bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTIM-06. DENDRITIC CELL VACCINE STUDY FOR RECURRENT, HIGH-GRADE GLIOMA: TISSUE-BASED RNA SEQUENCING AND SERUM CYTOKINE LEVELS AS POTENTIAL BIOMARKERS
Authors: De La Fuente Macarena , Koru-Sengul Tulay , Heros Deborah , Miao Feng , Marrero Alain Fernandez , Tejera Dalissa , Liendo Michelle , Khan Aisha , Ayad Nagi , Ivan Michael , Komotar Ricardo 
Published: December 2020

Abstract

BACKGROUND
Glioblastoma is the most common primary malignant brain tumor. Despite multimodality treatment approach, median progression-free survival (PFS) is only 8 months, median overall-survival (OS) 14 months and 5-year survival rate of under 10%. Dendritic cells (DCs) are the professional antigen presenting cells of the immune system. The rationale for sensitizing dendritic cells to a pool of non-selected tumor antigens is based on the marked heterogeneity present within glioblastoma tumor cells.

METHODS
Phase 1/feasibility study of DC vaccine for recurrent high-grade glioma was conducted. Pooled, non-selected tumor antigens collected via tumor cell lysate were used for DC sensitization. RNA sequencing analysis was performed on all tumor samples. Cytokine levels in serum were detected using a Luminex cytokine panel.

RESULTS
A total of 20 patients were enrolled onto this study (median age 58yrs, range: 39–74, 65% male). Pathology showed WHO grade IV glioblastoma in 14 (70%) and grade III anaplastic astrocytoma in 6 (30%) patients. IDH wild type in 19 (95%) patients. Treatment emergent adverse events (all grades, regardless of attribution) occurred in more than 15% of the patients (20% fatigue, 15% dizziness, 15% headache, none leading to treatment discontinuation). There were five grade 3–4 and none grade 5 events. One grade 4 event (seizure) probable related to investigational treatment leading to treatment discontinuation. Four grade 3 events (dysphasia, possible related; intracranial hemorrhage unrelated; muscle weakness, unlikely related and hematoma, unrelated). Median PFS was 3.8 months. Median OS was 11 months. RNA sequencing in tumor samples and correlation with cytokine levels in serum is currently been analyzed.

CONCLUSION
Tumor lysate pulsed DC vaccination demonstrates acceptable safety and tolerability in high-grade glioma patients. Evaluations of integrating molecular profiling RNA sequencing information and cytokine levels to identify potential subset of patients with significant clinical benefit will be provided.
CTIM-14. PELAREOREP AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) WITH STANDARD CHEMORADIOTHERAPY/ADJUVANT TEMOZOLOMIDE FOR GLIOBLASTOMA MULTIFORME (GBM) PATIENTS: REOGLIO PHASE I TRIAL RESULTS
Authors: Kendall Jessica , Chalmers Anthony , McBain Catherine , Melcher Alan , Samson Adel , Phillip Rachel , Brown Sarah , Short Susan 
Published: December 2020

Abstract

BACKGROUND
Oncolytic viruses represent a novel treatment approach in GBM through oncolytic targeting as well as local immune activation. We designed a phase Ib, open-label study of intravenous reovirus (pelareorep) with GM-CSF alongside standard chemoradiotherapy to assess safety and tolerability.

METHODS
15 patients with newly diagnosed GBM were treated with GM-CSF 50mg subcutaneously (days 1–3) and pelareorep (days 4–5) in weeks 1 and 4 of chemoradiotherapy, and week 1 of adjuvant temozolomide course: 7 patients received 1x1010TCID50 (dose level 1); 8 received 3x1010TCID50 (dose level 2). The primary objective was to determine the maximum tolerated dose of pelareorep and GM-CSF with standard chemoradiotherapy. Secondary objectives were to gain preliminary assessment of the activity of the combination and assess treatment compliance.

RESULTS
1 dose limiting toxicity (DLT) and 20 SAEs were experienced overall; median number of SAEs per patient was 2. Commonest SAEs were nervous system disorders, predominantly seizures. SARs included fever/flu-like episodes (n=5), fall (n=1) and headache (n=1). Two SUSARs occurred in dose level 2, classed as vascular disorders manifesting as hypotension episodes – one was a DLT. Suspected relationship of SARs: pelareorep (n=6); temozolomide (n=1); radiotherapy (n=1); all study drugs (n=1). 87% of patients (n=13) completed chemoradiotherapy without unplanned delays. Adjuvant treatment was delayed in 21% of cycles overall, with the majority due to inadequate haematology/biochemistry values (44% of delays). Pelareorep was omitted in 4 instances in 4 patients during chemoradiotherapy and omitted in 4 instances in 3 patients during adjuvant treatment.

CONCLUSION
We present the first clinical data using intravenous pelareorep with GM-CSF alongside standard chemoradiotherapy in patients with GBM, suggesting that the combination is tolerable. Further analysis is underway and efficacy results will be ready for presentation at the conference. This work was supported by CRUK, The Brain Tumour Charity, Yorkshire Cancer Research and Oncolytics Biotech Inc.
CTNI-03. IMAGING FEATURES OF LEPTOMENINGEAL METASTASES OF NON-SMALL CELL LUNG CANCER: A SINGLE-CENTER REAL-WORLD STUDY
Authors: Zhen Junjie , Wen Lei , Li Shaoqun , Lai Mingyao , Shan Changguo , Cai Linbo 
Published: December 2020

Abstract

BACKGROUND
According to EANO-ESMO clinical practice guidelines, the MRI findings of LM are divided into 4 types, namely linear enhancement (type A), nodular enhancement (type B), linear combined with nodular enhancement (type C), and sign of hydrocephalus (type D).

METHODS
The MRI features of brain and spinal cord in patients diagnosed with NSCLC-LM in Guangdong Sanjiu Brain Hospital from 2010 until 2019 were investigated, and then were classified into 4 types. The imaging features were analyzed.

RESULTS
A total of 80 patients were enrolled in the study. The median age of the patients was 53.5 years old, and the median time from the initial diagnosis to the confirmed diagnosis of LM was 11.6 months. The results of enhanced MRI examination of the brain in 79 cases showed that the number of cases with enhancements of type A, B, C and D were 50 (63.3%), 0, 26 (32.9%) and 3 (3.8%), respectively, and that LM with metastases to the brain parenchyma was found in 42 cases (53.2%). The results of enhanced MRI examination of spinal cord in 59 cases showed that there were only enhancements of type A and C in 40 cases (67.8%) and 3 cases (5.0%), and no enhancement sign in the other 16 cases (27.2%).

CONCLUSION
MRI examination of brain and spinal cord will improve the detection rate of LM. The MRI features of NSCLC-LM in real world are mainly characterized by the linear enhancements of brain and spinal cord, followed by linear combined with nodular enhancement. The enhancements of type B and type D are rare in clinic. Almost half of the patients have LM and metastases to the brain parenchyma. Therefore, the differentiation of tumor metastases is needed to be paid attention to for the early diagnosis and the formulation of reasonable treatment plans.
CTNI-21. SCALP SPARING RADIATION WITH CONCURRENT TEMOZOLOMIDE AND TUMOR TREATMENT FIELDS (SPARE) FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Miller Ryan , Song Andrew , Ali Ayesha , Bar-Ad Voichita , Martinez Nina , Glass Jon , Andrews David , Judy Kevin , Evans James , Farrell Christopher , Werner-Wasik Maria , Chervoneva Inna , Ly Michele , Palmer Joshua , Liu Haisong , Shi Wenyin 
Published: December 2020

Abstract

INTRODUCTION
Standard of care for glioblastoma includes concurrent chemoradiation and maintenance temozolomide (TMZ) with tumor treatment fields (TTFields). Preclinical studies suggest TTFields and radiotherapy work synergistically. We report our experience evaluating toxicity of scalp-sparing radiation with concurrent TTFields.

METHODS
This is a single-arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Patients (age≥ 18 years) with KPS≥ 60 with newly diagnosed glioblastoma were eligible. Patients received concurrent scalp-sparing radiation (60 Gy/30 fx), standard TMZ (75 mg/m2 daily), and TTFields. Maintenance therapy included standard TMZ and TTFields continuation. Radiotherapy was delivered through TTFields arrays. Primary endpoint was safety and toxicity of concurrent TTFields with chemoradiation.

RESULTS
We report the first eighteen patients on trial. Majority were male (66.7%) with median age 59 years (34 to 77). Median KPS was 90 (70–100). Median follow-up was 6.0 months (1.4 to 18.0). Twelve (66.6%) patients had unmethylated MGMT, five (27.8%) were methylated, and one patient’s status was not obtained. Scalp dose constraints were achieved, with mean dose having a median value of 7.4 Gy (4.3–13.2), D20cc median 23.2 Gy (17.7–36.8), and D30cc median 20.3 Gy (14.8–33.4). Only one possible Grade 3 toxicity was observed in a patient who experienced a seizure in month six of the maintenance phase. Skin toxicity (erythema or dermatitis) was limited to Grade 1 (83.3%) or 2 (5.6%) during the concurrent phase and resolved spontaneously or responded to topical medications. Other Grade 1 events included fatigue (47.3%), cognitive impairment (31.6%), pruritis (52.6%), headache (26.3%), dizziness (15.8%), and nausea (26.3%). Other Grade 2 events included fatigue (21.1%) and headache (10.5%). Nine patients (50%) had progression, with median PFS of 7.6 months (2.2–9.6 months).

CONCLUSIONS
Concurrent TTFields with scalp-sparing chemoradiation is a safe and feasible treatment option with limited toxicity. Future randomized prospective trials are warranted to define therapeutic advantages of concurrent TTFields with chemoradiation.
CTNI-27. FIRST-IN-PEDIATRICS PHASE I STUDY OF GDC-0084 (PAXALISIB), A CNS-PENETRANT PI3K/mTOR INHIBITOR, IN NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) OR OTHER DIFFUSE MIDLINE GLIOMA (DMG)
Authors: Tinkle Christopher , Huang Jie , Campagne Olivia , Pan Haitao , Onar-Thomas Arzu , Chiang Jason , Klimo Paul , Boop Rick , Patay Zoltan , Shulkin Barry , Lucas John , Merchant Thomas , Upadhyaya Santhosh , Robinson Giles , Vinitsky Anna , Stewart Clinton , Gajjar Amar 
Published: December 2020

Abstract

BACKGROUND
GDC-0084 is an oral, highly selective and potent inhibitor of class I PI3K and moderate inhibitor of mTOR, with an established adult maximum tolerated dose (MTD) of 60 mg/day and evidence of brain tumor penetration in adult recurrent glioblastoma.

METHODS
We used a rolling-6 design to evaluate the safety and pharmacokinetic (PK) properties and establish the pediatric MTD of once-daily GDC-0084 administered after focal RT in children with newly diagnosed DIPG and histone H3 K27M-mutant DMG. Non-compartmental plasma PK analyses were performed using samples collected on cycle 1 days 1–3 after single-dose and day 28 at steady-state.

RESULTS
Twenty-five patients have been enrolled, 16 of whom were treated at study dosage levels of 27 mg/m2 (n=11) and 35 mg/m2 (n=5). Two dose limiting toxicities (DLTs) observed at 35 mg/m2 were grade 3 mucositis and grade 3 rash. Grade 3 hyperglycemia was the only DLT at 27 mg/m2. The most frequent grade 3 or 4 adverse events attributed to GDC-0084 were rash (5 patients), neutropenia (4), and hyperglycemia (2). After single-dose, GDC-0084 exposures (AUC0-48h) at 27 and 35 mg/m2 were 3399±1301 and 4462±2868 hr·ng/mL, respectively. Mean GDC-0084 half-life was 20.6±9.1 hr, comparable to that observed in adults.

CONCLUSIONS
The dosage of 27 mg/m2 has been established as the pediatric MTD of GDC-0084, which is approximately equivalent to 80% of the adult MTD. At 27 mg/m2, GDC-0084 is well tolerated in children where the spectrum of toxicities is similar to those observed in adults and consistent with this class of agents.
CTNI-58. A PROSPECTIVE TRIAL OF RESECTION AND SURGICALLY TARGETED RADIATION THERAPY FOR INITIAL OR SALVAGE TREATMENT OF AGGRESSIVE MENINGIOMA
Authors: Rogers Leland , Nakaji Peter , Youssef Emad , Smith Kris , Thomas Terry , Zabramski Joseph , Dardis Christopher , Pinnaduwage Dilini , McBride Heyoung , Brachman David 
Published: December 2020

Abstract

INTRODUCTION
Achieving durable local control (LC) for aggressive or recurrent meningiomas remains problematic. Resection (R) alone is insufficient and even with the addition of radiation therapy (RT), outcomes are suboptimal in many series.

OBJECTIVE
Hypothesizing R plus Surgically Targeted Radiation Therapy (STaRT) may improve LC, we evaluated a permanently implanted brachytherapy device consisting of Cs-131 seeds positioned within modular resorbable collagen carrier/spacer tiles (GammaTile, GT Medical Technologies, Tempe AZ).

METHODS
From 2/2013-2/2018 recurrent and newly diagnosed aggressive meningiomas were treated on a prospective single-arm study (NCT#03088579). At completion of maximum safe resection the tumor bed was lined with collagen tiles imbedded with Cs-131, delivering 60–80 Gy at 5 mm depth. No additional local therapy was given absent progression.

RESULTS
35 meningiomas in 28 patients were treated; 29 recurrent (22 prior R+RT, 6 R only, and 1 RT only) and 6 without prior therapy. WHO grade was I in 2 patients, II in 28, and III in 5. Median age was 66 years (range 37–82), KPS 80 (70–100), female: male ratio 15:13. Mean time for implantation was 5 minutes. At a median radiographic follow-up of 25.5 months (range 0.1–71) LC was 80% (28/35) and median time to progression had not been reached (95% CI &gt; 35.6 months). LC at 12/24/36/48 months was 100/89/72/72% for all tumors, 100/93/79/79% for Grade II, and 100/50/0/0% for Grade III, respectively. No patient receiving STaRT as their initial RT failed. Median overall survival was 50 months. Four symptomatic adverse events occurred, 2 wound breakdowns requiring surgery and 2 radiation-related brain changes, medically treated.

CONCLUSION
R+STaRT demonstrates favorable safety and LC outcomes in this single-arm prospective trial that includes heavily pre-treated patients. A commercial version of the device recently received FDA clearance for use in newly diagnosed malignant or recurrent intracranial neoplasms including meningiomas.
CTNI-61. PILOT STUDY OF REPEATED PLANNED GLUCARPIDASE FOLLOWING HIGH DOSE METHOTREXATE (HD-MTX) IN CNS LYMPHOMA (CNSL)
Authors: Schaff Lauren , Lobbous Mina , Sener Ugur , Gavrilovic Igor , Miller Alexandra , Stone Jacqueline , Piotrowski Anna , Skakodub Anna , Madzsar Juli , Schumpp Alyssa , Acosta Edward , Ryan Kevin , Carlow Dean , DeAngelis Lisa , Nabors Louis , Grommes Christian 
Published: December 2020

Abstract
This study explores the repeated use of glucarpidase following HD-MTX in patients with CNSL. HD-MTX requires aggressive hydration and inpatient monitoring to prevent toxicity. Glucarpidase 50 units(u)/kg for delayed MTX clearance results in a reduction of systemic MTX levels without crossing the blood brain barrier. This study explores the use of 1000 or 2000 units of glucarpidase following repeated cycles of MTX 3–8 g/m2. Eligible adult patients had isolated CNSL, CrCl ≥ 60 mL/min, and KPS ≥ 50. Rituximab with MTX was administered for eight cycles. Glucarpidase was given 24 hours after each MTX infusion. MTX concentrations were monitored in serum and cerebrospinal fluid (CSF). Twelve patients enrolled to date and data are available for 50 doses of MTX (3 g/m2 (20), 6 g/m2 (21), 8 g/m2 (9)). Glucarpidase 1000u (14) or 2000u (36) resulted in at least a 95% reduction in serum MTX levels within 15 minutes following 49/50 doses. A 93% decrease was seen with the remaining dose. Glucarpidase was not detected in the CSF of 7 patients analyzed. Potentially cytotoxic MTX concentrations (10–6 M) were observed in CSF 1 hour (7/7) and 6 hours (4/7) after glucarpidase administration. Radiographic responses are evaluable in 9 patients: complete response (5), partial response (2), stable disease (1), and progressive disease (1). No grade 3 events were attributed to glucarpidase; one grade 4 event of anaphylaxis occurred. Anti-glucarpidase antibodies were detected in 2/5 patients analyzed. In summary, administration of low-dose glucarpidase 24 hours after MTX 3–8 g/m2 results in a reproducible rapid reduction in serum MTX levels in non-renally impaired patients. CSF MTX levels remain therapeutic and clinical response expected from MTX-based therapy does not appear compromised. Anti-glucarpidase antibodies may develop though significance remains unclear. Study is ongoing. Future directions will explore glucarpidase use for reduction of inpatient stay with HD-MTX.
DDRE-01. ACQUIRED AND INTRINSIC RESISTANCE TO VEMURAFENIB IN BRAFV600E-DRIVEN MELANOMA BRAIN METASTASES
Authors: de Gooijer Mark C , Zhang Ping , Buil Levi C M , Freriks Stephan , Li Gang , Beijnen Jos H , van Tellingen Olaf 
Published: December 2020

Abstract
BRAF V600-mutated melanoma brain metastases (MBMs) are responsive to BRAF inhibitors, but clinical responses are less durable than those of extracranial metastases. We studied the impact of the drug efflux proteins P-glycoprotein (P-gp; ABCB1) and breast cancer resistance protein (BCRP; ABCG2) at the blood-brain barrier (BBB) on the efficacy of vemurafenib against BRAFV600E-mutated A375 MBMs. We intracranially implanted A375 tumor cells in wild-type and Abcb1a/b;Abcg2-/- mice. We characterized the tumor BBB, analyzed drug levels in plasma and brain lesions after oral vemurafenib and determined the efficacy against brain metastases and subcutaneous lesions. MRI shows that A375 MBMs disrupt BBB integrity, but vemurafenib accumulation in MBMs was still reduced by P-gp/BCRP. Vemurafenib is also less efficacious against MBMs in wild-type mice compared to Abcb1a/b;Abcg2-/- mice. Vemurafenib efficacy against subcutaneous A375 tumors was similar in both strains. Even in Abcb1a/b;Abcg2-/- mice, A375 MBMs rapidly developed resistance, which was unrelated to pharmacokinetic issues or insufficient inhibition of MAPK/PI3K pathways. Taken together, these studies demonstrate that although the BBB is disrupted in MBMs, P-gp/BCRP still limit the efficacy of vemurafenib. Moreover, the response to vemurafenib is less and of shorter duration also due to rapidly acquired resistance, most likely by resorting to non-canonical growth signaling.
EPID-07. ACCESS TO GLIOBLASTOMA CLINICAL TRIALS FOR RURAL PATIENTS IN THE UNITED STATES FROM 2010–2020
Authors: Nevel Kathryn , Capouch Samuel , Arnold Lisa , Peters Katherine , Mohile Nimish , Thomas Alissa 
Published: December 2020

Abstract

BACKGROUND
Patients in rural communities have less access to optimal cancer care and clinical trials. For GBM, access to experimental therapies, and consideration of a clinical trial is embedded in national guidelines. Still, the availability of clinical trials to rural communities, representing 20% of the US population, has not been described.

METHODS
We queried ClinicalTrials.gov for glioblastoma interventional treatment trials opened between 1/2010 and 1/2020 in the United States. We created a Structured Query Language database and leveraged Google application programming interfaces (API) Places to find name and street addresses for the sites, and Google’s Geocode API to determine the county location. Counties were classified by US Department of Agriculture Rural-Urban Continuum Codes (RUCC 1–3 = urban and RUCC 4–9 = rural). We used z-ratios for rural-urban statistical comparisons.

RESULTS
We identified 406 interventional treatment trials for GBM at 1491 unique sites. 8.7% of unique sites were in rural settings. Rural sites opened an average of 1.7 trials/site and urban sites 2.8 trials/site from 1/2010–1/2020. Rural sites offered more phase II trials (63% vs 57%, p= 0.03) and fewer phase I trials (22% vs 28%, p= 0.01) than urban sites. Rural locations were more likely to offer federally-sponsored trials (p&lt; 0.002). There were no investigator-initiated or single-institution trials offered at rural locations, and only 1% of industry trials were offered rurally.

DISCUSSION
Clinical trials for GBM were rarely open in rural areas, and were more dependent on federal funding. Clinical trials are likely difficult to access for rural patients, and this has important implications for the generalizability of research as well as how we engage the field of neuro-oncology and patient advocacy groups in improving patient access to trials. Increasing the number of clinical trials in rural locations may enable more rural patients to access and enroll in GBM studies.
EPID-31. CONTEMPORARY MANAGEMENT OF GRADE 2 AND 3 GLIOMA IN ALBERTA AND MANITOBA, 2012–2016: COMPARISON OF TOLERABILITY AND OUTCOMES ACROSS CHEMOTHERAPY REGIMENS
Authors: Walker Emily , Easaw Jay , Davis Faith , Pitz Marshall 
Published: December 2020

Abstract

BACKGROUND
Grade II/III glioma are a significant source of morbidity and mortality, with disease behaviour ranging from relatively mild to aggressive. Phase 3 clinical trial data informed contemporary treatment paradigms, but the perceived differences in tolerability between temozolomide-based regimens and procarbazine, CCNU, and vincristine (PCV)-based regimens has resulted in different treatment approaches across centres. We compared the frequency of progression and adverse drug events (ADE) among patients given these two regimens.

METHODS
Grade II/III glioma patients were identified through cancer registries in Alberta and Manitoba. Clinical data was obtained through electronic medical records. We estimated the distribution of patient age and sex, molecular data, treatment details, ADE, and patient outcomes across groups treated by temozolomide or PCV.

RESULTS
From 2012–2016, 344 patients were identified. Of these, 51% received chemotherapy: 26 received PCV (5/6 cycles completed by 85%), 142 received temozolomide (5/6 cycles completed by 78%). PCV resulted in grade 3/4 ADE in 38% of cycles, most commonly bone marrow toxicity. Temozolomide resulted in grade 3/4 ADE in 6% of cycles, most commonly nausea and rash. Clinical progression events occurred in 23% and 30% of PCV and temozolomide patients, respectively. Radiological progression events occurred in 50% and 52% of PCV and temozolomide patients, respectively.

CONCLUSION
Systemic therapy is commonly given to patients with grade II/III glioma, with more temozolomide use compared to PCV. All patients had high completion rates of treatment despite more frequent grade 3/4 adverse events in patients treated with PCV. The frequency of progression was similar across groups.