bluuebunny/crossref_metadata_2025_split huggingface dataset:
P15.12.A BIUX2X2
Authors: Gromova E , Smirnova A , Kataeva G , Plakhotina N 
Published: September 2023

Abstract

BACKGROUND
Brain metastases occur in 20-40% of cancer patients. In connection with the development of radiosurgical treatment, the problem of differential diagnosis of continued tumor growth and post-radiation changes becomes relevant. The main method of radiosurgical treatment of secondary lesions is the Gamma-Knife. Positron emission tomography with 11C-Meth and 18F-FET is an important method in monitoring the treatment of patients with secondary brain tumors.

MATERIAL AND METHODS
We examined 73 patients with brain metastases. Of these, 36.36% were patients with breast cancer, 39.39% were patients with lung cancer, 9.00% were patients with melanoma, 6.06% were patients with kidney cancer, 9.09% were other nosology, which corresponds to the data on the frequency of metastasis to the brain of various types of cancers. All patients underwent MRI with standard sequences (T1, T2, FLAIR, T1+C) and PET-CT with 18F-FET. PET-CT was performed according to the standard protocol: scanning 20 minutes after the

INTRODUCTION
of the radiopharmaceutical, scanning time 20 minutes. The evaluation of PET images was carried out by a semi-quantitative method - TBR max.

RESULTS
The mean age of patients with breast cancer was 54.5 ± 10.4, which significantly differs from the mean age of patients with lung cancer (65.9 ± 8.7) and the mean age of patients with other primary cancers (62.8 ± 8, 8) (Kruskal-Wallis test: H(2, N=66)=13.99052 p=.0009). Differences in TBR max and the number of metastases in these groups are not significant, as well as, according to the Kaplan-Meier analysis, differences in the duration of the relapse-free period. However, differences in the duration of the relapse-free period in the groups after a single ( Median, Q1; Q3) (12.9, 10.5; 24.4) or multiple (7.5, 3.5; 10.5) radiosurgical treatment are significant ( Gehan's Wilcoxon Test, Test statistic = 2.063905 p = .03903). Based on the analysis of the data obtained, it was found that the threshold value TBR max &gt;=2.8 in 100% of cases indicates progression, TBR max &lt;=1.7 indicates a stable course. Whereas TBR max in the range from 1.7 to 2.8 (in 33 people from the examined group, i.e. in 50% of all cases) may indicate both progression and post-radiation changes, as well as confirmed positive dynamics.

CONCLUSION
Thus, we confirmed that the numerical value of TBR max is a relative indicator. And when interpreting PET data, we cannot rely only on the TBR max value in the range from 1.7 to 2.8 for a confident judgment about the genesis of increased RP uptake in tumors. In the absence of other markers of the development of progression (for example, the appearance of new pathological foci), to assess the dynamics and confidently identify post-radiation changes, a repeat PET study should be prescribed after 2-3 months with a preliminary MRI with contrast enhancement.
P15.14.A DIFFERENTIATE TREATMENT EFFECTS FROM DISEASE PROGRESSION IN TREATED BRAIN TUMOR: PROMISING RESULTS USING DELAYED CONTRAST MRI
Authors: Navarria P , Pessina F , Bellu L , Politi S , Savini G , Clerici E , Marini B , Scorsetti M 
Published: September 2023

Abstract

BACKGROUND
Treatment effects are reported in about 30% of treated glioma and brain metastases (BMs) characterized by increasing volume of contrast enhancing regions on MRI, similarly to tumor progression. Data interpretation are often difficult. The most methodology used to distinguish this 2 conditions is perfusion MRI; treatment effects are characterized by a decreased relative cerebral blood volume (rCBV) while persistent or progressive tumors by high rCBV. Limits of perfusion MRI are represented by overlap between two conditions, low spatial resolution, and presence of susceptibility artifacts. To overcome this crucial issue, encouraging results have been obtained using delayed contrast MRI that through contrast clearance analysis (CCA) allows to calculate high resolution maps called “treatment response assessment maps” (TRAMs). We prospectively evaluated patients with doubtful framework between treatment effects (TE) and tumor progression (TP) aiming to assess the ability of CCA in differentiate this two conditions in a cohort of treated brain tumor patients.

MATERIAL AND METHODS
Maps (TRAMS) were calculated through contrast clearance analysis (CCA) by subtracting ceT1MRI images acquired 5 minutes after contrast injection from images acquired at least 60-105 minutes after. Diagnosis of persistent tumors or disease progression was based on presence of contrast clearance (CC) region in blue, and treatment effects on contrast accumulation (CA) region in red. Data of CCA were compared to perfusion MRI. All images were uploaded, co-registered and elaborate into the image workstation of Brainlab. Whole tumor and enhancing tumor volumes were segmented and perfusion measures in area of signal alteration. TRAMs were generated and at last the calculation of effective volume of viable tumor tissue (CC region) and treatment-induced tissue changes within each lesion (CA region) have been calculated.

RESULTS
From February 2021 and November 2022, 62 patient (96 delayed-contrast-MRI) with doubtful framework between TE and TP underwent CCA and perfusion-MRI. Twenty-five treated for newly diagnosed glioma, 13 for recurrence, and 37 for BMs. Significantly increased rCBV value in CC regions compared to CA was observed (p=0.01). Patients with TP showed significantly greater CC that subjects with stable disease/partial response 33% vs 78% (p=0.01). TRAMs metric were in agreement with perfusion results. Greater accuracy of TRAMs compared to perfusion-MRI in discriminate TE from TP 81% vs 69% has been observed.

CONCLUSION
In our experience CCA tool compared to perfusion MRI had a greater accuracy in discriminating true tumor progression from treatment induced tissue changes, and can be of improvement in patient management.
P16.01.A THE CASE OF AGGRESSIVE DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR IN ADULT TREATED WITH CRANIOSPINAL IRRADIATION AND TEMOZOLOMIDE
Authors: Hwang J , Lee C , Yoon S , Kim M , Park K , Park S 
Published: September 2023

Abstract

BACKGROUND
Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare tumor, which was introduced as a separate entity in the 2016 World Health Organization classification of central nervous system tumors. It is most common in pediatric age, but very rare in adults. Literature demonstrates limited reports regarding treatment strategy in adult. We present a case of young female affected by DLGNT with aggressive behavior.

MATERIAL AND METHODS
A 28-year-old woman presented with severe headache and vomiting. Brain MRI showed diffuse leptomeningeal enhancement with hydrocephalus. At first, she was under suspicion of tuberculosis meningitis with mild increased protein level in CSF study. Her symptom rapidly improved after ventriculoperitoneal shunt and she started anti-tuberculosis medication. Despite 8-month of medication, her neurological status gradually deteriorated with paraparesis and follow-up MR images showed progression of disease. She underwent open biopsy of superficial brain lesions.

RESULTS
Intraoperatively, multiple nodular masses were attached inner side of dura mater and diffuse adhesion on subarachnoid space of brain surface. Histological examination revealed small round cells with oligodendroglial-like aspects. Immunohistochemistry showed positivity for Olig2, synaptophysin and S100. Chromosome 1p deletion was confirmed by FISH. Next-generation sequencing profile disclosed mutation of H3K28M, FGFR1 and ATRX. Diagnosis was consistent with DLGNT. She received craniospinal irradiation of 36 Gy in 20 fractions, then started chemotherapy with temozolomide (TMZ) at a dose 200mg/m2/day for 5 days in 4 weeks. After 4 cycles of TMZ, MR images demonstrated stable disease.

CONCLUSION
DLGNT is a very rare tumor in adult. Diagnosis needed high level of suspicion and histological confirmation. We present a very rare adult DLGNT patient with aggressive clinical features who showed stable state treated with craniospinal irradiation and TMZ chemotherapy.
P16.03.A DEVELOPMENT OF INTRATHECAL DRUG DELIVERY PLATFORM TO CURE BREAST CANCER LEPTOMENINGEAL DISEASE BY DENDRITIC CELL VACCINE IN PRECLINICAL MODEL
Authors: Law V , Snyder C , Macaisa L , Garg S , Czerniecki B , Forsyth P A 
Published: September 2023

Abstract

BACKGROUND
Leptomeningeal disease (LMD) is a rare form of metastasis in the meninges, a membrane surrounding the brain and spinal cord. Approximately 5% of advanced stage breast cancer (BC) will develop LMD and currently there is no cure. One reason for poor prognosis is the issue of drug accessibility to tumor sites due to the blood brain barrier (BBB) and blood-cerebral spinal fluid (CSF)-barrier. While the Ommaya reservoir is used clinically to overcome this challenge, there has not been an optimized preclinical model that allows researchers to adequately test novel therapies in the CSF space.

MATERIAL AND METHODS
The Forsyth lab have recently developed an MRI-compatible device called the “murine Ommaya” which mimics the Ommaya reservoir and allows repeated intrathecal (IT) administration of drugs in 3-7μl volume directly into CSF, bypassing BBB. In a joint effort with Dr. Czerniecki, whose lab have developed a pipeline for screening immunogenic MHC class II peptides from tumor-associated oncodrivers and subsequently generating tumor-targeting dendritic cells (DC), we have created a platform to IT deliver peptide-pulsed DCs directly targeting BC-LMD.

RESULTS
Currently, we have tested the efficacy of treatment in HER2+ LMD and triple negative breast cancer (TNBC) LMD models and found a very favorable response; LMD mice that received IT DC therapy exhibited reduced tumor burden and prolonged survival, and is more superior than systemic therapy. About 70% of mice from HER2+ LMD and 30% from TNBC LMD were cured of disease. Cured mice also exhibited resistance against LMD recurrence.

CONCLUSION
Our preliminary data suggest IT DC immunotherapy is effective against the incurable BC-LMD. We are currently investigating the mechanism(s) by which IT DC-initiated CD4 Th1 adaptive immune response against LMD. By using single-cell RNA-sequencing technique, we are analyzing the immune landscape in CSF tumor microenvironment in response to IT DC. FDA-approved phase I clinical trial has been funded by the US Department Of Defense. Future approach includes employing our IT DC vaccine platform in other cancer types, such as LMD from melanoma.
P17.03.A MAGIC-G1: A PHASE 1 DOSE-ESCALATION TRIAL OF WEEKLY INTRATUMORAL ADMINISTRATION OF THE SOLUBILISED FORMULATION OF PANOBINOSTAT (MTX110) IN PATIENTS WITH RECURRENT GLIOBLASTOMA (RGBM)
Authors: Desjardins A , Barnes H , Davies R , Grant G , Cavaliere R , Sauvageau E , Zamoryakhin D 
Published: September 2023

Abstract

BACKGROUND
One of the biggest challenges in treating rGBM is achieving high local drug concentration. Convection enhanced delivery (CED) is a ‘direct-to-brain’ drug delivery method that previously demonstrated its usefulness in overcoming the blood-brain barrier, while also limiting systemic toxicity. MTX110 (Midatech Ltd), a water-soluble formulation of panobinostat, has demonstrated cytotoxic activity in GBM cell lines, as well as safety and efficacy in two pediatric diffuse pontine glioma trials. Delivery of MTX110 via an implanted pump and CED catheter system in patients with GBM appears to be an attractive treatment option, that allows for therapeutic doses of the drug to be delivered weekly directly to the tumor, thus avoiding systemic administration and therefore toxicity.

MATERIAL AND METHODS
Eligibility includes adult rGBM patients with a single enhancing lesion ≤3cm in maximal diameter; ≥4 weeks after chemotherapy, bevacizumab, or study drug; adequate organ function; and KPS ≥60%. MTX110 is continuously infused over 48hrs weekly at a rate of 0.5mL/h, via a CED catheter implanted into the enhancing disease recurrence connected to a fully internalized pump system. After safety of a single patient treated at 60μM has been established, 3-6 patients will be treated with MTX110 at 90μM as a single agent (Cohort 1). Patients in cohort 2 will receive MTX110 in combination with lomustine at a starting MTX110 dose of 60 μM and following the same dose-escalation approach.

RESULTS
As of March 30, 2023, the 1st patient was treated in monotherapy at 60μM and has received 12 weekly infusions of MTX110. No dose-limiting toxicities were observed. Observed study related adverse events (AEs) included: grade 1 cognitive disturbance, headache, and seizure; grade 2 candida wound infection, erythema of the scalp, bruising, and hemiparesis; and grade 3 abdominal seroma at pump insertion site. Enrolment is ongoing and the next patient will receive the 90 μM dose.

CONCLUSION
Weekly intratumoral administration of MTX110 via a fully internally implanted CED pump system is feasible. Updated results will be presented.
P17.07.A REGORAFENIB IN RECURRENT GLIOBLASTOMA PATIENTS: AN ITALIAN OBSERVATIONAL, MULTICENTRIC AND PROSPECTIVE TRIAL (REGOMA-OSS)
Authors: Caccese M , Padovan M , Desideri I , Villani V , Simonelli M , Buglione M , Chiesa S , Franceschi E , Gaviani P , Stasi I , Caserta C , Brugnara S , Lolli I , Bennicelli E , Bini P , Cuccu A , Cerretti G , De Salvo G , Lombardi G 
Published: September 2023

Abstract

BACKGROUND
In the randomized phase 2 REGOMA trial, regorafenib has shown promising activity in recurrent glioblastoma patients with a significantly longer survival compared to the standard lomustine therapy. Subsequently, in Italy regorafenib was approved as second-line therapy by the Italian Medicines Agency. We performed a large multicenter, prospective and observational study to confirm REGOMA data in the real-world setting.

METHODS
Based on the REGOMA results, at least 150 patients had to be enrolled to estimate a 1-year survival rate with a precision of 7.8% and a confidence interval of 95%. Major inclusion criteria were: histologically confirmed diagnosis of glioblastoma according to WHO 2016, radiologically documented first relapse/progression after Stupp treatment, good performance status (ECOG PS 0-1), adequate hepatic and hematological function, stable or decreasing corticosteroid use within 7 days before starting regorafenib.Regorafenib has been administered at the standard dose of 160 mg/die for 3 weeks on/1 week off, until disease progression or unacceptable toxicity. Brain MRI has been performed within 14 days before starting regorafenib and then every 8-12 weeks. Primary endpoint is overall survival. Secondary endpoints include: progression-free survival, objective response rate, toxicity and quality of life. RANO criteria is used for response evaluation, CTCAE v. 5.0 for adverse events, EORTC QLQ-C30 and brain module BN20 for quality of life. Recruitment started in September 2020 and finished in October 2022. 191 recurrent glioblastoma patients were prospectively enrolled from 29 cancer centers in Italy: median age was 59 years (IQR 52.6-66.9), 68% male and 32% female, ECOG PS was 0 in 84 (44%), 115 pts (60%) undertook steroids at baseline. MGMT was methylated in 43% and IDH1/2 was wild-type in 92% of patients. The results from this large multicenter Italian study are expected in the second half of 2023.
P17.10.B VOLUMETRIC DIFFERENCES IN TARGET DEFINITON OF RECURRENT HIGH-GRADE GLIOMAS USING CONTRAST ENHANCED MRI VS.[18F] FDOPA PET IN RADIOSURGICAL PLANNING
Authors: Obad N , Tveiten Ø , Biermann M , Brekke J 
Published: September 2023

Abstract

BACKGROUND
Radiosurgical treatment of high-grade gliomas usually bases target definition on contrast-enhanced T1-weighted MRI images. Despite advances in several MRI techniques, a number of limitations exist, primarily due to the disruption of the blood-brain barrier, making the target delineation less accurate, particularly when treating recurrences. Several studies support the use of amino acid PET/MRI in distinguishing progression from post-operative/post-radiation inflammation. However, no established guidelines define the biological target volume when using amino acid PET/MRI in radiosurgical treatment planning. We aimed to explore the volumetric differences in target volumes obtained with standard contrast-enhanced MRI versus [18F]FDOPA PET in patients with recurrent high-grade gliomas (rHGG).

MATERIAL AND METHODS
Ten patients obtained [18F]FDOPA PET/MRI within 1 week before radiosurgical treatment. We co-registered these images with the 3D MPRAGE-MRI typically used for stereotactic target definition and performed a follow-up PET/MRI scan 4-6 weeks after treatment. We reviewed and compared the method of tumor delineation, target volumes, and stereotactic accuracy in both modalities.

RESULTS
Radiosurgical treatment delivers high radiation doses to defined targets. The target volume and the proximity to eloquent structures limit the dose, thus depending on high-accuracy imaging. The invasive nature of malignant brain tumors makes anatomical delineation insufficient, particularly when treating recurrences. In such cases, amino acid PET supplies additional information. However, the spatial resolution afforded by [18F]FDOPA uptake alone is insufficient for stereotactic definition, which to a large degree is based on contrast-enhanced T1-weighted MRI images in order to achieve the sub-millimeter resolution needed for radiosurgical planning. Hybrid PET/MRI allows the combination of metabolic information of [18F]FDOPA-PET with the anatomical precision of stereotactic MRI. In the recurrent setting, [18F]FDOPA-PET supplies the necessary information for targeting the biologically active tumour, differentiating it from radiation necrosis, thus limiting the target volumes. This enables us to treat the recurrent tumours more efficiently.

CONCLUSION
[18F]FDOPA-PET is a useful supplement in radiosurgical planning and treatment of rHGG. It is helpful in the delineation of the biologically active tumor, thus limiting the target volume significantly. This enables higher radiation doses and potentially more efficient treatment. Further results will be presented.
P17.11.A DEVELOPMENT AND CHARACTERISATION OF THE QCELL-R RECURRENT GLIOBLASTOMA PRIMARY CELL LINE RESOURCE: MODELS TO DRIVE BREAKTHROUGH DISCOVERIES IN BRAIN CANCER
Authors: Bradbrook K A , Baumgartner U , Smith F M , Johnston R , Harris L , Hoyte S , Lwin Z , Alexander H , Jeffree R , Day B W 
Published: September 2023

Abstract

BACKGROUND
Glioblastoma (GBM) is the most aggressive brain tumour in adults, with a median survival of only 15 months. Despite aggressive treatment with chemotherapy using temozolomide and radiotherapy, GBM has a high prevalence of recurrence with almost all cases recurring within the first year. This highlights a clear need to develop a deeper understanding of GBM recurrence and to develop effective models to test novel therapies. The vast inter- and intra-tumoural heterogeneity and tumour cell plasticity are complicating the development of effective therapies for brain cancer patients. Large-scale genomic analyses of primary and recurrent human GBM tumour samples have revealed a complex genomic architecture. However, the majority of GBM discovery science has been conducted in treatment naïve tumour models, which fail to capture therapy resistance and tumour evolution. Hence, these changes have been difficult to link to GBM growth and functional cell properties upon recurrence.

MATERIAL AND METHODS
To address this, we have developed the QCell-R resource, a collection of functional models of recurrent GBM. In collaboration with the Royal Brisbane and Women’s Hospital (RBWH), pair-matched patient tumour samples from the initial resection and at recurrence post-therapy have been collected. From these tissue specimens, in vitro cell lines in both 2D and 3D cultures and in vivo orthotopic xenograft models have been developed. Response to standard of care therapy (temozolomide and radiotherapy) were assessed using IncuCyte proliferation assays. Bulk mRNA, scRNA and exome sequencing were also performed.

RESULTS
QCell-R consists of 11 patient-derived recurrent GBM models, with the time between resections varying from 5-13 months. There are four pair-matched QCell-R models, as well as three standalone recurrent models. Response to standard of care therapy varied between models, with one model exhibiting a four fold higher growth rate-50 (GR50) after temozolomide treatment and a 2.7 fold increase in radiation resistance compared to the matched treatment naïve counterpart. The mRNA and scRNA sequencing has been compared to publicly available datasets to identify genes of interest that may be targetable in recurrence to test in these models.

CONCLUSION
QCell-R represents a valuable resource to define novel therapies for recurrent GBM. Elucidation of tumour heterogeneity and tumour evolution will identify targetable genes contributing to therapy resistance in these models. Identifying these targetable genes from QCell-R allows the development of novel treatments, creating strategies that may reduce the rate of recurrence by limiting therapy resistance and inhibiting recurrence-initiating cells.