bluuebunny/crossref_metadata_2025_split huggingface dataset:
CLRM-02. TRIAL IN PROGRESS: A PROSPECTIVE, MULTICENTER PHASE 2B STUDY TO ESTABLISH IMAGE INTERPRETATION CRITERIA FOR 18F-FLUCICLOVINE PET IN DETECTING RECURRENT BRAIN METASTASES AFTER RADIATION THERAPY (PURSUE)
Authors: Kotecha Rupesh , Chaglassian Alain , Tainer Nancy , Teoh Eugene J 
Published: September 2021

Abstract

BACKGROUND
Brain metastases represent the most common intracranial tumor in adults, occurring in 10-40% of cancer patients. Most patients undergo multimodal treatment approaches and post-treatment follow-up with conventional MRI (CE-T1-weighted and FLAIR/T2-weighted) of the brain is performed to monitor for disease recurrence. However, owing to the similar appearance of treatment-related changes like radiation necrosis with that of true recurrence, conventional MRI alone suffers from low specificity. Given the high mortality of patients with brain metastases and the considerable treatment-associated morbidity, a need remains for an imaging modality that accurately differentiates recurrence from treatment-related changes. Accurate imaging is key to preventing unnecessary surgery or changes in effective therapy in patients mistaken for disease progression as well as prevent continuation of ineffective therapy if radiation necrosis is incorrectly diagnosed. To this end, 18F-fluciclovine is a synthetic amino acid-based PET imaging agent that has potential to evaluate primary and metastatic brain cancers owing to its low normal background uptake in the brain and increased uptake in brain tumors.

METHODS
NCT04410367 is a prospective, open-label, single-arm, single-dose (185 MBq ± 20%) study with a primary objective to establish visual image interpretation criteria for 18F-fluciclovine PET studies of recurrent brain metastases. Forty subjects with solid tumor brain metastases who have undergone radiation therapy will be enrolled across ~8 US sites if they have a reference lesion considered equivocal on MRI for recurrent disease and are planned for craniotomy. Subjects will undergo 18F-fluciclovine PET &lt;42 days after the MRI and 1–21 days before planned craniotomy. Outcome measures comprise the diagnostic performance of 18F-fluciclovine PET at different thresholds of 18F-fluciclovine uptake compared with histopathology, subject- and lesion-level diagnostic performance based on established image interpretation criteria, and safety evaluations. Enrolment began in August 2020 and the trial is open at the time of submission.
CLRM-04. PHASE I/II SAFETY AND EFFICACY STUDY OF BET BROMODOMAIN INHIBITOR OTX-015 WITH OLAPARIB AND LOMUSTINE IN PATIENTS WITH RECURRENT GLIOBLASTOMA
Authors: Lam Fred 
Published: September 2021

Abstract
Standard of care for patients with glioblastoma (GBM) includes resection with concurrent temozolomide (TMZ) and radiotherapy, with inevitable disease recurrence. Upon recurrence, tumors are often resistant to first-line therapies and/or have infiltrated eloquent or deep brain regions, precluding repeat resection. There is currently no standard of care for recurrent GBM and patients succumb to their disease burden within 12- 15 months of their initial diagnosis of recurrence, exposing an unmet need to find novel therapies to treat recurrent disease. Bromodomain and extraterminal (BET) proteins are chromatin readers that affect transcription of genes. The oral BET inhibitor (BETi) OTX-015 has shown promise in a dose-escalation, phase I study in patients with acute leukemia and other BET inhibitors are currently in phase I studies for the treatment of primary brain tumors. We have recently shown that BET inhibition increases DNA damage and mitotic catastrophe in oncogenic cells by increasing transcription-replication conflicts and downregulating expression of key DNA damage checkpoint proteins, and have also shown its efficacy in decreasing tumor burden and improving survival when combined with TMZ in intracranial mouse models of glioma. We have also demonstrated that BETi's synergize with Olaparib by downregulating expression of the BRCA-driven DNA damage repair pathway and further leverages additive effects when triply combined with other DNA damaging agents such as Lomustine to decrease tumor burden and improve survival in patient-derived mouse models of GBM and medulloblastoma. We therefore hypothesize that the synergistic and additive effects of this triple combination seen in our preclinical studies will achieve therapeutic benefits in patients with recurrent GBM.
CLRM-05. DRUG-RELEASING MICRODEVICES TO PREDICT RESPONSES TO TARGETED THERAPIES IN PATIENTS WITH GLIOMAS
Authors: Blitz Sarah , Dominas Christine , Pannell Michael J , Chiocca E Antonio , Wen Patrick Y , Jonas Oliver , Peruzzi Pierpaolo 
Published: September 2021

Abstract
Genomic studies of tumor specimens are becoming standard of care in patients with gliomas to characterize druggable molecular features. Unfortunately, with the exception of IDH1-R132 mutation and MGMT promoter methylation, molecular markers have failed to predict clinical responses to drugs, and the impact of targeted therapies remains minimal. There is a need for a high-throughput, patient-specific, and significantly predictive method to inform a most effective personalized therapy. This pilot trial tests the safety and feasibility of drug-releasing microdevices which are temporarily implanted into the tumor during a standard craniotomy. They release microdoses of up to 20 drugs or drug combinations into surrounding tissue in a controlled spatial distribution. The devices, together with a cuff of surrounding tumor tissue, are removed at the end of surgery, and the tissue is analyzed for biological and molecular response markers allowing for in situ characterization of the drug efficacy. Four patients have been enrolled to date, out of a total planned of six. Two microdevices were implanted into each tumor (8 total devices). Average indwelling time in tumor tissue was 139 minutes. Eight devices (100%) were successfully retrieved, and all surgeries were completed without immediate (&lt;24 hours) or delayed (&lt;30 days) complications. Seven (87%) specimens were of adequate quality, allowing for planned histological and molecular studies. For all analyzed specimens, the intraoperative incubation time was sufficient to observe: 1) Drug concentration gradients; 2) Differential molecular signs of cell toxicity (DNA damage and Caspase 3 activation); 3) Whole genome transcriptional changes; 4) Tumor microenvironment composition; and 5) Preliminary evidence of concordance between the biological readout obtained from microdevice analysis and clinical response. Drug-releasing microdevices were well tolerated, seamlessly integrated in standard craniotomy workflow, and allowed for collection of a significant amount of data related to the differential efficacy of multiple drugs in a personalized manner.
IMMU-03. MULTICENTER RANDOMIZED PLACEBO CONTROLLED PHASE III TRIAL OF AN AUTOLOGOUS FORMALINFIXED TUMOR VACCINE (CELLM-001) FOR NEWLY DIAGNOSED GLIOBLASTOMAS
Authors: Muragaki Yoshihiro , Ishikawa Eiichi , Nitta Masayuki , Tamura Manabu , Ohno Tadao , Saito Taiichi , Tsuzuki Shunichi , Fukui Atsushi , Kawamata Takakazu 
Published: September 2021

Abstract

INTRODUCTION
The development of novel treatments for glioblastoma is desired and immunotherapy is theoretically expected for highly invasive glioblastoma. An autologous formalin-fixed vaccine (AFTV) derived from resected tumor tissue is stable, contains multiple tumor peptides, and could induce specific immunity. We have conducted three clinical trials in patients with glioblastoma, and the most recent trial was a double-blind, multicenter, phase IIb trial with 63 case enrollments. Although this Phase IIb study revealed no vaccine effects in the whole cohort (mOS: 25.6 months of AFTV group, 31.5 months of the placebo group), the 3-year PFS for patients with total tumor removal was 81% in the AFTV group versus 46% in the placebo group (P=0.067). AFTV vaccine (Cellm-001) may have an effect on certain patient subgroups, and a Phase III study has started in November 2021 (jRCT2031200153). Based on Phase IIb, the enrolled patients were those who could be completely resected on MRI. Cellm-001 administration to a patient in the placebo group at recurrence (crossover) was prohibited. In addition, photodynamic therapy (PDT) was added as a stratification factor because our retrospective study showed a good prognosis of 19 patients who underwent both PDT and AFTV (mOS 47.7 months).

PATIENTS AND METHODS
Trial design: double-blind (1: 1), phase III multicenter, registration 4 years, observation 2 years. ESTIMATED ENROLLMENT: 112 patients with primary glioblastoma (18-75 years old) whose contrast-enhanced lesion could be completely removed on the image and who received standard local radiotherapy and temozolomide chemotherapy. STRATIFICATION FACTORS: presence or absence of PDT, age, KPS. ADMINISTRATION METHOD: Intradermal administration 3 times before radiochemotherapy and 6 times in parallel with maintenance chemotherapy after completion. PRIMARY ENDPOINT: OS, secondary endpoints: PFS and adverse events. https://jrct.niph.go.jp/en-latest-detail/jRCT2031200153.

CONCLUSION
An investigator-initiated phase III trial will investigate the efficacy and safety of unique AFTV immunotherapy.
IMMU-05. A PHASE I STUDY IN PROGRESS OF HEGFRVIII-CD3 BI-SCFV (BRITE) IN PATIENTS WITH WHO GRADE IV MALIGNANT GLIOMA
Authors: Singh Kirit , Hotchkiss Kelly , Gedeon Patrick , Schaller Teilo , Herndon James , Archer Gary , Sampson John , Khasraw Mustafa 
Published: September 2021

Abstract

INTRODUCTION
Approximately 30% of glioblastomas harbor the tumor specific EGFRvIII mutation. hEGFRvIII-CD3 bi-scFv (Brain Bi-Specific T Cell Engager - BRiTE) is a novel bispecific antibody construct which can redirect a patient’s entire repertoire of T cells (TCR-agnostic) to specifically lyse EGFRvIII-positive tumor cells. Compared to CAR-T therapy, it offers a highly potent yet off-the-shelf approach for glioblastoma. BRiTE is now entering Phase I clinical trials (NCT04903795) and will be trialed as a monotherapy or with autologous T cell infusion. Migration of T cell binding macromolecules across the blood-brain barrier may be facilitated by activated T cells which adhere to the microvascular endothelium and enter the brain parenchyma. Concurrent administration of activated T cells could therefore enhance trafficking of BRiTE and other antibody-based macromolecules into the intracerebral compartment.

HYPOTHESIS
We hypothesize that treatment of EGFRvIII-positive WHO grade IV malignant glioma with BRiTE alone or with peripheral T-cell infusion is safe and can induce objective tumor shrinkage at tolerable doses.

TRIAL DESIGN/OBJECTIVES
A maximum of 18 patients with newly diagnosed or recurrent WHO grade IV malignant EGFRvIII+ glioma will be enrolled after undergoing standard of care treatment. The primary objective will be evaluating the safety of BRiTE alone and with autologous T cell infusion. Patients will receive a single BRiTE infusion, followed 14 days later by an infusion of activated autologous T cells and a second bolus BRiTE infusion. Dose escalation and de-escalation will be managed using a Bayesian optimal interval design. Secondary objectives will be to describe clinical benefit as determined by objective response rate per mRANO criteria, and to evaluate BRiTE pharmacokinetics in serum.

CONCLUSION
We describe a first-in-human trial of bispecific T cell engager therapy for glioblastoma. We also describe our novel approach for enhancing intracranial penetration of BRiTE using autologous T cell infusion.
IMMU-06. TARGETING IDH1 MUTANT GRADE II RECURRENT GLIOMAS USING A PEPTIDE VACCINATION STRATEGY
Authors: Mohan Aditya , Peters Katherine , Hotchkiss Kelly , Batich Kristen , Congdon Kendra , Vlahovic Gordana , Archer Gary , Norberg Pamela , Xie Weihua , Herndon James , Jaggers Denise , Landi Daniel , Johnson Margaret , Desjardins Annick , Friedman Henry , Yan Hai , Ashley David , Khasraw Mustafa , Reap Elizabeth , Sampson John 
Published: September 2021

Abstract

INTRODUCTION
While primary GBM is largely heterogeneous and devoid of homogeneously expressed neoantigens, mutant IDH1 (R132H) is a uniformly expressed hallmark in &gt;70% of low grade gliomas. As such, IDH1 mutations represent a potentially valuable vaccination target.

METHODS
Here, we report an update on the immunogenicity results of the mutant IDH1 peptide vaccine alone and in combination with temozolomide (TMZ). In the phase I RESIST clinical trial (NCT02193347), patients with recurrent and resectable IDH1 R132H mutant grade 2 glioma received peptide vaccinations composed of 500 µg of mutant IDH1 peptide and 150 µg of GM-CSF mixed 1:1 with Montanide adjuvant prior to surgical resection. Vaccines 1, 2, and 3 were given 15 (+/-) 3 days apart. 7-12 days after vaccine 3, patients underwent standard of care tumor (SOC) resection. After resection, patients with grade 2 gliomas were given up to 15 doses of peptide vaccine in combination with TMZ regimens while patients with transformed grade 3 gliomas were given up to 15 doses of peptide vaccine in combination with SOC radiation therapy + TMZ regimens. T cell responses against the mutant peptide were measured after vaccine 3 using IFN-γ ELISPOT and intracellular flow cytometry for IL-2, TNFα,and IFNγ.

RESULTS
3/20 patients were taken off the study before completion of study related activities. 1/20 patients progressed before completion of all vaccines. Out of 134 total doses of vaccine delivered, only one dose generated a grade 2 or higher injection site reaction according to the CTCAE guidelines. Vaccination with the mutant peptide led to an overall increase in IFN-γ+ spot-forming splenocytes specific to the mutant peptide (p=0.0408).

CONCLUSION
Administering the mutant IDH1 peptide vaccine in patients with recurrent IDH-mutant gliomas was able to induce anti-IDH1 R132H immune responses in this initial phase I study.
IMMU-08. PHASE II TRIAL OF PEMBROLIZUMAB AND LENVATINIB FOR LEPTOMENINGEAL METASTASES
Authors: Wang Nancy , Cahill Daniel , Oh Kevin , Cahill Jennifer , Gerstner Elizabeth , Brastianos Priscilla 
Published: September 2021

Abstract
Leptomeningeal metastasis (LMD) is a late complication of cancer with poor prognosis and median survival of approximately 4-6 weeks without treatment. Whole brain radiation remains the mainstay of treatment, however it can cause significant neurocognitive sequelae and has not been shown to prolong overall survival. Thus, new treatment strategies are urgently needed to improve outcomes in patients with LMD. Results from recent Phase 2 studies of immune checkpoint inhibitors in LMD shows promising improvement in overall survival. Combining anti-VEGF therapy and immunotherapy may control symptoms due to inflammation and tumor-induced irritation, minimize steroid use, and promote improved efficacy of immunotherapy through modulation of the tumor immune microenvironment. We designed a multi-institutional, single-arm Phase 2 study of pembrolizumab in combination with lenvatinib in patients with LMD from any solid tumor. The primary objective is to estimate the overall survival rate at 6 months (OS6). A Simon two-stage design with a total sample size of 19 evaluable patients will be used to compare a null hypothesis of OS6 of 25% against an alternative hypothesis of 55%. Secondary objectives include assessing safety of pembrolizumab and lenvatinib in this patient population, systemic response rate, intracranial/intraspinal response rate, and progression-free survival. We will also explore clinician-reported neurologic outcomes and patient-reported quality of life and symptom burden. Blood, cerebrospinal fluid, and tissue biomarkers will be analyzed to determine predictors of response. Patients must be on minimal doses of steroids prior to study enrollment and cannot have received prior immune checkpoint inhibitor or anti-VEGF therapy. Response to treatment will be determined using RANO-BM for intracranial disease and RECIST 1.1 for systemic disease. Study accrual is anticipated over 12-24 months with anticipated total study duration of 30 months.
NEIM-03. FEASIBILITY OF AUTOMATED ASSESSMENT OF PROGRESSIVE ENHANCEMENT ON MRI IN PATIENTS WITH NEWLY DIAGNOSED HIGH-GRADE GLIOMA USING A FEATURE-BASED ALGORITHM
Authors: Barboriak Daniel , Peters Katy , Friedman Allan , Friedman Henry , Desjardins Annick 
Published: September 2021

Abstract

BACKGROUND
Approximately 50% of patients with newly diagnosed high-grade glioma (HGG) develop progressive enhancement between their post-operative MRI scan and 12 weeks after radiation and temozolomide. Inter-reader variability on the assessment of progressive enhancement in this patient group is a significant barrier in designing multi-center biomarker trials to distinguish true progression from pseudoprogression. Although enhancement segmentation algorithms have become more widely available, more automated and reproducible techniques to identify patients who develop progressive enhancement are needed to facilitate acquisition of non-standard of care biomarkers when this occurs. We explored the feasibility of using a feature-based algorithm in tandem with freely available / open source automated segmentation algorithms to identify this subset of patients.

METHODS
An automated algorithm using subtraction of registered segmentations to detect new areas of localized thickness of enhancement was developed. Criteria for feasibility (50% within 95% CI of percent patients identified, and sensitivity of &gt;85% of patients assessed as progressed [P+] identified) were determined prospectively. The algorithm was implemented across five different automated enhancement segmentation techniques, then evaluated using a retrospective dataset of 73 patients with newly diagnosed HGG (age 50.8±13.2 years, 37 men, 36 women, 50 GBM, 23 Grade III). Standardized post-baseline brain tumor imaging protocol MR acquisitions were obtained on 1.5T and 3T scanners (GE and Siemens). On chart review, 53% of patients were assessed by neuroradiologists and/or neuro-oncologists as P+ (progression vs. pseudoprogression).

RESULTS
50% was within the 95% CI of percent of patients identified for all five segmentation algorithms. Sensitivity was over 85% for three segmentation algorithms, with the MIC-DKFZ algorithm having highest sensitivity of 92%. For this algorithm, specificity was 77%, PPV was 81% and NPV was 90%.

CONCLUSION
A feature-based algorithm in tandem with open source segmentation algorithms showed preliminary feasibility for automated identification of patients with progressive enhancement.
SCSS-02. INVOLVEMENT OF SUPPORTIVE CARE TEAM AND SOCIAL WORK IN NEUROONCOLOGY IN A TERTIARY CARE HOSPITAL
Authors: Puri Sushant , Huber Michael , Tuite Jason , Arzbaecher Jean , Nicholas Martin , Maraka Stefania 
Published: September 2021

Abstract

BACKGROUND/OBJECTIVES
Supportive Care and Social Work services are underutilized in Neurooncology. ASCO Quality Oncology Program Initiative (QOPI) includes emotional assessment by second and advance care planning (ACP) by third oncologic visit in solid malignancies. We looked (1) reason, location, and the duration from diagnosis for the involvement of supportive care teams and (2) what are the determining factors for advanced care planning in glioblastoma.

METHODS
After obtaining an IRB approval for the study, we performed a retrospective chart review of glioblastoma patients seen at University of Illinois Chicago 2015-2020 using the ICD Code C71.9 for malignant gliomas. Patients who had a pathologic diagnosis of glioblastoma, age &gt; 18 years, and had their entire neurooncologic care at UIC were included in the study. Demographic features, socioeconomic determinants, tumor characteristics, and treatment history were noted. Supportive Care Teams and Social Work notes were reviewed.

RESULTS
Out of the total 403 patients, there were 78 glioblastoma patients. A total 33 met the inclusion criteria. 10 out of 33 had been seen by the supportive care team. Patients in both groups were equally matched for demographics, socioeconomic determinants, and tumor characteristics. ACP were significantly better documented in the supportive care group (p = 0.035). Supportive Care teams were consulted much later after the disease diagnosis, usually in the inpatient setting mostly consulted for goals of care discussion and hospice enrollment. There was a significant positive correlation between the involvement of Supportive Care team and Social Work.

DISCUSSION
A multidisciplinary clinic including an inbuilt palliative and social work teams can improve the Quality of Life (QoL) in glioblastoma patients and their caregivers. ICD code 99497 for a dedicated ACP discussion by the neurooncologist can be used. An ongoing phase III RCT EPCOG aims to assess (QoL) in patients with glioblastoma receiving early palliative intervention.
SYST-07. PILOT STUDY UTILIZING THE HDAC INHIBITOR BELINOSTAT WITH CHEMORADIATION FOR NEWLY-DIAGNOSED GLIOBLASTOMA
Authors: Shu Hui-Kuo , Xu Karen , Ramesh Karthik , Huang Vicki , Gurbani Saumya , Schreibmann Eduard , Weinberg Brent , Sengupta Soma , Voloschin Alfredo , Holdhoff Matthias , Barker Peter , Kleinberg Lawrence , Olson Jeffrey , Shim Hyunsuk 
Published: September 2021

Abstract

PURPOSE
Glioblastomas (GBMs) are highly aggressive brain tumors with poor prognosis. Belinostat is a histone deacetylase inhibitor with blood–brain barrier permeability, anti-GBM activity, and potential to enhance chemoradiation. This clinical trial sought to determine a tolerable dose of concurrent belinostat and assess the clinical efficacy of combining this drug with standard-of-care therapy.

METHODS
13 patients each were enrolled in control and belinostat cohorts. The belinostat cohort was given a belinostat regimen (500-750mg/m2 1x/day x 5 days) every 3 weeks (weeks 0, 3, and 6 of RT). All patients received standard temozolomide and radiation therapy (RT). Patient outcomes included progression-free survival, overall survival (OS), and analysis of recurrence pattern of the recurrent gross tumor volume (rGTV).

RESULTS
Belinostat at 750 mg/m2 produce dose-limiting toxicities (DLTs) in 2 of 3 patients while belinostat at 500 mg/m2 did not result in DLTs. Median OS was 18.5 months for the belinostat cohort and 15.8 months for the control cohort (p=0.53). The rGTVs in the control cohort occurred in areas that received higher radiation doses than that in the belinostat cohort. For those belinostat patients that experienced out-of-field recurrences, tumors were detectable by spectroscopic MRI (sMRI) before RT. In particular, one belinostat patient had an IDH-mutant GBM that had an extraordinary response to therapy with significant shrinkage of enhancing tumor much greater than expected.

CONCLUSION
Belinostat given concurrently at 500 mg/m2 is well-tolerated. While median OS was not significantly increased for the belinostat cohort, recurrence analysis suggests better in-field control with belinostat, suggesting a radio-sensitizing effect. This study suggests that belinostat can act as a synergistic therapeutic agent for GBMs that may be further enhanced by sMRI-guided RT and may be particularly effective against IDH mutant tumors. A trial is currently in development using belinostat with sMRI-guided RT for IDH-mutant high-grade gliomas.