bluuebunny/crossref_metadata_2025 huggingface dataset:
P11.78.A BIUXX
Authors: Pantalone M , Rahbar A , Söderberg-Naucler C , Stragliotto G
Published: September 2023

BACKGROUND

Glioblastoma (GBM) is a tumor with dismal prognosis and the definition of novel therapeutic targets is a pressing matter in neuro-oncology. Several groups reported the presence of Cytomegalovirus (CMV) in GBM. This virus establish a life-long infection in the host and is able to induce the hallmarks of cancer. Thus, antiviral therapy targeting CMV may represent a valid therapeutic option for patients with GBM. Over the last 15 years we treated more than 150 patients with GBM at Karolinska Universiy Hospital with the antiviral drug valganciclovir as an add-on to standard therapy. We compared retrospectively survival of these patients with contemporary controls with similar clinical and demographic characteristics treated only with standard therapy and found that patients receiving the antiviral seemed to survive longer. In addition to the direct oncomodulatory effect of CMV in GBM cells, its reactivation may affect negatively fragile individuals such as patients with GBM. Indeed patients serologically positive for CMV survives shorter time compared to serologically negative patients. Also Goerig et al. showed that CMV may also be reactivated during irradiation of the brain and cause life threating encephalitis in as many as 48% IgG positive patients with brain tumors. This was linked to encephalopathy and to early mortality risk. Thus, a successful therapeutic strategy would be to start antiviral therapy before or concomitantly radio-chemotherapy since antiviral drugs could prevent CMV reactivation before the virus would be able to cause neurologic deterioration.

MATERIAL AND METHODS

we analyzed by prospectively collected serological data (IgG and IgM) for CMV of 42 patients with GBM treated with valganciclovir (n=22) or placebo (n=20) in a double blind setting before, during and after radio-chemotherapy and at 6 and 12 months follow ups. We built contingency table and performed Fisher´s exact test.

RESULTS

At the end of radiation therapy, 5 of 12 (41.6%) IgG positive patients in the placebo group were also IgM positive, showing an active/recent infection, while none of the 16 patients were IgM positive in the valganciclovir treated group (p=0.0067). Three of the 5 patients with CMV reactivation in the placebo group experienced also neurological deterioration and developed an early recurrence at just 3 months while none developed early recurrence in VGCV group.

CONCLUSION

Valgancicovir prevented CMV reactivation in patients with GBM undergoing chemo-radiotherapy in a prospective, randomize setting. Prophylactic antiviral treatment may therefore be used to prevent encephalopathy and to early mortality risk linked to CMV reactivation. The clinical value of these results will need to be confirmed in larger studies. In this regard, a randomized trial evaluating anti-CMV therapy in 220 patients with GBM (the VIGAS 2, NCT04116411) is currently ongoing at our institution.
P11.79.B MULTICENTRE MULTI-COMPONENT DATA COLLECTION TO DEFINE NEW PREDICTORS OF RELAPSE IN HIGH GRADE GLIOMA
Authors: Mrissa L , Satragno C , Savanovic M , Karakaya Y , Yuste C , Veres C , Sambourg K , Dautun L , Hachemi T , Cifliku V , Le A , Meyer P , Jenny C , Jacob J , Bombezin Domino A , Maingon P , Bockel S , Dhermain F , Noël G , Deutsch E , Robert C
Published: September 2023

BACKGROUND

The aim of our multi-centric study is to evaluate the predictive relapse factors for high-grade glioma patients.

MATERIAL AND METHODS

We studied retrospectively multi-centric cohort of high-grade glioma patients, from 2009 to 2021 at three French medical centers. This data collection was carried out as part of national funding to promote the integration of AI tools into clinical oncology routine (AI.DReAM project). Clinical, pathological, genomic, and radiotherapy data, with MR images before treatment and at relapse, were collected and are being analyzed.Relapse patterns were separated into radiotherapy and radiological-related patterns. The latter were defined based on T1-gadolinium and FLAIR sequences. We distinguished local and disseminated disease. We then sub-categorized into residual growth, new local or distal lesion, multi-focal and multi-centric relapse.We underwent a uni-variate analysis with the Chi-squared test and a multivariate analysis with logistic regression to find multi-centric relapse-related factors.

RESULTS

Overall, 976 files were collected. In this preliminary analysis, we evaluated data from 203 patients. Out of the latter, 70% were male. 28% of the patients were aged more than 69 years. 43% of patients underwent Gross Tumor Resection, and 36% had only biopsy. Considering that of 20,7% of patients underwent Subtotal Tumor Resection, less than 10% had a resection of more than 90%.23% of patients had multi-focal disease and 16,7% had multi-centric disease. 54,6% had temporal disease making it the most frequent site, 26,6% of patients had a deep location. Ventricular contact was noted in 58% of the cases. MGMT methylation was noted in 34% of the patients.The median radiation dose received was 60Gy [33Gy-72Gy]. 98,5% of patients received Temozolomide with radiation and 80% continued it in the adjuvant setting.The median progression-free survival was 7 months, and the median overall survival was 17,6 months [3 to 92 months].The univariate analysis showed a correlation between multi-centric or bilateral initial disease and multicentric relapse pattern (p=0.015 and p=0.012 respectively). The multivariate analysis showed no correlation between our data and the multi-centric relapse.

CONCLUSION

The preliminary results of our study did not find an association between the analyzed data and the multi-centric relapse pattern.The challenge set is ambitious, as there are no studies yet that identify the factors associated with the multi-centric relapse pattern.Further analyses, currently in progress, are needed for the cohort of 976 patients, taking into account disease and radiotherapy volumes. The final results will be presented at the congress
P11.81.B PRELIMINARY RESULTS FROM A RETROSPECTIVE STUDY OF AWAKE CRANIOTOMIES WITH INTRAOPERATIVE MAPPING IN YOUNG ADULTS WITH GLIOMA
Authors: Kønig A B , Engelmann C M , Skjøth-Rasmussen J
Published: September 2023

BACKGROUND

Awake craniotomy with intraoperative mapping (ACWM) has been proven beneficial in achieving maximal resection of gliomas in eloquent brain areas while preserving neurological function, thus maintaining onco-functional balance. The present study aimed to describe the intraoperative symptoms not related to resection induced deficits in young adult glioma patients during ACWM.

METHODS

A retrospective, descriptive study of young adults (18-39 years of age) with glioma operated with ACWM in Copenhagen between 2016 and 2022. Patients were identified using the hospital operation booking system cross-referenced with the patient coding system. All data was available in and extracted from the Epic Systems healthcare software used at the hospital.

RESULTS

So far 37 patients with glioma (median age 31 years, range 21-39 years; 51% females; 78% high-grade gliomas) have been included, constituting 46 planned ACWMs. Most patients (95%) reported some level of intraoperative pain and/or headache with 27% receiving supplemental local anesthetics and 63% receiving supplemental fentanyl or fentanyl analogues during the awake phase. The median for the immediate postoperative Numeric Pain Rating Scale was 1, range 0-7. Intraoperative non-localization specific symptoms included shivering (41%), fatigue (22%), nausea/vomiting (17%), emotionally overwhelm (15%), anxiety (5%) and postoperative vasovagal syncope (5%). Focal seizures were reported in 24% of patients while 1 patient was untimely converted to general anesthesia due to non-convulsive status epilepticus. Operations were terminated due to completed macro-radical resection (32%), reaching the functional limit of resection (63%) and severe fatigue (5%).

CONCLUSION

Our results represent the practice of a single institution and comply well with previous literature in terms of symptomatic complications not related to resection induced deficits. These symptoms are predominantly simple to manage without the need for untimely termination of surgery. Awake craniotomy with mapping is deemed well-tolerated by young adults and is considered beneficial in optimizing the onco-functional balance of selected glioma patients.
P12.11.B THE BIOLOGICAL CHARACTERISTICS OF HUMAN GLIOBLASTOMA ASSOCIATED MESENCHYMAL STEM CELLS
Authors: Yu Y , Wang J , Chen Z
Published: September 2023

BACKGROUND

Mesenchymal stem cells (MSCs) have been identified existing in the tumor microenvironment (TME) as one of the important stromal cells and can be isolated from various tissues. Recently, it has been reported that tumor-associated MSCs (TA-MSCs) are involved in tumorigenesis. Experimental studies revealed MSCs in glioblastoma progress with numerous controversies. The aim of this study was to determine the characteristics and clarify functions of MSCs in the glioblastoma microenvironment.

MATERIAL AND METHODS

Herein, 32 surgical specimens from patients with high-grade glioma were collected for primary culture of glioma mesenchymal stem cells (GMSCs). After being cultured for 3 passages, the surface antigens of GMSCs were identified by flow cytometry and the trilineage differentiation ability was determined in vitro. The related gene expression on RNA and protein levels was detected by PCR and flow cytometry. Proliferation, cell cycle, migration and invasion assays were used to make sure the characteristics of GMSCs. In addition, the effects of GMSCs on glioma cells were detected both in vitro and in vivo.

RESULTS

We observed that GMSCs showed a typical spindle-like shape and multipotency in vitro, similar to MSCs derived from bone marrow (BMSCs). GMSCs were strongly positive for the mesenchymal markers, especially CD90(Thy-1), while the expression amount for CD44, SOX2 and Nucleostemin were consistent among BMSCs, glioma cell line and primary tumor cells. Additionally, the results of proliferation, migration and invasion assays indicated GMSCs was a group of normal stem cells. We also demonstrated that GMSCs could promote GBM malignant progression by enhancing the migrative ability of tumor cells.

CONCLUSION

We successfully isolated and identified GMSCs from glioblastoma primary culture. The results verified the characteristics of GMSCs were similar to BMSCs, but different from glioma cells. Taken together, MSCs exist in the glioblastoma tumor microenvironment and they may play a crucial role in tumor initiation and invasive growth, which might serve as a potential target for cancer therapy.
P13.08.A JAKOB V. E. GERSTL, MBBS
Authors: Gerstl J V E , von Grothusen C A G , Kilgallon J L , Lindberg R , Onnela J , Smith T R
Published: September 2023

BACKGROUND

Pituitary adenomas are benign neoplasms which can have a profound impact on quality of life. In-situ assessments of patient quality of life with pituitary adenomas and recovery from surgery are limited; existing patient reported outcome measures are, moreover, biased by patient recollection. Smartphone-based digital phenotyping may provide a means of monitoring patient recovery and quality of life at a more granular and accurate level.

MATERIALS AND METHODS

Patients with pituitary adenomas were enrolled during preoperative clinic visits. Included patients installed the Beiwe application, which passively collected GPS data during patient follow-up. Dates of significant clinical events were recorded to assess how they affected mobility. Using a LOESS regression line, aggregate trends amongst patients who underwent transsphenoidal resection were established and compared to baseline values from preoperative patients awaiting surgery and non-operative controls.

RESULTS

As part of a still ongoing study, 35 Patients with pituitary adenomas were enrolled between October 2022 and February 2023. Of these, 13 underwent transsphenoidal resection, the remaining 22 patients were either waiting for surgery and/or served as non-operative controls. Patients undergoing transsphenoidal resection of pituitary adenomas spent more time at home, spent less time walking, walked fewer steps and traveled shorter distances away from home compared following surgery compared to baseline preoperative data and non-operative controls.

CONCLUSION

The authors were able to generate initial digital phenotypes for a cohort of pituitary patients based on passively collected smartphone GPS data; the authors also hope that these initial data may help in the establishment of an in-situ tool to monitor recovery following surgery for pituitary adenoma. It is the authors’ contention that such preoperative mobility metrics may be further utilized to predict postoperative outcomes following surgery which has been demonstrated in the general surgery setting. In the case of pituitary disease, these include postoperative CSF leak, infection, dysnatremia and hospital length of stay.
P13.10.A PREDICTING SURVIVAL OF GLIOBLASTOMAAFTER RADIOTHERAPY USING DEEP LEARNING AND NEUROIMAGING IN A MULTI-CENTRE COHORT
Authors: Chelliah A , Wood D A , Canas L S , Shuaib H , Linares C , Bassiouny A , Luis A , Young T , Roman A , Dragos C , MacDonald M , Lau Y H , Currie S , Fatania K , Frood R , Mathew R , Brock J , Chandy E , Tenant S , Rowland-Hill C , Williams M , Wang Q , Beaumont E , Lam T , Welsh L , Foweraker K , Lewis J , Thust S , Wastling S , Glendenning J , Brazil L , Swampillai A , Ourselin S , Modat M , Booth T C
Published: September 2023

BACKGROUND

Glioblastoma is an aggressive brain tumour routinely monitored with MRI. However, the potential to use imaging as a prognostic biomarker predicting survival after treatment starts is unclear. This study aims to predict survival within eight months of completing radiotherapy from MRIs using deep learning.

MATERIAL AND METHODS

The dataset consists of 206 prospective and retrospective consecutive patients with glioblastoma (WHO 2021) across 11 UK centres (short-term survival: N=64; 31.1%). Models were trained/validated on N=158 (76.7%) retrospective patients (3 centres). Two holdout sets were sampled: retrospective test set (N=19); and external, prospective test set (N=29; 8 separate centres). Dense convolutional neural networks were developed with separate branches for T1c-w and T2-w MR sequences; a third branch concatenates outputs from those branches to predict survival. Dense blocks used pretrained weights for an abnormality detection model. A semi-supervised approach was implemented; patients without known outcomes were added with pseudo-labels during training. Parameter tuning included the number of updated blocks, linear layer sizes, and weighting of pseudo-labels. Imaging models were compared to counterparts that apply non-imaging variables (demographics, MGMT status/%, treatment). Logistic regression, support vector classifier, and decision tree models were fit on non-imaging features alone with feature selection and mean/mode imputation. Combined imaging/non-imaging networks were developed that added a branch for non-imaging inputs.

RESULTS

The current best-performing imaging model used MR sequences alone (validation weighted-ROC=0.80, 95% CI=0.75-0.84; balanced accuracy=0.70, 95% CI=0.55-0.85). Among non-imaging models, the logistic regression model with feature selection performed best (validation weighted-ROC=0.59, 95% CI=0.56-0.63; balanced accuracy=0.59, 95% CI=0.56-0.63). Combined model development is ongoing.

CONCLUSION

This is the first known model applying deep learning to MRIs from multiple centres to distinguish patients with failure to respond to chemoradiotherapy, and those who survive the subsequent treatment window. Based on initial results, image-based models performed best at predicting survival. Such models could be used across centres to suggest closer monitoring and trial targeting of patients with expected short-term survival compared to treatment response.
P14.01.A LIQUID BIOPSY OF GLIOMA-RELATED GENES USING A NOVEL AMPLIFICATION TECHNIQUE
Authors: Adachi J , Suzuki T , Nishikawa R
Published: September 2023

BACKGROUND

In the pathological classification of brain tumors, newly revised in 2021, molecular genetic analysis of gliomas has become more important for diagnosis and understanding of the pathogenesis of gliomas. Gliomas are prone to recurrence and malignant progression, and collecting tumor tissue during every genetic analysis is highly invasive. Therefore, techniques have been developed to analyze tumor-derived circulating cell-free DNA (ccfDNA) in the cerebrospinal fluid as a substitute for tissue collection. However, the amount of ccfDNA derived from the cerebrospinal fluid is extremely small and the number of cases for whom genetic analysis is possible is currently limited. In this study, we attempted to establish a novel method for the integrated analysis of glioma-related genes by in vitro amplification of cerebrospinal fluid-derived ccfDNA from glioma patients and a highly sensitive assay. Methods : Tumor-derived ccfDNA was extracted and purified from 1 ml of cerebrospinal fluid obtained by lumbar puncture using the Maxwell RSC instrument in five glioma cases. Hot spots of mutations in IDH1 and H3F3A genes were analyzed by high resolution melting (HRM), TERT mutation by droplet digital PCR, MGMT promoter methylation by methylation-specific HRM, and chromosome 1p/19q loss by multiplex ligation-dependent probe amplification. For samples in which the amount of ccfDNA was too small to analyze, DNA was amplified approximately 500-fold by DNA polymerase using the GenomiPhi kit and analyzed by the same assay method. Results and

CONCLUSION

s : Although two of the five cases required amplification with the GenomiPhi kit, it was possible to analyze all cases for glioma-related genes as described above. Although the amount of ccfDNA obtained from low-grade gliomas and gliomas that are not in contact with the ventricles or subarachnoid space is small, this amplification method may increase the possibility of liquid biopsy using cerebrospinal fluid in gliomas.
P14.04.B CIRCULATING TUMOR CELLS AS A NON-INVASIVE GLIOBLASTOMA DIAGNOSTIC AND PROGNOSTIC TOOL
Authors: Lessi F , Morelli M , Franceschi S , Aretini P , Ferri G , Menicagli M , Pasqualetti F , Gambacciani C , Pieri F , Grimod G , Di Stefano A , Santonocito O S , Mazzanti C M
Published: September 2023

BACKGROUND

Circulating tumor cells (CTCs) detection in the blood of glioblastoma (GBM) patients can facilitate the assessment of tumoral information without the need for invasive approaches. Our aim is to use GBM CTCs to obtain knowledge about the tumor and improve the current GBM diagnosis and prognosis.

MATERIAL AND METHODS

We collected primary, matched recurrent GBM and healthy controls blood samples. CTCs were enriched from whole blood controls with Parsortix Cell Separation System and analysed on DEPArray system. CTCs were recognized by immunofluorescence with GFAP.The CTCs have been counted for all the samples. Copy Number Aberrations (CNAs) analysis was performed on CTCs. To compare CTCs genetic background with the same patient’s primary and recurrence tissues, whole exome sequencing (WES) was realized on tumor tissues. Recurrence of GBM was diagnosed according to the RANO criteria +/-path proven second surgery +/- FET PET imaging proven. We assessed tumor volume of contrast enhanced (CE) (as a surrogate marker of BBB damage) and nCE at the time of the CTCs collection by seminautomatic segmentation on ITKsnap software.

RESULTS

We found CTCs in GBM patients newly diagnosed at the time of first surgery (86%) but also at recurrence (100 %). Cell counting demonstrated in both primary and recurrent GBM patients’ blood a statistically significantly higher number of CTCs compared to healthy controls (average of cells number 15.8 vs 2.3). Interestingly, recurrent GBM patients showed more CTCs than primary GBM patients (average 9 vs 22.7). CNAs analysis confirmed the tumor status of the selected CTCs. Some of GBM classical mutations (in HTERT promoter, BRAF, PTEN, PI3KCA and EGFR genes) have been searched both in the tumor tissues and in the CTCs. HTERT was found mutated in CTCs of one patient’s tumor carrying mutant HTERT and wild type IDH1/2. We also included three IDH1 mutant glioma patients and one BRAFV600E mutant GBM patient in order to track these in CTCs. We did not find BRAF mutations in CTCs isolated from one recurrent BRAFV600E GBM patient with a very low allele frequency in the recurrent tumor (<1%).

CONCLUSION

We found CTCs in GBM patients newly diagnosed and at recurrence. Several factors may affect CTCs release such as tumor volume, CE and the CTCs genetic

BACKGROUND

, which seems to be heterogeneous. CTCs detection by our methodology could be helpful in the clinical setting for diagnostic, prognostic and theranostic purposes and for patients monitoring. Prospective study is ongoing in order to assess CTCs variations on and after therapy. This study, first investigated the genetic heterogeneity of CTCs released in the blood flow from the parental tumor.
P14.07.B CELL-FREE DNA IN LONGITUDINALLY-ACQUIRED CEREBROSPINAL FLUID FOR DISEASE MONITORING
Authors: Riviere-Cazaux C , Mo W , Dong X , Luo S , Wang A , Du P , Ghadimi K , Warrington A , Burns T
Published: September 2023

BACKGROUND

Few methods exist via which to assess treatment response with high fidelity in gliomas. Cell-free DNA (cfDNA) is of growing interest as a liquid biomarker in plasma and CSF and has been used in other cancer types to optimize therapeutic regimens for individual patients. While CSF has previously been used as a source of cfDNA for gliomas, it remains unknown how cfDNA abundance and sequencing change throughout treatment and inevitable recurrence. To that end, we leveraged our growing biobank of longitudinal CSF specimens, acquired via CSF access devices, to determine the potential utility of CSF cfDNA as a monitoring tool for treatment response in patients with gliomas.

MATERIAL AND METHODS

Longitudinal CSF specimens were acquired via Ommaya reservoirs (NCT04692337) or ventriculoperitoneal shunts (NCT04692324) in patients with brain tumors, including gliomas. cfDNA was extracted from 1-5 mL of CSF based on available sample volumes and quantified via Qubit. Next-Generation sequencing (PredicineCARE) or low-pass whole genome sequencing (LPWGS) was performed by Predicine, Inc based on the amount of cfDNA available.

RESULTS

CSF acquired prior to versus after resection demonstrated an increase in quantified cfDNA (2.97x, range: 1.58-5.26x), consistent with the impact of increased parenchymal disruption and closer contact with CSF. Thereafter, CSF cfDNA continued to decrease throughout chemoradiation and adjuvant treatment and increased at recurrence, including in patients co-enrolled in immunotherapy trials for IL-7 agonists and pembrolizumab. Interestingly, copy number burden (CNB) increased by the time of recurrence in three patients with known disease progression, and continued to decrease throughout immunotherapy treatment in one patient despite concerns of pseudoprogression. In one patient with a hypermutated glioblastoma, CSF cfDNA revealed over 59 genomic alterations, including MAP2K1, KIT, and PDGFRA, and over 100 more variants of unknown significance, each of which had been detected in sequencing of the tissue acquired at resection and subsequently decreased with chemoradiation. In another patient with a known progressing EGFR-amplified GBM, over 200 new variants were identified by the patient’s final sample and EGFR copy number increased from 2 to over 30.

CONCLUSION

Analysis of cfDNA over a patient’s disease course, including resection and treatment with standard-of-care and experimental therapies, may be of use for disease monitoring and treatment response. Further work is needed to evaluate these findings in a larger cohort of patients and to determine the sensitivity of changes in mutations, CNB, and cfDNA quantity for glioma disease burden.
P14.12.A PLASMA CFDNA LIQUID BIOPSY IN THE FOLLOW-UP OF HIGH-GRADE GLIOMAS
Authors: Pieri V , Berzero G , Paterra R , D'Alessandris Q , Sferruzza G , Pompeo E , Roncelli F , Nocera G , Bailo M , Barzaghi L , Castellano A , Falini A , Mortini P , Galli R , Finocchiaro G , Filippi M
Published: September 2023

BACKGROUND

As highlighted by the 2021 WHO classification of brain tumors, molecular characterization of gliomas is now critical to complement histopathological evaluation. However, intratumor heterogeneity may lead to surgical specimens not being fully representative of the whole tumor. Moreover, given the invasiveness of surgery, tissue analyses are not repeatable over time, thus limiting the possibility to monitor the response to therapies. In this context, we investigated the potential value of plasmatic cell-free DNA (PcfDNA) as a non-invasive ‘liquid biopsy’ marker of disease evolution.

MATERIAL AND METHODS

Patients’ blood was collected at 4 time points (TP), in parallel to clinical follow-up. A reproducible pipeline was optimized for blood withdrawal, centrifugation, plasma storage, cfDNA extraction from plasma by QIAamp MinElute ccfDNA Midi Kit (Quiagen) and cfDNA fluorometric quantification by Qubit (Thermo Fisher Scientific). MRI volumes were segmented in T1+contrast and T2-FLAIR sequences.

RESULTS

Fifty-four high-grade glioma patients and 14 healthy controls were enrolled. Blood samples were collected from all 54 patients at radiological diagnosis before surgery (TP0), from 33 patients after surgery (TP1), from 21 patients after radio-chemotherapy(TP2), from 10 patients at the first radiological progression (TP3). At T0, a significantly higher concentration of PcfDNA was detected in patients than in controls. IDH-wild-type gliomas showed a trend toward higher PcfDNA when compared with IDH-mutant gliomas. Digital-droplet PCR, performed at T0on PcfDNA of 4 patients with IDH-mutations in tumor tissues, identified the same IDH1-R132H mutation in all cases. When PcfDNA at TP0 was compared to that at TP1 of the same patient (n=33), there was a significant reduction of plasmatic cfDNA after surgery, mirroring the extensive tumor-resection shown by MRI. Finally, PcfDNA was evaluated in 10 patients until their radiological progression. Interestingly, PcfDNA levels not only followed the same trend of the volumes of T2-FLAIR hyperintensities and T1 contrast-enhancements, but were also mirrored by the evolution of KPS and NANO scores.

CONCLUSION

Preliminary results suggest that PcfDNA content may be an informative tool to complement MRI during the follow-up of high-grade gliomas.
P15.01.A FET PET SENSITIVITY IN PRIMARY BRAIN TUMORS ACCORDING TO CNS WHO 2021: VALUE AND PITFALLS IN PRESURGICAL IMPLEMENTATION
Authors: Oster C , Blau T , Keyvani K , Schmidt T , Lazaridis L , Sure U , Kleinschnitz C , Scheffler B , Herrmann K , Barbato F , Kebir S , Glas M
Published: September 2023

BACKGROUND

FET PET imaging has emerged as a valuable tool in the characterization of unclear brain lesions that cannot be clearly diagnosed with conventional diagnostic

METHODS

.In 2021,the Central Nervous System(CNS) World Health Organization(WHO) introduced significant changes in the classification of CNS tumors.Notably,under the new classification,certain cases of glioma may be reclassified as glioblastoma.Unfortunately,a subset of gliomas,as defined by the 2016 WHO classification,may exhibit no detectable FET uptake and lack contrast enhancement on MRI,which can lead to underestimation of such tumors and potentially result in inappropriate treatment decisions.

MATERIAL AND METHODS

In this study,we conducted a retrospective analysis of all patients who underwent FET PET imaging of the brain between 2017 and 2021,prior to their first surgical brain intervention.We obtained the results from presurgical MRI scans and categorized the lesions based on whether they exhibited contrast media enhancement or not,in addition to the postsurgical histopathologic diagnosis.Our analysis focused on identifying the number of cases in which the diagnosis of malignancy was underestimated in the context of the WHO 2016 classification.To further investigate these cases,we conducted NGS and 850k-analysis to reclassify the results in accordance with the new classification.Finally,we assessed the number of cases that were underestimated using the new classification criteria.

RESULTS

After enrolling 85 patients,our study found that according to the 2016 classification,preoperative imaging underestimated malignancy in 14 cases (16%) where histopathological analysis revealed high-grade malignant brain tumors.In 32 cases (27%), the preoperative imaging correctly suggested a malignant tumor,which was later confirmed by histopathological analysis after surgery.Additionally,22 cases were suggested to be low grade or benign,which was confirmed by postsurgical tissue analysis. Further analysis revealed that some patients diagnosed with low-grade glioma according to the WHO 2016 classification actually had molecular glioblastomas after reclassification.The final results of this reclassification after the CNS WHO 2021 will be presented at the annual meeting.

CONCLUSION

The findings of this study suggest that presurgical brain imaging,as per the WHO 2016 classification,may underestimate the malignancy of unclear brain lesions in up to 16% of cases.Our initial analysis also indicates that this underestimation may be more prevalent when using the new WHO CNS classification from 2021.Therefore,caution is advised when recommending non-surgical follow-ups in such cases, as it may lead to incorrect treatment decisions and worse patient outcomes.
P16.04.A THE PROGNOSTIC ROLE OF VENTRICULAR SIZE AND ITS DYNAMICS IN PATIENTS WITH LEPTOMENINGEAL METASTASIS FROM SOLID TUMORS
Authors: Le Rhun E , Devos P , Seystahl K , Jongen J , Gramatzki D , Roth P , van den Bent M J , Regli L , Brandsma D , Weller M
Published: September 2023

BACKGROUND

Hydrocephalus is a common radiological sign in patients with leptomeningeal metastasis (LM) from solid tumors and can be assessed using the Evans index (EI) with high interrater agreement. Here we explored the prognostic value of ventricular size at diagnosis and during the disease course of LM.

METHODS

We assembled a cohort of 113 adult patients with a diagnosis of LM from solid extra-CNS tumors and explored the prognostic association of ventricular size assessed by the EI at diagnosis, of its modification between diagnosis and evaluation at first follow-up (>21 days after diagnosis), and at first progression.

RESULTS

Median age was 58.2 years (interquartile range (IQR) 46.1-65.7), 41 patients (36%) were male, the most frequent cancers were lung cancer (n=39, 35%), breast cancer (n=36, 32%) and melanoma (n=23, 20%). The median EI at baseline was 0.28 (IQR 0.26-0.31) and the EI value was 0.27 or more in 67 patients (59%) and 0.30 or more in 37 patients (33%). Among patients with MRI follow-up, the EI increased by 0.01 or more in 19 patients (40%), including 9 of 29 patients (30%) and 10 of 17 patients (59%), respectively, without and with LM progression at first follow-up. At LM progression, an increase of EI of 0.01 or more was noted in 18 of 34 patients (53%). The median overall survival was 2.9 months (IQR 1-7.2). Patients with a baseline EI of 0.26 or less had a longer survival than those with an EI of 0.27 or more (5.3 months, IQR 2.4-10.8, versus 1.3 months, IQR 0.6-4.1) (p=0.006). Median survival was 3.7 months (IQR 1.4-8.3) with an EI of 0.29 or less versus 1.8 months (IQR 0.8-4.1) with an EI of 0.30 or more (p=0.109). Among patients with follow-up scans available, median overall survival was 9.7 months (IQR 5.6-21.4) for patients with stable or decreased EI at first follow-up as opposed to 6.4 months (IQR 3.2-10.5) for those with an increase in the EI (p=0.292).

CONCLUSION

The EI at baseline is prognostic in LM. An increase of EI during the follow-up is associated with inferior LM-progression-free survival. An independent validation cohort with larger sample size and evaluation of confounding factors will help to better define the clinical utility of EI assessments in LM.
P16.06.A INCIDENCE, FOLLOW UP AND OUTCOME IN INCIDENTAL MENINGIOMA IN THE GOTHENBURG REGION - WHAT HAS HAPPENED IN 10 YEARS?
Authors: Näslund O , Strand P S , Solheim O , Al Masri M , Rapi O , Thurin E , Jakola A S
Published: September 2023

BACKGROUND

Meningiomas constitute a large portion of brain tumors, with an often indolent natural course of disease. There a now more asymptomatic meningiomas diagnosed each year as compared to their symptomatic counterparts. With brain imaging widely available, increased findings of incidental meningiomas have emerged. There are many unique challenges to the management of incidental meningioma, where if no symptoms are present, there is a lack of evidence-based guidelines for follow-up and treatment. The aim of this study was to map the use of brain scanning, and the subsequent findings of presumed incidental meningioma between the years 2008-2009 and 2018-2019, and to study differences in follow-up, treatment, and outcome among these patients.

MATERIAL AND METHODS

Records of performed CT and MRI of the brain at the radiological departments at three hospital sites were retrospectively reviewed in search for patients with presumed incidental meningioma. Their medical health records were the used to study the natural course and clinical handling of these patients.

RESULTS

An almost identical number of patients underwent brain scanning at our three hospital sites during the two time periods (n=22 259 vs. 22 013). In 2018-2019, 25% more incidental meningiomas were diagnosed as compared to 2008-2009 (n=161 vs. 129). In the later years, patients had a higher median age (79 years vs. 73 years, p=0.03) and more often underwent brain imaging due to non-metastatic cancer (n=38 vs. 15, p=0.009). There were no differences in the indication for diagnostic scanning, nor management decision at time of diagnosis.

CONCLUSION

We could not show an increase in patients undergoing scanning of the brain between the two time periods studied, but with passing time it has become more common to frequently scan the brain of elder individuals, and individuals with cancer without metastases, perhaps due to improved treatment options for patients if metastatic disease was found. When an incidental meningioma was subsequently found, no differences could be seen in the clinical handling of the patients in terms of treatment or follow-up.
P16.09.B NEUROGENIC DYSPHAGIA IN MENINGEOSIS NEOPLASTICA PATIENTS
Authors: Lapa S , Harborth E , Manß C , Ronellenfitsch M , Steinbach J , Urban H
Published: September 2023

BACKGROUND

Meningeosis neoplastica (MN) occurs in 5-10 % of all cancers and is characterized by diffuse seeding of tumor cells in the cerebrospinal fluid (CSF) and meninges. Common clinical symptoms suggestive of MN include headache, cranial nerve (CN) deficits, psychiatric symptoms as well as paresthesia. Neurogenic dysphagia (ND) has been suggested a rare MN symptom resulting from affection of CN IX and X. The aim of this work was to investigate frequency, severity and pattern of malfunction of ND due to MN as well as to assess its impact on the rate of pneumonia and overall survival.

MATERIAL AND METHODS

The database of the Institute of Neurooncology of the University Hospital Frankfurt was screened for patients with MN diagnosed between March 2009 and July 2021 who received a systematic dysphagia assessment (DA). DA comprised a standardized clinical swallowing examination as well as an additional fiber optic endoscopic evaluation of the swallowing act (FEES) in case of suspected aspiration. Severity of dysphagia and extent of oral impairment were systematically recorded. In addition to demographics, clinical diagnoses, underlying cancer and treatment, information on radiological imaging including presence of contrast-enhancing lesions was collected.

RESULTS

A total of 262 patients with a diagnosis of MN were detected, 69 of whom (52 % women, mean age 61 ± 14 years) were included for further analysis. Underlying cancers included lung cancer (16 cases, 23 %), breast cancer (15, 22 %), as well as lymphoma and melanoma (each 7 cases, 10%). The remaining 24 patients suffered from cancer entities (ovarian cancer, gastrointestinal tumors or cancers of unknown primary). 46 patients (66.6 %) were diagnosed with ND, 15 of these patients required a feeding tube (FOIS 1-3). Dysphagic patients had an increased risk of pneumonia (p<0.001) and a shorter survival time compared to non-dysphagic patients (p=0.003). Affection of the cranial nerves affected CN V (n=6), CN VII (n=22), CN IX (n=21), CN X (n=7) and CN XII (n=12). There was no significant correlation between the presence of an ND and the above-mentioned cranial nerve deficits.

CONCLUSION

The results of this study show that ND is a common symptom in patients with MN and can also occur independently of paresis of CN IX and X. In addition, the presence of ND is associated with a higher rate of pneumonia and a shorter survival time. Therefore, patients with suspected or confirmed MN should receive a systematic dysphagia assessment. In addition, the presence of MN should also be considered in the differential diagnosis of unclear neurogenic dysphagia.
P17.01.A THE VALUE OF ETOPOSIDE FOR RECURRENT GLIOMA
Authors: van der Meulen M , Chahal M , Mason W P
Published: September 2023

BACKGROUND

There is currently no consensus on how best to treat diffuse glioma in adults at recurrence. Etoposide in combination with carboplatin and/or bevacizumab has been evaluated in recurrent glioma with modest efficacy. This retrospective study investigates the efficacy of etoposide monotherapy in adults with recurrent diffuse glioma.

MATERIAL AND METHODS

In this single center retrospective series, all adult patients with radiographically proven multiply recurrent diffuse glioma (WHO grade 2-4) treated with etoposide between 2016 and 2020 were evaluated. Progression-free survival (PFS) and overall survival (OS) after initiating etoposide were calculated for the total group and for different histologic tumor types. In addition, toxicity was recorded after initiation of etoposide.

RESULTS

48 patients with a median age 43 (range 24-78) were included. Etoposide was given as 3rd line of treatment in 18 patients (37.5%) and as 4th or 5th line of treatment in 30 patients (62.5%). The majority were diagnosed with a glioblastoma, WHO grade 4 (27, 56.3%). The median PFS was 8.6 weeks (95% confidence interval [CI]: 8.3-8.9). The median OS of the total population was 4.0 months (95% CI: 2.4-5.6). Patients with an oligodendroglioma had the best OS (median 13 months), compared to astrocytoma and glioblastoma, but the difference was not statistically significant (p=0.152). Etoposide was stopped due to progression or toxicity. Only 1 patient had a grade 3 toxicity.

CONCLUSION

Etoposide is a well-tolerated chemotherapy in adult patients with recurrent diffuse glioma, but has limited efficacy in this cohort of multiply recurrent and heavily pretreated patients.
P18.01.A A MORPHOMETRIC ANALYSIS OF 40 DRY ASIAN SKULLS TO INVESTIGATE ANATOMICAL VARIABILITY IN THE SUPRASELLAR REGION AND ITS IMPLICATIONS IN MENINGIOMA SURGERY
Authors: Geldart J
Published: September 2023

INTRODUCTION

Meningiomas are the most common type of primary brain tumour and when symptomatic, are usually treated by surgical resection. Removing skull-base meningiomas is challenging and subtotal resection remains common, despite utilising the latest surgical

METHODS

. In the suprasellar region, surgery is particularly high risk and carries a 10-20% rate of postoperative visual impairment. This morphometric analysis of 40 dry skulls furthers our understanding of anatomical variability of 3 structures in the suprasellar region: the limbus sphenoidale (LS), prechiasmatic sulcus (PS) and optic strut (OS). Understanding suprasellar anatomical variability is vital for neurosurgeons operating within the region to reduce complication rates and in achieving gross total resection.

METHODS

Variants of the LS (A, B and C) are defined according to descriptions used from a previous study. Curved and straight lengths of the LS are measured using metal callipers and string. Between the three variants, statistical analysis is used to compare differences in lengths, and the ratio between their curved and straight length. PS angle, length and width are measured according to previous studies’ definitions. OS position is determined by measuring its distance from the LS and a drawn midline. Skulls are grouped using PS variables and OS position according to adapted classification systems used in previous studies.

RESULTS

Variants A, B and C of the LS exhibited incidences of 33.33%, 52.82% and 15.39%, respectively. Limbus ratio was significantly different (p<0.05) between variants. Average sulcal angle was 32 ± 13.3°, whilst sulcal type ranked in prevalence: narrow flat sulci (34.21%)> very narrow steep (28.95%)> very narrow flat (21.05%) > narrow steep (15.79%). 32.50% and 18.42% of struts exhibited notable differences in their distances from the midline and from the LS, respectively.

CONCLUSION

The present study improves our understanding of the prevalence of anatomical variants within the suprasellar region and has implications for meningioma surgery. The type C variant is an overhanging ridge, underneath which meningiomas could be hidden from a surgeon’s view during transcranial procedures. Only two studies have previously documented the type C variant, whose incidence in the present study (15.39%) is within the boundaries of previous research; patients with this variant might require removal of the landmark during surgery to achieve gross total resection. The PS displayed varying degrees of steepness, and skulls were on average steeper than previously documented populations. A considerable proportion of skulls exhibited notable differences in left and right OS position. Establishing PS morphology and OS position preoperatively might be helpful in reducing the risk of visual impairment in future operations through better understanding the course of the optic nerve.
P19.05.A THE NEURONAL CORRELATES OF BRAIN TUMOR ASSOCIATED SEIZURES IN HUMAN AND MOUSE PERITUMORAL CORTEX
Authors: Bolleboom A , Bouwen B L J , Dirven C M F , Vincent A J P E , Gao Z
Published: September 2023

BACKGROUND

The occurrence of seizures is the most common comorbidity in malignant brain tumors. Recent advancements in the field of cancer neuroscience indicate that seizures can potentially influence brain tumor progression through intricate neuron-glioma interactions in the peritumoral infiltrated cortex of glioma patients. Therefore, understanding not only the tumor processes but also the neuronal properties in the tumor microenvironment could provide key insights into the relationship between epilepsy and tumor progression. To investigate this, we conducted a study to characterize neuronal alterations in glioma infiltrated neocortex of both patients and a glioma mouse model.

MATERIAL AND METHODS

Infiltrated peritumoral cortex was obtained from both epileptic and non-epileptic patients undergoing brain tumor surgery. Ex vivo brain slices were prepared and single-cell electrophysiology was performed on peritumoral neurons. High grade gliomas were induced into compound LoxP-conditional mice via stereotactic viral injection in combination with serial electro-corticographic activity to monitor epileptogenesis.

RESULTS

Ex vivo recordings from infiltrated human peritumoral cortex revealed electrophysiological and morphological alterations in neocortical neurons of patients experiencing seizures. Using an inducible immunocompetent high-grade glioma mouse model, we tracked the progression of cortical epileptogenesis during tumor infiltration. We observed several spatial and temporal changes in the peritumoral cortex of glioma mice, including progressive glial reaction and gradual neuronal reduction. We also identified intrinsic and network alterations in the cortical neurons of glioma mouse model, consistent with the electrophysiological characteristics of human peritumoral cortex prior to seizure onset.

CONCLUSION

Overall, our study demonstrated dynamic electrophysiological and histological changes in human and mouse peritumoral cortex during the course of tumor progression and epileptogenesis. These findings provide important insights into brain tumor associated seizures and cast light on new therapeutical targets for treatments.
P20.01.A CLINICAL APPLICATION OF RELATIONSHIP BETWEEN GENETIC ALTERATION AND INTRAOPERATIVE FLUORESCENCE ACTIVITY OF 5-AMINOLEVULINIC ACID IN BRAIN METASTASIS OF NON-SMALL CELL LUNG CANCER
Authors: Jeong H Y , Seo W J , Kim H G , Kim S H , Nam T M , Jang J H , Kim K H , Kim S H , Kim Y Z
Published: September 2023

BACKGROUND

Distant metastasis into major organ is a major cause of death in cancer patients. Especially, metastasis to brain is known to duplicate the mortality of cancer patients because brain metastasis makes patients neurologically independent in daily activities. Despite surgical resection of brain metastasis is a core strategy for management, it is not possible for all brain metastasis due to eloquent location, multiple lesions, or clinical condition of patient. With advancement of technology in brain tumor surgery, fluorescence image, such as 5-aminolevulinic acid (5-ALA), can help detect the residual tumor during surgery. Recently, genetic alteration of cancer is additionally considered as prognostic factor with being added into traditional prognostic system, such as GPA scoring system. The primary objective of this study is to examine the fluorescence patterns of 5-ALA in brain metastasis surgery and investigate the results of genetic alteration in brain metastasis using next generation sequencing technique.

MATERIAL AND METHODS

Medical records of patients with brain metastasis of non-small cell lung cancer at our center from January 2017 to June 2022. Among them, the patients who were treated with surgical resection under 5-ALA fluorescence image and had NGS results were included in the analysis.

RESULTS

Total 72 patients were eligible for analysis. Mean follow-up duration was 12.36 months. Recurrence occurred in 28 (38.9%) patients and 46 (63.9%) patients succumbed to NSCLC. Mean recurrence-free survival (RFS) was 14.57 months and mean overall survival (OS) was 16.29 months. Strong fluorescence was obtained in 56 (77.8%) patients during surgery. In the NGS data of brain metastasis, genetic alteration of cell cycle regulation, DNA repair, tumorigenesis, proliferation, epigenetic regulation, and cancer immunology were detected in 73.6%, 44.4%, 56.9%, 66.7%, 30.6%, and 2.8%, respectively. In multivariate analysis, KPS, RPA class, extent of resection, modality of adjuvant treatment, genetic alteration of cell cycle regulation and cellular proliferation were associated with RFS. Additionally, age, KPS, status of NSCLC, RPA class, GPA score, modality of adjuvant treatment, genetic alteration of cell cycle regulation and cellular proliferation were associated with OS.

CONCLUSION

The presenting study suggested that microscopic complete resection with assist of fluorescence image could improve clinical outcome, and strong fluorescence image could reflect the genetic alteration of cell cycle regulation and cellular proliferation which are poor prognostic factors.