bluuebunny/crossref_metadata_2025_split huggingface dataset:
P11.40.A Clinicopathological Analysis of High risk Pituitary Adenomas According to the 2017 WHO Classification System for Pituitary Neuroendocrine Tumors (PitNET)
Authors: Kim Y , Ahn S , Jeun S , Lee Y , Park J 
Published: September 2022

Abstract

Background
The 2017 WHO classification of pituitary tumors has revealed “high-risk pituitary neuroendocrine tumors (PitNETs)”, which were known to have high probability for recurrence. Tumor invasion was not included in the pathological grading and classification due to frequent lack of proper pathologic assessment. However, it mentioned tumor invasion as an important prognostic feature in identifying clinically aggressive adenomas.

Material and Methods
We performed a retrospective review of a prospectively collected dataset from January 2018 to March 2021. Patient’s clinical presentation, radiologic features, pathologic findings, and clinical outcome were gathered. Inter-group analysis was performed for high-risk versus low-risk tumors, and invasive versus non-invasive tumors.

Results
Among total 116 cases of PitNETs, high-risk and low-risk tumors were identified in 32 and 84 cases, respectively. The inter-group comparison showed no differences in clinical presentation, radiologic features, pathologic findings, and clinical outcomes.Invasive and non-invasive tumors were identified in 49 and 67 cases, respectively. The invasive group tumors were more symptomatic ( 29 (59.2%) vs. 30 (44.8%), p= 0.031), with larger tumor size over 40mm (9 (18.4%) vs. 1 (1.5%), p = 0.002), and more likely to have Knosp grade higher than 3. The gross-total resection was less achievable (7 (14.3%) vs 26 (38.8%), p = 0.007) However, Ki-67 index showed no significantly difference between the invasive group and non-invasive group (2.0 vs 2.0 , p= 0.556).

Conclusion
According to our study results, the pathologic diagnosis of a high-risk tumor does not necessarily seem to properly reflect the clinical aggressiveness. Tumor invasion, however, seems to better represent the aggressive tumors that requires proper and active treatment.
P11.41.B The Cost of Inpatient Care For Adult Primary Brain Tumour Patients in England
Authors: Kanso N , Le Calvez K , Mauricaite R , Williams M 
Published: September 2022

Abstract

Background
Primary brain tumours are rare, but are the cause of the most life-years lost of any cancer. Given their poor prognosis, questions about their treatment and care costs are important especially in publicly-funded healthcare systems. There is currently very little robust data on the cost of care for brain tumour patients. Here we present up-to-date estimations of the direct inpatient care costs of all adult primary brain tumour patients in England, with a specific breakdown of costs attributed to cranial glioblastomas and cranial meningiomas, the commonest primary brain tumours.

Material and Methods
GlioCova uses a linked English national cancer data on over 50,000 adult primary brain tumour patients diagnosed between 2013-2018, with data on secondary healthcare activities three months before diagnosis - the last three months of 2012, and follow-up data after diagnosis - up to the last admission of 2019. We examined inpatient care with a breakdown of costs attributed to different treatment types: neurosurgery, chemotherapy and radiotherapy. We used the NHS HRG4+ Reference Costs Grouper 2017/2018 to assign costs matched from the National Schedule of Reference Costs 2017/2018. We converted all values to 2021 using the Health CPI Index.

Results
There were a total of 51,775 adult primary brain tumour patients diagnosed in England in the 6 year period between 2013 and 2018. 48,608 of these were admitted to hospital between the last three months of 2012 and the end of 2019, of which we were able to assign costs to 47,521 patients (98%). Total inpatient costs for the whole brain tumour cohort were over £973 million during the time period (34% attributed to inpatient care for neurosurgery, chemotherapy, and radiotherapy). 14,691 (31%) of patients were diagnosed with a cranial glioblastoma, and 9,501 (20%) of patients were diagnosed with a cranial meningioma. Total inpatient costs were £349 million and £163 million for glioblastoma and meningioma respectively, with 34% again devoted to direct treatment costs.

Conclusion
The estimated direct inpatient care costs for all 51,775 primary brain tumour patients diagnosed in England between 2013 and 2018 were nearly £1 billion (£166 million/year cohort), 2/3 of which was not for direct treatment. This does not include outpatient chemotherapy and radiotherapy costs, other outpatient appointments, patient out-of-pocket costs, primary care, social care, or end-of-life care costs. Future work will examine variation in care and costs and extend the analysis to include outpatients. We hope these data will help make an economic argument for improving care for brain tumour patients. More information on GlioCova: https://blogs.imperial.ac.uk/gliocova/about-gliocova/.
P11.42.A Short course of Bevacizumab for differential diagnosis of tumor progression and radionecrosis or pseudoprogression after brain metastasis SRS
Authors: Nikitin K 
Published: September 2022

Abstract

Background
Despite use of modern MRI techniques (perfusion, spectroscopy, TRAMs, radiomics), PET and SPECT the differential diagnosis of radio-necrosis and tumor progression is still difficult in malignant gliomas and brain metastasis after radiotherapy or radiosurgery. For patients who have enlargement of brain metastasis after radiosurgery we suggest a new strategy to discriminate pseudoprogression and true progression - two intravenous infusions Bevacizumab in 5-7 mg/kg with 2-3 week interval and new contrast MR.

Material and Methods
We present 3 relevant clinical cases, all after LINAC-based SRS for brain metastasis.1st case - 49 y.o. female with ovarian cancer underwent SRS for two small closely seated metastases in temporal lobe, both metastasis had shrunk and remained stable until 34 months after radiosurgery a new asymptomatic contrasting lesion with edema developed on MRI adjacent to one of metastasis. Patient developed no other new brain or extracranial mets, so we proposed radionecrosis, but MR-perfusion data was ambiguous. 2nd case - 67 y.o. female with lung adenocarcinoma underwent SRS (27 Gy in 3 fractions) for solitary brain metastasis. 4 months after SRS metastasis partially regressed, but 4 months later a new contrast enhancement zone appeared on its periphery with edema. 18F-FET PET failed to differentiate recurrence and pseudoprogression. 3d case - 48 y.o. female with breast cancer underwent SRS (27 Gy in 3 fractions) for 3 brain metastases. All mets regressed during the next 7 months, but 3 months later one of them showed significant symptomatic enlargement with edema on MRI. All patients received two intravenous infusions Bevacizumab in 5-7 mg/kg with 2-3 week interval and new contrast MRI (1-2 week after second infusion).

Results
1st case - after two infusions of 6 mg/kg with a 3-week interval new contrasting zone disappeared and did not develop again for at least 6 months (with no chemotherapy), so we confirmed necrosis. 2nd case - substantial regression of pathological MRI changes was noted, which was stable for 3 months, diagnostic for pseudoprogression. 3d case - MRI showed substantial regress of contrasting lesion (diagnostic for necrosis), symptoms also regressed and 1 month later methionine PET showed no active tumor.

Conclusion
Our preliminary data suggest that use of two infusions of Bevacizumab and routine contrast MRI have very promising diagnostic value to rule out tumor growth after SRS of brain metastasis.
P11.46.A Whole exome sequencing identifies novel SLIT2 mutations in primary CNS lymphoma
Authors: Kaulen L D , Erson-Omay E Z , Henegariu O , Karschnia P , Huttner A , Günel M , Baehring J M 
Published: September 2022

Abstract

Background
Whole exome sequencing (WES) data on primary CNS lymphoma (PCNSL) is scarce and correlation with clinical observations is needed to facilitate personalized care. Here we present WES data of six PCNSL and correlate genetic findings with clinical outcome.

Material and Methods
WES was performed on paired blood and tumor DNA samples from six PCNSL patients to a median coverage of 100x (range: 73-135x) and 194x (range: 127-232x), respectively. Selected, novel mutations were validated with Sanger sequencing. Epstein-Barr virus (EBV) status was assessed in tumor tissue. Progression free survival (PFS) and overall survival (OS) were analyzed in our cohort and in an extension cohort from the cBio Cancer Genomics Portal using Kaplan-Meier method and log-rank tests. P values &lt; 0.05 were considered significant.

Results
We found a median of 22 (range: 11-68) somatic copy number variations, 171 (range: 82-298) somatic single-nucleotide variants and 11 (range: 0-22) somatic insertions/deletions per PCNSL. CDKN2A loss, identified in five samples, was the most commonly detected copy number alteration. PCNSL carried mutations in previously described PIM1, MYD88, CD79B or BTG genes. In three PCNSL, we identified novel SLIT2 mutations (p.N63S, p.T590M, p.T732S) clustered around the leucine-rich repeats (LRR) domains. WNT-reporter and NF-kB reporter luciferase assays suggested alterations were loss-of-function variants. SLIT2 mutations were associated with shorter PFS in our cohort and with shorter OS in an extension cohort of 1856 lymphoid malignancies from the cBio Cancer Genomics Portal.

Conclusion
PCNSL harbored previously unknown SLIT2 mutations clustered around domains that are critical for interaction with ROBO proteins. SLIT2 mutations may be predictive of less favorable outcome in PCNSL. Additional clinical and molecular evaluation of these mutations is warranted.
P11.53.B Efficacy and tolerability of regorafenib in pretreated patients with progressive CNS grade 3 or 4 gliomas
Authors: Werner J , Wolf L , Tscherpel C , Bauer E K , Wollring M , Ceccon G , Deckert M , Brunn A , Pappesch R , Goldbrunner R , Fink G R , Galldiks N 
Published: September 2022

Abstract

Background
The phase 2 REGOMA trial suggested an encouraging overall survival benefit in glioblastoma patients at first relapse treated with the multikinase inhibitor regorafenib. Here, we evaluated the efficacy and side effects of regorafenib in a real-life setting.

Material and Methods
From 2018-2021, 30 patients with progressive WHO CNS grade 3 or 4 gliomas treated with regorafenib (160 mg/d; first 3 weeks of each 4-week cycle) with individual dose adjustment depending on toxicity were retrospectively identified. Side effects were evaluated according to the Common Terminology Criteria for Adverse Events (version 5.0). MRI was obtained at baseline and after every second cycle. Tumor progression was assessed according to RANO criteria. After regorafenib initiation, the median progression-free survival (PFS) and overall survival (OS) were calculated.

Results
The median number of treatment lines before regorafenib was 2 (range, 1-4). The majority of patients (73%) had two or more pretreatment lines. At first relapse, 27% of patients received regorafenib. A total of 94 regorafenib cycles were administered (median number of cycles, 2; range, 1-9 cycles). Grade 3 and 4 side effects were observed in 47% and 7% of patients, respectively, and were not significantly increased in patients with two or more pretreatments (P&gt;0.05). The most frequent grade 3 or 4 side effects were laboratory abnormalities (62%). PFS was 2.6 months (range, 0.8-8.2 months), and the OS was 6.2 months (range, 0.9-24 months).

Conclusion
In patients with progressive WHO grade 3 or 4 gliomas, predominantly with two pretreatment lines or more, regorafenib seems to be effective despite considerable grade 3 or 4 side effects.
P11.54.A Factors effecting early diagnosis in neurolymphomatosis
Authors: Egert A , Karschnia P , Huttner A , Baehring J M , Kaulen L D 
Published: September 2022

Abstract

Background
Neurolymphomatosis is defined as infiltration of the peripheral nervous system by non-Hodgkin lymphoma (NHL). Given its rarity, correct diagnosis is often delayed. Here we assessed diagnostic work-up and factors affecting timely diagnosis at a tertiary referral center.

Material and Methods
The quality control database of the Section of Neuro-Oncology at Yale Cancer Center was searched for neurolymphomatosis cases seen between 2000 and 2021. Clinical, radiological and pathological findings were collected. Factors affecting the interval from symptom onset to diagnosis were investigated in univariate analysis using SPSS version 27. P-values &lt;0.05 were considered statistically significant.

Results
We identified 22 cases of neurolymphomatosis (primary n=7, secondary n=15) with secondary disease diagnosed a median of 16 months (range: 4-144) after NHL. Patients presented with painful polyneuropathy (n=16), painless polyneuropathy (n=4), cranial neuropathy (n=3), and autonomic neuropathy (n=1). Diagnosis was nerve biopsy-based (n=11) or resulted from integration of imaging findings (n=11) with NHL history (n=5) or detection of NHL in the cerebrospinal fluid (n=6), respectively. Lesions localized to nerve roots (n=16), peripheral nerves (n=12), plexus (n=10), cranial (n=3) or autonomic (n=1) nerves. Histologically, most cases were classified as diffuse-large B-cell lymphoma (n=18). Median interval from symptom onset to diagnosis was 3 months (range: 1-12). Secondary neurolymphomatosis (p=0.02) and FDG-PET imaging (p&lt;0.01) were associated with an earlier diagnosis.

Conclusion
Diagnosis of neurolymphomatosis requires a high degree of clinical suspicion with subsequent integration of clinical, radiological and pathological findings. FDG-PET, the imaging gold standard, and a known NHL history correlated with an earlier diagnosis.
P11.55.B Postoperative MRI is able to detect an unexpected residual tumor after surgery of brain metastases: experience from 5 specialized centers
Authors: Kiesel B , Kerschbaumer J , Prihoda R , Borkovec M , Thakur S , Mercea P , Feucht D , Steindl A , Berghoff A S , Furtner J , Leitner J , Romagna A , Schwartz C , Stefanits H , Marhold F , Rötzer T , Preusser M , Freyschlag C , Widhalm G 
Published: September 2022

Abstract

Background
Brain metastases (BM) constitute the most common central nervous system tumors. The treatment options of BM consist of surgery, radiotherapy, radiosurgery, chemotherapy, and immunotherapy. Regarding surgery in BM, the extent of resection (EOR) represents a crucial factor for patient prognosis. However, first studies using postoperative MRI demonstrated that an unexpected residual tumor after surgery of BM is not uncommon despite these tumors were considered to be well-demarcated. The aim of this study was thus to investigate in a large cohort including multiple neurosurgical centers the EOR following BM resection, potential risk factors for incomplete resection and postsurgical follow-up data.

Material and Methods
In the current retrospective study conducted at 5 specialized neurosurgical centers in Austria, we included patients with BM resection and available postoperative MRI. The EOR following BM resection was determined by postoperative MRI (complete vs incomplete resection). Additionally, the data on the intraoperative judgement of the EOR of the performing neurosurgeon were collected. Moreover, potential factors for incomplete resection including tumor localization, tumor volume, primary tumor, pattern of contrast media enhancement on imaging and tumor eloquence were investigated. Finally, the rate of local progression of BM after initial surgery was analyzed in the follow-up period and overall survival data were collected.

Results
Altogether, 548 patients with 649 surgically treated BM were included. According to postoperative MRI, complete resection was achieved in 407 (66%) of 649 BM and incomplete resection in 176 (29%) of 649 BM. Misjudgment of the EOR by the neurosurgeon was found in 25% of cases and resulted in an unexpected residual tumor which was evident on postoperative MRI in 122 (22%) BM. Preoperative tumor volume was significantly larger in incompletely resected BM. Moreover, local progression was significantly more common in cases with incompletely resected BM and was also associated with shorter overall survival.

Conclusion
Our data of this study including multiple centers indicate that postoperative MRI is capable to detect a relatively high rate of unexpected residual tumors following resection of BM. Since local progression was more common in BM with residual tumors and this was associated with shorter survival, special attention should be paid to achieve a complete tumor resection.
P11.63.B Thrombocytopenia limits the feasibility of salvage lomustine chemotherapy in recurrent glioblastoma: a secondary analysis of EORTC 26101
Authors: Le Rhun E , Oppong F B , Gorlia T , Weller M 
Published: September 2022

Abstract

Background
Chemotherapies used for the treatment of primary brain tumors frequently induce hematological toxicity. Thrombocytopenia represents the main cause of stopping chemotherapy for toxicity. Here we explored the incidence, and the consequences for treatment exposure and survival, of thrombocytopenia induced by lomustine chemotherapy at first recurrence of glioblastoma.

Methods
We performed a retrospective analysis of thrombocytopenia at first recurrence of glioblastoma, its consequences for treatment delivery, and associations with outcome in the phase II and III parts of EORTC 26101, a randomized trial designed to define the role of lomustine versus bevacizumab versus their combination in glioblastoma patients at first relapse.

Results
225 patients were treated with lomustine alone (median 1 cycle) (group 1) and 283 patients were treated with lomustine plus bevacizumab (median 3 lomustine cycles) (group 2). Among cycle delays and dose reductions of lomustine for toxicity, thrombocytopenia was the leading cause. Among 129 patients of group 1 and 187 patients of group 2 experiencing at least one episode of thrombocytopenia, 36 patients in group 1 and 93 in group 2 had their treatment modified because of thrombocytopenia. Lomustine was discontinued for thrombocytopenia in 16 patients (7.1%) in group 1 and in 38 patients (13.4%) in group 2. Patients with O6-methylguanine DNA methyltransferase (MGMT) promoter-methylated glioblastoma treated with lomustine alone experienced more interference with study treatment than patients with tumors without MGMT promoter methylation. On adjusted analysis accounting for major prognostic factors, treatment modification by thrombocytopenia was a positive prognostic factor for overall survival, and this effect was entirely driven by patients with tumors without MGMT promoter methylation only. Conversely, thrombocytopenia was associated with inferior progression-free survival in patients with MGMT promoter-methylated tumors, suggesting a link to insufficient lomustine exposure.

Conclusion
Drug-induced thrombocytopenia is a major limitation to adequate exposure to lomustine salvage chemotherapy in patients with recurrent glioblastoma. Its association with survival suggests that mitigating thrombocytopenia to allow enhanced drug exposure in patients with MGMT promoter methylated tumors might improve outcome.
P11.74.A Plexiform Neurofibromas prevalence and treatment modalities in a referral comprehensive cancer center
Authors: Ferreira M , Costa J , Antão D , Silva E , Passos J , Vilares M , Vasques H , Patrocínio I , Silva C , Santos F , Salgado D , Lacerda M 
Published: September 2022

Abstract

Background
Neurofibromatosis type 1 (NF1) is the most common tumor predisposition syndrome, with an incidence of 1/3500. Plexiform neurofibromas (PN) are benign tumors that can occur along the nerve sheath throughout the body, with unpredictable growth and with risk of malignant transformation. Symptoms will depend on their size and location, and include pain, deformity and functional impairment. There is a great variability in the PN severity and impact on quality-of-life (QOL). An unknown percentage of NF1 patients may need treatment, either medical and/or surgical.

Objectives
To assess the frequency of PN in a NF1 population followed in a comprehensive cancer center.

Material and Methods
Retrospective study. All patients with NF1 and PN followed in our center, between 31/12/2000 and 31/12/2021.

Results
Of 438 NF1 patients, 185 had PN (42%). 52 NF1 patients with PN were children (≤ 18). The most common symptoms were pain in 71 people (38,4%), deformity in 70 (37,8%) and functional impairment in 69 (37,3%). Several patients had a combination of these symptoms. Different treatment modalities were used for PN: medical, surgical or both. In this study, 54 patients (29,1%) were treated with MEK inhibitors (selumetinib), 74 patients (40%) were treated surgically and 12,4% (23) needed a combined approach (medical and surgical treatment).

Conclusion
PN are frequent in NF1 patients. A significant percentage is symptomatic and will require treatment, surgical, medical or both. There is no standard of care for PN NF1. The timing and sequence of medical and surgical treatment is yet to be defined.
P12.06.A Relationship between ascorbate and DNA methylation markers in clinical glioma tumours
Authors: Crake R L I , Burgess E R , Wiggins G A R , Magon N J , Das A B , Vissers M C M , Morrin H R , Royds J A , Slatter T L , Robinson B A , Phillips E , Dachs G U 
Published: September 2022

Abstract

Background
Members of the 2-oxoglutarate-dependent dioxygenase (OGDD) enzyme family play an important role in gliomas as they regulate epigenetic modifications and response to hypoxia. The OGDDs require 2-OG and O2 as substrates, and ferrous iron and ascorbate as cofactors. Both hypoxia and aberrant DNA methylation are prognostic indicators for gliomas. The ten-eleven translocase (TET) DNA demethylases are OGDDs that convert 5-methyl cytosine (5mC) to 5-hydroxymethylcytosine (5hmC), with 5hmC levels related to better prognosis. Despite this, there is limited data on the OGDD enzymes and their substrates/cofactors in glioma tissues. Our previous study showed an association between ascorbate content and markers of the hypoxic response in glioblastoma tissue. Here we determine whether there is an association between ascorbate and DNA methylation in glioma. In addition, we assess whether methylation of the methylguanine-DNA methyltransferase (DNA repair enzyme MGMT) promoter is associated with ascorbate content.

Materials and methods
Frozen clinical glioma samples from 37 patients (n=11 WHO grade I-III, n=26 glioblastoma) were obtained from the Cancer Society Tissue Bank (Ethics approval H19/163). Isocitrate dehydrogenase 1 (IDH1) mutation status was determined by sequencing. Samples were processed on dry ice in liquid nitrogen and analysed for ascorbate (high-performance liquid chromatography), global DNA methylation (mass spectrometry) and MGMT promoter analyses (methylation specific PCR).

Results
Many grade I-III tumours were IDH1 R132H mutant (6/11), and most glioblastomas were not (2/26). Glioblastoma had significantly lower ascorbate content than grade I-III tumours (p=0.026). Glioblastoma also had lower global 5hmC levels (p=0.0013). IDH1 R132H tumours tended to have a lower ascorbate content (p=0.09). Ascorbate and 5hmC levels were directly correlated (Spearman r= 0.466, p=0.004). However, cytosine and 5mC showed no association with grade or ascorbate. MGMT promoter methylation status was not associated with global methylation or ascorbate content (p=0.97, p=0.96, respectively).

Conclusion
Our data suggests that ascorbate supports TET activity in clinical glioma. It also appears that site-specific (promoter) methylation was not affected by ascorbate availability. These findings may have clinical implications, as higher 5hmC levels are associated with improved outcome, whilst continued MGMT suppression suggests chemotherapy responsiveness. However, evidence that raising tumour ascorbate leads to increased 5hmC levels, or an associated improvement in survival, requires intervention trials.