bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro antifungal activity of luliconazole against nondermatophytic moulds
Authors: Maeda Jun , Koga Hiroyasu , Yuasa Kou , Neki Daisuke , Nanjoh Yasuko , Inagaki Katsuhiro , Reangchainam Sutthirat , Kampirapap Kowit , Makimura Koichi , Harada Kazutoshi , Tsuboi Ryoji 
Published: November 2019

Abstract
In vitro antifungal activity of luliconazole against nondermatophytic moulds causing superficial infections was compared with that of five classes of 12 topical and systemic drugs. The minimum inhibitory concentration (MIC) of the drugs against the genera of Neoscytalidium, Fusarium, Aspergillus, Scedosporium, and Alternaria was measured via modified microdilution method. In results, the nondermatophytic moulds were found to be less susceptible to drugs to which Neoscytalidium spp. and Fusarium spp. were typically drug resistant. However, luliconazole was effective against all the genera tested, including afore-mentioned two species, and had the lowest MICs among the drugs tested.
Active galactic nuclei winds as the origin of the H2 emission excess in nearby galaxies
Authors: Riffel Rogemar A , Zakamska Nadia L , Riffel Rogério 
Published: November 2019

ABSTRACT
In most galaxies, the fluxes of rotational H2 lines strongly correlate with star formation diagnostics [such as polycyclic aromatic hydrocarbons (PAHs)], suggesting that H2 emission from warm molecular gas is a minor by-product of star formation. We analyse the optical properties of a sample of 309 nearby galaxies derived from a parent sample of 2015 objects observed with the Spitzer Space Telescope. We find a correlation between the [O i]λ6300 emission-line flux and kinematics and the H2 S(3) 9.665 $\mu\mathrm{ m}$/PAH 11.3  $\mu\mathrm{ m}$. The [O i]λ6300 kinematics in active galactic nuclei (AGNs) cannot be explained only by gas motions due to the gravitational potential of their host galaxies, suggesting that AGN-driven outflows are important to the observed kinematics. While H2 excess also correlates with the fluxes and kinematics of ionized gas (probed by [O iii]), the correlation with [O i] is much stronger, suggesting that H2 and [O i] emissions probe the same phase or tightly coupled phases of the wind. We conclude that the excess of H2 emission seen in AGNs is produced by shocks due to AGN-driven outflows and in the same clouds that produce the [O i] emission. Our results provide an indirect detection of neutral and molecular winds and suggest a new way to select galaxies that likely host molecular outflows. Further ground- and space-based spatially resolved observations of different phases of the molecular gas (cold, warm, and hot) are necessary to test our new selection method.
ATIM-02. A NEW SOURCE OF NEOANTIGENS FOR PEDIATRIC AND ADULT BRAIN CANCER VACCINES
Authors: Albert Johnston Stephen , Peterson Milene , Diehnelt Chris , Shen Luhui 
Published: November 2019

Abstract
The paucity of mutations in pediatric and adult brain tumors has limited the ability to design therapeutic personal cancer vaccines. However, we have discovered that, in contrast to mutations in DNA, RNA is a rich source of frameshift neoantigens produced by mis-splicing of exons or indels from transcription through micro satellites. We have found that in GBM there are an average of 4000 such FS neoantigens per patient and in DIPG an average of at least 500 FS neoantigens/patient. Approximately 20% of these neoantigens are frequently recurrent across different patients. This has allowed us to design pre-synthesized vaccines for each tumor type. The vaccines consist of 20 -30 FS epitopes that are predicted to be present in at least 20% of all patient’s tumor. Each patient would have a 90% chance of having at least 50% of the peptides in their tumor. This type of “FAST” vaccine is much less expensive than a personal vaccine, any patient could be treated and there would be no delay in producing the vaccine. We have directly compared the efficacy of a FAST and personal vaccines in a mouse model of breast cancer. We find that both approaches have comparable protection though there are some interesting differences. We suggest that FAST vaccines may be a useful approach to developing therapeutic vaccines for brain cancers. We also demonstrate that an array of the 400K possible FS neoantigen peptides can be used to assay which neoantigens the patient has developed antibodies to. This array was useful in discovering the FAST vaccine components and could also be used to determine the pre-existing overlap of a FAST vaccine with the patient’s immune response.
ATIM-05. A PHASE I STUDY TARGETING NEWLY DIAGNOSED GLIOBLASTOMA WITH ANTI-CD3 × ANTI-EGFR BISPECIFIC ANTIBODY ARMED T CELLS (EGFR BATS) IN COMBINATION WITH RADIATION AND TEMOZOLOMIDE
Authors: Fadul Camilo , Kim Jungeun , Thakur Archana , Purow Benjamin , Lopes Maria-Beatriz , Schiff David , Kassay-McAllister Jessica , Donahue Joseph , Liu Qin , Lum Lawrence 
Published: November 2019

Abstract
Overcoming the highly immunosuppressive glioblastoma (GBM) microenvironment is critical to successful immunotherapy. In a recently-launched phase I trial we are examining the safety and feasibility of a novel adoptive cell immunotherapy platform, activated T cells (ATC) with anti-CD3 X anti-EGFR bispecific antibody (EGFR BATs), for patients with newly-diagnosed GBM. Autologous T cells obtained before radiation and chemotherapy are expanded and activated, becoming cytotoxic T lymphocytes. We postulate that these activated T cells armed with bispecific antibody will enhance the response to radiation/temozolomide and potentially increase trafficking to the GBM microenvironment. In a 3 + 3 design dose-escalation trial, we will determine the maximum tolerated dose (MTD) of three dose tiers of EGFR BATs (80, 120 and 160 billion cells divided in eight infusions) in combination with radiation/temozolomide in patients with newly-diagnosed GBM. Patients undergo leukapheresis prior to initiating radiation/temozolomide. Patients receive EGFR BATs on days 14 and 21 after finishing concurrent RT/ temozolomide and on day 21 of six cycles of adjuvant temozolomide. We are measuring peripheral blood immune response before and after immunotherapy and correlating the results with patient characteristics and clinical outcomes. The first four patients have been treated at the first dose tier (80 billion cells) without any dose-limiting toxicity. Updated safety and feasibility results on the patients in the first two dose tiers will be presented, as well as immune monitoring studies, imaging studies, and clinical outcomes.
ATIM-10. CLINICAL PREDICTORS OF RESPONSE FOR RECURRENT/REFRACTORY GLIOBLASTOMA MULTIFORME (GBM) AND ANAPLASTIC ASTROCYTOMA (AA, WHO GRADE III) PATIENTS TREATED WITH THE ANTI-TGFß2 RNA THERAPEUTIC OT-101
Authors: Qazi Sanjive , Nam David , Hwang Larn , Trieu Vuong , Uckun Fatih 
Published: November 2019

Abstract

BACKGROUND
OT-101 is a first-in-class αTGF-ß2 RNA therapeutic and exhibits significant single-agent activity in patients with recurrent/refractory (R/R) GBM and AA. Here we report significant predictors of best overall response (BOR = CR, PR, stable disease >6 months) and improved OS for R/R GBM and AA patients after treatment with OT-101 on the Phase II study NCT00431561.

METHODS
A generalized linear model (GLM; Binomial distribution, logit function link function) was fitted to explore several clinical parameters as potential predictors for BOR. The parametric survival model fitted the time to death using linear regression to predict improved OS. The best fit model was chosen utilizing both Akaike information criterion (AIC) and Bayesian information criterion (BIC) from assessing Weibull, lognormal, exponential, Fréchet, and loglogistic distributions of the survival probabilities (JMP 10.02, SAS, Cary NC).

RESULTS
In both models, time from last chemo-/radiation therapy, time from first diagnosis and baseline hematological measurements (ALC, ANC and WBC) were removed from the model as they lacked significant predictive value. The final GLM (chi-square value = 39.7, df = 12, P< 0.0001) and OS (chi-square value = 56.0, df = 12, P< 0.0001) models contained 7 predictor variables measured in 67 evaluable patients: Baseline Karnofsky performance scale (KPS) score; composition of previous therapy; cancer subtype; steroid use; total OT-101 dose; age; and baseline 3D tumor volume for the target lesion. Three significant predictors were identified: Baseline KPS score (P[BOR] = 0.011; P[OS] = 0.0004), cancer subtype (P[BOR] = 0.017, P[OS] = 0.036) and steroid use (P[BOR] = 0.0067, P[OS] = 0.0022).

CONCLUSION
Being an AA patient rather than a GBM patient, having a higher baseline KPS score, receiving either no steroids or short-term steroids during management of AE are associated with BOR and improved OS for R/R GBM/AA patients treated with OT-101 as a single agent.
ATIM-12. AVELUMAB IN NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME-THE SEJ STUDY
Authors: Jacques Francois , Nicholas Garth , Lorimer Ian , Sikatifoko Victorine , Dumais Nathalie 
Published: November 2019

Abstract

INTRODUCTION
Glioblastoma Multiforme (GBM) has well documented systemic and local immunosuppressive mechanisms to escape immune surveillance. GBM tumor cells as well as the microglia within it have a high PD-L1 surface expression which may make it susceptible to anti-PD-L1 antagonism and ADCC with avelumab therapy. Combining immunotherapy to other chemotherapeutic agents have proven benefical in certain cancers. A clinical trial looking at adding avelumab to standard therapy in patients with newly diagnosed GBM is indicated.

METHODS
This is a single center, phase 2, open label study of avelumab 10 mg/kg Q2W for 156 weeks duration in patients receiving standard therapy for newly diagnosed GBM. Thirty patients will be entered into the study within 3 weeks of completing combined radiotherapy/temozolomide. Here we will report the results our second interim analysis when the first 20 patients will have completed 52 weeks or an end of study event which will occur in 10–2019.

RESULTS
The results will be presented at the meeting
ATIM-24. DOSE FINDING AND DOSE EXPANSION TRIAL OF D2C7 IMMUNOTOXIN (D2C7-IT) ADMINISTERED INTRATUMORALLY VIA CONVECTION-ENHANCED DELIVERY (CED) FOR RECURRENT MALIGNANT GLIOMA (MG)
Authors: Desjardins Annick , Randazzo Dina , Chandramohan Vidya , Peters Katherine , Johnson Margaret , Threatt Stevie , Bullock Chevelle , Jackman Jenny , Healy Patrick , Lipp Eric , Sampson John , Friedman Allan , Friedman Henry , Ashley David , Bigner Darell 
Published: November 2019

Abstract

BACKGROUND
D2C7-IT is a recombinant immunotoxin comprised of a dual-specific antibody fragment targeting EGFRwt and EGFRvIII and a genetically engineered form of the Pseudomonas exotoxin, PE38-KDEL. We report results of a phase 1 trial, with dose expansion at the selected phase 2 dose, evaluating D2C7-IT delivered intratumorally by CED.

METHODS
Eligible patients are adults with recurrent supratentorial WHO grade III or IV MG; solitary tumor; ≥4 weeks after chemotherapy, bevacizumab or study drug; adequate organ function; and KPS >70%. Two patients per dose level (DL) were to be enrolled in the dose escalation portion (dose range: 40ng/mL to 23,354ng/mL), followed by dose expansion at the selected phase 2 dose (DL13).

RESULTS
As of 6/07/2019, 51 patients have been treated; 10 patients on the phase 2 dose. Observed dose limiting toxicities include: grade 4 seizure (n=1) on DL3, grade 3 confusion and pyramidal tract syndrome (n=1) on DL13, and grade 4 cerebral edema (n=1) and grade 3 dysphasia (n=1) on DL17. Grade 3 or higher adverse events possibly related to D2C7-IT include: seizure (grade 4, n=2, grade 3, n=3), cerebral edema (grade 4, n=1), hydrocephalus (grade 3, n=5), headache (grade 3, n=4), hemiparesis (grade 3, n=4), dysphasia (grade 3, n=4), lymphopenia (grade 3, n=3), thromboembolic event (grade 3, n=3); and one each of grade 3 elevated ALT, urinary tract infection, fall, wound complication, generalized muscle weakness, confusion, encephalopathy, and somnolence. Fourteen patients are alive. Three patients have partial radiographic response and remain alive without additional therapy more than 46, 27 and 21 months after D2C7-IT infusion.

CONCLUSION
Dose level 13 was selected as the optimal phase 2 dose and patient accrual is ongoing on the dose expansion arm. Encouraging efficacy results have been observed. A trial of D2C7-IT with checkpoint inhibitor is planned to start in the near future.
ATIM-25. PD-1 INHIBITION CAN BE COMBINED WITH IL-12 IN SUBJECTS WITH RECURRENT GLIOBLASTOMA
Authors: Chiocca Ennio , Lukas Rimas , Rao Ganesh , Buck Jill , Demars Nathan , Smith Amy , Miao John , Zhou John , Gelb Arnold , Cooper Laurence 
Published: November 2019

Abstract
Monotherapy with intratumoral Ad-RTS-hIL-12 (Ad), a novel gene therapeutic conditionally expressing IL-12 under the transcriptional control of oral veledimex (V, 20 mg) acting via the proprietary RheoSwitch Therapeutic System® (RTS®), was shown in a phase 1 Main study (NCT02026271) to elicit a sustained intra-tumoral activated cytotoxic T-cell response with co-expression of PD-1. Additionally, the Main study showed improved median overall survival (mOS), compared to historical controls, in subjects with recurrent glioblastoma (rGBM) receiving Ad + V. Herein, we report updated findings from on an ongoing open label, dose-escalation Phase 1 substudy (NCT03636477) evaluating safety and tolerability of local, controlled IL-12 plus nivolumab in adult subjects with rGBM. Ad was administered by single intratumoral injection (2 x 1011 viral particles) on Day 0 plus V (10 and 20 mg) PO QD x 15 with nivolumab (1 and 3mg/kg) IV on Days -7, 15, then Q2W. Subjects have been accrued into three cohorts and follow-up is ongoing. Data from all three cohorts regarding dose escalation of V and nivolumab will be presented. The initial safety profile during V dosing period was similar to Ad+V monotherapy with adverse reactions being dose-related and rapidly reversible upon discontinuation of V. And those adverse reactions during the follow on nivolumab dosing were tolerable and manageable and consistent with nivolumab labeling, with no synergistic toxicities, and drug-related deaths. In the first two cohorts (where data is available), combination therapy improved the biomarker “cytoindex” (ratio of circulating CD8+ T cells to FoxP3+ regulatory T cells). (In the Main study, cytoindex correlated with overall survival). Controlled IL-12 production using Ad+V with nivolumab is a rational combination with initial data consistent with immune-mediated anti-tumor effects with a favorable safety profile. Further phase 2 investigation of Ad+V plus a checkpoint inhibitor in rGBM is planned.
ACTR-01. PHASE I/II STUDY OF TEMOZOLOMIDE PLUS NIMUSTINE CHEMOTHERAPY FOR RECURRENT MALIGNANT GLIOMAS: KYOTO NEURO-ONCOLOGY GROUP
Authors: Aoki Tomokazu , Arakawa Yoshiki , Ueba Tetsuya , Oda Masashi , Nishida Namiko , Akiyama Yukinori , Tsukahara Tetsuya , Iwasaki Koichi , Mikuni Nobuhiro , Miyamoto Susumu 
Published: November 2019

Abstract
The objective of this phase I/II study was to examine the efficacy and toxicity profile of temozolomide (TMZ) plus nimustine (ACNU). Patients who had received a standard radiotherapy with one or two previous chemoregimens were enrolled. In phase I, the maximum-tolerated dose (MTD) by TMZ (150 mg/m2/day) (Day 1–5) plus various doses of ACNU (30, 35, 40, 45 mg/m2/day) (Day 15) per 4 weeks was defined on a standard 3 + 3 design. In phase II, these therapeutic activity and safety of this regimen were evaluated. Forty-nine eligible patients were enrolled. The median age was 50 years-old. Eighty percent had a KPS of 70–100. Histologies were glioblastoma (73%), anaplastic astrocytoma (22%), anaplastic oligodendroglioma (4%). In phase I, 15 patients were treated at four cohorts by TMZ plus ACNU. MTD was TMZ (150 mg/m2) plus ACNU (40 mg/m2). In phase II, 40 patients were treated at the dose of cohort 3 (MTD). Thirty-five percent of patients experienced grade 3 or 4 toxicities, mainly hematologic. The overall response rate was 11% (4/37). Sixty-eight percent (25/37) had stable disease. Twenty-two percent (8/37) showed progression. Progression-free survival (PFS) rates at 6 and 12 months were 24% (95% CI, 12–35%) and 8% (95% CI, 4–15%). Median PFS was 13 months (95% CI, 9.2–17.2 months). Overall survival (OS) at 6 and 12 were 78% (95% CI, 67–89%) and 49% (95% CI, 33–57%). Median OS was 11.8 months (95% CI, 8.2–14.5 months). This phase I/II study showed a moderate toxicity in hematology and may has a promising efficacy in OS, without inferiority in PFS.
ACTR-20. EFFICACY OF INITIAL TEMOZOLOMIDE FOR HIGH-RISK LOW GRADE GLIOMAS IN A PHASE II AINO (ITALIAN ASSOCIATION FOR NEURO-ONCOLOGY) STUDY: A POST-HOC ANALYSIS WITHIN MOLECULAR SUBGROUPS OF WHO 2016
Authors: Rudà Roberta , Pellerino Alessia , Pace Andrea , Maria Carapella Carmine , Dealis Cristina , Caroli Manuela , Faedi Marina , Bello Lorenzo , Migliore Enrica , Marchese Giulia , Bertero Luca , Cassoni Paola , Soffietti Riccardo 
Published: November 2019

Abstract

BACKGROUND
The optimal management of high risk WHO grade II gliomas after surgery is still debated. The efficacy of initial temozolomide to delay radiotherapy and risk of cognitive defects could vary across the molecular subgroups of WHO 2016, but information on this issue are lacking.

PATIENTS AND METHODS
A post-hoc analysis has been performed on a cohort of high risk WHO grade II gliomas, who received initial temozolomide alone in phase II multicenter study, with the objective of re-evaluating the long-term results across the different molecular subgroups of the WHO 2016 classification. The primary endpoint of the study, carried out between 2007 and 2010, was response rate according to RANO, being seizure response, PFS and OS secondary endpoints.

RESULTS
Response rate (partial and minor responses) among oligodendrogliomas IDH-mutant and 1p/19q codeleted (76%) was significantly higher than that among diffuse astrocytomas either mutant (55%) or wild-type (36%). A reduction of seizure frequency >50% was observed in 87% patients and a seizure freedom in 72%. The probability of seizure reduction >50% was significantly associated with the presence of an IDH mutation. Median PFS, PFS at 5 and 10 years, median OS and OS at 5 and 10 years were all significantly longer in oligodendrogliomas IDH-mutant and 1p/19q codeleted. Of patients who did not recur or delay radiotherapy at recurrence for a median follow-up of 8.2 years, 67% and 59%, respectively, were oligodendrogliomas IDH-mutant and 1p/19q codeleted.

CONCLUSIONS
The post-hoc analysis of this phase II trial suggests that the beneficial effects of initial temozolomide prevail in oligodendrogliomas IDH-mutant and 1p/19q codeleted: thus, these tumors, when incompletely resected or progressive after surgery, especially when suffering from pharmacoresistant seizures, could receive temozolomide as initial treatment with radiotherapy and chemotherapy at recurrence. The trial was registered with EU Clinical Trials Register, EudraCT n. 2007/000386-38.
ACTR-38. A SINGLE CENTER STUDY: LONG-TERM OUTCOMES OF COMBINED CHEMORADIATION THERAPY WITH TEMOZOLOMIDE FOR NEWLY DIAGNOSED GLIOBLASTOMA IN KOREAN PATIENT
Authors: Go Kyeong-O , Young Yang Ha , Hwang Kihwan , Ho Han Jung , Soo Choi Hyoung , Jung Kim Yu , Woo Wee Chan , Ah Kim In , Choe Gheeyoung , Kim Chae-Yong 
Published: November 2019

Abstract
In newly diagnosed glioblastoma (GBM), Temozolomide (TMZ) during and after radiation therapy has become standard treatment. This study describes the long-term use and follow-up results of this therapy for GBM. From 2004 to 2013 in a single institute, 112 Korean patients with newly diagnosed GBM were analyzed retrospectively. The Kaplan-Meier method, the two-sided log-rank test and Cox’s regression analysis was used to determine survival and its affecting factors. The toxicities of TMZ were evaluated using CTCAE v5.0. During the median follow-up period of 18.8 months, median PFS and OS were 9.2 and 20.3 months, respectively. This better survival outcome than the Stupp’s original study might be probably a large treatment effect of a single institution, ethnicity, and associated genetic factors. The TMZ during radiation therapy was completed in 108 patients (96.4%) and TMZ after radiation therapy in 59 patients (52.7%). Eight patients presented with grade 3 or 4 hematologic toxic effects during the protocol. Sixty-six patients (58.9%) received salvage treatment because of the poor response to adjuvant treatment or progression of the disease who achieved completion of adjuvant treatment was shown significantly longer median OS (p= 0.007) and PFS (p< 0.001). Age (< 60 years), preoperative KPS score (≥ 90), the extent of resection (≥ 78% by volumetric measurement, gross total resection), and completion of the Stupp’s protocol were significant factors affecting better survival. Between the sexes, and ages over 65 years did not show any significant difference among their groups. With marginal significances, the mutated IDH-1 and the methylated MGMT promoter showed longer median PFS(p= 0.075 and 0.777, respectively) and OS (p= 0.085 and 0.131, respectively). TMZ during and after radiation therapy might be effective and safe for newly diagnosed Korean patients with GBM. Further studies about various clinical and genetic factors affecting better survival are mandatory.
ACTR-50. PRESERVATION OF NEUROCOGNITIVE FUNCTION & PATIENT-REPORTED SYMPTOMS WITH HIPPOCAMPAL AVOIDANCE (HA) DURING WHOLE-BRAIN RADIOTHERAPY (WBRT) FOR BRAIN METASTASES: LONG-TERM RESULTS OF NRG ONCOLOGY CC001
Authors: Armstrong Terri , Deshmukh Snehal , Brown Paul , Gondi Vinai , Benzinger Tammy , Gilbert Mark , Tome Wolfgang , Wefel Jeffrey , Bruner Deborah , Roberge David , Kundapur Vijayananda , Devisetty Kiran , Shah Sunjay , Usuki Kenneth , Baschnagel Andrew , Stea Baldassarre , Yoon Harold , Li Jing , Laack Nadia , Mehta Minesh , Kachnic Lisa 
Published: November 2019

Abstract

BACKGROUND
NRG-CC001 sought to evaluate the neuro-protective effects of avoiding the peri-hippocampal stem cell niche using intensity-modulated radiotherapy during WBRT.

METHODS
Patients with brain metastasis were stratified by RPA class and prior radiosurgery/surgery and randomized to WBRT+M or HA-WBRT+ Memantine (M) (30Gy in 10 fractions). Standardized NCF tests and the M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) were obtained at baseline, 2, 4, 6, and 12 months (mos). The primary endpoint was NCF failure defined using the reliable change index. Pre-specified secondary endpoints included patient-reported symptoms using the MDASI-BT. Time to NCF was reported as cumulative incidence (with death without NCF failure as a competing risk); between-arms differences were tested using Gray’s test. Deterioration at discrete time-points were tested using chi-square tests. MDASI-BT symptom burden, interference, and cognitive and neurologic burden were analyzed using mixed effects models and t-tests within the model using Hochberg’s multiplicity adjustment.

RESULTS
A total of 518 patients were randomized from 7/2016 to 3/2018. Median follow-up for alive patients was 12.1 mos, with no difference between arms in terms of toxicity, overall survival or intracranial progression-free survival. HA-WBRT+M was associated with lower risk of NCF failure (adjusted HR=0.739, 95% CI: 0.577–0.945, p=0.0.016), with differences first noted at 4 mos in Trail Making Test Part-B (23.3% vs. 40.4% deteriorated, p=0.012). Age did not dilute treatment effect. HA-WBRT+M was associated with reduced cognitive symptom burden in an imputed model (estimate=-0.29, p=0.0425), and also reduced overall symptom burden (p< 0.0001) and interference (p< 0.0016) at 6 mos.

CONCLUSIONS
The addition of HA to WBRT+M preserved NCF and reduced patient reported cognitive symptom burden, overall symptom burden and symptom interference and should be considered standard of care for any patient fit enough to have WBRT. Supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), DCP from the National Cancer Institute.