bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTIM-25. PHASE2B/3 STUDY OF NEOANTIGEN-SPECIFIC T CELL IMMUNOTHERAPY IN NEWLY DIAGNOSED O6 – METHYLGUANINE METHYLTRANSFERASE UNMETHYLATED (MGMT -) GLIOBLASTOMA
Authors: Tuncer Tolga , Salacz Michael , Milligan Brian , Sloan Andrew , Mammoser Aaron , Yu John , Aguiar Jean , Skikne Barry , Carter Wayne , Wood Gary 
Published: November 2024

Abstract
MGMT- glioblastoma (GBM) is the most common malignant primary brain tumor, yet outcomes have not improved in decades despite intensive investigations. TVI-AST-008 is a randomized clinical trial of a novel neoantigen-specific T cell immunotherapy regimen proven invariably curative in rodent models and clinically effective in trials of patients with relapsed/resistant GBM. TVAX neoantigen-specific T cell immunotherapy exploits the fact that cancer cells express neoantigens, and adoptive transfer can bypass the immunosuppressive milieu near the resection cavity. In this manner, TVAX effector T cells initiate apoptosis in any residual GBM. After pathologic confirmation, autologous GBM tumor tissue sent to the TVAX GMP manufacturing facility is irradiated and utilized for proprietary vaccine production. Patients are vaccinated with a series of two intradermal injections and the resulting cancer neoantigen-specific T cells are harvested by leukapheresis. These T cells are activated and proliferated ex vivo by TVAX manufacturing to generate effector T cells. These are re-infused following standard radio-chemotherapy, followed by low-dose interleukin-2 to further stimulate T cell proliferation. In the study, MGMT- GBM patients are randomly assigned to treatment or control arms. Patients in the treatment arm undergo vaccination, then standard concurrent IMRT-chemotherapy, followed by re-infusion of TVAX autologous effector T cells. Patients in the control arm undergo standard IMRT-chemotherapy followed by adjuvant chemotherapy with temozolomide. TVI-AST-008 is an ongoing, randomization-controlled study with Fast Track designation from the FDA. The primary end point is overall survival. Additional end points include progression free survival, safety and immune response. Patients are followed with physical exams and surveillance MRI for evidence of disease progression. The trial is targeted for 15 centers in the US.
CTIM-26. PHASE II STUDY OF AZELIRAGON IN COMBINATION WITH RADIATION THERAPY IN NEWLY DIAGNOSED PATIENTS WITH MGMT-UNMETHYLATED GLIOBLASTOMA
Authors: Huang Jiayi , Ahluwalia Manmeet , Boockvar John , Batiste James , Jaboin Jerry , Thotala Dinesh , Halasz Lia , Rammohan Nikhil , Ney Douglas , Malani Rachna , Chinnaiyan Prakash , Kotecha Rupesh R , Mehta Minesh , Marcus Stephen 
Published: November 2024

Abstract

BACKGROUND
Myeloid-derived suppressor cells (MDSCs) exacerbate immunosuppression and immune exhaustion in glioblastoma (GBM) and promote resistance to chemoradiotherapy. Preclinical data demonstrate that inhibiting the receptor for advanced glycation end-products (RAGE) pathway using azeliragon, when combined with radiation therapy (RT), can modulate MDSC accumulation in the tumor microenvironment and improve tumor control. CAN-401 is a phase II study evaluating the safety and preliminary clinical efficacy of combining azeliragon with RT for newly diagnosed IDH-wildtype MGMT-unmethylated glioblastoma (GBM).

METHODS
This multi-institutional, single-arm, open-label phase II study combines azeliragon with RT (60 Gy/30 fractions). Azeliragon is administered orally with a loading dose of 30 mg twice daily for 6 days before RT, followed by 20 mg daily during and after RT. If more than one dose-limiting toxicity occurs during the safety run-in of 6 patients, additional patients will be treated at de-escalated dose levels using the rolling six design. The study hypothesizes that azeliragon and RT will improve median progression-free survival (PFS) to 9.7 months compared to historical control of 5.7 months, corresponding to a hazard ratio of 0.58. The study aims to enroll 30 evaluable patients.

RESULTS
From December 2023 to May 2024, 10 patients were enrolled and treated with 20 mg of azeliragon daily, including 6 patients in the safety run-in. No dose-limiting toxicity was observed, hence no dose de-escalation was needed. The most common treatment-related adverse events (AEs) were grade 1, including fatigue and lymphopenia. There were no dose modifications or discontinuations due to treatment-related AEs. Enrollment is ongoing, and updated clinical outcomes will be reported.

CONCLUSIONS
Azeliragon at 20 mg per day with concurrent RT is well tolerated in patients with GBM. The phase II study is currently enrolling across 8 institutions in the United States (NCT05986851).
CTNI-01. INTERVENTION OUTCOMES OF ENHANCED RECOVERY AFTER SURGERY PROTOCOL VERSUS STANDARD CARE FOR GLIOMA PATIENTS IN SELECTED HOSPITALS IN DEMOCRATIC REPUBLIC OF THE CONGO: RANDOMIZATION AND STRATIFICATION OF PROVIDERS AND HOSPITALS
Authors: Kamabu Larrey Kasereka 
Published: November 2024

Abstract

BACKGROUND
Enhanced Recovery after Surgery (ERAS) protocols have shown promise in improving perioperative care and patient outcomes in various surgical specialties. Aim: This study will aim to assess the efficacy of ERAS compared to the current standard of care (SOC) for glioma patients in DRC hospitals.

METHODS
A pragmatic, multicenter, randomized controlled trial will be designed to evaluate the outcomes of glioma patients treated with ERAS protocols versus SOC in selected hospitals in DRC.

EXPECTED RESULTS
A total of 100 glioma patients will be included in this study, with 50 patients in the ERAS group and 50 in the SOC group. The primary analysis will reveal that the ERAS group will have significantly fewer post-operative complications (p &lt; 0.05) and a shorter length of hospital stay (p &lt; 0.05) compare to the SOC group. Patient satisfaction scores will also higher in the ERAS group. Subgroup analyses by hospital center will indicate consistent trends in favor of the ERAS protocol. Randomization of providers and stratification by hospital will aim to mitigate the influence of individual provider practices and hospital-specific factors on the study outcomes. This approach will be expected to enhance the validity of the results and ensure equitable representation across hospitals.

CONCLUSIONS
The unique design of randomizing providers and stratifying by hospital will be a critical component of this multicenter trial, which seeks to provide valuable insights into the potential benefits of ERAS protocols for glioma patients in DRC. The findings will guide clinical practice and healthcare policy in resource-constrained settings, ultimately improving the care and outcomes of glioma patients
CTNI-02. FLUORESCEIN-STAINED CONFOCAL LASER ENDOMICROSCOPY VERSUS CONVENTIONAL FROZEN SECTION FOR INTRAOPERATIVE HISTOPATHOLOGICAL ASSESSMENT OF INTRACRANIAL TUMORS
Authors: Wagner Arthur , Brielmaier Maria Charlotte , Kampf Charlotte , Baumgart Lea , Aftahy Amir Kaywan , Meyer Hanno-Sebastian , Kehl Victoria , Höhne Julius , Schebesch Karl-Michael , Schmidt Nils Ole , Zoubaa Saida , Riemenschneider Markus , Ratliff Miriam , Enders Frederik , von Deimling Andreas , Liesche-Starnecker Friederike , Delbridge Claire , Schlegel Jürgen , Meyer Bernhard , Gempt Jens 
Published: November 2024

Abstract

BACKGROUND
The aim of this clinical trial was to compare Fluorescein-stained intraoperative confocal laser endomicroscopy (CLE) of intracranial lesions and evaluation by a neuropathologist with routine intraoperative frozen section (FS) assessment by Neuropathology.

METHODS
In this phase II non-inferiority, prospective, multicenter, non-randomized, off-label clinical trial (Eudra-CT: 2019-004512-58), patients above the age of 18 years with any intracranial lesion scheduled for elective resection were included. The diagnostic accuracies of both CLE and FS referenced with the final histopathological diagnosis were statistically compared in a non-inferiority analysis, representing the primary endpoint. Secondary endpoints included the safety of the technique and time expedited for CLE and FS.

RESULTS
210 patients were included by 3 participating sites between November 2020 and June 2022. Most common entities were high grade gliomas (37.9%), metastases (24.1%), and meningiomas (22.7%), A total of 6 serious adverse events in 4 (2%) patients were recorded. For the primary endpoint, the diagnostic accuracy for CLE was inferior with.87 versus.91 for FS, resulting in a difference of.04 (95% confidence interval -.10;.02; p=.367). The median time expedited until intraoperative diagnosis was 3 minutes for CLE and 27 minutes for FS, with a mean difference of 27.5 minutes (standard deviation 14.5; p&lt;.001).

CONCLUSION
CLE allowed for a safe and time-effective intraoperative histological diagnosis with a diagnostic accuracy of 87% across all intracranial entities included. The technique achieved histological assessments in real-time with a tenfold reduction of processing time compared to FS, which may invariably impact surgical strategy on the fly.
CTNI-04. DECODING GLIOBLASTOMA SURVIVAL: UNRAVELING THE PROGNOSTIC POTENTIAL OF OLFACTORY FUNCTION IN A PROSPECTIVE OBSERVATIONAL STUDY
Authors: Oster Christoph , Matyar Aylin , Hummel Thomas , Hattingen Elke , Schmidt Teresa , Jokisch Martha , Jokisch Daniel , Ahmadipour Yahya , Sure Ulrich , Stuschke Martin , Tertel Tobias , Giebel Bernd , Kleinschnitz Christoph , Scheffler Björn , Deuschl Cornelius , Kebir Sied , Glas Martin 
Published: November 2024

Abstract

BACKGROUND
Olfactory impairment is a common neurologic deficit among glioblastoma patients.We have previously shown that glioblastoma patients with reduced smell sensitivity had lower overall survival rates compared to those with normal olfactory function.A notable limitation in that study was the unequal distribution of prognostic factors between the two groups,and the absence of continuous olfactory assessments during treatment to investigate if therapy-associated neurotoxicity could be a contributing factor to diminished olfactory acuity.In this trial olfactory function will be evaluated in glioblastoma patients as a prognostic marker with regard to overall survival,neurocognition and quality of life.

METHODS
This prospective,multicenter study is set to recruit 64 glioblastoma patients alongside 64 healthy controls.Stratification of participants is based on prognostically relevant variables such as resection status,MGMT-promoter-methylation-status,radiographic involvement of olfactory brain areas,olfactory function,age,and Karnofsky performance status scale.We utilize Sniffin´ Sticks to evaluate olfactory function through identification and threshold tests,and this assessment is carried out longitudinally throughout the therapy starting from tumor diagnosis.Infiltration of the olfactory nerves or olfactory brain are scrutinized using a high-resolution coronal T2-weighted sequence which is added to a dedicated brain tumor protocol.MRI images are independently reviewed by two board-certified radiologists from distinct institutions,who are blinded to the patients’ olfactory function status.Furthermore,quality of life data,neuropsychological testing,and psychosomatic screening are performed at specific intervals throughout the study.Also,we examine next-generation-sequencing results to investigate potential genetic associations with hyposmia in glioblastoma patients.

RESULTS
The first participant was enrolled in May 2023.Currently,16 patients and three controls are already enrolled(May 2024).Plans are underway to open a second study site in 2024,with the aim to complete recruitment by December 2025.Follow-up assessments will continue until December 2027.We anticipate that the final results of the study will be available in 2028.

CONCLUSIONS
In the process,this study is the first prospective study which investigates the olfactory function systematically as prognostic factor in glioblastoma patients.
CTNI-13. 18-FET-PET ENHANCED DIAGNOSIS OF PSEUDOPROGRESSION IN GLIOBLASTOMA IS AN INDEPENDENT PROGNOSTIC FACTOR FOR OVERALL SURVIVAL
Authors: Schmidt Teresa , Oezdemir Zeynep , Oster Christoph , Sure Ulrich , Hermann Ken , Stuschke Martin , Deuschl Cornerlius , Kleinschnitz Christoph , Müther Michael , Glas Martin , Kebir Sied 
Published: November 2024

Abstract

INTRODUCTION
Detecting pseudoprogression (PSP) in glioblastoma during first-line treatment remains challenging and has significant clinical implications for patient management. The detection of PSP has been shown feasible using FET-PET. The prognostic impact of FET-PET diagnosed PSP on overall survival is still uncertain, as retrospective studies provide limited insights due to the substantial differences in the distribution of prognostic factors between tumor progression (TP) and PSP groups. This study aims to address these uncertainties by leveraging advanced analysis techniques.

METHODS
Patients with newly diagnosed glioblastoma (WHO 2021) who underwent chemoradiation and contrast-enhanced MRI suspected for TP and subsequent FET-PET scan at Essen University Hospital were retrospectively evaluated. The modified Response Assessment in Neuro-Oncology (RANO) criteria were used to diagnose PSP. FET-PET analysis included mean (TBRmean) and maximum tumor-to-brain ratios (TBRmax). The two groups (TP/PSP) were balanced using a propensity score analysis including age at diagnosis, extent of resection, Karnofsky-Performance-Status Scale (KPS) and MGMT methylation status. Overall survival was predicted using Kaplan-Meier and multivariate analysis as well as conventional FET-PET parameters, PET/MRI volumetry, and FET/MRI-derived radiomics. An independent cohort was used for validation.

RESULTS
Out of the 165 patients analysed in this study, 38 were diagnosed with PSP. Following balancing analysis, our study cohort consisted of 40 patients (20 TP/20 PSP). Patients with PSP had a significantly longer mean overall survival (mOS) compared to those with TP (mOS TP 20.24 months; mOS PSP 33.25 months; p=0.0023). The multivariate Cox-Regression analysis confirmed PSP as a significant prognostic marker for overall survival (p=0.0153). Confirmation of these results on an independent validation cohort is pending and will be presented at the meeting.

CONCLUSION
This study shows that PSP is an independent prognostic factor for overall survival in newly diagnosed glioblastoma patients.
CTNI-14. RADIOTHERAPY VERSUS TMZ FOR HIGH-RISK LOW-GRADE GLIOMA. FINAL RESULTS AFTER MEDIAN FOLLOW-UP OF 13 YEARS OF PHASE III EORTC/NCIC-CTG/TROG/MRC-CTU (EORTC 22033-26033) STUDY
Authors: Baumert Brigitta G , Hegi Monika E , Van den Bent Martin , von Deimling Andreas , Gorlia Thierry , Hoang-Xuan Khe , Brandes Alba A , Sargos Paul , Taphoorn Martin , Vauleon Elodie , Phillips Claire , Kros Johan M , Bady Pierre , Wick Wolfgang , Enting Roelien , Reni Michele , Thiessen Brian , Dhermain Frederic , Bromberg Jacoline , Jacob Julian , Reijneveld Jaap C , Chinot Olivier , Gijtenbeek Anja , Rossiter John , Lentz Marie-Ange , Balana Carmen , Azevedo Ana Luisa Silva , Clement Paul M , Berghoff Anna , Tzuk Tzahala , Weller Michael , Nordal Robert , Rees Jeremy , Lacombe Denis , Mason Warren P , Stupp Roger 
Published: November 2024

Abstract

BACKGROUND
We previously reported on progression-free survival of our randomized phase 3 trial [Lancet Oncol. 2016;17:1521-1532]. Here we report results of long-term follow-up (FU) including overall survival (OS) and molecular subgroup analyses.

METHODS
487 patients were randomized between 2005-2012 to either standard radiotherapy (RT, 50.4 Gy/ 28 fractions) or primary dose-dense temozolomide [TMZ] chemotherapy (75 mg/m² daily x 21/28 days, up to 12 cycles). Treatment at progression was at investigators discretion and commonly included cross-over to the alternative treatment modality.

RESULTS
At a median follow-up of 13 years, 68% of patients had died. Median age at inclusion was 45 years (range 18-75), 96% had a performance status of 0-1. There was no significant difference in PFS nor OS: PFS was 3.6 years (95% CI: 3.0-4.1) and 3.1 years (95% CI: 2.7-3.6), HR 1.12 (95% CI: 0.92-1.36); OS 6.6 years (95% CI: 5.8-7.5) and 8.0 years (95% CI: 6.9-9.1), HR 0.87 (95% CI: 0.69-1.09), for RT or TMZ, respectively. Subgroup analyses were performed for patients when available tissue allowed for molecular analyses (n=351/487,73%). In astrocytoma, IDHmt/1p/19q non-codeleted (n = 178), median OS with RT was 6.6 years (95% CI: 5.3-7.6) and with TMZ was 6.7 years (95% CI: 5.7-8.0); HR 0.98 (95% CI: 0.67-1.44). For oligodendroglioma, IDHmt/codeleted (n = 109) median OS with RT was 12.9 years (95% CI: 9.4 - NE) and with TMZ 14.9 years (95% CI: 10.1 - NE); HR 1.01 (95% CI: 0.56-1.81). For a heterogenous group of IDHwt tumors (n = 64), median OS with RT was 2.5 years (95% CI: 1.8-3.3) and with TMZ 4.7 years (95% CI: 2.2-7.2); HR 0.37 (95% CI: 0.18-0.77).

CONCLUSIONS
Primary treatment with RT or TMZ provided comparable PFS and OS. Choice of primary treatment can be tailored to individual tumor characteristics and patient preference.
CTNI-23. DIFFERENT GUT MICROBIOTA COMPOSITION IS ASSOCIATED WITH CHEMOTHERAPY EFFICACY IN PATIENTS WITH DIFFERENT TYPES OF CENTRAL NERVOUS SYSTEM CANCER
Authors: Guo Chengcheng , Zhai Shijia , Chen Zhongping , Yin Lin , Zheng Yilin , Huang Guoxin 
Published: November 2024

Abstract

BACKGROUND
The relationship between central nervous system cancers and the gut microbiota (GM) is not well understood. The purpose of this study is to retrospective analyze the differences between the composition of the gut microbiota in patients with different neurologic tumors and their correlation with chemotherapy efficacy.

METHODS
A total of 44 patients participated in the study and were divided into four groups: gliocytoma (GA), medulloblastoma (MB), germ cell tumors (GT), and diffuse large B-cell lymphoma (DB) based on their pathological diagnosis. Fecal samples were collected from patients for 16S amplicon sequencing to analyze GM composition. Moreover, all the patients were classified into completed response (CR), stable disease (SD), and progressive disease (PD) groups based on the clinical outcomes of chemotherapy. PLS-DA analysis and heatmap analysis were used to reveal the correlation between GM composition and outcomes of chemotherapy.

RESULTS
Phyla taxa comparison showed the detailed GM composition among these four groups. The phylum of Bacteroidetes was higher in GA group when compared to the other groups. And the phylum of Fusobacteria could only be found in GA and MB groups while the phylum of Verrucomicrobia showed a significant accumulation in DB group. the genera of Ruminococcus, Gemmiger, and Parasutterella were accumulated in the patients with the completed response of chemotherapy. Besides, patients in SD group had higher abundance of the genera of Prevotella, Tyzzerella, and Odoribacter. While patients in PD group showed the higher abundance of Streptcoccus, Fusobacterium, Lachnospira, and Holemanella.

CONCLUSION
We firstly drew the GM composition profile of the patients with GA, MB, GT, and DB to show the different GM composition of the diseases. Moreover, the gut microbiota composition correlates with chemotherapy outcomes in central nervous system cancer patients so may serve as a potential biomarker for predicting chemotherapy efficacy.
CTNI-24. WF-1801: SINGLE ARM PILOT STUDY OF RAMIPRIL FOR PREVENTION OF RADIATION-INDUCED COGNITIVE DECLINE IN GLIOBLASTOMA PATIENTS RECEIVING CHEMORADIOTHERAPY
Authors: Cramer Christina , Dressler Emily , Smith Sydney , Page Brandi , Wefel Jeffrey , Gilbert Mark , Rapp Stephen , Ip Edward , Pugh Stephanie , Summrall Ashley , Weaver Kathryn , Lesser Glenn , Chan Michael 
Published: November 2024

Abstract

BACKGROUND
Patients with glioblastoma (GBM) experience cognitive decline after chemoradiation. Radiation therapy (RT) to the brain creates chronic inflammation believed to contribute to cognitive decline. Ramipril counteracts neuroinflammatory changes in pre-clinical models when given during RT.

METHODS
This prospective single arm study (WF-1801) coordinated by the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base assessed feasibility, tolerability, and potential efficacy of using ramipril in patients with GBM. Eligibility and treatment paradigms mirrored NRG/RTOG 0825 allowing for outcomes from the placebo arm to be used for comparison. Participants took ramipril during 6 weeks of chemoradiation with temozolomide and for 3 months after RT. Patients completed cognitive testing (HVLT-R, TMT, and COWA) and patient-reported outcomes at baseline, RT completion, and 1 and 4 months after RT. Co-primary endpoints were retention rate (compliance with 75% doses and completion of cognitive testing) and change in cognitive composite score 1 month after RT.

RESULTS
75 participants were accrued between 3/25/2019 and 11/14/23: 65% were male, 89% White, median age 63 years. The NRG/RTOG 0825 placebo cohort (n=247) was younger (median 57, p&lt;0.0001) with more White participants (95%, p=0.04). The overall retention rate in WF-1801 was 48% (one-sided 95% CI: 38%-100%); 61% completed &gt;=75% of doses; 57% completed cognitive testing at all time points. The median (range) change in cognitive composite score 1 month after RT was 0.01 (-82.6, 13.0) reflecting an improvement from baseline. However, this was not significantly different from the NRG/RTOG 0825 placebo group median of 0.10 (-48.2, 8.6); p=0.49.

CONCLUSION
The overall retention rate fell short of our pre-specified endpoint of &gt; 65%; however, medication compliance was high and well-tolerated in retained patients. Future investigations could identify patient subsets who may benefit more from concurrent ramipril. WF-1801 (NCT03475186) funded by UG1CA189824. NRG/RTOG-0825 (NCT00884741) funded by U10CA180868 and U10CA021661.