dataset:
CSIG-29. CLINICAL AND TRANSCRIPTOMIC DATASET IDENTIFIES LARGE CHANGES IN IMMUNE AND HORMONAL SIGNALING AMONGST RECURRENT PATIENTS WITH CRANIOPHARYNGIOMA
Authors: Joshi Nikhil , Crowley Julia , Mccormack Shana , Malbari Fatema , Kraya Adam , Kline Cassie 
Published: November 2023

Abstract

INTRODUCTION
Craniopharyngioma is a low-grade suprasellar brain tumor that often produces deficiencies of pituitary hormones, including growth hormone. Although epidemiological data are reassuring that growth hormone does not lead to craniopharyngioma recurrence, the theoretical risk is cause for concern. To address this and other questions related to the care of individuals with recurrent craniopharyngioma, we analyzed gene expression in craniopharyngiomas in the context of clinical data. We envision insights that could guide decisions about hormone replacement and tumor-focused treatment alternatives.

METHODS
Clinical information was abstracted for a cohort of individuals diagnosed with craniopharyngioma at the Children’s Hospital of Philadelphia between 2016 - 2020. In parallel, tumor transcriptomic data for patients with craniopharyngioma were collected from the Children’s Brain Tumor Network (CBTN) and matched to clinical data where applicable. Bulk RNA-sequencing analysis, pathway analysis, and immune deconvolution (xCell) of samples was performed in R to identify transcript-level changes that distinguish recurrent from initial craniopharyngioma.

RESULTS
CBTN data was available for 54 initial tumor samples and 17 recurrent tumor samples, with matched clinical data available for 33 samples (26 initial, 7 recurrent). We did not find differences in clinical characteristics between individuals with versus without recurrence. Pathway analysis notably suggested altered levels of antigen presentation (NES: 2.97), Programmed cell death (NES: 2.34), WNT signaling (NES: 1.97), and Growth Hormone Signaling (NES: -1.277) amongst recurrent samples when compared against initial samples. Deconvolution of samples showed altered levels of M2-like macrophages (39.2% increased) and CD4+ T-helper-2 cells (-54.7% decreased) in recurrent samples compared against initial samples. Preliminary work is being completed to frame these results in the context of available clinical neuroendocrine data.

CONCLUSION
This work highlights marked changes in immune and hormonal signaling in samples from recurrent craniopharyngioma tumors. These insights have potential therapeutic implications that deserve further investigation.
CSIG-33. A 2ND GENERATION IDO1 PROTEIN DEGRADER TO OVERCOME NON-ENZYME-MEDIATED IDO1-DEPENDENT IMMUNE SUPPRESSION FOR GLIOBLASTOMA
Authors: Bommi Prashant , Monsen Paige , Lauing Kristen , Zhai Lijie , Barton Kevin , Borys Ewa , Anderson Douglas , Prabhu Vikram , Thakkar Jigisha , Lukas Rimas , Schiltz Gary , Wainwright Derek 
Published: November 2023

Abstract
Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive rate-limiting enzyme that metabolizes the essential amino acid, tryptophan (Trp), into the downstream catabolite, kynurenine. IDO1 is expressed in &gt;90% of patient-resected glioblastoma (GBM). We recently validated that IDO1 can suppress the anti-brain tumor immune response and ablate immunotherapeutic treatment efficacy through non-metabolic IDO1 activity. To-date, most IDO1-targeted therapy has focused on inhibiting tryptophan metabolism. This class of drugs has failed to improve the overall survival of patients with cancer. To overcome this failure, we developed a therapeutic agent that inhibits both IDO1 enzyme- and non-enzyme-activities in the form of an IDO1-Proteolysis Targeting Chimera (PROTAC). We previously published the characterization of a 1st generation lead compound (Bollu et al., 2022; J. Med. Chem) with a DC50 for IDO1 of 0.329 µM in human GBM cells. In a more recent investigation, we discovered a 2nd generation IDO1-PROTAC, NU227326, with 30× more potency and a DC50 of 10.4 nM in human GBM cells. IDO1-expressing U87, U138, and patient derived xenograft (PDX) GBM43 were treated with either IDO1-PROTAC, IDO1-mutant-PROTAC, IDO1 enzyme inhibitor, or IDO1 siRNA. Transcriptomic analysis revealed differentially expressed genes that were commonly regulated after treatment with the IDO1-PROTAC as compared to treatment with the IDO1-mutant-PROTAC or IDO1 enzyme inhibitor groups in U87, U138, and GBM43 cells. Mass spectrometry discovered 34 unique proteins that were differentially expressed inside of human GBM cells and an additional 20 unique proteins that were identified in the supernatant of cultured human GBM cells after IDO1-PROTAC treatment. Meta-analysis of the transcriptomic and proteomic analyses identified a novel factor that was unique to IDO1-PROTAC treatment. IDO1-PROTAC treatment-enriched GO terms were associated with nucleoside kinase and metallocarboxypeptidase activities. This study discovered multiple new pathways that immunosuppressive IDO1 non-metabolically regulates in human glioblastoma cells.
RADT-04. DOSE PAINTING WITH THE GAMMA KNIFE LIGHTNING OPTIMIZER TO ESCALATE RADIATION DOSE TO RESIDUAL TUMOR WITHIN BRAIN METASTASIS RESECTION CAVITIES
Authors: Barbour Andrew , Gates Evan , Ford Eric , Phillips Mark , Halasz Lia 
Published: November 2023

Abstract

BACKGROUND
The novel Gamma Knife (GK) Lightning optimizer allows simultaneous automated optimization of multiple intracranial radiotherapy targets. We used this optimizer to create a dose-painting treatment plan where an escalated dose was prescribed to residual disease within a brain metastasis resection cavity. We validated this method by measuring dose-delivery accuracy using radiochromic film in an anthropomorphic phantom.

METHODS
A 15.7cc irregular contour was drawn to represent a brain metastasis resection cavity, a 2mm expansion contour created, and a 1.6cc contour drawn representing a nodule of residual disease. In GammaPlan v11.3.1, three targets were created with overlapping dose matrices. Targets were prescribed 3Gy (2mm expansion), 4Gy (resection cavity), and 5Gy (residual disease) in one fraction. On the GK Icon system, an occipital mold was made, an unexposed film placed in the phantom’s cranium, cone-beam coregistration conducted, and treatment delivered. The film was scanned and calibrated for absolute dosimetry. To evaluate dose-painting accuracy, global gamma index (GI) analyses were performed at various dose and distance tolerances, excluding points below 30% of the maximum dose.

RESULTS
An 18-minute treatment plan with 40 shots was created and delivered. Prescription isodose lines were 3Gy at 55% (2mm expansion, mean 4.8Gy), 4Gy at 69% (resection cavity, mean 5.2Gy), and 5Gy at 75% (residual disease, mean 6.1Gy). All target volumes had ≥ 99% prescription dose coverage and the maximum dose was 6.9Gy. Paddick conformality indices were 0.79 (2mm expansion), 0.74 (resection cavity), and 0.15 (residual disease). Gamma index pass rate/mean GI/median GI were 73%/0.68/0.55 at 1%/1mm tolerance, 85%/0.58/0.48 at 2%/1mm tolerance, and 97%/0.34/0.28 at 2%/2mm tolerance. An average of 17,883 points were evaluated per analysis.

CONCLUSIONS
We successfully performed GK dose painting with the Lightning optimizer, verifying dose delivery within clinically acceptable tolerances. Future work is needed to determine optimal dose levels for use in clinical practice.
RADT-06. IMPACT OF STATUS OF TUMOR PROGRESSION PRIOR TO STEREOTACTIC RADIOSURGERY ON LOCAL TUMOR CONTROL IN PATIENTS WITH TRIPLE-NEGATIVE BREAST CANCER BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY
Authors: Patel Reema , Xu Zhiyuan 
Published: November 2023

Abstract

INTRODUCTION
Prognosis in patients triple-negative breast cancer (TNBC) brain metastases remains poor owing to the lack of treatment targeting pathways. Furthermore, approaches–like surgical resection, stereotactic radiosurgery (SRS), and whole-brain radiation therapy–have variable efficacy depending on the degree of tumor burden. The cohort of patients benefit least to targeted therapy and immunotherapy, therefore, forming ideal candidates to evaluate the local tumor control attributed to SRS. This study aimed to characterize intracranial tumor response and clinical outcomes in the patient cohort. PATIENTS and

METHODS
This retrospective, single-center study included patients with confirmed TNBC brain metastases treated with SRS at the University of Virginia Health. Tumor response, new intracranial tumor development, and survival were investigated. 24 patients with 169 total treated lesions between 2007 and 2021 were assessed. The median age of patients at the initial treatment was 49.1 years.

RESULTS
One MRI within one month prior to SRS plus the treatment study MRI were evaluated. Tumor progression at the time of SRS led to worse local tumor control following the first SRS treatment (p &lt; 0.0001). 15.1% of total treated lesions demonstrated a complete response, while 48.5% had a partial response. 25.7% of lesions remained stable and 13.5% progressed. Three patients did not have any follow-up imaging to assess initial tumor response due to mortality. For patients with tumor progression, the progression-free survival was 4.93 months. Additionally, new intracranial metastases developed in ten patients over their treatment course. Median overall survival following the first SRS session was 9.83 months (range 0.9 - 37.7 months), with a 1-year and 2-year survival of 54.5% and 22.7%, respectively.

CONCLUSION
Tumor control in patients with TNBC treated with SRS is unfavorable. Tumor progression prior to SRS might lead to worse tumor control. Further study is warranted to evaluate this phenomenon in a large cohort of patients.
RADT-10. BRAINSTEM METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY: MASKED VS. FRAMED IMMOBILIZATION
Authors: Begley Sabrina , Goenka Anuj , Schulder Michael 
Published: November 2023

Abstract

BACKGROUND
Patients with brainstem metastases (BSM) have minimal surgical options due to high-risk anatomy. To review our efficacy treating BSM using Gamma Knife stereotactic radiosurgery (GK SRS), we compared results based on the utilization of mask-fixation (MF) or frame-fixation (FF).

METHODS
Data were retrospectively collected for 32 patients. Follow-up data for 49 lesions were analyzed for local control rate (LCR) and objective response rate (ORR).

RESULTS
Primary cancers included lung, breast, and melanoma; most lesions were pontine. MF was used in 18 patients. Average tumor volume was 0.99 cm3 (0.005 – 13.3 cm3). 39 lesions were treated with single fraction 16 Gy. 10 lesions were treated in 3-5 fractions with mean dose of 22.5 Gy. Mean follow-up was 14.2 months (1.2 - 48.2 months). 1-year LCR was 94.7%. ORR at last follow-up did not differ between MF vs. FF (p = .81). Average reduction of lesion volume at 6 and 12 months did not differ between MF vs. FF (64% vs 45%, p = .77; 70% vs 77%, p = .78). Failure occurred in a pontine colorectal cancer metastasis mask-immobilized for treatment with 14 Gy.

CONCLUSIONS
SRS for BSM achieved high LCR despite variability in tumor size and histology with no significant difference between MF vs. FF. Although trials have historically excluded patients with BSM, our data support SRS as a safe and efficacious treatment. This is the first study showing that MF provides equivalent, successful outcomes when compared to FF for patients with BSM.
RADT-20. STEREOTACTIC RADIOSURGERY FOR 15 OR MORE BRAIN METASTASES
Authors: Upadhyay Rituraj , Palmer Joshua , Perlow Haley , Schoenhals Jonathan , Ghose Jayeeta , Rajappa Prajwal , Blakaj Dukagjin , Beyer Sasha , Grecula John , Sim Austin , Hardesty Douglas , Elder J Bradley , Chakravarti Arnab , Thomas Evan , Raval Raju 
Published: November 2023

Abstract

BACKGROUND
Patients with ≥ 15 brain metastases(BM) continue to be treated with whole brain radiation therapy(WBRT), despite poor neurocognitive outcomes. We analyzed our institutional experience of treating these patients with stereotactic radiosurgery(SRS), with the aim of evaluating safety, cognitive outcomes, and survival.

METHODS
Patients who received SRS for ≥ 15 BMs in 1-5 fractions from 2014-2022 using the previously described single isocenter multi-target technique were included. Cognitive outcomes were objectively evaluated using serial Patient-Reported Outcome Measurement Information System(PROMIS) scores.

RESULTS
A total of 124 patients treated with LINAC-based SRS were included. The mean and median number of lesions treated per patient was 24.8 and 20, respectively (range 15 – 94). Most common primary histologies were lung(47.6%), melanoma(21.0%), and breast(14.5%). The median SRS dose was 24 Gy(range 18 – 30 Gy). The rate of any grade radiation necrosis (RN) and ≥ grade 3 RN were 15.3% and 3.2% respectively. New onset seizures were seen in 2.4% and alopecia in 2.4%. Median follow-up was 5.1 months(m). When cognitive data were available, 25 of 31 patients had a stable or improved PROMIS score. The 12m local control was 97.6% while overall intracranial control was 20.8%. One-year freedom from neurological death, leptomeningeal disease, and salvage WBRT were 85.6%, 87.6% and 71.7% respectively. Median overall survival(OS) from brain metastases diagnosis was 11.3m(95% CI 7.2m – 15.3m). On univariate analysis, no prior WBRT(p = 0.038), higher KPS(p = 0.002) and systemic therapy after SRS(p &lt; 0.001) predicted for improved OS.

CONCLUSIONS
We present here the largest study evaluating SRS for patients with ≥ 15 BMs. We found that SRS was safe, had favorable cognitive outcomes, and comparable survival outcomes to contemporary studies evaluating WBRT in this patient population. Our study supports further randomized studies comparing SRS and memory avoidance WBRT approaches for patients with ≥ 15 BMs.
RADT-21. LINEAR ACCELERATOR BASED RADIOSURGERY WITH DYNAMIC CONFORMAL ARCS FOR PATIENTS WITH MULTIPLE BRAIN METASTASES: A PROSPECTIVE COHORT STUDY
Authors: Huang Shih-Ting , Liu Yen-Ting , Chu Kuan-An , Huang Tsu-Hsien , Chen Sin-Yin 
Published: November 2023

Abstract

PURPOSE
Linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) is gaining popularity as an alternative due to its high delivery efficiency and improved accessibility. This study focuses on the radiosurgery protocol of a single institution, utilizing single-isocenter multi-target SRS treatment with an inverse-optimized dynamic conformal arc technique. Materials &

METHODS
A prospective cohort study was conducted from August 2020. The study protocol was approved by the Research Ethics Committee. Patients with brain tumors referred for SRS were treated based on the indications. Prescription doses were determined by target size and radiation oncologists. The protocol included a 1-2 mm expansion of tumors for the planning target volume (PTV), with a requirement of at least 85% PTV coverage. At least three non-coplanar arcs are needed. Competing risk survival analysis was used to assess the cumulative incidence of failure.

RESULTS
A total of 57 patients with 190 brain tumors underwent SRS in this study. 12 patients (21.1%) received at least 2 radiation courses for recurrent lesions. Tumor sizes ranged from 0.45 to 8.0 cm (median 1.41 cm). The maximal dose relation ranged between 71.5% and 91.4% (median 81.6). The conformal index ranged from 1.08 to 2.19 (median 1.19), and the dose gradient index ranged from 2.19 to 6.95 (median 3.59). The 1-year cumulative incidence of local failure and intracranial distant failure rates were 10.8% and 35.6%, respectively.

CONCLUSION
LINAC-based SRS using dynamic conformal arcs achieves optimal tumor coverage and a high dose gradient with ease. It demonstrates a low rate of local failure, effectively protects normal brain tissue, and allows for the postponement of whole brain radiotherapy, enabling patients to maintain a normal quality of life. In conclusion, LINAC-based SRS with dynamic conformal arcs may be a beneficial treatment option for brain metastases, even with a high lesion count, particularly in institutions equipped with LINAC.
RADT-23. STEREOTACTIC RADIOSURGERY FOR CYSTIC VESTIBULAR SCHWANNOMA - A SYSTEMATIC REVIEW
Authors: Torres Lisette , Mekonnen Mahlet , Furton Anna , Pandey Aryan , Vohra Sanah , Yang Isaac 
Published: November 2023

Abstract

BACKGROUND
Cystic vestibular schwannoma, also historically known as cystic acoustic neuroma, is a benign intracranial tumor that can form between the pons and the cerebellum in an area known as the cerebellopontine angle. These brain tumors can be treated with radiotherapy, surgical resection, or radiosurgery. However, there is no consensus on which treatment modality is the most effective with minimal to no complications.

METHODS
A comprehensive review of clinical articles reporting stereotactic radiosurgery treatment for cystic vestibular schwannoma was performed. PubMed, Web of Science, Cochrane, Scopus, and Embase were independently queried and the PRISMA guidelines were followed throughout the screening process. We identified high-quality studies representing data from 186 patients. We extracted patient demographics, tumor characteristics, type of stereotactic radiosurgery, dosage, tumor control rate, and follow-up time. All the available data points were used to evaluate the effect of stereotactic radiosurgery on tumor control rate for cystic vestibular schwannoma.

RESULTS
A total of 186 patients underwent stereotactic radiosurgery with Gamma Knife (n = 178) and CyberKnife (n = 8). The average tumor volume was 6.47 cm3 (range 4.82 – 8.4 cm3, SD ± 1.8). The average marginal and maximum doses were 12.8 Gy (12.5 -13 Gy, SD ± 0.25) and 24.9 Gy (23.8 - 26 Gy, SD ± 1.10), respectively. The average follow-up time was 63.5 months (53.5 – 74 months, SD ± 10.2). Following stereotactic radiosurgery treatment for cystic vestibular schwannoma across all studies, almost 92% of patients had tumor control at follow-up, (95%-CI: 91.4 - 91.6).

CONCLUSIONS
Our systematic review revealed that stereotactic radiosurgery can provide adequate tumor control for cystic vestibular schwannoma. Therefore, stereotactic radiosurgery is an effective treatment choice in patients with cystic vestibular schwannoma.
RADT-24. A PROSPECTIVE TRIAL EVALUATING THE EFFICACY OF REIRRADIATION TO BONY METASTASES WITH STEREOTACTIC BODY RADIATION THERAPY
Authors: Hammoudeh Lubna , Gunasti Lauren , Shin Kee-Young , Krishnan Monica , Hertan Lauren , Balboni Tracy 
Published: November 2023

Abstract

INTRODUCTION
Bone metastasis is common in advanced-stage cancer patients. While reirradiation of metastatic tumors offers significant symptom control, major limits exist on the possible dose delivered to previously irradiated disease sites. Stereotactic body radiation therapy (SBRT) offers the potential to avoid delivering toxic radiation doses to the spinal cord and other organs at risk by delivering large doses with steep dose gradients.

METHODS
We developed a prospective study including 44 patients with recurrent bone metastasis that were treated to assess the effectiveness of SBRT on local control at or before 6 months as a primary endpoint and local progression-free survival (LPFS), Progression-free survival (PFS), and overall survival (OS) as a secondary objective.

RESULTS
Patients median age was 62.5 years (22.7% female and 77.3% male). The majority of patients received reirradiation to a spinal lesion (29/44, 65.9%) of various primary disease sites predominantly prostate (13/44, 29.5%), lung (8/44, 18.2%), and renal cell (5/44, 11.4%). The most common dose prescriptions were 30 Gy in 5 fractions (24/44, 54.5%). Of the participants, 41 (93.2%) experienced local control at or before 6 months, with 3.6 median months to local progression for those who progressed. 48% and 36.5% of the cohort maintained LPFS at 2 years, and 3 years respectively with a local progression-free rate of 89.5% at 2 and 3 years. OS was maintained in 50.9% and 38.8% of patients at 2 years and 3 years respectively.

CONCLUSION
SBRT offers an effective and less toxic approach for the reirradiation of recurrent metastatic tumors as it can prevent associated toxicities to the surrounding normal tissues and maintain a local progression-free rate in a large percentage of patients. We believe that more clinicians should offer SBRT as an effective option for recurrent metastatic bone tumors especially involving the spinal vertebrae.
RADT-26. IMPROVING RADIATION TARGET VOLUME DEFINITION FOR GLIOBLASTOMA USING PREDICTIONS OF TUMOR RECURRENCE FROM MACHINE LEARNING AND PRE-RADIOTHERAPY ADVANCED MRI
Authors: Tran Nate , Luks Tracy , Ellison Jacob , Nair Devika , Li Yan , Jakary Angela , Liu Bo , Adegbite Oluwaseun , Villanueva-Meyer Javier , Butowski Nicholas , Clarke Jennifer , Chang Susan , Braunstein Steve , Lin Hui , Morin Olivier , Lupo Janine 
Published: November 2023

Abstract

INTRODUCTION
Standard-of-care (SOC) radiation therapy (RT) planning only utilizes a fairly 1.5-2cm uniform expansion of T2-weighted-FLAIR MRI lesion to generate a clinical target volume (2cm-CTV), without considering the spatial heterogeneity and infiltrative nature of glioblastomas. This study aimed to use multi-parametric MRI with 2 artificial intelligence (AI)-based approaches to predict regions of subsequent tumor progression and compare the resulting predictions to the 2cm-CTV, with the hypothesis that applying deep learning will lead to improved detection of subclinical disease that is under-treated, and more accurately delineate areas at higher risk for progression, than the uniform 2cm-CTV.

METHODS
We used normalized maps of anatomical, diffusion, and metabolic MRI post-surgical resection and before RT and chemotherapy from 72 patients newly-diagnosed with glioblastoma to train Random-Forest and deep-learning UNet models to identify voxels that later exhibit progression by either the contrast-enhancing-lesion (CEL) or T2-lesion (T2L). All models were trained/validated on 54 and tested on 18 patients after careful inter-exam alignment and normalization. Model performance was compared to the 2cm-CTV using a Progression-Coverage-Coefficient (PCC), a weighted Dice coefficient that accounts for tumor-size.

RESULTS
Random-Forest models were able to predict subsequent contrast-enhancing (CE) and T2 non-enhancing (NE) progression with an average respective test AUC of 0.88 and 0.82, with 15.6%/9.6% higher performance on patients who progressed early. The 2cm-CTV treatment plan achieved the highest sensitivity (0.833 vs 0.795) but also the lowest specificity (0.879 vs 0.935), over-treating normal-appearing-brain. Our deep learning model outperformed the 2cm-CTV in covering the progressed lesion, with the highest specificity (0.935 vs 0.879), PCC (0.741 vs 0.734), and had comparable sensitivity (0.795) to the 2cm-CTV, while sparing more normal brain compared to the 2cm-CTV.

CONCLUSION
This study demonstrates the potential benefit of using multi-parametric MRI with deep learning to assist in RT treatment planning to reduce excessive treatment of normal brain parenchyma.