bluuebunny/crossref_metadata_2025_split huggingface dataset:
P14.28 First report on the combination of axitinib and Tumor Treating Fields (TTFields) in three patients with recurrent glioblastoma
Authors: Keßler A F , Weiland J , Linsenmann T , Ernestus R , Hagemann C , Löhr M 
Published: September 2019

Abstract

BACKGROUND
Adding Tumor Treating Fields (TTFields) to first-line therapy in glioblastoma (GBM) demonstrated significantly improved survival in the EF-14 trial. Furthermore, in a post-hoc analysis of the EF-14 trial, median overall survival increased significantly upon recurrence (rGBM) for patients treated with bevacizumab (Bev) and TTFields compared to Bev monotherapy. Axitinib (Axi) is an orally available tyrosine kinase inhibitor which is approved for the treatment of metastatic renal cell carcinoma. It has a high affinity and specificity for vascular endothelial growth factor receptors, thereby acting similar to Bev. In phase 2 trials, Axi improved response rate and progression free survival in rGBM patients compared to historical controls with a manageable toxicity profile. We report on three rGBM patients treated with TTFields and Axi (AxiTTFields).

METHODS
A 53-year-old male patient (#1) presented with a multifocal and consistently progressing GBM after initial surgery, radiochemotherapy (RCT) and after 4 cycles of temozolomide (TMZ), combined with TTFields. To meet the urgent need of an alternative treatment, Axi (5mg twice a day) was added to the treatment regimen. In a 46-year-old male patient (#2), an early progress occurred after surgery, RCT and 3 cycles of TMZ combined with TTFields. Similarly to #1, Axi was added to the treatment regimen. In a 61-year-old male patient (#3) with a rGBM after surgery and RCT at the time of the 6th cycle of TMZ, TTFields therapy was initiated at recurrence and treatment regimen was adapted to AxiTTFields.

RESULTS
In these three patients, AxiTTFields was safe and feasible. #1 and #2 were on AxiTTFields therapy for more than 8 months, presenting an improved neurological status with a partial response in the MRI 3 months initiating the combined treatment of AxiTTFields. #3 declined in his neurological status without any change in the MRI monitoring and died 2.4 months after initiating AxiTTFields. Although, Axi as well as TTFields may cause skin irritations, none were observed in this case series. With an average of 77 % in these three patients, the TTFields usage rate was above the independent prognostic threshold of 75 %, underlining the feasibility of this approach. There were no additional adverse events due to the combined therapy of AxiTTFields.

CONCLUSION
In summary, AxiTTFields was feasible and safe in three rGBM patients. As the addition of Axi to TTFields therapy is a promising approach, we plan to investigate the safety and feasibility of this combination in a pilot trial. Further studies might explore effects on outcome and survival of AxiTTFields in rGBM.
P14.33 Adult brainstem gliomas in neurofibromatosis type 1 (NF1)
Authors: Guillamo J , Wang A , Ducray F , Barbarot S , Chinot O , Frappaz D , Bauchet L , Wolkenstein P , Laigle-Donadey F 
Published: September 2019

Abstract

BACKGROUND
The brainstem is the second location of brain tumors after optic pathways in NF1. In NF1 children, brainstem gliomas are usually indolent and have a better prognosis than their counterparts in non NF1 children. In contrast, the natural history and prognosis of adult brainstem gliomas in NF1 are nearly unknown.

MATERIAL AND METHODS
We conducted a retrospective analysis of medical records and MRI of adult NF1 patients followed for a brainstem glioma in 8 centers over a 17 years period (2000–2017). Clinical and imaging characteristics, management and outcome were analyzed.

RESULTS
Twenty five patients were included in the study (13 males and 12 females) with a median age of 32 (range 17–58). The epicenter of the tumor was located into the pons n=13 (52%), the mesencephalon n=7 (28%), the medulla oblongata n=5 (20%). On MRI, contrast enhancement was seen in 19 tumors (76%). Pathological examination was available in 13 tumors (52%) and showed a high grade astrocytoma (III or IV) in 9 tumors. Five patients were asymptomatic, 3 remained asymptomatic during the follow-up (median follow-up: 86 months, range 22–124). Twenty patients were symptomatic with a median duration of symptom of 2.5 months (range 1–10) before diagnosis. Among these symptomatic patients, 15 died from tumor progression despite treatment with radiation therapy and or chemotherapy. The median overall survival of symptomatic patients was 36 months.

CONCLUSION
Brainstem gliomas are rare tumors in adults with NF1. Unlike children, adult brainstem gliomas seem to have an unexpected poor prognosis, suggesting the disease may be different in adulthood.
P14.37 Depression in patients with primary brain tumors: Relation to clinical variables and tumor characteristics
Authors: John F , Barger G R , Mittal S , Juhasz C 
Published: September 2019

Abstract

BACKGROUND
Patients with brain tumor have an increased risk for depressive disorder, however, the association between depression and clinical or tumor-related variables remains mostly unclear. In this study, we analyzed the relation of depression to several clinical and tumor-related characteristics in patients with primary brain tumors.

MATERIAL AND METHODS
Sixty patients with newly-diagnosed (n=34) or recurrent (n=26) primary brain tumors (50 gliomas, 10 meningiomas) underwent testing with the Beck Depression Inventory-II (BDI-II). Relation of BDI-II scores to clinical and tumor-related characteristics, including age, Karnofsky Performance Status (KPS) scores, presence of antiepileptic, antidepressant, or steroid treatment, as well as tumor grade, lateralization, and lobar localization, were analyzed. In a subset of recurrent malignant glioma patients, the prognostic value of BDI-II scores on overall survival was also analyzed.

RESULTS
The mean total BDI-II score was 10±8 (range: 0–37); while 27% of patients (n=16) had BDI-II scores indicating at least mild depressive disorder (≥13), only a portion of them (17%) was on antidepressant treatment. No BDI-II difference was found between gliomas vs. meningiomas or newly-diagnosed vs. recurrent tumors; also, no association was found with any tumor-related characteristics. Antiepileptic or steroid therapy had no association with BDI-II scores, while higher BDI-II scores were observed in patients with ongoing antidepressant therapy (15±10 vs. 8±7, p=0.017). Higher BDI-II total and somatic subscale scores correlated with lower KPS scores (r=-0.32, p=0.014 and r=-0.31, p=0.017, respectively). In recurrent malignant glioma patients (n=18), higher depression scores were associated with shorter survival (hazard ratio: 3.7; 95% confidence interval: 1.0–13.6; p=0.048).

CONCLUSION
Depression affected more than ¼ of patients with primary brain tumors in this single-center cohort and was independent from most clinical and tumor-related characteristics, except KPS scores. Although most of these patients have mild depression that is often overlooked without targeted screening, higher BDI-II scores may predict shorter overall survival in recurrent malignant glioma patients. These data reinforce the importance of early recognition and treatment of depressive symptoms in patients with primary brain tumors.
P14.61 Tumor Treating Fields (TTFields) combined with lomustine (CCNU) and temozolomide (TMZ) in newly diagnosed glioblastoma (GBM) patients - a bi-centric analysis
Authors: Lazaridis L , Schäfer N , Schmidt T , Stoppek A , Weller J , Tzaridis T , Scheffler B , Pierscianek D , Kleinschnitz C , Stuschke M , Sure U , Herrlinger U , Kebir S , Glas M 
Published: September 2019

Abstract

BACKGROUND
TTFields combined with TMZ demonstrated significantly improved PFS, OS and long-term survival in newly diagnosed glioblastoma (ndGBM) patients, compared to TMZ monotherapy in the EF-14 trial; independent of MGMT-promotor methylation-status, age, grade of resection and performance status. Recently, improved efficacy of lomustine (CCNU)/TMZ compared to TMZ monotherapy in ndGBM patients with MGMT-promotor methylation was reported in the CeTeG trial (NOA-09). Taken into account that TTFields showed a strong safety profile as well as a high potential being combined with other modalities and the very encouraging results for methylated MGMT-promotor GBM patients in the CeTeG trial, there is a strong rationale in combining these treatment regimens. Here, we present a case series of patients receiving a combination of both modalities, TTFields and CCNU/TMZ.

METHODS
Patients with ndGBM and MGMT-promotor methylation underwent a combined therapy of TTFields plus CCNU/TMZ after surgery and radiochemotherapy. Safety, feasibility as well as first efficacy results of this combined therapy are reported at data cut-off (31.12.2018). Most recent data, including compliance to TTFields therapy, will be presented at the EANO annual meeting.

RESULTS
Twelve patients with MGMT-promotor methylated ndGBM (median, range: age 49.5, 26–69; KPS 90, 60–100) have been treated with a combination of TTFields plus CCNU/TMZ. The analysis included patients with complete resection (n=6), partial resection (n=5) as well as biopsy (n=1). CTCAE grade 3 hematotoxicities were observed in six patients, but were not considered to be related to the addition of TTFields to lomustine/TMZ. Medical device site reactions (low-grade skin reactions) were detected in five patients. At data cut-off, the analyzed patient population demonstrated a median PFS of 18.7 months, whereas the median OS was not yet reached.

CONCLUSION
The results of this analysis provide first indication that the combination of TTFields/lomustine/TMZ is safe and feasible. Moreover, the observed survival outcomes point to preliminary beneficial effects of the triple combination. Additional follow-up and a higher sample size is required and planned for further toxicity analysis and efficacy assessment of this combination.
P14.75 Active beam scanning proton therapy radiosurgery: early outcomes
Authors: Amelio D , Scartoni D , Righetto R , Fellin F , Giacomelli I , Turkaj A , Schwarz M , Amichetti M 
Published: September 2019

Abstract

BACKGROUND
Stereotactic radiosurgery (SRS) is an important treatment option for intracranial lesions and several photon-SRS techniques have been developed. Proton therapy (PT) has special characteristics that allow normal tissues to be spared better as well as greater homogeneity than with the use of photons, but limited data are available for proton-SRS. Nowadays, PT-SRS is delivered only with passive scattering technique while active pencil beam scanning (PBS) that is considered the most advanced proton technique has not been reported for SRS treatments yet. Here we report early clinical outcomes of PBS PT SRS.

MATERIAL AND METHODS
Between June 2017 and January 2019, 14 patients (pts) with 20 lesions underwent PBS PT SRS at our institution. Median age was 62 years (range, 28–87). Median Karnofsky performance status was 90 (range, 70–100). Six were male. Tumors included 16 meningiomas (MG) and 4 vestibular schwannomas (VS). Median GTV was 1.05 cc (range, 0.2–2.71). Dose prescription was 12 Gy radiobiologic equivalent (RBE) in one fraction for VS and 15 GyRBE in one fraction for MG. Pts were immobilized using a frameless system: Type-S proton overlay and Type-S proton mask (CIVCO medical solutions, Kalona, IA, USA) together with Moldcare headrest (Q-Fix systems, Avondale, PA, USA). All pts were treated with PBS PT using 2–3 fields with single field optimization technique, and using min-max robust robust optimization (2 mm setup errors, 3.5% range uncertainties), with a Monte Carlo algorithm and 1 mm grid size. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.0.

RESULTS
Median follow-up (FU) was 9 months (range, 3–22). All pts completed the treatment with excellent compliance and no side effects were registered during the procedure. Registered acute side effects include grade 1 (14%) fatigue, grade 2 (7%) headache, and grade 2 (28%) alopecia. There were no grade 3 or higher acute toxicities. Registered late side effects include grade 1 (7%) headache, and grade 1 (14%) alopecia. There were no grade 3 or higher late toxicities. Currently, absolute tumor control is 100% regardless the type of tumor. Despite the short FU radiological reduction was registered in 9 lesions (45%).

CONCLUSION
PBS PT SRS is a feasible and safe treatment in pts with MG or VS. A high radiological response rate was observed. Longer FU is necessary to assess definitive safety and efficacy.
P14.83 Adjuvant chemotherapy after severe myelotoxicity during temozolomide chemoradiation in gliomas. It is feasibile? The talian Multicentric Study (AINO)
Authors: Villani V , Fabi A , Gaviani P , Rudà R , Lombardi G , Simonetti G , Silvani A , Pronello E , Minniti G , Pace A 
Published: September 2019

Abstract

BACKGROUND
Malignant gliomas are aggressive primitive brain tumor in adults. Today, the standard of care is Temozolomide (TMZ) administered daily with radiation therapy, followed by adjuvant TMZ. TMZ treatment has been considered to have a low toxicity profile. However, during concomitant treatment some patient may develop a severe myelosuppression. This toxicity may be in some cases prolonged and lead to treatment discontinuation.

MATERIAL AND METHODS
We have retrospectively collected data from 5 italian neuro-oncological centers, about glioma patients who developed severe and prolonged hematological toxicity during concomitant chemoradiotherapy with TMZ. The purpouse of this study is to evaluate: percentage of patients receiving adjuvant chemotherapy after severe myelotoxicity; rate of toxicity observed during adjuvant chemotherapy.

RESULTS
54 glioma patients who developed myelosuppression of grade 3 or 4 were considered. Hystology was Glioblastoma in 45 patients (83%); 63% of patients were female. Myelotoxicity during concomitant phase occurred at a median of 4 weeks (range 1–8) from the start of treatment.After recovery of myelotoxicity 19 patients did not received any treatment while 35 (65%) were treated with chemotherapy (28 received standard TMZ, one TMZ with metronomic schedule, 2 lomustine and 4 other agents). Among patients treated with TMZ, 13 patients presented hematological toxicity grade 3–4 which required treatment discontinuation in 7 cases (20%).

CONCLUSION
we observed that 80 % of glioma patients presenting severe myelotoxicity during concomitant radiochemotherapy may be treated with maintenance TMZ after blood value recovery.
P14.90 Interleukin 6 is a useful marker for pseudotumoral inflammatory CNS lesions suspicious of lymphoma
Authors: Ungureanu A , Costopoulos M , Parratte T , Brinet A , Durand H , Gaultier C , Postert T , Hurstel R , Alamome I , Sellal F , Le Garff-Tavernier M , Ahle G 
Published: September 2019

Abstract

BACKGROUND
Interleukin (IL)-6 is a dual pro and anti-inflammatory cytokine and its presence in the cerebrospinal fluid (CSF) is considered as a marker of central nervous system (CNS) inflammation. Our aim was to analyze the diagnostic significance of CSF IL-6 levels among various CNS pseudotumoral inflammatory lesions (PIL) and primary CNS lymphoma (PCNSL).

MATERIAL AND METHODS
We retrospectively analyzed the CSF IL-6 concentrations in 43 patients with a differential diagnosis of PCNSL. Finally, 28 patients were positively diagnosed with PCNSL and 15 with other inflammatory CNS disorders. We verified the results with CSF IL-10, a biomarker for PCNSL. IL 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
In the PCNSL group, the median CSF IL-6 concentration was 8 pg/ml, interquartile range (IQR) 5 - 18.5. For the patients with other PIL the median concentration was of 70 pg/ml, IQR 5 - 1368. A group comparison disclosed significantly higher CSF IL-6 levels in patients with PIL compared to the group with PCNSL (p=0.032). Moreover, IL-6 was correlated with CSF cell count for the whole cohort (r=0.45, p=0.002), as well as for the PIL group (r=0.56, p=0.028), but not for the PCNSL group (r=0.3, p=0.13). We found significantly higher CSF IL-10 levels in patients with PCNSL compared to the group with other CNS inflammatory lesions (p<0.001).

CONCLUSION
Our study suggests that CSF IL-6 levels could represent, in addition to CSF IL-10, a useful biomarker in the diagnosis of CNS PIL that may mimic PCNSL.
P14.99 Clinical and biologic features predictive of survival after relapse of childhood medulloblastoma
Authors: Huybrechts S , Chivet A , Tauziede-Espariat A , Rossoni C , Indersie E , Varlet P , Puget S , Abbas R , Ayrault O , Guerrini-Rousseau L , Grill J , Valteau-Couanet D , Dufour C 
Published: September 2019

Abstract

BACKGROUND
Salvage therapy for recurrent medulloblastoma (MB) is not standardized. Factors associated with survival after recurrence have not been reported.

MATERIAL AND METHODS
Medical records were reviewed for 155 consecutive patients with newly diagnosed MB between 2007 and 2017, treated at Gustave Roussy and Hospital Necker. The following variables were collected for all patients: age at diagnosis, stage, histology (central review according to WHO 2016 classification), molecular subgrouping (DNA methylation), first-line treatment modalities, time to relapse, pattern of recurrence and current status.

RESULTS
A disease recurrence was observed in 47 patients (30%) at a median time of 15 months (range, 1–88 months). The 1-year survival after recurrence was 44% (CI 95%,29.6 to 58.8). The pattern of recurrence was local in 9 patients, metastatic in 21 and combined local and metastatic in 17 patients. The time to first recurrence, less or more than 12 months from diagnosis, was a predictor of post-recurrence overall survival (p < 0.0001) after adjustment for age, treatment, MYC amplification and molecular subgroups. Twenty-seven patients (57%) experiencing recurrent or progressive disease more than 12 months after diagnosis, had an estimated 1-year survival after recurrence of 100% (CI 95%, 100.0 to 100.0) vs 30% (CI 95%, 12.2 to 50.1) with an earlier recurrence. Early relapse was more frequent in children younger than 5 years of age at diagnosis (75% vs 37%, p =0.009), anaplastic/large cell MB (30% vs 3.7%, p=0.046) and Group 3 tumours (76.5% vs 20.8%, p=0.003). Other factors influencing post-relapse survival were metastatic disease and treatment modalities at diagnosis. Multivariable analyses will be presented.

CONCLUSION
The overall prognosis after relapse remains poor. Time to relapse is a significant prognostic factor for postrelapse survival and may help in the design of clinical trials evaluating new agents.
P14.100 Measurements of glioblastoma response to recurrence using spectroscopic measurements and MRI volumetry
Authors: Chombar J , Heintz A , Constans J 
Published: September 2019

Abstract

BACKGROUND
Glioblastoma is the most aggressive and common primary malignant brain tumor in adults. The prognosis of patients with glioblastoma remains poor with a median life expectancy of 15 to 17 months and a survival rate of 5% at five years.Spectroscopy is becoming more and more used and the ratios studied allow in some cases a better prediction, at the recurrence, of the survival between certain ratios such as: Cho / Cr, NAA / Cr, Lac / Cr. Being able to combine all these ratios can allow us to obtain an additional survival index to take into account.This is why our study assesses whether MRS is coupled with volume, it is predictive of survival of the patient at 7 months.

MATERIAL AND METHODS
Population: 30 Patients with glioblastoma treated with the STUPP protocol with and without bevacizumab at recurrence over a period of 36 months. Patients divided into three different groups depending on the type of resection (subtotal (20), partial (13), and biopsy (7)).MRI sequences every 2 months on MRI 3T and 1.5T. Sequences we used: diffusion, T2, T2 *, FLAIR, 3D FLAIR, 3D T1 with gadolinium injection; also monovoxel spectroscopy (TE at 35 and 144 ms, sometimes 288 ms). The volume variations (calculated by Aw.Server and ITK) are evaluated according to the RANO criteria.The MRS ratios (calculated by jMRUI) were clinically used are Cho / Cr (tumor proliferation), NAA / Cr (infiltration) and Lac / Cr (glycolytic metabolism). Longitudinal analyzes of volumes and ratios.

RESULTS
30 patients included in this study. The analysis of the results is that proliferation and / or glycolytic metabolism are more informative and predictive when there is absence of contrast enhancement, hyperperfusion or large volume variation. The global index (choline + lactate / NAA) could be a relevant criterion of judgment to better study the aggressiveness of the tumor and better predict the evolution of tumor volumes and survival. Intra-inter-operator differences on 2 segmentation software.

CONCLUSION
The study shows us and confirms that the widest possible resection is to favor. Spectroscopy ratios vary earlier than the volumetry and give more information on the tumor processes and is sometimes predictive of survival.
P14.111 Successful treatment of extensive metastatic disease with successive use of two different EGF receptor antagonists: case report and review of the literature
Authors: Megyesi J F , Macdonald D R 
Published: September 2019

Abstract

INTRODUCTION
EGFR-targeted agents can be useful in the treatment of systemic metastatic cancer including that which has spread to the brain. We present the case of a patient with two different EGFR mutations that responded to receptor blockade.

CASE REPORT
A 38 year old right-handed female presented with a one week history of progressive left-sided weakness and focal seizures. Neuroimaging revealed multiple enhancing brain lesions and a lesion in the left maxillary antrum. Body imaging revealed a right lung mass, hilar and mediastinal nodes and multiple bony lesions. Biopsy of the maxillary antrum lesion showed metastatic poorly differentiated adenocarcinoma, TTF-1 positive, suggesting a lung primary. ALK was not mutated but there was an EGFR mutation (exon 19 deletion). The patient underwent treatment with dexamethasone, levetiracetam, whole brain radiation and afatinib, an oral EGFR-targeted agent. Most of the brain lesions responded completely with only two small residual lesions. Seizures were controlled. There was major partial response from the systemic lesions. Two years later the patient was clinically well but the lung lesion, mediastinal nodes and bony lesions were all enlarging. A new pituitary lesion was identified on brain MRI. A liquid biopsy (blood) revealed a T790M mutation and the patient underwent stereotactic body radiation and EGFR-targeted therapy with osimertinib. All lesions responded to treatment and four years after initial diagnosis the patient is clinically well with stable disease.

DISCUSSION
Successful treatment of widespread metastatic disease is possible with the use of multiple EGFR-targeted agents in certain patients.