bluuebunny/crossref_metadata_2025_split huggingface dataset:
P14.05.B 2-HYDROXYGLUTARATE IN CEREBROSPINAL FLUID AS A MONITORING BIOMARKER FOR IDH-MUTANT GLIOMAS
Authors: Riviere-Cazaux C , Lacey J , Carlstrom L , Laxen W , Munoz-Casabella A , Hoplin M , Ikram S , bin Zubair A , Andersen K , Warrington A , Decker P , Kaufmann T , Campian J , Eckel-Passow J , Kizilbash S , Tortorelli S , Burns T 
Published: September 2023

Abstract

BACKGROUND
D-2-hydroxyglutarate (D-2-HG) is a well-established oncometabolite of isocitrate dehydrogenase (IDH) mutant gliomas. While prior studies have demonstrated that D-2-HG is elevated in the cerebrospinal fluid (CSF) of patients with IDH-mutant gliomas, no study has evaluated the ability of CSF D-2-HG to quantitatively monitor tumor burden and therapeutic response. Toward this goal, we are routinely obtaining CSF samples from patients prior to, during, and after treatment via intra-operative collection and CSF-access devices.

MATERIAL AND METHODS
Patients were enrolled into our Ommaya reservoir study (NCT04692337), which enables longitudinal access to CSF. The catheter for the implanted reservoir was placed within the surgical resection cavity following a standard-of-care resection. Intra-operatively collected CSF samples were also biobanked through Mayo Clinic’s Neuro-Oncology biorepository. CSF samples were also acquired via clinically indicated ventriculoperitoneal shunts (VP shunts) or external ventricular drains via our ongoing CSF biomarkers study (NCT04692324). D-and-L-2-HG were assayed from each CSF sample via gas chromatography-mass spectrometry (GC-MS) at Mayo Clinic’s Biochemical Genetics Laboratory.

RESULTS
CSF was collected prior to and after resection in patients via Ommaya reservoirs or VP shunts, all of whom underwent near gross total resections (&gt;95% of tumor volume). D-2-HG and the D/L ratio fell on average by 57.9% (range: 15.1%-98.6%) and 68.8% (range: 49.3%-98.9%), respectively, following resection. In one patient with a largely intraventricular grade 4 IDH-mutant astrocytoma, D-and-L-2-HG fell by 99.1% and 99.3% by post-operative day 2, consistent with the impact of ventricular contact on baseline CSF D-2-HG levels. In patients for whom CSF was collected throughout chemoradiation, with or without immunotherapy, D-2-HG and the D/L ratio continued to decrease over time, despite concern for pseudoprogression versus progression on imaging.

CONCLUSION
Our early experience with this strategy demonstrates the potential for intracranial CSF D-2-HG as a monitoring biomarker for IDH-mutant gliomas. Work is ongoing to evaluate the reproducibility of these findings in a larger cohort of patients with low or high-grade gliomas, in addition to the impact of tumor recurrence on 2-HG. Future studies will evaluate the impact of IDH inhibitors and other experimental therapies on CSF 2-HG levels for pharmacodynamic monitoring of treatment response.
P15.09.B ALONG-TRACT ANALYSIS OF DTI PARAMETERS TO DETECT EXTENSION AND DIRECTION OF WHITE MATTER ABNORMALITIES IN PATIENTS WITH DIFFUSE LOW GRADE DIFFUSE GLIOMAS
Authors: Fahlström M , Mirza S , Latini F 
Published: September 2023

Abstract

BACKGROUND
Diffuse Low-grade gliomas (DLGG) show extensive infiltration through white matter (WM) tracts. Diffusion tensor tractography with along-tract analysis (ATA) has been used to non-invasively assess the microstructural integrity of WM pathways. The possibility to detect the extension and direction of WM infiltration using local DTI-based parameters in DLGG has been investigated with different techniques but displayed inconsistent results. The aim of this study was to use ATA analysis to compare DTI parameters in white matter pathways invaded/spared by DLGGs.

MATERIAL AND METHODS
Fourteen patients with a diagnosis of DLGG were included. DLGGs were manually segmented based on 3D-FLAIR images spatially normalised to MNI space. DTI was acquired for all the subjects using a single-shot echo-planar sequence on a 3T with 48 sampling directions. DTI data was reconstructed within MNI space using q-space diffeomorphic reconstruction (QSDR) in DSI studio. Five bilateral sets of WM pathways were reconstructed based on the HCP-1021 template. ATA was performed for FA, AD and RD for all five bilateral WM pathways. In short, all WH pathways were stretched to the same length of 100 indices, FA, RD and AD were sampled for each index. An overlay of tumour 3D reconstruction was used to detect contact with WM pathways . Not affected WM pathways were considered normal and included as normal data. All WM pathways were compared individually and per index to the normal data using a z-test.

RESULTS
Eight patients had an IDH-mutated grade 2 astrocytoma, 6 had a 1p19q co-deleted grade 2 Oligodendroglioma. ATA analysis displayed a clear difference between invaded and non-invaded WM pathways in all the DTI parameters. In infiltrated pathways, the z-test displayed: 1) significant lower FA only within a limited tumoral area but not along the all infiltrated segment; 2) RD was significantly higher compared with normal data in a larger area even beyond the tumour borders; 3) AD was significant lower in the infiltrated WM pathways beyond the tumour borders.

CONCLUSION
s: ATA analysis is a sensitive and reliable method to detect the extension and the direction of diffusion abnormalities within and beyond the DLGG extension. Our results support other studies suggesting that FA is not an enough sensitive index to detect gliomas related WM abnormalities. A wider use of this method may be valuable to better plan the surgical resection of patients with DLGG or to tailor radiotherapy planning according to WM invasion.
P16.02.B DIAGNOSTIC ACCURACY OF CSF LIQUID BIOPSY AND MRI FOR LEPTOMENINGEAL METASTASES IN SOLID CANCERS: A META-ANALYSIS
Authors: Nakasu Y , Deguchi S , Nakasu S , Yamazaki M , Notsu A , Mitsuya K , Hayashi N 
Published: September 2023

Abstract

BACKGROUND
Leptomeningeal metastasis (LM) is a life-threatening and quickly advancing complication in patients with solid cancer. Reliable diagnosis is challenging. CSF cytology remains the standard diagnostic test for LM, though the sensitivity has been reportedly at un-satisfactory levels ranging 40 to 60% in the literature. We evaluated the diagnostic accuracy of CSF liquid biopsy and advanced magnetic resonance imaging (MRI) for detecting LM in patients with solid cancers.

MATERIAL AND METHODS
A systematic search was conducted to identify all published diagnostic accuracy studies on CSF liquid biopsies and MRI on electronic databases with registration for PROSPERO. Articles were selected based on pre-defined criteria following the PRISMA 2020 statement. Assessment of Risk of Bias (ROB) was based on QUADAS 2.

RESULTS
The search yielded 3790 citations to screen between January 2000 to March 2022. Ten studies with 668 patients were included in the final analysis: seven studies of circulating tumor cells (CTC), five studies of MRI, and two studies of cell-free tumor DNA (ctDNA). The pooled prevalence of LM was 50.9% (340/668). The sensitivity was calculated presenting synthetic results as follows: CTC, 87.0% [95% CI: 77.9-92.6]; ctDNA, 97.9% [19.3-100]; MRI 59.4% [60.7-76.9]; cytology, 71.9% [54.7-82.9].The synthesized specificity was as follows: CTC, 93.8% [86.9-97.2]; ctDNA, 89.0% [25.3-99.5]; MRI 97.6% [77.3-99.8]. The diagnostic odds ratio was 100.6 (29.38-344.09) for CTC and 93.3 (88.42-1034.05) for MRI. ROB assessment showed high risk sources in domains of patient selection and index test.

CONCLUSION
his study showed a better sensitivity of CSF cytology than the reports in the literature. Novel CSF liquid biopsies had sufficient sensitivities, and advanced MRI had a high specificity. Cytology and the new diagnostic methods are complementary and may offer early diagnosis and improved diagnostic accuracy for LM in patients with solid cancers. Further research is required to specify the threshold values and to construct standards of biomarker-driven and less invasive approach for individual cancers, and they would facilitate clinical trials for LM in the era of targeted therapy.
P16.08.A SINGLE-CELL MAPPING OF LEPTOMENINGEAL DISEASE IN GLIOBLASTOMAS
Authors: Sankowski R , Dalmau Gasull A , Khavaran A , Cahueau J , Prinz M 
Published: September 2023

Abstract

BACKGROUND
The leading edge of glioblastomas is characterized by the crowding of neoplastic cells around neurons and inside the perivascular space, a phenomenon known as satellitosis. Recent research has focused on the interaction between glioblastoma cells and neuronal networks, but the specific cells contributing to perivascular satellitosis have not been comprehensively studied.

MATERIAL AND METHODS
To address this gap, we conducted single-nucleus RNA sequencing on glioblastoma samples, dissecting the leptomeninges and tumor core from freshly resected tissue. As the brain parenchyma and perivascular space cannot be easily separated, we sampled tumor cells from the leptomeninges, the outer limit of the perivascular space. This approach harnesses the fact that the subarachnoid and perivascular spaces are directly connected. Thus, we could isolate perivascularly located tumor cells.

RESULTS
Our analyses revealed distinct transcriptional signatures between tumor cells from the leptomeninges and those from the tumor core. Tumor core-associated cells showed transcriptional programs related to hypoxia and collagen expression, while leptomeningeal tumor cells displayed programs related to axonal guidance, synaptic function, and extracellular matrix expression. Interestingly, there was significant overlap with previously published gene expression programs found in tumor cells integrating into neuronal circuits. Cell-cell interaction analysis identified interaction between tumor cells and the resident cell types of the perivascular space, including fibroblasts, perivascular macrophages and lymphocytes.

CONCLUSION
Our study provides a robust methodology for high-dimensional analysis of glioblastoma cells spreading through the perivascular space in human patients. Using this methodology we shed light on the biological processes of perivascular satellitosis and the spread of glioblastoma cells via pre-existing anatomical niches. Due to the distinct cellular composition of the perivascular space, the biology of satellitosis is distinct from the processes in the parenchyma. These findings have important implications for the development of targeted molecular therapies for glioblastomas.
P17.09.B REIRRADIATION AS A SALVAGE THERAPY FOR LOCAL GLIOBLASTOMA RECURRENCE
Authors: Lucas Calduch A , Macià Garau M , Villà Freixa S , Plans Ahicart G , Mesía Barroso C , Majós Torró C , Pons Escoda A , García Expósito N , Vilariño Quintela N , Mosteiro Lamas M , Velasco Fargas R , Simó Parra M , Cuadros Margarit R , Esteve Gómez A , Bruna Escuer J 
Published: September 2023

Abstract

BACKGROUND
There is a lack of successful strategies to treat glioblastoma (GB) recurrences. Reirradiation is one of them, but it only can be considered in a few patients with localized relapses. This review aims to analyse the role of reirradiation in this setting and the management difficulties associated with this strategy.

MATERIAL AND METHODS
We have retrospectively reviewed the outcome of GB patients treated with surgery and the standard Stupp regimen, that have received stereotactic radiotherapy (RT) at the time of a local in-field relapse in our centre, during the period from 2005 to 2022.

RESULTS
44 patients have been identified. The recurrence occurred at a median time of 9.7 months (m) after the end of the first RT. It was the first relapse in 89% of patients, and RT was given exclusively in 47.7% of cases. In the remaining patients, RT was combined with other treatments. The median maximum diameter of the relapse was 13.5 mm. Treatment schemes were mainly two: 35 Gy in 3.5 Gy daily fractions (52%) and 20 Gy in 5 Gy daily fractions (39%). Acute toxicity was mild, with worsening of previous neurological symptoms in only 15% of patients. After a median follow-up of 15 m, radiological responses were observed in 40% of patients, with a remarkable number of distant progressions in less than 6m (32.5%). The median time to progression was 4.8 m, being longer for patients treated at first relapse, females and with a Karnofsky index (KI) &gt;70. The diameter of the relapse showed a tendency to impact in time to progression, but no differences for RT dose, RT scheme or type of strategy (exclusive RT vs combined) have been detected. The median overall survival after reirradiation was 14.9 m. Related prognostic factors were KI &gt;70, size of the relapse (maximum diameter &lt;25 mm) and reirradiation given at first relapse. Radiological changes after reirradiation were commonly observed (47% of patients); differentiating them from true local progression was often difficult.

CONCLUSION
Reirradiation is a feasible and safe therapeutic option to treat localized GB relapses, able to control the disease for a few months in selected patients, especially those with first recurrences and small lesions. Further studies must be performed to improve the radiological evaluation in these patients and to determine the optimal combination with other treatment modalities.
P18.02.B RELATIONSHIP BETWEEN PROGESTERONE RECEPTOR EXPRESSION WITH HISTOPATHOLOGICAL GRADING IN MENINGIOMA
Authors: Rahmawati D , Retnani D , Holipah H , Damayanti Y 
Published: September 2023

Abstract

BACKGROUND
Meningioma is a group of mostly benign, slow-growing neoplasms that most likely derive from meningothelial cells of the arachnoid layer of the brain and spinal medulla. Meningiomas are found in one-third of all tumors in the central nervous system. Meningioma is three times more prevalent in women than in males, it is frequently related to hormones in women, particularly progesterone, which is considered to have the utmost impact on meningioma. Objective: this study aims at discovering the relationship between progesterone receptor expression and meningioma histopathological grading in Indonesia, especially at Saiful Anwar Hospital Malang. Method: This study employed a cross-sectional analytical observational research design. The study sample was a paraffin block of meningioma cases at The Anatomical Pathology laboratory of Saiful Anwar Hospital and The Medical Faculty of Brawijaya University, obtained from 2017 to 2020. The data were collected through histopathological preparations, immunohistochemical preparations, and immunohistochemical evaluation. The data analysis was performed by using SPSS version 20.

RESULTS
Most meningioma cases at Dr. Saiful Anwar Malang Hospital are women between 41 and 50 years. Then, it is located in the frontal part and acquired a grade of histopathology I and has a progesterone receptor expression score of 4. The chi-square test showed no significant association between progesterone receptor expression and histopathological grading of meningioma. At the same time, partial logistic regression tests showed no significant association between sex, age, and location with meningioma histopathological grading. In addition, multinomial logistic regression tests showed that the sex, age, and location did not significantly increase or decrease the risk (odds ratio) to the grade of meningioma histopathology.

CONCLUSION
This study showed no significant association between progesterone receptor expression and meningioma histopathological grading and no association between the sex, age, and location of lesions with meningioma histopathological grading and no significant increased risk of histopathological grading due to gender, age, or lesion location.
P18.03.A HYPOFRACTIONATION WITH OPTIMIZED STEREOTACTIC RADIOSURGERY PLANNING FOR SKULL BASE PERIOPTIC MENINGIOMAS
Authors: Cho Y , Yoon K , Lee D , Song S , Kim Y , Hong C , Kim J 
Published: September 2023

Abstract

BACKGROUND
Skull base perioptic meningiomas are challenging for stereotactic radiosurgery (SRS). The therapeutic window between tumor control and normal tissue complication is extremely narrow in these tumors, especially of large volume and/or in close proximity to the optic apparatus (OA). To minimize the risk of radiation toxicity, we optimized our SRS plans in terms of both steeper dose fall-off and dose-volume constraints for OA and delivered hypofractionation treatment.

MATERIAL AND METHODS
Thirty-one patients had been treated with hypofractionated SRS using the CyberKnife for perioptic meningiomas &gt; 10 cm3 in volume (median 18.9 cm3). Tumor locations were cavernous sinus (n=7), petroclival (n=6), and tentorial edge (n=6). Optimization in SRS planning was carried in two aspects: 1) for steeper dose fall-off, multiple virtual shells outside the target were introduced and appropriate dose limits (formulated from our own Gamma Knife data) were applied; and 2) to minimize the risk of optic neuropathy, dose-volume constraints for OA (from AAPM TG101) were applied. SRS was delivered in five daily fractions with a median cumulative dose 27.8 Gy.

RESULTS
With a median follow-up of 33 months, tumor control was achieved in 28 of 31 patients (90.3%). Treatment response on MRI included partial response (volume decrease &gt; 20%) in 17 patients, stable in 11, and progression (volume increase &gt; 20%) in 3. Neurological symptoms improved in 10 patients, unchanged in 20, and worsened in 1.

CONCLUSION
Our current results show a promising role of hypofractionated SRS with optimization in steeper dose fall-off and dose-volume constraints for OA for large-sized skull base perioptic megningiomas in terms of both tumor control and neurological outcomes.
P19.08.B INCREASED CORTICAL EXCITABILITY TO TRANSCRANIAL MAGNETIC STIMULATION CONTRIBUTE TO EPILEPTOGENESIS IN IDH1-MUTANT GLIOMAS
Authors: Naros G , Gorbachuk M , Machetanz K , Leao M T , Wang S , Honegger J , Tatagiba M 
Published: September 2023

Abstract

BACKGROUND
In-vitro studies indicate that gliomas with a mutation of the isocitrate dehydrogenase (IDH) increase neuronal excitability of the peritumoral cortex contributing to epileptogenesis in these patients. However, in-vivo evidence is missing. This study evaluates the electric characteristics of the brain-tumor-interface (BTI) relative to the IDH mutation status.

MATERIAL AND METHODS
To investigate peritumoral cortical excitability (CE), we applied 5258 pulses of transcranial magnetic stimulation (TMS) at the BTI of IDH-mutant (IDH-mt) and IDH-wildtype (IDH-wt) glial tumors in 39 patients. CE was assessed by the resting motor threshold (RMT) and the synchronized electromyographic (EMG) activity (i.e., event-related spectral perturbation, ERSP) after TMS. ERSP values were related to the IDH status, tumor grading, antiepileptic drug intake (AED) and the spatial relationship to the tumor borders.

RESULTS
There was not significant group difference in RMT. TMS to the BTI triggered an EMG synchronization decreasing linearly with the distance to the functional hotspot. In contrast, IDH-mt gliomas demonstrated an increased cortical output of the peritumoral brain tissue compared to IDH-wt gliomas. This effect was not attributable to AED intake or other histological and molecular characteristics. Notably, cortical hyperexcitability was detectable well beyond the tumor border.

CONCLUSION
s: This study provides in-vivo evidence of cortical hyperexcitability at the BTI of IDH-mt gliomas which could contribute to the epileptogenesis in these patients.
P20.03.A PREDICTING THE CLINICAL PHENOTYPE INNF2 RELATED SCHWANNOMATOSIS PATIENTS USING NEW GENETIC SCORES
Authors: Paterra R , Borghi A , Rosati N , Ibba M , Menicatti D , Moscatelli M , Vetrano I , Saini M , Nazzi V , Silvani A , Eoli M 
Published: September 2023

Abstract

BACKGROUND
NF2 related Schwannomatosis (NF2 -SCHW MIM # 101000) is a rare autosomal dominant familial cancer syndromes caused by mutations in the NF2 gene, mainly due to NF2 point mutations or intragenic deletions. NF2 patients. In 95% of patients, bilateral vestibular schwannomas are present, but NF2 -SCHW patients can develop other tumors and show ophthalmic and dermatological signs. Several studies established a genotype-phenotype correlations; the UK NF2 Reference Group proposed a Genetic Severity Score (GSS) based on the type and location of NF2 germline variant observed. Catasus et al. after validation of the score in a Spanish cohort suggested a new score based also on a functional assay of Merlin and its downstream pathways (FGSS). Recently Teranish et al. used targeted deep sequencing to predict functional prognosis in those patients.

MATERIAL AND
methods 70 patients (median age 40) were identified by scanning the electronic NF2-SCHW patient database at Fondazione IRCCS C. Besta, where the patients had undergone full neurological, ophthalmic, and audiological assessment. The median follow-up was 14 yrs. Clinical diagnosis was established following the Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis”. All patients underwent NF2, SMARCB1 and LZTR1 mutational screening by NGS and MPLA analysis using blood DNA or the tissue of two different tumors when available.NF2 gene germline pathogenic were found in 45 subjects (64%), in most cases NF2 point mutations, but in 4 cases and whole gene deletions was observed and in 2 a ring NF2 chromosome was identified, in four cases a mosaic NF2-SCH was identified and in 21 (30%) patients no pathogenic variant was found. We assessed NF2-SCHW clinical phenotype in relation to the UK GSS and FGSS to validate their use as clinical and research tools, despite the significant phenotypic variability observed.

RESULTS
The disease outcome differed significantly depending both on clinicaland genetic factors. Among these factors,” Age of symptom onset” “Truncating”, “Mosaic”, and “whole gene deletion” had the most significant effects on functional disability. Conclusion GSS and FGSS showed significant correlation with several measures, allowing stratification of patients with severe and mild disease but not with moderate phenotype. Furthermore, we provided evidence on correlation between whole NF2 deletion extent and phenotype severity. Large cohorts of NF2-SCHW patients are needed to identify more accurate scores, becoming useful tools for patient management.