bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Substrate Age on Oviposition Behavior of a Specialist Carrion Colonizer, Cochliomyia macellaria (Diptera: Calliphoridae)
Authors: Kotzé Zanthé , Tomberlin Jeffery K 
Published: December 2019

Abstract
The location and consumption of carrion by arthropods is a process that can be potentially distinguished temporally based on the makeup of the associated community. In fact, succession on carrion is a continuum of different generalist and specialist arthropods entering and leaving the system. Blow flies commonly associated with vertebrate remains are considered specialists due to their reliance on carrion as a source of food for offspring and protein for females. However, this specialization may come at a price; increased competition for resources and greater risk of local extinction. The present study examined the effects of the presence or absence of intraspecific colonization, carcass age, and exposure time on the colonization and oviposition responses of the specialist, primary colonizer, the secondary screw worm, Cochliomyia macellaria (Fabricius) (Diptera: Calliphoridae). Carcass age, exposure time, and colonization status significantly influenced the ovipositional response of C. macellaria. This species exhibited an oviposition preference for aged carcasses, with a tendency for higher oviposition after 8-h exposure time, but no preference between previously colonized or uncolonized carcasses. Mean egg hatch rate was also shown to be influenced by the aforementioned factors, with mean hatch rates varying between 81.26 and 90.97% across various treatments. These results provide insight into mechanisms driving succession on carrion, as well as highlight the variation observed in successional studies for the targeted species. Investigators relying on arthropod succession to indicate a time of colonization should proceed with caution in relying solely on the assumption primary colonizers only arrive and colonize fresh carrion.
ATIM-33. INTERIM RESULTS OF A PHASE II MULTI-CENTER STUDY OF ONCOLYTIC ADENOVIRUS DNX-2401 WITH PEMBROLIZUMAB FOR RECURRENT GLIOBLASTOMA; CAPTIVE STUDY (KEYNOTE-192)
Authors: Aiken Robert , Chen Clark , Cloughesy Timothy , Colman Howard , Daras Mariza , Groves Morris , Khagi Simon , Kumthekar Priya , Lang Frederick , Nassiri Farshad , Ong Shirley , Ramakrishna Rohan , Sonabend Adam , Vogelbaum Michael , Zadeh Gelareh , Agensky Laura , Bidwell Carin , Watkins Barry , Tufaro Frank , Peterkin Joanna 
Published: December 2019

Abstract

BACKGROUND
DNX-2401 (tasadenoturev) is a replication-competent, tumor-selective, oncolytic adenovirus. Phase I studies in adults with recurrent glioblastoma (rGBM) have demonstrated safety and encouraging clinical activity. A Phase II open-label, dose-escalating multi-center study in rGBM was initiated to evaluate DNX-2401 with pembrolizumab. Planned enrollment of 48 subjects is complete.

METHODS
Subjects ≥ 18 years, with a single tumor, KPS ≥ 70% and adequate organ function were enrolled sequentially into 3 cohorts of DNX-2401 (5e8vp, 5e9vp, 5e10vp). A single intratumoral injection of DNX-2401 was administered followed 7 days later by pembrolizumab (200 mg IV). Thereafter, pembrolizumab was infused Q3wks up to 24 months until progression or toxicity. 5e10vp was determined as the optimal dose and this cohort was expanded. Safety monitoring, assessments of response and survival follow-up are ongoing.

RESULTS
Nine subjects were treated in the escalation phase; 42 subjects received 5e10vp. No dose-limiting toxicity or unexpected safety issues were identified by an independent review committee, and there were no treatment-related deaths. Adverse events were primarily consistent with underlying disease, effects of the neuro-procedure, expected effects of pembrolizumab, and concomitant use of steroids/anticonvulsants per the standard of care. The majority of events were mild to moderate, and unrelated to DNX-2401. Headache and manageable vasogenic edema were the most common events related to DNX-2401 with pembrolizumab. For the 48 subjects who received pembrolizumab (median 6 cycles), median OS from DNX-2401 administration was 12 months (95% CI, 10.6–14.7), OS6 was 91%, and 47% experienced clinical benefit (stable disease or better). Four subjects (5e10) had a partial response (two with &gt; 94% regression of tumor), and three (5e8; 5e10[2]) are alive &gt; 20 months. Updated safety and efficacy results will be presented.

CONCLUSIONS
The data continue to demonstrate that DNX-2401 administered with pembrolizumab has an acceptable safety profile. Long-term survival and clinical benefit remain compelling.
ATIM-35. THE ASSOCIATIONS BETWEEN TOTAL LYMPHOCYTE COUNTS AFTER CONCOMITANT CHEMORADIATION WITH OVERALL SURVIVAL IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Ahn Stephen , Park Jae-Sung , Kil Hong Yong , Ho Yang Seung , Jeun Sin-Soo 
Published: December 2019

Abstract
Several studies have been conducted to determine the relationship between post-treatment total lymphocyte count (TLC) and overall survival (OS) in patients with malignant tumors including glioblastomas (GBMs). In this retrospective study, whether patients with newly diagnosed GBM experience significant lymphopenia after concomitant chemoradiation (CCRT) was evaluated, and whether TLC after this treatment is associated with OS in the treated population was examined. Using electronic medical records, all patients newly diagnosed with GBM between 2008 and 2016 at Seoul St. Mary’s Hospital were retrospectively examined. The eligible criteria included the following: 1) craniotomy with surgical resection or biopsy, 2) completion of CCRT, 3) accessible baseline and/or follow-up complete blood count (CBC). Median TLC significantly decreased after completion of CCRT, compared to TLC at baseline (1,742 versus 1,319 cells/mm3, P-value &lt; 0.001). Patients with TLC &lt; 1,200 cells/mm3 at 4 weeks after the completion of CCRT showed shorter survival than those with TLC ≥ 1,200 cells/mm3 with median OS of 14.5 versus 21.0 months (P-value = 0.017). Also, in multivariate analysis for OS, TLC &lt; 1,200 cells/mm3 at 4 weeks after the completion of CCRT (HR 1.97, 95% CI 1.61 – 2.25, P-value = 0.004) were significantly associated with shorter survival. The results from the present study indicate that treatment-related total lymphocyte counts after CCRT is associated with worse survival in patients with newly diagnosed GBM.
SURG-10. GRADE TWO GLIOMA SURGERY - A LARGE SINGLE CENTRE REVIEW OF CLINICAL, HISTOLOGICAL, GENETIC AND SURGICAL OUTCOMES
Authors: Richards Oliver , Kwon Churl-Su , Bolton William , Goodden John , Chumas Paul 
Published: December 2019

Abstract
We analysed the surgical outcomes in a large series of operated grade two glioma patients with emphasis on surgical resection volumes, histology, genetics and survival. All adult glioma patients (200) operated between 2009 and 2016 with histological confirmation of grade two glioma from a single United Kingdom unit were included. Baseline clinical data was obtained along with radiological assessment of the extent of tumour resection, histological diagnosis, mutation status and survival data. Univariate and multivariate statistical analysis was performed. Preliminary analysis of an initial 63 patients had an average follow up of 51 months. A mean tumour resection of 73.9% (Range 14.4–100%), with an average pre-operative tumour volume of 42.2cm3 was achieved. 48 patients underwent awake surgery. There was no significant difference between pre-operative Karnofsky score (93.0) and post-operative (91.6) function. IDH-mutant diffuse astrocytoma (55.5%), IDH-mutant 1p19q co-deleted oligodendroglioma (33.3%) and IDH wildtype diffuse astrocytoma (14.3%) were the commonest histological diagnoses. 32 patients underwent post-operative adjuvant oncology treatment, with 22 requiring repeat operation. Extent of resection in repeat surgeries was 58.6%. Preliminary statistical analysis on this initial sample has demonstrated that every additional year of age at diagnosis however is associated with a 0.5% reduction in resection (p=0.02) and a 0.2% decline in Karnofsky performance (p=&lt; 0.01). Patients with 1p19q co-deletion had a significant increase in progression free survival (PFS) (p=0.04). No significant variables were found to predict the risk of second surgery. Patients with eloquent tumour locations were significantly less likely to suffer post-operative neurological deficits (p&lt; 0.01) Provisional analysis of our case series demonstrates an excellent extent of resection for our cohort of grade two glioma patients. 1p19q co-deletion in this group was significantly associated with improved PFS. Full analysis of the entire patient cohort will be available in time for presenting.
SURG-14. DOES WAITING MATTER? HOW TIME FROM DIAGNOSTIC MRI TO SURGICAL RESECTION AFFECTS OUTCOMES IN NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Young Jacob , Muster Rachel , Chandra Ankush , Morshed Ramin , Aghi Manish 
Published: December 2019

Abstract
Surgical resection is standard of care for patients with lesions concerning for high-grade glioma on MRI scan. There is no consensus on the urgency of the procedure for patients with good clinical performance status. Treatment history and functional outcomes were collected retrospectively from the electronic medical record for 105 consecutive patients with newly diagnosed WHO Grade IV gliomas who underwent surgical resection at the University of California, San Francisco in 2014 and 2015 (41% female, average age = 61.25). Median preoperative KPS score was 80. Median wait time to surgery was 11 days after the initial MRI scan (range: 0–213 days). Mean tumor volume at the time of initial MRI scan was 29.0 cm3 (SD = 26.1 cm3), which did not significantly differ from the mean pre-operative tumor volume of 31.2 cm3 (SD = 27.3 cm3). In this retrospective cohort, patients with larger glioblastomas were taken to surgery more quickly. Patients who presented to the emergency room were more likely to wait less than 7 days (p &lt; 0.001). Patients who waited less than 7 days had a larger initial and pre-operative tumor volume compared to patients who waited between 7–21 days and patients who waited over 21 days (p=&lt; 0.001, p=&lt; 0.001). Tumor growth occurred in 10% of patients who waited one week or less, 26% of patients who waited one to three weeks, and 55% of patients who waited over 3 weeks. Overall survival was not significantly affected by wait time until tumor resection (p=0.52). Additionally, Tumor growth was not associated with postoperative outcomes including postoperative KPS score, postoperative deficits, 3-month follow up KPS score, overall survival, and survival after surgery. In conclusion, longer wait time to surgery does not impact overall survival, pre-, and post-operative KPS, but the tumor is likely to grow in the interim.
SCIDOT-29. EVALUATING THE FEASIBILITY OF INTRANASAL FLT DELIVERY FOR PET IMAGING OF PRIMARY BRAIN TUMORS
Authors: Carlisle Grant , Fowler Austin , Soma Joel , Drewes Lester , Friday Bret 
Published: December 2019

Abstract

INTRODUCTION
Glioblastoma (GBM) is an aggressive primary brain tumor with a dismal prognosis. Overall survival rates have been correlated to initial tumor resection making improved imaging techniques necessary for improved patient outcomes. Functional imaging with fluorothymidine (FLT) has been limited due to inefficient transfer through the blood-brain-barrier. In this experiment, we strived to test the efficacy of tritium-labeled-FLT (3H-FLT) delivery to brain tissue through intranasal (IN) versus intravenous (IV) administration in a rat model.

METHODS
Adult rats (Sprague Dawley, 180-200g) received 3H-FLT through either an IN or IV delivery method. At 5, 20, and 60 minutes, concentrations of 3H-FLT were measured in 16 brain regions as well as blood and non-target organs via isotope quantitation using scintillation detection. Pharmacokinetic parameters were calculated.

RESULTS
Intranasal olfactory bulb concentrations of 3H-FLT trended higher compared to IV olfactory bulb. All other brain region concentrations were insignificantly different. Kp (brain-blood ratio) values mimicked this trend. Secondary calculations were performed to evaluate intranasal CNS drug targeting. Initial trends showed a more effective IN drug penetration to the olfactory bulb, spinal cord, and hippocampus. Drug targeting efficiency (DTE%) was found to be highest in the olfactory bulb at 212%, but all other brain regions were greater than 100% suggesting more efficient drug targeting with intranasal administration. Nose-to-brain direct transport percentage (DTP%), and comparative brain bioavailability (B%) showed similar trends. Non-target tissues including heart, lung, adipose and skeletal muscle were collected in the 5- and 60-minute trials and found to be significantly higher than all brain concentrations.

CONCLUSION
Drug delivery calculations suggest increased efficacy with IN administration of FLT to all brain regions compared to IV administration. However, additional optimization is likely necessary to improve PET imaging of primary brain tumors using IN delivery due to the relatively small differences observed.
CBMT-37. OSMR CONTROLS CELLULAR RESPIRATION AND RESISTANCE TO THERAPY
Authors: Sharanek Ahmad , Burban Audrey , Jahani-Asl Arezu 
Published: December 2019

Abstract
Cytokines and their receptors play important roles in the regulation of cell fate, inflammation and immunity. The cytokine receptor for Oncostatin M (OSMR) drives brain tumor stem cell (BTSC) proliferation and tumorigenesis. Here, we report a novel role for OSMR in regulation of cellular respiration. Genetic knockdown of OSMR in BTSCs impairs mitochondrial biogenesis and oxidative phosphorylation. Importantly, blockade of OSMR signalling in BTSCs sensitizes them to ionizing radiation and Temozolomide in vitro and in vivo. This mechanism whereby OSMR regulates mitochondrial respiration and metabolism is conserved in post-mitotic neutrons. Thus, while OSMR is required for BTSC proliferation, OSMR confers resistance to therapy via enhancing mitochondrial respiration, independent of its role in proliferation. Our data suggest that therapeutic targeting of OSMR may be beneficial to eradicate quiescent tumour stem cells and tumour relapse.
PATH-50. ROUTINE MOLECULAR DIAGNOSIS OF GLIOMA PATIENTS USING A GLIOMA-SPECIFIC NGS PANEL
Authors: Yoshimoto Koji , Higa Nayuta , Yonezawa Hajime , Uchida Hiroyuki , Akahane Toshiaki , Tanimoto Akihide 
Published: December 2019

Abstract

AIM
The 2016 WHO classification requires molecular diagnosis in routine glioma diagnostics. However, analysis of key driver gene mutations and chromosome 1p/19q co-deletions cannot be performed in a single platform. In this study, we evaluated the feasibility of a glioma-specific NGS panel for molecular diagnosis of glioma patients.

MATERIALS AND METHODS
We developed a glioma-specific NGS panel consisting of 48 genes, including glioma-relevant key driver genes and 21 genes mapped to chromosome 1 and 19. DNA was extracted from formaldehyde fixed-paraffin embedded (FFPE) tumor tissues histologically identified by a pathologist, and from patient-derived blood as a control. In this system, we implemented a molecular barcodes method to enhance confidence in clinical samples and analyzed 80 glioma patients (Grade II: 17 cases, Grade III: 16 cases, Grade IV: 47 cases).

RESULTS
From these 80 cases, IDH1 and H3F3A mutations were detected in 23 cases (29%) and 2 cases (5%), respectively. The 1p/19q co-deletion was detected in 15 cases (19%), with all cases also containing IDH1 mutations. In Grade IV cases, EGFR, PDGFR, and FGFR mutations were detected in 6% (amp 19%), 9%, and 4% (amp 17%) of cases, respectively. PTEN, TP53, NF1, RB1, and CDKN2A mutations were detected in 37% (del 72%), 45% (del 13%), 21% (del 23%), 15% (del 60%), and 2% (del 53%) of cases, respectively.

CONCLUSION
Diagnosis of glioma patients with this glioma-specific NGS panel is feasible.
NCOG-03. COGNITIVE CONCERNS AND PERFORMANCE IN PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (mNSCLC)
Authors: Eggen Annemarie , Richard Nadine , Shen Gerald , Shultz David , Leighl Natasha , Liu Geoffrey , Sun Alexander , Bosma Ingeborg , Reyners Anna , Jalving Mathilde , Rodin Gary , Edelstein Kim 
Published: December 2019

Abstract

INTRODUCTION
Cognitive concerns and objective cognitive impairment are both common in cancer patients, although the relationship between these variables is uncertain. Brain metastases have the potential to affect both outcomes. We examined the relationships between cognitive concerns, cognitive performance, and psychological disturbance in mNSCLC patients with and without brain metastases.

METHODS
mNSCLC patients completed standardized neuropsychological tests (HVLT-R, TMTA/B, COWA) and questionnaires measuring cognitive and neurobehavioral concerns, depression, demoralization, self-esteem, illness intrusiveness, and physical symptoms. Perceived cognitive impairment was defined as FACT-Cog scores ≤1.5 SD below the normative mean. Impaired cognitive performance was defined as ≥2 test scores ≤1.5 SD or one test score ≤2.0 SD below normative means. Multivariate analyses used the mean composite of neuropsychological test z-scores (COG-comp). Progressive disease (extra- and/or intracranial) was defined as radiological progression or clinical deterioration within one month before the study.

RESULTS
74 patients participated (53% female; median age 62 (37–82); 30% EGFR mutated). Time since mNSCLC diagnosis was 11 months (median; 0–89). 50% had brain metastases, 21 of whom received cranial radiation (11 SRS, 10 WBRT±SRS). 27% reported cognitive concerns and 42% were impaired on objective testing (HVLT-R:34%, TMT:27%, COWA:16%). Neither was more common in patients with brain metastases. COG-comp (mean±SD: –0.39±0.91) was unrelated to cognitive concerns. In multivariate analyses, less depression (p&lt; 0.01) and illness intrusiveness (p=0.03), and absence of disease progression (p=0.03) were related to better perceived cognitive function. No significant associations were found between cognitive performance and demographic, disease, or psychological variables.

CONCLUSION
Cognitive impairment is common in mNSCLC patients with or without brain metastases, but is independent of cognitive concerns. Cognitive concerns which are linked to depression, illness intrusiveness and disease progression, may be more likely to reflect the impact of cognitive changes in daily life. Both merit further clinical and research attention.
NIMG-12. MULTICOLOURED-ASSISTED SURGERY FOR RESECTION OF HIGH GRADE GLIOMAS WITH 5-AMINOLEVULINACID
Authors: Charalampaki Cleopatra , Atanasopoulos Dimitrios 
Published: December 2019

Abstract

INTRODUCTION
Fluorescence guided surgery with the use of 5-aminolevulinacid (5 -ALA) is nowadays the state of the art treatment of high grade gliomas. However, intraoperative visualization of 5-ALA under dark blue light remains challenging, especially when leaking blood covers parts of the surgical field, where tumor fluorescence becomes invisible. To overcome this problem and combine the brightness of visible light with the information delivered by fluorescence we developed multispectral fluorescence, a technique able to project both information in real time to the surgeon’s eyes, and embedded it on a surgical microscope.

METHODS
We examined 40 patients with brain tumors who underwent surgery, using the MFL operative technique. The tumors involved comprised of 20 glioblastomas, 7 astrocytomas WHO III, 5 meningiomas and 8 metastatic tumors. The MFL technique with the real-time overlay of 5-ALA fluorescence and white light was intraoperatively compared to the classic blue filter detecting 5-ALA fluorescence.

RESULTS
The tumor was in all cases clearly visible and highlighted from the surrounding tissues. The pseudocolor we chose to visualize the tumor was green, representing 5-ALA fluorescence, with the surrounding brain tissueremained in its origin white color. In the cases where blood was covering the surgical field, orientation was easy to maintain, due to the additional information delivered from the white light image.

CONCLUSIONS
The MFL technique embedded on a surgical microscope opens the way for a precise and clear visualization of tumor 5-ALA fluorescence in real time under white light. It can be easily implemented in the resection of all tumors accumulating 5-ALA. Drawbacks of classic 5-ALA fluorescence such as hidden fluorescence because of overlying blood could be overcome with the presence of additional white light and the clear visualization of the exposed brain.
PDCT-03. CHEMOTHERAPY STRATEGIES FOR YOUNG CHILDREN NEWLY DIAGNOSED WITH MEDULLOBLASTOMA UP TO THE ERA OF MOLECULAR PROFILING – A COMPARATIVE OUTCOMES ANALYSIS
Authors: Finlay Jonathan , Mynarek Martin , Dhall Girish , Lafay-Cousin Lucie , Mazewski Claire , Ashley David , Leary Sarah , von Bueren Andre , Gerber Nicolas , Cohen Bruce , Robinson Giles , Russell Geyer J , Tait Diana , Stanek Joseph , Gajjar Amar , Rutkowski Stefan 
Published: December 2019

Abstract

BACKGROUND/OBJECTIVE
Survival had been poor in several multi-center/national studies since the 1980s attempting to delay, avoid or minimize brain irradiation in young children with medulloblastoma. The introduction of regimens in Germany incorporating both intravenous high-dose (HD-MTX) and intraventricular (IVENT-MTX) methotrexate, as well as regimens in North America incorporating marrow-ablative chemotherapy with autologous hematopoietic cell rescue (HDCx+AuHCR), have reported encouraging outcomes. The objective of this report is to perform a comparative outcomes analysis of these differing strategies.

METHODS
Data from 17 prospective multi-center trials published between 1990 and 2018 for children under six years old with medulloblastoma were reviewed; event-free (EFS) and overall survivals (OS) were compared.

RESULTS
Two trials using full-dose cranio-spinal irradiation with or without chemotherapy reported 5-year survivals of 32–38%. Three trials using standard chemotherapy with delayed irradiation reported 2-4-year EFS and OS of 23–34% and 31–46%. Two trials employing standard chemotherapy without irradiation reported 3-5-year EFS and OS of 22–33% and 34–43%. Four trials incorporating HD-MTX with or without IVENT-MTX reported 5-10-year EFS and OS of 56–59% and 67–80%, and 31% and 59% respectively; one trial with HD-MTX without IVENT-MTX for localized desmoplastic/nodular medulloblastoma (DN-MB) reported 2-year EFS and OS of 52% and 92%. Finally, five trials employing induction chemotherapy, with or without HD-MTX, followed by single or tandem HDCx+AuHCR have reported 3-5-year EFS and OS of 45–60% and 60–70%.

CONCLUSIONS
The best survivals are observed in trials including HD-MTX and IVENT-MTX or including HD-MTX during induction followed by HDCx+AuHCR. Because histology/biology (classic and large cell/anaplastic versus DN-MB; SHH versus non-SHH subtypes) have crucial prognostic roles, EFS and irradiation-free survival advantages require analysis in these settings. The benefit of these trials appears true for all young children with medulloblastoma. Risk-adapted treatment stratification for young children may be improved by molecular profiling of SHH- and non-SHH medulloblastoma.