bluuebunny/crossref_metadata_2025_split huggingface dataset:
P08.11.A A subgroup analysis of utilities from European patients using tumor treating fields for glioblastoma
Authors: Palmer J D , Proescholdt C , Chavez G , Furnback W 
Published: September 2022

Abstract

Background
Recently a large-scale, international survey was undertaken studying real-world Health-Related Quality of Life (HRQoL) outcomes for patients using Tumor Treating Fields (TTFields) for treatment of glioblastoma (GBM). It is the largest published HRQoL study in GBM to date (Palmer et al. 2021). The study issued the EuroQol 5-Dimension (EQ-5D) survey to 2,815 patients using TTFields therapy for GBM in the US (2,182 patients) and Europe (633 patients).

Material and Methods
We analyzed EQ-5D results reported from European patients using TTFields for GBM in the above study. We used a EuroQol-endorsed model (Andrade et al. 2020) to estimate health state utilities from these EQ-5D responses for application to the French population. A health state utility is a number that quantifies patient HRQoL, where 0 corresponds to dead, 1 corresponds to perfect health, and numbers in between 0 and 1 correspond to intermediate HRQoL. We additionally considered data on demographics, disease characteristics, and treatment details.

Results
We report final analysis of the 327 EQ-5D responses received from European patients, representing a response rate of 51.7% i.e. the majority of European patients surveyed. The median/mean age was 57.5/56 years. 36.5% of patients were female and 63.5% male. 64.5% of patients had not experienced disease progression while 35.5% were post-progression. 44% of patients reported no additional therapies were being used in addition to TTFields while 56% reported the current use of other therapies. The median/mean time-since-diagnosis was 16/21.4 months and the median/mean time-using-TTFields therapy was 10/14.3 months. The overall median/mean utility estimates were .871/.784. The median/mean utility estimates for patients who had not experienced disease progression were .901/.841, while those for patients who had experienced disease progression were .833/.701. The median/mean utilities for patients under 65 years of age were .872/.778 while for patients at or over 65 they were .855/.791. Univariate regression analyses show that greater than 15 months since diagnosis is correlated with improved utilities (p=.033). These analyses also show that greater than 10 months using TTFields therapy is correlated with improved utilities (p=.005). Multivariate analysis controlling for age, gender, disease progression, other therapies, and time-since-diagnosis still shows that longer time using TTFields is correlated with improved utilities (p=.004).

Conclusion
The high survey response rate and relatively high utility estimates for both progressed and non-progressed patients as well as patients both over and under 65 years of age indicates that many European patients with GBM using TTFields can expect good QoL. Results indicate that utilities for European patients with GBM are likely to improve with longer time using TTFields therapy.
P08.12.B Conceptual development of an intensive supervised exercise program for brain tumor patients: summary of clinical experience
Authors: Jost J , Brandt R , Altuner U , Müther M , Stummer W , Völker K , Wiewrodt R , Wiewrodt D 
Published: September 2022

Abstract

Background
Several studies have identified beneficial effects of physical activity on reducing cancer-related symptoms. However, the number of such studies in neuro-oncology is limited, and even today, brain tumor patients are often advised against physically strenuous exercise. Here we summarize our experience with an individualized training program in brain tumor patients over a period of more than 8 years.

Material and Methods
Patients with primary brain tumors were invited to participate in the individual training program as part of the psycho-oncological consultation. If interested and free of major comorbidity, a professional sport scientist/diploma coach individualized two 60-minute sessions/week adapted to the patients’ respective symptoms and trained them on a 1:1-basis. One session consisted of bicycle ergometry at an average workload of 75% of the max. age-adjusted heart rate (up to 95% at peak; continuous monitoring throughout entire session), the other session was progressive whole-body resistance training based on 10 separate, but standardized exercise tasks using the university’s training facilities. Both training sessions were complimented by challenging elements to improve coordination. Exercise tasks were adapted as needed, and exercise levels were enhanced over time, if possible.

Results
From 2011 to 2019, 45 patients (19 women, 26 men) aged 20-76 years (mean 49) with different tumor types (65% high-grade gliomas, 22% low-grade gliomas, 13% other) participated in the program. The majority of patients started the program following concurrent radio-chemotherapy and in parallel with adjuvant systemic therapy. On average, 41 training sessions were performed. No training-related adverse events (e.g., falls, head pain, etc.) occurred during the entire period. In a total of 1828 training sessions, two minor epileptic seizures occurred (1 speech arrest; 1 simple focal seizure, left hand affected). Both patients were familiar with the respective type of seizure before entering the program and training could be continued immediately, with reduced intensity. Seizures did not reoccur during subsequent training sessions.

Conclusion
This supervised intensive physical training program with submaximal exertion zones was feasible, safe, and highly rated by all participants. Based on these experiences and the reported well-being of the patients, we launched a prospective oligocentric study to objectify the improvements in physical performance and quality of life in patients with glioblastoma (ClinicalTrials.gov Identifier: NCT05015543).
P08.14.B Addressing and implementing coping strategies from pre-surgery can reduce anxiety and depression in the brain tumour population
Authors: hurwitz v , Lavrador J p , La J ,   Kings neuro-oncology, Brazil L , Al-Salihi O , Swampillai A , Bhangoo R , Vergani F , Ashkan K , Chia K , Hedges S , Suarez A , Kostick E , Robinson C 
Published: September 2022

Abstract

Background
Anxiety and depression is prevalent in oncology patients and disproportionately high in neuro-oncology. The screening tools are most frequently used when signs of depression are identified later in the patients pathway. The cognitive impact of a brain tumour means coping mechanisms are harder to integrate and retain. Anti-depressants and their impact on a brain tumour have long since been debated with no clear conclusion. Implementing a programme to address the anticipatory diagnosis of anxiety and depression from first contact potentially allows patients to discuss their mental health needs more openly.

Material and Methods
Patients are introduced to the concept of health related anxiety and depression following their first pre-assessment appointment, A combination of techniques are employed through different mediums including baseline assessment with EORTC QOL screening, MoCa assessment, CBT techniques, YouTube tutorials via the neuro-oncology cns channel and one to one sessions over six to nine sessions.

Results
Patients perceived quality of life is higher following completion of the programme. 75% of participants were able to identify coping strategies they had learnt and how and when to use them. Oncologists reported patients were better prepared for their results and initial oncology consenting appointment. High anxiety levels caused one participant to self-discharge prior to their surgery. On completion of four sessions they returned to the hospital and underwent awake craniotomy.

Conclusion
Identifying and implementing coping strategies at the earliest opportunity improves patients quality of life whilst living with a brain tumour. Anxiety and depression being discussed and the risk of developing either or both of these conditions allows for more effective prevention, awareness and diagnosis. There is the potential to further this work by looking at the impact on carers of early detection of patients anxiety and depression
P09.01.A Speak up - a film project about living with a brain tumor
Authors: Piil K , Mathiasen M , Raffnsøe I , Vollmer V , Risgaard K 
Published: September 2022

Abstract

Background
When a person is diagnosed with a brain tumor everyday life change completely. Patients experience severe and fluctuating symptoms and the relatives often become informal caregivers. Together they seek to manage the symptoms and maintain quality in daily living. Especially, cognitive impairments are difficult to manage and often associated with stigma. The purpose of this project was to create awareness and share knowledge about the challenges experienced by those living with a brain tumor and their informal caregivers. The creation of the films was chosen to be an appropriate medium to reach our targeted public population. Even though film cuts are time-consuming with several costs to produce, they have a beneficial perspective. Among the advantages of this media is that film cuts are easy to access and understand, simple to share on social media, and addresses universal and population-specific problems and concerns making the audience wide ranging. Thereby, the film cuts may help prevent prejudices and misunderstandings from arising, and also seek to provide patients with a language and courage to talk about difficult sensitive issues.The Danish Brain Tumor Association (Hjernetumorforeningen) has produced nine short films about being diagnosed with and living with a brain tumor diagnosis. We intend that the film cuts will support and inform patients, relatives/family, friends, and professionals to better understand the complex situations experienced by brain tumor patients.

Material and Methods
A screenwriter from The Ophelia School of Acting attended several network meetings held by the ‘Hjernetumorforeningen’ and interviewed patients, relatives, health care professionals and board members of ‘Hjernetumorforeningen’ to write the manuscript of each film. Patients and relatives were an ongoing active part of the development until the final product was agreed upon.

Results
In 2021, nine film cuts of 3-5 minutes premiered in an auditorium at the cinema Dagmar located in Copenhagen. Each film has a specific focus and outline complicated situations experienced from the time of being diagnosed to the establishment of having a new but changed everyday life: 1) A happy family, 2) The operation, 3) The message, 4) A new daily life, 5) Back to work, 6) Freja’s party, 7) Casework, 8) The family support group and 9) Talk about it.

Conclusion
The 9 short film cuts can be watched at The ‘Hjernetumorforeningens’ website, on YouTube, LinkedIn and on Facebook. The film cuts have gained international attention and can therefore be seen with English subtitles for international dissemination.
P09.02.B Engaging Parents in Neuropsychological Rehabilitation for Childhood Cancer Survivors: The I’M aware: Patients And Carers Together (ImPACT) Program
Authors: Wu L M , Henriksen L T , Buskbjerg C R , Lassen-Ramshad Y , Zachariae R , Evald L , Hasle H , Amidi A 
Published: September 2022

Abstract

Background
Cognitive impairment is the most common late effect in childhood cancer survivors (CCS). A third are likely to experience impairments in skills such as attention, processing speed, memory, and executive function. Neurobehavioral impairments are also observed in CCS (e.g., apathy) and may underlie cognitive impairment. Although these problems can impair quality of life, scholastic achievement and long-term socioeconomic outcomes, there is a dearth of research on interventions to treat cognitive impairment in CCS. Cognitive rehabilitation studies in CCS have focused primarily on computerized cognitive training and meta-cognitive strategy training, but with limited effects and poor study designs. They have lacked four key elements: 1) transfer of learning to real-world functional outcomes; 2) awareness training to enhance compensatory strategy use, particularly since CCS may experience neurological unawareness preventing the optimal application of strategies; 3) inclusion of parents that could enhance transfer of learning to the home; and 4) recognition of the inter-related nature of cognitive, neurobehavioral, and psychological functions. A novel, context-sensitive neuropsychological rehabilitation program has been developed for CSS to address these missing elements - the “I’M aware: Patients and Carers Together (ImPACT)” program - based on an evidenced-based approach pioneered at NYU Hospital in the US. In this protocol, the feasibility, acceptability, and preliminary efficacy of the ImPACT program (8 x 1 hour sessions) will be evaluated.

Material and Methods
Phase One will consist of semi-structured interviews with 5 to 10 CCS and their parents in order to review and refine procedures for the ImPACT program. In Phase Two, twenty participants will be randomized to a wait-list control (WLC) or intervention group. WLCs will not receive the intervention immediately, but will serve as the control comparison group. Measures of self- and parent-reported cognition, neurobehavioral function, and global function will be administered pre- and post- intervention, and 9 weeks later (or equivalent time points for WLCs).

Results
Results of this project will provide vital data in support of a future large-scale trial.

Conclusion
Findings could have implications for the management of cognitive and neurobehavioral impairment in CCS that could transform the nature of services provided to CCS. The program can be delivered remotely or in-person and harnesses existing supports in the child’s life to promote real-world functioning.
P09.03.A Associations of levetiracetam use with the safety and tolerability of chemoradiotherapy for patients with newly diagnosed glioblastoma
Authors: Seystahl K , Oppong F B , Le Rhun E , Hertler C , Stupp R , Nabors B , Chinot O , Preusser M , Gorlia T , Weller M 
Published: September 2022

Abstract

Background
Levetiracetam (LEV) is one of the most frequently used antiepileptic drugs (AED) for brain tumor patients with seizures. We hypothesized that toxicity of LEV and temozolomide-based chemoradiotherapy may overlap.

Patients and Methods
In a retrospective analysis of individual patient data using a pooled cohort of patients with newly diagnosed glioblastoma included in clinical trials prior to chemoradiotherapy (CENTRIC, CORE, AVAglio) or prior to maintenance therapy (ACT-IV), we tested associations of hematologic toxicity, nausea or emesis, fatigue, and psychiatric adverse events during concomitant and maintenance treatment with the use of LEV alone or with other AED versus other AED alone or in combination versus no AED use at the start of chemoradiotherapy and of maintenance treatment.

Results
Of 1681 and 2020 patients who started concomitant chemoradiotherapy and maintenance temozolomide, respectively, 473 and 714 patients (28.1% and 35.3%) were treated with a LEV-containing regimen, 538 and 475 patients (32.0% and 23.5%) with other AED, and 670 and 831 patients (39.9% and 41.1%) had no AED. LEV was associated with higher risk of psychiatric adverse events during concomitant treatment in univariable and multivariable analyses (RR 1.86 and 1.88, p&lt;0.001) while there were no associations with hematologic toxicity, nausea or emesis, or fatigue. LEV was associated with reduced risk of nausea or emesis during maintenance treatment in multivariable analysis (HR=0.80, p=0.017) while there were no associations with hematologic toxicity, fatigue, or psychiatric adverse events.

Conclusion
Any association of psychiatric adverse events with LEV did not persist beyond the concomitant treatment phase. Antiemetic properties of LEV may be beneficial during the maintenance temozolomide.
P09.06.B The effectiveness of antiepileptic drug tripletherapy in refractory epileptic glioma patients: a multicenter observational cohort study
Authors: van der Meer P B , Dirven L , Fiocco M , Vos M J , Kouwenhoven M C M , van den Bent M J , Taphoorn M J B , Koekkoek J A F 
Published: September 2022

Abstract

Background
About 10% of the glioma patients need antiepileptic drug (AED) tripletherapy due to refractory epilepsy. This study aimed to determine whether levetiracetam combined with valproic acid and clobazam (LEV+VPA+CLB), a commonly prescribed tripletherapy, has favourable effectiveness compared to other tripletherapy combinations in glioma patients.

Material and Methods
In this multicenter retrospective observational cohort study, the primary outcome was the cumulative incidence of treatment failure for any reason, from initiation of AED tripletherapy. Secondary outcomes included cumulative incidences of: 1) treatment failure due to uncontrolled seizures; 2) treatment failure due to adverse effects; and 3) recurrent seizure. Maximum duration of follow-up was 36 months.

Results
Ninety patients, from an initial cohort of n=1435 patients, received AED tripletherapy after second-line AED duotherapy treatment failure due to uncontrolled seizures. LEV+VPA+CLB was prescribed to 43 (48%) and other AED tripletherapy to 47 (52%) patients. The cumulative incidence of treatment failure for any reason of LEV+VPA+CLB did not significantly differ from other tripletherapy combinations (12 months: 47% [95%CI, 31-62%] versus 42% [95%CI, 27-56%], p=0.892). No statistical significant differences for treatment failure due to uncontrolled seizures (12 months: 12% [95%CI, 4-25%] versus 18% [95%CI, 8-30%], p=0.445), due to adverse effects (12 months: 22% [95%CI, 11-36%] versus 15% [95%CI, 7-27%], p=0.446), or recurrent seizure (1 month: 65% [95%CI, 48-78%] versus 63% [95%CI, 47-75%], p=0.911) were found.

Conclusion
LEV+VPA+CLB has not shown favourable efficacy or tolerability compared to other AED tripletherapy combinations in glioma patients. Therefore, we cannot specifically recommend CLB as tripletherapy add-on AED to LEV+VPA.
P09.07.A Signs and Symptoms in the last days of life of the glioblastoma patients - A Descriptive and Retrospective Study
Authors: Ferreira M , Vasconcelos L , Lacerda M , Costa J 
Published: September 2022

Abstract

Background
Despite scientific advances to develop techniques for early diagnosis and treatment of glioblastoma, the disease continues to have a remarkably poor prognosis. Studies have shown that in patients with glioblastoma, not only the presence of end-of-life signs and symptoms but also their frequency differs from those in the rest of cancer patients. The complexity of glioblastoma symptoms makes the integration of a palliative care philosophy essential.

Objective
To identify the main signs and symptoms that occur in patients with glioblastoma in their last seven days of life in a neuro-oncology ward.

Material and Methods
This was a descriptive and retrospective study regarding the signs and symptoms in the last seven days of life of patients with glioblastoma who were admitted to the neurology ward of a national oncology reference center. The patients were admitted after neuro-oncologist consultations between 2019 and 2020. The data collection instrument used was based on the document “The Last Hours of Living”. Confidentiality of the participants was guaranteed, and authorization was obtained from the institution’s ethics committee.

Results
The sample had 17 patients (13 men and 4 women), with an average hospital stay of 17.3 days. The men and women had average ages of 61.8 and 63 years, respectively. Clinical and nursing records revealed that the most prevalent signs and symptoms were “decreased level of consciousness” (94%); “rare and unexpected events” (94%); “respiratory dysfunction” (88%); and “loss of ability to swallow” (76%). In the last seven days of life, the approximate times of presentation for these signs and symptoms were: decreased level of consciousness, 6 days; rare and unexpected events, 2 days; respiratory dysfunction, 3 days; and loss of ability to swallow, 6 days. Support was requested from the in-hospital palliative care support team for 76.4% of patients.

Conclusion
The identification of reduced level of consciousness and alterations in swallowing as the most prevalent symptoms is consistent with the findings of previous studies. The prevalence of rare and unexpected events (such as fever, myoclonus and seizures) aligns with previous studies that indicated a difference in the signs and symptoms presented by patients with glioblastoma in the last days of life and patients with other oncological diseases. In this sense, the instrument used for data collection may not be the most appropriate for the population with primary central nervous system tumors. The decreased level of consciousness and impaired communication can complicate the assessment of signs and symptoms, such as pain, nausea, anxiety and depression. It is essential to conduct research studies with more representative samples. The recording of the signs and symptoms presented, as well as interventions and the evaluation of their effectiveness, are essential to ensure the quality of end-of-life.
P10.02.B The fragile balance between proliferation and neoplasia in neural stem cells: role of DIAPH3 in glioblastoma
Authors: Chehade G , Ruiz-Reig N , Raftopoulos C , Tajeddine N , Tissir F 
Published: September 2022

Abstract

Background
DIAPH3 belongs to the formin family of proteins that are master regulators of the cell cytoskeleton. DIAPH3 plays a key role in cytokinesis as well karyokinesis. Hence, in the mouse brain, DIAPH3-deficient neural stem cells exhibit abnormal cell division leading to aneuploidy and apoptosis of cells progeny. Given the importance of aneuploidy in cancer development and progression, we asked whether DIAPH3 loss could be involved in the genesis and the aggressiveness of brain tumors.

Material and Methods
We co-inactivated Diaph3 and Trp53 genes in the mouse cerebral cortex using the Emx1-Cre mouse line (Diaph3/Trp53 dcKO). As a control, we inactivated only Trp53 gene using the same Cre mouse line (Trp53 cKO). Mouse survival was analyzed, and tumors were collected for histological analysis as well as molecular characterization. Additionally, we measured DIAPH3 expression in human glioblastoma samples and studied its impact on patient overall survival.

Results
Diaph3/Trp53 dcKO develop brain tumors earlier compared to Trp53 cKO resulting in a decrease of mouse survival. Hematoxylin-eosin staining, as well as GFAP, OLIG2 and KI67 immunostainings strongly suggest that the tumors are glioblastomas. Quantitative reverse transcription PCR performed on biopsies from 73 patients uncover variable DIAPH3 expression levels in glioblastoma samples. Interestingly, multivariate Cox proportional-hazards analysis shows that low DIAPH3 expression predicts a worse overall survival, independently from other known prognosis factors.

Conclusion
On one hand, our study shows that DIAPH3 loss favors glioblastoma development in mouse, strongly suggesting a tumor-suppressor role for DIAPH3. On the other hand, the clinical study shows that DIAPH3 low expression has a negative impact on patient overall survival indicating that DIAPH3 loss may favor resistance to chemotherapy and/or radiotherapy.