bluuebunny/crossref_metadata_2025_split huggingface dataset:
P14.80 Advances in radiotherapy for brain tumors (benign, malignant and pediatrics tumors)
Authors: Theodorou M 
Published: September 2019

Abstract

BACKGROUND
New techniques in radiation oncology such as VMAT (volumetric modulated arc therapy), IGRT (image guidance radiotherapy) compare 3D-conformal technique offering better coverage of the target and more safety for the organs at risk for brain tumors such as Glioblastomas, low grade gliomas, pediatric tumors, meningiomas, pituitary adenomas, brain metastasis.

MATERIAL AND METHODS
Compare 3D-conformal treatment plans with VMAT -IGRT plan for Glioblastoma, pituitary adenoma, pediatric tumors, low grade gliomas, brain metastasis. Clinical target definition occur with Fusion of planing-MRI with Planing-CT inclusive preoperative and postoperative MRI to exact delineation of GTV (gross tumor volume), CTV (clinical target definition, PTV (planing tumor volume). contouring of organs at risk such as brainstemm, chiasm, N. opticus right and left, eye right and left, lens right and left, brain, cerebellum, internal ears.

RESULTS
VMAT treatment plans offer higher coverage of the target, higher homogenize radiation index and less radiation for the organs at risk. Due to the good safety of the organs at risk less toxicity during radiation was mentioned specially for neuroaxisradiation for medulloblastoma in children. The toleration during radiotherapy with VMAT technique is is much better than 3D conformal technique

CONCLUSION
VMAT technique offers higher radiation dose to the target and less radiation to the organs at risk with better toleration of treatment and less toxicity inclusive late side effects such as radionecrosis.
P14.84 Intraarterial chemotherapy and osmotic blood-brain barrier modification in the treatment of primary CNS lymphoma
Authors: Fortin D , Gahide G , Iorio-Morin C 
Published: September 2019

Abstract

BACKGROUND
Primary central nervous system lymphomas (PCNSL) are considered a rare and aggressive form of central nervous system (CNS) tumors. High-dose methotrexate has become the backbone of PCNSL treatment, and is recommended by the EANO guidelines. In most recent protocols, investigators tend to postpone or even avoid the use of radiotherapy; indeed, its use has become controversial with findings of associated severe neuro-toxicity, especially in elderly patients. To maximize delivery across the BBB, we use cerebral intra-arterial chemotherapy (CIAC) coupled with osmotic blood-brain barrier disruption (OBBBD). We hereby report our single-center experience over 18 years with the CIAC + BBBD technique using 2 different HD-MTX protocols.

MATERIAL AND METHODS
This phase II study was conducted at the Centre hospitalier Universitaire de Sherbrooke (CHUS) from November 1999 to May 2018. The protocol was approved by the institutional review board, and informed consent was obtained in accordance to institutional regulation in every patient After enrollment and initial evaluation, patients were treated every four weeks (1 cycle) for 12 cycles, unless progression. After general anesthesia, a transfemoral approach was used to catheterize either the right or left internal carotid artery or the dominant vertebral artery, depending on tumor(s) location. OBBBD was performed by infusing 20% mannitol in the selected vascular distribution for 30 seconds at a rate that fills the vascular distribution so as to maximize the contact of the mannitol with the endothelial cells.Two different chemotherapy regimens were sequentially used in this study. High-dose MTX (5 g IV) was the cornerstone of both regimens: the first regimen (1999 to 2007) also included etoposide phosphate IV (400 mg/m²) and cyclophosphamide IV (660 mg/m²), whereas the 2nd regimen (1998 to 2018) also included carboplatin IA (400 mg/m²).

RESULTS
The present analysis therefore concerns a cohort of 44 naive patients recruited over 18 years in a single center. Median follow-up was 38 months. Overall, a CR was induced in 34 patients (79%). Themedian time to CR was 7.3 months (IQR: 7.8). Of these 34 patients, 11 (25.6%) are still alive, and 9 of these are disease-free after treatment discontinuation. The actuarial median survival (MS) was 46.5 months (95% CI: 30.9–62.2) for the cohort. Survival was 88%, 64%, 54%, 39% and 18% at 1, 2, 3,5 and 10 years (Figure 1 and Table 2).The progression-free survival was 43.4 months (95% CI: 17.9–68.9). Five occurrences of vascular complications related to the treatment were observed (11.6%).
Conclusion: CIAC HD-MTX-based protocols with OBBBD is a safe and well-tolerated procedure for the management of primary CNS lymphoma. Our single center data suggests better PFS and survival outcomes compared to IV protocols with less hematologic toxicity and good tolerability, especially in the elderly.
P14.86 Bevacizumab-associated intracerebral hemorrhage in patients with CNS malignancy: A single-center retrospective cohort study
Authors: Clarke N , Ruff M 
Published: September 2019

Abstract

BACKGROUND
Gliomas are a known risk factor for the development of spontaneous intracranial hemorrhage (ICH) independent of therapies directed against them, with studies reporting an incidence of 1.9–3.8%. Bevacizumab (BEV) is a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF) FDA approved for recurrent glioblastoma. ICH is commonly considered to be a potential adverse effect of BEV use in patients with glioma, with previous retrospective studies describing incidence of intracerebral hemorrhage ranging from 1.9–3.3%.

Material and METHODS
We performed a single center (Mayo Clinic, Rochester, MN) retrospective chart review of all patients who received BEV therapy at our institution for a diagnosis of primary CNS malignancy. We used ICD-9 and ICD-10 codes to identify adult patients with primary CNS neoplasms that subsequently developed ICH.

RESULTS
We screened 10,507 adult patients with a diagnosis of primary CNS neoplasm treated at our center from 01/31/2008 to 12/31/2018 and found 644 patients treated with bevacizumab. Of these, 23 (3.6%) suffered an ICH within 12 weeks of a BEV infusion (median 9 days post infusion, 1–24 IQR). The dose of BEV in all hemorrhages was either 10 mg/kg every two weeks (n = 21) or 15 mg/kg every three weeks (n = 2). No patients treated with infusions at 7.5 mg/kg every three weeks (n = 79) or 5 mg/kg every two weeks (n = 17) suffered ICH events, however this did not meet significance (P = 0.06) when compared to patients on 10 mg/kg or above. The median ICH score was 1 (0–2 IQR). There was an increase in ECOG scores documented at clinical follow up following the hemorrhage compared to the pre-hemorrhage functional status (ECOG 3.28 versus 1.2, p = < 0.0001), with 13 patients (56%) having developed severe debility or death (ECOG 4 n = 3, ECOG 5 n = 10).

CONCLUSION
In our single-center cohort of patients with a primary diagnosis of CNS neoplasms treated with BEV, ICH occurred in 3.6% of patients. Those who experienced an ICH in proximity to BEV infusion had significant morbidity and mortality with a clear decline in functional status. There was a signal of dose response as far as ICH incidence in our cohort with dosages 10 mg/kg per infusion or above.
P14.87 Leptomeningeal dissemination in high grade glioma: Correlation of MRI, cytology and standard CSF indices
Authors: Durand H , Lamy F , Parratte T , Brinet A , Blain A , Lamy F , Gaultier C , Droy-Dupré L , Leblanc S , Oesterlé H , Olteanu S , Atlani D , Voirin J , Mokhtari K , Ahle G 
Published: September 2019

Abstract

BACKGROUND
Only few studies report the incidence of leptomeningeal dissemination (LMD) in patients with high grade glioma (HGG), although LMD is not a rare condition of recurrence. We aimed to describe the diagnostic features and treatment modalities in a series of patients treated for HGG in our institution.

METHODS
Review of clinical presentation, radiological features and CSF analysis in a case series.

RESULTS
17 patients from our institution were diagnosed with LMD. The diagnosis of LMD was based on magnetic resonance image and/or cerebrospinal fluid (CSF) analysis. The spectrum of clinical presentation was broad, mainly intracranial hypertension, impaired general condition, pain, worsening of pre-existing symptoms, and epileptic seizures. Median time from onset of clinical deterioration to diagnosis of LMD was 3 weeks (0–16). Leptomeningial involvement was reported in 6/17 at initial MRI reading, whereas reassessment with careful comparison to previous MRI showed signs of LMD in all patients. CSF analysis revealed pleocytosis (11/17), high proteinorrachia (13/17), elevated lactate levels (15/16), low glucose levels (5/17), and increased CSF pressure (5/9). Nevertheless, diagnostic accuracy of initial CSF cytological analysis was low (2/17). A reassessment of the specimen by an experienced neuropathologist disclosed 1 additional positive and 1 additional suspect cytology. After diagnosis of LMD, salvage treatments comprised Bevacizumab, Lomustine, Fotemustine, liposomal cytarabine and best supportive care. The median overall survival after the diagnosis was 3 months.

DISCUSSION AND CONCLUSIONS
LMD in HGG is not a rare condition of recurrence, and its outcome is poor. It remains a diagnostic challenge, as it may be overlooked on MRI follow-up at its early stage. In case of clinical progression with no overt cause reported on MRI, we recommend careful second MRI reading. In case of doubt lumbar puncture should be performed in order to prove LMD and eliminate infection (i.e. HSV). Upon standard CSF indices, elevated lactate levels should give rise to the suspicion of LMD. Cytological CSF analysis seems to be of low diagnostic yield: This may be improved by faster processing after sampling and by standardized workup including staining with IDH, GFAP and Olig2.
P14.93 The utility of the brain 18-FDG-PET and perfusion magnetic resonance imaging in the radionecrosis differential diagnosis
Authors: Mongay N , Vidal N , Lucas A , Macià M , Plans G , Fernandez-Coello A , Majos C , Rodriguez-Bel L , Alemany M , Bruna J 
Published: September 2019

Abstract

BACKGROUND
Radiation-induced necrosis (RDN) is a side effect observed in patients who underwent stereotactic radiosurgery (SRS) alone or combined with whole brain radiotherapy (WBRT) as treatment for their brain tumors. Nowadays, RDN diagnosis and differentiation from tumor progression using the standard imaging techniques represents a challenge, and histological diagnosis still is the gold standard.Our aim is to assess the positive and negative predictive values (PPV, NPV) of FDG-PET and perfusion magnetic resonance imaging (MRI) in RDN diagnosis.

MATERIAL AND METHODS
From our Pathology department database, all patients with RDN or mixed (tumor plus RDN) brain lesions diagnosis during last 5 years were reviewed. Demographic, clinical and oncologic treatment characteristics were recorded. MRI and FDG-PET images at the suspicion (clinical or radiological) of progression or RDN were registered and compared with the definite diagnosis provided by the tissue sample analysis. Sensitivity, specificity, as such as PPV and NPV for perfusion MRI sequences and FDG-PET image analysis were calculated.

RESULTS
162 patients underwent SRS+/- WBRT in a 5 year period. During follow-up, 11 patients had surgery-confirmed RDN. There are 11 patients (3 women) with 12 lesions, 3 from a breast cancer, 6 from a lung tumor, 1 from a melanoma, 1 atypical meningioma and 1 glioblastoma. 9 of them were treated with both SRS and WBRT, and the 3 others with WBRT alone. The mean age was 65.36 (range: 44–77) years. The median time between the completion of radiation therapy and the suspicion of RDN was 19.7 (range: 3–34) months. With the evolution, it was observed an evident increase in the size of surronding oedema (2–6 times) by FLAIR RMI. We estimate a PPV 0.40 and NPV 0.80 for perfusion MRI, and PPV 0.25 and NPV 0.75 for FDG-PET, respectively.

CONCLUSION
The diagnostic performance of both techniques in our series is low and similar to published data; therefore its results must be carefully interpreted in each case. It is peremptory to implement new diagnostic tools in the standard of care with better diagnostic outcomes.
P14.98 Improving the targeting of Gamma-Knife radiosurgery for recurrent high-grade gliomas (WHO grades III and IV) with 11C-Methionine PET/CT
Authors: Chaskis E , Van Simaeys G , Martens C , De Witte O , Goldman S , Lefranc F 
Published: September 2019

Abstract

BACKGROUND
The survival of the patients with high-grade gliomas may be improved through a multidisciplinary approach including stereotactic re-irradiation such as Gamma-Knife at recurrence in a selected population. We report our experience in targeting the hypermetabolic areas of high-grade gliomas using 11C-Methionine PET/CT in selected patients.

MATERIAL AND METHODS
We retrospectively evaluated the local response in patients treated by Gamma-Knife for recurrent high-grade gliomas in our Institution between 2000 and 2018, targeting the hypermetabolic area with Methionine PET/CT.

RESULTS
We included 25 patients bearing high-grade gliomas (14 female, 11 male) with a median age of 45 years (5–64). There were 11 WHO grade III gliomas (6 astrocytomas, 5 oligodendrogliomas) and 14 glioblastomas. A total number of 33 Gamma-Knife procedures were performed. In all patients, the targeting was based on the hypermetabolic area as defined by Methionine PET/CT. Four patients were treated concomitantly on 2 or more targets. One patient was treated twice on different targets. We observed a positive response in 29 Gamma-Knife procedures, after a median interval of 2 months (1–33) and no response after 4 procedures (4 glioblastomas). In most cases, progression after Gamma-Knife was observed 4 months after irradiation.

CONCLUSION
Targeting the hypermetabolic areas with Methionine PET/CT was associated with favorable response in most patients treated by Gamma-Knife radiosurgery for local high-grade gliomas recurrence. Our results must be confirmed by a prospective study with regular and homogeneous morphological and metabolic monitoring.
P14.103 Patterns of diffuse glioma progression
Authors: Kobyakov G L , Belyashova A , Trunin Y , Absalyamova O , Lodygina K , Kobiakov N 
Published: September 2019

Abstract

BACKGROUND
According to WHO 2016 Classification, all gliomas are considered potentially malignant. Earlier it was thought that the ultimate goal for treatment is local control of tumor growth: maximal surgical resection with subsequent local radiotherapy +/- chemotherapy. Disease progression was primarily linked only to local relapse. In the recent years, different progression patterns of diffuse glioma were identified: from distant growth into an anatomically unrelated area far from primary lesion, to bone metastases and even to visceral organ metastases.

MATERIAL AND METHODS
In this study we analyzed glioblastoma progression patterns in a cohort of 170 patients, who received radiation therapy as one of the treatment options for local relapse in Burdenko Neurosuregry Institute. All patients had a first relapse of glioblastoma at the age of 16 to 74 years old, 72 patients were female and 98 male. All patients initially underwent surgery and local radiotherapy (in combination with temozolomide) for a solitary supratentorial lesion of glioblastoma. Various methods of radiotherapy (including radiosurgery and hypofractionated radiation therapy) were used as one of the treatment options for recurrent tumor. One of our aims was to evaluate glioblastoma progression patterns in this cohort.

RESULTS
Comparing neuroimaging data at the time of tumor progression with initial MRI we found that in 127 of 170 patients disease progression was identified anatomically close to the primary tumor site, i.e. disease progressed as a local relapse. Recurrent lesions without obvious anatomical relation to primary site were identified in 33 patients (19.4%); in particular, 7 patients had a lesion in contralateral hemisphere, one patient had spinal subarachnoid dissemination. A combination of local and distant tumor progression was identified in 10 of these 33 patients.

CONCLUSION
We identified the following progression patterns for diffuse glioma based to these data and previous clinical experience: (a) local brain relapse - anatomically close to the primary lesion; (b) brain and spinal subarachnoid spread; (c) distant relapse - anatomically unrelated to primary tumor (can be both in ipsilateral or contralateral brain hemisphere); (d) local tumor progression as infiltration of soft tissues of the head and cranial bones; (e) regional lymph node metastases; (f) distant metastases - skeletal bone metastases and/or visceral organ metastases. Naturally, different combinations of these diffuse malignant glioma progression patterns are possible. A quite high incidence and differences between diffuse glioma progression patterns require a more thorough evaluation both because of treatment strategies as well as to understand the origins of glial tumors (e.g. Why in some cases of complete remission at the primary tumor site there is tumor progression in contralateral hemisphere?)
P14.104 The outcomes of conservatively observed asymptomatic nonfunctioning pituitary adenomas with optic nerve compression
Authors: Hwang K , Kim Y , Kim C , Han J 
Published: September 2019

Abstract

BACKGROUND
We investigated the natural history of asymptomatic nonfunctioning pituitary adenomas (NFPAs) abutting on optic nerve.

MATERIAL AND METHODS
Eighty-three patients with asymptomatic NFPAs with documented optic nerve compression on magnetic resonance imaging (MRI) at the time of detection between 2000 and 2016 were included in this study. Patients were evaluated with a hormone test, visual acuity test, visual field test and MRI at the time of diagnosis, and then, yearly, without any treatment (including surgery and radiation).

RESULTS
The mean age was 57.7±13.6 (range, 15 - 81) years. The mean follow-up duration was 66.6±39.0 (range, 12 - 184) months. Tumor volume growth ≥ 20% was observed in 64 (77.1%) patients. Ten (12.2%) patients experienced any kind of hormonal dysfunction, and gonadotropin deficiency was the most common type of hormonal deficiency [n=9 (10.8%)]. Visual deterioration quantified by Visual Impairment Scale was seen 27 (32.5%) patients. There was no statistically significant factor for tumor growth or visual aggravation. Fourteen (16.9%) patients eventually underwent tumor resection. From multivariate analysis, the significant predictors for eventual surgical intervention were cavernous sinus invasion (OR=20.95; 95% CI, 2.754–159.3; p=0.003) and last follow-up visual field defect score (OR=1.170; 95% CI, 1.049–1.305; p=0.005). All patients who underwent surgery did not experience any neurologic or endocrinological deficits postoperatively.

CONCLUSION
The clinical outcomes of conservatively observed NFPAs with optic nerve compression can be acceptable. The decision for surgical intervention should be made by balancing the risk and benefits.
P14.106 One-year survival of radiotherapy vs conservative therapy in patients with metastatic brain disease in Cipto Mangunkusumo General Hospital 2014–2016
Authors: Aninditha T , Pratama P Y , Imran D , Aman R A , Werdhani R A , Sofyan H R , Odilo J , Ranakusuma T A S 
Published: September 2019

Abstract

BACKGROUND
There are several palliative treatment choices in patients with brain metastasis. Radiotherapy is one of palliative treatment modality in brain metastasis. The role of radiotherapy in metastatic brain disease has already been established. Patients with metastatic brain disease also treated conservatively. Sole conservative treatment were also done in regarding qualification of patient. This study aimed to compare radiotherapy and conservative treatment in one-year survival on brain metastasis patients.

MATERIAL AND METHODS
This study was a retrospective cohort study. The data acquired from Dept. of Neurology Cipto Mangunkusumo General Hospital between 2014–2016. Subjects with metastatic brain disease underwent radiotherapy and conservative treatment were included in this study. Sex, age, marital status, survival time, were retrieved from the subjects. The follow-up period were 1 year. Univariate analysis were done using t-test and chi-square test. Multivariate analysis were done using Log-rank test and Cox regression.

RESULTS
There were 41 subjects included in the study. Of 41 subjects, 21 (51.2%) underwent radiotherapy. The mean age of subjects underwent radiotherapy were 53.3 (SD ±12.6) vs 43.1 (SD ±14.7) in subjects with conservative management (P = 0.022). Women accounted for 27 out of 41 (65.9%) subjects. Married subjects accounted for 32 out of 41 (78%) subjects. There were no significance difference of treatment choices between married and unmarried subjects (P = 0.130). At the end of follow-up period, only 4 (19%) subjects from conservative treatment and 2 (10%) subjects from radiotherapy treatment survived (P = 0.854). Median survival of radiotherapy treatment were 5 month and 4 month in conservative treatment. Palliative treatment didn’t raise risk of death compared to conservative treatment [Hazard Ratio (HR) 0.94, 95% Confidence Interval (CI): 0.48–1.85, P = 0.867).

CONCLUSION
Radiotherapy treatment didn’t increase one-year survival in patients with metastatic brain disease. Other confounding factors that influenced survival should be included in further study to understand factors that interact with palliative treatment in brain metastases.
P14.108 Bevacizumab versus alkylating chemotherapy in recurrent glioblastoma
Authors: Seystahl K , Hentschel B , Loew S , Gramatzki D , Felsberg J , Herrlinger U , Westphal M , Schackert G , Thon N , Schlegel U , Tatagiba M , Pietsch T , Reifenberger G , Löffler M , Wick W , Weller M 
Published: September 2019

Abstract

BACKGROUND
The use of alkylating chemotherapy versus bevacizumab for recurrent glioblastoma remains controversial. Here we tested the hypothesis that the activity of alkylators, but not that of bevacizumab, would be associated with the O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status

PATIENTS AND METHODS
We analyzed a cohort of patients treated at centers of the German Glioma Network or the University Hospital Zurich with alkylating agent-based chemotherapy (n=260) or bevacizumab without or with irinotecan (n=84) for first recurrence of glioblastoma. Outcome was stratified for MGMT status and cross-over to bevacizumab or alkylators at further tumor progression.

RESULTS
Median post-recurrence survival-1 (PRS-1) for patients receiving alkylating agent chemotherapy at first recurrence was longer than for patients receiving bevacizumab (11.1 versus 7.4 months, p<0.001). The use of alkylating agents was associated with longer PRS-1 for patients with a methylated versus an unmethylated MGMT promoter (p=0.017). For patients receiving bevacizumab, PRS-1 was not different with or without MGMT promoter methylation. PRS-1 was longer in the group receiving alkylating chemotherapy compared to bevacizumab for patients with a methylated (p<0.001) or unmethylated MGMT promoter (p=0.034). For patients with alkylators at first recurrence receiving bevacizumab at any further recurrence, PRS-1 was longer than in patients receiving bevacizumab first and alkylators thereafter (p=0.002).

CONCLUSION
This study confirms limited value of bevacizumab in recurrent glioblastoma independent of MGMT status. Alkylating agents have activity in recurrent glioblastoma, especially in the context of a methylated MGMT promoter.