bluuebunny/crossref_metadata_2025 huggingface dataset:
P23.06.A LONG-TERM OUTCOMES OF RADIOTHERAPY FOR SKULL BASE AND NECK PARAGANGLIOMAS
Authors: Alonso Becerra M , Lucas Calduch A , Macià Garau M , Garcia Exposito N , Lozano Borbalas A , Plans Ahicart G , Rosselló Gómez A , Fernández Coello A , Vidal Sarro N , Modolell Farré I , Sancho Kolster I , Majós Torró C , Pons Escoda A , Simó Parra M , Velasco Farga R , Cifré Serra P , Bruna Escuer J , Álvarez Renuncio A , Lin Y , Martínez Ávila L , Moretti M , Ruiz Domínguez M , Martín González L , Balcells Quintana C
Published: October 2024

BACKGROUND

Management of skull base and neck paragangliomas remains controversial, with treatment options including observation, surgery, embolism, and radiotherapy, either alone or in combination, depending on tumor size and patient comorbidities. Surgical interventions, including embolism, can risk complications involving lower cranial nerves and bleeding, which is a significant downside for benign tumors. Radiotherapy has been described as a feasible option for growing or symptomatic unresectable paragangliomas, providing both local control and minimal side effects.

MATERIAL AND METHODS

A retrospective analysis was conducted on patients undergoing radiotherapy, with or without previous approaches, at our institution.

RESULTS

From January 2009 to December 2022, 19 patients with skull base and neck paragangliomas underwent radiotherapy. Median age at treatment was 61 years (range 39-85), being 79% male and 21% female. Eight patients (42%) had been previously treated with surgery (4 patients) or embolization (4 patients). The rest of the patients (58%) were treated only with radiotherapy. Most paragangliomas were jugular (57%), while the remaining were tympanic (16%), jugulotympanic (16%), and carotideal (2%). Depending on the volume of treatment, two modalities of radiotherapy were decided. Most patients (84%, 16 patients) were treated with fractionated stereotactic radiotherapy (FSRT) (50 Gy in 25 fractions), with a median Planning Target Volume (PTV) of 43.1 cm3 (range 4.2 - 157.7). The other group (16 %, 3 patients) received radiosurgery (single dose of 15 Gy), with a median PTV of 1.1 cm3 (range 0.87 - 1.53). Clinical and radiologic outcomes were assessed over a median follow-up of 61 months (range 8-155). Two patients were lost from follow-up. No late toxicities were observed. Symptom relief was achieved in all cases, at least partially. There was no clinical worsening related to radiotherapy at long term follow up. Radiologically, local control was obtained in 94.7% of patients: all lesions remained stable, with no significant shrinkage, except for one paraganglioma treated with FSRT that progressed.

CONCLUSION

Paragangliomas can be successfully treated with radiotherapy, with a high local control probability at long term follow-up, with low acute toxicity and without worsening of previous symptoms.
P24.01.A A UK-WIDE SURVEY OF THE HOLISTIC NEEDS OF SELF-IDENTIFIED CLINICALLY VULNERABLE PATIENTS WITH A NEW DIAGNOSIS OF GLIOMA
Authors: Lorimer C , Jameson M , Thomson A , Ali U , Bulbeck H , Byrne A , Cooper S , Meldrum S , Melhuish S , Mills S , Oberg I , Robson S , Brock J
Published: October 2024

BACKGROUND

A multidisciplinary research group, established by NCRI, identified that research into holistic needs of patients with malignant gliomas and their caregivers remains sparse. A large proportion of patients in this cohort are considered ‘clinically vulnerable’ including older and frail patients. This UK wide survey sought to identify key areas requiring greater research and intervention with a specific focus on the clinically vulnerable subgroup.

MATERIAL AND METHODS

Patients who identified as clinically vulnerable by themselves or their caregiver and had received a diagnosis of glioma were invited via leaflets and social media platforms to respond to a 21 question online survey, hosted by BrainsTrust. Questions focussed on support, information and treatments offered at initial diagnosis. Quantitative and qualitative data was collected and analysed using descriptive statistics and narrative analysis.

RESULTS

The survey received 70 responses; 57 patients, 13 caregivers. 47 female, 23 male. The mean age of respondents was 46 (range 21-76 years). 64% of respondents felt listened to by their medical team, however only 43% of respondents felt they fully understood the information they received in the consultation. Only 29% reported remembering all the information they were given once home, fewer than half (47%) of respondents received written information to take away. 50% respondents felt that all and 33% felt that some of their questions were answered by their medical team. Only 50% of respondents reported being assigned a key worker, and 43% felt they could contact their key worker when they needed. Questions regarding specific needs gave great insight into areas where these needs are not being met; 70% wanted support with fatigue, with 36% actually receiving this, 47% wanted support with memory changes but only 19% received this. 49% of respondents wanted involvement from the neuropsychology team, with 26% receiving this. Conclusion: The results of this survey demonstrate areas where brain tumour care services are not meeting the needs of this self-identified clinically vulnerable patient group. Overall there was no category of need that was fully met which identifies the requirement for consistently structured assessment and intervention.
P24.02.A INSIGHTS FROM A CASE OF TRANSTENTORIAL HERNIATION IN A LEFT ANTERIOR-THIRD PARASAGITTAL MENINGIOMA PRIOR TO SURGERY: A SYSTEMATIC REVIEW AND ILLUSTRATIVE CASE
Authors: Torio J R , Buenviaje V , Meceda E
Published: October 2024

BACKGROUND

Meningiomas account for one-third of all CNS tumors and categorized into three grades by the WHO. While tumor size has been identified as an independent risk factor, surgery has been established as primary treatment. Prior studies have identified links between prognosis and factors like tumor characteristics and patient demographics, yet studies regarding outcomes of patients with pre-operative herniation complicated by socio-economic delays in treatment remains unexplored, prompting our study to investigate this specific population’s outcomes.

MATERIAL AND METHODS

We report a case of a 55-year-old female managed as a case of left anterior third parasagittal meningioma who underwent Bifrontal craniotomy excision of tumor (Simpson I) with resection of anterior third superior sagittal sinus and did a systematic search using MeSH keywords “Meningioma”, “Herniation”, and “Outcomes”. Six studies were included in the final qualitative analysis.

RESULTS

A review of six studies included 75 patients with meningiomas revealed a female predominance (66.7%) and an average age of 52.3 years, with tumors primarily located at the falx (90.67%). Surgical interventions predominantly involved gross total tumor resection (79.45%), yielding favorable outcomes in 83.09% of cases with low morbidity (13.33%) and mortality rates (1.41%), although pre-operative complications such as intratumoral hemorrhage and herniations were noted, and the recurrence rate varied across studies with a median follow-up ranging from 1 to 36 months.

CONCLUSION

Meningiomas manifest symptoms gradually depending on tumor location, with peritumoral brain edema contributing significantly to morbidity. While delays in surgery often influenced by socioeconomic factors are associated with unfavorable outcomes, underscoring the importance of timely intervention to prevent disease progression and enhance patient quality of life.
P24.04.A PATIENT AND PUBLIC INVOLVEMENT IN A NEURO-ONCOLOGICAL RESEARCH PROJECT
Authors: Nordentoft S , Guldager R , Mathiesen T , Pappot H , Piil K
Published: October 2024

BACKGROUND

Development and implementation of an intervention targeting a specific population can be significantly enhanced through the integration of Patient and Public involvement (PPI). The aim of this study is to apply PPI in the process of developing a supportive group intervention for caregivers to patients diagnosed with a glioblastoma.

MATERIAL AND METHODS

Establishment of a national PPI panel including current or bereaved caregivers to patients diagnosed with a glioblastoma was recruited through the Danish Brain Tumor Association (Hjernetumorforeningen). Terms of reference for the panel have been established, describing purpose, terms, and meeting format. Online Team meetings and a face-to-face co-creative workshop with the panel was conducted in corporation with the Danish Knowledge Center for User Involvement in Health Care. Next step, the level and value of caregiver involvement will be measured by using the Patient Engagement in Research Scale (PEIRS-22), to gain knowledge on how meaningful the caregivers experienced their engagement in the research process.

RESULTS

A national panel of current and bereaved caregivers (n=10) was engaged in the PPI-process and provided valuable knowledge to the development of the intervention. Ongoing online Team meetings were held every second month with the panel, video-recorded, and subsequently transcribed. This process aimed to identify themes within the topics discussed with the panel and to ensure inclusion of the caregivers’ insight and needs in the design of the intervention. The purpose of the workshop was to target the further development of the intervention and to gain more structure in the design. Creating a collaborative PPI-process with the panel included thorough preparation for each meeting with a pre-distributed agenda. Preparing the caregivers for the topics to be discussed, ensured to gain the requested information, and meanwhile creating an open and inviting forum were important element of the process.

CONCLUSION

PPI in current co-creating process was a time consuming yet valuable process, where caregivers’ experiences and perspectives were addressed in the design and development of a supportive group intervention.
P25.01.B ASSOCIATION BETWEEN EXPOSURE TO AIR POLLUTION AND BRAIN TUMOR INCIDENCE IN THE UNITED STATES
Authors: Price M , Neff C , Ballard C , Hsu H , Kruchko C , Barnholtz-Sloan J S , Ostrom Q T
Published: October 2024

BACKGROUND

Air pollution contains known human carcinogens. Prior studies evaluating an association between pollution exposure and central nervous system tumors (BT) are inconclusive. Using multiscale geographically-weighted linear regression (MGWR), we investigated the association between average county-level air pollution and geographic variation of glioblastoma and tumors of the meninges (ToM) incidence in the United States (US).

MATERIAL AND METHODS

Annual county-level air pollution from 2000-2016 was obtained from the Environmental Protection Agency’s Air Quality Index (AQI) which analyzes daily ambient air concentration for ozone and particulate pollution in participating US counties. County-level annual age-adjusted incidence rates (AAAIRs) of glioblastoma and ToM per 100,000 population (>20 years old) between 2004-2020 were estimated using data from the Central Brain Tumor Registry of the United States, which aggregates data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program. Counties with missing data were excluded. The 2016-2020 American Community Survey data were used to identify county sociodemographic and average exposure indoor/workplace pollution. Spatial patterns were visualized using Moran’s I measure and the global G-statistic analyses computed in R. Variables were mean normalized and regressed in a MGWR model using county centroids in the Spatial Analysis Research Center’s MGWR 2.2 program to assess geographically-varying effects of the independent variables.

RESULTS

Data was available from 1,109 counties. Significant spatial clusters and outlier counties were identified for both tumor types (glioblastoma Moran’s I=0.126, p <0.001, G-statistic=0.003; ToM Moran’s I=0.487, p <0.001, G-statistic=0.003). When restricted to significantly high/low counties (p <0.05), low-rate clustering for glioblastoma was observed in Alaska, Arizona, Virginia, and parts of the central mid-west. High-rate clustering was observed in parts of the north, mid-west, and northeast. ToM showed low-rate clustering in northwest, Virginia, Kansas, and parts of the north mid-west, with high-rate clustering in Washington, Utah, Colorado, and Wisconsin. MGWR model showed that in both tumor types, increased AQI (glioblastoma mean βMGWR 0.06; MoT mean βMGWR 0.12) was associated with increased tumor incidence. This association was present in 45% and 59% of counties, respectively.

CONCLUSION

This is the first study applying a MGWR model to assess geospatial associations between ambient air pollution and BT incidence, allowing for magnitude, direction, and significance of coefficients to change across geographic space. and allows for more accurate identification of geographic regions affected by potential BT health disparities.
P25.05.A THE IMPACT OF THE COVID-19 PANDEMIC ON NEURO-ONCOLOGY: REPORT FROM THE DUTCH BRAIN TUMOUR REGISTRY
Authors: Ho V K Y , Koekkoek J A F , Wagemakers M , de Vos F Y F , Nabuurs R J A , Wester G , Bongers E M , Nogarede C O , Walenkamp A M E , van Dis V , Maas S L N , de Witt Hamer P C , Compter A , Seute T
Published: October 2024

BACKGROUND

The COVID-19 pandemic affected all healthcare domains, including neuro-oncology. This study investigated the effects of the COVID-19 pandemic on the diagnosis, treatment and outcomes of adult patients with a glioma or meningioma in the Netherlands.

MATERIAL AND METHODS

Patients diagnosed in 2020 were divided into 5 periods, based on the severity of the COVID-19 pandemic in the Netherlands, and compared to patients diagnosed in the same period in the years 2017-2019.

RESULTS

The number of meningioma diagnoses decreased during the first 3 periods of the COVID-19 pandemic, and patients diagnosed in 2020 differed in their socioeconomic status from those diagnosed in 2017-2019. Glioma patients diagnosed in 2020 more often received adjuvant chemotherapy. Those aged 70+ years were more often treated with chemoradiotherapy instead of radiotherapy following neurosurgery. Both glioma and meningioma patients diagnosed in 2020 experienced a somewhat longer time to neurosurgery, with a median difference of 2 (95%-confidence interval [CI]: 1-3) and 4 days (95%CI: 0-8), respectively, while their time to initial adjuvant therapy was shortened, with a median difference of -1 (95%CI: -2-0) and -2 days (95%CI: -22-20), respectively. No difference was detected in patients’ overall survival.

CONCLUSION

The COVID-19 pandemic mostly impacted meningioma incidence during the first four months of 2020. With relatively limited adjustments, the neuro-oncology field was able to cope with the challenges posed by the pandemic.
P26.01.B A PHARMACOLOGICAL SURVEY ACROSS GLIOMA STEM CELL PHENOTYPES REVEAL NOVEL GLIOBLASTOMA DRUG-TARGETS, DRUG REPURPOSING OPPORTUNITIES AND FUTURE DRUG COMBINATION STRATEGIES
Authors: ELLIOTT R J R , Furqan M , Nagle P , Munro A , Drake C , Dawson J C , Brunton V , Frame M , Carragher N O
Published: October 2024

BACKGROUND

Owing to the lack of therapeutic advancement in the treatment of glioblastoma (GBM) over the past two decades, Cancer Research UK has designated malignant brain tumours a ‘strategic priority⋯ as a cancer of unmet need’. The inter- and intra-molecular heterogeneity of glioblastoma presents significant obstacles to effective clinical progression of novel treatments. Phenotypic drug screening is ideally suited to heterogeneous diseases, where targeting specific oncogenic drivers (such as EGFR) are broadly ineffective. Phenotypic hits can then be used to systematically identify synergistic combinations which overcome variable therapeutic response observed across multi-cell panels. Synergistic drug combinations between approved drugs (or drug candidates in early clinical trials) provides a repurposing context that could accelerate the bench to bedside model. Our preliminary objective was to incorporate a panel of patient derived GBM stem cell lines into an unbiased ‘cell painting’ assay to quantify multiple GBM stem cell phenotypes and create an updated pharmacological survey by screening these cell lines across several drug libraries containing commercially available, FDA approved and/or Phase I/II/III compounds.

MATERIAL AND METHODS

We profiled patient derived GBM stem cells against several thousand annotated compounds covering multiple doses, using our established image-based high throughput screening protocols. Multiplexed ‘cell painting’ dyes were used to quantify in detail the cellular response to each drug via CellProfiler image analysis software. Data processing, QC, dimensionality reduction and hit thresholding was carried out primarily using Stratominer-HCA platform. Putative hits based on phenotypic distance and potency were selected for validation and further characterisation.

RESULTS

Predominant drug sensitivities include the highly potent but expected pan-cytotoxic effects of compounds that target microtubules, the proteasome, topoisomerases, DNA/RNA synthesis and histone deacetylases. Beyond these, approximately 50 compounds have been selected for further studies including mechanism-of-action and pathway profiling, dose-ratio matrix combination testing in 2D and 3D GBM models, neuronal cytotoxicity and in vivo proof-of-concept studies via intracranial implantation.

CONCLUSION

Our preliminary results serve as a foundation for a systematic approach to identify novel drug combinations including combinations that could be used concurrently with standard treatment protocols for GBM.
P26.02.A AN IN VITRO MULTIDIMENSIONAL DRUG ASSESSMENT TOOL FOR PERSONALIZED PREDICTION OF DRUG RESPONSE AND RESISTANCE IN HUMAN GLIOBLASTOMA ORGANOIDS
Authors: Camenisch S , Mathews L , Hoch T , Neidert M , Zeitlberger A , Hundsberger T , Jochum W , Vélez Char N , Ayala V , Wick P
Published: October 2024

Glioblastoma (GBM) is a highly aggressive brain tumor treated with surgery, radiotherapy, and concomitant as well as maintenance temozolomide (TMZ). Despite treatment adherence to this so called Stupp’s regime, patient survival is typically less than 18 months, with high relapse rates. Current pre-clinical drug research is performed with cell line or patient-derived xenografts or with in vitro 2D models. These models lack inter- and intratumoral heterogeneity as well as a tumor microenvironment, thus bench to bed translational issues occur. Using patient-derived glioblastoma organoids (PDOs) the necessary cell heterogeneity can be provid-ed by growing them out of micro-dissected biopsy samples from 3 different GBM tumor sub-regions (pe-riphery, contrast-enhancing zone and tumor core). PDOs are considered in vitro models with high clinical rel-evance to evaluate the anticancer potential of novel preclinical drugs. In this project, we translated the Stupp’s regime to an in vitro multidimensional drug assessment tool using our in vitro GBM model. This tool allows us to monitor drug response over time and predict the performance of preclinical drugs with high predictability. The multidimensional drug assessment tool was initially optimized with TMZ in glioblastoma spheroids and then extended to PDOs. Our assessment included a morphological analysis, 2D & 3D confocal imaging, NGS mutational profiling, apoptotic/necrotic cell fraction assessment, cell metabolic activity assays (XTT), and su-pernatant-based cell toxicity assays (LDH). The apoptotic cell fraction was detected by looking at nuclear morphology in H&E stained tissue slices and detected using a pre-trained AI-driven image readout software. Over the duration of 14 days, GBM spheroid and organoids were treated according to the adapted in vitro Stupp’s regime and TMZ was monitored with our in vitro multidimensional drug assessment tool. Multiple concentrations and time points were evaluated to detected TMZ effect on tumor size reduction, metabolic activity, cytotoxicity, appearance of new drug-induced mutations, and extent of apoptosis and necrosis. GBM models treated with clinically relevant TMZ concentration (100 uM) were approximately 33% smaller after 10 days and metabolic activity decreased by up to 53%. Further preclinical drug candidates will be compared to TMZ performance and clinical data. To conclude, we are confident that this dynamic and multidimensional screening tool using physiologically relevant patient-derived GBM models provides high predictive power in order to assist preclinical anti-GBM drug screening and can address current translational issues persisting in drug development.
P26.07.A FGFR1 INHIBITION SENSITIZES GLIOBLASTOMA STEM CELLS TO TUMOR TREATING FIELDS
Authors: Gouaze-Andersson V , Deshors P , Cohen-Jonathan Moyal E
Published: October 2024

BACKGROUND

Glioblastoma (GBM) is the most lethal primary brain tumor in adult and is known to be particularly aggressive and resistant despite a treatment associating surgery and radio-chemotherapy. Over the last few decades, only few therapeutic advances have been achieved on GBM, but Tumor Treating Fields (TTFields) have recently improved outcomes of clinical trials. TTFields are a non-invasive, physical, local therapy relying on the delivery of alternating electrical fields with low intensity and intermediate frequency and are now a part of the first-line clinical treatment for GBM. Although TTFields increase patient’s survival, GBM is still an incurable disease with recurrences due to treatment resistance. Therefore, there is a need to understand mechanisms of GBM resistance to TTFields and to identify new therapeutic targets. One of the causes of resistance is the presence of Glioblastoma Stem Cells (GSC) known to be radio- and chemo-resistant and responsible for tumor regrowth. We have previously shown that tyrosine kinase receptor FGFR1 controls GBM agressiveness as well as GSC invasion and radioresistance and that its inhibition leads to radiosensitization through increasing mitotic cell death and microenvironment modulation. Because one of the main mechanisms of action of TTFields is mitotic disturbance and because TTFields act synergistically in vitro with irradiation, we hypothesize that targeting FGFR1 could sensitize GSC to TTFields.

MATERIAL AND METHODS

In this work we used a panel of primary GSC established from patient’s surgical GBM sample to test the potential role of FGFR1 in GSC response to TTFields. For this purpose, GSC were treated for 72 h with TTFields at 200 kHz which is the same frequency delivered to the patient receiving this therapy. TTFields treated GCS were also treated with siRNA targeting FGFR1 or pemigatinib, which is an inhibitor of FGFR1-3.

RESULTS

TTFields treatment increases expression and activation of FGFR1. Treatment of GSC with pemigatinib decreases FGFR1 expression and inhibits FGFR1 signaling pathway even when TTFields are applied. We demonstrated that pemigatinib, as well as FGFR1 silencing with RNA interference, sensitizes all GSC used in our experiments to TTFields by decreasing their survival. Finally, the adjunction of pemigatinib to treatment combining irradiation (IR) and TTFields also sensitizes GSC by inducing a further decrease in the repair of IR-induced DNA damages.

CONCLUSION

These results demonstrated that FGFR1 inhibition in concomittance with TTFields application as standard GBM treatment would improve patient prognosis.
P26.08.B LASER-ASSISTED FABRICATION OF AN IN VITRO 3D-ENGINEERED BLOOD-BRAIN/TUMOR BARRIER MODEL
Authors: Barin N , Balcioglu H E , Accardo A , French P
Published: October 2024

BACKGROUND

Efficient drug delivery to brain tumors is greatly hindered by the blood-brain barrier (BBB). Although different in vitro BBB models have been developed, they do not capture the capillary dimensions, incorporate multiple cell types, feature biomimetic flows, and/or provide sufficient 3D cell-to-cell contact. We aimed to develop a model for the blood-brain/tumor barrier (BBTB) that incorporates these characteristics simultaneously.

MATERIALS AND METHODS

3D micro-porous capillary-like structures (µPCs) that mimic the brain capillary dimensions were fabricated using two-photon polymerization (2PP), a 3D light-assisted printing technique that enables precise microscale fabrication. These structures serve as a scaffold for culturing and organizing various BBTB cell types. µPCs are fabricated at the intersection of two channels within a microfluidic slide, facilitating controlled fluid flow inside and outside the µPCs using a pressure-driven pump. Human umbilical vein endothelial cells (HUVECs) and the U87 glioblastoma cell line are utilized. Immunofluorescence staining (using CD31, tubulin, actin, and DAPI) and scanning electron microscopy are performed to assess cell colonization.

RESULTS

Initially, we cultured endothelial cells on µPCs under static conditions (i.e. without fluid flow). We optimized µPC designs by modifying channel and rod diameters, alignment, and pore sizes to improve structure stability, confocal microscopy visibility, and cell colonization. These experiments resulted in a design that achieved complete endothelial cell coverage. We also confirmed that the µPCs setup allows co-cultures of glioblastoma and endothelial cells. Next, we 3D printed the 2PP-fabricated µPCs within single-channel microfluidic slides that allowed control of internal fluid flow within the µPCs. When endothelial cells were perfused through the µPCs under biomimetic flow rates, after three days of culture, they uniformly covered the surface of µPCs. We also developed a protocol for precise printing of µPCs in 2-channel slides. The first channel enables internal fluid flow within the µPCs, where endothelial cells are cultured via physiological microfluidic flows. The second channel controls the external flow surrounding the µPCs, where astrocytes, pericytes, and glioma cells can be cultured in static conditions. We will use this setup to soon perform co-cultures of endothelial cells, gliomas and pericytes.

CONCLUSION

We designed a representative model for the BBTB capillaries, using a hybrid approach that combines 2PP and microfluidics. To ensure the BBTB model’s physiological relevance, future assessments will include cellular adherence, cellular spatial distribution, expression of integrity proteins, basal lamina formation, and vessel permeability. This work was partly funded by the Dutch Research Council via the ENW-XS grant N. OCENW.XS23.2.105.
P27.01.A ANLOTINIB COMBINED WITH RADIOTHERAPY IN THE TREATMENT OF ADULT NEWLY MALIGNANT BRAINSTEM GLIOMA PATIENTS: A MULTICENTER, PHASE II STUDY
Authors: Chen Y , Li P
Published: October 2024

BACKGROUND

Due to the challenging location, adult malignant brainstem glioma can not undergo aggressive surgery and is associated with a quite poor prognosis. Effective therapy regimens for this disease have not been developed. This study assessed the efficacy and safety of anlotinib, a multitarget tyrosine kinase inhibitor, combined with radiotherapy in treating this group of patients.

MATERIAL AND METHODS

This is an ongoing phase II, multicenter, single-arm trial investigating the safety, tolerability, and activity of anlotinib combined with radiotherapy in malignant brainstem glioma. Eligible participants include adults (18-70 years old) with newly diagnosed malignant (WHO III - IV) brainstem glioma based on histology or radiology who are radiotherapy (RT), chemotherapy, immunotherapy, or biotherapy naïve. Patients with Karnofsky score < 40 and a life expectancy < 3 months are excluded. All participants received 54-60 Gy radiotherapy (RT,1.8-2.0 Gy per fraction, five days per week). Anlotinib (10mg, orally, daily, d1-14/3 weeks) concurrently administered with radiotherapy, then consolidatedly used until disease progression or occurrence of intolerable adverse events. The primary objective includes disease control rate (DCR) and 6-month progression-free survival rate (6m-PFS). The secondary objective includes overall survival (OS), and toxicity profile (NCT04668508).

RESULTS

As of January 31, 2024, 19 participants have enrolled, all patients have completed radiotherapy. Sixteen patients who with a follow-up of 6 months or longer were included in the analysis for this report. The median age is 32 (range 18-68) years old. The median follow-up is 22.7 (range 6.0-38.3) months. Seven patients were pathologically diagnosed and nine patients were radiologically diagnosed with high-grade glioma. The DCR is 100% (Stable disease, SD: 16/16) at the end of radiotherapy and is 100% three months after radiotherapy (Partial response, PR: 2/16; SD: 14/16). The median PFS is 11.7 months, 95%CI 6.9-16.4, and the 6m-PFS and 1 year-PFS rates are 74.0% 11.2% and 36.3% 13.3%. The median OS is 18.7 months, 95%CI 10.7-34.7, the 6m-OS and 1 year-OS rates are 93.3% 6.4%and 58.3% 15.0%. No death occurred during the treatment. No ≥ grade 3 adverse events were observed up to the last follow-up (January 31, 2024) of this study.

CONCLUSION

Anlotinib combined with radiotherapy is efficacious and well-tolerated and might be a treatment option for newly diagnosed malignant brain stem glioma in adults.
P27.02.A ANTI-EPILEPTIC WITHDRAWAL IN GLIOMAS: A RETROSPECTIVE STUDY IN A SINGLE SCOTTISH TERTIARY CENTRE
Authors: Merchant F , Molinari E
Published: October 2024

BACKGROUND

Seizures are common in brain tumours (BTs). With no fixed guidelines to guide anti-epileptics (AEDs) discontinuation in BTs, we evaluated factors influencing the decision to discontinue AEDs and its outcome.

MATERIAL AND METHODS

Retrospective study on single regional centre for neuro-oncological service from April 2018 to April 2023. Eligible BT patients were seizure free ≥ 1 year post surgery, had histologically confirmed gliomas (WHO grade I-IV) and underwent gross total resection. We analysed separately patients who were weaned after being started on AEDs prophylactically. Primary outcomes were: (1) shared decision-making outcome and (2) seizure recurrence. Data analysed included tumour characteristics, antitumour treatments and seizure freedom.

RESULTS

Over 2020-2023, 30/240 patients (13%) met the selection criteria for AED withdrawal and 22/30 (73%) were agreeable to AEDs withdrawal. 9/22 (41%) of those who withdrew AEDs had seizure recurrence, with 6/9 (67%) having a seizure within 6 months following withdrawal. 5/9 (55%) had tumour progression within 3-6 months of having a seizure. None of those who remained on AEDs had seizure recurrence.A shorter BT related epilepsy (BTRE) duration (p<0.01) and radiotherapy treatment (p<0.05) resulted in decreased seizure recurrence following withdrawal. Most patients were on Levetiracetam monotherapy and our data did not allow comparison with other AEDs.

CONCLUSION

In 73% of patients, a shared decision process led to AEDs withdrawal, with 59% remaining seizure free. Lower recurrence risk was linked to shorter BTRE duration and radiotherapy. Further studies are required to better stratify patients at higher risk of seizure recurrence.
P27.06.B EFFECT OF CHOLINE ALPHOSCERATE ON THE SURVIVAL OF GLIOBLASTOMA PATIENTS
Authors: KIM Y
Published: October 2024

BACKGROUND

Cognitive impairment often occurs in glioblastoma (GBM) patients due to the tumor itself and treatment side effects. Choline alphoscerate (L-alpha-glycerylphosphorylcholine, GPC) is frequently used to compensate for cognitive impairment in GBM patients. This study was conducted to determine whether GPC affects the overall survival (OS) and progression-free survival (PFS) of GBM patients.

MATERIAL AND METHODS

From 2011 to 2020, 187 isocitrate dehydrongenase (IDH)-wild-type GBM patients were analyzed. The patients were classified based on whether GPC was continuously used for at least 3 or 12 months (mos) after GBM diagnosis.

RESULTS

Although GPC usage (≥3 mos) did not make significant differences in survival extension, median OS in the long-term GPC group (≥12 mos) was longer with statistical significance, compared to the control group (<12 mos) (38.3 vs. 24.0 mos, p = 0.004). In addition to younger age, supratentorial location, complete resection, and MGMT promoter methylation, long-term use of GPC (≥12 mos) was significantly associated with longer OS in multivariate analysis (p = 0.019, hazard ratio [HR] 0.532, 95% confidence interval [CI] 0.314-0.900).

CONCLUSION

Despite the limitations of this study, long-term GPC use was possibly associated with prolonged survival in GBM patients. Multi-center prospective randomized studies with a large number of patients are needed to validate these findings.
P27.12.B IMPACT OF SEQUENCING TEMOZOLOMIDE TO DEFINITIVE RADIOTHERAPY IN GRADE-II GLIOMA- A CLINICAL AUDIT
Authors: Kumar N , Tiwari A , Madan R , Saroya B , Tripathi M , Chatterjee D , Ahuja C , Devi H , Singla N , Shah D , Singh A , Sahoo S , Chhabra R
Published: October 2024

BACKGROUND

For low-grade Gliomas (LGG), total surgery remains the cornerstone of treatment; recent studies have demonstrated a remarkable improvement in overall survival (OS) when PCV chemotherapy is added to the radiation therapy treatment regimen for patients with low-grade Gliomas. In clinical practice, multi-agent PCV chemotherapy is being replaced with the Alkylating and oral drug Temozolomide (TMZ) for its better compliance in terms of administration and side effects. Thus, we performed a clinical audit to evaluate the role of TMZ instead of PCV in treating patients with LGG.

MATERIAL AND METHODS

Objectives- 1-Τo understand the pattern of use of temozolomide along with adjuvant radiotherapy in Grade 2 Glioma and its impact on outcome. 2-Quantify the impact of concurrent and adjuvant chemotherapy on the survival of Grade II Gliomas 3-Difference in the survival of Oligodendroglioma and Astrocytoma with respect to adjuvant treatment. All patient data from 2014 to 2020 was extracted in this clinical audit. Patients with the diagnosis of Grade II oligodendroglioma and Grade II astrocytoma were recorded. Information was recorded regarding surgical details, radiotherapy, and concurrent and adjuvant therapy. The patient’s last follow-up date was recorded. These patients were divided into five groups depending on the adjuvant treatment received after surgery. Group 1: Received External Beam Radiotherapy with concurrent and adjuvant chemotherapy (XRT+CC+ACT) Group 2: Received External Beam Radiotherapy and concurrent Chemotherapy (XRT+ CCT) Group 3: Only External Beam Radiotherapy (XRT) Group 4: No Adjuvant treatment (No Treatment) Group 5: External Beam Radiotherapy followed by adjuvant chemotherapy (XRT + ACT)

RESULTS

There were 469 patients with grade 2 glioma, including both Astrocytoma (n=192) and Oligodendroglioma(n=223). There was no difference in survival between Grade 2 ODG and Astrocytoma, with mean survival of 29.33 (±28.03) months and 28.53(±28.3) months (p=0.4). In patients with Grade 2 astrocytoma, the highest estimated survival was seen in Group 5 (39.63±7.34 months) and the lowest in Group 4 (7.24±2.27 months) with significant p-value (0.0001). In Patients with Grade 2 Oligodendroglioma, the highest estimated survival was seen in Group 5 (44±6.49 months) and the lowest in Group 3 (32.98±3.49 months) with non-significant p-value (0.4).

CONCLUSION

In the lack of definitive data on the role of adjuvant treatment in grade II Glioma, our study provides convincing evidence for the use of adjuvant Temozolomide in low-grade Glioma. Our study revealed that adjuvant Chemotherapy with Temozolomide after Radiotherapy results in better overall survival
P27.19.A RAPID EARLY PROGRESSION IN GLIOBLASTOMA: A CASE-CONTROL EVALUATION OF CLINICAL OUTCOMES AND ADVANCED IMAGING BIOMARKERS
Authors: Waqar M
Published: October 2024

BACKGROUND

In glioblastoma patients, Rapid Early Progression (REP) refers to tumour growth between the time of surgery and postoperative chemoradiotherapy. It has a high incidence although relatively little is known about the phenomenon. The aim of this study was to characterise REP using clinical and advanced imaging data in the context of a case control study, to control for key confounders. We only included patients undergoing gross-total resection (GTR) to eliminate bias from extent of resection.

MATERIAL AND METHODS

Ethical approval was obtained. We reviewed an institutional database of newly-diagnosed glioblastomas undergoing GTR (2015-2021). Supratentorial IDH-wildtype glioblastomas were included with magnetic resonance imaging (MRI) scans available at the postoperative and radiotherapy planning time points. REP was defined as a nodular increase in enhancement located within/around the surgical cavity, occurring within 6 weeks of surgery, that was not accounted for by areas of diffusion-restriction on the postoperative MRI scan. Patients with REP were propensity-score matched to a control group based on clinical features. REP and control cases were compared on the basis of: clinical outcomes such as overall survival (OS) and progression-free survival (PFS; progression was defined as post-chemoradiotherapy progression); and advanced imaging using radiomics applied to preoperative T1 post contrast/Fluid Attenuated Inversion Recovery (FLAIR) sequences (Pyradiomics package) and the Apparent Diffusion Coefficient (ADC) derived from diffusion-weighted MRI.

RESULTS

60 patients undergoing GTR were included. 8 cases met the definition of REP such that the overall incidence after GTR was 13%. REP cases were matched to 16 control patients. After matching, there was no significant difference in baseline variables between REP and control cases except preoperative performance status, which was worse in REP cases (median Eastern Cooperative Oncology Group [ECOG] 2 vs. 1). REP was associated with a shorter median OS (9 vs. 17 months, p = 0.038) and PFS (5 vs. 9 months, p = 0.029). The incidence of REP was higher in patients over 65 (6/22, 27%) and significantly fewer REP patients in this category received radical postoperative chemoradiotherapy versus controls (Fisher’s Exact, p=0.023). REP and control cases had similar radiomic profiles and there was no significant difference in mean ADC between the groups in enhancing (p=0.99) or non-enhancing FLAIR hyperintense regions (p = 0.67).

CONCLUSION

REP cases had a worse performance status from diagnosis and received less radical postoperative chemoradiotherapy protocols compared to controls, yielding a significantly shorter median OS/PFS. Our results highlight that REP is a significant prognostic variable yet does not have a distinct biomarker. Our ongoing work will explore potential tissue biomarkers of REP.
P27.20.B RARE NEUROLOGICAL PRESENTATION OF BING NEEL SYNDROME AND TREATMENT PERSPECTIVES: A CASE SERIES
Authors: Giglio P , Malvaso A , Bini P , Diamanti L , Marchioni E
Published: October 2024

BACKGROUND

Bing-Neel syndrome (BNS) is a rare complication of Waldenström macroglobulinemia (WM) stemming from direct invasion of the central nervous system by malignant lymphoma cells. BNS patients present with gradually progressive symptoms (e.g. headache, nausea, vomiting, cranial neuropathies), rarely accompanied by aphasia and cognitive decline resulting from involvement of brain parenchyma

. MATERIAL AND METHODS

Three cases (68 y, F; 69 y, F; 74 y, M) of patients affected by WM and diagnosed with BNS are illustrated here. Clinical data have been collected from medical records for all patients.

RESULTS

A 68 year old female, a 69 year old female and a 74 year old male presented with aphasia, limb ataxia, behavioral changes and memory loss. The second patient also developed anti-MAG polyneuropathy. Obstructive hydrocephalus due to CNS invasion by previously unknown lymphoplasmacytic lymphoma was the inaugural manifestation of disease in the third patient; furthermore, BNS represented the initial presentation of WM in the second patient, whereas CNS involvement became apparent 7 years after disease onset in the first patient. Brain and spinal magnetic resonance imaging revealed brain leptomeningeal contrast enhancement in all patients with associated spinal leptomeningeal enhancement in the first two patients. The cerebrospinal fluid (CSF) analysis showed an increased WBC count (14/mm^3 and 27/mm^3) and elevated CSF/serum albumin transfer index (1,8% and 0,7%) in the first and the third patients. Monotypic CD20+, CD19+, CD5-, CD23-, CD10- lymphocytes with kappa chain monoclonal restriction were observed in all patients. Hence, a definitive diagnosis of BNS was made in all cases and immunosuppressive therapy was started with poor clinical improvement. Lastly, Ibrutinib was administered obtaining clinical and radiological benefits in all patients after 12 months of follow-up.

CONCLUSION

We suggest that the occurrence of rare, but typical neurological presentations in patients with WM could be clinically relevant and life threatening. Furthermore, BNS might be the initial clinical manifestation of WM. According to our monocentric experience and recent literature, BNS patients treated with Ibrutinib may reach high rates of 2-year event-free survival. However, randomized controlled trials are required to define the role of Ibrutinib as an important therapeutic option in BNS.
P27.21.A RE-RESECTION FOR RECURRENT GLIOBLASTOMA - DOES TIMING MATTER?
Authors: Alhalabi O , Dao Trong P , Mironov K , Nabiev K , Gareib A N , Jordan M , Joser S , Krieg S M , Unterberg A W , Jungk C
Published: October 2024

BACKGROUND

Surgery for recurrent glioblastoma (GBM) has the potential of prolonging patient survival. However, the impact of the timepoint of re-resection after tumor suspicion on post-surgical survival and neurological deterioration remains unclear.

MATERIAL AND METHODS

Patients undergoing first re-resection for recurrent WHO grade 4 IDH-wildtype GBM were analyzed retrospectively. Post-surgical neurological deterioration and post-surgical survival of patients undergoing early surgery (within 3 weeks) after suspected recurrence were compared to those receiving surgery later than 3 weeks. In addition, volumetric analyses were used to determine tumor burden and location.

RESULTS

103 consecutive patients (mean age: 59 years; 64 males and 39 females) undergoing first re-resection for recurrent GBM from 2018 to 2022 were included. Gross total resection (GTR) had been achieved in 93 patients (91%) at first diagnosis and was achieved in 96 patients (93%) at repeat surgery. Intraoperative MRI-guided resection was performed in 84 (82%) cases and 5-ALA was applied in 8 (8%) cases, with neuromonitoring utilized in 14 (14%) cases. The median time interval between first and second resection was 341 days (IQR 343 days) while the median time interval between suspected tumor recurrence and re-resection was 20 days (IQR 23 days). Surgery was delayed beyond 3 weeks after suspected recurrence in 49 cases (mean interval 11 in the ‘early’ vs 187 days in the ‘late’ group, p<0.001) due to salvage chemotherapy/targeted therapy in 18 cases, suspicion of pseudo-progression in 7 cases and patient preference in 24 cases. Compared to patients receiving ‘early’ repeat surgery, this delay was not associated with a higher rate of immediate (14/54 vs 10/49 patients, p=0.508) or permanent (3/54 vs 4/49 patients, p=0.600) post-operative neurological deterioration. Median survival after repeat surgery was 220 days and did not significantly differ between early and late surgery (212 in the late vs 243 days in the early group, p=0.682). Volumetric analyses revealed no significant differences in tumor volume or localization pertaining to eloquence.

CONCLUSION

Timing of surgery for suspected first recurrence of GBM did not impact on functional outcomes and post-surgical survival. In general, satisfactory rates of postoperative neurological deficits and post-surgical survival in this contemporary cohort of patients with repeat surgery for recurrent GBM could be achieved.
P27.23.A SKULL REMODELING SURGERY IN COMBINATION WITH TUMOR TREATING FIELDS THERAPY FOR FIRST RECURRENT GLIOBLASTOMA. FINAL RESULTS FROM OPTIMALTTF-2, A MULTI-CENTER, RANDOMIZED, CLINICAL TRIAL
Authors: Mikic N , Skjøth-Rasmussen J , Rom Poulsen F , Johannes Laursen R , Lukacova S , Møller S , Aaquist Haslund C , Hedegaard Dahlrot R , Solheim O , Solheim T S , Sørensen J H , Wong E T , Korshøj A R
Published: October 2024

BACKGROUND

There are no standardized treatments for first recurrent glioblastoma (rGBM) and the prognosis in the clinical trial population is approximately 6-9 months. Skull remodeling surgery (SR-surgery) aims to optimize Tumor Treating Fields therapy (TTFields) by surgically removing areas of the low conductive skull and thereby increasing the electric field intensity directly into the tumor. In silico work suggests SR-surgery increases the electric field intensity by ~30-100% and OptimalTTF-1 (pilot trial) suggests the intervention is safe with a median overall survival (mOS) of 15.5 months.

MATERIAL AND METHODS

OptimalTTF-2 is a randomized, comparative, multi-center, investigator-initiated, interventional clinical phase 2 trial aiming to examine the efficacy and safety of TTFields and physicians’ best choice oncological therapy with or without SR-surgery for 84 rGBM patients. SR-surgery was standardized with in silico work to consist of five burr holes, each 15mm in diameter, directly over the tumor resection cavity with the transducer arrays overlapping. The trial was active nationwide in Denmark from 2020-2024. Major eligibility criteria include age ≥18 years, histopathological confirmed 1st recurrence of supratentorial glioblastoma, KPS ≥ 70, and focal tumor. The primary endpoint is overall survival after 12 months (OS12), while secondary endpoints include PFS, QoL, ORR, QoL, KPS, steroid dose, and toxicity.

RESULTS

52 patients were included in the prespecified interim analysis. 26 randomized to intervention, and 26 to control. The median age of 60 years [31-80]. Baseline characteristics were balanced without statistical differences. Intent-to-treat analysis showed that the OS12 was 56% [35-73%, 95%CI] vs. 50% [29-68%, 95%CI], p =0.65, and mOS was 14.09 months [7.9 -,95%CI] vs. 10.97 months [6.5-17.3, 95%CI], p=0.41, for intervention and control, respectively. No statistically significant difference between the arms in toxicity or QoL. Conditional power calculation also suggested a low survival benefit for the planned cohort of 84 patients.

CONCLUSION

The interim analysis did not show an advantage from SR-surgery, and the trial was terminated early based on the low expected survival benefit for the entire cohort. Examination of potential negative outcome modifiers, that may attentuate the increased electric field intensity from SR-surgery are needed in the post hoc analysis.