bluuebunny/crossref_metadata_2025_split huggingface dataset:
P18.50.A TUMOR VOLUMES AND FEASIBILITY OF EXTENSIVE RESECTION IN NON-CONTRAST ENHANCING GLIOBLASTOMAS THAT LACK HIGH GRADE HISTOLOGICAL FEATURES: A SINGLE CENTER STUDY
Authors: Lakerveld S , Wijnenga M M J , Maas S L N , van Dis V , Smits M , Tesileanu M , Dubbink H J , French P J , Vincent A J P E , van den Bent M J 
Published: October 2024

Abstract

BACKGROUND
The clinical course and management of non-contrast enhancing glioblastomas that also lack the classic high grade histological features (non-CE GBMs) is unclear. Data on survival, clinical management including surgical therapies are sparse and conflicting. In this study we therefore investigated tumor volumes, surgical and postsurgical therapies and survival outcome of a single center cohort from the Netherlands.

MATERIAL AND METHODS
We identified adult cases of non-CE GBM in the Brain Tumor Center at Erasmus MC Cancer Institute in Rotterdam, the Netherlands from 2003-2024. Cases with ring-like contrast enhancement and/or central necrosis at time of diagnosis were excluded. Patients were classified as glioblastoma using a glioma-tailored NGS panel. Pre-and postoperative tumor volumes were segmented manually using open source software ITK-SNAP. Pre- and postoperative volumes were set equal when only a biopsy was performed. Clinical information and postoperative therapies were retrospectively collected from patient records. Overall survival was calculated from time of diagnostic MR scan.

RESULTS
We identified 77 patients with available imaging data. Median age of patients was 59 years. The presenting symptom was an epileptic seizure in 66.2% of patients. Tumor localization in 60 out of 77 patients involved mainly the temporal lobe. As initial surgical strategy 59 patients underwent a biopsy (stereotactic or open), and only 18 patients a resection (of which 5 were awake). In most cases a clinically relevant resection was considered not feasible. Of the 18 resected patients, 4 patients underwent a second resection at progression. Of the 59 biopsied patients, 5 underwent a subsequent resection, and 5 a second biopsy as the first biopsy was inconclusive. Patients that underwent a resection had higher KPS scores (≥90 in 95.7% vs 55.6%, P= 0.003), and lower rates of gliomatosis cerebri (8.7% vs 53.7%, P &lt;0.001). Median preoperative tumor volume was 65 cc. In only 3 of 18 resected patients the postoperative tumor volume was ≤5 cc. After diagnosis, 41 patients underwent radiotherapy with concurrent temozolomide, of which 12 with a hypofractionated scheme. 12 patients only received radiotherapy and 13 patients only chemotherapy. Median OS was 21.1 months, with no significant difference in OS observed between the resection and biopsy group.

CONCLUSION
In this series on non-CE GBMs with low grade histological features, a clinically relevant resection was not feasible in most cases because of pre-operative size of the lesion and location, only in 3 patients a small postoperative volume of ≤5cc was achieved. This may contribute to the poor outcome of these patients compared to other series.
P18.51.A UNIQUE GENETIC AND EPIGENETIC ALTERATIONS IN GLIOBLASTOMA VERY LONG-TERM SURVIVORS (VLTS): INSIGHTS FROM TWO CLINICAL CASES
Authors: Anghileri E , Pollo B , Calatozzolo C , Lazzarini E , Patrizi S , Pedace L , Barresi S , Patanè M , Maddaloni L , Lamperti E , Indraccolo S , Paterra R , Miele E 
Published: October 2024

Abstract

BACKGROUND
Glioblastoma (GBM) 5-year survival (LTS) and a 10-year survival (VLTS) rate are extremely low, reaching 7% and 4.7% respectively (2020 CBTRUS Statistical Report). The biological mechanisms that drive the prolonged clinical outcomes remain significantly understudied.

MATERIAL AND METHODS
As part of a recent study on LTS (PMID: 38423245), here we detail two out of the 17 VLTS cases, addressed with extensive molecular analyses.

RESULTS
Patient AR 10-046 was a 31-year-old female with a left fronto-parietal giant cell GBM (gcGBM), treated with surgery, radiotherapy and chemotherapy. After 6 months from the diagnosis, she recurred and underwent tumor exeresis and adjuvant TMZ, maintaining disease stability for a total of 243 months. According to the v12.5 BTC the tumor was assigned to the methylation subclass pedHGG_RTK1a subtype (score &gt;0.99), frequently associated with Lynch syndrome (LS). Indeed, we detected MSH6 mutation in tumor DNA as well as in peripheral lymphocyte. We detected high Tumor Mutational Burden. Interestingly, the Copy Number Variation (CNV) plots showed chromosome 1q gain and chromosome 13 loss with no other typical GBM alterations.Patient AR 10-037 was a 70-year-old male with left temporal lobe GBM treated with surgery, adjuvant radiotherapy and chemotherapy, achieving a survival of 73 months. Histology was classical GBM. The tumor was assigned to the pedHGG_MYCN subclass with a suboptimal score (0.5). At CNV examination, apart from the canonical chromosome 7 gain and chromosome 10q loss, we observed MDM2 gene amplification and possible rearrangements on chromosome 12 and 18 with the typical aspect of a chromothripsis (CT), confirmed by RNASeq analysis. Our case presented CT on chr12 harboring two putative gene fusions: CPSF6::CPM and PTPRR::RAB3IP never reported in the literature.

CONCLUSION
We described two cases of VLTS patients with peculiar molecular profile, widening the scenario of clinical and molecular variability that can be found in such patients. Further studies are still needed to identify the biological mechanisms causing such prognosis, with a fundamental contribution from molecular analyses, including DNAm profiling, NGS and RNAseq.

FUNDING
RRC Italian Ministry of Health
P18.53.A USING THE PATTERN OF 5-AMINOLEVULINIC ACID (5-ALA) POSITIVE RESIDUE TO PREDICT THE OUTCOME OF GLIOBLASTOMA PATIENTS
Authors: Manik V , Sim V , MacDonald M , Mannava A , Soumpasis C , Kalaitzoglou D , Ashkan K , Bhangoo R , Gullan R , Brazil L , Al-Salihi O , Vergani F , Chia K , Swampillai* A , Lavrador* J P 
Published: October 2024

Abstract

BACKGROUND
Glioblastoma multiforme (GBM) portends poor prognosis despite multiple attempts at finding newer therapies. The current standard of care remains maximal safe resection. 5-ALA guidance helps to maximise the resection extent but complete removal is not always possible. It is unclear, if the residual 5-ALA pattern can predict the outcome of patients with GBM.

MATERIALS & METHODS
Patients with GBM treated at our centre between January 2018 - July 2019 were included if they had 5-ALA based tumour excision & were planned for adjuvant treatment per Stupp. Patient, tumour & treatment related factors were collected. Operation notes were reviewed to determine the pattern of 5-ALA residual & classified as no residue if there was no visible 5-ALA left at the end of resection; focal residue if 5-ALA positive tissue left involved 1-2 walls; or diffuse residue if all walls were involved. Date of relapse & date of death were collected to compute progression free survival (PFS) & overall survival (OS) respectively. Data was analysed in SPSS™ v29, Kaplan Meier curves were used for survival analysis with log rank testing to compare between groups.

RESULTS
Total of 23 eligible patients were identified. Median age was 58 (32 - 70), majority were males (n=15). No residual 5-ALA was seen in 12, 8 had focal & 3 had diffuse residual. There was moderate correlation (f=0.453, p=0.03) between 5-ALA residual & the extent of resection however the positive (58.3%) & negative (63.6%) predictive values were low. The quantity of 5-ALA residual, no or focal residual vs diffuse residual, was predictive of overall survival 18.2 vs 9.3 months (p &lt; 0.001) as well as progression free survival 10.9 vs 4.5 months (p = 0.006). The impact on overall survival was maintained even when the groups were stratified with age (65 and above or less than 65, p=0.006) or with their MGMT status (unmethylated or methylated, p=0.002). Cox proportional hazard showed that older age (p=0.004), unmethylated MGMT (p=0.031), intra-operative ventricular involvement (p=0.005) & diffuse 5-ALA residue (p=0.003) all had a negative impact on overall survival. A sub-group analysis, did not show any difference between the no residual and focal residual 5-ALA groups for OS (p = 0.548) or PFS (p = 0.498).

CONCLUSION
Diffuse pattern of 5-ALA residual had a negative impact on the oncological outcome of patients treated with 5-ALA guided maximal safe resection followed by oncological treatment, even when adjusted for established risk factors like age & methylation status.
*-joint authors
P19.01.A A SYSTEMATIC REVIEW OF THE NEUROSURGICAL MANAGEMENT OUTCOMES OF POSTERIOR PETROUS MENINGIOMAS
Authors: Awuah W , Ali S , Tan J , Adebusoye F , Shah M , Boye A , Sanker V , Tenkorang P , Chidi-Ikeji S , Frimpong M , Abdul Rahman T , Attalah O 
Published: October 2024

Abstract

BACKGROUND
Posterior petrous meningiomas (PPMs) present challenges in neurosurgical practice due to their proximity to critical neurovascular structures. Surgical management necessitates consideration of tumour characteristics and adjacent structures to optimise outcomes and minimise complications. Despite advancements in techniques and imaging, determining the optimal surgical approach and outcomes for PPMs remains an area of ongoing investigation. Understanding surgical outcomes and factors influencing postoperative recovery is crucial for informing clinical decisions and enhancing patient care.

MATERIALS AND METHODS
Databases such as PubMed/Medline, Web of Science (WOS) and Cochrane Library were systematically searched from their inception to April 2024. Among the retrieved articles were 10 retrospective studies, 2 case series, and 9 case reports encompassing a cohort of 622 patients who had undergone various procedures for PPMs. A meticulous quantitative analysis was conducted on the individual patient data extracted from these sources, allowing for a comprehensive examination of the aggregated findings. Additionally, a qualitative analysis was performed on available individual patient data, utilising the Chi-Squared Test methodology to explore potential associations between preoperative symptoms, surgical approach, and postoperative outcomes. In this analysis, a significant threshold of p &lt; 0.05 was employed to determine noteworthy correlations.

RESULTS
Our search revealed studies with 622 individuals (468 females and 154 males), with a mean age of 54.92 years. Quantitative analysis revealed some degree of hearing loss as the predominant symptom (32%). For treatment, the retrosigmoid approach was most common (63%), followed by the translabyrinthine approach (16%). Resections were mostly total, with the most common postoperative complications being neurological deficits of the 8th cranial nerve (21%). Postoperative facial nerve function was fully preserved in 71.5% of patients, and 36.5% retained unimpaired hearing. Qualitative analysis indicated significant associations between postoperative hearing status, surgical approach (p = 0.001), and neurological deficits (p = 0.003).

CONCLUSION
Preliminary evidence from this systematic review suggests that the surgical approach matters when it comes to avoiding sequelae arising from surgical treatment of PPM. Specifically, the widened retrolabyrinthine approach shows promise in reducing neurological deficits, while the retrosigmoid approach appears favourable for preserving postoperative auditory function. However, given the limited scope of the current literature, further research is warranted to corroborate these findings and enhance our understanding of optimal surgical strategies for PPM management.
P19.07.A INCREASED LOCAL TUMOR CONTROL AFTER POSTOPERATIVE RADIOTHERAPY IN RECURRENT MOLECULARLY HIGH-RISK WHO GRADE 1 MENINGIOMAS
Authors: Deng M Y , Maas S N , Debus J , Sahm F , König L 
Published: October 2024

Abstract

BACKGROUND
Despite an overall favorable prognosis, early recurrences occur in a significant proportion of WHO grade 1 meningiomas following surgical resection. Given a wide variety of institutional preferences, individualized patient circumstances, and a lack of level 1 evidence, there are no standardized guidelines for the treatment of recurrent WHO grade 1 meningiomas, in particular to the requisiteness of radiotherapy and its timing. Our study assessed the local tumor control after postoperative radiotherapy in recurrent molecularly high-risk WHO grade 1 meningiomas.

MATERIAL AND METHODS
Patients with primary WHO grade 1 meningioma and DNA methylation profiles (n=224) were retrospectively screened for recurrences (n=31). The local 3-year progression-free survival (PFS) after primary resection, as well as recurrence resection, was determined using Kaplan-Meier analysis. Integrated risk scores were calculated for primary and recurrent WHO grade 1 meningiomas.

RESULTS
Primary WHO grade 1 meningiomas were completely resected (GTR) in 81.3% (182/224). The 3-year PFS was 95.4% for molecularly prognostically favorable (IntS-low) versus 71.1% for prognostically unfavorable (Int-S-int/high) primary WHO grade 1 meningiomas. None of the patients received postop-RT after primary resection. After recurrence resection (n=31, Int-S-low: 14/31, Int-S-int/high: 17/31), 85% of subtotally resected meningioma recurrences received postop-RT. Notably, the local 3-year PFS for clinically-molecularly prognostically unfavorable recurrences (STR, Int-S-int/high) after postop-RT was 85.9%.

CONCLUSION
Postop-RT in molecularly prognostically unfavorable, recurrent WHO grade 1 meningiomas after STR may lead to improved local tumor control. Future matched-pair analyses with patients with recurrent WHO grade 1 meningiomas are warranted to further illustrate the benefit of postop-RT after recurrence resection.
P22.05.B DIFFERENCES IN END-OF-LIFE CARE AND PLACE OF DEATH IN PATIENTS WITH MALIGNANT BRAIN TUMOUR: A SWEDISH REGISTRY STUDY
Authors: Ozanne A , Öhlén J , Nyblom S , Jakola A S , Smits A , Larsdotter C 
Published: October 2024

Abstract

BACKGROUND
The treatment in malignant brain tumour is multimodal and consists of a combination of surgery, radiotherapy, and chemotherapy. The average survival differs depending on e.g. degree of malignancy and location. Potential palliative needs also need attention. This preliminary study seeks to utilize registry data to identify the place of death among adult people with malignant brain tumours in Sweden between 2013 and 2019. It aims to explore potential associations between the place of death and factors such as medical diagnosis, official palliative care status, sociodemographic characteristics, health service utilization, and healthcare service characteristics at the end-of-life.

MATERIAL AND METHODS
This is a population-level registry study examined the place of death among adults who died of malignant brain tumours in Sweden. Data was retrieved from the Swedish National board of Health and Welfare (NBHW), the Swedish Register of Palliative Care (SRCP), and Statistics Sweden (SCB). Descriptive statistics, univariable and multivariable binary logistic regression analyses are performed.

RESULTS
Preliminary results show that 3888 adults died of malignant brain tumours between 2013 and 2019 (41.4% female). In total, 64.4% did not have the palliative care diagnosis Z51.5, and this percentage varied depending on location of their death. Additionally, 57.2% did not have access to specialised palliative care at their place of death. Notably, among those who died in a nursing home, 80.0% lacked this access. Among those who died in a hospital, 53.5% had experienced one transfer to the hospital in the last month of life, and 41.8% had undergone two or more transfers. Notably, the odds ratio of dying in a hospital versus at home was higher for patients with more transfers. Additionally, the odds ratio of dying in a hospital compared to dying at home was higher in the Stockholm region but lower in the Western, South-eastern, and the Southern regions.

CONCLUSION
A minority of patients had access to specialised palliative care, despite being diagnosed with a malignant brain tumour, and this varied depending on the location of their death. Moreover, notable regional disparities were observed between deaths that occurred in hospitals versus at home. These findings underscore the presence of unequal End-of-life palliative care and highlights the need for additional investigation.
P26.03.B AN INTERNATIONAL ACCELERATOR PROGRAMME FOR NOVEL BRAIN TUMOUR THERAPIES
Authors: Aitken C K , Huskens N , Bushby K , Noble K , Hamerlik P , Kobayashi D , Mathew R , McCall J , Plummer R , Rahman R , Lopez J 
Published: October 2024

Abstract

BACKGROUND
Developing a comprehensive translational programme for brain tumours involves navigating numerous challenges, including robustness of preclinical studies, clinical trial design, safety, understanding and addressing regulatory requirements, and commercialisation. Recognising the difficulty of this journey, the Brain Tumour Research Novel Therapeutics Accelerator (BTR-NTA) was launched in 2023. The BTR-NTA is an accelerator programme providing independent expert guidance to de-risk drug or device development through systematic evaluation. The international, multidisciplinary BTR-NTA Committee spans expertise across the entire therapeutic development pipeline. Supported by Brain Tumour Research, the BTR-NTA programme is free for academic groups and available for a nominal meeting contribution fee for industry applicants.

MATERIAL AND METHODS
Researchers at any stage of therapeutic development may apply to BTR-NTA. Accepted applicants proceed as follows: 1. Applicants outline their current and prospective data and findings. The proposal and all supporting materials are covered under a confidentiality agreement that protects applicants’ intellectual property; 2. Proposals are reviewed by the BTR-NTA Committee; 3. Applicants and BTR-NTA Committee meet in-person to constructively evaluate the work; and 4. Applicants receive a comprehensive report with feedback on strengths, identification of potential risks, and guidance on next steps. The BTR-NTA Committee dedicates time for in-person meetings with each applicant, and extensive time pre- and post-meeting.

RESULTS
Since the launch of the BTR-NTA in 2023,13 international research groups have applied to the programme and three therapeutic applications have been advanced to the in-person review by the BTR-NTA Committee. Of the applicants who provided feedback on the BTR-NTA programme, all intended to adjust or refine their future work based on the BTR-NTA Committee’s input and the average rating of the programme’s helpfulness was 9.5 out of 10.

CONCLUSION
BTR-NTA reviews will continue to take place bi-annually, with capacity to provide support for up to four research groups per review. The ultimate goal of the BTR-NTA is to help researchers with a potential therapy for brain tumours navigate the development journey and reach the clinic in an efficient way. This programme will support development of novel therapies to improve outcomes for patients with brain tumours.
P26.06.B EVALUATION OF THE ANTITUMOR EFFECT OF A CHEMOTHERAPY-LOADED DEVICE FOR THE TREATMENT OF PRIMARY BRAIN TUMORS
Authors: Déry L , Charest G , Guérin B , Akbari M , Fortin D 
Published: October 2024

Abstract

BACKGROUND
Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor in adults. It is characterized by its infiltration of the brain parenchyma, making complete surgical resection impossible. It is also resistant to radio-chemotherapy. Tumor recurrence is therefore inevitable, and median survival is just over 14 months. The location of these tumors also means that they are protected from chemotherapy by the presence of the blood-brain barrier (BBB). Currently available treatments are inadequate and do not provide optimal tumor control. We believe that treatment localized directly at the tumor site will eliminate a greater number of infiltrating tumor cells while significantly reducing systemic toxicity.

MATERIAL AND METHODS
For this project, we are collaborating with a team specializing in bioengineering, who have produced a biomaterial enabling the gradual release of various agents. Our aim is to use this biomaterial to deliver chemotherapeutic agents to the tumor site through the surgical cavity. We evaluated the antitumor potential of biomaterial loaded with different chemotherapies. Cell-based assays were carried out using glial tumor cells in the presence of the biomaterial containing chemotherapeutics. Cell viability readings were taken at different times to observe the antitumor effect of the selected neoplastic agents. A survival study was realized with the Fischer F98 rat model, which underwent partial tumor resection followed by injection of biomaterial containing chemotherapy. Histological studies of brains and resected tissues were carried out to assess the effect of the biomaterial on the brain environment.

RESULTS
In vitro assays showed a strong cytotoxic effect against glial tumor cells at 24h, 48h and 72h of biomaterial-drug incubation. The combination of two chemotherapeutic agents showed the best cytotoxic effect on glial tumor cells. We also performed a partial tumor resection and insertion of the chemotherapy-loaded biomaterial into the surgical cavity of the F98 glioma bearing rat. Similar to in vitro studies, the combination of two antineoplastic agents shows a significant improvement in animal survival.

CONCLUSION
In conclusion, the in vitro and in vivo results of this study show that the combination of chemotherapy has the greatest antitumor effect. We hope that these exciting results will lead to the development of a new treatment for patients with glioblastoma and potentially other diseases where complete tumor resection is impossible.

SUPPORT/ DISCLOSER
Funding was provided by donations and scholarships: La rose des vents, Fondation du Centre Hospitalier Universitaire de Sherbrooke (CHUS), Centre de recherche du CHUS (CRCHUS), Centre d’imagerie moléculaire de Sherbrooke (CIMS) and Centre d’excellence en Neurosciences de l’Université de Sherbrooke (CNS). All authors declare that they have no competing financial interests.