bluuebunny/crossref_metadata_2025_split huggingface dataset:
P14.23 Risk of venous thromboembolism (VTE) in grade II-IV gliomas as a function of molecular subtype
Authors: Diaz M , Jo J , Schiff D 
Published: September 2019

Abstract

BACKGROUND
VTE affects up to 30% of patients with glioblastoma (GBM, WHO grade IV), but little is known about its incidence in lower-grade gliomas (LGG, WHO grade II-III). It has been suggested that isocitrate dehydrogenase (IDH) mutation status dramatically decreases the incidence of VTE in glioma patients, through a combination of F3 promoter hypermethylation leading to lower expression of the procoagulant protein tissue factor, and an increased production of D-2-hydroxyglutarate, which has anticoagulant properties (Unruh et al, 2016). Our objective was to determine the incidence of VTE in LGG and stratify VTE risk by molecular subtype in gliomas grade II-IV.

MATERIAL AND METHODS
We performed a retrospective analysis of 590 glioma patients with molecular testing seen at our institution (UVa) from January 2005 to August 2017. We divided LGG patients into 3 groups: IDH-wildtype (IDHwt); IDH-mutant (IDHmt), 1p/19q-codeleted; and IDHmt, 1p/19q-intact. GBM patients were divided according to MGMT methylation status. Estimates of cumulative incidence of VTE were calculated with death as competing risk, and significance testing was determined using the Fine and Gray model.

RESULTS
Of 256 LGG patients (147 grade II and 109 grade III), 81 were IDHwt, 113 IDHmt and 1p/19q-codeleted, and 62 IDHmt and 1p/19q-intact. There were 334 GBM patients, with MGMT methylation status available in 263 (98 (37%) methylated and 165 (63%) unmethylated). With a median follow-up of 545 days, the overall incidence of VTE was 8.2% for grade II, 9.2% for grade III and 30.5% for grade IV. The 6-, 12- and 24-month VTE incidence was 4.1%, 4.8% and 5.4% respectively for grade II, 4.6%, 7.3% and 9.2% for grade III and 23.1%, 26.6% and 29% for grade IV. In LGG patients, VTE incidence was slightly higher in IDHwt tumors (11.1%) vs IDHmt, 1p/19q-codeleted (8.8%) and IDHmt, 1p/19q-intact tumors (4.8%). However, this difference was not statistically significant (IDHwt vs IDHmt, 1p/19q-codeleted, sub-distribution hazard ratio (SHR)=1.67, 95% CI=0.59–4.72; IDHwt vs IDHmt, 1p/19q-intact, SHR=1.87, 95% CI=0.54–6.53). In GBM patients, there was no difference in the VTE incidence according to MGMT methylation status (SHR=0.99, 95% CI=0.64–1.54).

CONCLUSION
In our cohort, the risk of VTE in GBM patients was consistent with historical data; patients with LGG also had a higher VTE risk compared to the general population. In contrast to other retrospective studies in which the incidence of VTE for grade II-IV IDHmt gliomas was 0% (Unruh et al, 2016; Nazari et al, 2018), our data suggest that VTEs do occur in IDHmt LGG patients, although at a lower rate than in IDHwt. MGMT methylation does not seem to influence the incidence of VTE. VTE risk stratification in GBM patients based on IDH mutation is forthcoming.
P14.24 Bevacizumab treatment in atypical disseminated choroid plexus papilloma in adult patients
Authors: Colò F , Larrouquere L , Rivoirard R , Loiseau H , Lortholary A , Mervoyer A , Catry-Thomas I , Frappaz D 
Published: September 2019

Abstract

BACKGROUND
Choroid plexus tumours represent less than 1% of brain tumours. Low-grade papilloma may be treated with gross total surgical resection, while in disseminated progressive atypical choroid plexus papilloma (APP), there is no standard treatment: various chemotherapy regimens have been reported. Since this tumour is characterized by a rich vascular component, antiangiogenic therapy is an attractive treatment. The use of Bevacizumab has already been reported in three patients. Authors expand this experience with 5 further patients diagnosed with progressive APP treated with bevacizumab.

MATERIAL AND METHODS
Patients were recruited through the weekly Adolescent Young Adult French web conference. They have been treated with bevacizumab 10 mg/kg by intravenous injection each 2 to 3 weeks. Their clinical status and radiological response are reported: Karnofsky Index (KI), Pain Scale (PS) and RANO criteria were used.

RESULTS
All our patients had a progressive disease prior to bevacizumab. Pt 1: 41 years old; APP with cranio-spinal dissemination; Previous treatments: local and cranio-spinal irradiation in 2012 and in 2014; surgery: complete and partial resection in 2010, 2014, and VP shunt in 2018; Bevacizumab: total of 33 cures in 18 months. Result: radiological and clinical stabilization. Pt 2: 58 years old; APP with cranio-spinal dissemination; Previous treatments: surgery: VP shunt and gross total resection, in 2006; VP shunt, in 2011. Bevacizumab: total of 4 cures, in 2 months. Result: radiological and clinical stabilization. Pt 3: 34 years old; APP with cranio-spinal dissemination; Previous treatments: surgery: gross total resection, in 1992, and shunt in 2008. Bevacizumab: total of 21 cures, in 21 months. Result: radiological and clinical stabilization. Pt 4: 63 years old; APP with cranio-spinal dissemination; Previous treatments: surgery: surgical resection and VP shunt in 2013; chemotherapy: temozolomide. Bevacizumab: 29 months (still treated). Result: radiological and clinical stabilization. Pt 5: 62 years old; APP with cranio-spinal dissemination; Previous treatments: surgery: gross total resection in 1999 and VP shunt in 2009; chemotherapy: Carboplatin Vespesid. Bevacizumab: 23 cures, in 14 months. Result: radiological stabilization and clinical amelioration.

CONCLUSION
Despite their previous worsening disease, all patients obtained a stabilization or amelioration of their IK and PS under bevacizumab. Bevacizumab should be evaluated in a multicentric trial as standard therapy for disseminated metastasized progressive choroid plexus tumours.
P14.26 Autoimmune disease-associated primary CNS lymphoma: Meta-analysis and review of literature
Authors: Kaulen L D , Baehring J M 
Published: September 2019

Abstract

BACKGROUND
Recent studies suggest a relatively high prevalence of autoimmune diseases (AD) among primary CNS lymphoma (PCNSL) patients, however the literature is limited to case reports. To gain a better understanding of AD-associated PCNSL we reviewed all previous cases described in the literature.

MATERIAL AND METHODS
We mined the MEDLINE database using the search terms ‘central nervous system lymphoma’ or ‘CNS lymphoma’ along with AD-related terms, such as ‘immunosuppression’, ‘autoimmune’, the name of various AD, or commonly prescribed immunosuppressants. We selected 35 records for qualitative synthesis of data. We identified 43 AD-associated PCNSL in the literature and added five unpublished cases from our institution. Clinical, imaging and outcome data were collected.

RESULTS
Most prevalent ADs were systemic lupus erythematosus (22.9%), multiple sclerosis (18.8%) and myasthenia gravis (14.6%). Male-to-female ratio was 1:2 and median age at diagnosis was 57 years (range: 2.5–88). Most common immunosuppressants included prednisone (58.7%), mycophenolate (43.5%), and azathioprine (41.3%). Median interval from diagnosis of AD until diagnosis of PCNSL was 96 months (range: 11–360). Lesions typically localized to the hemispheres (64.1%) and displayed peripheral contrast enhancement (75.8%). Histology revealed diffuse large-B-cell lymphomas (76.7%) and Epstein-Barr virus (EBV) positivity (78.4%). Treatment included reduction of immunosuppression (100%) and chemotherapy (85.4%) in most cases. Median overall survival was 31 months.

CONCLUSION
AD-associated PCNSL are characterized by peripheral contrast enhancement on imaging and EBV positivity. AD that require severe immunosuppression appear over-represented. Median interval of immunosuppression and overall survival seem longer than in other immunodeficiency-associated PCNSL.
P14.36 Treatment patterns by O6-methylguanine DNA methyltransferase promoter (MGMT) status in newly-diagnosed glioblastoma multiforme (GBM): a multi-country chart review study
Authors: Fu A Z , Thompson G J , Hall J P , Bailey A , Kemp J , Lee C 
Published: September 2019

Abstract

INTRODUCTION
This study explored the relationship between MGMT testing and treatment patterns of patients with newly-diagnosed GBM from France, Germany, Italy, Spain, the UK (EU5), and Canada.

MATERIALS AND METHODS
Medical oncologists and neuro-oncologists across EU5 and Canada completed a point in time, cross-sectional survey for the next eight GBM patients seen between May and July 2016 (GBM Disease-specific ProgrammeTM). Statistically significant differences (p<0.05) between groups are presented.

RESULTS
A total of 241 physicians reported on 1,747 GBM patients. 1L patients had mean age 59.7 years (SD=12.3) and 36% were female. Of 1,113 (64%) patients who had an MGMT test performed with results recorded (tested), 58% (n=651) were methylated and 42% (n=462) were unmethylated. The remaining 634 patients (36%) were MGMT untested or awaiting MGMT results at time of survey (untested). Overall, 63% of patients received surgery prior to their 1L drug therapy, 78% received radiotherapy (RT; mean 4.3 sessions) in conjunction with 1L drug therapy, 90% received corticosteroids during RT, and 89% received temozolomide (TMZ). Patients who received corticosteroids during RT received similar drug treatments to those that did not, but were less likely to receive surgery prior to 1L treatment (65% vs 83%). MGMT-tested patients were more likely to receive surgery (66% vs 57%) and RT (81% vs 71%) than untested patients. Tested patients were also more likely to receive TMZ (92% vs 83%), and less likely to receive procarbazine+/lomustine+/vincristine (PCV; 3% vs 7%) or other chemotherapies (5% vs 11%). For 1L patients that experienced side effects, the most common effects included fatigue (74%), nausea (60%), and appetite loss (59%). Untested patients were more likely to stop their 1L drug treatment due to progression/recurrence of GBM (44% vs 36%). Patients who received surgery prior to 1L treatment were more likely to receive TMZ than those who did not (93% vs 82%). Among MGMT tested patients at 1L, methylated patients were more likely to receive RT (84% vs 78%) and TMZ (95% vs 89%) than unmethylated patients, and less likely to receive PCV (2% vs 5%) or other chemotherapy (4% vs 7%). Methylated patients with reported treatment-related side effects were less likely to experience dehydration (0% vs 10%), loss of strength/unusual weakness (5% vs 25%), memory problems (16% vs 35%), and nausea (51% vs 75%).

CONCLUSIONS
More than one-third of GBM patients in EU5 and Canada are not tested for MGMT-methylation. Untested patients are less likely to receive standard treatments than tested patients. Generally, TMZ is used in most patients regardless of MGMT testing and status. MGMT-methylated patients are more likely to receive standard treatments and experience fewer side effects than MGMT-unmethylated patients.
P14.44 Survival benefit of lobectomy over gross-total resection without lobectomy in cases of glioblastoma in the noneloquent area: a retrospective study
Authors: Roh T , Kang S , Hong C , Chang J 
Published: September 2019

Abstract

BACKGROUND
Following resection of glioblastoma (GBM), microscopic remnants of the GBM tumor remaining in nearby tissue cause tumor recurrence more often than for other tumors, even after gross-total resection (GTR). Although surgical oncologists traditionally resect some of the surrounding normal tissue, whether further removal of nearby tissue may improve survival in GBM patients is unknown. In this single-center retrospective study, the authors assessed whether lobectomy confers a survival benefit over GTR without lobectomy when treating GBMs in the noneloquent area.

MATERIAL AND METHODS
The authors selected 40 patients who had undergone GTR of a histopathologically diagnosed isocitrate dehydrogenase (IDH)-wild type GBM in the right frontal or temporal lobe and divided the patients into 2 groups according to whether GTR of the tumor involved lobectomy, defined as a supratotal resection (SupTR group, n = 20) or did not (GTR group, n = 20). Progression-free survival (PFS), overall survival (OS), and Karnofsky Performance Status (KPS) scores were compared between groups (p ≤ 0.05 for statistically significant differences).

RESULTS
The median postoperative PFS times for each group were as follows: GTR group, 11.5 months (95% CI 8.8–14.2) and SupTR group, 30.7 months (95% CI 4.3–57.1; p = 0.007). The median postoperative OS times for each group were as follows: GTR group, 18.7 months (95% CI 14.3–23.1) and SupTR group, 44.1 months (95% CI 25.1–63.1; p = 0.040). The mean postoperative KPS scores (GTR, 76.5; SupTR, 77.5; p = 0.904) were not significantly different. In multivariate analysis, survival for the SupTR group was significantly longer than that for the GTR group in terms of both PFS (HR 0.230; 95% CI 0.090–0.583; p = 0.002) and OS (HR 0.247; 95% CI 0.086–0.704; p = 0.009).

CONCLUSION
In cases of completely resectable, noneloquent area GBMs, SupTR provides superior PFS and OS without negatively impacting patient performance.
P14.49 Primary central nervous system lymphoma presenting as dementia: do not forget IL10 in CSF analysis
Authors: Blain A , Brinet A , Berthel M , Camoyret A , Gaultier C , Droy-Dupré L , Oesterlé H , Hurstel R , Debliquis A , Costopoulos M , Le Garff-Tavernier M , Sellal F , Ahle G 
Published: September 2019

Abstract

BACKGROUND
Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that aﬀects the central nervous system without systemic involvement. Clinical presentation depends on its localization: Focal deficits usually lead to prompt neuroradiologic evaluation, whereas cognitive or behavioral changes can lead to diagnostic delay. Rapidly progressive dementia (RPD), defined as a 1- to 2-year course from symptom onset to cognitive and functional debilitation, is a clinical presentation of PCNSL and thus a potentially curable cause of dementia, leading to death if it remains untreated. Nevertheless, its diagnosis is frequently delayed as other origins (CJD, autoimmune, paraneoplastic, infectious, and neurodegenerative disorders) are more frequently considered. We aimed to describe diagnostic features and treatment modalities in a series of patients presenting with RPD diagnosed as PCNSL.

METHODS
Patients with RPD and final diagnosis of PCNSL were retrospectively identified from 2012 to 2019 from the database of our academic teaching hospital. Clinical presentation, neuroimaging, and cerebro-spinal fluid (CSF) analysis were assessed from their medical records. Interleukin (IL) 10 and 6 concentrations were measured by flow cytometry using the cytometric bead array (CBA) technique (BD Biosciences) with a detection limit set at 2.5 pg/ml.

RESULTS
50 patients with diagnosis of PCNSL were identified, 7 (3 women, 4 men) presented with RPD.Median age was 69 years (range 59–84). Time from symptom onset to diagnostic confirmation of PCNSL ranged from 1–12 months (median 3). All patients presented with cognitive impairment (disorientation, memory disorders), accompanied by psycho-behavioral disorders in 6 of them. MRI disclosed enhancing lesions in all patients. Lumbar puncture was performed in 5 patients. All of them presented pleiocytosis, and lymphomatous meningitis was detected in 4/5 of them by cytology or flow cytometry (FCM). Elevated interleukin 10 (IL-10) was found in all patients with available CSF sample, 4 of them had an IL-10/IL-6 ratio >1.

DISCUSSION AND CONCLUSION
Patients presenting with rapidly progressive dementia should be evaluated for treatable forms of dementia. PCSNL has to be considered as soon as possible as diagnostic delay impacts its outcome. Imaging studies, usually contrast-enhanced MRI, is recommended, although nonspecific findings are not uncommon, especially in case of non-enhancing lesions. CSF sampling can help to prove diagnosis of PCNSL by cytology (generally associated with FCM), but it requires an experienced cytologist and immediate sample analysis.IL10 and IL10/6 ratio can be used as a more easily available marker to support suspicion of PNSCL, leading to further specific workup.

ACKNOWLEDGMENTS
NENO & LOC Network
P14.51 Brain mapping for mentalizing in GBM patient
Authors: Chung D , Yoon W 
Published: September 2019

Abstract

BACKGROUND
Glioblastoma is a disease with very poor outcome. Most patients underwent maximal safe resection, especially focusing in the preservation of motor and language function. However, many caregivers were suffered from the blockage of emotion communication with patients. So the definition of maximal safe resection must include the preservation of cognition and mentalizing of patients. Here we present the experience of brain mapping in awake surgery to preserve mentalizing.

MATERIAL AND METHODS
A 61-year-old male patient with headache was transferred to our hospital because of brain tumor on CT scan checked in another hospital. On the initial MRI, multi-septate cystic tumor was shown on left medial prefrontal area. The patient was recommended the surgical resection, but patient discharged with the denial of the operation. Ten days later, patient visited our hospital again with slowness of response by the enlargement of tumor size. The tumor extensively involved left cingulum and corpus callosum at anterior part. On diffusion tensor image, tumor located at mediosuperior part of inferior fronto-occipital fasciculus (IFOF). The patient showed deficit of visual and verbal memory, generative naming ability, and phonemic generative naming ability on preoperative neuropsychological test (SNSB-II). Pyramid and palm tree test (PPTT) and ‘Reading the Mind in the Eyes’ test (RMET) were also performed to evaluate the semantic association function and mentalizing preoperatively.

RESULTS
The patient underwent awake surgery with asleep-awake-asleep technique. The tumor was resected until identification of incorrect response to PPTT or RMET on subcortical stimulation (Ojeman stimulator, 1.5mA, 60Hz, biphasic). The histopathologic diagnosis was glioblastoma. Small part of tumor was remained on cingulum, but patient was discharged without change of mentalizing.

CONCLUSION
Although the patients with glioblastomas show poor outcome, we think that it is important to consider the cognition and mentalizing of patients for emotion communication with caregivers. With awake surgery, mentalizing can be preserved in selective patients.
P14.67 Somatostatin receptor targeted radioligand therapyin head and neck paraganglioma
Authors: Müther M , Roll W , Stegger L , Zinnhardt B , Schäfers M , Weckesser M , Rahbar K , Stummer W 
Published: September 2019

Abstract

BACKGROUND
Surgical resection is the therapy of choice in head and neck paraganglioma. However, surgery is associated with significant morbidity depending on tumor size and localization. In case of progressive residual or recurrent disease, new and less aggressive therapeutic options are warranted. Somatostatin receptor (SSTR) targeted therapies pose a promising alternative, as SSTRs are upregulated in paragangliomas. Only few studies provide evidence on efficacy of 177Lu-DOTATATE therapy in these patients. The aim of this study was to evaluate the efficacy of peptide receptor radiotherapy (PPRT) with 177Lu-DOTATATE for head and neck paragangliomas.

METHODS
A total of seven consecutive patients (mean age: 60 years, range: 14–84) with progressive head and neck paragangliomas (3 carotid body tumors, 4 jugulotympanic paragangliomas), treated with PRRT using 177Lu-DOTATATE, were included in this retrospective analysis. Therapy response was assessed by interim and post-therapy 68Ga-DOTATATE-PET-CT and MRI according to morphological and SSTR imaging parameters. Therapeutic uptake was classified on177Lu-DOTATATE scintigraphies 48h p.i. according to the Krenning scale. Longer-term clinical and imaging-based outcome were evaluated.

RESULTS
Patients received a median of 4 cycles (range: 3 to 5) of PRRT with 177Lu-DOTATATE (mean injected dose 7.3 GBq). Interim and post-therapy staging showed at least stable disease in all patients. Tumor uptake in 48h p.i. 177Lu-scintigraphies was moderate to high in all patients (Krenning scale; median: 3; range: 2–4). Furthermore, none of the patients showed progressive disease during the median follow-up time of 28 months (range: 6–37 months).

CONCLUSION
SSTR targeted therapy using 177Lu-DOTATATE shows promising efficacy and may lead to long lasting stable disease.
P14.68 Life expectancy in biopsied GBM patients: a single-centre experience
Authors: Kalita O , Sporikova Z , Halaj M , Cwiertka K , Vaverka M , Hrabalek L , Trojanec R , Hajduch M , Drabek J , Vrbkova J 
Published: September 2019

Abstract

BACKGROUND
The prognosis for patients with GBM remains dismal. The most aggressive multimodal therapy (maximally radical and safe tumour resection, followed by the Stupp protocol oncotherapy) has yielded the best treatment outcomes. Only a small proportion of patients initially undergo brain tumour biopsy. Our aim is to evaluate therapy results of biopsied GBM patients.

MATERIAL AND METHODS
We followed all glioma patients from June 1, 2006. Information on surgeries, patient clinical condition, imagings, and results of histological, immunohistochemical, molecular genetic, and cytogenetic investigations was gathered. For this study, we selected a group of biopsied GBM patients in a period from June 1, 2006 to December 31, 2016. Needle biopsy (stereotactic, or navigated) was advised for unresectable tumours, for patients with unfavourable clinical conditions (KS<60), and for older patients (with age being the only surrogate criterion). Whenever possible, the patients were recommended Stupp protocol oncotherapy. Clinical and MRI follow-up after surgery was carried out (OS, PFS) until the patient’s demise.

RESULTS
Sixty adult GBM patients (27 females and 33 males) with their age ranging from 30 to 85 years old and with a mean age of 66.8 years were enrolled in this study. The diagnosis of GBM was established by biopsy. Fourteen of them (23%) had radiotherapy only. Five patients (8%) were able to receive the Stupp protocol oncotherapy. Forty-one patients (69%) had an unfavourable physical condition which was a contraindication to radiotherapy or chemotherapy, respectively. The average OS was 3.8 months. A limited number of samples were available for IDH status investigation. All of the seventeen GBMs were IDH wild-type.

CONCLUSION
The initial surgical treatment strategy in GBM patients must be in the hands of an experienced neurosurgeon. Biopsy is required even when no further tumour-specific therapy is recommended. Regardless of the treatment strategy (resection or biopsy), multisite tumour sampling should be acquired. In our opinion, a decision to perform needle biopsy should be restricted to patients with unfavourable clinical conditions (age, KS, comorbidities, etc.), to large and deep-located brain tumours very often involving midline structures (corpus callosum, thalamus, basal ganglia), and to older patients. In accordance with these principles, we selected a small GBM patient group (12% of all GBM patients) with very limited life expectancy. The rationale for brain tumour biopsy is prevention of histological misdiagnosis and collection of biomarker data. But only the limited size of the tissue samples obtained was a significant obstacle to comprehensive cytogenetic investigation. We also recommend not to include biopsied GBM patients in studies with patients who had a radical resection. Supported by Ministry of Health of the Czech Republic, grant nr. NV19-04-00281.