bluuebunny/crossref_metadata_2025_split huggingface dataset:
NCOG-27. A SINGLE-INSTITUTION RETROSPECTIVE SERIES OF SARS-COV-2 INFECTION IN ADULT GLIOMA PATIENTS
Authors: Lanman Tyler , Ruiz Amber , Nagpal Seema 
Published: November 2022

Abstract
A subset of cancer patients is particularly vulnerable to SARS-Cov-2 infection; however, real-world outcomes-based data on primary central nervous system tumor patients is sparse. This retrospective case series describes a cohort of adult glioma patients seen at Stanford Cancer Center between 1/20/2020 through 5/24/2022 who contracted SARS-Cov-2. We identified 18 patients with a diagnosis of glioma, with a median age of 54 years, who were infected with Covid-19. One patient contracted Covid-19 twice during this two-year period. Of these patients, four had pathology confirmed low-grade glioma, defined as oligodendroglioma or astrocytoma WHO grade 2, and 14 patients had high-grade glioma, defined as astrocytoma or glioblastoma WHO grade 4. Median KPS at time of infection was 70. Six individuals had notable cardiovascular comorbidities including coronary artery disease, obesity, and/or diabetes. All but one patient was vaccinated against Covid-19, and 6 were taking dexamethasone at the time of infection. Three patients required hospital admission for management of Covid-19 symptoms, although none required ICU-level of care. None died from Covid-related complications; however, two died from complications of their underlying cancer at the end of study. Our data suggest that glioma patients seen at Stanford Cancer Center do not experience an exceptionally high Covid-19 infectivity, hospitalization, or mortality rate, especially when compared to other vulnerable populations such as lung cancer patients. High vaccination rates, fairly low prevalence of cardiovascular comorbidities, and adherence to pandemic precautions among this cohort may have contributed to these results.
NCOG-28. LEEDS LOW GRADE GLIOMA SERVICE 2010-2022: A 12-YEAR EXPERIENCE
Authors: Kalra Neeraj , Livermore James , Spink Suzanne , Boyer Gillian , O'Malley Lianne , Flatley Michael , Maguire Melissa , Fairclough Sam , Wright Elizabeth , Armstrong Caroline , Stephenson Elisa , Ewan Seonaid , Cooper Sara , Guy Danielle , Saunders David , Igra Mark , Macmullen-Price Jeremy , Currie Stuart , Zaman Arshad , Derbyshire Catherine , Chakrabarty Arundhati , Gooden John , Chumas Paul , Mathew Ryan 
Published: November 2022

Abstract

INTRODUCTION
We present our 12-year experience of the surgical management of lower-grade gliomas (LGGs) by a multidisciplinary team in a large tertiary UK brain tumour centre.

METHODS
Retrospective analysis of all adult patients who underwent surgery in the Leeds Low Grade Glioma Service between January 2010 and January 2022. Data collected included demographics, procedure type, extent of resection, histological diagnosis, morbidity, mortality, tumour location, seizure control, adjuvant therapy, cognitive outcomes, progression-free survival (PFS) and overall survival (OS). Results were statistically analysed by Kaplan-Meier and Log Rank (Cox Proportional Regression Hazard) Testing (p&lt; 0.05).

RESULTS
254 patients underwent surgery between 2010-2022. Of these, 77 patients underwent a second resection surgery, 9 a third, and 1 patient had a total of 4 resections. 184 operations were carried out awake, 115 asleep and 42 patients underwent biopsy only. The most common histology at initial surgery was astrocytoma, IDH1m, WHO Grade 2 (41.7%) with oligodendroglioma, IDH1m, WHO Grade 2 being the second most common. The majority of tumors were located in the right frontal lobe (24%) followed by the left frontal lobe (18%). 32% of tumors were on the left side. The median time between diagnosis and first surgery was 36.5 months. 8 patients died during this time frame, 7 who had resection, 1 had biopsy.

CONCLUSION
Our experience of the surgical management of LGG over the last 12 years shows that maximal safe surgical resection remains important as first-line treatment. Greater extent of resection (EOR) can delay transformation, control seizures and improve survival. Awake surgery is well tolerated and can preserve eloquent function. A multidisciplinary team approach achieves the best outcomes, and is appreciated by our patients
NCOG-30. MULTISESSION RADIOSURGERY FOR UNFAVORABLE NONFUNCTIONING PITUITARY MACROADENOMA: 5-YEAR OUTCOMES FROM A SINGLE INSTITUTION PROTOCOL
Authors: Bhatnagar Akrita , Carrasquilla Michael , Nayar Vikram , Collins Brian , Collins Sean , Anaizi Amjad , Watson Joseph , Jean Walter C , Harris Brent , Conroy Dylan , Suy Simeng , Ebadirad Nelya , Aulisi Edward 
Published: November 2022

Abstract

Nonfunctioning macroadenoma is a commonly diagnosed pituitary tumor. Resection is the favored treatment, with radiosurgery often utilized for residual or progressing disease. Long-term outcomes are established for single-session radiosurgery, but mature outcomes are lacking for multisession radiosurgery. We report our institution’s 5-year efficacy and safety results for unfavorable nonfunctioning pituitary macroadenoma patients treated with 5-fraction robotic radiosurgery. Between 2010-2020, patients who completed 5-fraction radiosurgery for the treatment of unfavorable nonfunctioning pituitary macroadenomas were included. A tumor was considered unfavorable if the gross tumor volume (GTV) was larger than 5 cc or if it closely approached a critical structure (optic apparatus, brainstem or pituitary gland). Local control was calculated using the Kaplan-Meier Method.

RESULTS
Twenty predominately female patients (60%), age from 21-77 (median: 53 years) were included in this study. All underwent primary resection. Indications for radiosurgery included unresectable recurrence (85%) and residual disease progression (70%). Median tumor volume was 3.4 cm3 (range: 0.3-20.8 cm3) and 40% of the tumors were suprasellar. A mean dose of 30 Gy (range: 25Gy-30Gy), was delivered to a median isodose line of 80% (range: 75%-89%). Toxicity was minimal with 12 patients (40%) developing acute short-lived headaches and 1 patient (5%) developing a brief ipsilateral 6th nerve palsy. There was no radiation induced optic or pituitary dysfunction identified in this cohort. At a median follow up of 5 years local control at 5 years was 95%. There was 1 in-field failure pathologically confirmed following surgery for pituitary tumor hemorrhage and 2 radiographically confirmed out-of-field failures in patients with large tumors (&gt; 20 cc) treated with lower doses (25 Gy).

CONCLUSIONS
The treatment of unfavorable nonfunctioning pituitary macroadenoma with 5-fraction robotic radiosurgery provides excellent local control to date, with minimal toxicity. Continued follow-up for the long term optic and pituitary function preservation and tumor control is needed.
NCOG-32. PROGNOSTIC SIGNIFICANCE OF PREOPERATIVE NEUTROPHILIA AND LEUKOCYTOSIS IN CNS LYMPHOMA
Authors: Khan Osaama , Ordon Matt , Gibson Will 
Published: November 2022

Abstract

OBJECTIVE
The purpose of this study is to assess the prognostic value of preoperative neutrophilia and leukocytosis in a retrospective analysis of patients presenting with biopsy proven primary CNS lymphoma (PCNSL). This research is an extension of the growing body of evidence that preoperative hematologic values correlate with overall and progression free survival amongst solid tumors, including those involving the central nervous system. Methodology: Retrospective analysis of 50 patients with biopsy proven PCNSL. Preoperative complete blood counts (CBC) were collected alongside other clinical data including imaging characteristics (focal versus multifocal), molecular subtype, and neutrophil-leukocyte ratio (NLR). Survival time starting at time of biopsy was evaluated using Cox proportional hazard models and log-rank tests.

RESULTS
32 patients met eligibility criteria. Based upon the early data, only the NLR showed statistical significance on univariate analysis (HR 1.092 P=.002 CI 1.06-1.15) Multivariate analysis failed to show a statistical relationship when the independent variables age at diagnosis, preoperative leukocytosis, ANC/ALC, and WBC. The NLR approached statistical significance with multivariate analysis (HR 1.17 P= .053 CI .99-1.57). Molecular subtyping and imaging characteristic analysis is ongoing, and is not included in this analysis (including GCB subtype, MYC gene mutation). Future Direction: Studies like ours are necessary to ensure a cheap, repeatable, and universally available test for PCNSL patients. Preliminary analysis showed a trend towards significance when evaluating the NLR on multivariate analysis. More data is required to further elucidate these findings. Analysis is ongoing and will include other prognostic variables, including molecular profile and imaging characteristics.
NCOG-34. METASTATIC PAPILLARY TUMOR OF THE PINEAL REGION: ROLE OF STEREOTACTIC IRRADIATION AND ADJUVANT TEMOZOLOMIDE
Authors: Koshy Amily , Kim Esther , Higgins Shannon , Haggiagi Aya 
Published: November 2022

Abstract

INTRODUCTION
Papillary tumor of the pineal region (PTPR) is a very rare tumor comprising &lt; 1% of all intracranial neoplasms. It was first included as a distinct tumor entity in the 2007 World Health Organization classification. Due to its rarity, only anecdotal data is currently available to guide management. However, with these tumors being recognized more frequently, further molecular observations and therapeutic experiences are necessary. Herein, we report an unusual case of PTPR with a previously treated leptomeningeal metastasis (LM) whom we successfully managed with Gamma Knife Radiosurgery (GKRS) and adjuvant temozolomide at time of distant brain parenchymal tumor progression. CASE REPORT: A 41-year-old man presented with headache and diplopia in 2015, MRI brain revealed a large cystic enhancing lesion in the pineal region protruding into the third ventricle and causing obstructive hydrocephalus. He had a ventriculoperitoneal shunt placed and underwent partial tumor resection. He then transferred care to our institution and a gross total resection was achieved. Pathology confirmed PTPR. A repeat MRI 15 months later showed evidence of radiographic LM in the cerebellum and he underwent craniospinal proton radiation therapy. He remained stable until January 2020 when a new left temporal heterogeneously enhancing multicystic lesion was identified on surveillance MRI. He underwent subtotal resection of this intra-axial lesion. Histological features of the tumor were similar to his initial tumor. Somatic tumor mutation testing using FoundationOne®CDx did not reveal targetable molecular alterations. Following surgery, he received GKRS and six cycles of adjuvant temozolomide. At 21-month follow up, patient continues to do well.

CONCLUSION
To our knowledge, this is the first case to describe a metastatic brain intraparenchymal PTPR. We also describe a first case of successful therapeutic strategy for a distant recurrence of PTPR.
NCOG-40. UTILITY OF THE SEIZURE CONTROL COMPOSITE INDEX (RANO-SCCI) IN EVALUATING SEIZURES IN CNS TUMOR PATIENTS
Authors: Miller Hope , Christ Alexa , Grajkowska Ewa , Acquaye Alvina , Adegbesan Kendra , Boris Lisa , Burton Eric , Chambers Claudia , Choi Anna , Evans Karen , King Amanda , Komlodi-Pasztor Edina , Leeper Heather , Levine Jason , Lindsley Matthew , Lollo Nicole , Mentges Kelly , Panzer Marissa , Penas-Prado Marta , Pillai Valentina , Polskin Lily , Reyes Jennifer , Roche Kayla , Rogers James , Sahebjam Solmaz , Sass Dilorom (Delia) , Shuboni-Mulligan Dorela , Stockdill Macy , Theeler Brett , Wall Kathleen , Wollet Alex , Wu Jing , Diarte Jose , Gilbert Mark , Avila Edward , Armstrong Terri , Vera Elizabeth 
Published: November 2022

Abstract

BACKGROUND
Seizures are a common symptom in patients with CNS tumors. The RANO-Seizure Control Composite Index (RANO-SCCI) was developed to monitor seizures over time by patients and clinicians. We describe the use of the RANO-SCCI as part of the NCI NOB-Natural History Study.

METHODS
Patients completed a RANO-SCCI prior to their clinic appointment with results shared with clinicians who then completed a RANO-SCCI as part of the same appointment. Seizure reports were tallied by respondent type and further by tumor type and grade. Concordance between patient and clinician report was also investigated.

RESULTS
One hundred fifty-seven patients underwent 250 clinical evaluations. Participants were primarily white (82%) males (57%) with median age 47 years (range: 19 – 78). Most had high grade (60%) primary brain (86%) tumors, were in surveillance (76%), with no prior recurrence (57%) and KPS ≥ 90 (76%). Half of patients and 62% of clinicians reported the patient ever having a seizure. The 12% discordance were all where the patient did not report a seizure, but clinicians did. There was good agreement on seizure reporting since last visit (74% patients, 78% clinicians), and anti-seizure medication use (51% patients, 57% clinicians). Seizures were reported more frequently in patients with high-grade tumors (WHO Grade 3 or 4) (60% patients, 76% clinicians) versus low-grade (WHO Grade 1 or 2) (51% patients, 59% clinicians), and among patients with oligodendrogliomas (71% patients, 85% clinicians) versus non-oligodendroglioma tumors (54% patients, 68% clinicians).

CONCLUSIONS
The RANO-SCCI was used for self-report and clinician report of seizure activity. A higher frequency was reported among oligodendroglioma and high-grade tumors. Disparities between patient and clinician responses may reveal a limitation in the patient’s ability to recognize and assess their seizure symptoms. Further work will investigate reporting congruence and associations with clinical and demographic characteristics.
NCOG-43. A RETROSPECTIVE ANALYSIS OF THE IMPACT OF THE COVID-19 INFECTION ON NEURO-ONCOLOGY CARE AND PATIENT OUTCOMES: A TWO-SITE STUDY
Authors: Johnson Margaret , Durling Jennifer , Brown Casey B , Khasraw Mustafa , Petitt Zoey , Cort Nicole , Lipp Eric S , Buckley Evan D , Herndon James E , Kam Waynekid , Gao Karen , Chheda Milan G , Butt Omar H 
Published: November 2022

Abstract

BACKGROUND
COVID-19 radically changed neuro-oncology care. In this retrospective study, we examine the impact of COVID-19 infection on neuro-oncological care and clinical outcomes in two geographically separate populations.

METHODS
Descriptive statistics compared demographic and clinical history extracted from the medical records of COVID-19 positive patients with primary brain tumors treated between 3/1/2020 and 3/31/2021. All subjects were unvaccinated given our cohort pre-dates the ubiquitous availability of vaccines. Patients were treated at Washington University (WashU) in St. Louis, MO and Duke University in Durham, NC. Each site’s respective institutional review board approved the study, with a data transfer agreement in place.

RESULTS
We identified 62 total (WashU=13; Duke=49) subjects with positive COVID-19 infection. Patients were predominantly white (85.5%), male (56.5%), with KPS &gt;=70 (82.3%) and never smoked (69.4%). WashU patients tended to be older with grade 4 tumors, but this was not significant. At the time of COVID infection 35.5% of patients were receiving cancer-directed therapy. Notably, 37.1% experienced delayed care due to a COVID-19 diagnosis, most often for scheduled systemic treatment or radiation treatment. A further 37.1% had an ER visit, hospitalization, or ICU stay attributed to COVID-19. Of the 17 patients who died during the study period, 4 deaths were attributed directly to COVID-19 and not to their underlying brain tumor or other cause. Finally, telehealth use differed between sites (84.6% at WashU vs 14.3% at Duke). However, this difference could not be attributed to patient age, performance status, or distance from treating institution.

CONCLUSION
COVID-19 infection led to treatment delays and death for a subset, but not the majority of neuro-oncology patients. Telehealth use varied between sites and was not associated with commonly held assumptions about patient distance or performance status, suggesting evolving practice norms following telehealth’s introduction. Study limitations include a small sample size
EXTH-01. INTRATHECAL DELIVERY OF DENDRITIC CELL VACCINE ERADICATES TUMOR GROWTH AND PROTECTS AGAINST LEPTOMENINGEAL DISEASE RE-INOCULATION IN HER2+ AND TRIPLE NEGATIVE BREAST CANCER LMD XENOGRAFT MODELS
Authors: Law Vincent , Kodomudi Krithika , Snyder Colin , Forsyth Peter , Czerniecki Brian 
Published: November 2022

Abstract

BACKGROUND
Leptomeningeal disease (LMD) occurs in approximately 5% of patients with breast cancer and has a median survival of 2-4 months. We found a loss of the anti-HER2 and anti-HER3 CD4 Th1 immune responses in breast cancer patients. In pre-clinical and clinical trials, the administration of class II HER2 peptide-pulsed dendritic cell vaccine (HER2-DCV) partially restores anti-HER2 Th1 immune responses with pathologic complete responses in HER2+ breast cancer patients. Here, we examined the intrathecal (IT) delivery of HER2/HER3-DCV in breast cancer-associated LMD immunocompetent animal models.

METHODS
Luciferase-labeled HER2+ TUBO breast cancer cells were injected into the cisterna magna of BALB/c mice to produce LMD. We used our Murine Ommaya (mimics an Ommaya reservoir in patients) for the IT administration of DCVs into the CSF. RESULTS AND

DISCUSSION
breast cancer-LMD mice were randomized into following groups: 1) HER2-DCV IT 2) HER3-DCV IT 3) HER2/HER3-DCV IT. The median survival of untreated (control) group was 15 days. All groups given DCV IT prolonged survival (p&lt; 0.001). Interestingly, HER2-/HER3-DCV IT was able to rescue disease mice (71% in HER2+ breast cancer-LMD and 28% in triple negative breast cancer-LMD) and showed complete tumor regression. Some surviving mice were immune to subsequent tumor rechallenge. In mice CSF, we found evidence of CD4+ and CD8+ T-cells infiltration, and robust IFN-g and IL18 response upon DCV treatment.

CONCLUSIONS
Our preclinical data supported a clinical trial (submitted) of the IT delivery of DCV in breast cancer patients with LMD.
EXTH-02. ANTI-TUMOR EFFECTS AND IN VIVO DYNAMICS OF EPCAM-DIRECTED CAR T-CELLS FOR BRAIN METASTASES FROM LUNG CANCER
Authors: Xu Tao , Karschnia Philipp , Cadilha Bruno , Dede Sertac , Lorenz Michael , Seewaldt Niklas , Nikolaishvili Elene , Müller Katharina , Blobner Jens , Teske Nico , Langer Sigrid , Obeck Hannah , Lorenzini Theo , Mulazzani Matthias , Zhang Wenlong , Ishikawa-Ankerhold Hellen , Buchholz Veit R , Subklewe Marion , Thon Niklas , Straube Andreas , Tonn Joerg-Christian , Kobold Sebastian , von Baumgarten Louisa 
Published: November 2022

Abstract

BACKGROUND
Lung cancer patients are at a high risk for brain metastases, and affected patients frequently succumb to their intracranial disease. Chimeric Antigen Receptor (CAR) T-cells emerged as a powerful cell-based immunotherapy for hematological malignancies; however, it remains unclear whether CAR T-cells represent a viable therapeutic avenue for brain metastases.

METHODS
A fully immunocompetent, orthotopic cerebral metastasis model was established in mice by combining a chronic cranial window with repetitive intracerebral two-photon laser scanning microscopy. This approach enabled the in vivo-characterization of fluorescent CAR T-cells and tumor cells on a single-cell level over weeks. Intraparenchymal injection of EpCAM-expressing Lewis lung carcinoma cells was performed, and EpCAM-directed CAR T-cells (EpCAMCAR T-cells) were injected into the adjacent brain parenchyma after brain tumor formation.

RESULTS
All mice had visible tumor take with rapidly growing lesions following intracranial tumor cell injection. In mice treated with EpCAMCAR T-cells, we observed substantial CAR T-cell accumulation within the tumor compared to controls treated with undirected T-cells. This was paralleled by lower velocities of EpCAMCAR T-cells, characterizing antitumor cytotoxicity due to ‘immune cell’-‘tumor cell’ contacts. Consequently, treatment with EpCAMCAR T-cells resulted in reduced tumorous growth as determined per in vivo-microscopy (median tumor area on day 10: 1.8 versus 10.8 mm2; p=0.001) and immunohistochemistry of excised brains. However, the number of intratumoral EpCAMCAR T-cells within the tumor markedly decreased during the observation period, pointing towards insufficient persistence. Accordingly, survival was prolonged in mice receiving EpCAMCAR T-cells but long-lasting remission was rare (median survival: 15 versus 13 days; p=0.012). No CNS-specific or systemic toxicities of EpCAMCAR T-cells were encountered.

CONCLUSION
Our findings indicate that EpCAMCAR T-cells injected into the cerebral parenchyma may safely induce relevant anti-tumor effects in brain metastases from lung cancer. Strategies improving the CAR T-cell persistence within brain metastases are warranted to further boost the therapeutic success.
EXTH-07. AN ANTISENSE OLIGONUCLEOTIDE AGAINST TUMOR MICROTUBES IN GLIOBLASTOMA AS A NEW THERAPEUTIC OPTION TO IMPROVE TUMOR SPECIFIC THERAPY
Authors: Weil Sophie , Azorín Daniel Domínguez , Jung Erik , Higgins Josie , Mohammed Hafeez , Reckless Jill , Ramsden Nigel , Keller Peter , Grainger David , Wick Wolfgang , Winkler Frank 
Published: November 2022

Abstract
Glioblastomas are known to be highly therapy resistant tumors. The description of tumor microtubes (TMs) as long cellular protrusions that connect glioblastoma cells to a network resistant against all standard therapies advanced the basic biological understanding of the disease and offers a new therapeutic target. An antisense oligonucleotide (ASO) against the production of a protein involved in formation and function of TMs was developed and tested in a xenograft mouse model of human glioblastoma cells. After the implantation of fluorescent tumor cells under a chronic cranial window and the establishment of the tumor, the ASO treatment was started with a continuous micropump application directly into the central nervous system (CNS) and treatment effects were observed in a two-photon microscope. Furthermore, co-treatment with irradiation was tested and tumor size as well as protein expression evaluated in and ex vivo. This led to the conclusion that the setup of combined continuous pump application and two photon microscopy is technically feasible and tolerable. It offers the possibility of applying compounds directly into the CNS under live and longitudinal readouts. The fluorescently tagged ASO was traced in the brain parenchyma over weeks proving a high stability of the compound. In combination with radiotherapy, animals treated with the active ASO against the protein of formation and function of TMs showed a smaller tumor size than animals treated with radiotherapy and the non-targeting ASO. The targeted protein was expressed less in the treated animals then the animals receiving the control ASO and the extend of protein expression correlated with tumor size. Hence, after successful therapies with ASOs in other neurologic diseases and the need for better therapeutic options for glioblastoma patients, the development of an ASO against a protein involved in the TM formation and function offers a new therapeutic option with high translational potential.