bluuebunny/crossref_metadata_2025_split huggingface dataset:
P11.03.B BXQ-350: Modulating ceramide and Sphingosine-1-Phosphate for anti-tumor activity and potential mitigation of chemotherapy induced peripheral neuropathy
Authors: Tapolsky G H , Morris J C , Yilmaz E , Villano J L , Muller C , Curry, III R C , Puduvally V K , Wise-Draper T M , Takigiku R , Wesolowski R 
Published: September 2022

Abstract

Background
Sphingolipids are a class of bioactive signaling molecules implicated in multiple cellular processes and molecular pathways. Many publications have indicated that among these sphingolipids, sphingosine-1-phosphate (S1P) is a key sphingolipid that promotes cancer cell survival and proliferation, activates multiple oncogenic pathways, and stimulates immuno-suppressor cell populations promoting a pro-tumoral microenvironment. Many of these publications have also implicated S1P with chemotherapy induced peripheral neuropathy, a debilitating and serious side effect that may impact therapeutic treatments and patient’s quality of life.

Material and Methods
BXQ-350 is a nanovesicle of Saposin C, an allosteric activator of sphingolipid metabolism, that has broad anticancer activity, potentially in part by lowering systemic S1P levels. BXQ-350 was investigated in a Phase 1 dose-escalation safety study in an all-comer cancer patients with advanced solid malignancies, including CNS tumors (NCT02859857) to determine its safety profile and its potential clinical activity as a single agent in cancer patients. Samples were collected to determine pharmacokinetics and explore potential biomarkers.

Results
11 patients (~15% of evaluable patients) with advanced disease had a clinical benefit and amongst these, 8 patients (~11% of evaluable patients) had PFS&gt; 6 months with 2 patients still on study five years after enrollment. Analysis of patient’s samples revealed that BXQ-350 decreases systemic S1P levels in the majority of the patients experiencing a clinical benefit. In addition, several patients with established CIPN spontaneously reported improvements of their symptoms shortly after BXQ-350 administration. Analysis of these patients’ samples also revealed that S1P systemic levels had decreased, as well as pro-inflammatory cytokines associated with CIPN.

Conclusion
While these results are exploratory and preliminary in nature, they suggest that BXQ-350’s mechanism of action may represent a novel anti-cancer approach that may also mitigate CIPN.
P11.05.B Communication in neuro-oncology multidisciplinary team meetings (MDTM's)
Authors: van der Bruggen S C P , Beerepoot L , Janssens M , Schouten A , Leenders R 
Published: September 2022

Abstract

Background
The aim of MDTM’s is to ensure that all patients receive qualitative care from appropriately skilled professionals. However, empirical research shows that multidisciplinary team discussions do not always live up to their positive expectations. In discussions the team cycles through three main communicative phases: exploration, discussion and conclusion. The goal of this study is to gain insight in the structure of regional neuro-oncology MDTM’s and find an overarching reason why some discussions follow a different structure (or phase shifts) than others.

Material and Methods
We recorded 14 neuro-oncology MDTM’s in an non-academic Dutch Hospital by audio and video. All recordings were transcribed into time stamped sequences of verbal contributions. Every time stamped sequence was coded using a developed coding scheme.

Results
In total 14 regional Neuro-oncology MDMT’s were recorded, this resulted in 437 patient case reviews and 12512 coded verbal contributions. In each meeting the uniquely contributing members ranged from 12-21 members (M= 15.5, SD = 2.71) from 5 different institutions. The average of different disciplines was 7 disciplines (M=7.14, SD = 0.77). In 41% of the patient discussions there are two or three contributing disciplines in the decision making process. The maximum number of uniquely participating members in a patient discussion is 8 members. In only 28% of the case discussions 5 or more participants participated. Different categories for discussing a patient in an MTDM were found, these categories varied in specificity. From high to low specificity we found: justifying actions, pathology reviews, action-directed questions and open questions. We also found that in 20% of all patient case discussions the teams bypass the discussion phase.

Conclusion
MDTM’s are widely accepted and implemented. Therefore we should gain more insight in the structure and functioning of such teams. We found that there are different reasons for presenting a case which vary in their specificity. Our findings show that teams seem to deviate from the overall communication structure by bypassing the discussion phase in 20% of the cases. We also found that in 28% of patient discussions more than five participants contributed to the discussion. A future direction of organisation of MDTMs could be to clearly categorize on beforehand the patient questions in order to make the MDTM more efficient. Further analysis will include quality evaluation of MDTM’s, in neuro-oncology and other oncology domains. Support/Disclosure: this research is funded by WeCare (an collaboration between Tilburg University and Elisabeth-Tweesteden hospital).
P11.07.B What is the role of brain biopsy in the diagnosis of brain lesions?
Authors: Sivakanthan T S , Joannides A 
Published: September 2022

Abstract

Background
Brain biopsies have a role in establishing histological diagnoses for intrinsic tumours not amenable to surgical resection or lesions with an uncertain radiological diagnosis. Despite their utility, they are associated with several risks, particularly surgical complications and non-diagnostic samples. On this background, this study sought to determine the diagnostic yield and outcomes of brain biopsies carried out in a tertiary centre and explore factors which could influence the overall success of such procedures.

Material and Methods
All non-endoscopic brain biopsy procedures performed over a 1-year period (01/04/2020 to 01/04/2021) at one of the largest neurosurgical units in the UK were included. Hospital electronic records were used to identify eligible patients and determine relevant patient, procedure and outcome data. Mortality data were obtained with a minimum follow-up period of 1 year.

Results
A total of 75 cases were identified, including 55 burr hole biopsies and 20 open procedures. Overall, 16 (21%) biopsies were non-diagnostic, including 25% of burr hole biopsies and 10% of open biopsies. Procedures performed by a consultant had a lower non-diagnostic rate (17%) than cases with no consultant involvement (27%). Suspected inflammatory conditions had a higher non-diagnostic rate (55%) than suspected tumours (11%). Excluding non-diagnostic cases, histological diagnosis was in line with suspected pre-operative diagnosis in 70% of cases. Post-operative complications included 3 symptomatic haematomas and 1 subdural empyema, which led to one post-operative death. A total of 40 (55%) patients died within the follow-up period, including 10 (13%) within 60 days of their procedure. Six-month and 1 year survival rates were 35% and 26% for glioblastoma, respectively, and 70% and 70% for lymphoma. The majority (68%) of patients with a performance status (PS) of 3 or 4 prior to surgery died within 1 year, as compared to 42% with a PS of 0-2.

Conclusion
Brain biopsies are an important adjunct to managing CNS lesions due to the limitations of a radiological diagnosis alone. The diagnostic yield was greater for suspected neoplastic lesions, in cases with consultant involvement, and with open procedures.
P11.08.A Clinical practice evidence for perampanel in epilepsy patients with tumour aetiology
Authors: Coppola A , Izumoto S , Rodríguez-Osorio X , Wu T , D’Souza W , Maschio M , Goldman S , Valente Fernandes M , Villanueva V 
Published: September 2022

Abstract

Background
Real-world studies can provide information on those patients routinely excluded from clinical trials such as epilepsy patients with tumour aetiology. Perampanel (PER) is a once-daily oral anti-seizure medication for focal-onset seizures, with or without focal to bilateral tonic-clonic seizures, and generalised tonic-clonic seizures. This study evaluated PER’s effectiveness and safety when used in everyday clinical practice to treat epilepsy patients with tumour aetiology.

Material and Methods
Patients with epilepsy with tumour aetiology were identified from a pooled analysis of 44 prospective/retrospective/cross-sectional clinical practice studies. Retention was assessed after 3, 6 and 12 months of PER treatment. Effectiveness assessments comprised responder rate (≥50% seizure frequency reduction), seizure freedom rate (no seizures since at least the prior visit), and the proportions of patients with unchanged or worsening seizure frequency. Adverse events (AEs), psychiatric AEs, and AEs leading to discontinuation were also evaluated.

Results
Overall, 127 patients with focal-onset and/or generalised-onset seizures with tumour aetiology were identified (mean age, 46.6 years; 54.8% male; mean duration of epilepsy, 9.7 years). Seizure types at baseline were focal-onset only (97.6%), generalised-onset only (1.6%), and focal-onset and generalized-onset (0.8%). Mean (standard deviation) PER doses at baseline and last visit were 2.6 (1.4) and 5.8 (2.5) mg/day, respectively. At 3, 6 and 12 months, retention rates were 88.0%, 79.5% and 65.3%, respectively. Reasons for discontinuation included AEs (16.8%) and lack of efficacy (5.3%). Mean time under PER treatment was 11.0 months. At 12 months, 71.2% of patients were responders and 38.3% were seizure free; 11.9% and 3.4% of patients had unchanged and worsening seizure frequency, respectively. At the last visit (last observation carried forward), responder and seizure freedom rates were 66.9% and 34.2%, respectively, and the percentages of patients with unchanged or worsening seizure frequency were 15.3% and 6.8%, respectively. AEs were reported for 36.2% of patients, most frequently dizziness/vertigo (13.8%) and somnolence (9.5%). AEs led to discontinuation of 16.8% of patients over 12 months and 13.0% of patients experienced psychiatric AEs.

Conclusion
PER was effective and generally well tolerated when used to treat patients with epilepsy with tumour aetiology in clinical practice. Supported by Eisai
P11.09.B Chemotherapy is an efficient treatment in primary CNS MALT lymphoma
Authors: Desjardins C , Larrieu-Ciron D , Choquet S , Mokhtari K , Charlotte F , Nichelli L , Mathon B , Ahle G , Le Garff-Tavernier M , Dehais C , Hoang-Xuan K , Houillier C 
Published: September 2022

Abstract

Background
Mucosae-associated lymphoid tissue (MALT) lymphomas are a rare and still poorly understood form of primary central nervous system lymphoma (PCNSL). The aim of this study was to better describe these tumors and their management, and to better appreciate their long-term prognosis after treatment.

Material and Methods
Adult immunocompetent patients with primary CNS MALT lymphoma (PCNSML) were retrospectively selected from the database on PCNSL of the Pitié-Salpêtrière Hospital. All cases had double-read for pathology.

Results
Eleven PCNSML representing 1.7% of the 662 PCNSL included in the database were selected, There were 9 women and two men, all immunocompetent. Their median age was 56 years (min 29; max 78). The median time from first symptoms to diagnosis was 13 months and the median KPS at diagnosis was 90. Location was dural in 8 cases, suggestive of meningioma in 7 cases and of subdural hematoma in 1 case, and parenchymal in 3 cases. The disease was unifocal/localized in 4 cases and multifocal/diffuse in 7 cases. In 3 cases, it was the second reading that allowed making the diagnosis. In first-line treatment, all patients received chemotherapy (CT): “systemic” CT, i.e usually used in systemic MALT lymphomas, in 7 cases (n=7) and “CNS” CT, i.e usually used in CNS lesions in 4 cases. CT was preceded by surgery in 4 cases. No patient received radiotherapy in first line. According to the IPCG (International PCNSL Collaborative Group) criteria, the overall response rate was 7/11 (64%). At latest news, 5 patients had a persistent contrast enhancement, stable without any treatment since a median of 57 months, raising the question of complete response despite persisting contrast enhancement. No patient developed neurotoxicity except for one of the 2 patients who subsequently received radiotherapy. The median follow-up was 109 months. The median progression-free survival was 78.0 months (95% CI [43.4;NA[) and the 10-year overall survival rate was 90% (95% CI [0.7;1[).

Conclusion
This series confirms the classical clinical and radiological presentation of PCNSML. Compared to the literature where the treatment was based on radiotherapy in almost two thirds of cases, the therapeutic approach presented here appears unconventional. This is the first series demonstrating that chemotherapy is an efficient treatment in PCNSML, with an excellent long-term outcome and the absence of neurotoxicity, and calling into question the relevance of the IPCG criteria for the evaluation of their therapeutic response.
P11.12.A Primary central nervous system neuroblastoma and ganglioneuroblastoma in adult patients. Clinical and molecular features
Authors: Nechaeva A , Matsko M , Zrelov A , Ulitin A 
Published: September 2022

Abstract

Background
The clinical, morphological, molecular features, treatment modalities, and survival of primary central nervous system neuroblastoma and ganglioneuroblastoma (CNS-NB and CNS-GNB) in adult patients are still poorly understood.

Material and Methods
The study included 15 patients with CNS-NB and 16 patients with CNS-GNB aged 18 years and older who were treated in our clinic from 2008 to 2020. Clinical, radiological data and surgical results were analyzed. Analysis of tumor molecular profile was performed using the gene panel, which contained the majority of clinically significant genes.

Results
Progression-free survival (PFS) and overall survival (OS) were higher in patients with CNS-NB than in patients with CNS-GNB. Median PFS in patients with CNS-NB and CNS-GNB was 156 and 46 weeks, respectively (p=0.022), and median OS was 541 and 82 weeks, respectively (p=0.00045). In both groups, disease progression was more favorable for tumor localization in the cerebral hemispheres without involvement of basal structures (p &lt;0.05). Differences for OS in patients with CNS-NB were obtained when tumor volume was removed by more than 50% with a median OS of 541 weeks (p=0.042) compared to biopsy. In patients with CNS-GNB, total resection of the tumor increased both PFS and OS compared to subtotal resection (p=0.014 and p=0.017), respectively. In patients with CNS-NB, no benefit was observed for any of the different first-line chemotherapy regimens (p &gt; 0.05). In the group of patients with CNS-GNB, 6 cycles of temozolomide increased median PFS compared to other chemotherapeutic regimens (p=0.026). In CNS-NB, a high level of expression was observed only in the βIII-tubulin gene (54%, 7/13). In CNS-GNB, high levels of expression were found in three genes: PDGFR-α (54%, 7/13), VEGF (54%, 7/13), and βIII-tubulin (85%, 11/13). No statistically significant effect of mutation in IDH1(R132H) gene on median PFS and OS was observed. The OS of patients with CNS-NB and CNS-GNB was influenced by low or medium levels of VEGF expression (p=0.006), and the OS was influenced by three genes: ERCC1 (p=0.03), MGMT (p=0.029) and VEGF (p=0.002).

Conclusion
The morphologic type of the tumor determined survival. In both groups, median PFS and OS were influenced by tumor localization. The most important prognostic marker in adult patients with CNS-NB and CNS-GNB was VEGF, while MGMT and ERCC1 were predictive markers.
P11.17.B Molecular characterization of primary central nervous system lymphoma vs non-CNS lymphoma and correlation between mutational profile and treatment response
Authors: Tuohy K J , Wirk B , Aregawi D , Xiu J , Sumrall A , Glantz M 
Published: September 2022

Abstract

Background
Primary central nervous system lymphoma (PCNSL) is a unique type of non-Hodgkin lymphoma restricted to the central nervous system. Most cases are diffuse large B-cell lymphomas, but prognosis is far less favorable compared to extracerebral cases. Many mutations found in PCNSL converge on the NF-κB signaling pathway, leading to downstream activation of B-cell receptor (BCR) and NF-κB pathway. The differences in mutation frequency when compared to non-CNS lymphoma and how mutational profiles affect treatment response are not well understood. We compared the genomic profile of PCNSL and non-CNS lymphoma, evaluated the association between specific molecular alterations and survival, and analyzed the association between various mutations and response to therapy.

Materials and Methods
A total of 60 patients with PCNSL, 8 with secondary CNS lymphoma, and 202 with non-CNS B-cell lymphomas underwent molecular profiling at Caris Life Sciences (Phoenix, AZ). Analyses included next-generation sequencing of DNA (592 Genes, NextSeq or WES, NovaSeq) and RNA (WTS, NovaSeq). X2/Fisher’s-exact U tests were used for comparison, and significance was determined as p-value adjusted for multiple comparison by the Benjamini-Hochberg method (q&lt;0.05). Overall survival (OS) was calculated from the start of temozolomide (TMZ) or tissue collection to last contact using insurance claims data.

Results
When compared to non-CNS lymphomas, PCNSL tumors showed significantly higher mutation rates in MYD88 (70% vs. 7%), PIM-1 (58% vs. 7%), CD79B (42% vs. 3%) and higher rates of TMB-High (cutoff 10mut/MB; 28% vs. 10%) (q&lt;0.01). In addition, mutations in CARD11 (12% vs. 4%) and IRF4 (8% vs. 1%) trended to be more prevalent in PCNSL (p&lt;0.05). In contrast, mutations in KMT2D (35% vs. 16%), EZH2 (13% vs. 2%), CREBBP (22% vs. 7%), TNFRSF14 (10% vs. 0) and BCL2 (19% vs. 2%) trended to be more prevalent in non-CNS lymphomas compared to PCNSL (p&lt;0.05). In patients with PCNSL, there was no difference in survival in those with or without MYD88, PIM1 or CD79B mutations. No between-group differences were observed in the small cohort of patients with secondary CNS lymphoma (n=8). In the subgroup in whom these data were available, 25% of tumors were MGMT methylated, 71% had a “high or intermediate” tumor mutational burden, 8% were MSI high, and 54% were PD-L1 expression positive when tested by immunohistochemistry. Patients with PCNSL had worse overall survival (OS) than non-CNS lymphomas (30 vs 81 months, p&lt;0.001).

Conclusion
MYD88, PIM-1, and CD79B mutations are more frequent in PCNSL compared to non-CNS lymphomas, but none of these mutations affected OS. Only 25% of PCNSL patients are MGMT methylated, but a majority have expression of PD-L1 suggesting a benefit from PD-1-targeted therapy. Response and survival in patients with mutation-guided therapy will be presented.
P11.20.A Correlation between thyroid function and regorafenib activity in recurrent IDH wild-type(IDHwt) glioblastoma(GBM) patients: a large monocentric study
Authors: Caccese M , Padovan M , Cerretti G , Cavallin F , Zagonel V , Lombardi G 
Published: September 2022

Abstract

Background
Glioblastoma is the most frequent CNS malignant tumor, with high aggressiveness and poor prognosis. Regorafenib has recently demonstrated promising activity in terms of survival in recurrent glioblastoma patients. The impact of thyroid function on regorafenib activity has alreasy described in in patients with other types of tumors. This study aimed to investigate the relationship between baseline thyroid variables (TSH, fT3, fT4, fT3/fT4 ratio) and survival in IDHwt GBM patients who were treated with regorafenib.

Material and Methods
We retrospectively evaluated all consecutive recurrent IDHwt GBM patients who were treated with regorafenib at the Veneto Institute of Oncology in Padua (Italy) for which baseline thyroid function assessment was available prior to starting regorafenib. Major inclusion criteria were: histological diagnosis of IDHwt glioblastoma, regorafenib as second-line treatment, basel thyroid values available.The relationships between baseline thyroid variables (TSH, fT3, fT4, fT3/fT4 ratio) and outcomes (PFS, OS) were investigated with Cox regression models, where thyroid variables were modeled with first order polynomial or restricted cubic splines.

Results
We enrolled 108 recurrent IDHwt glioblastoma patients treated with regorafenib at our center From November 2015 to January 2022: 70% were male and median age was 50 years old. All patients received post-surgical treatment with concomitant chemotherapy and subsequent temozolomide according to Stupp protocol as first-line therapy. 32 patients (30%) underwent a second surgery upon recurrence. From starting regorafenib the median follow-up was 7.3 months (IQR 4.0-12.7). MedianPFS was 2.2 months (95% CI 2.0 to 3.4), and PFS rate was 43-13-4% at 3-6-12ms, respectively. MedianOS was 10.4 months (95% CI 7.5 to 14.5), and OS rate was 92-70-46% at 3-6-12 months, respectively. Disease Control Rate (DCR) was 42.7%. Univariate analysis suggested that the relationship between PFS and baseline fT4 may be modelled with first order polynomial (linear term p=0.06, non-linear term p=0.61) and also suggested a non-linear relationship between PFS and baseline fT3/fT4 (linear term p=0.06, non-linear term p=0.04).When adjusting for major clinical confounding factors (age, ECOG PS, second surgery, MGMT), multivariate analysis identified that baseline fT4 (as a continuous variable) is an independent risk factor for PFS (HR 1.09, 95% CI 1.02 to 1.17; p=0.02). We did not find any statistically significant associations between all baseline thyroid variables with OS and response.

Conclusion
Our study demonstrated fT4 value to be a predictive biomarker of PFS in recurrent glioblastoma patients treated with regorafenib. No correlation was showed between baseline thyroid function and survival.