tbuckley/cabot-search huggingface dataset:
P17.24.A STEREOTACTIC RADIOSURGERY FOR INTRACRANIAL METASTASES IN OLDER PEOPLE: RIGHT FOR ALL?
Authors: S Main, L Rajkumar, S Bhusal, K Chia, O Al-Salihi, L Brazil, A Swampillai, S Hassan, Y Akhtar, A Mazumder, M MacDonald, V Manik
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Stereotactic radiosurgery(SRS) is an established treatment for local control of intracranial (IC) metastatic disease. Clinical trials under-represent older people. Older patients may have complex additional co-morbid conditions. This study addresses SRS for brain metastases in older patients. MATERIAL AND METHODS Retrospective observational study of ≥75 years receiving SRS for IC metastatic disease November 2017-November 2023(N=96). Patients were treated at a single tertiary centre in the UK with Linac-based SRS. Patients treated more than once in the study period were included in survival analysis from incident treatment. Rockwood frailty scores (RFS) were assigned retrospectively. Adverse events assessed by hospital admissions or additional steroid requirements related to SRS and within six months of treatment. Data collected from electronic patient records. Survival analysis conducted with Kaplan Meier methodology and Cox proportional hazard modelling using the R language. RESULTS Median age was 78(75-93) &amp; 241 metastases were treated. Lung cancer (55.2%) was the most common primary tumour followed by melanoma (27.1%) and most were treated for a single lesion (65.6%) (range 1-18). For 81.8% of patients, this was the first episode of treatment for IC disease; 4 had received craniotomy and adjuvant SRS as part of an initial treatment strategy. Over half (55.2%) of patients received further systemic therapy for their primary. Median total planning treatment volume 2.18cc (0.1-17.3cc). Post SRS, 38.2% of patients were admitted to hospital and 36.4% required additional steroids. There is a correlation of tumour volume with both admission and need for additional steroids (0.38, p≤0.001; 0.38, p≤0.001).Median overall survival (mOS) is 13.1months (mo) (95%CI:8.7-24.8mo). On univariate analysis, first or subsequent brain treatment (p=0.026), number of previous lines of systemic therapy (P=0.0036), subsequent systemic therapy (p≤0.001), RFS (p≤0.001), total PTV volume (p=0.013); and tumour type (p≤0.001) all predict survival. The number of lesions treated and radiological disease control at the point of referral were not statistically significant. Variables identified as statistically significant in univariate models were included in Cox proportional hazard model: RFS (Hazard ratio (HR) 1.91, p=0.04); subsequent systemic therapy (HR: 0.50, p=0.020) and first or subsequent brain treatment (HR: 0.25, p=0.026) were independent predictors of survival. CONCLUSION SRS remains an effective treatment in those ≥ 75. A major factor in predicting survival is patient frailty and their ability to receive subsequent systemic therapy. Hospital admission were seen in a third of patients and correlates with the tumour volume which signifies the importance of careful patient selection.
P20.08.B CLINICAL SEVERITY GRADING OF NF2-RELATED SCHWANNOMATOSIS
Authors: A Lawson McLean, D Löschner, S Farschtschi, N Dengler, A Neumeister, C Senft, S Rosahl
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Nf2-related schwannomatosis (NF2) is a genetic disorder linked to tumours in the nervous system, but the extent of radiological tumour burden doesn’t always align with the diverse disabilities patients face. Additionally, there lacks a validated clinical classification for assessing disease severity.This study proposes a clinical classification comprising three severity grades, aiming to enhance communication among caregivers regarding individual patients and aid in clinical management. MATERIAL AND METHODS The records of 196 patients were reviewed to identify the most common diagnoses with significant impacts on daily tasks, social interactions, and life expectancy, resulting in seven main categories. Each category was assigned one point. Using a training set, three severity grades were established: grade 1 (mild NF2) with 0 points, grade 2 (moderate NF2) with less than 3 points, and grade 3 (severe NF2) with 3 or more points. The grading system was then evaluated for inter-rater reliability and clinical significance. RESULTS Substantial inter-rater reliability was observed among three raters with varying levels of clinical experience (Fleiss’ kappa = 0.62). The severity grades showed significant correlations with hospitalization rates, number of operations, and reliance on implants such as cochlear implants, auditory brain-stem implants, or ventriculoperitoneal shunts. CONCLUSION This simple and rater-independent scoring system comprising three grades effectively reflects the clinical disease severity of NF2 patients. This system may facilitate communication among medical personnel of diverse backgrounds and experience levels and provides a valuable clinical tool for decision-making and research in NF2 management.
P17.23.B SINGLE INSTITUTION RETROSPECTIVE ANALYSIS OF COMPLICATIONS ASSOCIATED WITH SURGICAL DEBULKING OF BRAIN METASTASIS: SINGLE VS MULTIPLE LESIONS
Authors: S Kannan, Y Liew, A Ray, G Hall, I Phang, A Hazra
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Surgical resection of brain metastasis is associated with complications, which worsens patient’s quality of life, resulting in oncological treatment delays and death. Surgical complication data aids decision making, leads to objective risk benefit analysis and informed consent. The aim of this study is to quantify the impact of the number of intracranial metastases on the rate and types of post-operative complications. MATERIAL AND METHODS Retrospective analysis on adult patients with brain metastasis, who underwent surgical debulking between 2017 and 2023 at Royal Preston Hospital. Data collected included demographics, primary tumour, number of lesions, 30-days post-operative complications, 30-days post-operative mortality and palliation, Karnofsky-Performance Score (KPS), and first vs. repeat resection. Univariate analysis carried out using R studio software. RESULTS Our patient cohort (n=226), 80 (35.6%) experienced post-operative complications. Top-five most common complications were Hospital-acquired pneumonia (HAP) (n=30, 13.3%), surgical site infection (SSI) (n=23, 10.2%), wound dehiscence (n=11, 4.9%), thromboembolic events (n=14,6.2%) and CSF leak (n=8, 3.5%). Average length of admission was 19.9 days (1-120) for patients with complications compared to 6.9 days (2-31) for patients without complications. Thirty (37.5%) patients with complications were readmitted. One-hundred twenty-seven patients (56.1%) had solitary lesion and 99 patients (43.9%) had multiple lesions. The most common primaries for patients with solitary lesion were lung (n=51, 40.2%), breast (n=25, 19.7%), and gastrointestinal (n=21, 16.5%). Whereas the most common primaries for multiple metastases were lung (n=41, 41.4%), breast (n=18, 18.2%), and skin (n=18, 18.2%). Amongst patients with complications, 45 (45.5%) had multiple metastases whilst 35 (27.6%) had solitary. The most common complications for patients with solitary lesion were HAP (n=10, 7.9%), SSI (n=9, 7.1%) and thromboembolism (n=8, 6.3%). Common complications for multiple lesions were HAP (n=20, 20.2%), SSI (n=14, 14.1%) and wound complications (n=10,10.1%). Patients with multiple metastases had higher 30-days post-operative palliation [(n=12) 12.1% vs (n=0) 0% solitary) and higher 30-days mortality [(n=4) 4% vs (n=4) 3.1% solitary). Multiple metastases were statistically significant for complications (p=0.005), HAP (p=0.006) and 30-days palliation (n=0.0001) but not statistically significant for SSI, 30-days mortality or thromboembolism. Conclusion: Surgical debulking is associated with significant post-operative complications, especially patients with multiple metastases with 16% either dying or not receiving any further treatment. Furthermore, 14.1% develop serious complications requiring further surgical interventions whilst 34.3% requires medical treatment.
P20.11.A DIAGNOSTIC DELAY OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL) MAY BE CAUSED BY INFLAMMATORY DIFFERENTIAL DIAGNOSES
Authors: I Beyer, M Proescholdt, I Wiesinger, E Bumes, T Haedenkamp, A Fischl, D Lee, O Koelbl, N O Schmidt, C Wendl, T Pukrop, S Mayer, M J Riemenschneider, R Linker, P Hau
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND PCNSL is a rare extranodal subtype of B-cell non-Hodgkin lymphoma initially located in the central nervous system. It can only be finally diagnosed with tissue sampling. Therefore, tumor biopsy and staging examinations beforehand can delay diagnosis. Consequently, PCNSL at histological diagnosis has often already evolved for a prolonged time. However, late therapy start may worsen treatment outcomes. A clearer delineation of PCNSL-specific clinical and imaging features that leads to an earlier diagnosis might accelerate start of therapy and improve prognosis. We here performed a retrospective analysis to construct a pathway that enhances this process. MATERIAL AND METHODS Clinical and imaging data of patients with histologically confirmed PCNSL diagnosed between 2012 and 2022 and hospitalized in the University Hospital Regensburg, was collected retrospectively from the local clinical management systems and tumor registry. Data included demographic, prognostic and clinical data incl. neurocognitive function (NCF), neuropathological and laboratory data, and magnetic resonance imaging (MRI). Descriptive analyses and univariate and multivariate analyses were performed. Survival data was calculated using the Kaplan Meier-method. RESULTS A retrospective cohort of 108 patients was investigated. Median time to diagnosis (TTD) was 40 (range, 6-1,100) days and median time to hospitalization (TTH) was 14 (range, 0-700) days. Median overall survival (OS) was 20 months (range, 0.5-125+). There was no significant correlation between TTD and OS (r= 0.001, p=0.990) nor between TTD and progression free survival (PFS) (r=0.031, p=0.756). However, TTH correlated significantly to TTD (r=0.429, p&amp;lt;0.001). Most common symptoms at incidence were cognitive decline (N=63, 59%) and psychiatric symptoms (N=41, 38%). Together, 6% of patients had positive McDonald criteria that would have defined autoimmune disease. MRI was the diagnostic technique with the greatest variation of differential diagnoses, including primary brain tumors in 44% of patients. Abnormal memory in NCF was detected as risk factor for decreased OS (HR=3.237, CI=1.111-9.434; p=0.023) and increased TTH (partial eta squared=0.279; p=0.024). CONCLUSION We conclude from our data that a delayed diagnosis of PCNSL cannot be verified as a causal factor for decreased OS or PFS. The relevance of a delayed diagnosis therefore may be restricted to certain subgroups who show a more dynamic disease. In relation to this hypothesis, the positive correlation of TTH to TTD suggests, that a subgroup of PCNSL may have a less dynamic course leading to a prolonged diagnostic period. Whereas symptoms like cognitive decline and psychiatric symptoms are typical for PCNSL, typical patterns in MRI do not occur and the rate of false negative diagnoses is high.
P20.10.B CLINICAL, PATHOLOGICAL, AND GENOMIC FEATURES OF INFRATENTORIAL IDH-MUTANT GLIOMAS
Authors: L WANG
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Isocitrate dehydrogenase (IDH) 1/2 mutations are rare in infratentorial gliomas, which of clinico-molecular characteristics of infratentorial IDH-mutant gliomas have not been well characterized. MATERIAL AND METHODS In the current study, a series of 12 cases of infratentorial IDH-mutant gliomas were described for clinical, pathological, and genomic characteristics. RESULTS The median age of this cohort at diagnosis was 41-year-old (range: 10-67). 9 tumors were located in posterior fossa, including 5 (41.7%) were only in the brainstem and 4 (33.3%) were present in both brainstem and cerebellum, and 3 (25%) in spinal cord. Histopathologic diagnosis of twelve cases are all diffuse astrocytoma. Eight cases were low-grade astrocytoma (WHO grade 2) including one with concomitant KIAA1549-BRAF fusion and IDH mutation in pediatric spinal cord astrocytoma, and four high-grade astrocytoma (WHO grade 3). Comprehensive genomic profiling revealed that Non-canonical IDH (50%, 6/12) and TP53 (75%, 9/12) mutations were more frequent in infratentorial IDH-mutant astrocytomas than supratentorial cases. While ATRX mutation (33.3%, 4/12) and MGMT promoter methylation (41.7%, 5/12) were less frequent (p&amp;lt;0.005). No mutations of H3.1, H3.3, TERT, homozygous deletion of CDKN2A/B, or co-deletion of 1p/19q were detected. CONCLUSION Our data revealed infratentorial IDH-mutant gliomas have distinct clinical, pathological, molecular, and prognostic characteristics, differed from supratentorial cases.
P25.02.A GLIOBLASTOMA RESEARCH FROM 1938 TO 2021: INCREASED SURVIVAL, CHANGING TREATMENT REGIMES, AND GENDER DISPARITIES IN AUTHORSHIP
Authors: J Breu, K Nenning, B Baumann, D Nam, A Woehrer
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Glioblastoma is the most common and aggressive malignant brain tumor in adults with continued poor prognosis. While the long-lasting gold standard RT-TMZ was eventually refined by incorporating tumor treating fields as well as lomustine for subsets of patients, patient outcomes showed only modest improvements over the decades. Here, we set out to map patient outcomes according to type of study, treatment approach and publication year. Additionally, we explore geographic origin and sex differences in authorship per study type to track disparities in glioblastoma research. MATERIAL AND METHODS We conducted a systematic literature search using the terms “glioblastoma” AND “overall survival” at PubMed.gov. We manually reviewed 20,047 articles from 1938 to 2021 and included 2,232 ones that reported median overall survival for human subjects. Study type was categorized as case series, clinical trials (CTs), randomized controlled trials (RCTs), meta-analysis and population-based studies. For each study, treatment, number of subjects, and authorship details were extracted. RESULTS 65.5% of articles were case series followed by 23.9% CTs. Overall, median OS was 13.1 months for all studies and increased from 11.3 months in 1938-2000 to 14.3 months in 2001-2021. Population-based studies reported the lowest median OS (9.0 months). Survival increases were similar for studies reporting radiotherapy (r=0.32), chemotherapy (r=0.27) and temozolomide (r=0.20). No significant survival increases were observed in studies reporting targeted therapies (r=0.22), tumor treating fields (r=0.23), bevacizumab (r=0.02) and immunotherapies (r=-0.10). Despite making up only 5.6% of all studies, RCTs had the highest cumulative impact factor and citation count. While US-based researchers dominated across all study types, 25.2% of articles were authored by females as first and 18.5% as last authors. Only for meta analysis, gender parity seemed to be achieved in first authorship (46.2% female first). Women continued to be under-represented, particularly as last authors in range from 15.4% to 22.5% across study types. CONCLUSION Almost 100 years of reported survival of patients with glioblastoma document a consistent, but slow increase in survival, with overly optimistic survival reported in non-population-based studies. Research by women as first authors shows an upward trend, although gender equality has not been achieved yet, particularly in last authorship.
P18.49.B TOWARDS INTEGRATING IMAGING AND IMMUNOLOGY IN GLIOBLASTOMA: MAPPING BLOODIMMUNE SYSTEM METRICS TO TUMOR MAGNETIC RESONANCE IMAGE DATA
Authors: J Heugenhauser, C Visus, J Buchroithner, C Marosi, K Rössler, T Felzmann, G Widhalm, M Nowosielski, F Erhart
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Glioblastoma is the most aggressive and most frequent primary brain tumor. Glioblastoma is highly immunology-driven because a large portion of its cell mass consists of immune cells. In addition to immunology, imaging is a second important scientific field when it comes to glioblastoma. Regarding imaging, the VASARI brain tumor morphology classification system has been gradually accepted as a valuable tool. Despite the importance of both, imaging and immunology, for glioblastoma characterization, these two disciplines have been kept surprisingly separate. Integrating them more seems worthwhile and valuable. MATERIAL AND METHODS 76 patients from a previous glioblastoma immunotherapy study were assessed ex post with regard to the accessibility of tumor imaging data and peripheral blood immunology metrics at the start of the study, i.e. at baseline. For 41 patients both were acquirable. Magnetic resonance images were then studied via volumetric analysis as well as VASARI morphology assessment. The therewith generated 27 imaging variables were integrated with 67 peripheral blood immunology metrics that had been measured via FACS and PCR. Finally, a screening for associations between these variables was performed. RESULTS In a first comprehensive mapping, 94 imaging-immunology correlations were present. Importantly, the edema volume seemed associated with CD56+CD16- natural killer cells, characteristics of the contrast-enhancing margin were associated with various cytotoxic T cell species and the necrosis volume was associated with mRNAs in the blood that indicate specific immunopolarization (IFN-γ, GATA3, ROR-gt). Curiously, the location of the tumor location also apparantly had a role as e.g. some blood helper T cell species seemed more frequent in patients with central/bilateral tumors or with tumors in the Broca region. CONCLUSION We here contribute first data that tumor imaging features and peripheral blood immunology metrics can be associated in glioblastoma. Via exploring the intersection between imaging and immunology in glioblastoma science, we advance basic tumor biology aspects and pioneer novel directions for continuative research.
P18.29.A METHYLATION PATTERN OF ANDROGEN RECEPTOR REGULATORS IN ADULT-TYPE DIFFUSE GLIOMAS
Authors: L Gatto, S Asioli, L Morandi, V Di Nunno, A Tosoni, S Bartolini, L Griva, S Melotti, M Foschini, E Franceschi
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Androgen receptor (AR) is a ligand-mediated transcription factor that belongs to the superfamily of steroid receptors. AR is overexpressed in several solid tumors and is a potential therapeutic target. The AR gene is located on X chromosome at Xq11-12. In addition to AR, a group of genes involved in the regulation of AR function and expression are located on X chromosome: FLNA, UXT genes and the MAGE family genes, (MAGEA1, MAGEA2, MAGEA3, MAGEA9, MAGEA11, MAGEC1, MAGEC2). Our study aims to characterize AR in adult-type diffuse gliomas, evaluating the AR status and the methylation pattern of AR regulatory genes. MATERIAL AND METHODS In this retrospective analysis we included patients diagnosed with adult-type diffuse gliomas grade 2 or 3 or 4 according to WHO 2021 classification, treated at our institution. Immunohistochemistry (IHC) and gene methylation analysis were performed to evaluate AR expression and its regulatory status. RESULTS We included samples from 50 patients (M:F=26:24). Immunohistochemical AR positivity was predominant in males (p= 0.04) and in patients with glioblastoma IDH-wild type compared to lower grade adult-type diffuse gliomas (p= 0.04). AR positivity was more frequent in astrocytomas IDH-mutant compared to oligodendrogliomas IDH-mutant and 1p19q codeleted (p= 0.02). Moreover, AR expression was more frequent in MGMT unmethylated gliomas compared to MGMT methylated tumors (p=0.02). AR was found hypomethylated in cases with immunohistochemical positivity AR (Kruskal Wallis&amp;lt;0.05). UXT, MAGEA1and MAGEA1-11 were hypermethylated in AR positive gliomas (Kruskal Wallis&amp;lt;0.05). AR hypomethylation was deeper in GB (Kruskal Wallis&amp;lt;0.05). CONCLUSION AR overexpression seems to be predominant in male patients with high-grade unmethylated adult-type diffuse gliomas. The AR gene promoter is hypomethylated in AR positive adult-type diffuse gliomas. Methylation pattern of AR regulatory genes located on X chromosome regulate AR expression. These data suggest that AR signaling may be promising for potential treatment using antiandrogen therapies.
P10.23.B PREDICTING LOCAL CONTROL OF BRAIN METASTASES AFTER STEREOTACTIC RADIOSURGERY: A FUSION OF CLINICAL, RADIOMICS AND DEEP LEARNING FEATURES
Authors: H Kanakarajan, W De Baene, M Sitskoorn, P Hanssens
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Timely identification of local failure after Stereotactic Radiosurgery (SRS) offers the opportunity for appropriate treatment modifications that may result in improved treatment outcomes, patient survival, and quality of life. Previous studies showed that the addition of either radiomics or deep learning features to clinical features increased the accuracy of the models in predicting local control (LC) of brain metastases after SRS. To date, however, no study combined both radiomics and deep learning features together with clinical features to develop machine learning algorithms to predict LC of brain metastases. In this study, we examined whether a model trained with a combination of all these features could predict LC better than models trained with only a subset of these features. MATERIAL AND METHODS Pre-treatment brain MRIs and clinical data were collected retrospectively for 129 patients at the Gamma Knife Center of Elisabeth-TweeSteden Hospital (ETZ), Tilburg, The Netherlands. The patients were split into 103 patients for training and 26 patients for testing. The segment-based radiomics features were extracted using the radiomics feature extractor of the python radiomics package. The deep learning features were extracted using a fine-tuned 3D ResNet model and then combined with the clinical and radiomics features. A Random Forest classifier was trained with the training data set and then tested with the test data set. The performance was compared across 4 different models trained with clinical features only, clinical and radiomics features, clinical and deep learning features, and clinical, radiomics and deep learning features. RESULTS The prediction model with only clinical variables demonstrated an area under the receiver operating characteristic curve (AUC) of 0.82 and an accuracy of 75.6%. The prediction model with the combination of clinical and radiomics features demonstrated an AUC of 0.880 and an accuracy of 83.3% whereas the prediction model with the combination of clinical and deep learning features demonstrated an AUC of 0.863 and an accuracy of 78.3%. The best prediction performance was associated with the model that combined the clinical, radiomics and deep learning features with an AUC of 0.886 and 87% accuracy. CONCLUSION Machine learning models built on radiomics features and deep learning features combined with patient characteristics show potential to predict LC after SRS with high accuracy. The promising findings from this study demonstrate the potential for early prediction of SRS outcome for brain metastasis prior to treatment initiation and might offer the opportunity for appropriate treatment modifications that may result in improved treatment outcomes, patient survival, and quality of life.