bluuebunny/crossref_metadata_2025 huggingface dataset:
P09.01.B 18-FET-PET ENHANCED DIAGNOSIS OF PSEUDOPROGRESSION IN GLIOBLASTOMA IS AN INDEPENDENT PROGNOSTIC FACTOR FOR OVERALL SURVIVAL
Authors: Schmidt T , Oezdemir Z , Oster C , Sure U , Hermann K , Stuschke M , Deuschl C , Kleinschnitz C , Müther M , Glas M , Kebir S
Published: October 2024

BACKGROUND

Detecting pseudoprogression (PSP) in glioblastoma during first-line treatment remains challenging and has significant clinical implications for patient management. The detection of PSP has been shown feasible using FET-PET. The prognostic impact of FET-PET diagnosed PSP on overall survival is still uncertain, as retrospective studies provide limited insights due to the substantial differences in the distribution of prognostic factors between TP and PSP groups. This study aims to address these uncertainties by leveraging advanced analysis techniques.

MATERIAL AND METHODS

Patients with newly diagnosed glioblastoma (WHO 2021) who underwent chemoradiation and contrast-enhanced MRI suspected for TP and subsequent FET-PET scan at Essen University Hospital were retrospectively evaluated. The modified Response Assessment in Neuro-Oncology (RANO) criteria were used to diagnose PSP. FET-PET analysis included mean (TBRmean) and maximum tumor-to-brain ratios (TBRmax). The two groups (TP/PSP) were balanced using a propensity scoreanalysis including age at diagnosis, extent of resection, Karnofsky-Performance-Status Scale (KPS) and MGMT methylation status. Overall survival was predicted using Kaplan-Meier and multivariate analysis as well as conventional FET-PET parameters, PET/MRI volumetry, and FET/MRI-derived radiomics. An independent cohort was used for validation. Results: Out of the 165 patients analysed in this study, 38 were diagnosed with PSP. Following balancing analysis, our study cohort consisted of 40 patients (20 TP/20 PSP). Patients with PSP had a significantly longer mean overall survival (mOS) compared to those with TP (mOS TP 20.24 months; mOS PSP 33.25 months; p=0.0023). The multivariate Cox-Regression analysis confirmed PSP as a significant prognostic marker for overall survival (p=0.0153). Confirmation of these results on an independent validation cohort is pending and will be presented at the meeting.Conclusion: This study shows that PSP is an independent prognostic factor for overall survival in newly diagnosed glioblastoma patients.
P10.03.B A NOVEL MACHINE LEARNING (ML) MODEL INTEGRATING CLINICAL AND MOLECULAR DATA TO PREDICT RESPONSE TO SECOND LINE TREATMENT IN RECURRENT IDHWT-GLIOBLASTOMA (RGBM)
Authors: Polano M , Cella E , Padovan M , Bosio A , Bertero L , Caccese M , Cerretti G , Rudà R , Toffoli G , Lombardi G
Published: October 2024

BACKGROUND

Nitrosoureas (lomustine/fotemustine) and antiangiogenic drugs (bevacizumab or regorafenib) are second-line treatment options for patients with rGBM, but to date predictors of efficacy are lacking. We aimed to develop a multi-classification ML algorithm to predict the response to different second line therapies.

MATERIAL AND METHODS

We conducted a retrospective study to assess the combined predictive value of molecular profiles (tested by FoundationOne®CDx on tissue) and clinical data (clinical-pathological and treatment characteristics) in a cohort of patients with first rGBM treated with Regorafenib, Lomustine/Fotemustine or Bevacizumab from Oct 2019 to Jan 2023. WHO2021 classification was used for pathological diagnosis, and RANO criteria for neuroradiological response evaluation.ML was applied using a gradient boosting framework that uses tree-based algorithms LightGBM to integrate clinical and genomic data. In this context we apply the ML approach to identify the best responders. Matthews correlation coefficients (MCC) were used as a metric. To create a multi-classification model, we included all the cases with complete information (gene mutations and clinical data). Best responders were labeled for having a median progression free survival (mPFS) above the third quartile for each treatment performed in the second line in recurrent glioblastoma.

RESULTS

153 patients, treated with Regorafenib (n=95), Bevacizumab (n=19), Nitrosoureas (n=39) were enrolled. The mPFS in each treatment cohort was 2.1 ms (95% CI 1.9-3.3), 3.6 ms (95% CI 2.1-4.8) and 3.0 ms (95% CI 2.4-5.7), respectively. The mOS from the start of treatment was12 ms (95% CI 9.1-14), 7.0 ms(95% CI 6.0-11), and 8.0 ms (95% CI 5.0-13). By performing the multi-classification model we obtained a MCC of 0.32. The SHAP analysis showed age at diagnosis, gender, methylation status and CDKN2B, CDKN2A, PTEN, EGFR, TP53, MTAP mutational status as the most important predictors.These variables were ranked in a different order for each second-line treatment, thus demonstrating that the multi-classification ML approach could discriminate which patients are likely to benefit from each second-line treatment.

CONCLUSION

The multi-classification ML model developed in this study was able to identify clinical and molecular signatures of rGBM responding to second-line with bevacizumab or regorafenib or nitrosoureas.This model could be useful to choose the more effective second-line therapy in rGBM patients.
P10.09.A BLOOD-BASED CLASSIFICATION OF IDH-STATUS OF NON-ENHANCING GLIOMAS: A MACHINE LEARNING APPROACH
Authors: Hadad S , Warrier G , McCoy L , Hansen H , Chen J , Rice T , Wrensch M , Taylor J , Clarke J , Wiencke J , Molinaro A
Published: October 2024

BACKGROUND

Non-invasive determination of IDH mutational status in patients with glioma could offer significant therapeutic opportunities. While IDH wildtype tumors (e.g., GBM) typically show enhancement on MRI, IDH mutant tumors often lack this enhancement. However, relying solely on anatomic radiology may lead to misclassification, and currently, tissue acquisition is the primary method for assessing IDH status in gliomas. This limitation hampers the development of neoadjuvant or intraoperative therapeutic strategies based on IDH status; thus, more minimally invasive methods to determine IDH status are needed. In this study, we assessed immune cell proportions, which vary by glioma subtype, from pre-surgery peripheral blood samples as an alternative method of classifying the IDH status in gliomas without enhancement.

MATERIAL AND METHODS

First, we employed a highly accurate large language model (GPT-4-Turbo-128k) with over 99% accuracy to read radiology notes and exclude patients with enhancing gliomas. Then, we identified twelve immune cell subtypes from whole blood using deconvolution algorithms based on DNA methylation data. These immune cell subtypes, along with patient age, were integrated into a machine learning model (random forest) to predict IDH status (wildtype vs. mutant), leveraging conditional Generative Adversarial Networks to generate synthetic data and mitigate bias in the datasets. Two independent datasets were included for training and validating the model.

RESULTS

The random forest model had an area under the ROC curve (AUC) of 0.90 and accurately identified IDH status in 81% of a training set of 287 gliomas (65 wildtype and 222 mutant tumors at varied time points after diagnosis). In an independent validation data set of 99 gliomas (6 wildtype and 93 mutant) from pre-surgery blood samples, the AUC was 0.93, and accuracy predicted IDH status in 92% of cases with a sensitivity of 93% and specificity of 83%.

CONCLUSION

We could accurately predict IDH status in pre-surgical peripheral blood samples from patients with non-enhancing gliomas. This minimally invasive approach is a promising step toward reducing risk and exploring opportunities for earlier therapies based on IDH status.
P12.12.B IMMUNOTHERAPY WITH CAR T-CELLS IN THE TREATEMENT OF RECURRENT GLIOBLASTOMAS: A SYSTEMATIC REVIEW
Authors: Souza P H L , Fracaroli N O , Almeida I M , Suaid R G , Guaresqui H A , Motta R N T , Monici V C , Moysés R C A , Moraes G A , Ramalho A O , Berriel C C , Bellotti G K , Nogueira B V
Published: October 2024

BACKGROUND

Glioblastomas are common malignant tumors in the central nervous system. Currently, the standard of treatment (SOD) for this kind of disease is maximum surgical resection associated with postoperative chemotherapy. However, the current SOD for this tumor still promotes a strict prognosis, with a median Overall Survival (mOS) of less than 24 months. In consequence, many studies are carried out in order to explore new treatment strategies; among those studies, Chimeric Antigen Receptor (CAR) T-cell therapy stands out. This therapy offers a promising alternative for treating those neoplasias resistant to conventional treatment. Therefore, we conducted a systematic review aiming to consolidate and summarize current knowledge on the efficacy of CAR T-cell therapy specifically for glioblastoma.

METHODS

We searched Medline, Embase, and Web of Science databases following Cochrane and PRISMA guidelines. bThe endpoints of this systematic review were mOS, T-cell persistence, and maximum tolerated dose of CAR-T cell.

RESULTS

The analysis included 8 studies with a total population of 70 patients diagnosed with recurrent glioblastoma treated with CAR T-cells The pooled data of mean Overall Survival was 265,57 days. Of the 70 patients, only 5 had complete tumor regression, while 36 had tumor progression.

CONCLUSION

This systematic review showed that CAR T-cell therapy does not seen to be an optimal treatment for recurrent glioblastoma patients due to its low tumor regression rate and high tumor progression. However, current research needs to solidify the evidence base before its widespread clinical use in treating recurrent glioblastoma can be justified.
P13.01.A 11C-METHIONIN PET FOR RADIOTHERAPY TREATMENT PLANNING IN PATIENTS WITH RAPID EARLY PROGRESSION AFTER GLIOBLASTOMA SURGERY: PROSPECTIVE PHASE II TRIAL
Authors: Kazda T , Lakomy R , Hynkova L , Pospisil P , Vasina J , Belanova R , Prochazka T , Rehak Z , Adam J , Sana J , Burkon P , Slavik M , Selingerova I , Jancalek R , Fadrus P , Kalita O , Polachova K , Stepankova T , Lojova M , Slampa P
Published: October 2024

BACKGROUND

Radiotherapy (RT) is a standard treatment for nearly all glioblastoma patients following initial surgery. Few retrospective studies indicate negative prognostic instances of progression during the planning magnetic resonance (MR) (up to 1 week before initiating RT), termed Rapid Early Progression (REP). The optimal RT management for REP patients remains uncertain. The objective of this prospective phase II trial (NCT05608395) is to assess impact of 11C-Methionine PET used for RT planning in REP glioblastoma patients. It is one of the first prospective clinical interventional trials focused on this specific cohort of patients.

MATERIAL AND METHODS

We enrolled glioblastoma, IDHwt, or Astrocytoma, IDHmt, WHO grade IV patients, who developed REP characterized by 1) increase in postoperative residuum by ≥ 25%, 2) appearance of new contras enhancing lesion, 3) unequivocal progression of the unresected satelite. Patients received treatment based on the Stupp or Perry protocol. Treatment response was evaluated using RANO criteria. RT target volumes were delineated as follows: Gross tumor volume included tumor cavity, enhancing lesion and 11C-MET PET (1.3 tumor-to-background ratio). The clinical target volume was GTV plus a modified 2cm margin reflecting surrounding organs at risk. Volumetric analyses of different radiotherapy target volume were performed using EclipseTM software including patterns of failure.

RESULTS

During 12/2020 - 12/2023, total of 31 patients were enrolled (16 treated via abbreviated RT course); median age 60 years, ECOG 0-1 in 28 patients, median follow up 20 months. No effect of 11C-MET PET - based radiotherapy treatment planning of GBM patients with REP was observed on PFS (median 3.4 months comparing to 4.9 in historical control cohort) and OS (12.3 months comparing to 15.7 months). Median MET volume was 7.3cm3 (43% of MRI volume), MET avidity was presented in 7 patients et least 1cm beyond MRI volume. Central recurrence was presented in 87% patients.

CONCLUSION

The optimal treatment of patients with REP is unknown and needs to be studied in more details including dose escalation studies with reduced target margins potentialy directed also by aminoacid PET examination. Adjustment of target radiotherapy volumes using 11C-MET PET did not lead to improved PFS or OS. Supported by NU20-03-00148.
P13.10.A NORADRENERGIC AGONISTS AS NEW TREATMENT OPPORTUNITY AGAINST RADIATION-INDUCED COGNITIVE DECLINE
Authors: De Bie I , Berden L , Peeters B , Vanhove C , Boterberg T , Tabury K , Primac I , Raedt R , Benotmane R
Published: October 2024

BACKGROUND

Pediatric patients undergoing cranial irradiation are at risk of developing neurocognitive impairments. Mechanistically, radiation-induced injury to the hippocampi could play an important role in this debilitating condition, by inducing loss of neural stem/progenitor cells (NSCs/NPCs) and neuroinflammation, eventually leading to hippocampal atrophy. Noradrenergic (NA) agonists can potentially mitigate this radiation-induced cognitive decline by reducing cell death and inflammation. Therefore, we hypothesize that pharmacological boosting of NA will attenuate radiation-induced impairments in neurogenesis and decrease neuroinflammation, resulting in decreased memory dysfunction.

MATERIAL AND METHODS

Mice were irradiated with a single fraction of 10 Gy at P22. Reboxetine and Atipamezole were administered as 7 daily intraperitoneal injections, starting immediately after radiation. Sham therapy was administered in an identical manner by injecting equivalent volumes of sterile 0.9% NaCl. At 6 hours, 1 week, and 1 month post-radiation, radiation-induced NSCs/NPCs death, deficits in neurogenesis, and inflammation were investigated with histology. Additionally, at 1 month post-irradiation, hippocampal atrophy and memory deficits were investigated by ex-vivo MRI and a behavioral test battery, respectively.

RESULTS

We report that Reboxetine and Atipamezole significantly mitigate radiation-induced toxicity in the hippocampi. At 6 hours post-irradiation, NA agonists reduce radiation-induced apoptosis and microglial inflammation compared to sham treatment. A substantial reduction in the number of NSCs/NPCs and immature neurons within the hippocampal dentate gyrus was observed at both 1 week and 1 month post-irradiation. This deleterious effect of irradiation on neurogenesis was significantly attenuated by Reboxetine and Atipamezole, at both timepoints. Considerable hippocampal volume loss was observed after radiotherapy, which was prevented by both drugs. Finally, behavioral testing revealed that treatment with Reboxetine after radiotherapy successfully mitigated radiation-induced deficits in working and reference memory.

CONCLUSION

The present findings document the marked benefits of NA treatment against radiation-induced hippocampal NSCs/NPCs death, impaired hippocampal neurogenesis, neuroinflammation, and hippocampal atrophy. Additionally, we demonstrate that Reboxetine is able to mitigate radiation-induced memory dysfunction, which highlights the potential of NA treatment for resolving long-standing complications faced by pediatric brain tumor survivors. This project is supported by BOF (Bijzonder Onderzoeksfonds) - Ghent University (I. De Bie is a PhD fellow, grant number 01D07923).
P14.03.B A PROSPECTIVE MULTI-CENTERED, ASSESSOR BLINDED INTERIM STUDY FOR BRAIN TUMOR DIAGNOSIS BY USING CONFOCAL FLUORESCENCE ENDOMICROSCOPY (CCELL - EX VIVO)
Authors: Kang S , Byun Y , Hong D , Won J , Kang H , Kim J , Lee S , Kim M , Kim Y , Park K , Kong D , Park C
Published: October 2024

BACKGROUND

To address an intraoperative brain tumor diagnosis by frozen section(FS) which is time-consuming and traumatic, confocal laser endomicroscopy (CLE) has actively been explored as a promising alternative tool. In this study, we aimed to demonstrate that novel CLE image evaluation by a neuropathologist is as effective as frozen section diagnosis for histopathological assessment during brain tumor surgery.

MATERIAL AND METHODS

Utilizing a novel confocal endomicroscopy (cCeLL) wherein tissues were pretreated with indocyanine green, a prospective multicenter, assessor-blinded interim analysis was conducted at three tertiary medical institutions in the Republic of Korea. Patients newly diagnosed with brain tumors between May 2023 and April 2024 were included. Each tissue sample was divided into three smaller pieces for permanent section analysis, frozen section analysis and cCeLL-Ex vivo imaging. A designated neuropathologist interpreted all cCeLL-Ex vivo images. Statistic evaluation was performed by comparing both frozen section analysis and cCeLL-Ex vivo with permanent H&E diagnosis. The total time from sample preparation to diagnosis was also calculated.

RESULTS

A total of 274 samples were acquired from 242 patients. The predominant tumor types were meningioma (32.1%), glioma (24.8%) and pituitary adenoma (9.49%). The majority of tissue samples (86.9%) were obtained from the tumor core. Non-diagnostic tissues constituted 4.38% in frozen section and 6.57% in cCeLL-Ex vivo imaging. The diagnostic accuracy of cCeLL-Ex vivo was on par with frozen section analysis, with 96.1% and 96.9%, respectively. Both methods demonstrated comparable diagnostic sensitivity (FS vs cCeLL-Ex vivo: 99.2% vs 98.3%) and specificity(FS vs cCeLL-Ex vivo: 76.0% vs 77.8%). There were no statistically significant differences in diagnostic accuracy between frozen section (FS) and cCeLL imaging for each tumor type. The average number of cCeLL images required for neuropathologic assessment was 15.84, varing based on the tumor type, with a range of 5.05 to 27.8. The mean duration from sample preparation to diagnosis was 8 minutes and 40 seconds in cCeLL-Ex vivo and 24 minutes and 35 seconds in frozen section (p-value < 0.001).

CONCLUSION

cCeLL-Ex vivo has shown promising tool as an alternative intraoperative brain tumor diagnosis compared to frozen section analysis. Future studies are anticipated to further validate its clinical utility and provide additional evidence supporting the potential of cCeLL imaging in clinical practice.
P14.14.A INTRA-ARTERIAL CHEMOTHERAPY TREATMENT FOR RELAPSING GLIOBLASTOMA: RESULTS FROM A FIVE-YEAR SERIES
Authors: Roy L , Roy M , Gahide G , Latulippe J , Fortin D
Published: October 2024

BACKGROUND

Glioblastoma (GBM) is the most common and aggressive type of primary brain tumour in adults. The GBM malignant phenotype depicts anarchic invasion of the brain parenchyma as well as radio-/chemoresistant properties. The complete surgical resection is unachievable and responses to standard therapy are invariably transient. In addition to the malignant GBM phenotype, the blood-brain barrier (BBB) is one of the prominent features that limits the efficacy of chemotherapy. Indeed, this facet of the brain’s blood vessels significantly blocks the passage of numerous therapeutic molecules from the blood stream to the brain. Tumour progression often occurs during or after standard first-line therapy which includes radiotherapy with concomitant and adjuvant temozolomide. The median overall survival (OS) is 14.6 months, but recurrence occurs on average only seven months after the initial diagnosis. At relapse, there is no consensus on the standard of care and the median OS ranges between three and nine months. At our institution, we use intra-arterial infusion to treat relapsing GBMs. This delivery strategy bypasses the first pass and significantly increases the local peak plasma concentration and area under the curve. This leads to a 3 to 5 fold increase of the chemotherapy concentration in the glioma-infiltrated brain parenchyma. Over the last 15 years, we have treated more than 722 patients for a total of 3600 intra-arterial chemotherapy (IAC) procedures.

MATERIAL AND METHODS

In this revision of the 2018-2023 series, we treated 59 relapsing GBM patients. Every IAC procedure was completed every four to six weeks. We reviewed the medical files to follow treatment evolution, tumour response and for grades 3 and 4 toxicity.

RESULTS

During this five-year period, a total of 406 arteriographic procedures were completed. The following chemotherapeutic agents were used: carboplatin, melphalan, methotrexate, Caelyx, carboplatin + melphalan, carboplatin + methotrexate, carboplatin + etoposide phosphate or melphalan + methotrexate. The median OS from diagnosis and relapse were 24 and 9 months respectively. A total of 28 patients suffered one or more grade 3 hematological toxicity events (17% of IAC cycles). Likewise, 24 grade 4 hematological toxicity events occurred in 16 patients (6% of IAC procedure).

CONCLUSION

In comparison with published clinical trials results, the data from our series suggest that IAC is a promising strategy for the treatment of relapsing GBM. We will gather more data and perform uni- and multivariate analyses. Moreover, we will soon begin a randomized clinical trial to test the combination of carboplatin + etoposide phosphate and carboplatin + Caelyx in the treatment of relapsing GBM. Furthermore, we are currently conducting preclinical experiment using topotecan, cytarabin and paclitaxel to determine their effectiveness in the IAC setting.
P14.16.A IS A LINAC WITH A 5MM MLC WIDTH REALLY A BARRIER TO IMPLEMENTING A HIGH-QUALITY COMPLEX SRS SERVICE?
Authors: Dean C , Bowles S , MacDougall N , Cook J , Rozati H , Lewis R
Published: October 2024

BACKGROUND

Stereotactic Radiosurgery (SRS) for patients with intracranial disease is increasing, especially for smaller and more numerous metastases. In England, Varian HyperArc using a Truebeam linac is nationally commissioned via benchmarking.

HyperArc contains SRS-specific optimisation and non-coplanar VMAT delivery and is an attractive option due to its cost effectiveness compared with competing specialised platforms such as Elekta GammaKnife and Accuray CyberKnife.

Depsite these benefits, the treatment of small targets or those with highly complex shapes is dominated by specialised platforms with a largely stated reason being perceived concern over delivered dosimetric certainty. This work assesses achievable dosimetric accuracy for complex SRS using Varian HyperArc suing a standard 120-leaf 5mm width MLC.

MATERIAL AND METHODS

Four patients with small and/or complex PTVs previously treated with CyberKnife at our institution were identified:26 metastases 24Gy/1f (PTV min. volume 0.01cc);5 metastases 24 Gy/1f (PTV min. volume 0.11cc);Pituitary adenoma 25Gy/1f (PTV width min. 5 mm near optics);Acoustic neuroma 21 Gy/3f (PTV width min. 3 mm near cochlea).

Patients were re-planned with HyperArc using 4 arcs at 6FFF, emulating the prescription dose spillage (PDS) & modified gradient index (mGI) achieved in the CyberKnife plans. Plans were produced in Eclipse v17.1, calculated using the AAA algorithm (v 17.1.0.1) on a 1mm calculation grid. The plan was then transferred to a CT scan of an in-house water equivalent phantom containing radiochromic EBT3 film in clinically meaningful coronal and sagittal dose planes and re-calculated.

All plans were delivered under image guidance and the 2D film dosimetry was compared with the calculated dose from Eclipse using a global 5%/1mm (TH 20%) gamma test using well-established absolute dose film methodology in Sun Nuclear SNC Patient (v 8.2).

RESULTS

In all cases, HyperArc had very similar plan quality to CyberKnife, with maximum dose gradients between 20-23% of prescription dose per mm beyond the PTV (up to 5.8Gy/mm). Up to 1mm geometric offset was permitted to allow for imaging localization & film registration uncertainty in the analysis. Mean gamma pass rates were 93.3% pre-alignment and 98.5% post-alignment.

CONCLUSION

The very high gamma pass rates achieved in this novel work illustrate excellent delivered dose accuracy for high-quality SRS plans.

The use of a radiochromic film dosimetry allows for the demonstration of such accuracy using a standard Truebeam linac without the use of a high-definition MLC even for the smallest and most complex SRS targets.

This work enables us to re-think previously held beliefs around perceived dosimetric limitations of multi-arc VMAT with a 5 mm MLC width for the delivery of high-quality SRS. Removing this barrier could start to bridge the existing gap in worldwide SRS service provision for patients.
P14.17.B MINI-CRANIOTOMY FOR RESECTION OF INTRA-AXIAL TUMOURS: EVALUATION OF TECHNIQUE USING PROPENSITY-SCORE MATCHING
Authors: Waqar M , Dainton A , Abdelaal A , Nambiar R , Maye H , Karabatsou K , D'Urso P
Published: October 2024

BACKGROUND

Minimally-invasive neurosurgical techniques are increasingly utilised in neurosurgery and there is growing evidence to support their use in intra-axial tumour resection. In this case control study, we compare outcomes between patients undergoing mini-craniotomy and larger sized craniotomies for intra-axial tumours using propensity-score matching.

MATERIAL AND METHODS

Review of prospective institutional database (N = 465) of adult patients undergoing intra-axial tumour resection from 2014-2021. Propensity-score matching was used to create matched groups of patients who had a mini- (≤3 cm), intermediate-sized (3-5cm) and standard (>5cm) craniotomies. Outcomes included extend of resection, length of postoperative stay and 6-month complications.

RESULTS

138 patients were included distributed equally between mini- (46), intermediate-sized (46) and standard (46) craniotomy groups. The primary comparison was between the mini- and standard craniotomy groups. There was no significant difference in baseline characteristics between these groups except craniotomy size (2.8 cm vs. 6.1 cm, p<0.001). Importantly, the maximum tumour diameter was similar between the groups (p=0.116). A significantly greater proportion of patients in the mini-craniotomy group had a gross-total or near total resection (80% v 52%; p=0.014). Patients in the mini-craniotomy group had a shorter mean length of post-operative hospital stay at 5 days compared to 7 days (p=0.001). There was no statistical difference in the rate of 6-month complications between the two groups (p = 0.197). A secondary analysis compared the mini- and intermediate-sized craniotomy groups. The mini-craniotomy group had a shorter mean length of postoperative stay (p=0.002) and greater proportion of gross-total/near total resections (p=0.008).

CONCLUSION

Mini-craniotomy was associated with superior extent of resection and a lower length of postoperative stay. It demonstrated non-inferiority for post-operative complications. This report adds to the growing literature demonstrating the safety, feasibility and efficacy of mini-craniotomy in neuro-oncological surgery.
P14.22.B THE ROLE OF AMINO ACID PET IN RADIOTHERAPY TARGET VOLUME DELINEATION FOR ADULT-TYPE DIFFUSE GLIOMAS: A SYSTEMATIC LITERATURE REVIEW
Authors: Horsley P , Bailey D L , Schembri G , Hsiao E , Drummond J , Back M F
Published: October 2024

BACKGROUND

Amino acid positron-emission tomography (AA-PET) is an emerging tool to complement magnetic resonance imaging (MRI) in glioma management. This purpose of this review was to summarise the existing literature examining use of early post-operative AA-PET for radiotherapy target volume delineation.

MATERIAL AND METHODS

A systematic search of the MEDLINE and EMBASE databases was conducted using search terms related to PET, amino acid tracers, radiotherapy and gliomas. Eligible studies included those with 20 or more patients that examined post-operative AA-PET prior to adjuvant radiotherapy and reported outcomes related to radiotherapy target volumes, relationship of PET-defined volumes to patterns of failure and/or outcomes of PET-guided radiotherapy.

RESULTS

The search yielded 534 unique studies for abstract and title screening, 71 of which proceeded to full-text review and 20 met eligibility criteria for inclusion. In all studies, the diagnosis for either all or the majority of included patients was glioblastoma. Eight studies compared PET- to MRI-derived target volumes with the consistent finding that the volumes were complementary. Seven studies related PET-derived volumes to the location of subsequent failure and consistently found AA-PET to be a strong predictor of failure location. Three studies reported outcomes of AA-PET-guided radiotherapy at standard doses. Survival outcomes were similar to trials in which radiotherapy volumes were generated based on MRI alone. Four studies reported outcomes following AA-PET-guided dose-escalated radiotherapy using a variety of regimens with mixed results with respect to patterns of failure and survival. We hypothesise that substantial differences in biologically effective dose (BED) and target volume delineation strategies between studies may have influenced the observed differences in outcomes.

CONCLUSION

Post-operative AA-PET is a promising complementary tool to MRI for radiotherapy target volume delineation, with potential benefits requiring further validation including margin reduction, reduced geographical miss and facilitation of dose-escalation. Prospective dose-escalation trials using the combination of MRI and AA-PET for target volume delineation seem warranted with close attention to BED of the chosen radiation schedule. Focused research in the setting of grade 2-3 and IDH-mutant gliomas is lacking.
P14.24.A USE OF OMMAYA RESERVOIR FOR INTRATHECAL CHEMOTHERAPY AND DISEASE MONITORING IN ROUTINE CLINICAL PRACTICE: ASSESSMENT OF SAFETY AND EFFICACY
Authors: Harahsheh E , Shah S , Butterfield R , Ariete C , Lyons M , Krishna C , Fortin-Ensign S , Zimmerman R , Bendok B R , Mrugala M M
Published: October 2024

BACKGROUND

Leptomeningeal disease (LMD) carries poor prognosis with an average survival of 3-6 months after diagnosis. Ommaya reservoirs (OR) are an accessible alternative to serial lumbar punctures for delivery of intrathecal chemotherapy (IC) and disease monitoring but are not widely used. Intraventricular administration of chemotherapy may be associated with superior efficacy and improved patient comfort. The purpose of this study was to assess safety and efficacy of IC and disease monitoring via OR in routine clinical practice.

MATERIAL AND METHODS

Patients who received at least one administration of IC via OR for LMD between 2017 and 2022 were included. Demographics, treatment type, complications and outcomes were recorded.

RESULTS

We identified 22 patients (17 females, 5 males) with mean age 50.9 ± 14.8 years. The primary tumors were: breast (12), leukemia (3), ovarian carcinoma (3), CNS lymphoma (1), urothelial carcinoma (1), spinal melanocytoma (1), and high-grade glioma (1). A total of 208 OR injections were performed [median was 9 OR injections per patient, interquartile range (IQR) (5, 13)]. Five patients (23%) experienced mild adverse events of grade 2 or lower by Common Terminology Criteria for Adverse Events. Overall risk of adverse event from injection was 3.4% (7/208). Eight patients (36.3%) converted into negative CSF cytology (median 1 month following first injection), and 18 patients (82%) had clinical or radiological progression of their LMD (median 2 months following first injection). Eleven patients (50%) died of their LMD during follow-up. Median OS and PFS from the first injection were 5.3 months [95% CI 4.8-NE (not estimable)] and 4.3 months [95% CI 1.8-16.0], respectively.

CONCLUSION

Use of OR in routine clinical practice is a safe and feasible option and should be strongly considered for treatment and frequent disease monitoring of patients with LMD, especially in the era of circulating tumor cells analysis. The median OS in our cohort is comparable to prior published series.
P16.02.A FRENCH NATIONAL STUDY ON THE EPIDEMIOLOGY OF CHILDHOOD BRAIN TUMORS
Authors: Khettab M , Chirpaz E , Zouaoui S , Ah-pine F , Rigau V , Rolland A , Darlix A , Ng S , Roujeau T , Bauchet L
Published: October 2024

BACKGROUND

Primary central nervous system tumors (PCNST) in children aged 0 to 19 years are a heterogeneous group of pathological entities that continue to present significant challenges. This abstract provides exhaustive data on histologically confirmed pediatric PCNST cases in France.

MATERIAL AND METHODS

Patients were identified from the French Brain Tumor Database, a comprehensive national database. The study included children (0 to 19 years) who were diagnosed with histologically confirmed PCNST between 2006 and 2015. For each histological subtype, including rare variants, data such as the number of cases, incidence rates, gender distribution, and surgical approach (resection or biopsy).

RESULTS

Between 2006 and 2015, a total of 6,691 cases of newly diagnosed and histologically confirmed primary central nervous system tumors (PCNST) were recorded in France, with a gender distribution of 3,692 males and 2,999 females. The principal histological categories included 4,863 neuroepithelial tumors (72.68%) including 2,829 gliomas (42.29%), 819 neuronal and mixed neuronal-glial tumors (12.24%), and 1,005 embryonal tumors (15.02%). Additionally, there were 746 tumors of the meninges (11.15%), which included 140 meningiomas (2.09%), 551 mesenchymal tumors (8.23%), and 55 other types (0.82%). Other categories reported were 251 tumors of cranial and paraspinal nerves (3.75%), 223 germ cell tumors (3.33%), 284 craniopharyngiomas (4.24%), and 324 other types (4.84%).The overall crude incidence rate (CR) was 4.334 per 100,000 person-years, with age-specific rates of 4.418 per 100,000 for ages 0-4 years, 4.184 per 100,000 for ages 0-14 years, and 4.789 per 100,000 for ages 15-19 years. Age-standardized incidence rates (adjusted to European, US, and world standard populations), demographic characteristics, along with other relevant data, will be further elaborated in the presentation. In addition, specific attributes for the age groups of 0-4 and 15-19 years, relating to histological subtypes and sex predominance, will be provided in detail. For example, anaplastic ependymomas constituted 101 out of 171 cases (59.06%) in the 0-4 years age group, compared to 16 out of 99 cases (16.16%) in the 15-19 years age group. Embryonal tumors represented 422 out of 1,715 cases (24.61%) in the 0-4 years age group, and 100 out of 1,835 cases (5.45%) in the 15-19 years age group. Among mesenchymal tumors, lipomas accounted for 98 cases in the 0-4 years age group and 10 cases in the 15-19 years age group.

CONCLUSION

To our knowledge, this constitutes the most extensive report of histologically confirmed PCNST cases diagnosed in children and adolescents within the French population. The report meticulously details all histological subtypes along with their respective frequencies and distributions. The findings hold significant implications for epidemiology, clinical practice, and future research.
P16.05.A PEDIATRIC NEUROFIBROMATOSIS 1-RELATED AND NOT-RELATED OPTIC PATHWAY GLIOMA TREATED WITH FIRST LINE CHEMOTHERAPY: A SINGLE-CENTER EXPERIENCE
Authors: Castelli B , Fonte C , Tellini M , Di Nicola M , Guidi M , Giunti L , Marzano C , Tirinnanzi B , La Torre C E , Buccoliero A M , Giordano F , Marchiori V , Maimone F , D’Incerti L , Bacci G M , Scagnet M , Genitori L , Sardi I
Published: October 2024

BACKGROUND

Optic pathway gliomas (OPG) are low-grade tumors (LGG) that affect the precortical visual pathway, representing 3-5% of pediatric brain tumors, more often diagnosed before the age of 5 years. Although histologically benign, due to their location and thus their unresectability, they carry considerable morbidity, bringing to progressive visual loss. In up to 20% of cases they are detected in patients with neurofibromatosis type 1 (NF1). Consolidated chemotherapy regimen with or without biopsy or debulking, if feasible, remains so far the standard management, moving to new personalized frontiers.

MATERIAL AND METHODS

In Meyer Children’s Hospital IRCCS Neuro-oncology Unit in Florence (Italy), from February 2013 to April 2024, for visual impairment at diagnosis or for disease progression, thirty-seven OPG patients (female/male ratio 1.3, median age at onset 4 years) completed the first line LGG chemotherapy (carboplatin-etoposide scheme adopted in our institution, built upon the INT Milan strategy and the standard SIOP LGG trial). Fourteen patients (37.8%) presented NF1-related OPG diagnosis, mostly made on a clinical/neuroradiological data. Response was assessed according to RAPNO criteria.

RESULTS

Non-NF1 OPG patients debuted at a lower median age (3 years) and mostly in a chiasmatic-hypothalamic location, predominantly with a pilocytic astrocytoma histology and manifested with nystagmus, secondarily with visual impairment. Despite the most frequent pre-chiasmatic involvement, during follow-up NF1 patients surprisingly presented a mean and median higher thickness (μm) of the retinal nerve fiber layer (RNFL) on optic coherence tomography (OCT) compared to non-NF1 patients, tested in the majority of patients (mean right RNFL 74.4 versus 58.0, median 66.0 versus 50.0, mean left RNFL 77.2 versus 55.3, median 73.0 versus 49.5). Four non-NF1 patients progressed during treatment or immediately afterwards. Considering the whole follow-up from the stop therapy (median time 5 years), non-NF1 patients progressed by far much more (15/23, 65.2% with one death versus 2/14, 14.3%). Overall survival was 97.3%.

CONCLUSION

NF1-related and not related pediatric OPG represent two distinct subgroups, with different clinical and prognostic characteristics. In agreement to other series our data show that non-NF1 OPG are less chemotherapy responsive than NF1-related OPG, surely due to the molecular landscape at the basis of tumor growth, warranting the needing of precision medicine directed to targets also in first- line treatment. A worse OCT outcome was found in the former cohort.
P16.10.A UNRAVELING THE CLINICAL IMPLICATIONS OF TRIM24::NTRK2 FUSION GENE IN PEDIATRIC HIGH-GRADE GLIOMA: A CASE STUDY
Authors: Karlsson I , Keane S , Deland L , Lindlöf A , Kling T , Olsson Bontell T , Fagman H , Nilsson J , Nilsson D , Sabel M , Carén H , Abel F
Published: October 2024

BACKGROUND

High-grade gliomas are among the deadliest of all childhood cancers and the leading cause of cancer-related mortality in children. The standard treatment is resection followed by chemotherapy, most often temozolomide and radiation therapy. Unfortunately, there is no evidence that temozolomide influences survival in pediatric patients and only a limited number of new drugs have been identified for specific subgroups of tumors. The identification of fusion genes as possible drivers of the disease offers an opportunity for targeted therapies. We present a case of a six-year-old patient with a novel TRIM24::NTRK2 fusion positive epithelioid glioblastoma with subsequent relapses.

METHODS

We investigated the ramification of this fusion and evolution of the tumor through whole genome sequencing, RNA-sequencing and DNA methylation profiling, and studied the effect of the patient’s treatment using patient-derived cell cultures.

RESULTS

Our studies show that the TRIM24::NTRK2 fusion has oncogenic abilities but loses its importance as the tumor evolves. In addition, we demonstrate an increased drug resistance over time, further indicating the diminished driver function of the fusion.

CONCLUSION

The use of resequencing revealed parallel development of tumor subclones with different genomic alterations, highlighting the importance of genomic profiling from various parts of the tumor.

FUNDING

This work was supported by the Swedish Research Council, the Swedish Childhood Cancer Foundation, and the Swedish Cancer Society
P17.01.A ANAMNESTIC RADIOLOGICAL METASTASES OUTCOME SURGICAL SCORE (ARMO-S). A PURPOSE OF A PREDICTIVE SCORING SYSTEM FOR SURGICAL BRAIN METASTASES
Authors: Armocida D , Ius T , Cofano F , Tartara F , Salvati M , Frati A , Garbossa D
Published: October 2024

BACKGROUND

Several risk stratification scores have been suggested to aid prognostication and guide treatment strategies for brain metastases (BMs). However, the current scores do not focus on the specific neurosurgical population, therefore not predicting short-term mortality and postoperative performance status.

MATERIAL AND METHODS

This retrospective observational study of 362 consecutive patients treated with surgery for BMs aims to identify the factors associated with post-surgical outcomes and propose a surgery-specific prognostic score for patients with BMs candidate for open surgery.

RESULTS

Factors significantly associated with OS and performance status in multivariate analysis were age, KPS, surgical site, synchronous debut of BM, number, tumor volume, seizure, extra-cranial metastases, and deep-seated location. The variables were incorporated into the Anamnestic Radiological Metastases Outcome Surgical score (ARMO-S). The values range between 0 and 10. Patients were divided into two groups (low-risk and high-risk) based on each significant subgroup’s median survival and performance status with an optimal cutoff value determined as 4. The two groups have significant differences in OS (9.6 versus 14 months, p = 0.0048) postoperative KPS (90 versus 70, p=0.012) and KPS at last follow-up evaluation (75 versus 30, p<0.001)

CONCLUSION

ARMO-S is a simple and comprehensive score for BM patients selected for neurosurgery, as it incorporates the main factors of the most important prognostic scores, implementing them with more surgery-specific predictive elements such as tumor location and volume, presence of seizures at onset, and involvement of eloquent brain areas.
P17.04.B CIRCULATING TUMOR CELL NUMBERS IN CSF HAVE ADDED PROGNOSTIC VALUE IN PATIENTS WITH LEPTOMENINGEAL METASTASES
Authors: van Kessel E , Woerdman N , Pluim D , Milojkovic B , van den Broek D , Brandsma D
Published: October 2024

BACKGROUND

Approximately 10% of patients with solid tumors develop leptomeningeal metastases (LM). Median survival rates are low in patients with LM but can vary significantly and are dependent on various patient-, tumor-, and treatment-related factors. Advanced techniques for circulating tumor cell enumeration in cerebrospinal fluid (CSF) can help in diagnosing patients with LM, but they may also have value in prognostication. Our aim was to investigate whether circulating tumor cells (CTCs) in CSF are of added value in survival prediction in LM patients.

MATERIAL AND METHODS

We performed a single-center retrospective study in a cohort of patients with LM from an epithelial tumor, diagnosed at the Netherlands Cancer Institute - Antoni van Leeuwenhoek, a tertiary comprehensive cancer center. CTCs in CSF were enumerated by an Epithelial Cell Adhesion Molecule (EpCAM - based immunoflow cytometry method) at the diagnosis of LM. The added prognostic value of CTCs in CSF on top of known clinical prognostic factors for LM, was assessed. We compared Cox proportional hazards regression models with and without CTCs by means of loglikelihood ratio tests (LRT) and discriminative performance measures.

RESULTS

We included 103 eligible patients who were diagnosed with either possible (n=10), probable (n=7), or definitive LM (n=86) according to EANO-ESMO guidelines, with a median survival of 129 days. All patients with possible LM at diagnosis, were found to actually have LM during clinical and radiological follow-up. CTCs in CSF were of significant added prognostic value upon the following known predictors of LM; gender, age, WHO performance score, brain metastases, primary tumor type, targetable driver mutation, systemic progression at diagnosis of LM and switch of systemic therapy. This was indicated by a loglikelihood ratio test with a p-value of ≤ 0.01 and an Area Under the Curve (AUC) of 0.723 (with CTC) versus 0.710 (without CTC). Sensitivity analyses in subgroups with only patients with definitive or probable LM showed similar results. Additionally, the median amount of CTCs differed significantly between the following survival groups: < 6 weeks: 103.9 CTCs/ml; 6 weeks to 6 months: 41.3 CTCs/ml; > 6 months: 5.8 CTCs/ml, with ANOVA p-value =0.031.

CONCLUSION

Our findings indicate that the number of CTCs in CSF, as measured by EpCAM immunoflow cytometry, is of additional prognostic value to other well-known predictors of survival in LM. The number of CTCs in CSF should be taken in account when assessing the prognosis of patients with LM of solid tumors.
P17.06.B CSF DRAINAGE IN LEPTOMENINGEAL DISEASE: SURGICAL AND SURVIVAL OUTCOMES IN VENTRICULO-PERITONEAL SHUNT VS. RICKHAM RESERVOIR PATIENTS
Authors: Alhalabi O T , Klein L , Büsken C , Mellal A , Wasilewski D , Buszello C , Cossu G , Eyüpoglu I Y , Unterberg A W , Vajkoczy P , Messerer M , Misch M , Krieg S M , Juratli T A , Younsi A
Published: October 2024

BACKGROUND

Leptomeningeal disease (LMD) usually represents a terminal condition that can cause symptomatic hydrocephalus. With improved survival rates under systemic therapy, the role of cerebrospinal fluid (CSF) drainage via ventriculo-peritoneal shunt (VPS) or Rickham reservoir placement for symptom control is gaining more relevance. This study aimed to describe surgical and survival outcomes of hydrocephalic LMD patients after surgical drainage in a contemporary cohort.

MATERIAL AND METHODS

A multi-center retrospective analysis of adult patients with VPS or Rickham reservoir placement for CSF drainage in the presence of LMD with malresorptive hydrocephalus between 2017 and 2022 was performed. Patients with occlusive hydrocephalus were excluded. Clinical, surgical and survival data were collected and compared.

RESULTS

A total of 119 patients with a median age of 53 (42-77) years (40 males, 79 females) were included. Of those, 64 underwent VPS (54%) and 55 (46%) Rickham reservoir placement. The most common underlying oncological conditions were breast cancer (n=67, 56%) and non-small cell lung cancer (n=25, 21%). The median time between primary tumor and LM diagnosis was 23 months (0 to 180 months) and 44 patients (37%) had end-stage disease at primary tumor diagnosis. Moreover, 79 (66%) patients showed solid intraparenchymal cranial metastases, for which only 20 patients (17%) had received surgical resection. Most patients (n=95, 80%) presented with symptoms of intracranial hypertension, which were relieved in 79% (n=51/64) after surgery. Compared to VPS placement, Rickham reservoirs were associated with lower complication (11% vs. 30%, p=0.01) and revision (9% vs. 23%, p=0.049) rates. Median overall survival from surgery was 90 (23 -148) days, and longer in VPS patients (107 days) compared to Rickham patients (83 days). However, this difference did not reach statistical significance (p=0.512).

CONCLUSION

While surgical CSF drainage in patients with LM disease relieves symptoms of intracranial hypertension in many cases, median survival remains expectedly low. Compared to Rickham reservoir placement, VPS bears higher rates of complications and revisions without a clear survival benefit. Nevertheless, decision-making regarding surgical CSF drainage and more importantly VPS or Rickham reservoir placement in LMD patients retains an individual and palliative nature.