bluuebunny/crossref_metadata_2025_split huggingface dataset:
P14.19 Regorafenib in recurrent glioblastoma patients: a large real-life experience
Authors: Caccese M , Cerretti G , Padovan M , Zagonel V , Lombardi G 
Published: September 2021

Abstract

BACKGROUND
Regorafenib (REG), an oral multikinase inhibitor of angiogenic, stromal, and oncogenic receptor tyrosine kinases showed encouraging benefit in recurrent GBM patients enrolled in the randomized, phase 2 REGOMA trial. We investigated the clinical outcome and safety of REG in a real-life population of recurrent glioblastoma patients treated at Veneto Institute of Oncology as off-label use.

MATERIAL AND METHODS
Patients receiving REG at Veneto Institute of Oncology (Padua, Italy) were entered prospectively on a clinical database. Data were retrospectively analyzed. The primary endpoints of the study were overall survival (OS) and safety. The major inclusion criteria were: histologically confirmed diagnosis of GBM, disease progression as defined by RANO criteria after surgery followed by radiochemotherapy with temozolomide, ECOG PS ≤ 2; PTS with ≥ 2 prior lines of therapy were excluded. According to original schedule, patients received REG 160 mg once daily for the first 3 weeks of each 4-week cycle until disease progression, death, unacceptable toxicity, or consent withdrawal. Kaplan-Meier method was used to estimate the survival curves, RANO criteria for radiological assessment, CTCAE v5.0 for drug related adverse events.

RESULTS
From February 2018 to September 2020, 54 consecutive patients were treated with REG and enrolled in this study: median age was 56, ECOG PS 0–1 in 91% of patients, MGMTmet in 53%, second surgery at the time of relapse were performed in 30% of enrolled patient, 41% of patients underwent steroids at baseline. At the time of analysis, median follow-up was 11.1 ms, 30 PTS (56%) had died and 50 PTS (93%) had progressed. Median OS was 10.2 ms (95%CI, 6.4–13.9), 12m-OS was 43%; median PFS was 2.3ms (95%CI, 1.3–3.3) and 6m-PFS was 18%. All patients were evaluable for response: disease control rate (DCR) was 46.3%; stable disease was reported in 38.8% and partial response in 7.4%. Age, MGMT status and corticosteroid use at baseline were not statistically significant on multivariate analysis for OS. Grade 3 drug-related adverse events (AEs) occurred in 10 patients (18%) and the most frequent were hand-foot skin reaction, asthenia and increased lipase and transaminases; 1 PT (2%) reported a grade 4 AE (rash maculo-papular). AEs led to REG dose reductions in 37% of patients and, it was permanently discontinued in 5%. No death was considered to be drug-related.

CONCLUSION
We reported a large, mono-institutional “real world” experience of REG in recurrent glioblastoma patients. Overall, results are close to those reported in REGOMA trial although, we showed a longer OS. Toxicity was moderate and manageable. Encouraging clinical benefits of REG in recurrent GBM population were confirmed.
P14.22 Quality indicators in neuro-oncology: modified Delphi process for the development of a quality indicator set for assessment of glioma care
Authors: Vanhauwaert D J , Pinson H , De Schutter H , Van Eycken E , De Vleeschouwer S , Boterberg T 
Published: September 2021

Abstract

BACKGROUND
Quality Indicators (QIs) are important tools to assess the quality and variability of oncological care. However, their application in neuro-oncology is limited. The objective of this study was to develop a set of QIs for glioma, covering process and outcome indicators.

METHODS
First a systematic literature search was performed in peer-reviewed papers and grey literature to identify existing QIs in neuro-oncology and guidelines or recommendations that could be translated into new QIs. The PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) checklist and flow diagram were taken into account. The search strategy focused on diagnostics, treatment, follow-up and survival. For each (set of similar) recommendation(s) a QI was created that could easily be translated into a measurable proportion. Concordant QIs were rationalized to further reduce redundancy. Secondly a two round Delphi survey was organized amongst a multidisciplinary expert panel that was asked to score relevance for all proposed QIs. The panel consisted of neurosurgeons(4), radiation(3) and medical(3) oncologists, pathologists(3), radiologists(2), neurologists(1), nuclear medicine physicians(2) from university and non-university centers, and representatives of the Belgian Cancer Registry.

RESULTS
The conducted literature search in PubMed and Embase yielded 2392 abstracts. After screening and duplicate removal, 221 full text articles were assessed of which 79 were retained. In addition 28 references from the Grey literature were added. In total 240 recommendations and 30 QIs could be identified in this way. After translation of these recommendations into a measurable proportion, merging with the QIs found as such in the literature and rationalization, 148 QIs were presented to the expert panel. In the Delphi survey 15 of the 19 (79%) invited experts responded and eventually consensus was reached on 46 QIs that were considered relevant for the assessment of 6 different domains of neuro-oncological care: diagnosis and imaging (10), surgery (4), pathology (6), radio/chemotherapy (14), recurrence (5) and supportive treatment (7).

CONCLUSION
A set of 46 QIs grouped in 6 categories to assess the quality of care of glioma patients was developed. These QI’s are readily applicable dependent on the availability of population-based health care data
P14.30 Voxelwise analysis of spatial distribution of postoperative ischemia in diffuse glioma
Authors: van der Boog A T J , David S , Steennis A M M , Snijders T J , Dankbaar J W , Robe P A , Verhoeff J J C 
Published: September 2021

Abstract

BACKGROUND
Surgical treatment of diffuse glioma is performed to reduce tumor mass effect and to pave the way for adjuvant (chemo)radiotherapy. As a complication of surgery, ischemic lesions are often found in the postoperative setting. Not only can these lesion induce neurological deficits, but their volume has also been associated with reduced survival time. Prior studies suggest areas with a singular vascular supply to be more prone to postoperative ischemic lesions, although the precise cause is yet unknown. The aim of this study was to explore the volumetric and spatial distributions of postoperative ischemic lesions and their relation to arterial territories in glioma patients.

MATERIAL AND METHODS
We accessed a retrospective database of 144 adult cases with WHO grade II-IV supratentorial gliomas, who received surgery and postoperative MRI within 3 days in 2012–2014. We identified 93 patients with postoperative ischemia, defined as new confluent diffusion restriction on DWI. Ischemic lesions were manually delineated and spatially normalized to stereotaxic MNI space. Voxel-based analysis (VBA) was performed to compare presence and absence of postoperative ischemia. False positive results were eliminated by family-wise error correction. Areas of ischemia were labeled using an arterial territory map, the Harvard-Oxford cortical and subcortical atlases and the XTRACT white matter atlas.

RESULTS
Median volume of confluent ischemia was 3.52cc (IQR 2.15–5.94). 23 cases had only ischemic lesion in the left hemisphere, 46 in the right hemisphere and 24 bilateral. Median volume was 3.08cc (IQR 1.35–5.72) in left-sided lesions and 2.47cc (1.01–4.24) in right-sided lesions. Volume of ischemic lesions was not associated with survival after 1, 2 or 5 years. A cluster of 125.18cc was found to be significantly associated with development of postoperative ischemia. 73% of this cluster was situated in the arterial territory of the right middle cerebral artery (MCA), limited by the border of the posterior cerebral artery (PCA), and the watershed area between the right MCA and the right anterior cerebral artery (ACA). Significant areas were located in the frontal lobes, spanning into the right temporo-occipital region, and predominantly included right and left thalamus, caudate nucleus, putamen, pallidum, as well as right temporal gyri and insular cortex, and parts of the right corticospinal tract, longitudinal fasciculi and superior thalamic radiation.

CONCLUSION
We found slightly more and larger ischemic lesions in the right than left hemisphere after glioma resection. A statistically significant cluster of voxels of postoperative ischemia was found in the territory of the right MCA and watershed area of the right ACA. Exploration of the spatial distribution of these lesions could help elucidate their etiology and form the basis for predicting clinically relevant postoperative ischemia.
P14.32 Patterns of invasion in Glioblastoma have unique radiological features, varied response to radiotherapy and long term outcomes
Authors: Uday Krishna A S , Nargund A , Santosh V , Mathew S , Thimmiah N , A A , V L 
Published: September 2021

Abstract

BACKGROUND
To assess the correlation of the three patterns of invasion of Glioblastoma (GB) with the respective MRI features, response to radiotherapy and disease free survival

MATERIAL AND METHODS
Histopathology of 62 patients with Glioblastoma who had undergone maximal safe resection (MSR)/ stereotactic biopsy (STB) & referred for adjuvant therapy was reviewed to assess the pattern of invasion. Three patterns were observed- single cell infiltration (pattern 1), perineuronal satellitosis (pattern 2) and vessel cooption (or perivascular spread, pattern 3), majority also had diffuse infiltration pattern in the background. The pre and post operative MRI scans were utilized for RT planning of 3DCRT/ IMRT/ VMAT, the modality decided by the treating oncologist. RT volumes were as per ESTRO-ACROP guidelines. Duration of radiotherapy- the Stupp regimen or a short course of hypofractionated radiotherapy (HFRT) (35Gy/10Fr- planned gap- completion of total dose) was based on the extent of resection (EOR) and KPS at the time of RT. Correlation of the pattern of invasion, MRI characteristics of each on the response to radiotherapy as assessed by RANO criteria and survival was analysed with the help of SPSS V21.

RESULTS
MRI findings after stratification of 62 patients, median age 43 years(18–70), M:F::42:20) into type 1:17, type 2:21 and type 3:24- patterns of invasion, were cortical tumours (subtle enhancement) close to SVZ, solid (+/- cystic) lesion in the eloquent cortex or large mass effect crossing the barriers respectively. OS of entire cohort at 1 year was 75%, with significant differences among groups (82% vs. 85% vs. 50%). Among pattern 1, those patients with IDH mutant (20%) & mean dose to C/L SVZ of 30Gy or more had longer DFS at 1 year (89% Vs. 38% & 85% vs. 0%, p&lt;0.05). In pattern 2, EOR (gross total or near total resection Vs. only STB) showed a better DFS at 1 year (90% vs. 40%, p=0.095). In patients with pattern 3, 40% had post op KPS of &lt;80 and 20% of them underwent HFRT who showed higher CR/PR rates compared to the conventional RT. HFRT in low KPS with m-MGMT showed higher local control at 6 months (100% Vs. 66%, p= 0.02).

CONCLUSION
Glioblastoma has three patterns of invasion with unique MRI features and aggressiveness for each. Identification of this may guide choice of adjuvant therapy, patterns of failure and therapy resistance
P14.36 Characterising Meningiomas in young patients under 40
Authors: Attia M , Mirkin Y , Hershkovitch R , Cohen Z R , Zibly Z , Zauberman J , Wohl A , Harnof S , Spiegelmann R , Hadani M , Furman O , Zach L 
Published: September 2021

Abstract

BACKGROUND
Meningiomas are the most common primary CNS tumor in adults, with a median age at diagnosis of 65 years and a female to male ratio of 2–3:1 (except in grade II, III meningiomas). Younger patients usually have a genetic background or history of prior radiation exposure. Based on population-level studies, approximately 80–85% of meningiomas are WHO grade I (benign), 15–18% grade II (atypical), and 1–3% grade III (anaplastic). This case series describes a single center experience of the presentation and pathology of meningiomas in patients under the age of 40.

MATERIALS AND METHODS
We reviewed the Sheba Medical Center Neurosurgery and radiotherapy databases containing patients who were operated on for meningioma between the years 2011–2020. Patients under 40 were selected and information from digital medical records was gathered on these patients, including pathology reports, surgical reports, clinical and radiological data, and the use of radiotherapy or medical treatments.

RESULTS
Of 600 patients in the database, 49 patients under 40 (8.3%) were identified and 54 tumors were reviewed (five patients were operated on for multiple meningiomas). 31 patients were female (63%); 2 were under 20 years old, 15 were age 20–29 and 32 were age 30–39 at first presentation. Seven patients had received prior radiation therapy for a childhood malignancy. 28 meningiomas were histology confirmed grade I (52%), 22 were grade II (41%), 2 were grade III (4%), and 2 (4%) were grade undetermined. 22 tumors were located in the skull base (41%) and 32 (59%) in the brain convexity. Of the skull base tumors, 16 were grade I, 5 were grade II, and one was grade III. Of the convexity tumors, 12 were grade I, 16 were grade II, and 2 were grade III. Median follow-up was 35 months, and longest follow-up time was 98 months. Six patients were treated with additional radiotherapy after surgery.

CONCLUSION
Our experience with meningioma patients under 40 revealed a different grade segregation than the older population, with younger patients showing a higher incidence of grade II tumors. These tumors are generally more aggressive, and require careful resection and consideration for post-surgical radiotherapy. Further validation with population based databases is required.
P14.54 Primary central nervous system lymphoma of the spinal cord: a LOC network cohort study
Authors: Valyraki N , Ahle G , Tabouret E , Houot R , Jardin F , Ghesquieres H , Choquet S , Moles M , Hoang-Xuan K , Houillier C 
Published: September 2021

Abstract

BACKGROUND
Primary central nervous system lymphoma (PCNSL) mainly affects the brain (&gt;90% of the cases), Very little data can be found in the literature on PCNSL with spinal cord localization.

MATERIAL AND METHODS
We present a retrospective study based on the French LOC network database. We selected adult immunocompetentpatients, with a histological or cytological diagnosis of PCNSL, and a spinal cord localization at initial diagnosis.

RESULTS
Of the 2043 PCNSLof the LOC database newly diagnosed since 2011, 14 patients (9 men, median age 68, median Karnofsky performance status 50%)met the selection criteria. The median diagnostic delay was 82 days (min 15-max 1080) compared to 35 days in primary cerebral lymphomas. At diagnosis, walking was impossible in 7/14 patients and 5/14 had indwelling urinary catheter. On MRI, 100% had enlargement of the spinal cord with homogeneous contrast enhancement in 13/14 cases. Spinal cord lesions were unique in 9/14 patients and multiples in 5/14 patients. CSF IL10 level was increased in 6/7 patients. Brain lesions were found in 9/14 patients, located in the posterior fossa in 5/9 cases. The diagnosis was made either on a brain biopsy (N=6), a spinal cord biopsy or surgery (N=5) or the cytologic analysis of the CSF (N=3).4/5 patients had neurological sequel after spinal cord biopsy or surgery. All the patients were treated by high-dose methotrexate-based chemotherapy, followed by spinal cord irradiation (N=1) or autograft (N=2). There was an overall response rate of 71% (complete response in 8/14). 8/14 patients relapsed, 5 in the brain, 2 in the spinal cord, and 1 both in the spinal cord and in the brain. 2-year PFS and OS were 45% and 64%, respectively. Among the long-term responders, 50% remained in wheel chair, while only 10% could walk normally.

CONCLUSION
Considering the high risk of a spinal cord biopsy,the rarity of the disease, as well as the numerous differential diagnoses, the diagnosis of spinal cord lymphoma is difficult. Searching for other lymphomatous locations or assaying CSF IL10 may be helpful in this disease where delay in diagnosis is often prolonged et can cause irreversible handicap.
P14.56 Pattern of care of Brain Tumor patients in the last months of life: analysis of a cohort of 3045 patients in the Lazio region in the last 10 years
Authors: Pace A , Belleudi V , Pinarelli L , Villani V , Poggi F , Benincasa D , Davoli M 
Published: September 2021

Abstract

BACKGROUND
The final days of life of Brain Tumor patients (BT) present special challenges and often palliative care approach is underutilyzed. Several studies reported that BT patients in the last months of life receive frequent hospital readmissions and ER accesses as result of bad quality of End of Life care. Early integration of pallative care has been demonstrated to improve quality of care in advanced stage of disease and quality of death in cancer patients. With the aim to evaluate pattern of treatment and the rate of hospital readmission in the last months of life, we retrospectively analyzed a consecutive serie of BT patients discharged after a diagnosis of BT.

MATERIAL AND METHODS
Data regarding hospital readmission and treatment received in the last two months of life were collected from the Lazio Region Healthcare database. Adult patients discharged with diagnosis ICD-9 191.* between 1/1/2010 until 31/12/2019, were included in this study.

RESULTS
6672 patients were identified and 3045 who have died before 31/12/2019 were included (median age 67 y;M1700). In the last two month of life 42.6% received hospital reamission (4.6% intensive care unit) and 37.9% had ER accesses. 24.5% received chemotherapy and 12.1% radiotherapy. In the last 30 days 33% were readmitted in hospital and 24.2% were admitted in ER. 11.7% were treated with chemotherapy and 6% with radiotherapy.

CONCLUSION
Strategies to improve quality of care at the end of life and to decrease re-hospitalization and futile treatments are becoming increasingly important to improve quality of death and to reduce costs of Healthcare System.
P14.67 Long-term results of gamma knife radiosurgery for treatment of intracranial glomus jugulare tumors
Authors: Emad Eldin R M , Abdel Karim K M , El-Shehaby A M N , Reda W A , Nabeel A M , Tawadros S R 
Published: September 2021

Abstract

BACKGROUND
Glomus Jugulare tumors are benign but locally aggressive ones that represent a therapeutic challenge. Previous studies about the use of Gamma Knife Radiosurgery (GRS) in those tumors have documented good results that needed larger number of patients and longer follow up periods to be confirmed.

MATERIAL AND METHODS
Between August 2001 and December 2017, 70 patients with glomus jugulare tumors were treated at the Gamma Knife Center, Cairo. They were 46 females and 24 males. The mean age was 48 years (16–71 years). Nineteen of these patients were previously operated, 5 were partially embolized, 3 underwent embolization and subsequent surgery and 43 had gamma knife as their primary treatment. Volume-staged gamma knife radiosurgery was used in 10 patients and single-session in 60 patients, with a total of 86 sessions. The mean target volume was 12.7 cm3 (range 0.2 to 34.5 cm3). The mean tumor volume was 15.5 cm3 (range 0.2 to 105 cm3). The mean prescription dose was 14.5 Gy (range 12 to 18 Gy).

RESULTS
The mean follow up period was 60 months (range 18 to 206 months), and by the time of the data analysis, two of the patients were dead (66 and 24 months after GK treatment). The tumor control was 98.6% (69/70). Thirty-two tumors became smaller and 37 were unchanged. The symptoms improved in 36 patients, were stable in 32 patients, and worsened in 2 patients who developed a transient facial palsy and worsened hearing. Symptomatic improvement began before any reduction in tumor volume could be detected, where the mean time to clinical improvement was 7 months whereas the mean time to tumor shrinkage was 18 months.

CONCLUSION
This study about the long term follow up of the GKR for the intracranial glomus jugulare tumors confirmed that this is a highly effective and safe treatment. This data shows that the clinical improvement is not correlated with the radiological volume reduction.
P14.72 Involving patients and caregivers in the production of guidelines for palliative care in primary brain tumours: identification of intervention priorities
Authors: Pace A , Solari A , De Panfilis L , Lissoni B , Pronello E , Rudà R , Silvani A , Salmaggi A , Merli R , De Paula U , Bertocchi E , Verza M , Veronese S 
Published: September 2021

Abstract

BACKGROUND
Involving patients and caregivers is an important component of clinical guideline development. The three main Italian scientific associations for neurology, neuro-oncology and palliative care (SIN-AINO-SICP) recently appointed a joint task force (TF) of clinicians and researchers to develop specific guidance on palliative care of people with primary brain tumours, following the GRADE approach. To identify clinical questions meaningful to the patients and caregivers, a qualitative approach was used.

MATERIAL AND METHODS
Based on the existing literature and on consensus, the TF identified nine intervention areas, whose relevance was apprised by patients (via personal semi-structured interviews) and bereaved caregivers (via focus groups, FGs) from five tertiary neuro-oncology centres. Participants were prompted to provide their personal disease-related experience, and were asked to elicit the areas that mostly impacted their own lives. Interviews and FGMs were audio-recorded, transcribed and analysed using thematic analysis.

RESULTS
Twenty interviews and five FGs (28 caregivers) were completed between late 2020 and early 2021. Preliminary findings show that all the pre-specified areas were defined as important by participants. Most discussed topics were communication, organization and service satisfaction, cognitive and psychological issues, and advance care planning (ACP). Caregivers focused their discussions on the need for patient psychological support, difficulties experienced with symptoms control (e.g. epileptic seizures, behavioural changes), communication and organizational issues.

CONCLUSION
Participation of Italian patients with brain tumours and family caregivers was high and information-rich. All of the nine guideline intervention areas were considered important, communication, care organization, symptom control and ACP being the most discussed.