bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACTR-15. PHASE 1 TRIAL OF A KETOGENIC DIET IN PATIENTS RECEIVING STANDARD-OF-CARE TREATMENT FOR RECENTLY DIAGNOSED GLIOBLASTOMA
Authors: Gresham Gillian , Amaral Lauren , Lockshon Laura , Levin Dana , Rudnick Jeremy , Provisor Arlene , Shiao Stephen , Bhowmick Neil , Irwin Scott , Freedland Stephen , Hu Jethro 
Published: November 2019

Abstract

BACKGROUND
There is abundant interest in the potential therapeutic and supportive role of a ketogenic diet (KD) in patients with glioblastoma (GBM). The KD is a high fat/low carbohydrate metabolic therapy that modulates several of the bioenergetic and biosynthetic pathways that are dysregulated in GBM. To date, studies of the KD in cancer patients have been limited in scope. This study will provide preliminary evidence on the safety and feasibility of a 16-week ketogenic diet in patients with GBM.

METHODS
This is an open-label single-arm feasibility trial being conducted at Cedars-Sinai Medical Center. We will recruit 20 recently diagnosed GBM patients who are receiving standard-of-care (SOC) treatment. Patients may enroll within 3 months of diagnosis, thus allowing patients who have already begun SOC chemoradiation the opportunity to participate. Excluded are patients with a KPS < 70, BMI < 22, or on high doses of steroids. Consenting patients will maintain a 16-week ketogenic diet (KD) supervised and monitored by study dietitians (RD). The primary outcome of safety will be assessed by monitoring weight, BMI, and adverse events. Secondary outcomes are: 1) Adherence to the KD, as assessed by BID blood glucose and ketone levels; 2) Time to progression and overall survival from date of KD initiation 3) Mean change in overall QOL, as measured using the QLQ30 and QLQ-BN20 questionnaires; and 4) Mean change in cognitive scores at 16 weeks from baseline. Exploratory outcomes include metabolic, inflammatory, and immune biomarkers; gut microbiota analysis; large oncosome analysis; and daily activity assessed with a wearable activity monitor. This novel trial incorporates multiple digital devices and mobile applications into the study design. Accrual is ongoing with 10 patients currently enrolled (NCT03451799).
ACTR-17. DIAGNOSTIC UTILITY OF SERUM microRNA CLASSIFICATION IN DIFFUSE GLIOMA
Authors: Ohno Makoto , Matsuzaki Juntaro , Kawauchi Junpei , Aoki Yoshiaki , Miura Junichiro , Takizawa Satoko , Kato Ken , Sakamoto Hiromi , Matsushita Yuko , Takahashi Masamichi , Miyakita Yasuji , Ichimura Koichi , Narita Yoshitaka , Ochiya Takahiro 
Published: November 2019

Abstract
To improve clinical outcomes, a less invasive screening test for detection of diffuse glioma is needed. The purpose of this study is to establish models using serum microRNAs (miRNAs) to distinguish between diffuse glioma patients from non-cancer controls (Glioma Index) and between glioblastoma (GBM), primary central nervous system lymphoma (PCNSL), and metastatic brain tumors (Meta) (3-Tumor Index). A total of 580 patients, including 266 with brain or spinal tumors and 314 non-cancer controls, were analyzed. Non-cancer control samples were collected from the National Cancer Center Biobank and members of the general population undergoing routine health examinations. Expression of serum 2565 miRNAs was assessed in each sample, and the expression profiles were compared between diffuse glioma patients and non-cancer controls, and between GBM, PCNSL, and Meta. Diagnostic models were established using a training set, and diagnostic performance was confirmed in validation and exploratory sets and area under the receiver operating curve (AUC), sensitivity, specificity, and accuracy were used to evaluate their diagnostic performances. The Glioma Index was constructed using three miRNAs. The AUC was 99%, with sensitivity of 95% and specificity of 97% in the validation set. The Glioma Index classified 93% of PCNSL, 89% of Meta, 91% of benign brain tumors, and 0% of spinal tumors as positive in the exploratory set. The 3-Tumor Index was constructed using 48 miRNAs and had an accuracy of 0.80 in the validation set, positively detecting 94.1% of GBM, 80% of Meta, and 50% of PCNSL. In conclusion, we developed novel serum miRNA discriminant models to detect diffuse glioma from non-cancer control and to discriminate tumor histology. These models could serve as less invasive screening tools or complementary diagnostic tools, thereby decreasing neurosurgical risks.
ACTR-18. A PHASE IB/II CLINICAL TRIAL OF DODECAFLUOROPENTANE EMULSION (DDFPE) AS A RADIOSENSITIZER IN GLIOBLASTOMA
Authors: Lickliter Jason , Ruben Jeremy , Jennens Ross , Kichenadasse Ganessan , Gzell Cecelia , Mason Ralph , Carmody Raymond , Becker Jennifer , Stea Baldassarre , Zhou Heling , Sellenger Michael , Longacre Olivia , Graham Kaitlin , Unger Evan 
Published: November 2019

Abstract

BACKGROUND
Tumor hypoxia decreases the response of glioblastoma multiforme (GBM) to radiotherapy (RT) and chemotherapy (temozolomide[TMZ]). The purpose of this study was to evaluate the safety and efficacy of a novel oxygen therapeutic, dodecafluoropentane emulsion (DDFPe), in chemoradiation treatment of GBM and stratify the results based on predicted TMZ response.

METHODS
With ethics approval and informed consent, 11 adult GBM patients were enrolled. Patients were administered DDFPe via IV infusion (2% w/vol at doses of 0.05, 0.1 or 0.17 mL/kg) within 5–30 minutes prior to each 2 Gy fraction of RT (30 fractions over 6-weeks) while breathing supplemental oxygen. Patients also received standard concurrent and adjuvant TMZ. To evaluate the reversal of tumor hypoxia, patients underwent oxygen-sensitive (TOLD) MRI before and after DDFPe administration. Patients were also studied with serial MRI scans per standard of care and followed for survival.

RESULTS
The non-serious adverse events considered by the investigator to be possibly, probably, or definitely related to DDFPe administration included fatigue (n=4), headache (n=2) and decrease in platelet count (n=2). Serious adverse events included two patients with symptomatic radiation necrosis: one patient at each of dose levels 0.1 and 0.17 mL/kg. Enrollment continued at the 0.1 mL/kg dose without additional significant DDFPe-related toxicity. Historically, the average overall survival for GBM patients is about 14.6 months. The median overall survival for the study was 591 days, or 19.4 months. According to independent review of the serial MR images, the median time to progression was 555 days, or 18 months, compared to a historical control of 6.9 months. TOLD MRI showed a trend in improved tumor oxygenation.

CONCLUSION
Although small, this trial shows that DDFPe used as a radiosensitizer appears to be safe and may provide some survival benefit. The FDA has allowed a Phase II clinical trial to assess its effectiveness.
ACTR-31. THE USE OF TTFIELDS FOR NEWLY DIAGNOSED GBM PATIENTS IN GERMANY IN ROUTINE CLINICAL CARE (TIGER: TTFIELDS IN GERMANY IN ROUTINE CLINICAL CARE)
Authors: Bähr Oliver , Tabatabai Ghazaleh , Fietkau Rainer , Goldbrunner Roland , Glas Martin 
Published: November 2019

Abstract

OBJECTIVE
Survival for the most common brain tumor, glioblastoma (GBM), has not improved since 2005, despite numerous phase 3 trials. The phase 3 EF-14 trial demonstrated significantly improved overall, progression-free and long-term survival in newly diagnosed GBM (ndGBM) patients by addition of TTFields to adjuvant temozolomide chemotherapy. As there is very high interest among prescribing physicians from all disciplines to further evaluate these effects in routine clinical care, the aim of the TIGER study is to assess safety and efficacy of TTFields in routine care and reasons for patients refusing TTFields treatment, quality of life, treatment duration and compliance.

METHODS
The TIGER study is a multi-centre, prospective, non-interventional study in Germany (NCT03258021). All ndGBM patients who are eligible for TTFields therapy are asked for consent for study-participation and comprehensively introduced to the therapy to allow them to make a conscious positive or negative therapy decision. At baseline and 2–4 months after treatment start, demographic data, the QoL and reasons for therapy decision are evaluated utilizing the EORTC-QLQ-C30/BN-20 and TTFields questionnaire. Inclusion of 1000 patients is planned (500 with positive/negative treatment decision, respectively) with a follow-up period of 18 months.

RESULTS
At the last data cut-off (May 2019), 497 patients have made a decision regarding treatment with TTFields. Within this population, 84% of patients decided to undergo TTFields therapy. The median age of patients included in the trial is currently 58.3 years (19–85). 91% of patients report that the prospect of treatment success considerably or strongly affects treatment decision. Most recent data will be presented at the meeting.

CONCLUSION
Systematic and prospective data assessment for using TTFields in routine clinical care including patient’s therapy decision can be evaluated in TIGER. Additionally, the study supports the analysis of treatment duration and usage rate, which could drive future assessment of TTFields treatment duration.
ACTR-33. INFIGRATINIB (BGJ398) IN PATIENTS WITH RECURRENT GLIOMAS WITH FIBROBLAST GROWTH FACTOR RECEPTOR (FGFR) ALTERATIONS: A MULTICENTER PHASE II STUDY
Authors: Lassman Andrew , Sepúlveda-Sánchez Juan , Cloughesy Timothy , Gil-Gil Juan , Puduvalli Vinay , Raizer Jeffrey , De Vos Filip , Wen Patrick , Butowski Nicholas , Clement Paul , Groves Morris , Belda-Iniesta Cristobal , Steward Keith , Rowsey Steven , Ye Yining , Roth Patrick 
Published: November 2019

Abstract

INTRODUCTION
FGFR mutations and translocations occur in approximately 10% of glioblastomas (GBMs). FGFR3-TACC3 fusion is predictive of response to FGFR tyrosine kinase inhibitors pre-clinically and clinically. Infigratinib (BGJ398) is a selective small-molecule pan-FGFR kinase inhibitor with anti-tumor activity in several solid tumors with FGFR genetic alterations.

METHODS
Open-label phase II trial of adults with recurrent high-grade gliomas following failure of initial therapy (NCT01975701). Tumors harbored FGFR1-TACC1 or FGFR3-TACC3 fusions, activating mutations in FGFR1, 2 or 3, or FGFR1, 2, 3, or 4 amplification. Oral infigratinib was administered 125 mg d1–21 q28d. Prophylaxis for hyperphosphatemia was recommended. Primary endpoint: 6-month progression-free survival (6mPFS) rate by RANO (locally assessed); goal of >40%.

RESULTS
As of Sep 2017, 26 patients (16 men, 10 women; median age 55 years, range 20–76 years; 50% with ≥ 2 prior regimens) were treated; 24 (92.3%) discontinued for disease progression (n=21) or other reasons (n=3). All had FGFR1 or FGFR3 gene alterations; 4 had >1 gene alteration. Estimated 6mPFS rate was 16% (95% CI 5.0–32.5%); median PFS was 1.7 months (95% CI 1.1–2.8 months); median OS was 6.7 months (95% CI 4.2–11.7 months); ORR was 7.7% (95% CI 1.0–25.1%). Best overall response was: partial response 7.7% (FGFR1 mutation n=1; FGFR3 amplification n=1); stable disease 26.9%; progressive disease 50.0%; missing/unknown 15.3%. Most common (>15%) all-grade treatment-related adverse events (AEs) were hyperphosphatemia, fatigue, diarrhea, hyperlipasemia, and stomatitis. There were no grade 4 treatment-related AEs. Eleven patients (42.3%) had treatment-related AEs requiring dose interruptions/reductions (most commonly hyperphosphatemia).

CONCLUSIONS
Infigratinib induced partial response or stable disease in approximately one-third of patients with recurrent GBM and/or other glioma subtypes harboring FGFR alterations. Most AEs were reversible and manageable. Further potential combinations are being explored in patients with proven FGFR-TACC fusion genes; analysis of biomarker data is ongoing.
ACTR-40. PHASE 2 SAFETY AND EFFICACY OF AR-67 (7-T-BUTYLDIMETHYLSILTYL-10-HYDROXYCAMPTOTHECIN) IN PATIENTS WITH RECURRENT GLIOBLASTOMA MULTIFORME (GBM) OR GLIOSARCOMA
Authors: Kumthekar Priya , Raizer Jeffrey , Cavaliere Robert , Devoe Craig , Jensen Randy , Stieber Volker , Runk Tina , Grewal Jai , Brownell Elise , Zukiwski Alex , Proniuk Stefan , Arnold Susanne , Vredenburgh James 
Published: November 2019

Abstract

BACKGROUND
AR-67 (formerly DB-67) is a novel 3rd generation camptothecin with improved safety and lipophilicity than current drugs in this class. Safety and efficacy of AR-67 were evaluated in a Phase 2 study in recurrent GBM/gliosarcoma in adult patients.

METHODS
AR-67 (7.5 mg/m2) was administered once daily by IV infusion for 5 consecutive days on a 21-day cycle. Cohort 1 patients (N=31/46 enrolled) had not received (or had not recently failed) bevacizumab. Cohort 2 patients (N=13/46 enrolled) had failed bevacizumab within 90 days before screening. Cohort assignments for 2/46 patients were undetermined. Tumor response was assessed ≥14d after every second cycle and before every third cycle using MRI. Primary endpoints were 6-month PFS (Cohort 1), and 2-month PFS (Cohort 2).

RESULTS
45/46 patients received ≥ one dose of AR-67; one patient (Cohort 1) died prior to dosing. Efficacy: 6/30 (Cohort 1) and 2/13 (Cohort 2) treated patients achieved the primary endpoints of 6- and 2-month PFS, respectively. Across the study, PR was the best overall response in 3/45 treated patients, all in Cohort 1. SD was the best overall disease response in 7/45 treated patients (5 in Cohort 1 and 2 in Cohort2). Safety: AR-67 was well tolerated; 17 patients (38%) exhibited serious adverse events (SAEs) including headache and Grade 4/5 muscular weakness (2.2%). Most TEAEs were mild/moderate in intensity and Grade 1–3 intoxicity. Notably absent was Grade 4 diarrhea, a hallmark of other approved camptothecin chemotherapies.

CONCLUSIONS
AR-67 was well tolerated and exhibited a safety profile consistent with or better than currently approved camptothecins. 6/30 treated patients in Cohort 1 and 2/13 patients in Cohort 2 achieved the primary endpoints of 6- and 2-month PFS, respectively. PR was the best overall response in 3/45 treated patients and SD was the best overall response in 7/45 patients.
ACTR-41. AN ARGUMENT THAT MORE ADJUVANT TEMOZOLOMIDE THERAPY IS BETTER FOR GLIOMA PATIENTS
Authors: Levin Victor , Patel Alyssa , Le Amy , Thomas Piia , Scott Peak 
Published: November 2019

Abstract
Current guidelines for adjuvant temozolomide (TMZ) treatment of glioma patients advocates 6 to 12 monthly cycles. Is that best? Will patients who receive > 12 cycles live longer? To find out, we conducted a 10-year (2006–2016) chart review of 1300 glioma patients treated at NorCal Kaiser Permanente facilities to determine the impact of dose-week (AUC) quartiles and duration of TMZ therapy quartiles on median overall survival (mOS) in new low- and mid-grade gliomas (Group A) and glioblastoma (Group B) patients. Group A had 357 patients with WHO grade II and III astrocytic and oligodendroglial tumors; Group B had 943 patients with glioblastoma. The median AUC in Group A was 337 mg/m2 (IQR 129, 1095) and the median weeks of TMZ 15 (IQR 1, 42). In Group B, median AUC was 210 mg/m2 (IQR 79,581) and median weeks of TMZ 24 (IQR 9. 45). Based on quartile ranking of AUC, a higher AUC was found to be associated with longer mOS in Group A and B. In Group A, for increasing AUC quartiles, mOS was 134, 146, 369, and 397 weeks (p=0.0014); for Group B, mOs were 30, 48, 74, and 117 weeks (p< 0.0001). Based on increasing quartiles for TMZ treatment duration for quartiles 2–4, Group A patient mOS increased from 122 weeks to 431 weeks (p = ns) and Group B patients, increased mOS from 51 to 143 weeks (p< 0.0001). This retrospective analysis of 10-years of neuro-oncology practice brings into question limiting TMZ dose in WHO grade 2–3 glioma and WHO grade 4 glioblastoma patients as higher dose toleration and longer duration of treatment appears to be associated with longer mOS in both groups. Or does it show that patients who do well elect to take TMZ longer and maybe these findings reflect reverse causality?
ACTR-42. PI3K/mTOR PATHWAY ACTIVATION SELECTED PHASE II STUDY OF EVEROLIMUS (RAD001) WITH AND WITHOUT TEMOZOLOMIDE IN THE TREATMENT OF ADULT PATIENTS WITH SUPRATENTORIAL LOW-GRADE GLIOMA [NCT NCT02023905]
Authors: Taylor Jennie , Molinaro Annette , Rodriguez Almaraz Eduardo , Downey Ciara , Phillips Joanna , Ann Oberheim-Bush Nancy , Butowski Nicholas , Chang Susan , Berger Mitchel , Prados Michael , Haas-Kogan Daphne , Clarke Jennifer 
Published: November 2019

Abstract
Functional activation of the PI3K/AKT/mTOR pathway is seen in ~50% of low-grade gliomas and correlates with worse survival. Everolimus is a selective inhibitor of mTOR that targets mTOR-raptor signaling, halting proliferation and indirectly inhibiting angiogenesis. This phase 2 study evaluated the efficacy of everolimus in untreated grade II diffuse glioma. Patients were stratified by 1p19q status and PI3K pathway activation (via phosphorylation of PRAS-40) into three arms: 1) 1p19q intact, PRAS-40 phosphorylated received everolimus monotherapy; 2) 1p19q intact, PRAS-40 not phosphorylated received everolimus with temozolomide; and 3) 1p19q co-deleted received everolimus monotherapy. Primary outcome was landmark PFS-33 months for Arms 1 and 2; and PFS-38 months for Arm 3 (null hypothesis 50% for all arms individually). Key eligibility criteria included central pathology confirmation, no prior treatment, and initiation of everolimus within 120 days of most recent tissue sampling. From 05/2014 to 07/2018, 27 patients were enrolled – 16 into Arm 1; 2 into Arm 2; and 9 into Arm 3. Median age at enrollment was 38 years (range 21 – 65); median KPS 90 (range 70 – 100) and a majority were male (74%). Although follow-up is not complete, as of 05/2019 11 of 16 patients had progressed prior to 33 months in Arm 1, and 5 of 9 patients had progressed prior to 38 months in Arm 3. Toxicity was as expected with frequent grade 1/2 AEs of diarrhea, rash, and mucositis. Headache was the most common grade 3 AE and was seen in three cases. The study was closed prematurely secondary to slow accrual and loss of drug support. Updated survival data as well as results of secondary and exploratory analyses will be reported. In summary, everolimus was well tolerated in previously untreated low-grade gliomas. However, it failed to meet primary outcome of extending PFS in this population.
ACTR-47. PHASE-III TRIAL OF STANDARD CHEMOTHERAPY VS. CHEMOTHERAPY GUIDED BY CANCER STEM CELL TEST IN RECURRENT GLIOBLASTOMA (NCT03632135)
Authors: Ranjan Tulika , Aregawi Dawit , Lu-Emerson Christine , Schroeder Jason , Anderson Mark , Chaudhary Rekha 
Published: November 2019

Abstract
Stupp treatment protocol for patients with glioblastoma (GBM) has improved the median overall survival to 14.6 months. However, no investigations have defined effective strategies against recurrence and the prognosis of recurrent GBM patients remains poor. Personalized medicine with assay-guided treatment targeting chemotherapy resistant cancer stem cells (CSCs) alongside the bulk tumor cells is a new paradigm in cancer treatment that may result in improved patient’s outcome. We are using ChemoID, a CLIA and CAP certified CSC cytotoxicity assay for predicting response to chemotherapeutic agents. Our prospective analysis of 61 GBM patients demonstrated that ChemoID-guided treatment significantly improved tumor response. For every 5% increase in cell kill of CSCs by assay-guided chemotherapy, 12-month patient response (non-recurrence of cancer) increased 2.5-fold, OR=2.3 (p=0.01). We also found that median recurrence time was 20-months versus 3-months for patients with a positive (>40% cell kill) CSC test versus negative, whereas median recurrence time was 13-months versus 4-months for patients with a positive (>55% cell kill) bulk test versus negative. We are conducting a multi-institutional phase-III clinical trial (NCT03632135) to determine the clinical validity of the ChemoID assay as a predictor of clinical response in recurrent GBM. The study has been designed as a parallel group controlled clinical trial and the participants are randomized to either standard of care chemotherapy chosen by the physician or ChemoID-guided therapy. Response to therapy will be measured by MRI imaging using RANO criteria. Primary endpoint of median overall survival (OS) and secondary endpoints of OS at 6, 9, and 12 months, median progression free survival (PFS), PFS at 4, 6, 9, and 12 months, objective tumor response, time to recurrence, and quality of life will be measured. Trial is open and currently 22 subjects have been enrolled. Interim analysis of the trial will be conducted in approximately 12 months.
ACTR-49. INITIAL EXPERIENCE WITH SCALP PRESERVATION AND RADIATION PLUS CONCURRENT ALTERNATING ELECTRIC TUMOR-TREATING FIELDS (SPARE) FOR GLIOBLASTOMA PATIENTS
Authors: Song Andrew , Ly Michele , Bar-Ad Voichita , Werner-Wasik Maria , Glass Jon , Martinez Nina , Andrews David , Judy Kevin , Evans James , Farrell Christopher , Shi Wenyin 
Published: November 2019

Abstract

INTRODUCTION
Standard of care for glioblastoma includes concurrent chemoradiation and maintenance temozolomide with electric tumor treatment fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. We report our initial experience evaluating toxicity and tolerability of scalp-preserving radiation with concurrent TTFields.

METHODS
We conducted a single arm pilot study. Adult patients (≥ 18 years old) with KPS ≥ 60 with newly diagnosed glioblastoma were included. All patients received concurrent scalp-preserving radiation (60 Gy in 30 fractions), standard temozolomide (75 mg/m2 daily), and TTFields (200 kHz; ≥ 18 hr daily). Maintenance therapy included standard temozolomide and TTFields. Radiation treatment was delivered through TTFields arrays. Our primary endpoint was safety and toxicity for concurrent TTFields with chemoradiation in newly diagnosed glioblastoma.

RESULTS
Here we report the first seven patients on the trial. Five were male, and 2 female, with median age 58 y/o (range 49–73). Median KPS was 90. Median follow-up was 5.2 months (range 1.4–11.2). MGMT status was unmethylated for 6 patients, and one unknown, and no IDH mutations. Four (57.1%) received gross total resection and three (42.9%) had subtotal resection. All patients completed concurrent chemoradiation plus TTFields without radiation or TTFields treatment interruption or discontinuation. There was no related Grade 3 or higher toxicity. Skin toxicity (erythema, dermatitis, pruritus) was noted in all patients, however, limited to Grade 1 or 2 which resolved spontaneously or responded to topical medications. All patients were alive at time of writing. Two (28.6%) patients had progression, of which one (at 9 months) continued TTFields and temozolomide with bevacizumab, while the other (at 4 months) discontinued TTFields and underwent re-resection with bevacizumab.

CONCLUSIONS
Concurrent TTFields with scalp-preserving chemoradiation is a safe and feasible treatment option with limited toxicity. Future randomized prospective trial is warranted to define therapeutic advantages of concurrent TTFields with chemoradiation.