bluuebunny/crossref_metadata_2025_split huggingface dataset:
P11.42.A LONG- AND SHORTIME SURVIVORS WITH GLIOBLASTOMA IDENTIFIED BY FLT PET/MR AND METABOLOMICS
Authors: Sandström M , Larhed S , Axelsson J , Björblom B , Asklund T 
Published: September 2023

Abstract

BACKGROUND
Patients with glioblastoma still have a dismal prognosis despite multimodal treatment with surgery and radiochemotherapy. Sometimes these patients also suffer from difficulties in the interpretation of outcome from treatment. Since most patients affected by glioblastoma have a short survival it is of outermost importance that ineffective treatment is discontinued in time to spare them from unwanted side effects.

MATERIAL AND METHODS
48 patients with suspected glioblastoma were included in a clinical study at Umeå University Hospital between the years 2015-2019. Patients were treated according to clinical routines with surgery and radiochemotherapy and within the framework of the study they performed up to four 18F-flourothymidine (FLT) PET/MR and serial blood-tests for metabolomics. Blood samples were analyzed at Metabolon, USA and the metabolomic pattern were compared with clinical and radiomic data.

RESULTS
The measures of standardized uptake values (SUV) and tumor volumes show a higher SUV for short-time survivals compared to long-time survivors but only a significant difference for the MR-measures Vtumor, Vtotal after 6 weeks of treatment. Regarding blood samples the metabolite patterns could separate patients living long (&gt;3 years) and patients living short (&lt;500 days) in blood samples taken both preoperatively and after six weeks of radiochemotherapy.

CONCLUSION
New methods are needed to accurate assess prognosis and outcome of treatment for patients with glioblastoma. This clinical study gives new insights in foreseeing prognosis for patients with glioblastoma by using 18F-flourothymidine (FLT) PET/MR and also by serial blood sampling during treatment. Both results of FLT PET/MR and the impact of metabolomics will be presented and discussed at the conference.
P11.43.B HIGH-RESOLUTION NERVE ULTRASOUND IN NEUROFIBROMATOSIS TYPE 1
Authors: Noordhoek D C , Mann E , Ennik T , van Dijk S A , Drenthen J , Taal W 
Published: September 2023

Abstract

BACKGROUND
Patients with neurofibromatosis type 1 (NF1) can develop plexiform neurofibromas (PN). PN are peripheral nerve sheath tumors that can cause pain, neurological deficit and can transform into malignant peripheral nerve sheath tumors (MPNST). High-resolution ultrasound (HRUS) is suggested as a quick and cost-effective technique, as compared to whole-body MRI, for screening NF1 patients for PN. Our aim is to describe the variety of HRUS nerve abnormalities in NF1 patients and to study the link between nerve morphology and nerve function.

MATERIAL AND METHODS
We selected patients with a clinical diagnosis of NF1, with or without symptoms related to the peripheral nervous system (PNS) such as pain, sensory disturbances or loss of strength. Patients were invited for a study visit including neurological examination, nerve conduction studies (NCS) and HRUS. One-sided NCS were performed of the median and ulnar nerve (motor and sensory), peroneal and tibial nerve (motor) and sural nerve according to standard protocol. We visualised the brachial plexus, median-, radial-, ulnar-, peroneal-, tibial-, and sural nerves on both sides using HRUS. The cross-sectional area (CSA) of the nerve was measured at predefined anatomical sites, and additional sites in case of focal nerve enlargement.

RESULTS
We enrolled 60 NF1 patients, of which 57% had PNS-related symptoms. One third of our patients had neurological deficits during physical examination. We found nerve enlargement with HRUS in 48 out of 60 patients (80%), this was not significantly different between patients with PNS symptoms or without PNS symptoms (82% vs 77% respectively, p=0.602). In 82% of the patients with PNS symptoms, their symptoms were likely to be related to one or more nerve enlargements. Nine of these patients had clinical and neurophysiological signs of carpal tunnel syndrome. Different patterns of nerve enlargement were identified. 46% had isolated nerve enlargements, 25% had diffusely enlarged nerves and 29% had a mixture of diffusely enlarged nerves with isolated nerve enlargements. The majority of the patients with nerve enlargement on HRUS had no abnormalities on NCS (65%).

CONCLUSION
The majority of NF1 patients have nerve enlargements as seen by HRUS, however we have shown that nerve enlargements can often be asymptomatic and do not always lead to impaired nerve function. To determine whether patients have PN cannot be based solely on clinical evaluation of symptoms. HRUS might have an application as a screening tool for NF1 patients in clinical practice. However, further research is needed to describe growth of nerve enlargements, the impact of intra- and interobserver variability on CSA measurements and to improve our knowledge on the link between nerve morphology and nerve function in NF1.
P11.60.A RACTAC TRIAL: PHASE II MULTICENTRIC ITALIAN TRIAL ON REPOSITIONING OF THE ANTIPSYCHOTIC DRUG CHLORPROMAZINE AND ITS COMBINATION WITH TEMOZOLOMIDE IN MGMT UNMETHYLATED GLIOBLASTOMA PATIENTS
Authors: Pace A , Lombardi G , Villani V , Benincasa D , Abruzzese C , Cestonaro I , Corrà M , Cerretti G , Caccese M , Silvani A , Gaviani P , Giannarelli D , Paggi M G 
Published: September 2023

Abstract

BACKGROUND
The poor prognosis of patients affected by glioblastoma (GBM) prompts the search for new and more effective therapies, particularly for GBMs with unmethylated MGMT. In this regard, drug repurposing, can represent a safe and inexpensive way to bring novel pharmacological approaches from bench to bedside. Chlorpromazine, a medication in use since six decades for the therapy of psychiatric disorders, shows in vitro features that make it eligible for repositioning in GBM therapy. In our experimentation on six GBM cell lines, chlorpromazine inhibited cell viability in an apoptosis-independent way, induced polyploidy, reduced cloning efficiency as well as neurosphere formation and downregulated the expression of stemness genes. Notably, we found that chlorpromazine synergized with temozolomide, in reducing cell viability and strongly cooperated in reducing cloning efficiency and inducing cell death in vitro for all the GBM cell lines assayed.

MATERIAL AND METHODS
With these assumptions, we started a multicentric Phase II clinical trial on newly diagnosed GBM patients with unmethylated MGMT by adding chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol. The experimental procedure involves the combination of CPZ with standard treatment with TMZ in the adjuvant phase of the Stupp protocol. CPZ was administered orally at a dose of 50 mg/day - GG 1-28 - of every cycle of the adjuvant treatment with TMZ. . Efficacy outcomes were evaluated using Kaplan-Meier methodology. OS was measured from diagnosis to death; PFS was determined from radiotherapy to the first sign of PD or death due to any cause.

RESULTS
The trial was closed on December 2022. 53 patients have been enrolled, 39 male, 14 female. 21 patients completed 6 cycles of treatment, without relevant toxicity.The results shows a median PFS of 7 months (St.Dev. 5,7) and a median OS of 15 months (St.Dev. 6,9). 23 patients are still alive (43%)

CONCLUSION
The addition of Chlorpromazine to the standard adjuvant chemotherapy with temozolomide was well tolerated in newly diagnosed Glioblastoma unmethylated patients, with promising impact on outcome measures. On the basis of the RACTAC trial

RESULTS
, a phase II multicentric trial evaluating Chlorpromazine added to standard treatment (RT+TMZ+adj TMZx 6 cycles plus CPZ) in newly diagnosed Glioblastoma patients is in preparation
P11.69.B INTRAVENOUS THROMBOLYSIS WITH OR WITHOUT ENDOVASCULAR TREATMENT FOR SUSPECTED ISCHEMIC STROKE IN PATIENTS WITH INTRACRANIAL TUMORS
Authors: Seystahl K , Martinez-Majander N , Salerno A , Beyeler M , Erdur H , Marto J P , Hametner C , Zedde M , Pezzini A , Leker R R , Altersberger V L , Costamagna G , Serôdio M , Migliaccio L , Pascarella R , Zini A , Razaqi L , Béjot Y , Jung S , Gensicke H , Padjen V , Ringleb P , Nolte C H , Heldner M R , Michel P , Engelter S T , Wegener S , Weller M 
Published: September 2023

Abstract

BACKGROUND: AND OBJECTIVES
Intravenous thrombolysis (IVT) for suspected ischemic stroke in patients with intracranial neoplasms is off-label. However, data on risks of intracranial hemorrhage (ICH) is scarce.

METHODS
In a multicenter registry-based analysis within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration, we assessed frequencies of symptomatic and fatal ICH after IVT for suspected ischemic stroke in patients with intracranial tumors by descriptive statistics and analyzed associations with clinical and imaging characteristics by binary logistic regression. Definition of symptomatic ICH was based on the clinical criteria of the European Cooperative Acute Stroke-II trial including hemorrhage at any site in cranial imaging and concurrent clinical deterioration.

RESULTS
Screening data of 21,289 patients from 14 centers, we identified 105 patients receiving IVT, among them 29 patients (28%) with additional endovascular treatment, with suspected, i.e. imaging-based, or histologically confirmed diagnosis of intracranial tumors. Among 104 patients with CT or MRI after IVT available, symptomatic and fatal ICH were observed in nine and four patients (9% and 4%). Among 82 patients with suspected or confirmed meningioma, symptomatic and fatal ICH occurred in six and three patients (7% and 4%). In 18 patients with intra-axial suspected or confirmed primary or secondary brain tumors, there was one symptomatic nonfatal ICH (6%). Out of four patients with tumors of the pituitary region, two patients (50%) had symptomatic ICH including one fatal ICH (25%). Tumor size was not associated with occurrence of symptomatic ICH (Odds ratio 2.8, 95% CI 0.3-24.8, p=0.34).

CONCLUSION
In our dataset from routine clinical care, we provide insights on the safety of IVT for suspected ischemic stroke in patients with intracranial tumors, a population that is commonly withheld thrombolysis in clinical practice and prospective trials. Except for a potential high risk of symptomatic ICH after IVT in patients with tumors of the pituitary region, frequencies of symptomatic ICH in patients with intracranial tumors in our cohort appear to be in the upper range of rates observed in previous studies within the TRISP cooperation. These results may guide individual treatment decisions in patients with acute stroke and intracranial tumors with potential benefit of IVT.
P11.70.A EQUITY IN GENOMIC TESTING: LESSONS LEARNT FOLLOWING THE ROLLOUT OF AN AMBITIOUS GENOMIC TESTING STRATEGY FOR NEUROLOGICAL TUMOUR PATIENTS IN THE UNITED KINGDOM
Authors: Huskens N , Aitken C , Watts C , Kurian K 
Published: September 2023

Abstract

BACKGROUND
The NHS England Genomic Test Directory now offers extensive genomic testing to brain tumour patients including whole genome sequencing (WGS), methylation arrays, gene panels, and other targeted mutation tests. Comprehensive genomic testing enables precise diagnosis and prognosis, tailoring of treatment, and research into new actionable targets. Despite the ambitious plans and potential for significant patient benefits, the Tessa Jowell Brain Cancer Mission (TJBCM) identified variation in deployment of these tests across Neuro-Oncology Centres in the UK. Based on these findings, we aimed to further understand the variation. We aimed to uncover drivers to delivering a successful genomic testing programme and identify local and national barriers to rolling out extensive genomic testing.

MATERIAL AND METHODS
As part of the TJBCM Centre of Excellence Programme, 90% of Neuro-Oncology Centres in the UK provided self-reported data on volumes of genomic testing for brain tumour patients. Subsequently, structured interviews were conducted with neuro-oncologists, neuropathologists, neurosurgeons, clinical scientists and other stakeholders from these Centres to further evaluate the state of genomic testing.

RESULTS
Accessibility to WGS varied from no access, to Centres where WGS was available in a limited capacity, to Centres where WGS was accessible but not scalable or timely. Bottlenecks were identified throughout the WGS pathway including inadequate tumour tissue, sample processing and transport delays, and insufficient clinical scientists to interpret results. As such, no UK Centre interviewed had sufficient capacity to offer WGS to all neurological tumour patients in a timely manner using NHS-accredited pathways. Interviews showed geographic variability in access to basic molecular tests such as methylation array and CDKN2A/B which are required for diagnostics and prognostics. There was also a strong reliance on a small number of laboratories to provide methylation array, resulting in backlogs. Common drivers to effective delivery of genomic testing included funded posts for research nurses, innovative systems for delivery of tumour samples from surgery to the laboratory, dedicated staff who advocated for genomic testing, and well-established Genomic Tumour Advisory Boards for test interpretation.

CONCLUSION
Impressive progress has been made in the last two years yet there remains a mismatch between what the National Genomic Test Directory dictates, and what can currently be delivered in a manageable timeframe. Inconsistencies in infrastructure, funding and training are preventing UK Centres from delivering the intended world-leading genomic testing. Barriers to address vary from simple changes at a local level, to national coordination and funding so that genomic testing will be equally accessible to all brain tumour patients in the UK.
P11.73.B COMPARING GAMMA KNIFE RADIOSURGERY WITH MICROSURGERY AND THEIR RISK-BENEFIT-RATIO OF TUMOR CONTROL AND FACIAL DETERIORATION IN LARGE VESTIBULAR SCHWANNOMAS (KOOS III-IV)
Authors: Wang S , Ebner F , Rizk A , van Eck A , Horstmann G , Tatagiba M , Naros G 
Published: September 2023

Abstract

BACKGROUND
The level of evidence to provide treatment recommendations for vestibular schwannoma (VS) is low. Both stereotactic radiosurgery (SRS) and microsurgical resection (SURGERY) are available as treatment options for VS. If treated with monotherapy alone, SRS has shown to be inferior in tumor control, but superior in facial nerve preservation compared to SURGERY. The aim of this study was to analyze the risk-benefit-ratio in the treatment of large VS (Koos III-IV) comparing SRS and SURGERY.

MATERIAL AND METHODS
This is a retrospective dual-center cohort study enrolling consecutive patients with solitaryVS between 2005 und 2011 to enable follow-up of up to 10 years. Tumor size was classified by Koos Classification. Clinical state was reported by House and Brackmann (H&B) and Gardner-Robertson (G&R) scale (with H&B and G&R 1-2 considered as good outcome), and Recurrence-free-survival (RFS) was assessed radiographically by contrast-enhanced MR imaging. As an expression of success/harm, the absolute risk reduction (ARR) and risk increase (ARI) were calculated as the difference between incidence of recurrences and facial deterioration rates in patients treated with SRS and SURGERY, respectively. ARR and ARI were used to derive additional estimates of treatment effectiveness (in SURGERY), i.e. the number-to-operate (NNO) and the number-to-harm (NNH), respectively.

RESULTS
The study population included N=901 patients, who were treated in both centers. N=492 (55%) were large VS (Koos III-IV). Of them N=260 (53%) were treated with SRS and N=232 (47%) with SURG. The SRS treatment arm presented with a recurrence rate of 14.2%, and SURGERY with 3.0%. Therefore, ARR for recurrence was 11.21% (95% CI: 6.4%-16.0%) with a NNO of 9 (95% CI: 6.3-15.6) in SURGERY meaning that one in every 9 patients will benefit from SURGERY treatment. When analyzing facial nerve deterioration (facial paresis HB&gt;2 and facial spasm) in large VS, SRS presented with 6.9%, and SURGERY with 12.5% adverse facial nerve outcome resulting in an ARI of 5.6% (95%CI: 0.3%-10.8%) and a NNH of 18 (95%CI:9.2-312.1).

CONCLUSION
The analysis of the different proportion in success/harm in the management of large VS (SRS vs. SURGERY) in this cohort yielded in a low NNO, combined with a high NNH. This shows that SURGERY was superior to SRS considering tumor control in large VS (Koos III-IV). Still, the direct translation of these results into treatment recommendations is not self-evident, but multi-faceted: This analysis is a vivid representation of a dilemma well-known to neuro-oncological surgeons - the negotiation between tumor control and functional outcome. Large VS should be treated in specialized centers, which have enough experience to ensure a high-rate of facial preservation in large VS (Koos III-IV).
P11.78.A BIUXX
Authors: Pantalone M , Rahbar A , Söderberg-Naucler C , Stragliotto G 
Published: September 2023

Abstract

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

Abstract

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