bluuebunny/crossref_metadata_2025_split huggingface dataset:
P14.59 Post-Market Surveillance Data of the EMEA region indicate good tolerability of TTFields in WHO Grade III Glioma
Authors: Keßler A F , Ritz R 
Published: September 2019

Abstract

BACKGROUND
Despite considerable progress in molecular characterization and evidence for certain regimens, treatment of grade III gliomas is still ambiguous and, with surgery, radiotherapy and chemotherapy, in analogy to grade IV glioma treatment. Tumor treating fields (TTFields) therapy proved to be effective as an additional anti-mitotic treatment in glioblastoma and is available in several countries. While TTFields in grade III glioma are being investigated in several clinical trials, we report an analysis of surveillance safety data in patients with grade III glioma already treated with TTFields in the EMEA region.

METHODS
We reviewed post-marketing surveillance data of the EMEA region. Using the MedDRA body system with system organ class and preferred terms, adverse events reported in the subgroup of patients with grade III glioma treated with TTFields were systematically analysed. Patients with diagnosis of anaplastic astrocytoma and anaplastic oligodendroglioma were included.

RESULTS
This analysis includes 142 patients with grade III glioma treated with TTFields in the EMEA region. Median age was 47 years (range 5–78 years). 64% of the patients reported at least one adverse event. With an incidence of 35%, skin reaction was the most common reported adverse event, none of them were severe. 29 % of the patients reported general disorders, including general health deterioration (15%) and fatigue/malaise (6%). Adverse events related to the nervous system were reported in 26% of patients; seizures were noted in 9% and headache in 7% of patients.

CONCLUSION
The retrospective analysis of available post-market surveillance data of EMEA patients with grade III glioma showed no occurrence of serious adverse events that were associated with TTFields. Skin reaction, as the most commonly reported adverse event, but also other reported adverse events had comparable incidences to the rates observed in the phase III trials for patients with recurrent (EF-11) and newly diagnosed GBM (EF-14). In summary, this analysis identifies no additional safety signals on the use of TTFields in the treatment of patients with grade III glioma. Future results of clinical trials in these indications will give further insight into safety and efficacy in this subgroup.
P14.62 Safety and adverse event profile post-market surveillance analysis of Tumor Treating Fields (TTFields) in EMEA
Authors: Schmidt T , Kebir S , Lazaridis L , Stoppek A , Glas M 
Published: September 2019

Abstract

BACKGROUND
Tumor Treating Fields (TTFields) are established as modality in glioblastoma (GBM) therapy. GBM is the most aggressive brain tumor in adults, constituting approximately 15 % of all primary brain tumors. At diagnosis, a considerable subgroup of GBM patients is ≥65 years of age. The phase 3 EF-14 trial demonstrated a significant improvement of progression free, overall and longterm survival in newly diagnosed GBM (ndGBM) patients by the addition of TTFields compared temozolomide therapy. No treatment limiting systemic adverse events in the EF-14 trial for ndGBM or in the EF-11 trial for recurrent GBM (rGBM) were observable. Here, we present post-market surveillance data from patients in the EMEA region including elderly patients (≥ 65 years) treated with TTFields.

METHODS
Based on the MedDRA body system (system organ class) and preferred terms surveillance data of patients in the EMEA region were assessed. Additionally, surveillance data of patients < 65 as well as ≥ 65 years of age in this region were separately analyzed.

RESULTS
A total of 11,048 patients were treated with TTFields (ndGBM 53.3 %, rGBM 39.5 %, other diagnoses 7.2 %) of whom 2,252 (20.4 %) patients were treated in the EMEA region. 19.6 % of patients treated in this region were ≥65 years of age at the time of TTFields therapy initiation. One or more adverse events were reported by 64 % of EMEA patients < 65 and in 67 % of elderly EMEA patients. The most prevalent adverse event in both age groups was skin reactions, occurring in 30 % of patients < 65 years of age and 33 % elderly patients. Likewise, further adverse events in elderly patients in the EMEA region were comparable to patients younger than 65 years of age, e.g. heat sensation (< 65; ≥ 65: 4 %; 4 %) and general physical health deterioration (14 %; 18 %).

CONCLUSION
These real-life data demonstrate a good safety profile of TTFields in elderly patients as well as in patients < 65. The most frequent registered adverse event was skin reaction, which is in line with the results of the phase 3 EF-11 trial for rGBM and the EF-14 trial for ndGBM patients. In summary, these results from post-marketing surveillance emphasize the safety of TTFields in GBM treatment, particularly in the elderly population.
P14.82 Combining therapy with recombinant human endostatin and cytotoxic agents for recurrent disseminated glioblastoma: a retrospective study
Authors: Zhang J 
Published: September 2019

Abstract

BACKGROUND
The optimal chemotherapeutics of recurrent disseminated glioblastoma has yet to be determined. We analyzed the efficacy and safety of temozolomide (TMZ) and irinotecan (CPT-11) combined with recombinant human endostatin (rh-ES) in patients with recurrent disseminated glioblastoma.

MATERIAL AND METHODS
We retrospectively reviewed 30 adult patients with recurrent disseminated glioblastoma treated with this combination chemotherapy from November 2009 to August 2018. TMZ was given orally 200mg/m2 for 5 days in each 28-day cycle (5/28d). CPT-11 was administrated 125 mg/m2 for patients not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or 340 mg/m2 for patients receiving EIAEDs on day 1 and day 15; rh-ES was administrated 15 mg/d, daily for 14 days of each 28-day treatment cycle.

RESULTS
Primary endpoint was progression-free survival at 6 months (6m-PFS). The 6m-PFS was 23.3%. The median PFS was 3.2 months. The overall survival rate (OS) at 12 months was 28.6%. The median OS was 6.9 months. Six out of 30 (20%) patients demonstrated partial radiographic response and 11/30 (36.7%) remained stable. The PFS of the 6 patients who got partial response was 5.8, 6.3, 6.9, 13.6, 15.8, 16.6 months, respectively, and the median time interval of first response was 4 (range, 2.0–6.6) months. The most common adverse events were hematologic toxicity and gastrointestinal reactions. The Grade ≥3 adverse event was mainly hematologic toxicity. The adverse events were manageable.

CONCLUSION
Rh-ES, in combination with cytotoxic drugs, was an alternative effective regimen with manageable toxicity in treatment of recurrent disseminated glioblastoma.
P14.89 What happens after 15 years? A clinical picture of a cohort of survivors of CNS tumors treated with whole-brain irradiation in a National Cancer Center
Authors: Espírito Santo V L , Passos J , Pimentel T , Nunes J , Costa I , Salgado D 
Published: September 2019

Abstract

BACKGROUND
Radiotherapy (RT) is standard curative treatment for many tumours, specially brain tumours. However, RT causes damage to normal brain tissue due to genetic instability, impairment of synaptic plasticity and increased oxidative stress and inflammation. With improved treatment, patient survival also increased in years, making long-term effect of RT more evident. Late toxicities of RT are well described for pediatric survivors but there is scant literature on late toxicities in adult survivors and, in general, the adult brain is considered less susceptible to radiation damage.

MATERIAL AND METHODS
Retrospective analysis of adult patients treated with whole-brain RT with more than 15 years of follow-up. Clinical charts were reviewed to collect clinical, demographic and outcome data.

RESULTS
From 18 patients found (mean age at diagnosis of 27 years, 13 male/ 5 female), 5 were diagnosed with medulloblastoma, 5 CNS lymphoma, 5 with germinoma, 3 with ependymoma and 1 with teratocarcinoma. Most common presentations were headache (61,1%), seizure (16,7%) and dizziness (16,7%). 5 patients (27,8%) had hydrocephalus at diagnosis. All patients received whole-brain RT (mean 40Gys, varying between 21 to 60Gys), alongside with complete surgical resection in 11 patients (61,1%) and chemotherapy in 10 patients (55,6%). Mean follow-up time was 23,6 years and only 1 patient died due to lymphoma recurrence 16,7 years after the initial diagnosis. During follow-up, all patients had late RT induced changes, leukoencephalopathy in 16 patients (88,9%; mean 8,6 years after RT), ischemic stroke in 9 patients (50,0%; mean 16,0 years after RT), cerebral microbleeds in 14 patients (77,8%; mean 15,4 years after RT), cognitive decline in 12 patients (66,7%; mean 15,8 years after RT), radio-induced meningioma in 3 patients (16,7%; mean 18,1 years after RT) and epilepsy in 2 patients (11,1%; mean 10,5 years after RT). Also 1 patient had neurosensorial loss 14,2 years after RT and another one had subarachnoid haemorrhage due to ruptured aneurysm 19 years after RT.

CONCLUSION
Our results show that late RT induced effects are progressive and irreversible in the adult survivors, in a very similar manner as has been reported in the pediatric survivors. The impact on quality of live is increasing as patients survive longer. RT is still an important tool in neuro-oncology, but its role in curing brain tumors needs further study.
P14.95 Is the pathological-grade relevant in “IDH-wild type, TERT-mutant” diffuse-gliomas? An analysis in 147 patients
Authors: Danyeli A E , Akyerli C B , Dinçer A , Coşgun E , Abacıoğlu U , Pamir M , Özduman K 
Published: September 2019

Abstract

BACKGROUND
Although the word “glioblastoma” still denotes a grade-IV pathology, basic molecular studies have clearly indicated that a significant proportion of lower-grade gliomas harbor genetic alterations typical of glioblastomas. Based on these findings cIMPACT-NOW update 3 has defined an entity called the “diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”. A TERT-promoter mutation is one of these typical molecular markers of glioblastomas. In this study we analyzed IDH-wild type, TERT-mutant diffuse gliomas of different pathological grades to look for differences in demographic, clinical and survival characteristics.

MATERIAL AND METHODS
147 adult hemispheric diffuse-gliomas with wild-type IDH1/2 and mutant TERT-promoter (C228T or C250T) were retrospectively analyzed. Primary thalamic, cerebellar brainstem or spinal cases were excluded. 126 (86%), 16(11%) and 5(3%) patients were WHO grade IV, III and II respectively. After surgical treatment or stereotactic biopsy all patients underwent chemoradiation. Median follow-up was 16mo (1–110). Tumors of different grades were compared for age, gender, multifocality, gliomatosis pattern, Ki-67 index, progression-free survival and overall-survival.

RESULTS
Mean age at presentation for grade II, III and IV were comparable (58.1, 58 and 58.1; ANOVA, p=0.72). There was a slight male predominance in both lower-grades and WHO-grade IV (M:F ratios 1.625 and 1.74). Mean Ki-67 index was significantly higher in higher grades (0.06, 0.14 and 0.25 for grades II, III and IV; ANOVA, p=0.001). Multifocality was comparable (chi-sq, p=1) in lower-grades (3/21; 14.3%) vs. WHO-grade IV (18/126; 14.3%). Gliomatosis pattern was comparable (chi-sq, p=0.095) in lower-grades (2/21; 9.5%) vs. (3/126; 2.3%). Median recurrence free survival (RFS) was 16 months (0–63) in lower-grades and 8months (1–50) in WHO-grade IV. PFS was significantly different between 3 WHO-grades (Log rank, p=0.007) and also between lower-grades and WHO-grade IV (Log rank, p=0.002). Median overall survival was 26 months(2–110) in lower-grades and 15mo(1–91) in WHO-grade IV. OS was significantly different between 3 WHO-grades (Log rank, p=0.014) and also between lower-grades and WHO-grade IV (Log rank, p=0.007).

CONCLUSION
Increasing pathological grades of hemispheric “IDH-wild type, TERT-mutant diffuse gliomas” have similar demographic and clinical characteristics but incrasing proliferation indices, decrasing progression free survival and shorter overall survival. The findings may be suggesitve of different grades of one common tumor entity.
P14.97 High risk of venous thromboembolism in patients with brain metastases from non-small cell lung cancer
Authors: Mir Seyed Nazari P , Ay C , Steindl A , Gatterbauer B , Frischer J M , Dieckmann K , Widhalm G , Hainfellner J A , Pabinger I , Preusser M , Berghoff A 
Published: September 2019

Abstract

BACKGROUND
Venous thromboembolism (VTE) is a common complication in patients with cancer. In general, patients with metastatic disease are at highest risk. Lung cancer belong to those tumor entities with a particularly high risk of VTE, ranging between 3–13.8%. However, little is known about the VTE rate in lung cancer patients with brain metastases.

MATERIAL AND METHODS
Our study was conducted in the framework of the Vienna Brain Metastasis Registry. Clinical data and VTE events during the course of the disease were recorded via retrospective chart review. In this analysis, non-small cell lung cancer (NSCLC) patients with a resection of brain metastases at the Medical University of Vienna between 2006 and 2010 were included.

RESULTS
In total, 69 NSCLC patients with brain metastases were analyzed. Overall, 69.6% (48/69) patients had an adenocarcinoma, 13% (9/69) a squamous cell carcinoma, 8.7% (6/69) a large cell carcinoma and 8.7% (6/69) other primary tumor histologies. After cancer diagnosis, 20.3% (14/69) patients developed VTE during the course of the disease. Of those, 85.7% (12/14) thromboembolic events occurred after the diagnosis of brain metastases.

CONCLUSION
Based on our data, patients with brain metastases from NSCLC have a very high VTE risk. Further investigations are needed in order to identify patients with distinct VTE risk profiles. Patients at high risk might potentially benefit from primary thromboprophylaxis over the high risk of intracerebral bleeding.
P14.102 Cerebellar atrophy patterns in paraneoplastic cerebellar degeneraiton and spinocerebellar ataxia 1 (SCA1)
Authors: Vialatte de Pémille C , Psimaras D , Adanyegu I , Graus F , Dürr A , Honnorat J , Delattre J , Alentorn A 
Published: September 2019

Abstract

BACKGROUND
Brain and more specifically cerebellar atrophy is a major radiological finding in both Paraneoplastic Cerebellar Degeneration (PCD) with anti-Yo antibodies and Spinocerebellar Ataxia type 1 (SCA1).We sought to analyze the different brain volumetric patterns of cerebellar atrophy in these diseases.

MATERIAL AND METHODS
We performed a retrospective multicentric study (Paris, Lyon, Barcelona reference centres) with either anti-Yo PCD (n=16) or SCA1 (n=17) and 30 healthy subjects paired by age. We used VolBrain and CERES algorithms to obtain the brain and cerebellum segmentation, respectively as well as the cortical thickness. We used a Sparse Canonical Correlation Analysis (SCCAN) and Voxel Brain Morphometry (VBM) with family wise error correction to analyze volumetric differences between the different conditions.

RESULTS
SCA patients were younger than PCD patients (p<0.05, ANOVA). In univariate analysis, most of the atrophic regions (p<0.05) were common between PCD and SCA1 compared to controls. Isolated cortical thickness and grey matter analysis showed predominant atrophy in PCD patients. Multivariate analysis using SCCAN and VBM confirmed these results. We identified a particular atrophy pattern in PCD patients involving lobules III to VII. We observed a more diffuse atrophy distribution in SCA1 patients and a lower cortical atrophy in PCD patients.

CONCLUSION
We described the specific pattern of topographic cerebellar atrophy in PCD and SCA1 patients. The cerebellar atrophy in PCD is mainly localized in the neocerebellum.
P14.118 Carboxypeptidase G2 (CPG2) rescue after high dose methotrexate (hdMTX) chemotherapy for Primary CNS Lymphoma (PCNSL). A French LOC network study
Authors: Garcilazo Y J , Soussain C , Tabouret E , Ahle G , Schimitt A , Waultier A , Blonski M , Liou-Schischmanoff A , Hoang-Xuan K , Houillier C 
Published: September 2019

Abstract

BACKGROUND
CPG2 is an efficient rescue recombinant bacterial enzyme that cleaves MTX into inactive metabolites. As hdMTX is the key agent in PCNSL, delayed MTX excretion (DME), and/or MTX induced nephrotoxicity (MIN) may expose the patients to severe toxicities and prevent the further use of the drug. Little is known on the use of CPG2 and its impact on patient outcome.Objective: To describe the clinical characteristics, indications, risk factors, outcomes of PCNSL patients treated with CPG2.

MATERIAL AND METHODS
Retrospective analysis of patients from the LOC network database with histologically proven PCNSL, aged >18, who received CPG2 following hdMTX.

RESULTS
From 2011 to 2018, 41(3%) of 1236 patients treated with hdMTX used CPG2. Median age: 70 years [46–86], sex ratio M/F 3.6, median KPS 70. Indications of CPG2 were DME (12%), MIN (34%), both (49%). 37/41 (90%) of the patients had either a cardiovascular history (CVH) (76%) or a preexisting chronic kidney disease (CKD) (56%) and 59% had at least one additional risk factor: delayed MTX elimination or renal toxicity in prior cycles (20%), other grade III-IV toxicity (20%), concomitant drugs interfering with MTX excretion (29%), active infection (22%), hypoalbuminemia (59%). Median hdMTX dose was 3 g/m2 [1–3.5], median number of MTX injection received at the time of CPG2: 2[1–6]. At time of the CPG2 administration, median serum creatinine was 185 μmol/l [108–410] and median serum MTX: 25 μmol/l [1–240]. 24% of patients underwent hemodialysis, 76% return to baseline creatinine, in a median of 30 days; no MTX related deaths were reported. Extrarenal grade III-IV toxicities: lymphopenia (46%), neutropenia (22%), mucocutaneous toxicity (15%), thrombopenia (12%), hepatotoxicity (12%), sepsis (12%). Median time to chemotherapy resumption: 26 days (cytarabine-based or hdMTX rechallenge). HdMTX was reintroduced safely in 14 patients (34%) but one. The outcome (ORR, PFS OS) was similar with that expected of patients who would not have had toxicity to MTX.

CONCLUSION
In our study, a small number of patients have received CPG2 regarding the incidence of MIN and DME, probably due to treatment cost. The high frequency of risk factors points out the need of careful attention of this issue and for adapted hdMTX protocol for this vulnerable population. CPG2 treated patients do not have a worse prognosis than expected. A controlled study is warranted to compare the cost/benefit of the management of MIN /DME with or without CPG2.
P14.120 Phase II study of weekly carboplatin in pretreated adult malignant gliomas
Authors: Villani V , Pace A , Vidiri A , Tanzilli A , Sperati F , Terrenato I , Carosi M , Casini B , Maschio M , koudriavtseva T , Cognetti F , Fabi A 
Published: September 2019

Abstract

BACKGROUND
Patients with relapse of recurrent glioma have a poor outcome and limited treatment options. The aim of this study is to investigate the clinical benefit and tolerability of weekly intravenous administration of carboplatin-based monotherapy in adult glioma patients who had progressed from previous chemotherapy lines based on temozolomide and nitrosoureas

MATERIAL AND METHODS
This was a single arm, Phase II study. Eligibility criteria included progressive or recurrent malignant glioma after radiotherapy and chemotherapy-based treatments and Karnofsky Performance Status (KPS) > 60.

RESULTS
Thirty-two patients (median age: 43.5 y) were enrolled to receive weekly carboplatin monotherapy in intravenous mode of administration. The median duration of response was 7.3 months with an overall disease control rate of 31.3%. Median progression-free survival (PFS) was 2.3 months while overall survival (OS) was 5.5 months. Patients achieving clinical benefit exhibited a longer PFS (4.6 vs 1.5 months; p>0.001) and OS (7.9 vs 3.2 months; p=0.041) compared to those not achieving clinical benefit.

CONCLUSION
Our findings show that single agent, weekly, intravenous carboplatin may have a role in the treatment patients with recurrent malignant glioma
P14.122 Integrin α5 is a poor prognostic factor in patients with glioblastoma treated by the Stupp protocol
Authors: Etienne-Selloum N , Prades J , Bello Roufai D , El Azumi F , Boone M , Sevestre H , Trudel S , Coutte A , Desenclos C , Constans J , Chauffert B , Dontenwill M 
Published: September 2019

Abstract

BACKGROUND
Integrin α5β1 was suggested to be involved in glioblastoma (GBM) aggressiveness through preclinical studies and genomic analysis of several cohorts of patients. However, protein expression data are still missing to confirm this hypothesis. Our aim was to investigate the prognostic value of integrin α5 protein expression level in GBM.

MATERIAL AND METHODS
We retrospectively determined the protein expression level of integrin α5 using immunochemistry in tumors from patients treated in 6 French centers. Paraffin sections of GBM were labeled by immunofluorescence and analyzed by confocal microscopy. The corresponding clinical and survival data have been identified and analyzed. The primary end-point was overall survival (OS).

RESULTS
Out of 297 patients newly diagnosed with GBM between 2006 and 2013, 152 met the inclusion criteria (scheduled for initial treatment with the Stupp protocol, age > 18 years) and 95 tumor samples were suitable for immunohistochemical analysis. The median age is 58 years, (64 men, 34 women). Most of patients received macroscopic (43%) or partial (36%) surgery. In univariate analysis using the Log Rank test, high integrin α5 expression level was associated with poor prognosis (PFS: hazard ratio (HR) = 1,696, p=0,0355; OS: HR=1,598, p = 0,0508). Corresponding median OS were 15,6 versus 19,2 months. Similarly, OS was significantly reduced with age (> 60 years), lower resection degree, higher RPA (recursive partitioning analysis) score and non-methylated MGMT (O-6-methylguanine-DNA methyltransferase) promoter. In the subgroup of patients who received the full initial protocol (temozolomide treatment together with radiotherapy and later as adjuvant treatment; n=58) mean OS was strongly reduced when integrin α5 expression level was high (15,6 versus 22,8 months, p=0,0162) suggesting an impact of integrin signaling on temozolomide response in GBM.

CONCLUSION
Our study validates for the first time that the high protein level expression of α5 integrin is associated with poor prognosis in GBM. It also confirms its potential as a therapeutic target and its likely role in resistance to temozolomide as previously shown in preclinical study.