bluuebunny/crossref_metadata_2025_split huggingface dataset:
P01.07.A Neurocognitive outcomes after proton beam therapy for skull base tumours
Authors: Gaito S , Hwang E , Aznar M , France A , Sitch P , Crellin A , Holtsman A L , Pan S , Whitfield G , Smith E 
Published: September 2022

Abstract

Background
Evidence suggests that Proton Beam Therapy (PBT) may lessen the risk of neurocognitive decline (NCD) by reducing the dose to the normal brain as compared to conventional photon radiotherapy (XRT). We report the incidence of moderate-severe (Grade ≥3) NCD in adults treated for skull base chordomas and chondrosarcomas within the United Kingdom’s Proton Overseas Programme (POP).

Material and Methods
Baseline (pre-PBT) and follow-up clinical outcomes data were prospectively collected as part of a national PBT-outcomes registry, which started in 2008 . This registry is curated by a dedicated Proton Clinical Outcomes Unit. Specifically, late toxicities ≥G3 as per CTCAE (Common Terminology Criteria for Adverse Events) v4.0 definition, occurring later than 90 days after treatment completion, were recorded. This study focuses on the incidence of memory impairment (MI) in the adult (≥25 y) cohort.

Results
Between 2008-2018, 141 adult patients were treated for skull base chordomas (77 patients, 54.6%) and chondrosarcomas (64 patients, 45.4%) via the POP (the majority -62.8%- treated at the University of Florida PBT Institute). Median age at treatment was 51 years (range 26-77). Median prescription dose was 73.8 GyRBE (70-75.6), with a median dose per fraction of 1.8 Gy (1.2-2.1). Of note, the median dose for chondrosarcomas was 70.2 GyRBE (70-75.6), whereas the median dose for chordomas was 73.8 GyRBE (72-75.6). Median follow up was 39 months (0-138). On clinical assessment, 4 patients (2 chordomas, 2 chondrosarcomas) were reported with G3 MI after a median time of 43 months (27-49). None of them had impaired memory at baseline, nor relevant neurological comorbidities. Median age of those who developed G3 MI was 63 y (39-70). Median prescription dose was 72.9 GyRBE (70-73.8). Plans were available for 3 of these 4 patients. Relevant dose statistics to hippocampi and temporal lobes were extracted. Dmean to the omo- and contralateral hippocampi in these 3 patient plans were: patient 1) 33.7 and 11.6 GyRBE; patient 2) 28.1 and 24.4 Gy; patient 3) 8.7 and 8.2 GyRBE, respectively. V20 to the omo- and contralateral temporal lobes in the same patients were: patient 1) 47% and 10%; patient 2) 29% and 28.7%; patient 3) 30% and 28%, respectively. Suggested constraints for these structures are: Dmean &lt; 20 Gy to the hippocampi and V20Gy &lt;10% to the temporal lobes.

Conclusion
Our results indicate that adult patients undergoing high dose radiation for radioresistant tumours may experience detrimental effects on memory. Neurocognitive baseline and follow-up assessment is not routinely performed in this age group but might be appropriate to explore which domains of cognitive function are mainly affected. Larger cohorts are warranted to establish predictive factors and better understand dose volume effect of brain structures and neurocognitive sequelae.
P01.14.B Visuospatial selective attention deficit after resection of right hemisphere gliomas: a multivariate lesion symptom mapping and diffusion tractography study
Authors: Puglisi G , Viganò L , Sciortino T , Leonetti A , Rossi M , Conti Nibali M , Gay L , Fornia L , Cerri G , Bello L 
Published: September 2022

Abstract

Background
The ability to select relevant information to current behavioural goals despite concomitant distractors (i.e. selective attention) is crucial for daily life. Despite the implication of fronto-parietal network in sustaining visuospatial selective attention has been considered crucial, the role of subcortical structures is still unclear. Aim of this study was to evaluate the impact of neurosurgical removal of right gliomas on visuospatial selective attention performances.

Material and Methods
The visuospatial selective attention domain was assessed pre- and postoperatively (1 month follow-up) in 73 patients operated for right hemisphere gliomas. Support-vector-regression lesion-symptom mapping and disconnectome analysis (Lesion Quantification Toolkit, HCP 1065 data) were used to evaluate the relationship between the resection cavities and the postoperative performance on a standardized selective attention test. To test and refine the atlas-based results, in a subset of 17 patients with preoperative diffusion tractography, the postoperative outcome was correlated with the percentage of disconnection for different white matter tracts.

Results
Results showed that resection of a cluster enclosing the SMA-complex and the surrounding white matter was significantly associated with a decline in visuospatial selective attention performances (p&lt;.05). Disconnectome analysis at population level revealed that the deficit was significantly correlated with the resection of superior cortico-striatal fibres, superior thalamic radiations, corticopontine projections, callosal connections and fibres of the frontal aslant tract. Within all the cortico-subcortical terminations of these tracts, disconnection of streamlines of the SMA-complex was the most associated with selective attention deficits. Tractography in single patients confirmed the population level results and suggested that ventro-lateral resections in case of inferior frontal or insular tumours significantly disconnecting the frontal aslant tract but sparing superior projection fibres were not associated with any postoperative disturbances.

Conclusion
Results show converging evidence to support a critical role for the SMA/preSMA and its projections in maintaining efficiency of attentive control. The present results reveal the importance of a fronto-medial descending connectivity in mediating the voluntary control of visuospatial selective attention. From a surgical standpoint, to avoid postoperative deficits, it seems crucial to preserve SMA projection pathways, while the disconnection of the frontal aslant tract is feasible without any postoperative decline.
P01.15.A Longitudinal assessment of neurocognition and quality of life in low-grade glioma patients receiving first-line Temozolomide
Authors: Darlix A , Fabbro M , Monnier M , Castan F , Coutant L , Denis E , Carriere M , Menjot de Champfleur N , Rigau V , Duffau H , Guerdoux E 
Published: September 2022

Abstract

Background
While maximal safe resection is the first therapeutic option in patients with newly-diagnosed diffuse low-grade glioma (DLGG), the timing and choice of further treatments (chemotherapy, radiation therapy or combinations of both) remain controversial. Because the expected survival is long in these young patients, the oncological impact of treatments must be balanced with the possible side effects, in particular regarding neurocognitive functioning and quality of life (QoL). Temozolomide (TMZ), an alkylating agent, is widely used in this setting. Here we aimed at evaluating the feasibility of a longitudinal neurocognitive and QoL assessment in DLGG patients receiving TMZ.

Material and Methods
We conducted a prospective study including adult DLGG patients receiving TMZ as first-line treatment after surgical resection(s) or biopsy. Neurocognition and QoL were evaluated longitudinally until progression. The feasibility was evaluated in terms of participation and compliance of a complete neurocognitive and QoL assessment (defined as the completion of these assessments at baseline, 6 months and 12 months). Secondary objectives were the description of the proportion of patients with changes in neurocognitive or QoL scores on TMZ.

Results
Of 29 eligible patients, 26 accepted to enter the study (participation rate 86.7%): 57.7% men, median age 45y. Tumor type was distributed as follows: astrocytoma, IDH-mutant 13/26, astrocytoma, IDH wild-type 1/26 and oligodendroglioma, IDH mutant and 1p19q codeleted 12/26. The compliance rate was 95.6% (evaluable in 23 patients as 3 patients had tumor progression within the first 12 months of TMZ). After TMZ, 13.6% of patients experienced a decline of the MoCA score as compared to baseline (from normal to abnormal). Cognitive complaints according to the FACT-COG assessment were stable for 90.9%. The complete cognitive and QoL evaluations (baseline and after 12 months of TMZ) will be presented.

Conclusion
Our data shows that a longitudinal evaluation of cognition and QoL is feasible in low-grade glioma patients. It suggests that first-line TMZ does not negatively affect neurocognition and QoL. These results must be evaluated in the long-term setting (evaluations ongoing) and confirmed in a larger, multicenter cohort.
P01.16.B Neurocognitive outcome and seizure freedom after awake surgery of gliomas
Authors: Reitz S , Behrens M , Lortz I , Conradi N , Rauch M , Filipski K , Voss M , Kell C , Czabanka M , Forster M 
Published: September 2022

Abstract

Background
Gliomas are often diagnosed due to epileptic seizures as well as neurocognitive deficits. First treatment choice for patients with gliomas in speech-related areas is awake surgery, which aims at maximizing tumor resection while preserving or improving patient’s neurological status. The present study aimed at evaluating neurocognitive functioning and occurrence of epileptic seizures in patients suffering from gliomas located in language-related areas before and after awake surgery as well as during their follow up course of disease.

Material and Methods
In this prospective study we included patients who underwent awake surgery for glioma in the inferior frontal gyrus, superior temporal gyrus, or anterior temporal lobe. Preoperatively, as well as in the short-term (median 4.1 months, IQR 2.1-6.0) and long-term (median 18.3 months, IQR 12.3-36.6) postoperative course, neurocognitive functioning, neurologic status, the occurrence of epileptic seizures and number of antiepileptic drugs were recorded.

Results
Between 09/2012 and 09/2019, a total of 27 glioma patients, aged 36.1 ± 11.8 years, were included. Tumor resection was complete in 15, subtotal in 6 and partial in 6 patients, respectively. While preoperatively impairment in at least one neurocognitive domain was found in 37.0% of patients, postoperatively, in the short-term, 36.4% of patients presented a significant deterioration in word fluency (p=0.009) and 34.8% of patients in executive functions (p=0.049). Over the long-term, scores improved to preoperative baseline levels. The number of patients with mood disturbances significantly declined from 66.7% to 34.8% after surgery (p=0.03). Regarding seizures, these were present in 18 (66.7%) patients prior to surgery. Postoperatively, 22 (81.5%) patients were treated with antiepileptic drugs with all patients presenting seizure-freedom.

Conclusion
In patients suffering from gliomas in eloquent areas, the combination of awake surgery, regular neurocognitive assessment - considering individual patients′ functional outcome and rehabilitation needs - and the individual adjustment of antiepileptic therapy results in excellent patient outcome in the long-term course.
P01.18.B Structural abnormalities related to chemotherapy in cancer survivors: an ALE meta-analysis of neuroimaging studies
Authors: Ahmed Y , Al-Bzour A , Al-Majali G , Ababneh O , Ibrahim R , Al-Khalili A , Hamza A , Alzghoul S , Al-Mannai R , Z Alawneh K , Al-Hayek K , Al Qawasmeh M 
Published: September 2022

Abstract

Background
Chemotherapy induced cognitive impairment (CICI) is a term used for the cognitive dysfunction reported with non-central nervous system cancer patients during or after chemotherapy. Recent neuroimaging studies have shown decreased activation in cancer patients during cognitive tasks post-chemotherapy. Structural changes are sought to be associated with cognitive decline in cancer survivors after chemotherapy. Here we aim to investigate the neuroimaging findings of structural abnormalities and gray matter alterations associated with chemotherapy in cancer survivors.

Material and Methods
A systematic search through PubMed database for peer-reviewed English-language studies yielded a total of 302 studies. Eligible studies were included in the activation likelihood estimation (ALE) meta-analysis if they reported coordinates in a stereotactic format (MNI or Talairach space) for voxel-based morphometric (VBM) studies on gray matter volume and post-chemotherapy cancer survivors compared to matched healthy controls. GingerALE (3.0.2) software from Brainmap.org was used to perform the ALE meta-analysis with threshold settings of uncorrected P-value &lt; 0.001 for multiple comparisons.

Results
The study sample included 299 patients comprised of breast cancer survivors (BCS), childhood acute lymphocytic leukemia (ALL) survivors, ovarian cancer survivors (OCS) and lung cancer with 279 matched healthy controls from 12 studies and 21 experiments. ALE-maps for post-chemotherapy cancer survivors showed reduced gray matter volume in comparison to healthy controls in the left inferior frontal gyrus, right thalamus, right superior frontal gyrus, right medial frontal gyrus and right cerebellum (peak coordinates: [-43,40,-6], [23,-29,2], [14,30,55], [9,57,-16], [9,-78,-41] respectively, and cluster size of 544 mm3, 312 mm3 and 257 mm3, 296 mm3, 297 mm3 respectively).

Conclusion
This is the first ALE meta-analysis that studied the converged areas of reduced gray matter volume in post-chemotherapy cancer survivors. Our findings of reduced gray matter volume in frontal regions and cerebellum might be responsible for the cognitive dysfunction in executive function, attention, and memory observed in cancer survivors. Further studies are needed to assess the impact of different chemotherapeutic regimens related to CICI .
P01.19.A The temporo-parieto-occipital junction in the non-dominant hemisphere as a challenging hub for glioma surgery: functional and oncological outcomes
Authors: Conti Nibali M , Puglisi G , Leonetti A , Rossi M , Gay L , Sciortino T , Mattioli L , Gambaretti M , Viganò L , Bello L 
Published: September 2022

Abstract

Background
The temporo-parieto-occipital junction (TPOJ) in the non-dominant hemisphere is a complex region intersected by multiple white matter bundles (Optic radiations, Inferior-fronto-occipital tract, inferior-longitudinalis-tract, superior-longitudinalis-tract, vertical-occipital-tract, medial-dorsal-longitudinal-tract, parietal-aslant-tract), subserving several high-level neurological functions such as spatial recognition, visual agnosia, visual field, attention and working memory. Few data are available on the optimum brain mapping strategy to be adopted for resecting tumors involving this area. Ideally it should allow surgeon to effectively identify several tracts and safely preserve all functions.

Material and Methods
We developed a proper protocol to approach this complex area integrating, in awake condition, intraoperative visual test (iVT) to mapping visual field, semantic association test (SRAT) to prevent visual agnosia and preserve working memory, hand manipulation task (hMT) to preserve spatial abilities. We reviewed its efficacy in a series of 38 patients with tumors involving non-dominant TPOJ, looking to functional (neurologic-neuropsychological) and oncological (EOR) outcomes. we perform a lesion symptom map and a disconnectome analysis to evaluate what region predict a decline in neuropsychological function and which tract of white brain matter are correlated in the decline of performance.

Results
Feasibility was high and all patients were able to perform and complete the protocol, which lasted, on the average11 min cortically and 25 min subcortically. Specificity was &gt;95%. Immediate post-operative deficits were documented in 87.4% of patients, permanent in 3.9% (visual field, visual spatial abilities). Attentive and emotional domains were those mostly affected in the neuropsychological evaluation. Lesion symptom mapping and disconnectomic analysis showed that the postoperative decrease in neuropsychological performance was associated with resection of a cluster of voxels corresponding to the anterior portion of the temporo-parietal junction. The white matter tracts mainly involved were the anterior and posterior segment of the middle longitudinal fasciculus (aMdLF and pMdLF) and the parietal aslant tract (PAT).

Conclusion
Effective and safe resection of tumors involving non-dominant TPOJ is feasible. The adoption of a specific brain mapping protocol in awake setting is recommended to achieve a full functional preservation and extend tumor resection. Further analysis should be performed to assess the role of this subcortical tracts.
P02.04.A Preoperative neutrophil, thrombocyte and monocyte to lymphocyte ratios as independent prognostic factors for patient survival in WHO 2021 glioblastoma multiforme
Authors: Lyutfi* E , Stoyanov* G S , Dzhenkov D , Ivanov B D , Kaprelyan A , Ghenev P , Georgiev K 
Published: September 2022

Abstract

Background
Glioblastoma (GBM) is the most common malignant primary central nervous system (CNS) tumor. It is a fast-growing and extremely aggressive malignancy with a short postoperative survival time of little more than a year. The tumor-immune system interactions are complex and can be measured as local phenomena - e.g., tumor-infiltrating lymphocytes, or as systemic events - e.g., lymphopenia, neutropenia, etc. with cell numbers allowing for estimation of the type of immune reaction against the tumor.

Material and Methods
A retrospective non-clinical approach was utilized for the means of the study. Patients with a histologically and molecular verified GBM, corresponding to the guidelines of 2021 WHO CNS tumor classification, diagnosed in a three-year interval (February 2018-2021) in a single tertiary healthcare institution were included. Patients with infectious, inflammatory, autoimmune, and hematological diseases, as well as those with malignancy in another location, were excluded. Data regarding patient demographics, and preoperative peripheral blood cell counts (neutrophils, platelets, and monocytes in a ratio to lymphocytes) were compared with postoperative patient survival. Preoperative ratios were calculated as absolute values. For cutoff values we used generally accepted ones - &gt;4 for neutrophil to lymphocyte (NLR), &gt;200 for thrombocyte to lymphocyte (TLR), and &gt;0.25 for monocyte to lymphocyte ratios (MLR). Results were statistically analyzed with MedCalc version 19.7.1 and the Kaplan-Meier method.

Results
A total of 22 patients fit the established criteria, with a male to female ratio of 2.14:1, mean age of 66.23 years, and mean survival of 255.72 days (8.04 months, range 24-801 days). Eight patients had an elevation of NLR and five of PLR, with no statistical correlation to survival. Six patients had an increase in MLR with a statistically significant (p=0.0044) shorter postoperative survival. Synergic increase in NLR and PLR did not show significance, while synergic increase with MLR showed no added benefit, as did comparison within MGMT promoter methylation groups.

Conclusion
Elevation in NLR, PLR, and MLR is a good independent prognostic marker for postoperative patient survival in histologically and mutationally verified GBM.

Acknowledgments
* contributed equally to the work and should be considered co-first authors.Financing: Medical University - Varna Scientific Fund, grant number 19010 and National scientific fund - young researchers (Republic of Bulgaria) grant number 2990/07.06.2021
Ethical approval: Medical University - Varna committee on scientific ethics approval protocol number 93/21.05.2020
P02.05.B Targeted therapies of Glioblastoma using single cell sequencing and drug-response analysis in a phase 2 clinical trial setting
Authors: Lü M , Hendriksen J , Urup T , Hamerlik P , Wennerberg K , Lassen U , Skovgaard H , Weischenfeldt J 
Published: September 2022

Abstract

Background
Glioblastoma is an aggressive brain tumour with a median survival of less than 15 months despite aggressive standard treatment consisting of neurosurgery, radiotherapy plus concomitant and adjuvant chemotherapy with temozolomide. There is no standard treatment at recurrence, and all have limited efficacy. In this study we will enroll glioblastoma patients from the Danish clinical trial “Protarget” to get a better understanding of resistance mechanisms and vulnerabilities in glioblastoma to give personalized medicine to glioblastoma patients at recurrent disease. We hypothesise that two connected factors are responsible for the failure to successfully target glioblastoma: i) intra-tumour heterogeneity and within this ii) cancer stem cells.

Material and Methods
We will use tumour tissue from glioblastoma patients included in the Danish phase 2, prospective, non-randomized clinical trial “Protarget” to establish short-term cultured neurospheres to preserve the heterogeneity of the tumour including cancer stem cells. We will then perform single cell RNA sequencing before and after drug screening. This setup will allow for a new approach to identify drug vulnerabilities at the single cell level. If successful in identifying drugs that leads to a clinical response, according to the "ProTarget" guidelines, we will consider scaling up the effort, to allow broader evaluation of efficacy. Our plan is to enroll 10 patients as a start. Patients will be selected based on ProTarget inclusion criteria and molecular profiling. We will further select patients with the following characteristics:1. IDH wildtype 2. High tumour purity (&gt;50%). 3. High degree of intra-tumour heterogeneity.

Results
Enrollment for "Protarget" began in 2020 and our cohort will be part of this study, which is why enrollment has already started, but the first patient has not been enrolled yet. Clinical trial registry number for "Protarget" is NCT04341181.

Conclusion
This new and flexible approach to identify drug vulnerabilities at the single cell level in glioblastoma in order to find targeted therapies is a promising tool for future treatment of glioblastoma patients.