bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relative baryon-dark matter velocities in cosmological zoom simulations
Authors: Conaboy Luke , Iliev Ilian T , Fialkov Anastasia , Dixon Keri L , Sullivan David 
Published: September 2023

ABSTRACT
Supersonic relative motion between baryons and dark matter due to the decoupling of baryons from the primordial plasma after recombination affects the growth of the first small-scale structures. Large box sizes (greater than a few hundred Mpc) are required to sample the full range of scales pertinent to the relative velocity, while the effect of the relative velocity is strongest on small scales (less than a few hundred kpc). This separation of scales naturally lends itself to the use of ‘zoom’ simulations, and here we present our methodology to self-consistently incorporate the relative velocity in zoom simulations, including its cumulative effect from recombination through to the start time of the simulation. We apply our methodology to a large-scale cosmological zoom simulation, finding that the inclusion of relative velocities suppresses the halo baryon fraction by 46–23 per cent between z = 13.6 and 11.2, in qualitative agreement with previous works. In addition, we find that including the relative velocity delays the formation of star particles by ∼20 Myr on average (of the order of the lifetime of a ∼9 M⊙ Population III star) and suppresses the final stellar mass by as much as 79 per cent at z = 11.2.
Commensal transient searches in eight short gamma-ray burst fields
Authors: Chastain S I , van der Horst A J , Rowlinson A , Rhodes L , Andersson A , Diretse R , Fender R P , Woudt P A 
Published: September 2023

ABSTRACT
A new generation of radio telescopes with excellent sensitivity, instantaneous uv coverage, and large fields of view, are providing unprecedented opportunities for performing commensal transient searches. Here, we present such a commensal search in deep observations of short gamma-ray burst fields carried out with the MeerKAT radio telescope in South Africa at 1.3 GHz. These four hour observations of eight different fields span survey lengths of weeks to months. We also carry out transient searches in time slices of the full observations, at time-scales of 15 min and 8 s. We find 122 variable sources on the long time-scales, of which 52 are likely active galactic nuclei, but there are likely also some radio flaring stars. While the variability is intrinsic in at least two cases, most of it is consistent with interstellar scintillation. In this study, we also place constraints on transient rates based on state-of-the-art transient simulations codes. We place an upper limit of 2 × 10−4 transients per day per square degree for transients with peak flux of 5 mJy, and an upper limit of 2.5 × 10−2 transients per day per square degree for transients with a fluence of 10 Jy ms, the minimum detectable fluence of our survey.
PL01.5.A NEOADJUVANT CAMRELIZUMAB AND APATINIB IN PATIENTS WITH RECURRENT HIGH-GRADE GLIOMAS:PRIMARY REPORT OF AN OPEN LABEL PHASE II STUDY
Authors: Chen Z , Guo C , Yang Q , Hu W , Cao X , Liao Y , Zhang J , Jiang X , Li D , Chen Y 
Published: September 2023

Abstract

BACKGROUND
Recurrent high-grade gliomas (HGG) is a challenge with a poor prognosis and limited treatment options. A study has reported that neoadjuvant immunotherapy upregulates PD-L1 expression and CD8+T cell infiltration, which is expected to improve the survival of HGG. Our study (NCT04588987) aimed to assess the efficacy and safety of perioperative camrelizumab (anti-PD-1 antibody) and apatinib (antiangiogenic agent) in patients with recurrent HGG.

METHODS
Patients with recurrent HGG received 14 days of neoadjuvant treatment with camrelizumab (intravenous injection 200 mg on day 1) and apatinib (oral 250 mg per day on days 1-7), followed by surgery for recurrent tumor. Sequential therapy began 2 weeks after surgery with the biweekly camrelizumab (200mg) and 4 weeks after surgery with the daily apatinib (250mg) until investigator-assessed progressive disease or unable to tolerate toxicity. The primary endpoint was overall survival (OS).

RESULTS
Between Oct 9, 2020 and Feb 14, 2023, 18 patients have been enrolled (14 for recurrent glioblastomas, 3 for anaplastic astrocytoma and 1 for anaplastic oligodendroglioma). At the data cut-off (Mar 31, 2023), 16 patients discontinued study treatment (12 cases of disease progression, 1 case of liver function injury, 1 case of COVID-19 infection, 1 case refused treatment and 1 case died before progression). The median treatment time for camrelizumab and apatinib were 4.8 (95% CI: 3.8-5.9) months and 5.2 (95% CI: 3.9-6.4) months, respectively. The median OS was 12.9 months (95% CI: 9.3-16.4) with a median follow-up time of 17.5 (95%CI:9.0-26.1) months. The median PFS was 4.8 months (95% CI: 4.4-5.2). Nine (50%) patients occurred grade 3 treatment-related adverse events (TRAEs). Decreased lymphocyte count (22.2%, 4/18), hypertension (16.7%,3/18) and Increased aspartate aminotransferase (11.1%,2/18) were the most common grade 3 TRAEs, and there were no grade 4 or 5 TRAEs.

CONCLUSION
This combination therapy in recurrent HGG demonstrated encouraging efficacy, and TRAEs are manageable.Keywords: Apatinib, Camrelizumab, Neoadjuvant therapy, Recurrent high-grade gliomas.
KS03.6.A HIGH RATE OF MULTIFOCAL RELAPSE AND SUBSEQUENT POOR PROGRESSION-FREE SURVIVAL POST SALVAGE RADIATION THERAPY FOR WHO GRADE 2-3 MENINGIOMA MANAGED WITH INITIAL SURGERY ALONE
Authors: Back M , Horsley P , Yim J , Drummond J 
Published: September 2023

Abstract

BACKGROUND
Optimal initial management for patients with localised high risk meningioma remains uncertain with long natural history disease promoting the option of delaying adjuvant radiation therapy until relapse. This study assessed patterns of relapse and survival in a cohort of patients with high-risk meningioma managed with initial surgical therapy alone.

MATERIAL AND METHODS
Consecutive patients with meningioma referred for radiation therapy (IMRT) between January 2008-December 2021 were entered into an ethics approved database managed by the Neuro-oncology MDT. Categorisation and subsequent management plans were based by grade on WHO2007-2016 classification. Immediate or delayed referral pathway for IMRT was individualised by neurosurgical team. At time of subsequent referral for IMRT at relapse patients had tumour site / volume determined by MRI and Dotatate PET. Tumour volume, site of relapse in relation to initial cavity and number of recurrent foci of disease were recorded. For patients subsequently receiving IMRT an integrated-boost, generally 60Gy/54Gy, was used. Primary endpoints were site of relapse in relation to initial surgical cavity, number of foci, and median time from initial surgery. Secondary endpoints were median progression-free(mRFS)/overall survival(mOS) calculated from start salvage IMRT compared to cohort of intercurrent patients managed at initial diagnosis.

RESULTS
One hundred and five patients with meningioma were referred, with median follow-up for survivors of 3.6yrs (q1-3:1.5-7.7yrs). Median age was 59.2yrs; 59% had convexity meningioma; WHO2016 grade was G3 in 21%; Atypical(G2) in 66% and G1/no biopsy in 9% of patients. Twenty-two patients have subsequently relapsed post IMRT; with sixteen deceased for 8yrPFS and 8yrOS of 63.5% and 73.5% respectively. Forty-nine(46%) of patients were referred for IMRT at relapse, of which 39% had repeat resection prior to IMRT referral; and 14% were WHO2016 G3 at most recent resection. Based on MRI/Dotatate 61% had more than one focus of tumour around initial surgical cavity. Subsequent to salvage IMRT, fifteen of the 49 patients have had further relapse and eleven are deceased. Patients managed at relapse had worse PFS with 55.1% 8yrPFS vs 78.0% 8yrPFS (p=0.03); however equivalent OS with 68.8% 8yrOS vs 79.4% 8yrOS (p=0.62).

CONCLUSION
Patients with G2/3 meningioma managed with surgery alone upfront more often had relapses that were multifocal that were not managed with further salvage surgery. The subsequent progression-free survival was poor with a high rate of subsequent relapse post salvage IMRT, especially when compared to patients managed with IMRT at time of initial diagnosis.
JS06.4.A MULTI-OMIC CHARACTERIZATION OF LUNG CANCER BRAIN METASTASIS REVEALS THE METABOLIC VULNERABILITY AS A NOVEL THERAPEUTIC TARGET
Authors: Duan H , Wei S , Liu Y , Zhang G , Mou Y 
Published: September 2023

Abstract
Lung cancer brain metastases (LC-BrMs) are frequently associated with dismal mortality rates in patients with lung cancer; however, standard of care therapies for LC-BrMs are still limited in their efficacy. A better understanding of the molecular mechanisms and tumor microenvironment of LC-BrMs will provide us with new insights into developing novel therapeutics for treating patients with LC-BrMs. Here, we performed integrated analyses of both bulk and single cell genomic transcriptomic and proteomic data derived from five published and two newly generated patient cohorts, totaling 141 patients with paired and unpaired primary lung cancer and LC-BrM. This was subsequently validated by immunohistochemistry (IHC) and multiplexed immunofluorescence (mIF) staining. LC-BrMs exhibited significantly lower tumor mutational burden but higher intra-tumor heterogeneity. We observed that mutations in a subset of genes were almost always shared by both primary lung cancers and LC-BrM lesions, including TP53, MUC16, LRP1B, KRAS, FAT3, and NF1. In addition, the genome-wide landscape of somatic copy number alterations (SCNAs) was found to be similar between primary lung cancers and LC-BrM lesions. Nevertheless, three regions of focal amplification were significantly enriched in LC-BrMs, including 11q13.1, 14q11.2, and 12p13.31. Integrated analyses of transcriptional and proteomic data revealed mitochondrial-specific metabolism was activated in LC-BrMs and accompanied by a suppressed tumor immune microenvironment, which was further corroborated by IHC and mIF data. Importantly, targeting oxidative phosphorylation with gamitrinib in combination with anti-PD1 immune checkpoint blockade (ICB) therapy significantly improved the survival of mice with LC-BrMs. In conclusion, our findings not only provide comprehensive and multi-omic perspectives of the molecular mechanisms of LC-BrMs but also contribute to the development of potential therapeutic strategies with the goal of translating it into clinical trials for patients with LC-BrMs.
JS07.5.A PROGNOSTIC FACTORS ASSOCIATED WITH POOR OUTCOME IN ADULT PATIENTS WITH MEDULLOBLASTOMA
Authors: GARCILAZO-REYES Y J , Dal-Col P , Bielle F , Mokhtari K , Feuvret L , Jacob J , Duran-Pena A , Capelle L , Savatovsky J , Bourdeaut F , Masliah-Planchon J , Cacho-Díaz B , Hoang-Xuan K , Idbaih A , Laigle-Donadey F 
Published: September 2023

Abstract

BACKGROUND
Medulloblastoma (MB) is a rare tumor in adults. Current recommendations are based on scarce data available in adults, and mostly derived from pediatric series. Prognostic factors have not been uniformly defined in adults to date.

MATERIAL AND METHODS
We retrospectively collected all cases of adult patients diagnosed and treated between 1995 and 2019 in our institution for histopathological proven MB. We described patient´s characteristics, disease features, treatment modalities and studied the prognostic factors for survival outcomes using univariate and multivariate analysis.

RESULTS
We identified a total of 89 cases. Male gender (66%), lateral cerebellar location (48%), desmoplastic/nodular histology (43%), Sonic Hedgehog molecular group (76%) and Chang´s M0 (72%) were the most frequent patient´s and disease characteristics. Patients mostly achieved complete resection/near total resection (62%); surgery followed by chemotherapy/radiotherapy (CT/RT) was the most frequent initial strategy (76%), favoring carboplatin-based regimens (70%), posterior fossa RT ≥50 Gy (71%) and craniospinal RT ≥ 30 Gy (59%) as the most frequently regimen used. According to the Association of French Speaking Neuro-oncologists and the European Reference Network on Rare Adult Cancers risk scales (ANOCEF and EURACAN), we found 44 and 48% of intermediate-risk patients and 49 and 45% of high-risk patients, respectively. Both cerebral and spinal presentation at diagnosis was documented in 16 (18%) patients. Complete response was achieved in 71(80%) patients. Nine was the maximal number of progressions documented, 35(39%) patients relapsed, CT was the preferred strategy at relapses, privileging carboplatin-based regimens at first relapse. The median overall survival (mOS) was 124.42 months (95%CI 68.53 - 180.11) and the median progression free survival (mPFS) was 30.48 months (95%CI 13.46 - 47.51), the 5-year OS was 53% and the 5-year PFS was 51%. In multivariate analysis, Chang´s ≥ M2 metastatic classification (p=0.001), no CT in association to RT (p=0.005), and lower doses on craniospinal RT &lt;30 Gy (p=0.015) were associated with poor prognosis for OS; Chang´s ≥ M2 (p=0.009) was also a prognostic factor for poor PFS.

CONCLUSION
This study dedicated specifically to adult MB patients suggests relevant prognostic factors for adult MB patients. We identify Chang´s ≥ M2 as poor prognostic factor of OS and PFS, and we confirm that the use of CT/RT at diagnosis and RT doses ≥ 30 Gy are associated with better survival in adults MB.
OS02.4.A IMPACT OF SURGERY ON SURVIVAL IN PATIENTS WITH MULTIPLE BRAIN METASTASES
Authors: Sagerer A , Buszello C , Lucas M , Eyüpoglu I , Hennig S , Schackert G , Juratli T 
Published: September 2023

Abstract

BACKGROUND
Surgical resection of brain metastases (BM) alleviates symptoms and can improve patients’ survival. However, the benefit of resection in multiple BM is controversial due to patients’ limited life expectancy. Therefore, we investigated the impact of resection of multiple BM on patients’ survival.

MATERIAL AND METHODS
We reviewed clinical data from 544 patients (216 female, 328 male) who underwent surgery for BM in our hospital between 2010 and 2022. Overall survival (OS) was estimated using the Kaplan-Meier estimator. In addition, follow-up data, adjuvant treatment and tumor recurrence data were collected.

RESULTS
We identified 280 patients (51.5%) with one and 264 patients (48.5%) with two or more BM. Bronchial carcinoma represented the most common primary tumor entity (n= 185, 88 one and 97 multiple BM), followed by melanoma (n= 109, 44 one and 65 multiple BM), breast cancer (n= 54, 31 one and 23 multiple BM), gastro-intestinal tumor (n= 64, 39 one and 25 multiple BM) and lastly cancer of unknown primary (CUP) (n= 29, 11 one and 18 multiple BM). We then compared the survival between patients with a single with those with multiple BM. The median OS of all patients with one BM was with 11.6 months significantly longer than those with two or more BM (7.3 months, p&lt; 0.001, 95% CI one vs. multiple BM: 8.6-14.5 vs. 6.2-8.4 months, respectively). Notably, 29.3% of patients with one BM and 16.5% with multiple BM lived longer than 24 months after resection (long-term survivor, p= 0.001). Regarding primary tumor histology, patients with breast cancer with a single BM had a significant longer OS with 19.7 compared to patients with multiple BM (5.0 months, p= 0.031). Remarkably, 33.3% of all long-term survivors with breast cancer had multiple BM. Patients with a single BM originating from other cancers showed a superior but yet not significant OS in comparison with their counterparts with multiple BM after resection. This included: gastro-intestinal cancer 12.2 vs. 6.5 months (p= 0.160), melanoma 11.6 vs. 7.3 months (p= 0.236) and CUP 3.0 vs. 2.7 months (p= 0.258). The long-term survivor rate of patients with resected multiple BM varied between 20.6% in melanoma and 7.4% in patients with CUP.

CONCLUSION
Despite limited prognosis in patients with multiple BM, surgical resection should be considered as an effective treatment option. Our study shows that a substantial subset of patients with multiple BM who underwent resection survive longer than 24 months after resection.
OS06.7.A SOMATOSTATIN RECEPTOR SUBTYPE EXPRESSION AND RADIOMICS FROM DWI-MRI REPRESENT STANDARDIZED UPTAKE VALUES (SUV) OF68GA-DOTATOC PET IN PATIENTS WITH MENINGIOMA, A TRANSLATIONAL STUDY
Authors: Iglseder S , Iglseder A , Beliveau V , Heugenhauser J , Gizewski E , Kerschbaumer J , Stockhammer G , Uprimny C , Virgolini I , Dudas J , Nevinny-Stickel M , Nowosielski M , Scherfler C 
Published: September 2023

Abstract

BACKGROUND
In this translational study, we first aimed to analyse the expression of somatostatin receptor subtype (SSTR) 2A, 2B and 5 and their correlation with the maximum standardized uptake value (SUVmax) of 68Gallium DOTA-D-Phe1-Tyr3-octreotide Positron Emission Tomography (68Ga-DOTATOC PET) in patients with meningioma. Secondly, we aimed to develop a radiomic model based on apparent diffusion coefficient (ADC) maps derived from diffusion weighted magnetic resonance images (DWI MRI) to reproduce SUVmax.

MATERIAL AND METHODS
A total of 51 patients who underwent MRI and 68Ga-DOTATOC PET prior to surgical resection of intracranial meningioma were included in the imaging part of the study. SUVmax were quantified from the PET images. Segmentation of the post-contrast T1-weighted (cT1) MR images served as regions of interest and were mapped to the co-registered ADC maps. A total of 1940 radiomic features were quantified from the tumor area for each ADC map. A random forest regression model was trained to reproduce SUVmax values. The model was evaluated within a repeated nested cross-validation design. The training included a feature selection was done in two-steps using a minimum redundancy maximum relevance feature selection and a recursive feature elimination based. The expression of SSTR subtypes 2A, 2B and 5 was quantified in 18 surgical specimen of meningioma and compared to SUVmax values.

RESULTS
The SUVmax values predicted by the random forest models correlated significantly with the observed values (p &lt; 0.05) for all 100 repeats with a mean Pearson’s r = 0.42 ± 0.07 SD and a RMSE = 28.46 ± 0.16. The expression of SSTR subtypes 2A, 2B and 5 correlated significantly with the SUVmax values (p&lt;0.001, R2=0.669; p=0.001, R2=0.393; and p=0.012, R2=0.235, respectively).

CONCLUSION
In this translational study, SSTR subtypes 2A, 2B and 5 correlate significantly with SUVmax. We developed a random forest regression model using radiomic features to reproduce SUVmax from 68Ga-DOTATOC PET in meningiomas.
OS08.7.A DEPRESSIVE SYMPTOMS IN ASSOCIATION WITH TUMOR LOCATIONS AT DIAGNOSIS IN PATIENTS WITH DIFFUSE GLIOMA
Authors: van Genderen* M N G , Belgers* V , Douw L , Barkhof F , Klein M , Niers J M , Eijgelaar R S , de Witt Hamer P C 
Published: September 2023

Abstract

BACKROUND
Depressive symptoms are common in glioma patients and occur more frequent than in patients with other cancer types. The presence of tumors in specific brain regions that potentially disturb brain functions could contribute to this difference. These lesions may cause an inadequate emotional response to an incurable and lethal disease with consequences for patient counseling and neurosurgical strategies. In this study, we examine the association between brain tumor location and depressive symptoms at presentation in patients with diffuse glioma using several methods for lesion symptom mapping.

MATERIAL AND METHODS
The retrospective cohort consisted of patients with diffuse glioma who had a preoperative MR-scan and completed the Center for Epidemiologic Studies Depression scale (CES-D) before treatment. We classified patients based on unexpectedly low ( ≤6), intermediate (7-20) and unexpectedly high (&gt;20) CES-D scores. Tumors were segmented in 3D and corresponding white matter disconnectomes were derived from normative tractography. We first correlated tumor and disconnectome with CES-D using sparse canonical correlation analysis to identify clusters of associated brain voxels. Next, we assessed the association between tumor locations and CES-D category using Bayesian multivariable categorical regression analysis of patient and tumor characteristics, including the overlap of tumors and disconnectomes with specific brain atlas structures, the probability of disconnection of white matter tracts, and functional network changes in local efficiency and eigenvector centrality.

RESULTS
We included 201 patients with a median age of 45 years (range 18-81), consisting of 62% males and 29% grade 4 gliomas. CES-D was completed a median of three weeks before surgery, was unexpectedly low in 29% and unexpectedly high in 15% of patients. Tumors located in the left (L) pallidum and right (R) thalamus were related to unexpectedly low CES-D, whereas tumors in the L hippocampus, L nucleus accumbens and R putamen were related to unexpectedly high CES-D. Disconnection of the R temporal subsection of the cingulum bundle, L optic radiation, L superior longitudinal fasciculus I and L uncinate fasciculus (UF) were related to unexpectedly low CES-D, whereas disconnection of the R corticospinal tract, R fornix, and L UF were related to unexpectedly high CES-D. Neither voxel clusters nor network measures were associated with CES-D.

CONCLUSION
Both unexpectedly low and unexpectedly high depressive symptom burden is common in patients with diffuse glioma at presentation. These dysfunctional emotional responses may be associated with the location of the tumor. Awareness of this phenomenon may be important in patient counseling and neurosurgical strategies.
* these authors contributed equally