bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface Proteome of Plasma Extracellular Vesicles as Biomarkers for Pneumonia and Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Authors: Jung Anna Lena , Møller Jørgensen Malene , Bæk Rikke , Griss Kathrin , Han Maria , Auf Dem Brinke Kristina , Timmesfeld Nina , Bertrams Wilhelm , Greulich Timm , Koczulla Rembert , Hippenstiel Stefan , Suttorp Norbert , Schmeck Bernd
Published: September 2019

Background

Community-acquired pneumonia (CAP) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) represent a major burden of disease and death and their differential diagnosis is critical. A potential source of relevant accessible biomarkers are blood-borne small extracellular vesicles (sEVs).

Methods

We performed an extracellular vesicle array to find proteins on plasma sEVs that are differentially expressed and possibly allow the differential diagnosis between CAP and AECOPD. Plasma samples were analyzed from 21 healthy controls, 24 patients with CAP, and 10 with AECOPD . The array contained 40 antibodies to capture sEVs, which were then visualized with a cocktail of biotin-conjugated CD9, CD63, and CD81 antibodies.

Results

We detected significant differences in the protein decoration of sEVs between healthy controls and patients with CAP or AECOPD. We found CD45 and CD28 to be the best discrimination markers between CAP and AECOPD in receiver operating characteristic analyses, with an area under the curve >0.92. Additional ensemble feature selection revealed the possibility to distinguish between CAP and AECOPD even if the patient with CAP had COPD, with a panel of CD45, CD28, CTLA4 (cytotoxic T-lymphocyte-associated protein 4), tumor necrosis factor–R-II, and CD16.

Conclusion

The discrimination of sEV-associated proteins is a minimally invasive method with potential to discriminate between CAP and AECOPD.
The Pselaphini (Coleoptera: Staphylinidae: Pselaphinae) of the Subantarctic and Chatham Islands of New Zealand; Description of Five Species and One Genus
Authors: Owens Brittany E , Leschen Richard A B , Carlton Christopher
Published: September 2019

The staphylinid subfamily Pselaphinae is generally depauperate at high latitudes. We examine one exception, the tribe Pselaphini, at the southern extreme of its global distribution, the New Zealand subantarctic islands and the Chatham Islands, an archipelago farther north. Currently, only two species are known from remote Campbell Island (Pselaphotheseus hippolytae Park and P. ihupuku Carlton and Leschen). A new genus, Pselaphopluteum gen. nov. (type species, Pselaphopluteum motumaha sp. nov.) and two new species, Pselaphopluteum motumaha sp. nov. and Pselaphaulax dracophyllum sp. nov., from the Auckland Islands, are added to the subantarctic fauna. Pselaphophus atriventris Westwood, introduced from Australia, is currently the only species known from the Chatham Islands, although several unidentified species were noted by Emberson (Emberson, R. M. 2002. The beetle (Coleoptera) fauna of the Chatham Islands: additions and corrections. N.Z. Entomol. 25: 69–77.). Three new species are described from the Chatham islands: Pselaphaulax caeruleus sp. nov., Pselaphaulax flavus sp. nov., and Pselaphaulax traversi sp. nov. Potential biogeographic implications of these new taxa are discussed within the context of the overall New Zealand fauna of Pselaphini, which is the subject of ongoing study.
Beyond ‘African Solutions to African Problems’ at the Extraordinary African Chambers and ‘Distant Justice’ at the International Criminal Court
Authors: Bouwknegt Thijs B
Published: September 2019

The trial of Chad’s former President Hissène Habré in 2015 was heartily anticipated and then heralded as an ‘African solution to African problems’. In myriad ways, the Extraordinary African Chambers (EAC) in Senegal’s court system indeed picketed a momentous transitional justice experience. It was simultaneously international, regional and local. It applied the universal jurisdiction principle. It judged a former and foreign head of state. It dealt with a ‘cold case’ from the Cold War. This was unprecedented in Africa and elsewhere. Crucially, the Habré trial departed from a ‘distant’, alienating trend of symbolic justice for African atrocities promised by the International Criminal Court (ICC). In Dakar, justice was pursued, performed and profited by those indirectly and directly victimized by the accused, while the passionate courtroom dynamics were palatably and transparently broadcasted. Notwithstanding these topical novelties, this article traces a more complex, more remote, and at times forgotten genealogy of transitional justice in Africa. By historicizing, contextualizing and exemplifying the Habré trial in light of unseen precedents from, inter alia, Congo Free State, Namibia, Equatorial Guinea and Ethiopia, it seeks to add historical layers of complexity to portrayals of Africa as passive object in the evolution of international criminal justice.
The Malabo Protocol, the ICC, and the Idea of ‘Regional Complementarity’
Authors: Nimigan Sarah
Published: September 2019

The African Union (AU) has taken steps to regionalize international criminal law through the expansion of the African Court of Justice and Human Rights (ACJHR) vis-à-vis the Malabo Protocol. The principle of complementarity is a cornerstone of the Rome Statute of the International Criminal Court (ICC). The Rome Statute crystallizes a complementary relationship between the ICC and domestic legal systems under Article 17 but makes no mention of regional or ad hoc jurisdictions. Prospects for including regional jurisdictions within the principle of complementarity are contingent upon a positive judicial interpretation of the principle and clearly established obligations at each level. It will necessarily require funding and support by states. Such an approach will contribute to the ongoing development of a robust system of international criminal justice. In order to effectively resolve the issue of competing mandates and effective domestic implementation, a cooperative model needs to be espoused. Although hypothetical at present, the idea of ‘regional complementarity’ is one worth thinking about in the context of constructive reform at the ICC. The prospective ACJHR offers a useful framework to analyse the potential role of regional mechanisms within the international criminal law project, broadly considered.
PL2.1 Exploiting the DNAM-1 system for chimeric antigen receptor (CAR) T cell therapy of glioblastoma
Authors: Weiss T , Meister H , Weller M , Sentman C , Roth P
Published: September 2019

BACKGROUND

Cancer immunotherapy with genetically engineered T cells that express a chimeric antigen receptor (CAR) has led to impressive responses in extracranial malignancies and is also explored against glioblastoma. However, CAR T cell strategies that are currently being explored against glioblastoma target single tumor antigens, which are non-homogeneously expressed and are prone to antigen escape. Furthermore, the immunosuppressive brain tumor microenvironment hampers anti-tumor efficacy.

METHODS

By immunohistochemistry and flow cytometry, we investigated the expression of CD155 and CD112, which are ligands to the activating immune cell receptor DNAX accessory molecule-1 (DNAM-1), in human and mouse glioma cell lines as well as in human glioblastoma samples. To understand their functional role, we generated CD155 or CD112 knock-out glioma cell lines using CRISPR/Cas9 and studied proliferation, sensitivity to irradiation or temozolomide as well as migration. To exploit the promiscuous binding features of DNAM-1, we generated different first or second-generation CAR T cells that use DNAM-1 as a tumor-binding domain. Subsequently, we investigated their anti-tumor activity in vitro in co-culture assays and in vivo in syngeneic orthotopic murine glioma models.

RESULTS

CD155 and CD112 are homogenously expressed in human and mouse glioma cell lines and human glioblastoma tissues. Knock-out of these ligands affected the migration of tumor cells, but did not affect proliferation or sensitivity to irradition or temozolomide. DNAM-1-based CAR T cells demonstrated high cytolytic activity and effector cytokine secretion in vitro. In vivo, DNAM-1 based CAR T cells reached to the tumor site in the brain upon intravenous administration, prolonged survival of orthotopic glioma-bearing mice and led to a durable anti-tumor response in a fraction of mice. The treatment was tolerated without toxicities.

CONCLUSION

We elucidated the tumor-intrinisic role of CD155 and CD112 and provide the first systematical preclincal assessment of DNAM-1 CAR T cells against glioma. These findings provide a rationale to test this immunotherapeutic strategy also in human glioma patients.
PL3.4 Intrinsic tumor plasticity in Glioblastoma allows for recreation of stem like-states and efficient tumor cell adaptation to new microenvironments
Authors: Golebiewska A , Dirkse A , Buder T , Yabo Y A , Poovathingal S , Muller A , Nazarov P V , Herold-Mende C , Bjerkvig R , Skupin A , Deutsch A , Voss-Bohme A , Niclou S P
Published: September 2019

BACKGROUND

Cellular heterogeneity has been well established within numerous cancer types, including malignant brain tumours. Initially, cancer stem cells (CSC) have been accounted for formation of phenotypic heterogeneity and tumor progression in glioblastoma (GBM). Recent data, however, suggest that CSCs may not represent a stable entity and intrinsic plasticity plays a key role in tumor adaptation to changing microenvironments. The question arises whether CSCs are a defined subpopulation of tumor cells or whether they represent a changing entity that any cancer cell can adopt depending on the environmental conditions.

MATERIAL AND METHODS

Intra-tumoral phenotypic heterogeneity was interrogated at the single cell transcriptomic and proteomic level in GBM patient-derived orthotopic xenografts (PDOXs) and stem-like cultures. Tumor cell subpopulations were further classified based on expression of four stem cell-associated membrane markers (CD133, CD15, A2B5 and CD44). The resulting 16 subpopulations were FACS isolated and functionally analyzed. Mathematical Markov modelling was applied to calculate state transitions between cell states.

RESULTS

GBM patient biopsies, PDOXs and stem-like cell cultures display remarkable stem cell-associated intra-tumoral heterogeneity. Independent of marker expression, all analysed tumor subpopulations carried stem-cell properties and had the capacity to recreate phenotypic heterogeneity. Mathematical modeling revealed a different propensity in reforming the original heterogeneity over time, which was independent of the proliferation index but linked to tumorigenic potential. Although subpopulations varied in their potential to adapt to new environments, all were able to reach a steady state microenvironment-specific equilibrium.

CONCLUSION

Our results suggest that phenotypic heterogeneity in GBM results from intrinsic plasticity allowing tumor cells to effectively adapt to new microenvironments. Cellular states are non-hierarchical, reversible and occur via stochastic state transitions of existing populations, striving towards an equilibrium instructed by the microenvironment. Our data provides evidence that CSCs do not represent a clonal entity defined by distinct functional properties and transcriptomic signatures, but rather a cellular state that is determined by environmental conditions, which has implications for the design of treatment strategies targeting CSC-like states.
OS2.2 Chemotherapy for spinal gliomas in adults
Authors: Gramatzki D , Felsberg J , Bähr O , Hentschel B , Westphal M , Schackert G , Tonn J C , Herrlinger U , Löffler M , Pietsch T , Steinbach J , Reifenberger G , Roth P , Weller M
Published: September 2019

BACKGROUND

Chemotherapy is a treatment option in patients diagnosed with anaplastic gliomas or glioblastomas of the spinal cord, or with recurrent lower graded WHO spinal gliomas that are no longer amenable to local treatment. The low incidence of spinal cord gliomas, particularly in adults, limits the ability to perform clinical trials. The role of chemotherapy in these tumors has remained unclear.

MATERIAL AND METHODS

We performed a retrospective study of 22 patients diagnosed with spinal gliomas who were treated with chemotherapy at any time during the disease course. Benefit from chemotherapy was estimated by applying Response assessment in neuro-oncology criteria. Data on radiotherapy, as well as the number of neurosurgical interventions were taken into consideration.

RESULTS

Most patients were diagnosed with astrocytoma WHO grade I-IV (N=14), the remaining patients were diagnosed with ependymoma (N=8). Median follow-up from start of chemotherapy was 92 months (95% CI, 72.6–111.4). The O6-methylguanyl-DNA-methyltransferase(MGMT)promoter methylation status was available in tumors of 12 patients: 9 tumors (75%) had an unmethylated MGMTpromoter. More than 50% of the patients had more than one neurosurgical intervention. After prior surgery 10 patients in the first-line setting had chemotherapy combined with radiotherapy, while 3 patients received chemotherapy only. The remaining 9 patients had initially received radiation therapy and chemotherapy was given at time of recurrence. In patients diagnosed with astrocytoma mainly temozolomide (TMZ) was applied (N=10), while one patient received CCNU and three patients had combination chemotherapy. Patients diagnosed with ependymoma had hydroxyurea (N=1), CCNU (N=1), TMZ (N=3) or combination chemotherapy (N=3). In the group of patients who had chemotherapy combined with radiation, response rates were as follows: anaplastic astrocytoma 3 stable diseases (SD), glioblastoma 1 complete response (CR) and 1 SD, and anaplastic ependymoma 1 SD. After chemotherapy in the group of patients previously irradiated, the following response rates were observed: 1 SD in pilocytic astrocytoma, 1 SD in diffuse astrocytoma, 3 SD in myxopapillary ependymoma, and 2 SD and 1 partial response (PR) in anaplastic ependymoma. All other patients experienced progressive disease. There was no indication for a favorable prognostic role ofMGMTpromoter methylation.

CONCLUSION

Spinal cord gliomas represent a heterogeneous group of tumors. Survival outcomes in response to chemotherapy in adult spinal glioma patients vary substantially, but individual patients appear to derive benefit from chemotherapy.
OS2.4 Using FineSA MRI for early detection of Spinal Metastases
Authors: Niina A , Davies A , Farooq N , Rowley K , Elias K , Collins I
Published: September 2019

BACKGROUND

Early detection of spinal metastases is important to facilitate early management and delay vertebral fracture or metastatic cord compression. The gold standard investigation to detect spinal metastasis is MRI, but it cannot quantify the metastasis and prognosis is poor due to its late presentation. Fine Structural Analysis (FineSA) is a custom software added to MRI using a non-radiating proprietary data acquisition technique. It analyses data at a resolution 10 times higher than MRI to quantify the trabecular microstructure which has the potential to enable early detection and management of vertebral fracture or metastatic cord compression.

MATERIAL AND METHODS

18 patients with known, symptomatic spinal metastases from Swansea Bay University Health Board and 11 age and sex-matched control subjects were recruited to have a FineSA MRI Spine. FineSA analysed and produced a structural spectrum of a defined area from the metastatic lesion. Statistical comparisons were made with the control data by extracting several metrics from the spectra, which were represented as an index score relative to a normal range.

RESULTS

Preliminary results using One Way ANOVA show a highly significant difference in trabecular microstructure between patients with spinal metastases and the age and sex-matched control patients, where p= 3.99e-11.

CONCLUSION

Preliminary results show that there is a highly significant difference between metastatic and control bone structure. Follow-up of the patients after one year will look at if fracture has occurred and whether there is a difference in the FineSA index score between the two groups. FineSA has the potential to be used to identify which metastatic lesions are most likely to be symptomatic and fracture, so that targeted radiotherapy can be done before symptoms are either present or intrusive.
OS5.4 Characteristics of adult diffuse H3K27M-mutant gliomas at recurrence
Authors: Hodroj K , Meyronet D , Barritault M , Bourg V , Cohen-Moyal E , Cartalat S , Ameli R , Berhouma M , Honnorat J , Ducray F
Published: September 2019

BACKGROUND

Adult diffuse H3K27M-mutant gliomas are rare and associated with a poor prognosis but could benefit in the next future from specific therapeutic strategies. In this context, the aim of the present study was to describe the characteristics of these tumors at recurrence.

MATERIAL AND METHODS

We retrospectively analyzed the characteristics of a series of 27 adult diffuse H3K27M-mutant gliomas at recurrence

RESULTS

Median age at diagnosis was 37 years. Initial treatment consisted of temozolomide radiochemotherapy (n=17, 62%), radiotherapy alone (n=1, 4%), chemotherapy alone (n=4, 15%), wait and see (n=1, 4%) and palliative care (n=4, 15%). Median PFS and median OS were 11 and 22 months in the whole series and 15 and 29 months in the patients who were treated with temozolomide radiochemotherapy. The pattern of recurrence could be analyzed in 19 patients. Ten patients (50%) demonstrated a local recurrence, five patients a local and distant recurrence (25%), two patients only a distant recurrence (10%) and two patients a leptomeningeal progression (10%). At recurrence, 15 patients received an oncological treatment that consisted of an alkylating chemotherapy (n=5), a bevacizumab based chemotherapy regimen (n=9) and of radiotherapy (n=1). Median PFS and OS after first recurrence in these patients were 6 and 14 months, respectively. An activating FGFR1 mutation was identified in 4 out of the 9 patients in whom it was assessed.

CONCLUSION

At recurrence, adult diffuse H3K27M-mutant gliomas are associated with a high rate of distant locations. A subset of patients harbor targetable FGFR1 activating mutations.
OS7.7 Educational program for caregivers of patients with brain tumors: AGAPE
Authors: Bourien H , Larible-Lefort C , Pelotte E , Le Brun F , Vauleon E
Published: September 2019

BACKGROUND

Patients with brain tumors suffer from physical, neurocognitive, and psychological decline. Among the potential evolutions of the disease, patients become dependent on caregivers. Nearly half suffer from anxiety or depression, which can significatively impact their quality of life. Better medical information and more effective integration of the caregivers are positively received. Patients and caregivers need more information on supportive care and the specificities of brain tumors. Educational programs may help them better support this new caregiving role and give them more information on the disease.

MATERIALS AND METHODS

At the Comprehensive Cancer Centre in Rennes, we have created an educational program for caregivers of patients with brain tumor, called AGAPE. The aim of AGAPE is to explain more precisely the medical aspects of brain tumors, describe resources that are available to caregivers, and allow a moment of exchange between caregivers. A medical oncologist and a nurse specialized in neuro-oncology organize the program divided into three workshops. During the first workshop, neurocognitive symptoms that may be presented by the patients as well as therapeutics are discussed. The second workshop aims to provide information on instrumental and human resources available, as well as on psychometrics, nutrition, and palliative care units. The last workshop gives each caregiver the opportunity to share their difficulties. In order to objectively evaluate the impact of AGAPE, caregivers are asked to complete a quality of life questionnaire after each workshop: CargoQoL (Caregiver Oncology Quality of Life). We retrospectively analyzed CargoQoL scores for each caregiver during their participation in AGAPE in order to evaluate the impact of AGAPE on the caregiver’s quality of life.

RESULTS

From February 2015 to February 2018, 9 three-month sessions were organized, allowing 45 caregivers to participate. Data for the years 2018 and 2019 are currently being updated. Each group of 3 to 4 caregivers met once a month for a period of 3 months. Final analysis of CargoQoL was based on 21 caregivers (responses with excessive missing data and the experience of caregivers who assisted to only one of the workshops organized every 3 months were not taken into account). For the 9 items of CargoQoL, there was no decrease in quality of life between the first and the last workshop. Even though these findings are not significant, caregivers seem to have a better relationship with healthcare providers and better self-esteem after attending the AGAPE workshops.

CONCLUSION

Diagnosis of brain tumors impacts the quality of life of both patients and caregivers. The assessment of the caregivers’ needs is essential in order to support them in caring for their loved ones and to include them in the healthcare process. AGAPE educational programs help caregivers maintain their quality of life.
OS9.2 Radiomics analysis of lower-grade gliomas, a POLA Network study
Authors: Younan N , Douzane H , Duran-Pena A , Nichelli L , Garcilazo Y , Dehais C , Ducray F , Carpentier C , Mokhtari K , Figarella-Branger D , Delattre J , Idbaih A , Alentorn A
Published: September 2019

BACKGROUND

Lower-grade gliomas (LGG) are divided into three histo-molecular groups: i) IDH-wildtype, ii) IDH mutant and 1p19q intact and iii) IDH mutant and 1p19q co-deleted. The current classification has improved the clinical stratification and its reproducibility. However, LGGs are still associated with an important degree of clinical heterogeneity. We sought to analyze the cross-talk between the spatial distribution and the quantitative imaging features (radiomics) with the clinical evolution and their molecular background (radiogenomics).

MATERIAL AND METHODS

We performed a retrospective multicentric study from 4 cohorts of high-grades gliomas (POLA Network, TCGA, REMBRANDT and LGG-1p19q), totaling 900 gliomas. We performed N4 and WhiteStripe imaging corrections to standardize MRI intensities. We used ITK-SNAP to obtain a mask of the different habitats of the tumor. Then we used PyRadiomics to obtain 2616 radiomic features per sample. We used plsRcox for fitting several Cox model in high-dimensional settings. We assessed the performance of the difference Cox model with the Harrel’s concordance index. We used a Sparse Canonical Correlation analysis to analyze the spatial distribution of the tumors.

RESULTS

Radiomics features allow identification in an unsupervised manner IDH-mutant gliomas with a median AUC of 0.96 [0.92–0.98]. Interestingly, in the analysis of survival, radiomics features provided additional information to clinical or genetics covariates and the model with only radiomics features obtained a C-Index of 0.78 [0.72–0.82]. In addition, survival model with the best performance in the prediction of overall survival was the one combining radiomics, clinics and genetics features with a C-Index 0.85 [0.82–0.92] and was validated in the other cohorts. The analysis of spatial distribution showed a very strong distribution of 1p19q co-deleted oligodendrogliomas in the frontal lobes.

CONCLUSION

Radiomics features may provide additional relevant clinical information by improving the prognosis of LGG. Radiomics allow non-invasive prediction of the most relevant molecular alterations of LGG.
OS9.4 The added value of radiomics to a clinical prognostic model in patients with low-grade glioma
Authors: van Riel M , Incekara F , van der Voort S , Wijnenga M , Klein S , van den Bent M , Smits M
Published: September 2019

BACKGROUND

In recent years, radiomics has become of increasing interest in studies of patients with low-grade glioma (LGG). Imaging features extracted from Magnetic Resonance Imaging (MRI) have shown to have the potential to predict genotype and overall survival in patients with LGG. However, until now, the potential of radiomics to add prognostic value to clinical prognostic models has hardly been investigated.The purpose of this study is to investigate the added prognostic value of quantitative magnetic resonance imaging features to a clinical prognostic model for patients with LGG.

MATERIAL AND METHODS

This retrospective cohort study included adult patients with newly diagnosed LGG who underwent tumor resection or biopsy between October 2002 and March 2017 at the Erasmus MC, University Medical Center Rotterdam (EMC). A set of 77 imaging features were extracted from preoperative T1w and T2w magnetic resonance sequences. These included first order histogram, texture, shape and location features of the volume of interest. The primary outcome of our study was overall survival (OS) and the secondary outcomewas progression-free survival (PFS).

RESULTS

A total of 259 patients were included. The median follow-up was 5.3 years (interquartile range, 3.4–8.2). The median OS was 9.08 years (95% CI: 6.70–11.5). Four imaging features increased the fit of our clinical prognostic model for OS significantly: T1 local binary pattern peak (hazard ratio (HR) 1.028, p=0.041), T2 histogram energy (HR 1.000, p<0.001), T2 histogram peak (HR 1.000, p=0.002) and standard deviation of radial distance (SDRD) (HR 1.412, p<0.001). The median PFS was 4.14 years (95% CI: 3.49–4.79). Only one imaging feature increased the fit of our clinical prognostic model for PFS significantly: standard deviation of radial distance (HR 1.278, p=0.006).

CONCLUSION

This study demonstrates that several radiomics features have the potential to help predict OS and PFS in patients with LGG more accurately than models constituted only by clinical features. In our study, four quantitative MRI features were found to be of added prognostic value. However, future studies should validate our results.
OS9.8 Genomic landscape of medulloblastoma in adults
Authors: Goschzik T , zur Mühlen A , Dörner E , Waha A , Friedrich C , Hau P , Pietsch T
Published: September 2019

BACKGROUND

Medulloblastoma (MB) is a rare disease in adults. Therefore, only few cohorts have been studied so far.

METHODS

Histological features were evaluated and annotation of the tumors to WNT-MB, SHH-MB, and non-WNT/non-SHH-MB was performed by immunohistochemistry. Systematic analysis of tumor samples for genome-wide copy alterations was done by molecular inversion probe array. WNT- and SHH-activated MB were screened by NGS panel and Sanger sequencing for known MB-related genes.

RESULTS

The cohort of tumors from 117 patients contained 14.5% WNT-MB, 63.2% SHH-MB, and 22.2% non-WNT/non-SHH MB. Classic histology was found in WNT-MB, non-WNT/non-SHH-MB and 22% of SHH-MB; 78% of SHH-MB showed desmoplastic/nodular histology. In WNT-MB, CTNNB1 mutations were found in 88.2% and monosomy 6 in 52.9% of cases. In SHH-MB, PTCH1 mutations were present in 40% of cases and chromosome 9q loss including the PTCH1 locus was the most frequent copy number event in SHH-MB (50%), while SMO and SUFU mutations were found only in 15.4% resp. 7.7%. Mutations in the TERT promoter region were found in 92.3% of SHH-MBs. Only 2 (3%) of the SHH-MB were TP53-mutated (1.7% of the whole cohort). In non-WNT/non-SHH-MB, isochromosome 17q was the most frequent chromosomal alteration (84.6%). A previously published whole chromosomal aberration (WCA) signature with ≥1 WCA was found in 69.2% of cases. For 85 cases, survival data were available. WNT-MB presented no relapses (5-year OS: 100%), while SHH-MB with wildtype TP53 and non-WNT/non-SHH-MB showed similar outcomes (5-year OS: 78.1% and 69.1%, respectively). Both SHH-MB patients with mutant TP53 died of disease. Patients with non-WNT/non-SHH-MB characterized by the cytogenetic WCA phenotype showed - as described in pediatric standard-risk MB - significant better overall survival compared to patients with tumors lacking any WCA (p=0.01).

CONCLUSIONS

Adult MB represent four defined biological/genomic entities. In contrast to previously published data adult patients with WNT-MBs showed excellent survival. However, the number of patients with WNT-MB was limited so that this result has to be interpreted with caution. While in our cohort SHH-MB-TP53wt were standard risk independent of their mutational or chromosomal status, non-WNT/non-SHH-MB patients could be divided into two risk-groups according to the presence or absence of WCA in the tumors as previously published for childhood standard-risk MB by our group.
OS10.5 Outcome of unresectable de novo IDH wild-type GBM: A decade analysis of factors influencing survival
Authors: Hamdan A , Homyer K , Swan G , Bankov G , Alfadhel S , Sinan L , Aw A , Grivas A
Published: September 2019

BACKGROUND

Patients with unresectable GBM represent an understudied and underpowered disease subgroup for which limited outcome data exist to support treatment recommendations. In this study, we present a ten-year analysis on outcome of unresectable GBM patients at our unit.

MATERIAL AND METHODS

We collected data for all consecutive adult de novo IDH wild-type (IDHwt) GBM patients who had undergone biopsy at our unit (2009–18, N= 177) and analysed those that had complete data on performance status, radiology, MGMT status, and adjuvant treatment (N= 156). We used step-wise cox proportional hazards regression to analyse factors associated with survival and outcomes.

RESULTS

Of 156 patients, mean age was 60.8 years old (range 19–89, 34/21.8% >69 years old), 63 (40.4%) were females, and 50 (32.1%), 26 (16.7%) and 12 (7.7%) had multifocal, butterfly or both lesion types respectively. 101 (64.7%) patients had good performance status (ECOG 0–1), and 49 (31.4%) had methylated MGMT lesions. Adjuvant treatment modalities were best supportive care (41, 26.3%), RT only (33, 21.2%), TMZ only (20, 12.8%), RT and TMZ (10, 6.4%), concurrent TMZ/RT only (29, 18.6%) and concurrent TMZ/RT plus adjuvant TMZ [TMZ/RT+TMZ] (23, 14.7%).

Median OS was 6.1 months (range 0–50.7), with 22% and 2% 1- and 2-year OS respectively. Patients who were MGMT methylated, had good performance status, and received TMZ/RT+TMZ had the highest survival (median OS 18.7 vs 5.5 months, P<0.0001).

Multivariate analysis revealed factors associated with worse OS; these include male sex (HR 1.6, 95%CI 1.1–2.2), unmethylated MGMT (1.8, 1.3–2.8), poor performance status ie ECOG>1 (2.4, 1.6–3.3), not receiving TMZ/RT+TMZ (3.1, 1.8–5.1). In addition, univariate analysis initially revealed that older age (>69yrs) was significantly associated with poorer outcome, however in multivariate analysis, this effect was obliterated (HR 1.3, 95%CI 0.9–2.1).

CONCLUSION

In this study, we provide one of the largest series of unresectable IDHwt GBM outcome in the literature. Survival of patients harbouring unresectable IDHwt GBM can be unexpectedly long, and may even reach nearly twice that of the unselected, biopsy-only GBM patients receiving TMZ/RT+TMZ studied in the original Stupp trial (median OS of 9.4 months). For this subgroup of IDHwt GBM patients, advanced age may not necessarily predict poor outcome, once adjusted for other outcome predictors. Future randomised trials looking into unresectable IDHwt GBM should stratify patients according to the factors revealed above.
P03.02 Risk of leptomeningeal dissemination in patients treated with postoperative stereotactic radiotherapy of brain metastases
Authors: Mousli A , Bihin B , Gustin T , Koerts G , Mouchamps M , Daisne J F
Published: September 2019

Background

There is a body of evidence that the risk of leptomeningeal dissemination (LMD) is increased in the postoperative stereotactic radiotherapy (SRT) of brain metastases (BM) compared to adjuvant whole brain radiotherapy (WBRT). The proposed mechanism is an iatrogenic tumor dissemination into the cerebrospinal fluid at time of surgery. Including a wider volume of meningeal wall and the entire surgical track in the definition of the postoperative SRT clinical target volume (CTV) to decrease LMD is still controversial. The aim of this study was to retrospectively analyze the outcome of adjuvant SRT targeted at resection cavities of BM without previous WBRT.

MATERIAL / METHODS

We reviewed 70 patients treated with postoperative SRT for BM. Stereotactic planning computed tomography and planning MRI were imported into iPlan RT image software for image registration and TV delineation. The CTV consisted of any residual enhancement and all resected cavity including a safety margin of 1 to 2 mm. Only in cases of superficial initial tumor with meningeal contact was the CTV enlarged to the adjacent meningeal wall, but never included edema or the entire surgical track. Patients underwent regular follow-up MRI. The cumulative incidence rates of LMD was retrospectively calculated as well as patterns of failure.

RESULTS

The most common histological type was non small cell lung cancer in 61.4%. There were 38.6% infratentorial locations and 37.2 % superficial lesions. En bloc resection was achieved in 60% and compete resection in 75.7%. After a median imaging follow up time of 16.7 months, 54.3% of patients experienced distant brain failure. LMD occurred in 9 of 70 patients (12.9 %) at a median time of 10.7 months. Survival without LMD was 88% at 1 year (IC 95% 79%-97%) and 82% at 2years (IC 95% 72%-94%). In three quarter of cases, LMD interested superficial lesions. In univariate analysis, survival rates without LMD at 1 year for superficial and deep lesions were 88 % and 94 %, respectively (p=0.49). We report only one recurrence in the surgical track (1.42%).

CONCLUSION

The risk of LMD was comparable to the literature (11–17%). Superficial lesions were slightly more likely to relapse in the meninges, but it was non-significant. The risk of recurrence in the surgical track is negligible. Our results do not support the current guidelines recommending the systematic inclusion of the surgical track and the related meninges in the CTV.
P03.07 Radiosurgical managementof trigeminal schwannomas: A single center experience
Authors: Emad Eldin R M , El-Shehaby A M , Abdel Karim K , Reda W A , Nabeel A , Tawadros S
Published: September 2019

BACKGROUND

Trigeminal schwannomas are a rare form of intracranial schwannomas. They can occur anywhere along the track of the trigeminal nerve, including the middle, posterior fossa or both. It can even extend extracranially. The variability of its location and extent, in addition to its close proximity to critical neurovascular structures makes surgical intervention challenging. Taking from the success of treating vestibular schwannomas with stereotactic radiosurgery, it has been used as an alternative to surgery for the treatment of trigeminal schwannomas. Because these tumors are rare more clinical evidence is required to assess the response of these tumors to stereotactic radiosurgery.The aim of this study was to evaluate the efficacy and complications associated with treatment of the trigeminal schwannomas by gamma knife radiosurgery.

MATERIAL AND METHODS

The study included 51 patients with trigeminal schwannomas not associated with NF2, treated by Leksell gamma knife. There were 25 males and 26 females. The mean age at presentation was 43 years. The patients underwent a total of 58 gamma knife sessions (44 single and 7 volume-staged sessions). Eight patients had previous surgery. The tumor nature was solid in 46, cystic in 3 and mixed in 2 patients. The mean target volume was 8.5 cc (0.6–30.7 cc) with the mean overall tumor volume being 9.6 cc (0.6–31.1 cc). The mean prescription dose was 12 Gy.

RESULTS

The mean follow up was 57 months (12–152 months). The tumor shrank in 23 (45%) patients and remained stable in 25 (49%). Tumor progressions occurred in 3 (6%) patients. The tumor control rate was 92%. The progression-free survival at 5,7 and 10 years was 95%, 88% and 79%, respectively. Clinical improvement occurred in 27 (53%) patients and was significantly associated with tumor shrinkage (p 0.03). Twenty patients (39%) remained clinically unchanged. Adverse radiation events occurred in 7 patients and were significantly associated with target and overall tumor volume (p 0.028 and 0.004).

CONCLUSION

Gamma knife radiosurgery appears to be an effective and safe adjuvant and primary treatment modality for trigeminal schwannomas. Large tumors should be debulked first before radiosurgery, when feasible.
P03.08 Large cerebral arteriovenous malformations management with Volume-staged gamma knife radiosurgery
Authors: Emad Eldin R M , Reda W A , El-Shehaby A M , Abdel Karim K , Nabeel A , Tawadros S
Published: September 2019

BACKGROUND

Large cerebral arteriovenous malformations (AVM) pose a management dilemma because of the limited success of any single treatment modality by itself. Surgery alone is associated with significant morbidity and mortality. Similarly, embolization alone has limited efficacy. Volume-staged gamma knife radiosurgery (VSGR) has been developed for the treatment of large AVMs, to increase the efficacy and improve safety of treatment of these lesions. The aim of the study was to assess the efficacy and safety of VSGR technique for the treatment of large cerebral AVMs.

METHODS

The study included patients treated by VSGR between May 2009 and July 2015. All cases had large AVMs (>10 cc). These were 29 patients.

RESULTS

Twenty-four patients completed radiographic follow up with 15 obliteration cases (62.5%). There was a total of 56 sessions performed. The mean AVM volume was 16 cc (10.1–29.3 cc). The mean prescription dose was 18 Gy (14–22 Gy). The mean follow up duration was 43 months (21–73 months). One patient died during follow up from unrelated cause. Two cases suffered haemorrhage during follow up. Symptomatic edema developed in 5 (17%) patients. The factors affecting obliteration were smaller total volume, higher dose/stage, non-deep location, compact AVM, AVM score less than 3, >18 Gy dose and <15 cc total volume. The factors affecting symptomatic edema were smaller total volume and shorter time between first and last sessions (p 0.012). T2 image changes were affected by SM grade 3 or more (p 0.013) and AVM score 3 or more (p 0.014).

CONCLUSION

VSGR provides an effective and safe treatment option for large cerebral AVMs. Smaller AVM volume is associated with higher obliteration rate.
P04.01 Return to work i patients with low grade glioma
Authors: Rydén I
Published: September 2019

BACKGROUND

We now treat patients with low-grade gliomas (LGG) more aggressively as this prolong survival. Patients are typically in working age, but their ability to return to work (RTW) following treatment has not been studied. We aimed to study patterns of sick leave and return to work among LGG patients in Sweden. In addition, we explored predictors for RTW following LGG diagnosis.

MATERIAL AND METHODS

We performed a nationwide register-based study of patients with grade II diffuse LGG. Data on adult patients aged 18–60 years with a histopathological diagnosis of LGG between 2005–2015 were obtained from the Swedish Brain Tumor Registry (n=381). A matched control sample (n=1900) was acquired from Statistics Sweden. Patients and controls were linked to the social insurance agency data for individual information on sick leave and disability compensation. Multivariable logistic regression was used in order to find predictors for RTW.

RESULTS

One year prior to surgery there was no apparent difference between cases and controls with 90 % working. Among LGG patients there was a rapid increase in sick leave starting approximately six months prior to surgery, while the proportion of controls on sick leave remained constant. One year after surgery, 53 % had returned to work with 29 % working full time. Independent predictors for patients working one year after surgery were higher age (OR 0.96, 95 % CI 0.93–0.99, p <0.01) and more days absent from work prior to procedure (OR 0.91, 95 % CI 0.97-0.95, p <0.001), both negatively associated with RTW.

CONCLUSIONS

In this cohort, more than half of the patients being diagnosed with LGG RTW within one year. Higher prior absence from work and higher age are risk factors for no-RTW. This study provides new information on rates of and factors influencing RTW in patients with LGG.

FUNDING

This project was funded by research grant from the Swedish Research Council (2017-00944).
P04.04 Different stages of astrocytoma in young adult patient
Authors: Susanti E , Kamarlis R , Suci Rahayu N
Published: September 2019

BACKGROUND

astrocytoma is a type of cancer that involve brain parenchym or spinal cord. It arises from glial cells, called astrocytes-star shaped cells which function as supportive tissue of the brain. About 50% of primary brain tumors are astrocytomas. It’s more common in men than women and most often occur at the age of after 45. There are several types of astrocytoma and some of them grow faster than other. We found a rare case where different stages of astrocytoma occur in different areas of the brain and where the latter seemed to show up just within 8 months after the first.

MATERIAL AND METHODS

a 43 year old male patient admitted to neurology ward after a convulsion and hemiparesis on the left extremities. Patient was known to have suffered from astrocytoma in the frontal lobe in October 2017, and had undergone craniectomy evacuation and subsequent radiotherapy which was completed in March 2018. A few months while during recovery at home, patient complained about headache which increased in intensity over a period of 3 months before admission. The first and only convulsion occurred just 12 hours before admission, while left side weakness occurred 7 days prior. Patient underwent a series of radiologic examination after the radiotherapy and also while admitted into hospital. We found a new and large mass in the right temporoparietal lobe from the latest head ct scan. This large mass was not found from the last MRI and head ct scan which was done 8 months prior. pathology anatomy examination was done to the first and second mass found.

RESULTS

Pathology anatomy examination depicted different stages from the two masses, the first one was pleomorphic xanthoastrocytoma (WHO grade II) and the second one was pilocytic astrocytoma (WHO grade I)

CONCLUSION

pleomorphic xanthoastrocytoma (WHO grade II) and pilocytic astrocytoma (WHO grade I) both are considered low grade glioma. neverthless treatment for this devastating disease still far from favorable result or outcome
P09.04 Natural history of meningiomas: review with meta-analyses
Authors: Nakasu S , Nakasu Y
Published: September 2019

BACKGROUND

A recent investigation using MRI showed 2.5% frequency of meningioma as an incidental finding in the population-based neuroimaging study. Although observation has been a mainstay in asymptomatic meningiomas, it may increase the risk of surgery due to enlargement of the tumors and aging of patients. It is important to characterize tumors that will grow to be symptomatic in order to select appropriate treatments and radiological follow-up.

MATERIAL AND METHODS

We reviewed 26 studies (3 from the same institute) that analyzed natural courses in asymptomatic or untreated meningiomas. Radiological progression of tumor was redefined as tumor growth by 15% of initial volume or more whenever possible. To adjust the difference of follow-up interval in each study, the percentages of growing tumors in each study were compared with each mean follow-up period. Individual data were extracted from seven studies for univariate or multivariate analyses. Weighted meta-analyses were performed using the 25 studies.

RESULTS

In time-growth rate analysis, nearly 70% of meningiomas showed radiological progression defined by a volume criteria and the rate approached plateau at 5–6 years. Meta-analyses showed that each radiological progression, growth speed (annual volume change (AVC) or relative growth rate (RGR)) and symptomatic progression had different factors related to their progression. Age, calcification and high intensity on T2 weighted image related to radiological progression and growth speed but not to clinical progression. In individual data analyses, tumor size (diameter 2.6cm (AUC 0.773; specificity 0.759, sensitivity 0.800), volume 5.6cm3 (AUC 0.775, specificity 0.717, sensitivity 0.800)) was a possible marker for symptomatic growth.AVC (>= 2.1cm3/year) was the strongest indicator for clinical progression. In the group of >=2.1cm3/year, Kaplan-Meier analysis showed that progression free rate was 69.3% at 3 years, and reached to 55.4% at 6 years whereas 100% in slower growth group.

CONCLUSION

Radiological features may not be very much useful for prediction of clinical progression except for perifocal edema. This may be due to dynamic changes of these radiological markers in a long term. Initial quantitative tumor size and growth speed especially AVC were reliable factors for decision of treatment for asymptomatic meningiomas.
P09.06 Risk factors associated with Meningioma in a Cohort of 2 Million Israeli Adolescents
Authors: Yust-Katz S , Derzane E , Keinan L , Amiel A , Honig A , Laviv Y , Kanner A , Twig G , Siegal T
Published: September 2019

Background: Meningiomas are the most common primary central nervous system tumors. Risk factors including- obesity, height, history of allergy/atopy or autoimmune diseases, have been assessed with conflicting results. In this study, we reviewed the database of a large cohort of Israeli adolescents in order to assess potential risk factors for the development of meningiomas.

Methods: This study analyzed a cohort of 2,035,915 Jewish men and women who underwent compulsory physical examination as part of screening for army drafting between the age of 16 to 19 from 1948 to 1991. Meningioma incidence was identified by linkage to the national cancer registry. Cox proportional hazard models were used to estimate the hazard ratios for meningioma according the several risk factors including sex, BMI, height, history of allergic and autoimmune disease.

Results: Linkage of the adolescent military database with the Israeli cancer registry revealed 480 cases of meningioma. The median age at diagnosis of meningioma was 42.1 ± 9.4 (range 17.4–62.6). On univariate analysis, only gender (female) and height were significantly associated with the risk of meningioma for the whole study population (p<0.01 for both variables). When analyzed separately for gender- height was significant only for men. Spline analysis in the men group showed the minimum risk at a height of 1.62 meters and a statistically significant increase in the risk for meningioma at heights taller than 1.85 meters. BMI was not associated with an elevated risk of meningioma even when analyzed separately for gender. Past medical history including asthma, diabetes, and other atopic and autoimmune diseases were not found to be associated with the risk of meningioma.

Conclusion: In this large population study, we found that sex and taller height in adolescent males was associated with an increased risk of meningioma.