bluuebunny/crossref_metadata_2025_split huggingface dataset:
P14.64 Primary Central Nervous System Lymphoma (PCNSL) with HD- MTX based chemotherapy: tolerability and results
Authors: Silvani A , Anghileri E , Simonetti G , Eoli M , Finocchiaro G , Pollo B , Farinotti M , Fariselli L , Gaviani P 
Published: September 2019

Abstract

BACKGROUND
Primary Central nervous system (CNS) lymphomas (PCNSL) are extranodal, malignant non- Hodgkin lymphomas of the diff use large B-cell type, confined to CNS. It accounts for up to 1% of all lymphomas and about 3% of all CNS tumours. The incidence continues to rise in immuno- competent elderly patients.Although the prognosis of PCNSL remains poor, it has improved in the past two decades as a result of better treatment strategies. However, treatment recommendations still result mainly from retrospective series or single-arm phase 2 studies and a few three completed randomised trials. We described a series of patients with newly diagnosis of PCNSL treated with modified-schedula published by Omuro

MATERIAL AND METHODS
Patients was treated with HD-MTX, procarbazine, vincristine, received four 28-day cycles of chemotherapy, on schedule: HD-MTX (3·5 g/m²) days 1 and 15; Procarbazine (100 mg/m²) on days 1–7. Vincristine (1·4 mg/m²) on days 1 and 15. Toxicity was assessed with Common Terminology Criteria for Adverse Events version 4. The International PCNSL Collaborative Group Response Criteria were used for response assessment. Endpoints include overall survival (OS) and adverse events (AE).

RESULTS
21 immunocompetent patients (12 females and 9 males) were retrospectively studied, among 2014 to 2019. Median age at diagnosis 61 years (range 41–76). Median KPS at diagnosis was 70 (range 40–100). Clinical and radiological data and treatment related toxicity were described

CONCLUSION
Present combination regimen is effective; however, AE incidence is high, and often induces schedule modification
P14.65 Anaplastic pleomorphic xanthoastrocytoma: literature review& case report
Authors: Agabekyan G , Kobyakov G , Lodygina K , Kobyakov N , Absalyamova O , Ryzhova M , Inozemcevа M , Poddubsky A 
Published: September 2019

Abstract
Pleomorphic xanthoastrocytoma (PXA) is a rare glial brain tumor. 9% to 30% cases have anaplastic features which determine poor prognosis. Anaplastic features may be found either in primary tumor or in recurrent PXA in any time frame. According to WHO 2016 Brain Tumor Classification, anaplastic pleomorphic xanthoastrocytoma (aPXA) was reclassified as grade III tumor (previously grade II). Characteristic features for aPXA are mitotic index of 5% or higher and worse 5-year survival rates in comparison with PXA: 57.1% and 90.4%, respectively. About 6% cases have TP53 gene mutation. About 60–78% tumors are BRAF-mutated, which is a potential target for therapy. Currently there are ongoing clinical trials to determine efficacy of BRAF and MEK inhibitors in pediatric patients with high-grade glioma with BRAF mutation. There is a number of publications showing positive outcome of targeted therapy both in children and adults. Treatment protocol for aPXA has not been defined. Case report Patient N. 14-y.o. female. MRI showed tumor of left occipital lobe. 02.03.2016 stereotactic biopsy was performed. Histological examination revealed diffuse astrocytic glioma WHO grade III-IV. Radiation therapy was performed, after which patient’s condition abruptly deteriorated with back pain, patient became almost unable to walk, however control MRI showed no signs of spinal dissemination. 01.12.2016 surgery to remove left occipital lobe tumor was performed. 07.12.2016 MRI showed contrast enhancing lesions throughout entire length of the spinal cord. Histological examination revealed aPXA gr. III, Ki-67 up to 8%. From December to June 2017 patient received 6 cycles of chemotherapy with temozolomide. Molecular testing discovered BRAF V600 mutation in exon 15. Chemotherapy regimen was thereby changed to vemurafenib 1920 mg/day from July 2017. After a month of treatment patient developed cutaneous toxicity and the dose was lowered to 960 mg/day. Patient’s condition improved: back pain syndrome regressed, lower extremity muscle strength increased, patient became able to walk. MRI 03.12.2017 revealed an increase of contrast enhancing lesion and T2-FLAIR hyperintense signal area in left occipital lobe, no progression in spinal cord. Methionine PET/CT was performed, the findings were evaluated as a combination of radiation necrosis and glioma growth. In view of MRI and PET/CT findings, amount of time passed after radiation therapy, we decided to include bevacizumab 400 mg every 2 weeks in the regimen. Since January 2018 patient is receiving vemurafenib 960 mg/day and bevacizumab 400 mg every 2 weeks. There is a marked positive dynamic in clinical findings and imaging data (MRI and PET/CT). We report the patient with aPXA and prolonged response to targeted therapy. The presence of the BRAF V600E mutation was possibility of treatment which led to successful results.
P14.66 TTFields dose distribution and tumor growth patterns confirm clinical activity of TTFields: MRI analysis of the randomized phase 3 EF-14 trial
Authors: Kebir S , Ballo M T , Jeyapalan S , Toms S A , Hottinger A , Pollom E , Glas M 
Published: September 2019

Abstract

BACKGROUND
The randomized phase 3 EF-14 trial showed that the addition of tumor treating fields (TTFields) to temozolomide (TMZ) treatment improved survival in newly diagnosed glioblastoma patients over TMZ alone. As TTFields delivery is designed to optimize dose at the tumor bed, we hypothesized that tumor recurrence is likely to occur in distant sites and we investigated the pattern of tumor growth at relapse in due consideration of TTFields dose intensity distribution.

METHODS
Patients on therapy for more than 2 months who exhibited radiological progression were included in the study (treatment: N=280/466, control: N=122/229) Contrast-enhanced T1-weighted scans at baseline and at relapse served for segmentation of enhancing tumor and necrosis. Lesions outside a proximal boundary zone of 20mm surrounding lesions identified at baseline were defined as distal. In addition, infratentorial progression was assessed. Moreover, we identified patients treated with TTFields with sufficient MRI data for dose calculations and radiographically confirmed tumor relapse (N=225/466). TTFields intensity distributions were computed in a finite element method applied in a realistic head model with virtual transducer arrays. TTFields dose density (mW/cm3) was defined as TTFields power loss density multiplied by average patient compliance during the first 6 months of therapy. At baseline, regions of residual tumor and regions of normal brain were identified to calculate TTFields dose within each of these regions and noted its relationship with subsequent recurrence.

RESULTS
Distal progressions were more common in the TTFields arm (18% vs. 8%). Infratentorial progression was seen in 4% of the treatment arm vs. 0 patients in the control. Lesions at progression were more distant from the original lesion in the TTFields arm (57.0 + 26.2 mm vs. 46.6 + 14.8 mm). Local tumors grew at a significantly lower pace in the TTFields arm as compared to the control arm (3.6 + 14.5 ml vs. 8.3 + 17.9 ml). The average dose density in areas of enhancing tumor that regressed to normal was higher than in the areas of normal brain that progressed to enhancing tumor (0.84 mW/cm3 vs. 0.75 mW/cm3). Regardless of the expansion margin used for analysis, TTFields dose density in areas of normal brain that remained normal at the time of progression was higher than in the areas that progressed to enhancing tumor.

CONCLUSIONS
TTFields appear to induce distant tumor growth pattern and are associated with a lower tumor growth rate. In addition, the importance of dose density at the tumor bed is stressed as higher dose densities were seen in areas of normal brain that remain normal at the time of progression providing further rationale for carefully planning array placement to maximize delivery to areas at higher risk of recurrence. Taken together, these findings confirm the clinical activity of TTFields.
P14.71 Tumor Treating Fields combined with radiotherapy and temozolomide for newly diagnosed glioblastoma: final safety and efficacy results from a pilot study
Authors: Grossman R , Bokstein F , Blumenthal D , Ben Harush C , Limon D , Ram Z 
Published: September 2019

Abstract

BACKGROUND
Tumor Treating Fields (TTFields) are a non-invasive, loco-regional, anti-mitotic treatment consisting of low intensity alternating electric fields. The combination of TTFields with maintenance temozolomide significantly improved survival versus temozolomide alone in the phase 3 EF-14 study in newly diagnosed glioblastoma (ndGBM). In preclinical studies, TTFields increased the number of glioma cells undergoing cellular death following radiotherapy (RT) by inhibiting DNA damage repair, suggesting a radio-sensitizing effect of TTFields. This pilot study is the first to evaluate the safety and feasibility of administering TTFields concomitant to RT and TMZ in ndGBM patients.

MATERIAL AND METHODS
Patients diagnosed with ndGBM were treated with TTFields/RT/TMZ followed by maintenance TMZ and TTFields for up to 24 months. TTFields (200kHz) were delivered for >18 hours/day while the transducer arrays were removed during delivery of RT. TMZ was administered at a dose of 75 mg/m2/daily for 6 weeks and RT at a total dose of 60 Gy. The primary endpoint was safety of the combined TTFields/RT/TMZ; secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicity. Adverse events (AEs) were graded according to CTCAE V4.0.

RESULTS
10 ndGBM patients that recovered from maximal debulking surgery or biopsy were enrolled at a single center in Israel between April and December 2017. Five patients (50%) had undergone gross total resection while the rest had biopsy only. Eight of the patients were male, median age was 59, median KPS was 80 and median dose of RT was 60 Gy. Six patients (60%) reported at least one AE. The most common AE was TTFields-related skin toxicity, reported in four patients (40%), all of which were grade 1–2 in severity. Two patients reported serious AEs (seizures and general deterioration) that were considered unrelated to TTFields. Median PFS with RT/TMZ/TTFields was 10.5 months. Median OS has not yet been reached.

CONCLUSION
The proportion of patients with TTFields-related skin toxicity was similar to that reported in ndGBM patients in the randomized Phase III study (52%), where patients started TTFields at least 4 weeks after RT. No other TTFields-related toxicities were reported and there were no increase in RT- or TMZ-related toxicities as a result of combining TTFields with RT in addition to TMZ. Based on the safety and preliminary efficacy results of this pilot study, a phase II randomized study has been initiated to investigate the efficacy of concomitant RT/TMZ/TTFields in 60 ndGBM patients.
P14.72 Multicentric glioblastoma - A retrospective study of imaging characteristics, treatment approach, pattern of relapse and survival
Authors: Benouaich Amiel A , Khasminsky V , Gal O , Fichman S , Weiss T , Siegal T , Yust-Katz S 
Published: September 2019

Abstract

BACKGROUND
Multicentric glioblastoma (m-GBM), defined as well separated tumoral foci, is a rare GBM variant comprising 6–13% of all GBM cases. Published data regarding m-GBM is scarce and is largely reporting on multicentric enhancing foci. We performed a retrospective study to determine the incidence, imaging characteristics, treatment approach, pattern of relapse and prognosis of m-GBM.

MATERIAL AND METHODS
The neuropathological database of our institution was surveyed for histological diagnosis of adult GBM diagnosed between 01/01/2015 and 31/05/2018. All pre-operative MRI were reviewed to identify patients with m-GBM. We included in the definition of m-GBM well separated enhancing as well as non-enhancing tumor foci. The medical records and follow-up MRI studies were reviewed in order to retrieve the data.

RESULTS
Of the 170 patients with newly diagnosed GBM 14 (8%) presented with m-GBM. All of them had at least one enhancing lesion and 11 (78.5%) patients had additional well separated non-enhancing tumor foci. The total number of lesions was 37 (19 enhancing and 18 non-enhancing) with a median number of lesions per patient of 2 (range 2 to 4). Median age at diagnosis was 66 (range: 49–79) years. Nine of the patients (64%) underwent surgical resection of the enhancing component whereas 5 patients had only a biopsy. Median follow up was 14.3 (range: 2–30) months. All but one patients were treated by standard concurrent radiotherapy with temozolomide. Median progression free survival is 6.2 (range: 0–13.3) months. Five of the 18 non-enhancing tumor foci eventually displayed contrast enhancement during the course of the disease. At last follow up, 12 patients died, with an overall survival of 12.3 months. Information regarding radiation fields, pattern of disease progression and molecular profile will be presented at the meeting.

CONCLUSION
m-GBM presents therapeutic dilemas regarding the optimal surgical approach and radiation field planning. Better understanding of the disease course and pattern of progression may help to optimize the therapeutic approach implying particularly to non-enhancing tumor foci.
P14.74 Remarkable response to Combined BRAF and MEK Inhibitors in two Adults with leptomeningeal carcinomatosis secondary to Pleomorphic Xantoastrocytoma grade II with BRAFv600E mutation
Authors: Eoli M , Pollo B , Silvani A , Paterra R , Erbetta A , Anghileri E , Gaviani P , Finocchiaro G 
Published: September 2019

Abstract

BACKGROUND
Several cancers with the BRAF V600E mutations have been successfully treated with targeted therapy. Pleomorphic xanthoastrocytoma (PXA) is a rare brain tumor, with an incidence of 0.07cases per 100,000. The BRAFV600 mutation is present in 38–60% of PXA. Typical treatment is gross total resection, followed by radiotherapy and cytotoxic chemotherapy at recurrence

MATERIAL AND METHODS
Two cases are described.

RESULTS
The first case is a 37 old man with a left temporal lobe lesion who underwent a craniotomy with total tumor resection. Histological diagnosis was PXA WHO grade 2with BRAF V600E mutation.Five months after, MR imaging of his brain and spine showed tumor progression with extensive leptomeningeal disease. The patient received adjuvant brain and spinal radiotherapy Two weeks after, due to rapid clinical worsening he had a new brain and spinal MRI showing hydrocephalus and progression of the pachymeningeal-based masses and received an emergency ventricular -peritoneal shunt. Given the genetic analysis, the extent of disease and rapidity of the progression, BRAF and MEK inhibitors, dabrafenib (150 mg, twice daily) and trametinib (2 mg, daily) were started. Remarkably, within 2 week of initiating dual-targeted therapy, the patient experienced a dramatic improvement in consciousness and overall strength; brainand spinal MRI revealed initial reduction of the leptomenigeal enhacement and no evidence of progression of the intraparenchymal disease. The therapy was well-tolerated. Currently, after sixteen months,the patient remains on treatment with a consistent functional status improvement and no radiological evidence of disease progression. The second case is a 51 old women who developed leptomeningeal carcinomatosis seven year after resection of a frontal left PXA WHO grade 2 with BRAFv600E mutation. The patient had received brain radiotherapy five years after diagnosis and Cyber Knife for tumor progression. Ten months later MR imaging of his brain and spine showed tumor progression with extensive leptomeningeal disease, she was treated with temozolomide for 8 after clinical and radiological worsening she had a second surgery with resection of recurrent frontale left lesion Histopathology PXA WHO grade 2 with BRAF V600E mutation. She developed hydrocephalus, received an emergency ventricular -peritoneal shunt. BRAF and MEK inhibitors, dabrafenib (150 mg, twice daily) and trametinib (2 mg, daily) were started three months ago with initial clinical benefit

CONCLUSION
All patients with PXA should be tested for the BRAFV600 mutation, since, in these cases, targeted therapy with BRAF and MEK inhibitors seems to be a useful option for salvage treatment.
P14.77 Reduced dose craniospinal irradiation (CSI) is feasible for standard risk adult medulloblastoma (MBL) patients similarly to pediatric population
Authors: Massimino M , Sunyach M , Gandola L , Pecori E , Spreafico F , Bonneville Levard A , Biassoni V , Schiavello E , Diletto B , Stefini R , Frappaz D 
Published: September 2019

Abstract

BACKGROUND
MBL is the most common malignant pediatric brain tumor but represents 1% of adult brain tumors. Recent molecular classification suggests that MBL is not the same disease in children and adults. For standard risk pediatric medulloblastomas current therapy includes CSI at reduced doses (23.4Gy) associated with chemotherapy. Most adult patients with similar risk factors still receive CSI at 36 Gy±chemotherapy (CT): in the adult series treated according to the HIT protocol (CSI 35.2 Gy + boost to 55.2 Gy to posterior fossa followed in most patients by maintenance CT with lomustine, vincristine and cisplatin) a 73% 5-year PFS was reported {Friedrich, Eur J Cancer 2013}, so far the best published data. Hence retrospective experience of 23.4 Gy together with CT for adult patients in some institutions is worthwhile reporting.

MATERIAL AND METHODS
We gathered M0 patients, aged over 18 years with medulloblastomas and no/minimal post-surgical residues/no biological negative factor, between 1996–2018 in Centre Léon Bérard of-Lyon and Fondazione IRCCS Istituto Nazionale dei Tumori-Milan.

RESULTS
Forty-four patients were included, median age 26 (18–48) years,20 females. Median follow-up 90 months(10–227). Thirty-six and 8 received 23.4Gy and 30Gy CSI, respectively, + posterior fossa/tumor bed boost and CT in all: pre-RT (carbo/VPx2 courses or 8 drugs-in-one day x 2 courses (13 patients)) and/or post-RT (carbo/VPx2 courses in 11 and 8 drugs-in-one day x 2 courses in 10; CDDP/VCR/CCNU x 8courses in other 22).
The 5/10 year PFS and OS were respectively 80.9±6.5%/76.8±7.4% and 88.4±5.5%/73.1±8.5%. Median progression time was 44 months.
Relapses (8) were local (4), local+CSF or spine or bone in one instance each and bone only in one.
Among variable considered, higher CSI dose than 23.4 Gy, pre-RT CT did not influence PFS, while females had a trend to better PFES and OS (P=0.07).

CONCLUSION
These combined series present results comparable to - or even better than- those obtained after high CSI doses highlighting the need for treatment redefinition in adults.
P14.91 Study glycolytic metabolism in 1H-MRS monovoxel in the most aggressive part of 62 glioblastomas before and after 18 months of treatment
Authors: Heintz A , Boussida S , Saida Z , Chombar J , Lefranc M , Desenclos C , Galmiche A , Chauffert B , Boone M , Constans J 
Published: September 2019

Abstract

BACKGROUND
To study the relationship between glycolytic metabolism, tumor proliferation, survival and treatment response in patients with glioblastoma (GBM).

MATERIAL AND METHODS
Patients: 62 patients with glioblastoma, all having a STUPP Protocol (radiotherapy and concomitant chemotherapy), were selected and separated into 2 groups: Biopsies (30) and resections (32). In total, 269 NMR spectra (PRESS at GE 1.5T and 3T; multi-TEs TE=35ms and TE=144ms) were acquired. Processing: MRS data were processed with jMRUI software and quantitated using HLSVD and QUEST algorithms. Statistical analysis of longitudinal MRS data (every 3 months)

RESULTS
1H-MRS glucose (Glc/tCr) and lactate (Lac/tCr) measurements are highly correlated before the beginning of treatment. This correlation is less obvious after 3, 6, 9 and 12 months of treatment. Proliferation is also strongly correlated with Lactate and Glucose before the beginning of treatment in both groups, whereas these correlations decrease in resected patients.The variability of ratios follow-up is higher in biopsied patients. Tumoral proliferation (tCho/tCr) and Glucose ratio (Glc/tCr) levels decreased along the follow-up. Although, the Lac/tCr ratio progressively decreased, its level remains high until 6 months. After 15 months of treatment, glucose increased although the lactate decreased.

CONCLUSION
The study of glycolytic metabolism in GBM could be used to evaluate the response to treatment. Being able to have a treatment response biomarker at 3 months, especially for patients who could not be resected could help to monitor and adapt treatment. The increase of Glucose at the end of the follow-up shows the interest of spectral and metabolic follow-up of glioblastoma after 18 months of treatment.
P14.96 Gliomatosis cerebri imaging pattern: a treatment-independent marker for worse overall survival in WHO grade II and III gliomas
Authors: Divé I , Steidl E , Wagner M , Burger M C , Franz K , Harter P N , Bähr O , Fokas E , Herrlinger U , Steinbach J P 
Published: September 2019

Abstract

BACKGROUND
The term gliomatosis cerebri (GC) refers to glial brain tumors with widespread tumor expansion affecting three or more cerebral lobes. Formerly considered a distinct tumor entity, recent studies found no difference in the mutational profile of glial tumors with GC growth pattern compared to non-GC gliomas. Thus, in the new WHO classification of brain tumors, GC is no longer included as a separate diagnosis. While the presence of gliomas with GC growth pattern is associated with worse overall survival (OS), the underlying factors remain to be identified. Here, we asked whether differing therapeutic strategies in first line treatment could account for the worse outcome of patients with GC growth pattern and grade II and III histology.

MATERIAL AND METHODS
From the patient data bank of the University Cancer Center (UCT) Frankfurt, 47 patients with histological diagnosis of WHO grade II or III glioma, and with record of GC imaging pattern were identified. GC tumor expansion was confirmed by review of MRI scans prior to treatment initiation. Patients with WHO grade II or III glioma without GC growth pattern served as control cohort (n=379). IDH mutational status was available for 75% of GC tumors (IDH R132H mutated 32%; non-mutated 43%) and 69% of non-GC tumors (IDH R132H mutated 57%; non-mutated 12%).

RESULTS
Within the GC patient cohort, patients with tumors without contrast enhancement, lower WHO grade and mutated IDH status showed better OS. Compared to the control cohort, patients with GC had significantly shorter OS. This was independent of histological diagnosis or IDH mutation status. Patients with GC more frequently underwent radiochemotherapy (17% vs. 9% in the non-GC cohort), and drastically more often received chemotherapy alone (51% vs. 5%). We then analyzed OS in GC and non-GC patients that had received the same first line treatments. For radiochemotherapy in GC versus non-GC patients, OS was 1.1 years vs. 12.7 years (p =0.0075, log-rank test). For upfront chemotherapy alone, OS was significantly shorter in the GC cohort than in the non-GC cohort (3,6 years vs. undefined, p =0.0016, log-rank test).

CONCLUSION
Differences in first-line treatment cannot account for the worse prognosis of patients with GC imaging pattern. Further studies are needed to pinpoint biological or clinical factors that might influence responsiveness to therapy and prognosis of GC tumors.