bluuebunny/crossref_metadata_2025_split huggingface dataset:
P27.19.A RAPID EARLY PROGRESSION IN GLIOBLASTOMA: A CASE-CONTROL EVALUATION OF CLINICAL OUTCOMES AND ADVANCED IMAGING BIOMARKERS
Authors: Waqar M 
Published: October 2024

Abstract

BACKGROUND
In glioblastoma patients, Rapid Early Progression (REP) refers to tumour growth between the time of surgery and postoperative chemoradiotherapy. It has a high incidence although relatively little is known about the phenomenon. The aim of this study was to characterise REP using clinical and advanced imaging data in the context of a case control study, to control for key confounders. We only included patients undergoing gross-total resection (GTR) to eliminate bias from extent of resection.

MATERIAL AND METHODS
Ethical approval was obtained. We reviewed an institutional database of newly-diagnosed glioblastomas undergoing GTR (2015-2021). Supratentorial IDH-wildtype glioblastomas were included with magnetic resonance imaging (MRI) scans available at the postoperative and radiotherapy planning time points. REP was defined as a nodular increase in enhancement located within/around the surgical cavity, occurring within 6 weeks of surgery, that was not accounted for by areas of diffusion-restriction on the postoperative MRI scan. Patients with REP were propensity-score matched to a control group based on clinical features. REP and control cases were compared on the basis of: clinical outcomes such as overall survival (OS) and progression-free survival (PFS; progression was defined as post-chemoradiotherapy progression); and advanced imaging using radiomics applied to preoperative T1 post contrast/Fluid Attenuated Inversion Recovery (FLAIR) sequences (Pyradiomics package) and the Apparent Diffusion Coefficient (ADC) derived from diffusion-weighted MRI.

RESULTS
60 patients undergoing GTR were included. 8 cases met the definition of REP such that the overall incidence after GTR was 13%. REP cases were matched to 16 control patients. After matching, there was no significant difference in baseline variables between REP and control cases except preoperative performance status, which was worse in REP cases (median Eastern Cooperative Oncology Group [ECOG] 2 vs. 1). REP was associated with a shorter median OS (9 vs. 17 months, p = 0.038) and PFS (5 vs. 9 months, p = 0.029). The incidence of REP was higher in patients over 65 (6/22, 27%) and significantly fewer REP patients in this category received radical postoperative chemoradiotherapy versus controls (Fisher’s Exact, p=0.023). REP and control cases had similar radiomic profiles and there was no significant difference in mean ADC between the groups in enhancing (p=0.99) or non-enhancing FLAIR hyperintense regions (p = 0.67).

CONCLUSION
REP cases had a worse performance status from diagnosis and received less radical postoperative chemoradiotherapy protocols compared to controls, yielding a significantly shorter median OS/PFS. Our results highlight that REP is a significant prognostic variable yet does not have a distinct biomarker. Our ongoing work will explore potential tissue biomarkers of REP.
P27.20.B RARE NEUROLOGICAL PRESENTATION OF BING NEEL SYNDROME AND TREATMENT PERSPECTIVES: A CASE SERIES
Authors: Giglio P , Malvaso A , Bini P , Diamanti L , Marchioni E 
Published: October 2024

Abstract

BACKGROUND
Bing-Neel syndrome (BNS) is a rare complication of Waldenström macroglobulinemia (WM) stemming from direct invasion of the central nervous system by malignant lymphoma cells. BNS patients present with gradually progressive symptoms (e.g. headache, nausea, vomiting, cranial neuropathies), rarely accompanied by aphasia and cognitive decline resulting from involvement of brain parenchyma

. MATERIAL AND METHODS
Three cases (68 y, F; 69 y, F; 74 y, M) of patients affected by WM and diagnosed with BNS are illustrated here. Clinical data have been collected from medical records for all patients.

RESULTS
A 68 year old female, a 69 year old female and a 74 year old male presented with aphasia, limb ataxia, behavioral changes and memory loss. The second patient also developed anti-MAG polyneuropathy. Obstructive hydrocephalus due to CNS invasion by previously unknown lymphoplasmacytic lymphoma was the inaugural manifestation of disease in the third patient; furthermore, BNS represented the initial presentation of WM in the second patient, whereas CNS involvement became apparent 7 years after disease onset in the first patient. Brain and spinal magnetic resonance imaging revealed brain leptomeningeal contrast enhancement in all patients with associated spinal leptomeningeal enhancement in the first two patients. The cerebrospinal fluid (CSF) analysis showed an increased WBC count (14/mm^3 and 27/mm^3) and elevated CSF/serum albumin transfer index (1,8% and 0,7%) in the first and the third patients. Monotypic CD20+, CD19+, CD5-, CD23-, CD10- lymphocytes with kappa chain monoclonal restriction were observed in all patients. Hence, a definitive diagnosis of BNS was made in all cases and immunosuppressive therapy was started with poor clinical improvement. Lastly, Ibrutinib was administered obtaining clinical and radiological benefits in all patients after 12 months of follow-up.

CONCLUSION
We suggest that the occurrence of rare, but typical neurological presentations in patients with WM could be clinically relevant and life threatening. Furthermore, BNS might be the initial clinical manifestation of WM. According to our monocentric experience and recent literature, BNS patients treated with Ibrutinib may reach high rates of 2-year event-free survival. However, randomized controlled trials are required to define the role of Ibrutinib as an important therapeutic option in BNS.
P27.21.A RE-RESECTION FOR RECURRENT GLIOBLASTOMA - DOES TIMING MATTER?
Authors: Alhalabi O , Dao Trong P , Mironov K , Nabiev K , Gareib A N , Jordan M , Joser S , Krieg S M , Unterberg A W , Jungk C 
Published: October 2024

Abstract

BACKGROUND
Surgery for recurrent glioblastoma (GBM) has the potential of prolonging patient survival. However, the impact of the timepoint of re-resection after tumor suspicion on post-surgical survival and neurological deterioration remains unclear.

MATERIAL AND METHODS
Patients undergoing first re-resection for recurrent WHO grade 4 IDH-wildtype GBM were analyzed retrospectively. Post-surgical neurological deterioration and post-surgical survival of patients undergoing early surgery (within 3 weeks) after suspected recurrence were compared to those receiving surgery later than 3 weeks. In addition, volumetric analyses were used to determine tumor burden and location.

RESULTS
103 consecutive patients (mean age: 59 years; 64 males and 39 females) undergoing first re-resection for recurrent GBM from 2018 to 2022 were included. Gross total resection (GTR) had been achieved in 93 patients (91%) at first diagnosis and was achieved in 96 patients (93%) at repeat surgery. Intraoperative MRI-guided resection was performed in 84 (82%) cases and 5-ALA was applied in 8 (8%) cases, with neuromonitoring utilized in 14 (14%) cases. The median time interval between first and second resection was 341 days (IQR 343 days) while the median time interval between suspected tumor recurrence and re-resection was 20 days (IQR 23 days). Surgery was delayed beyond 3 weeks after suspected recurrence in 49 cases (mean interval 11 in the ‘early’ vs 187 days in the ‘late’ group, p&lt;0.001) due to salvage chemotherapy/targeted therapy in 18 cases, suspicion of pseudo-progression in 7 cases and patient preference in 24 cases. Compared to patients receiving ‘early’ repeat surgery, this delay was not associated with a higher rate of immediate (14/54 vs 10/49 patients, p=0.508) or permanent (3/54 vs 4/49 patients, p=0.600) post-operative neurological deterioration. Median survival after repeat surgery was 220 days and did not significantly differ between early and late surgery (212 in the late vs 243 days in the early group, p=0.682). Volumetric analyses revealed no significant differences in tumor volume or localization pertaining to eloquence.

CONCLUSION
Timing of surgery for suspected first recurrence of GBM did not impact on functional outcomes and post-surgical survival. In general, satisfactory rates of postoperative neurological deficits and post-surgical survival in this contemporary cohort of patients with repeat surgery for recurrent GBM could be achieved.
P27.23.A SKULL REMODELING SURGERY IN COMBINATION WITH TUMOR TREATING FIELDS THERAPY FOR FIRST RECURRENT GLIOBLASTOMA. FINAL RESULTS FROM OPTIMALTTF-2, A MULTI-CENTER, RANDOMIZED, CLINICAL TRIAL
Authors: Mikic N , Skjøth-Rasmussen J , Rom Poulsen F , Johannes Laursen R , Lukacova S , Møller S , Aaquist Haslund C , Hedegaard Dahlrot R , Solheim O , Solheim T S , Sørensen J H , Wong E T , Korshøj A R 
Published: October 2024

Abstract

BACKGROUND
There are no standardized treatments for first recurrent glioblastoma (rGBM) and the prognosis in the clinical trial population is approximately 6-9 months. Skull remodeling surgery (SR-surgery) aims to optimize Tumor Treating Fields therapy (TTFields) by surgically removing areas of the low conductive skull and thereby increasing the electric field intensity directly into the tumor. In silico work suggests SR-surgery increases the electric field intensity by ~30-100% and OptimalTTF-1 (pilot trial) suggests the intervention is safe with a median overall survival (mOS) of 15.5 months.

MATERIAL AND METHODS
OptimalTTF-2 is a randomized, comparative, multi-center, investigator-initiated, interventional clinical phase 2 trial aiming to examine the efficacy and safety of TTFields and physicians’ best choice oncological therapy with or without SR-surgery for 84 rGBM patients. SR-surgery was standardized with in silico work to consist of five burr holes, each 15mm in diameter, directly over the tumor resection cavity with the transducer arrays overlapping. The trial was active nationwide in Denmark from 2020-2024. Major eligibility criteria include age ≥18 years, histopathological confirmed 1st recurrence of supratentorial glioblastoma, KPS ≥ 70, and focal tumor. The primary endpoint is overall survival after 12 months (OS12), while secondary endpoints include PFS, QoL, ORR, QoL, KPS, steroid dose, and toxicity.

RESULTS
52 patients were included in the prespecified interim analysis. 26 randomized to intervention, and 26 to control. The median age of 60 years [31-80]. Baseline characteristics were balanced without statistical differences. Intent-to-treat analysis showed that the OS12 was 56% [35-73%, 95%CI] vs. 50% [29-68%, 95%CI], p =0.65, and mOS was 14.09 months [7.9 -,95%CI] vs. 10.97 months [6.5-17.3, 95%CI], p=0.41, for intervention and control, respectively. No statistically significant difference between the arms in toxicity or QoL. Conditional power calculation also suggested a low survival benefit for the planned cohort of 84 patients.

CONCLUSION
The interim analysis did not show an advantage from SR-surgery, and the trial was terminated early based on the low expected survival benefit for the entire cohort. Examination of potential negative outcome modifiers, that may attentuate the increased electric field intensity from SR-surgery are needed in the post hoc analysis.
P27.25.A THE UTILITY OF INTRAOPERATIVE MRI IN THE RESECTION OF RECURRENT GBM: A SINGLE-CENTER RETROSPECTIVE ANALYSIS
Authors: Alhalabi O , Dao Trong P , Mironov K , Nabiev K , Gareib A N , Jordan M , Joser S , Krieg S M , Unterberg A W , Jungk C 
Published: October 2024

Abstract

BACKGROUD
Intraoperative magnetic resonance imaging (iMRI) guidance for the resection of newly diagnosed glioblastoma (GBM) has been shown to be comparable to fluorescence guidance. However, the role of iMRI-guided resection in the recurrent setting remains unclear. In this study, we aimed to examine the utility of iMRI in the resection of recurrent GBM.

METHODS
Patients undergoing re-resection for the first recurrence of WHO grade 4 IDH-wildtype GBM were retrospectively analyzed. The utility of iMRI (1.5T) guidance with respect to intraoperative decision-making for additional tumor resection and residual nodular contrast enhancing (CE) tumor on early postoperative MRI (epMRI, within 48 hours, 3T) scans was assessed.

RESULTS
103 consecutive patients (mean age: 59 years; 64 males and 39 females) undergoing re-resection for first GBM recurrence in the years 2018 to 2022 were included. iMRI-guided resection was performed in 84 (81%) cases and 5-ALA was applied in 8 (8%) cases. In 11 cases (11%), neither was applied. In 77/84 (92%) patients of the iMRI group, a gross total resection (GTR; defined as no residual nodular CE tumor) was intended. After iMRI, additional resection was carried out in 53/84 cases (63%) while a GTR was already achieved in 28/84 cases (33%). In the remaining 3 cases, additional resection was not possible due to functional reasons. On epMRI, a GTR was achieved in 63/84 (75%) cases. In 17 cases (20%), residual CE was detected on epMRI (GTR not intended in 3 cases). In 28 cases with intraoperatively assumed GTR, epMRI confirmed GTR in 25 cases (89%, mismatch in 3 cases, 11%), which was higher than in cases with additional intraoperative resection after iMRI (GTR in 42 out of 53 cases, 82%, p=0.07). In the remaining 11/53 cases, residual CE tumor was detected despite additional intraoperative resection (18%). Hence, GTR was achieved in 63 out of intended 77 patients (81%). Postoperative neurological deficits were noted in 11/53 patients with additional resection (20%) compared to 3/28 patients without additional resection (10%, p=0.126) and were mostly transient (permanent deficits 3/53 and 1/28 patients, respectively). In this cohort, median survival after repeat surgery was 220 days.

CONCLUSION
iMRI provides valuable information on residual CE tumor for intraoperative decision making concerning additional tumor resection in the setting of recurrent GBM. A mismatch between GTR assessed on iMRI and epMRI could be attributed to different magnetic field strengths.
P27.26.B TUMOR GROWTH RATE IN RECURRENT GLIOBLASTOMA: WHEN TO PLAN THE BASELINE SCAN?
Authors: Dobber L , Geurts M , van den Bent M 
Published: October 2024

Abstract

BACKGROUND
Little is known about the growth rate of glioblastoma once disease progression occurs. This is relevant for the timing of baseline imaging for second-line treatment in clinical trials and subsequent response monitoring. If a tumor grows rapidly in the period between imaging and therapy initiation, adequate response assessment may be hindered leading to false interpretations of progression to the experimental treatment. Recommendations on the interval duration between baseline scanning and treatment initiation are inconsistent between the RANO 2.0 criteria and various study protocols. We assessed whether the tumor area differs between the scan showing progressive disease (‘progression scan’) and the scan for study entry (‘baseline scan’) to determine the tumor growth rate.

MATERIAL AND METHODS
Patients who participated in a prospective clinical intervention for their first glioblastoma recurrence in the Erasmus MC and who had two available MRI scans with measurable disease made within ≤35-day interval between the progression scan and baseline scan were included. Main exclusion criterion was tumor re-resection. Tumor areas (2D) were assessed by three independent observers (per RANO). The percentage change in tumor area was calculated and compared to RANO’s ≥25% definition of disease progression. We chose a 17-day cut-off as landmark to evaluate the number of patients with tumor progression considering this is the maximum interval allowed by recent studies (e.g. NCT01986348, NCT04910022).

RESULTS
Fifty-three patients were included. Mean time between the progression scan and the baseline scan for study entry was 20 days. Mean tumor areas at progression and baseline scan were 1223mm2 (range, 128-4397) and 1405mm2 (range, 239-4493), respectively (mean difference in tumor area of 182mm2 (95% confidence interval (CI), 114-249mm2, p&lt;0.001). This corresponds to a 15% tumor area growth (CI, 9-21%, p&lt;0.001) between scans. Most tumor areas (47/53) increased in the short time interval between imaging. Eighteen out of 53 patients had formal disease progression (≥25%) within the 35-day interval. One third of the patients (7/19) who had two scans within 17 days had ≥20% tumor area increase and 5/19 patients had ≥25% tumor area increase.

CONCLUSION
We demonstrate the fast growth rate of recurrent glioblastoma. To properly assess the effect of second-line treatment, we emphasize the importance of baseline imaging as close as possible to starting with trial treatment: even a 17-day interval may result in misinterpretation at the first follow-up moment. Trial protocols must consider enrolling patients based on the scan demonstrating progression and perform baseline imaging 1-2 days prior to starting treatment.
P27.28.B UPSKILLING AND CONNECTING THE NEURO-ONCOLOGY WORKFORCE THROUGH A FREE, COMMUNITY-LED NATIONAL PLATFORM: REFLECTIONS ON TWO YEARS OF THE TESSA JOWELL ACADEMY
Authors: Allen B , Goetz C , Wright A , Huskens N , Bushby K 
Published: October 2024

Abstract

BACKGROUND
The Tessa Jowell Academy is a community platform that connects and upskills the neuro-oncology workforce through training, educational resources, peer-to-peer learning and networking opportunities. Informed by the findings of the Tessa Jowell Centre of Excellence review process, which identified best practice, variation and common challenges, it uses a grassroots community-led approach to disseminate excellence in treatment, care and research and collaboratively build solutions to national challenges. We reflect on two years of success connecting and training NHS clinicians and researchers.

MATERIAL AND METHODS
The Academy empowers the neuro-oncology community to jointly tackle challenges by: • Sharing knowledge: through tailored neuro-oncology webinars and training courses, a clinical trial finder, and a charity directory, all designed and delivered by the community in prioritised areas. • Connecting professionals: through networks and working groups, a peer-to-peer connect service and tailored centre support, directly connecting professionals both across the country and between specialties, breaking down siloes and creating a coherent and connected neuro-oncology community. All Academy features are designed and delivered by the community, in response to the most pressing needs facing the UK neuro-oncology workforce. Membership is open for free to all NHS professionals, individuals based in UK academic institutions and partners of the Tessa Jowell Brain Cancer Mission (TJBCM).

RESULTS
In two years the Academy has supported an unprecedented community-building project, with over 1,200 members from 31 NHS centres, 2,400 workshop registrations, 24 national working groups and networks, and 200 members actively involved in task-and-finish groups. The Academy has tackled siloed working practices, helping doctors, nurses and allied health professionals (AHPs) working in single-handed, isolated settings to connect with peers and learn best practice. The first scenario-based supportive care training for neuro-oncology AHPs was delivered, with three more planned and Academy groups are now developing specialty-specific guidelines in areas such as neuropsychology and physiotherapy to standardise practice across the UK.

CONCLUSION
The Academy’s success has only been possible due to the extraordinary level of engagement from the adult neuro-oncology community. Through this community-led approach, the Academy will continuously build on the excellence of the community in a solution-focused manner, with an expansion planned for the paediatric neuro-oncology community. The TJBCM will continue working with this community, generating learnings that can easily be applied to other cancers and rare diseases.
P27.32.B V-REX RANDOMIZED TRIAL
Authors: Dhayalan D 
Published: October 2024

Abstract

IMPORTANCE
Current guidelines for treating small- to medium-sized vestibular schwannoma recommend either upfront radiosurgery or waiting to treat until tumor growth has been detected radiographically.

OBJECTIVE
To determine whether upfront radiosurgery provides superior tumor volume reduction to a wait-and-scan approach for small- to medium-sized vestibular schwannoma.

DESIGN, SETTING, AND PARTICIPANTS
Randomized clinical trial of 100 patients with a newly diagnosed (&lt;6 months) unilateral vestibular schwannoma and a maximal tumor diameter of less than 2 cm in the cerebellopontine angle as measured on magnetic resonance imaging.

INTERVENTIONS
Participants were randomized to receive either upfront radiosurgery (n = 50) or to undergo a wait-and-scan protocol, for which treatment was given only upon radiographically documented tumor growth (n = 50). Participants underwent 5 annual study visits consisting of clinical assessment, radiological examination, audiovestibular tests, and questionnaires.

MAIN OUTCOMES AND MEASURES
The primary outcome was the ratio between tumor volume at the trial end at 4 years and baseline (V4:V0). There were 26 prespecified secondary outcomes, including patient-reported symptoms, clinical examinations, audiovestibular tests, and quality-of-life outcomes. Safety outcomes were the risk of salvage microsurgery and radiation-associated complications.

RESULTS
Of the 100 randomized patients, 98 completed the trial and were included in the primary analysis (mean age, 54 years; 42% female). In the upfront radiosurgery group, 1 participant (2%) received repeated radiosurgery upon tumor growth, 2 (4%) needed salvage microsurgery, and 45 (94%) had no additional treatment. In the wait-and-scan group, 21 patients (42%) received radiosurgery upon tumor growth, 1 (2%) underwent salvage microsurgery, and 28 (56%) remained untreated. For the primary outcome of the ratio of tumor volume at the trial end to baseline, the geometric mean V4:V0 was 0.87 (95% CI, 0.66-1.15) in the upfront radiosurgery group and 1.51 (95% CI, 1.23-1.84) in the wait-and-scan group, showing a significantly greater tumor volume reduction in patients treated with upfront radiosurgery (wait-and-scan to upfront radiosurgery ratio, 1.73; 95% CI, 1.23-2.44; P =.002). Of 26 secondary outcomes, 25 showed no significant difference. No radiation-associated complications were observed.

CONCLUSION AND RELEVANCE
Among patients with newly diagnosed small- and medium-sized vestibular schwannoma, upfront radiosurgery demonstrated a significantly greater tumor volume reduction at 4 years than a wait-and-scan approach with treatment upon tumor growth. These findings may help inform treatment decisions for patients with vestibular schwannoma, and further investigation of long-term clinical outcomes is needed.