bluuebunny/crossref_metadata_2025_split huggingface dataset:
INNV-13. SYNERGISTIC EFFECT OF COLD ATMOSPHERIC PLASMA IN COMBINATION WITH TEMOZOLOMIDE TO TREAT GLIOBLASTOMA IN A NON-INVASIVE MOUSE XENOGRAFT MODEL
Authors: Adhikari Manish , Soni Vikas , Hayk Simonyan , Young Colin , Sherman Jonathan , Keidar Michael 
Published: December 2020

Abstract

INTRODUCTION
A primary limitation in anti-cancer therapy is the resistance of cancer cells to chemotherapeutic drugs. However, combination therapy may be an effective approach for reducing drug derived toxicity and evading drug resistance, resulting in improved clinical treatment of cancer. Our prior work demonstrated effective treatment of glioblastoma (GBM) with cold atmospheric plasma (CAP) technology with minimal effect to normal cells. Consequently, CAP may serve as a strong candidate for combination therapy with the classical antineoplastic alkylating agent Temozolomide (TMZ) to treat GBM.

OBJECTIVES
To determine the in vivo co-efficacy of CAP and TMZ to “sensitize” GBM.

METHODS
An in vivo study was performed using the CAP jet device (He-gas) to determine the effect of combined CAP–TMZ treatment. U87MG-luc glioblastoma cells were implanted intracranially in athymic nude NU(NCr)-Foxn1nu/immunodeficient mice. He-CAP (or control He alone) was non-invasively applied over the skin for 60sec to developed tumors on the first day of the treatment followed with 6.5 mg/kg TMZ or vehicle control treatment for 5 days for two weeks (n=5/group). In vivo bioluminescence imaging was used to monitor tumor volume on the 6th, 9th and 13th treatment day.

RESULTS
In vivo bioluminescence imaging revealed a marked 8.0±3.2 fold increase in tumor volume in control animals (He-vehicle). Treatment with He-TMZ (6.7±2.5 fold) or CAP-vehicle (4.8±1.7 fold) in isolation had minimal effect in preventing tumor growth. However, combined CAP-TMZ co-treatment virtually prevented increases in tumor volume over 2 weeks (1.8±0.2 fold).

CONCLUSIONS
Collectively, these findings indicate an effective synergistic treatment method for GBM combining CAP with TMZ. Future investigations look to incorporate radiation into the treatment regimen as well as primary GBM cell models.
INNV-17. NEXT GENERATION SEQUENCING IMPACTS OUTCOMES IN RECURRENT PRIMARY GLIOBLASTOMA: A SINGLE-CENTER RETROSPECTIVE ANALYSIS
Authors: Zeitouni Daniel , Catalino Michael , Wise Jordan , Pietrosimone Kathryn , McCabe Sean , Rashid Naim , Khagi Simon 
Published: December 2020

Abstract

BACKGROUND
GBM is driven by various genomic alterations. Next generation sequencing (NGS) may reveal targetable alterations. The goal of this study was to describe how NGS can inform targeted therapy (TT) selection.

METHODS
The medical records of patients (pts) with GBM from 2017–2019 were reviewed. Pts with actionable mutations were included in the analysis. At first progression (PD1), two cohorts of pts were defined: cohort A received TT, while cohort B received physician’s choice chemotherapy (PCC). Regression analyses were used to determine OS and PFS between cohorts. A stratified cox model was utilized to assess the effect of TT, where KPS level (low vs high) was utilized as a stratification factor. A heat map was generated describing the landscape of mutations. Disease response in cohort A was graded per RANO criteria.

RESULTS
There were 38 GBM pts with actionable alterations. Cohort A had 15 (39%) pts and cohort B had 23 (61%) pts. Of the 26 common alterations, 11 (42%) were deemed actionable. Pts with higher KPS were more likely to receive TT. Pts with a KPS ≥ 70 had a longer PFS while on TT. Although not well powered, pts in cohort A had a longer median OS relative to cohort B (HR 0.37 CI 0.10–1.38). The objective response rate (ORR) was 93%, with afatinib and cabozantinib resulting in complete response, one pt had progressive disease while on TT.

CONCLUSION
NGS for recurrent GBM yields a high rate of actionable alterations. Pts that go on TT are often younger and with higher KPS. This likely plays into their improved survival; however, it is notable that the high ORR reflects the value of NGS in deciding on TT to match alterations that are likely to respond. In conclusion, patient selection and availability of NGS impacts outcomes in recurrent GBM.
INNV-19. ANAPLASTIC CEREBELLAR EPENDYMOMA IN AN ADULT FEMALE PRESENTING WITH TONSILLAR HERNIATION SUCCESSFULLY TREATED WITH CHEMOTHERAPY: A CASE REPORT
Authors: Guerrero Victor , Manalo-Igot Mary Ondinee 
Published: December 2020

Abstract

INTRODUCTION
Ependymomas are slow-growing neuroectodermal tumors that may arise from various parts of the central nervous system. Anaplastic ependymoma represents 3–5% of ependymomas and is rarely found in the cerebellum in adults. In this paper, we discuss a case of an adult female with anaplastic cerebellar ependymoma who underwent surgery and chemotherapy for tonsillar herniation.

CASE PRESENTATION
This is a case of a 58-year-old Filipino female with a five-month history of dizziness, headache, nausea and vomiting. Cranial computed tomography (CT) scan revealed presence of hydrocephalus with enhancing lesions at the right cerebellum. The patient underwent ventriculoperitoneal shunting (VPS) with sub-total excision and biopsy of the right cerebellum. Histology and immunochemistry were consistent with a high-grade anaplastic ependymoma (WHO Grade III). Cerebrospinal fluid and spinal magnetic resonance imaging (MRI) were all negative for tumor. The initial plan was to undergo limited field external beam radiation therapy to the cerebellum, however the patient was lost to follow-up. Two months after surgery, she presented with similar symptoms and MRI revealed tonsillar herniation and recurrence of mass compressing the fourth ventricle, pons, and medulla oblongata, thus medical decompression and urgent chemotherapy with cisplatin and etoposide was started. After 4 sessions of chemotherapy, repeat cranial MRI revealed resolution of tonsillar herniation and interval regression of the mass.

CONCLUSION
This paper presented a rare case of anaplastic cerebellar ependymoma with tonsillar herniation who was successfully treated with chemotherapy. Radiotherapy is the standard of care following surgical resection, but the management of our case showed that chemotherapy is also effective in cases when the presentation is herniation.
NCMP-01. THE ROLE OF VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR INHIBITORS IN PREVENTING CEREBRAL RADIATION NECROSIS: A RETROSPECTIVE COHORT STUDY
Authors: Alnahhas Iyad , Rayi Appaji , Palmer Joshua , Raval Raju , Folefac Edmund , Ong Shirley , Giglio Pierre , Puduvalli Vinay 
Published: December 2020

Abstract

INTRODUCTION
Radiation necrosis (RN) is a potential complication after radiation therapy to primary brain tumors and brain metastases. The pathophysiology of RN is not well understood but it is hypothesized that vascular endothelial growth factor (VEGF) plays an important role. Bevacizumab, a monoclonal antibody against VEGF-A, is often successful in the management of RN. The objective of this study is to assess whether VEGF receptor (VEGFR) inhibitors, a group of oral tyrosine kinase inhibitors (TKIs), can prevent or reverse cerebral radiation necrosis

METHODS
We retrospectively studied a cohort of 102 patients with renal cell carcinoma (RCC) and brain metastases seen at The Ohio State University James Cancer Center between 01/01/2011 and 04/30/2019. We identified those who developed RN and analyzed the temporal relationship between the use of VEGFR TKIs and the development of RN.

RESULTS
The cumulative incidence of RN in our cohort is 13.7% after radiation treatments that included LINAC-based stereotactic radiosurgery, fractionated stereotactic radiotherapy, or Gamma Knife radiosurgery. There was no statistically significant difference in the cumulative incidence of RN between patients taking TKIs and patients who were off TKIs (9.9% and 11.5% respectively, p= 0.741). The median time to development of RN was only numerically shorter in patients taking TKIs (151 versus 315 days, p=0.315). One patient developed RN after stopping cabozantinib. Three other patients developed RN while on cabozantinib. Two patients developed RN while on pazopanib, and 3 patients developed RN while on sunitinib. One patient was started on axitinib during active RN without significant improvement subsequently.

CONCLUSIONS
VEGFR TKIs do not consistently prevent or reverse cerebral radiation necrosis and do not seem to have the efficacy that bevacizumab has against RN.
NCMP-09. POSTMORTEM STUDY OF ORGAN SPECIFIC TOXICITY IN GLIOBLASTOMA PATIENTS TREATED WITH A COMBINATION OF TEMOZOLOMIDE, BEVACIZUMAB AND IRINOTECAN
Authors: Zhu Jay-Jiguang , Lu Guangrong , Rao Mayank , Zhu Ping , Linendoll Nadine , Tian Xuejun , Pilichowska Monika , Wu Julian , Glass William , Bhattacharjee Meenakshi , Ballester Leomar Y , Chen Lei , Zhang Rongzhen , Pillai Anil , Buja L Maximilian , Hunter Robert 
Published: December 2020

Abstract
Combined chemotherapy with temozolomide (TMZ), bevacizumab (BEV) and irinotecan (IRI) [TBI] has been used in patients with recurrent or progressive high-grade gliomas. Patients tolerated the regimen well with increased frequency of reversible clinical myelosuppression (CM), hypertension and proteinuria. However, organ-specific toxicities have never been evaluated by post-mortem examination. From 2009 to 2019, post-mortem examinations were performed in seventy-six decedents, including gliomas (N=68, 44/M and 24/F, median age: 59, ranging 23–80 years old) and brain metastases (N=8, 5/M and 3/F, ranging 39–75 years old). Twenty-four glioma subjects were treated with 1–25 cycles TBI (median 5.5) at glioma recurrence. All subjects’ clinical information, treatment histories and adverse events were collected. Five (7.7%, 5/65) glioma decedents (excluding three glioma patients who never received TMZ) permanently discontinued TMZ due to severe CM during concurrent chemoradiation therapy. There is no significantly elevated severity of CM from TBI when compared to standard of care therapies, nor when comparing extended TMZ treatment to the standard 12 cycles of TMZ. However, exposure to IRI significantly increased the CM occurrence (p&lt; 0.05). Among glioma decedents, the most common cause of death was tumor progression (63.2 %, N=43), followed by aspiration pneumonia (48.5%, N=33). No deaths were attributed to acute toxicity from TBI. An electromicroscopic (EM) examination was performed in addition to routine autopsy procedures to investigate the cause of hypertension and proteinuria frequently developing in patients received BEV therapy. Ultrastructural evidence of thrombotic microangiopathy was observed in the kidneys among BEV users; however, it is difficult to conclude such changes were related to BEV due to rapid autolytic changes and artifacts. CONCLUSION: IRI, not the extended use of TMZ, significantly increased the frequency of reversible CM in recurrent glioma patients. There are no unexpected adverse events or organ-specific toxicities detected among glioma decedents who received the TBI regimen.
NCMP-25. CLINICAL FEATURES, NEUROLOGIC RECOVERY, AND RISK PREDICTION OF POST-OPERATIVE POSTERIOR FOSSA SYNDROME: A PROSPECTIVE STUDY
Authors: Khan Raja B , Patay Zoltan , Kilmo Paul , Huang Jie , Onar-Thomas Arzu , Kumar Rahul , Boop Frederick A , Raches Darcy , Conklin Heather , Sharma Richa , Simmons Andrea , Sadighi Zsila , Gajjar Amar 
Published: December 2020

Abstract

INTRODUCTION
Posterior fossa syndrome (PFS) is a known consequence of medulloblastoma resection. Our aim was to clinically define PFS, its evolution over time, and ascertain risk factors for its development and poor recovery.

METHODS
Children with medulloblastoma treated at St Jude Children’s Research Hospital from 6/2013-7/2019 received standardized neurological examinations, before and periodically after radiation therapy. Most (98.3%) were enrolled on the ongoing multi-institutional protocol (SJMB12; NCT 01878617).

RESULTS
Sixty (34%) of 178 evaluated children had PFS. Forty (23%) had complete mutism (PFS1) and 20 (11%) had diminished speech (PFS2). All children with PFS had severe ataxia and 42.5% of PFS1 had movement disorders. By multivariable analysis, younger age (p=0.0005) and surgery in a low-volume surgery center (p=0.0146) increased PFS risk, while SHH tumors had reduced risk (p=0.0025). Speech and gait returned in PFS1/PFS2 children at a median of 2.3/0.7 and 2.1/1.5 months respectively, however, 12 (44.4%) of 27 PFS1 children with 12 months of follow-up were non-ambulatory at one-year. Movement disorder (p= 0.037) and high ataxia score (p&lt; 0.0001) were associated with delayed speech recovery. Older age (p= 0.0147) and high ataxia score (p&lt; 0.0001) were association with delayed gait return. Symptoms improved in all children but no child with PFS had normal neurologic examination at a median of 23 months after surgery.

CONCLUSION
Categorizing PFS in to types 1 and 2 has prognostic relevance. Almost half of the children with PFS1 remained non-ambulatory at 12-month follow-up. Surgical experience was a major modifiable contributor to the development of PFS.
NCOG-01. STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES AT THE GUY’S CANCER CENTER, LONDON: AN AUDIT FOR THE FIRST 17 MONTHS
Authors: Bhadra Kallol , Al-Salihi Omar , Hassan Sheila , Swampillai Angela , Blythe Kirsty , Forner Samantha , Sisodia Caroline , Brazil Lucy 
Published: December 2020

Abstract

INTRODUCTION
Stereotactic radiosurgery (SRS) commenced at Guy’s Cancer Hospital in August 2017. We report our first seventeen months’ data (August 2017 to December 2018) for brain metastases SRS.

METHOD
Patients referred via Neuro Oncology MDT were assessed for suitability for SRS via clinical review and 1mm-slice MRI. Treatment was planned on Eclipse v15.6 and delivered using Truebeam STx Linac(FFF) and Align RT v5.1 for matching. Dose prescription, according to departmental protocol, was set at 100% isodose, ranging from 18Gy to 25Gy, with fractionation varying from single to five fractions depending on factors including size, volume and locations. Post-treatment, patients were discharged back to their primary treating team for 3-monthly MRI.

RESULTS
Between Aug-17 to Dec-18, 70 patients with brain metastases were treated with a total of 122 lesions. Mean age was 66 years (range 37-93) and Median follow-up 9 months. Primary tumour sites mainly included lung 34(48.5%), breast 16(22.8%) and melanoma 17(24.3%). Brain-only metastases, including small volume primary with brain metastases were found in 85.4% cases, whilst visceral disease with brain metastases were found in 14.5% patients. Out of 122 lesions, the majority were treated in the primary setting; 95(77.8%) vs 27(22.1%) in the adjuvant setting. At 9-months follow up, local failure rate was in 26(21.3%) sites and 17 new sites in distant brain appeared. 31(44.2%) patients received no systemic therapy after SRS, whilst immunotherapy was received by 14(20%), with the remaining receiving hormones or chemotherapy. Median Overall Survival was 9.2 months (95% CI: 4.5-13.8) and Median progression-free survival was 5.9 months (95% CI: 7.0-10.4).

CONCLUSION
Overall Survival results were encouraging with initial auditing proving SRS as effective approach. Local control rates correlate well with randomized control trials results for SRS in brain metastases.
NCOG-04. PRETREATMENT VOLUME OF MR-DETERMINED WHITE MATTER INJURY (WMI) PREDICTS NEUROCOGNITIVE DECLINE AFTER HIPPOCAMPAL AVOIDANT (HA) WBRT+MEMANTINE FOR BRAIN METASTASES: SECONDARY ANALYSIS OF NRG ONCOLOGYCC001
Authors: Bovi Joseph , Pugh Stephanie , Brown Paul , Gondi Vinai , Wefel Jeffrey S , Tome Wolfgang A , Gilbert Mark , Robinson Cliff , Benzinger Tammie L S , Sabsevitz David , Lee Karen , Paulson Eric , Kundapur Vijayananda , Roberge David , Kaufman Isaac , Shah Sunjay A , Usuki Kenneth Y , Stea Baldassarre D , Yoon Harold A , DeMora Lyudmila , Mehta Minesh , Kachnik Lisa 
Published: December 2020

Abstract

PURPOSE
Previous secondary analysis of NRG/RTOG 0933 provided hypothesis-generating data supporting a relationship between larger volumes of MR-determined pre-treatment WMI and developing neurocognitive decline following HA-WBRT. The current study examines the relationship between pre-treatment WMI and neurocognitive function (NCF) following WBRT+memantine +/-HA in a substantially larger cohort.

METHODS
NCF testing was performed at baseline,2,4,6,and 12 months post-WBRT, and included Hopkins Verbal Learning Test–Revised (HVLT-R), Trail Making Test (TMT) Parts A and B, and Controlled Oral Word Association (COWA). Pre-treatment WMI was measured by FLAIR volume corrected for whole brain volume and corrected for the FLAIR volume associated with metastases (FLAIR/(whole brain volume – metastasis FLAIR volume). Pearson correlation coefficients were used to assess association between pre-treatment WMI and change from baseline for each standardized NCF score.

RESULTS
Of 518 randomized patients, 442 (217,WBRT+Memantine; 225,HA-WBRT+Memantine) had WMI data and were included. In the entire cohort, mean FLAIR volume was 9.3cc (0.1-68.2cc), mean metastases FLAIR volume was 61.5cc (0-423.5cc), mean Whole Brain volume was 1336.4cc (949.4-2397.8cc). At 2 months, there were no significant correlations between neurocognitive test change scores and pre-treatment WMI volume. However, at 4 months, both HVLT-R Total Recall and TMT Part B change score and pre-treatment WMI volume were significantly negatively correlated on the HA-WBRT+Memantine arm (ρ=-0.22 p=0.042 and ρ=-0.27, p=0.013). At 12 months, both TMT Part A and TMT Part B change scores and pre-treatment WMI volume were significantly negatively correlated on the HA-WBRT+Memantine arm (ρ=-0.30, p=0.046 and ρ=-0.53, p&lt; 0.001).

CONCLUSIONS
Pre-treatment WMI volume was a significant imaging-biomarker predictor of post-treatment neurocognitive decline at 4-and 12-months following HA-WBRT+Memantine. This suggests patients with greater pre-treatment WMI were more susceptible to neurocognitive decline, specifically when undergoing HA-WBRT, but not following standard WBRT. Dose heterogeneity inherent to HA-WBRT delivery may contribute to these findings and are hypothesis generating.
NCOG-06. A NOVEL ONLINE CALCULATOR PREDICTING SHORT-TERM POSTOPERATIVE OUTCOMES IN METASTATIC BRAIN CANCER PATIENTS
Authors: Khalafallah Adham , Jimenez Adrian , Patel Palak , Huq Sakibul , Azmeh Omar , Mukherjee Debraj 
Published: December 2020

Abstract

BACKGROUND
Establishing predictors of hospital length of stay (LOS), discharge deposition, and total hospital charges is essential to providing high-quality, value-based care. Though previous research has investigated these outcomes for patients with metastatic brain tumors, there are currently no tools that synthesize such research findings and allow for prediction of these outcomes on a patient-by-patient basis.

OBJECTIVE
We sought to develop a prediction calculator that uses patient demographic and clinical information to predict extended hospital length of stay, nonroutine discharge disposition, and high total hospital charges for patients with metastatic brain tumors.

METHODS
Patients undergoing surgery for metastatic brain tumors at a single academic institution were analyzed (2017-2019). Multivariate logistic regression was used to identify independent predictors of extended LOS (&gt; 8 days), nonroutine discharge, and high total hospital charges (&gt; $45,660.00). p &lt; 0.05 was considered statistically significant. C-statistics and the Hosmer-Lemeshow test were used to assess model discrimination and calibration, respectively.

RESULTS
A total of 222 patients were included in our analysis, with a mean age of 62.2 years. The majority of patients were male (52.7%) and Caucasian (76.6%). Our models predicting extended LOS, nonroutine discharge, and high hospital charges had optimism-corrected c-statistics &gt; 0.7, and all three models demonstrated adequate calibration (p &gt; 0.05). The final models are available as an online calculator (https://neurooncsurgery.shinyapps.io/mets_brain_cancer_calculator/).

CONCLUSIONS
Our models predicting postoperative outcomes allow for individualized risk-estimation for patients following surgery for metastatic brain cancer. Our results may be useful in helping clinicians to provide high-value care and to ensure optimal patient outcomes
NCOG-14. PSYCHOSOCIAL OUTCOMES IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1 AND PLEXIFORM NEUROFIBROMAS
Authors: Puccetti Diane , Mission Paige , Damodharan Shawn 
Published: December 2020

Abstract

OBJECTIVE
This case series seeks to examine neurocognitive outcomes, social-emotional functioning, and family burden in young children diagnosed with Neurofibromatosis, type 1 (NF1) with early growing plexiform neurofibromas (PNFs).

BACKGROUND
Neurofibromatosis, type 1 (NF1) is a common predisposing chronic disease arising in early childhood, with an incidence of approximately 1:3000. Though NF1 displays a wide range of phenotypic variability, the primary feature of the disease is peripheral nerve sheath tumors called neurofibromas. Less is well known regarding the broader neurocognitive and social-emotional profile in presentations with more complex tumor growths, namely PNFs, which are present in at least half of the NF1-affected population.

METHODS
Participants with NF1 and PNFs (n=2) aged 6-7years completed comprehensive neuropsychological evaluations and parents completed measures of quality of life, social-emotional/behavioral functioning of child, parental stress, family adaptability, and family cohesion.

RESULTS
Outcomes suggest broad neurocognitive dysfunction (e.g., executive functioning deficits, attention problems, visual-motor delays, and poor motor coordination), social-emotional challenges (e.g., symptoms of anxiety and depression, and poor social skills), and familial distress.

CONCLUSIONS
Findings indicate the value of early and frequent monitoring of children with PNFs in medical systems and multi-disciplinary teams, and the importance of early intervention for both children and families.