bluuebunny/crossref_metadata_2025_split huggingface dataset:
NCOG-53. PREDICTORS OF ENDOCRINE OUTCOME AFTER ENDOSCOPIC TRANSSPHENOIDAL SURGERY FOR NON-FUNCTIONING PITUITARY ADENOMAS
Authors: Hwang Jenie , Yum Diane , Chicoine Michael , Dacey Ralph , Osbun Joshua , Rich Keith , Zipfel Gregory , Klatt-Cromwell Cristine , Mcjunkin Jonathan , Pipkorn Patrik , Schneider John , Silverstein Julie , Kim Albert 
Published: December 2020

Abstract

BACKGROUND
Although endoscopic transsphenoidal surgery (ETSS) is an established treatment for patients with nonfunctioning pituitary adenomas (NFPAs), data are limited regarding the rates and predictors of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS.

OBJECTIVE
To analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA.

METHODS
Among a cohort of 601 consecutive patients who underwent ETSS for NFPA between 2010 and 2018 at Washington University in Saint Louis, recovery or development of new hypopituitarism was retrospectively analyzed in 209 patients.

RESULTS
Preoperative endocrine deficits were observed in 59.8% of patients (125/209), and the deficit rates were 76.8% for male gonadal axis (86/112), 42.5% for thyroid axis, 25.8% for growth hormone axis, and 15.8% for cortisol axis. Recovery of preoperative pituitary deficit was noted in all four axes, with highest recovery in the cortisol axis with a 1-year cumulative recovery rate of 44.3%. New-onset postoperative hypopituitarism occurred most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Multivariate analyses revealed axis-specific predictors of postoperative recovery and de novo deficiency. Older age was a negative predictor for recovery of both male hypogonadism (P= 0.04) and adrenal insufficiency (P=0.046), and a larger tumor volume was a negative predictor for recovery of hypothyroidism (P=0.043). Although higher body mass index was generally associated with any new postoperative pituitary deficit (P=0.03), most predictors of new onset deficits also differed by hormone axis.

CONCLUSIONS
Dynamic changes in pituitary hormonal levels were observed in a significant fraction of patients following ETSS in NFPA patients. The specific hormonal axis dictated postoperative endocrine vulnerability, recovery, and predictors of recovery or loss of endocrine function.
NIMG-57. ASSOCIATION OF RADIOMICS BASED TUMOR SHAPE IRREGULARITY MEASURES AND GAMMA KNIFE DOSE PLANNING INDICES IN VESTIBULAR SCHWANNOMAS
Authors: Sümer Esra , Tek Ece , Şengöz Meriç , Pamir M Necmettiin , Dinçer Alp , Özcan Alpay , Özduman *Koray , Öztürk-Işık *Esin 
Published: December 2020

Abstract
Gamma knife radiosurgery (GKRS) delivers an unevenly distributed radiation dose to a tumor, with a sharp falloff outside the target. Although the dose inhomogeneity within a tumor is strongly influenced by its shape, routine GKRS dose planning does not account for it. We hypothesized that shape irregularity measures were correlated with treatment planning indices, and might provide insight during treatment planning. The aims of this study were to quantify the shape irregularity measures in vestibular schwannomas, estimate their correlations with core radiosurgical planning measures, and define the most predictive shape feature for dose effectiveness. METHODS: Four dose plan indices, which were the selectivity index (SI), gradient index (GI), efficiency index (EI), and Paddick’s conformity index (PCI) were estimated from the GKRS plans of 234 vestibular schwannomas. All dose plans were prepared using Gamma Plan 10.0 and above and all treatments were delivered using a perfexion/ICON platform. Three-dimensional (3D) tumor models were rendered using 3D Slicer Software from segmented T1-weighted MR images. Sixteen irregularity measures were calculated for each tumor using Radiomics in MATLAB. Spearman correlation coefficients (r) were computed to find associations of the dose plan indices with the irregularity descriptors. The most predictive shape feature for dose efficiency was identified using the least absolute shrinkage and selection operator (Lasso). RESULTS: The shape irregularity measures were negatively correlated with SI, EI, and PCI, and positively correlated with GI. Volumetric index of sphericity (VioS) had the highest correlations with SI (r = 0.63, p= 3.27E-23), GI (r= -0.58, p= 1.10E-19), EI (r = 0.69, p= 0.00), and PCI(r= 0.68, p = 6.73E-28), and Lasso feature selection identified VioS as the most important feature for predicting all dose plan indices. CONCLUSION: VioS provides a numerical quantification of tumor shape irregularity, and it is highly correlated with the GKRS dose planning indices. *indicates co-senior authors
NIMG-62. AMPHETAMINE-ASSOCIATED CNS VASCULITIS MASQUERADING AS TUMOUR
Authors: Shivaprasad Akhil , Qasim Muhammad , Langford Lauren , Fuller Gregory , El-Naggar Adel K , Vishwanathan Ashwin , Tremont-Lukats Ivo , Majd Nazanin 
Published: December 2020

Abstract
Amphetamine-associated CNS vasculitis is controversial. There are few reports but none as a tumor mimic to our knowledge. We describe a pathology-proven, amphetamine-associated CNS vasculitis resembling a tumor. A 41-year-old man presented with six weeks of progressive confusion and left-sided weakness. CT head reported a right thalamic mass with vasogenic edema. Laboratory tests were unremarkable except for cannabinoids and amphetamine in urine. MRI brain showed enhancement in right frontotemporal lobe, basal ganglia, and thalamus concerning for glioblastoma multiforme. After high-dose IV dexamethasone, an initial biopsy showed reactive gliosis, perivascular lymphocytic cuffing by CD3+, rare CD20+ cells and no infection. He continued to decline. MRI 22 days after admission showed increased T2/FLAIR hyperintensity, multifocal areas of enhancement, microhemorrhages, and ischemia. High-grade glioma, lymphoma and infectious encephalitis remained on differentials. Treatment included broad-spectrum antibiotics and acyclovir. Biopsy on 23rd day showed reactive gliosis with parenchymal macrophage infiltration and perivascular cuffing with mixed inflammatory infiltrates. CSF: slightly elevated WBCs (8/µL), elevated protein (139mg/dL), normal glucose, and no infection. MRI whole spine and CT body were unremarkable. The patient was transferred to MDACC 5.5 weeks after initial presentation. He was alert with expressive aphasia, right gaze preference, left hemiplegia, and right hemiparesis. He underwent a right anterior temporal lobectomy. Pathology showed extensive cortical laminar and white matter necrosis with macrophage infiltration and microglial activation. In areas of the preserved cortex, vasculocentric lymphocytic aggregates were present and reticulin staining showed lymphocytic infiltration of the vascular walls. Immunophenotyping (CD3, CD20) showed an almost pure T-cell population. The predominance of intramural T-lymphocytes reflected a vasculitic process. The final diagnosis was cerebral vasculitis with subacute infarction. The patient died six days later. The autopsy findings were identical to the previous resection without evidence of systemic inflammation.
PATH-27. CLINICAL, RADIOLOGIC AND PROGNOSTIC PROFILE OF IDH WILD TYPE DIFFUSE ASTROCYTOMA WITH MOLECULAR FEATURES OF GLIOBLASTOMA
Authors: Akintola Oluwatosin , Samore Wesley , Alvarez Maria Martinez-Lage , Gerstner Elizabeth 
Published: December 2020

Abstract

BACKGROUND
cIMPACT-NOW-3 recommends that IDH-wildtype diffuse astrocytic glioma Grade II or III with EGFR amplification, or combined whole chromosome 7 gain and whole chromosome 10 loss, or TERT promoter mutation should receive an integrated classification: Diffuse astrocytic glioma, IDH-wildtype with molecular features of glioblastoma, WHO grade IV. The aims of this study were: Outline the features of a cohort of patients with molecular glioblastoma according to the above criteria; Assess clinical and molecular factors that may inform prognosis; Determine if cIMPACT-NOW-3 recommendation changed clinical practice and clinical trial enrolment.

METHODS
61 patients diagnosed with IDH-wildtype diffuse astrocytic glioma Grade II or III and EGFR amp or mTERT or chromosome (+7/-10) between 2011 and 2019 at MGH were included in this single center retrospective cohort study. Data collected: sex, age, extent of surgery, functional status, histological grade, molecular diagnostics and treatment. Progression was defined using RANO criteria, progression was quantified in terms of months from the initial surgery. Survival was defined in terms of months from initial surgery to date of death or last known visit.

RESULTS
mOS was 16 months, mPFS was 9 months. 14 patients (23%) survived &gt; 24 months, 7 ≥ 36 months (mOS 32 months; 9 deceased). The probability of survival in patients with markedly enhancing tumors was 0.5 at 3 months versus 0.5 at 11 months in non-enhancing tumors. The probability of survival in patients who underwent biopsy only was 0.5 at 5 months compared to 0.5 at 12 months in patients with maximally resected tumors. 1 patient was enrolled in a clinical trial at diagnosis. 6 were enrolled at time of recurrence.

CONCLUSIONS
mOS and pFS in the deceased patients was comparable to historical data on survival in IDH wild-type glioblastomas. Inclusion criteria in clinical trials have not reflected the cIMPACT-NOW-3 recommendation so far.
PATH-42. COMBINED NEXT GENERATION SEQUENCING AND IMMUNOHISTOCHEMISTRY IN THE DIFFERENTIAL DIAGNOSIS OF A PROGRESSIVE NEURONAL-GLIAL TUMOR: A COMPOSITE NEOPLASM
Authors: Kelly Nicholas M , Valyi-Nagy Tibor , Coleman Louis , Slavin Konstantin , Kpshy Matthew , Michals Edward , Arzbaecher Jean , Miller Clinton , Mohapatra Gayatry 
Published: December 2020

Abstract

BACKGROUND
Neuronal-Glial tumors (NGT) are rare neoplasms typically benign, and characterized by various admixtures of neuronal and glial components. Occasionally these tumors transform to higher grades and rarely develop other histologic features inconsistent with a neuroepithelial origin, raising the question of histogenesis. We present a case of World Health Organization (WHO) grade I ganglioglioma (GG) diagnosed in a 28 year old man whose tumor, over a period of 8 years, progressed to anaplastic ganglioglioma (AGG, WHO grade III) and ultimately AGG with high grade sarcomatoid features. The sarcomatoid component eventually outgrew the NGT components, resulting in the patient’s death. We used next generation sequencing (NGS) and immunohistochemistry to characterize the genetic changes associated with these events.

METHODS
Tissues representing NGT and sarcomatoid components were macrodissected from 6 samples representing the tumor during its evolution from low to higher grades. DNA and RNA were extracted from these samples and NGS performed using the Oncomine Comprehensive Panel. Whole exome sequencing was performed using DNA from the 6 tumor samples and adjacent non-neoplastic tissue.

RESULTS
The original tumor, WHO grade I ganglioglioma had a BRAF V600E mutation. Seven years later, the AGG component had the BRAF V600E, absent in the sarcomatoid component, which had a CDKN2A homozygous deletion. The following year, the sarcomatoid component appeared to predominate and had an additional PIK3CA activating mutation. The NGT component retained the original BRAF mutation but no others. Hierarchical clustering of genome-wide variants identified two distinct cell populations emerging over time: GG progressing to AGG and sarcomatoid tumor.

CONCLUSIONS
Based on these results, we propose two distinct tumor cell populations: GG/AGG and sarcomatoid component, evolving over time and resulting in what is commonly considered a collision tumor, two independent tumors adjacent to each other.
QOLP-02. PATIENT-REPORTED OUTCOMES FOLLOWING PERTUZUMAB PLUS HIGH-DOSE TRASTUZUMAB IN PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER (MBC) AND CENTRAL NERVOUS SYSTEM (CNS) PROGRESSION POST-RADIOTHERAPY
Authors: Kumthekar Priya , Sahebjam Solmaz , Pegram Mark , Ibrahim Nuhad , Sussell Jesse , Nicholas Alan , Fung Anita , Cheng Anna , Lin Nancy U 
Published: December 2020

Abstract
Effective therapies are needed for the treatment of patients with HER2-positive MBC who develop brain metastases. In the open-label, phase II PATRICIA study (NCT02536339), 40 patients with HER2-positive MBC with CNS metastases and CNS progression post-radiotherapy (median age 48 years [range, 34–69]; prior CNS treatment [whole brain radiotherapy 71%, stereotactic radiosurgery 59%, both 31%]) were enrolled to receive pertuzumab plus high-dose trastuzumab (6-mg/kg weekly) until CNS or systemic disease progression or unacceptable toxicity. Following a median (range) treatment duration of 4.5 (0.3–37.3) months, the CNS-confirmed objective response rate per Response Assessment in Neuro-Oncology Brain Metastases criteria (primary endpoint) was 11% (95% confidence interval: 3.03, 25.42), and the clinical benefit rate at 4 months was 68%, indicating sustained clinical stability. Patient-reported outcomes (PROs) were evaluated using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT), which includes sub-scales for symptom severity (average of 13 core symptom and 9 brain-tumor specific items) and symptom interference (average of 6 interference-with-life items representing overall symptom distress). Among 36 patients included in the PRO analyses, mean (standard deviation [SD]) symptom severity scores at baseline and weeks 12 and 28 were 1.65 (1.62), 2.24 (2.14), and 1.94 (2.55), respectively. Mean (SD) symptom interference scores at baseline and weeks 12 and 28 were 2.51 (2.63), 2.81 (3.39), and 1.76 (2.43), respectively. Mean (SD) changes in symptom severity and interferences scores from baseline to week 12 were 0.34 (1.54) and 0.33 (3.08), respectively. On average, patients who did not achieve stable disease or better in the CNS following treatment had worsened symptom severity and symptom interference scores over 12 weeks, while those with stable disease or better in the CNS exhibited stable or improving scores. Pertuzumab plus high-dose trastuzumab provided clinical benefit to the majority (68%) of patients in PATRICIA, without a decrement in quality of life.
RADT-10. SURVIVAL IN PATIENTS FULFILLING CCTG CE.7 ELIGIBILITY CRITERIA: EVALUATING INITIAL STEREOTACTIC RADIOSURGERY FOR 5-15 BRAIN METASTASES
Authors: Gurewitz Jason , Donahue Bernadine , Silverman Joshua S , Benjamin Carolina , Bernstein Kenneth , Kondziolka Douglas 
Published: December 2020

Abstract

INTRODUCTION
The suitability of stereotactic radiosurgery (SRS) in patients with 5-15 brain metastases (BM) is being evaluated in the ongoing CCTG CE.7 randomized trial testing SRS against HA-WBRT. Our study examines the survival of patients with 5-15 BM treated at initial SRS.

METHODS
Review of our Gamma Knife registry identified 163 patients who fulfilled CCTG CE.7 eligibility criteria.

RESULTS
92 females (56%) and 71 males (44%) with median age of 51.6 years (23-98.9) and primary diagnoses of lung (n = 108, 28 EGFR/ALK mutations), breast (n =14, 1 Her2+), melanoma (n = 27, 9 BRAF+), and 14 other were identified. 145 had active extracranial disease (89%); median KPS was 90 (50-100). Median number of tumors at first SRS was 8.2; 114 patients (70%) had 5-9 and 49 (30%) had 10-15 tumors. 73 patients (45%) had subsequent SRS to a median of 19 (6-84) cumulative subsequent tumors at a median time to 2nd treatment of 3.9 months (0.7-30.3). 32 patients (20%) had a 3rd SRS and 24 patients (15%) had 4 or more treatments. 16 patients (10%) received WBRT after initial SRS. 73 patients (45%) were alive at time of data analysis. Median OS from initial SRS for all patients was 15.5 months and was 15, 17.6, 13.4, and 8.7 months, for breast, lung, melanoma, and other respectively. Median OS with 5-9 metastases vs 10-15 metastases was 17.5 vs. 13.3 months (p=.15). Median OS with vs without subsequent SRS was 21.8 vs 8 months (p=.0013).

CONCLUSION
Patients with 5-15 BM treated with initial SRS can achieve survivals that compare favorably with or better than those of WBRT. These findings potentially challenge the assumption that such patients may be better candidates for HA-WBRT than upfront SRS. Our experience supports the ongoing efforts to prospectively evaluate upfront SRS in these patients.
RADT-36. PROSPECTIVELY ASSESSED TUMOR CONTROL AND TOXICITY OF BENIGN INTRACRANIAL PATHOLOGIES TREATED WITH AUTOMATED VMAT RADIOSURGERY – INITIAL 2 YEAR EXPERIENCE WITH FIRST 100 PATIENTS
Authors: Thomas Evan , Mullins Clarence , Bredel Markus , Dobelbower Michael , Willey Christopher , Spencer Sharon , Guthrie Barton , Riley Kristen , Markert James , Fiveash John , Boggs Drexell 
Published: December 2020

Abstract

BACKGROUND
HyperArc is a treatment planning technology that automates treatment planning and delivery of single-isocenter VMAT radiosurgery (SRS). The technique generates high quality, rapidly deliverable plans. It is unknown whether HyperArc is effective for commonly-encountered, benign, intracranial conditions managed with SRS. Under IRB-approved prospective registry, we collected data on treatment planning/delivery, and clinical outcomes of non-malignant conditions managed with single-fraction or fractionated SRS since deployment in October 2017.

METHODS
Patients received either single-fraction or fractionated SRS with HyperArc™ (Varian Medical Systems) between October 2017 & October 2019. Patients with &lt; 3 months follow-up were censored. All patients treated received prescription dose to ≥ 99% of gross tumor volume without PTV expansion. All treatments were delivered on Varian Edge linac with 10MV flattening-filter free beam at 2400 MU/min with high-definition (2.5mm) multi-leaf collimator. Standard pathology-specific outcomes and toxicities were assessed. Significant CNS toxicity was defined as Grade 3 or higher event by CTCAE.

RESULTS
Total of 100 targets (min=0.13cc, max=58.9cc) were treated. 55 received single-fraction SRS (12-22Gy), two received 2-fraction fSRS boost (12Gy) following fractionated treatment, and 43 received 5-fraction fSRS (25-30Gy). The most common pathology was meningioma (n=55), followed by AVM (n=18), non-secretory pituitary adenoma (n=12), acoustic schwannoma (n=9), secretory pituitary adenoma (n=3), glomus tumor (n=2), pineocytoma (n=1), and paraganglioma (n=1). Follow-up ranged from 1.2 to 19.5 months (median 7.2). There were three local failures, all in atypical meningiomas. One patient in the cohort experienced ≥Gr3 toxicity. Each radiosurgery session used median of 3 arcs, with median treatment and beam-on time of 12.03 and 2.3 minutes. Plan quality was excellent; median RTOG conformity was 1.15, and median Paddick GI was 3.52.

CONCLUSION
Although HyperArc was developed for automated multiple-metastasis radiosurgery, we found it effective and efficient for benign intracranial indications too. Early clinical outcomes appear congruent with historical controls.
RADT-47. A MULTICENTER OBSERVATIONAL STUDY OF SURGICALLY TARGETED RADIATION THERAPY (START) USING IMPLANTED CS-131 SEEDS IN A COLLAGEN-BASED CARRIER TILE IN INTRACRANIAL BRAIN NEOPLASMS - PROTOCOL IN PROGRESS
Authors: Nakaji Peter , Brachman David , Misell Lisa 
Published: December 2020

Abstract

INTRODUCTION
Post-resection radiotherapy (RT) is the most effective adjuvant treatment for brain tumors. However, there is no current consensus as to the “best” type of post-resection RT, either at diagnosis or recurrence. The use of internally placed radiation (brachytherapy) allows immediate initiation of RT when residual tumor burden is minimal, which theoretically should lessen the risk of recurrence. Brachytherapy placement intraoperatively allows more precise identification of the tumor margins than by postoperative imaging. Traditional brachytherapy methods have several drawbacks, including uneven dose distribution, long operating room times, a need for expensive equipment, and/or frequent adverse events (AE). To address these issues, a device with Cs-131 radiation seeds in a resorbable collagen-based carrier tile (GammaTile, GT Medical Technologies, Tempe AZ) was developed and is described as Surgically Targeted Radiation Therapy or STaRT. The device has demonstrated excellent safety and local control in early commercial use.

OBJECTIVE
The objectives of this registry study are to evaluate real-world clinical outcomes and patient reported outcomes that measure the effectiveness and safety of STaRT.

METHOD
Patients (N=600) with surgically resected (R) brain tumors of any pathology who have undergone STaRT are eligible. Accrual to start at 20+ sites in Q3 2020. Data collected includes local control, overall survival, QOL, neurocognition, functional decline, and surgical and radiation associated AE’s. Data will be collected at 1, 3, 6, 9, and 12 months, then every 6 months through 5 years.

RESULT
Data will be used to benchmark clinical outcomes of STaRT therapy and allow for comparisons to existing standard-of-care treatments.

CONCLUSION
This will be the first observational registry study of R+STaRT, delivered by Cs-131 sources in permanently implanted resorbable collagen tile carriers. The outcome measures captured will allow for evaluation of the potential risks and benefits of this treatment approach for patients in a real-world setting.
RBIO-04. NEW THERAPEUTIC DELIVERY METHODS FOR TUMOR-TREATING FIELDS FOR HIGHER EFFICACY
Authors: Carlson Kristen , Bomzon Zeev , Arle Jeffrey 
Published: December 2020

Abstract
Tumor-treating fields (TTFields) are the fourth modality of glioblastoma (GBM) treatment and in conjunction with chemotherapy can increase overall survival of GBM patients up to 60 months. However, in vitro and in animal models TTFields show 100% efficacy on a variety of tumor cell types including GBM cells when field strength is 4 V/cm, versus ~2 V/cm that is the clinical delivery target, TTFields are delivered transcranially. TTFields finite element modeling studies, supported by similar transcranial electric stimulation studies, show that the principal obstacle to delivering 4 V/cm is the electrically resistive skull. Our modeling shows the biophysics is more complicated than these findings. For instance, electrically-conductive cerebrospinal fluid regions surrounding the grey matter and in ventricles shunt electric current from anode to cathode, hindering delivery of the current required to produce 4 V/cm at the tumor/peritumor target. Thus, we consider two new delivery methods for TTFields. First, the transcranial array can be made more focal and directional, following modeling and development of electrode arrays used in spinal cord and deep brain stimulation. Our finite element modeling shows that similarly-designed TTFields electrode arrays can deliver field strength focally to a tumor target approaching 4 V/cm. Second, pre- or post-resection, TTFields can be delivered via electrode arrays surgically placed in the tumor or tumor resection cavity (intra-tumoral delivery), circumventing the resistive skull and CSF shunting effects. Such intra-tumoral arrays can deliver 4 V/cm to the tumor/peritumor region, opening up the potential to replicate clinically the 100% efficacy of TTFields in vitro and in animal models. Thus, new TTFields delivery may lead to unlimited survival of GMB patients via a side-effect free treatment modality.