bluuebunny/crossref_metadata_2025_split huggingface dataset:
P11.16.A Questioning convention - is intrathecal chemotherapy (ITC) necessary for patients with newly diagnosed primary central nervous system lymphoma (PCNSL): combined results from three independent cohorts
Authors: Tuohy K , Aregawi D , Seidel S , Rieger L , Klapschus O , Zacharia B , Korfel A , Schlegel U , Glantz M 
Published: September 2022

Abstract

Background
Despite beguiling responses to initial therapy in many patients, PCNSL remains a therapeutic challenge. Relapse is common, cures are elusive for most patients, and overall response are disappointing compared to other diffuse large B-cell lymphomas. High-dose methotrexate-based therapies have become the standard of care, with many variations, but there is no consensus, and very little data regarding the role of ITC in the initial treatment of patients with PCNSL.

Material and Methods
We collected study-level and where possible, patient-level data from three independent clinical trials comparing adults with newly diagnosed PCNSL treated with regimens that differed based on the use of ITC. Patient characteristics, overall (OS) and progression-free survival (PFS), and characteristics of relapse were examined. The frequency of lymphomatous meningitis at diagnosis based on the location of CSF sampling - ventricular vs. lumbar - was also investigated. Complete data retrieval for this updated analysis has allowed us to combine data from the three studies and calculate summary statistics using a random effects model and inverse variance technique. In addition, predictors of OS and PFS were modeled using a Cox proportional hazards technique.

Results
The three cohorts were treated with: HD MTX/rituximab/ifosfamide followed by either HD MTX/cytarabine/ifosfamide (group Ia), or cytarabine/thiotepa and autologous stem cell transplant (group Ib) (n=80); HDMTX/vinca alkaloids/ifosfamide/cytarabine (group II) (n=83); or HD MTX/rituximab (group III) (n=49). ITC consisted of MTX/cytarabine/prednisolone (group Ia only, n=43); MTX/cytarabine/prednisolone (group II, n=65); or liposomal cytarabine (group III, n=21). One- and two-year OS was better in the ITC chemotherapy compared to the no-ITC group (RR 1.25 [1.16-1.34] and 1.20 [1.14-1.26] respectively, p&lt; 0.001 for both comparisons). One-year PFS was also improved in the ITC group (RR 1.12 [1.01-1.25], p=0.031). Two-year PFS was not statistically different between groups (RR 1.20 [0.90-1.59], p=0.220). Relapse involving the CSF was more frequent in the non-IT chemotherapy group (RR 2.31 [2.03-2.62], p&lt; 0.001). CSF cytology was positive in 81% of ventricular specimens vs 14.3% of lumbar specimens (p&lt; 0.001).

Conclusion
This analysis of three independent cohorts of adults with newly diagnosed PCNSL suggests (when ventricular rather than lumbar CSF is sampled) that lymphomatous meningitis is dramatically more frequent, and perhaps universal. Including ITC as part of the initial treatment regimen increased both OS and PFS substantially. A randomized controlled trial is urgently required.
P11.18.A Localizing value of EEG recordings in patients with glioblastoma
Authors: Silvaieh S , Marko M , Trimmel K , Zulehner G , Berghoff A , Preusser M , Schmook M , Ulbrich L , Hainfellner J A , Widhalm G , Rössler K , Berger T , Pataraia E , Grisold A 
Published: September 2022

Abstract

Background
Glioblastoma is associated with a high risk of epileptic seizures ranging from 40% to 60%. Before the advent of modern imaging techniques, electroencephalography (EEG) was a critical component in evaluating patients with space-occupying lesions. In this retrospective single-center study, we aimed (1) to characterize a cohort of patients with glioblastoma with regards to EEG monitoring, seizure frequency and the frequency of prescribed anti-seizure medications (ASM) and (2) to assess the value of EEG as a localizing technique in patients with glioblastoma.

Material and Methods
We reviewed the charts of 179 patients with glioblastomas between January 1st, 2020 and January 1st, 2022, treated at the Medical University of Vienna. The diagnosis was based on MRI and/or confirmed by biopsy according to the 2016 World Health Organization Classification of Tumors of the Central Nervous System. Patients who received an in-house EEG as part of their diagnostic work-up were included if an MRI/CT scan was available (within an average time of +/-60 days). For localization, focal slowing (theta/delta activity) and/or epileptiform discharges were considered. EEG rating was performed by a board-certified electrophysiologist blinded for the diagnosis and MRI/biopsy findings.

Results
We included 52 patients (29.05% of screened cohort) with at least one EEG and MRI or CT scan performed before or after EEG, following inclusion criteria (median: 2 days; mean: 6 days; range: -29 to 52), in the final analysis. Clinical seizure activity and/or epileptiform discharges on EEG were detected in 46 patients (88.46%), and 48 patients (92.31%) were on ASM.
An IDH-wildtype glioblastoma was diagnosed in 45 patients (86.54%), 4 had an IDH-mutant glioblastoma (7.69%), and in 3 patients, IDH-status was unknown (5.77%). In 22 patients (42.31%), biopsy revealed a positive MGMT promoter methylation status, while 28 were unmethylated (53.84%), and two patients had an unknown MGMT promoter methylation status (3.85%). Intermittent and/or continuous focal slow-wave activity was registered in 45 patients (86.54%). In comparison, epileptiform discharges could only be found in 13 patients (25%). When compared to MRI/CT scans, the hemispheric tumor localization could be determined in 42 cases (80.77%). Moreover, the affected brain lobe was accurately predicted in 35 patients (67.31%). Three patients had diffuse EEG changes (5.77%), and EEG was unremarkable in 7 patients (13.46%).

Conclusion
Overall, our presented data indicate that the hemispheric localization of glioblastoma can be reliably predicted by EEG recordings, while a precise (brain lobe-specific) localization was only possible in around two-thirds of cases.
P11.19.B Bevacizumab in recurrent WHO grade 2-3 gliomas
Authors: Annakib S , Rigau V , Darlix A , Gozé C , Duffau H , Bauchet L , Mollevi C , Fabbro M 
Published: September 2022

Abstract

Background
Medical management of recurrent WHO grade 2-3 (rGII/III) gliomas is not well established. Bevacizumab (BEV) is an option at malignant recurrence. Yet, very few data are available in this indication. The aim of this study is to describe clinical outcomes in patients treated with BEV.

Material and Methods
A retrospective study was conducted including patients treated by BEV for a rGII/III glioma at our institution (2011 - 2019). Data were collected from medical records. Tumor samples were reviewed according to the WHO 2016 classification. Efficacy was assessed according RANO criteria. Progression Free Survival (PFS) and Overall Survival (OS) from BEV initiation were estimated using the Kaplan-Meier method. A Cox proportional hazards model was performed to estimate Hazard Ratios with 95% Confident Intervals (CI).

Results
A total of 81 patients was included (sex ratio: 1.6 M/W, median age at diagnosis: 38). Among them, 46 patients (56.8%) had a grade 2 and 35 (43.2%) a grade 3 glioma. The histological forms were astrocytoma (grade 2 -3) IDH mutated in 27 patients (33.3%), IDHwt in 15 patients (18.5%) and oligodendroglioma (grade 2 - 3) in 13 patients (16%). Twenty-six patients were not reclassified. Previous treatment included tumor resection for all patients (second intervention in 22.2%). First-line medical treatment consisted of chemotherapy in 60.5% patients before any radiotherapy. Chemotherapy was rechallenged in 52 patients (64.2%). All patients but one received radiation therapy and 19 patients (23.5%) received a reirradiation. BEV was administered at 10 or 15mg/kilogram every 2 or 3 weeks. All patients had a contrast enhancement on MRI at baseline. Median number of BEV cycles was 7 [1-79], in association with chemotherapy in 45.7%. Partial response, stable disease and progressive disease was observed in 27.2%, 22.2% and 50.6% respectively. Median OS from BEV introduction was 7.6 months (95% CI [5.5;9.9]). Median PFS was 4.9 months (95% CI [3.7;6.1]). In univariate analysis, grade 2 (Odd Ratio (OR)=0.41, 95% CI [0.17;1.02], p=0.054), Ki67&lt;7% (OR=0.41, 95% CI [0.15;1.21], p=0.079) and initial total surgical resection (OR=2.75, 95% CI [0.68;11.11], p=0.097) showed a trend for delayed progression. BEV was stopped for progression in 70.4%, for toxicity in 8.6% and for others reasons in 21% patients. Twenty-four patients (29.6%) discontinued BEV without progression (medical decision, BEV toxicity or patient decision). Presence of 1p19q codeletion (OR=0.24, 95% CI [0.07;0.84], p=0.023) and age ≥ 38 (OR=0.36, 95% CI [0.13;0.99], p=0.042) at diagnosis were more frequent in this sub-population. Out these of 24 patients, 8 showed survival from 3 months to 5 years without any other treatment.

Conclusion
BEV can be a good option for patients with rGII/III glioma. One third of them stopped treatment without progression, reaching a survival of several years for some of them.
P11.23.B Neurological symptoms independently associate with overall survival in patients with melanoma brain metastases
Authors: Steindl A , Heimbach K , Ressler J , Gatterbauer B , Dieckmann K , Widhalm G , Preusser M , Berghoff A 
Published: September 2022

Abstract

Background
Based on the the rising detection of asymptomatic brain metastases (BM) and the remarkable intracranial responses of targeted- and immunotherapy in specific subgroups of asymptomatic BM patients, we aimed to evaluate the clinical characteristics and prognostic value of neurological symptoms in BM from melanoma.

Material and Methods
670 patients with newly diagnosed melanoma BM were identified from the Vienna Brain Metastasis Registry. We performed retrospective chart review and statistical outcome analyses.

Results
370/670 (55.2%) patients presented with neurological symptoms including neurological deficits (316/370; 85.4%), signs of increased intracranial pressure (126/370; 34.1%) and epileptic seizures (53/370; 14.3%). 57.6% (80/139) of patients with BRAF mutated melanoma presented with asymptomatic BM at diagnosis. Absence of neurological symptoms at BM diagnosis was associated with a longer median overall survival after time of BM diagnosis (7 vs. 5 months; p&lt; 0.001; log-rank test). In multivariate analysis with the diagnosis-specific graded prognostic assessment (DS-GPA: HR:1.4; 95% CI, 1.25-1.48; p&lt;0.001) and the graded prognostic assessment for melanoma using molecular markers (Melanoma-molGPA: HR:0.8; 95% CI, 0.66 -0.92; p&lt;0.001), the presence of neurological symptoms (HR 0.8; 95% CI, 0.69 -0.96; p=0.003/ HR:0.6; 95% CI, 0.59-0.72; p&lt;0.001) was found to be independently associated with survival prognosis from time of BM diagnosis respectively.
Conclusion:
Neurological symptoms at the time of BM diagnosis are an independent and strong prognostic factor in melanoma BM patients. Our results argue for the integration of neurological symptoms into the prognostic assessment of patients with BM from melanoma.
P11.24.A The anisotropic component of the decomposed diffusion tensor predicts overall survival in patients with glioblastoma
Authors: Simon N L , Sinha R , Sravanam S , Mayrand R , Li C , Wan Y , Wei Y , Price S 
Published: September 2022

Abstract

Background
The diffusion tensor can be decomposed into isotropic (DTI-p) and anisotropic (DTI-q) components (Peña et al., 2006). Regions of DTI-q abnormality have a high tumour burden and increased surgical resection of abnormal DTI-q positively correlates with overall survival (OS) (Yan et al., 2017). We aimed to establish if median voxel DTI-q (MVQ) or a distribution measure of DTI-q (DMQ) could act as a neuro-imaging biomarker, to predict OS in patients with glioblastoma.

Material and Methods
Diffusion tensor decomposition was used to create DTI-p and DTI-q maps, using FSL software (FMRIB Software Library, Oxford). MVQ and DMQ (the 95th centile minus the 5th centile of the DTI-q distribution, divided by the MVQ) were calculated from the preoperative whole brain (WB), contrast-enhancing (CE), and non-contrast-enhancing (NCE) hemisphere DTI-q maps, using fslstats, for 33 patients with glioblastoma. Using R Studio, multiple linear regression (MLR) models were computed to establish if MVQ or DMQ of the WB, CE and NCE hemispheres or age, significantly predicts OS. The Breusch-Pagan Test, on package “lmtest” in R, was calculated for all MLR models, to determine if heteroscedasticity was present and, if so, bootstrapped multiple regression (BMR) models were computed using package “boot” in R.

Results
Evidence for heteroscedasticity was present in MLRs that modelled the relationship between DMQ of WB, age, and OS (BP = 6.032, p = 0.014) and DMQ of CE hemisphere, age, and OS (BP = 7.163, p = 0.028). In the BMR of WB DMQ, age, and OS, the 95% bias-corrected accelerated confidence intervals (BCa-CI) for the WB DMQ regression coefficient was 133.5 - 1851.4 and included the WB DMQ estimated coefficient of 803.9. The BMR of CE hemisphere DMQ, age, and OS, computed a 95% BCa-CI for the CE hemisphere DMQ coefficient of 101.8 - 1579.6, containing the CE hemisphere DMQ coefficient estimate of 612.414. For both BMRs, the 95% BCa-CI for age coefficients crossed a value of 0. From computed MLR models, WB MVQ (t = -2.569, p = 0.015), CE hemisphere MVQ (t = -2.143, p = 0.040), NCE hemisphere MVQ (t = -2.567, p = 0.015) and NCE hemisphere DMQ (t = 2.39, p = 0.024) were significant predictors of OS. Age did not significantly predict OS in any models and was not significantly related to WB, CE and NCE hemisphere MVQ or DMQ.

Conclusion
WB, CE and NCE hemisphere MVQ and DMQ predict OS in our tested subgroup of patients with glioblastoma. Age is not a significant predictor of OS and does not significantly correlate with MVQ or DMQ. The median value and distribution spread of DTI-q may act as a prognostic biomarker in glioblastoma, facilitating patient stratification.
P11.29.B Risk factors associated with the presence of brain metastasis at the moment of diagnosis in non-small cell lung cancer patients. Retrospective case series
Authors: Martín-Abreu C M , Fariña-Jerónimo H , Plata-Bello J 
Published: September 2022

Abstract

Background
Lung cancer is the second most frequent neoplasm worldwide and the leading cause of cancer death in both sexes. Furthermore, it is the most common origin of brain metastases. The aim of this study is to identify clinical, histological, and molecular variables associated with a higher risk of presenting brain metastases at the moment of diagnosis in patients with lung cancer.

Material and Methods
A single-center retrospective case series analysis of patients with a new diagnosis of lung cancer (from January 2015 to December 2018) was performed. A total of 723 total patients with a new diagnosis of non-small cell lung cancer (NSCLC) were identified. Only patients with a brain imaging study at the time of diagnosis were included in the analysis. Non-parametric statistical tests were used to compare patients with or without metastases at the moment of diagnosis. A uni- and multivariate analysis were performed to identify risk factors associated with the presence of brain metastases at NSCLC diagnosis. Statistical significance was considered when p&lt;0.05.

Results
We included 135 patients with a new diagnosis of lung cancer and with brain imaging study at the time of diagnosis (mean age at diagnosis of 64.69 years [SD= 10.34]; 71.9% men). The most common histology was adenocarcinoma (67.1%) followed by squamous carcinoma (25.2%). Brain metastases were present in 40% of patients at diagnosis. No significant differences in clinical, histological and molecular variables was identified between patients with or without brain metastases. In any case, as expected, the survival analysis showed that brain metastasis at diagnosis was associated with a worse overall survival (Log-Rank test, p&lt;0.01).The univariate analysis showed that presenting neurological symptoms (OR=19.5, p&lt;0.0001 CI [7.895-47.65]), histology of adenocarcinoma (OR= 2.113, p&lt;0.014 CI [1.160-3.849]) and the presence of visceral metastases (OR= 14.444, p&lt;0.0001 CI [6.161-33.86]) were associated to the presence of brain metastases at diagnosis. The presence of metastases limited to the thorax (OR= 0.019, p&lt;0.001 CI [0.003-0.146] was associated to be free of brain metastasis at NSCLC diagnosis. However, only neurological symptoms (OR= 20.290, p&lt;0.0001 CI [4.953-83.118]), presenting visceral metastases (OR= 4.451, p&lt;0.010 CI [1.458-13.777]) and/or metastases limited to the thorax (OR= 0.066, p&lt;0.024 CI [0.006-0.010]) reached statistical significance in the multivariate analysis.

Conclusion
Neurological symptoms and the presence of visceral metastases are independent predictors or presenting brain metastasis at the moment of diagnosis in lung cancer patients. On the other hand, the presence of lung cancer disease confined in the thoracic cavity is associated with a lower risk to present brain metastasis
P11.33.B Tumour Treating Fields (TTFields; 200 kHz) with chemo-radiation and maintenance TTFields/temozolomide as first-line treatment for newly-diagnosed glioblastoma: The phase 3 TRIDENT Trial (EF-32)
Authors: Shi W , Kleinberg L , Jeyapalan S A , Goldlust S A , Nagpal S , Roberge D , Nishikawa R , Grossman R , Glas M 
Published: September 2022

Abstract

Background
Tumour Treating Fields therapy (TTFields; 200 kHz) is a noninvasive, loco-regional, antimitotic treatment approved for newly diagnosed glioblastoma (ndGBM) and mesothelioma. In the phase 3 EF-14 trial, TTFields/temozolomide (TMZ) significantly increased overall survival (OS) and progression-free survival (PFS) vs TMZ alone in patients with ndGBM. TTFields-related adverse events (AEs) were mainly dermatological with no increases in systemic toxicity. In preclinical models, the addition of TTFields to radiotherapy (RT) increased the therapeutic effect. In 2 clinical pilot phase 2 studies, TTFields added to RT/TMZ was reported as feasible and well-tolerated.

Material and Methods
TRIDENT (EF-32; NCT04471844) is an international, phase 3 randomised trial comparing TTFields (200 KHz, ≥ 18 h/day)/RT/TMZ vs RT/TMZ alone. Eligibility criteria include histologically confirmed ndGBM, ≥ 18 years of age (≥ 22 years of age; US), Karnofsky Performance Status ≥ 70, life expectancy ≥ 3 months, adequate organ function and eligible for RT/TMZ - participants will be stratified by extent-of-resection and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. During the initial 6-week investigational period, patients in the experimental arm will receive continuous TTFields and concomitant RT/TMZ whilst patients in the control arm will receive only RT/TMZ. Subsequently, all patients will receive TTFields and 6 cycles of maintenance TTFields/TMZ. TTFields will continue for 24 months or until second disease progression per Response Assessment in Neuro-Oncology (RANO), whichever occurs first. The primary endpoint is median OS. Secondary endpoints include median PFS (RANO), 1- and 2-year survival rates, overall radiological response (RANO), PFS6, PFS12, severity and frequency of AEs (Common Terminology Criteria for Adverse Events v5.0), post-treatment pathological changes in resected GBM tumours, quality-of-life per EORTC QLQ-C30, OS correlation to TTFields duration-of-usage, and neurological assessment per NANO (Neurological Assessment in Neuro-Oncology) and RANO criteria. Survival will be measured from time-of-randomisation. Sample size (N = 950; randomised 1:1) was powered for a hazard ratio &lt; 0.8 with a 5% type I error. The hypothesis, that first-line TTFields/RT/TMZ can significantly improve OS vs RT/TMZ, will be tested using a stratified log-rank test.
The study is currently open to enrollment in locations in Austria, Belgium, Czech Republic, France, Germany, Israel, Switzerland, and across the US.
P11.35.B The clinical course of long-term survivors after the diagnosis of brain metastasis
Authors: Jünger S T , Meissner A , Ruge M I , Rueß D , Goldbrunner R , Grau S 
Published: September 2022

Abstract

Background
To asses demographic and clinical parameters, treatment, and course of disease in patients surviving longer ≥ 5 years after the diagnosis of brain metastasis (BM).

Material and Methods
We retrospectively identified patients who were treated for BM and survived ≥ 5 years after initial BM diagnosis. We analysed and described clinical and treatment related parameters with respect to histology, time to occurrence and systemic/ BM-specific treatment.

Results
We included 48 patients with a mean age of 55 years (range 33-81, SD 12) at diagnosis of primary tumor and 58 (range 41-84, SD 20) at initial BM diagnosis. Histology was non-small-cell lung cancer in 18 (37.5%), melanoma in 14 (29.2%), breast cancer in 11 (22.9%), renal carcinoma in 2 (4.2%), and small-cell lung cancer, cancer of unknown primary and gastrointestinal cancer in one case each (2.1%). Treatment for primary tumor included resection (83.3%), chemotherapy (43.8%), radiation (33.3%), interferon therapy (18.8%), and immuno-/targeted therapy (25%). Most patients received a combination of latter. The mean interval between primary tumor and BM diagnosis was 36 months (range -2 to 277; SD 57). At the time of BM diagnosis, 50% of patients presented with systemically stable disease, 66.7% showed BM related symptoms, 92% showed a KPS ≥70. Most patients had 1 BM (72.9%), while 20.9% had 2-3 and 6.3% &gt;3. Initial treatment for BM comprised resection (60.4%), stereotactic radiosurgery (27.2%), whole-brain-radiation therapy (8.4%), and interstitial brachytherapy (4.2%). Approximately half of the patients (52.1%) suffered from ≥1 BM relapse at initial treatment site. At the time of the analysis, 13 (27.1%) patients had died; cause of death was mostly unknown, in two patients each, systemic/cerebral cause was confirmed. The mean overall survival (OS) was 131 months (range 64-344, SD 68) and 95 (range 60-246, SD 36) after diagnosis of primary tumor and BM, respectively. All patients suffering from melanoma who had received interferon therapy (n=8) survived. Neither systemic status at BM diagnosis nor the administration of novel treatment agents or chemotherapy after BM diagnosis showed an impact on OS (p=0.642, p=0.177 and p=0.628, respectively). Further survival analysis was omitted due to subgroup sizes.

Conclusion
Despite the usually fatal course after BM development, some patients show long-term survival. Whether specific genetic parameters have a particular impact in this subgroup of patients, warrants further investigation.