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Advanced incurable diseases are often accompanied by numerous losses and burdens as the disease progresses, leading to a loss of autonomy, self-determination, and dignity for those affected, all of which can subsequently promote feelings of loneliness at the end of life. Declining health, increasing symptom burden, loss of social roles, and the fear of death and dying are among the key risk factors for loneliness towards the end of life. In this article, we provide an overview of the different dimensions of loneliness experienced at the end of life. We discuss existential loneliness alongside emotional and social loneliness, explore causes and health implications of loneliness at the end of life, suggest diagnostic tools for assessing loneliness, and finally provide recommendations for addressing emotional, social, and existential loneliness at the end of life. The loneliness of caregivers is also discussed. We suggest that addressing social and emotional loneliness early in the course of a terminal illness is crucial. Palliative, psychological, and spiritual support can strengthen interpersonal relationships, foster a sense of meaning and purpose, and alleviate the adverse effects of loneliness on mental and physical health as well as quality of life. In contrast, existential loneliness is considered an expression of profound emotional maturity and can offer opportunities for inner growth, contributing to a more refined sense of self while reinforcing identity, dignity, and transcendence at the end of life., (© 2024. The Author(s).)

Background: The aim is to implement knowledge of basic palliative care in selected departments by the Hub and Spokes model. Methods: Implementation of basic palliative care was designed as a stepwise training model by skills lectures over a time period of 2 years. In each of the six selected oncological and nononcological departments, one physician and two nurses were trained in semi-annual half-day meetings as expert representatives within their departments. Results: Semi-structured interviews were conducted to assess implementation outcomes with 12 nurses and 6 physicians. Overall acceptability was high for all departments and professions. Feasibility was given in all departments. Adoption and penetration of a trained expert representative differed between medical and nursing professions. Implementation was more appropriate in the stationary sector. Implementation costs were low. Conclusion: Expansion of the system into a second follow-up period, including more departments, is planned to ensure sustainability.

Introduction: The topic of death and the dying is a crucial aspect of patient care, especially for individuals with terminal illnesses. However, discussions about death and dying are often avoided during patient interactions. In this article, our aim is to explore the reasons behind our fear of death and dying and to assess the importance of addressing these issues in shaping and cultivating relationships with our patients and in our personal lives. We argue that being open to impermanence is a valuable tool in our work with patients and their families and should be integrated into conversations with them. Furthermore, discussions about death and dying should play a central role in medical and nursing education as well as professional development., Competing Interests: Die Autorinnen und Autoren haben keine Interessenkonflikte im Zusammenhang mit diesem Artikel deklariert, (© 2024 Aerzteverlag medinfo AG.)

Background: This study extended the original Dignity Therapy (DT) intervention by including partners and family caregivers (FCs) of terminally-ill cancer patients with the overall aim of evaluating whether DT can mitigate distress in both patients nearing the end of life and their FCs., Methods: In this multicenter, randomized controlled trial (RCT), a total of 68 patients with life expectancy < 6 months and clinically-relevant stress levels (Hospital Anxiety Depression total score; HADS tot  ≥ 8) including their FCs were randomly assigned to DT, DT + (including their FCs), or standard palliative care (SPC) in a 1:1:1 ratio. Study participants were asked to complete a set of questionnaires pre- and post-intervention., Results: The coalesced group (DT and DT +) revealed a significant increase in patients' perceived quality of life (FACIT-Pal-14) following the intervention (mean difference 6.15, SD = 1.86, p < 0.01). We found a statistically significant group-by-time interaction effect: while the HADS tot of patients in the intervention group remained stable over the pre-post period, the control group's HADS tot increased (F = 4.33, df = 1, 82.9; p < 0.05), indicating a protective effect of DT. Most patients and their FCs found DT useful and would recommend it to other individuals in their situation., Conclusions: The DT intervention has been well-received and shows the potential to increase HRQoL and prevent further mental health deterioration, illness burden and suffering in terminally-ill patients. The DT intervention holds the potential to serve as a valuable tool for facilitating end-of-life conversations among terminally-ill patients and their FCs. However, the implementation of DT within the framework of a RCT in a palliative care setting poses significant challenges. We suggest a slightly modified and less resource-intensive version of DT that is to provide the DT inventory to FCs of terminally-ill patients, empowering them to ask the questions that matter most to them over their loved one's final days., Trial Registration: This study was registered with Clinical Trial Registry (ClinicalTrials.gov -Protocol Record NCT02646527; date of registration: 04/01/2016). The CONSORT 2010 guidelines were used for properly reporting how the randomized trial was conducted., (© 2024. The Author(s).)

Background: Access to palliative care is often limited for challenging and vulnerable groups, including persons with substance use disorders. However, with optimized healthcare options and liberal substitution policies, this patient group is likely to increase over the upcoming years, and comorbidities will also influence the need for palliative support. Here, we aim at analyzing characteristics and specific challenges associated with substance use disorders (SUD) in palliative care., Methods: We retrospectively reviewed all patients diagnosed with substance use disorder that were treated at our Competence Center Palliative Care within the University Hospital Zurich, Switzerland between 2015 and 2021. Patient characteristics, including age, gender, duration of hospitalization, as well as specific metrics like body mass index, distinct palliative care assessment scores, and in-hospital opioid consumption were retrieved from the electronic patient files. Demographics and clinical data were analyzed by descriptive statistics, and compared to those of a control group of palliative care patients without SUD. An opioid calculator was used to standardize opioid intake based on morphine equivalents for meaningful comparisons., Results: The primary characteristics revealed that the majority of individuals were single (56%), had no children (83%), lived alone (39%), and were either unemployed or recipients of a disability pension (in total 50%). Nicotine (89%), opioids (67%), and alcohol (67%) were the most used substances. We identified various comorbidities including psychiatric illnesses alongside SUD (56%), hepatitis A, B, or C (33%), and HIV infection (17%). Patients with SUD were significantly younger (p < 0.5), predominantly male (p < 0.05), and reported a higher prevalence of pain (p < 0.5) compared to the standard cohort of palliative patients. Regarding the challenges most frequently reported by healthcare practitioners, non-compliance, multimorbidity, challenging communication, biographical trauma, lack of social support, and unstable housing situations played a key role., Conclusion: Patients with SUD represent a complex and vulnerable group dealing with multiple comorbidities that profoundly affect both their physical and psychological well-being. Understanding their unique characteristics is pivotal in providing precise and suitable palliative care., (© 2024. The Author(s).)

Background: The limitation of life sustaining treatments (LLST) causes ethical dilemmas even in patients faced with poor prognosis, which applies to many patients admitted to a Neurocritical Care Unit (NCCU). The effects of social and cultural aspects on LLST in an NCCU population remain poorly studied., Methods: All NCCU patients between 01.2018 and 08.2021 were included. Medical records were reviewed for: demographics, diagnosis, severity of disease, and outcome. Advance directives (AD) and LLST discussions were reviewed evaluating timing, degree, and reason for LLST. Social/cultural factors (nationality, language spoken, religion, marital status, relationship to/sex of legal representative) were noted. Associations between these factors and the patients' sex, LLST timing, and presence of AD were evaluated., Results: Out of 2975 patients, 12% of men and 10.5% of women underwent LLST (p = 0.30). Women, compared to men, more commonly received withdrawal instead of withholding of life sustaining treatments (57.5 vs. 45.1%, p = 0.028) despite comparable disease severity. Women receiving LLST were older (73 ± 11.7 vs. 69 ± 14.9 years, p = 0.005) and often without a partner (43.8 vs. 25.8%, p = 0.001) compared to men. AD were associated with female sex and early LLST, but not with an increased in-hospital mortality (57.1 vs. 75.2% of patients with and without AD respectively)., Conclusions: In patients receiving LLST, the presence of an AD was associated with an increase of early LLST, but not with an increased in-hospital mortality. This supports the notion that the presence of an AD is primarily an expression of the patients' will but does not per se predestine the patient for an unfavorable outcome., (© 2024. The Author(s).)

Background: Digital health technologies have potential to transform palliative care (PC) services. The global aging population poses unique challenges for PC, which digital health technologies may help overcome. Evaluation of attitudes and perceptions combined with quantification of prior use habits favor an understanding of psychological barriers to PC patient acceptance of digital health technologies including artificial intelligence (AI)., Objectives: We aimed to evaluate the attitudes and perceptions of PC patients regarding a broad range of digital health technologies used in their routine monitoring and treatment and identify barriers to use., Methods: We used a 39-item questionnaire to evaluate acceptance and use of smartphone-based electronic patient report outcome measures, wearables, AI, data privacy, and virtual reality (VR) in 29 female and male PC inpatients., Results: A majority of patients indicated an interest in (69.0%) and positive attitude toward (75.9%) digital health technologies. Nearly all (93.1%) patients believe that digital health technologies will become more important in medicine in the future. Most patients would consider using their smartphone (79.3%) or wearable (69.0%) more often for their health. The most feasible technologies were smartphones, wearables, and VR. Barriers to acceptance included unfamiliarity, data security, errors in data interpretation, and loss of personal interaction through AI., Conclusion: In this patient survey, acceptance of new technologies in a PC patient population was high, encouraging its use also at the end-of-life., Competing Interests: No competing financial interests exist., (© Stefan Wicki et al., 2024; Published by Mary Ann Liebert, Inc.)

Background: The value of early integration of palliative care has been demonstrated increasingly for the past years in both oncological and nononcological diseases. Outpatient palliative care services might represent a feasible approach to implement supportive care in early disease. In this study, we aimed at evaluating which patients use and benefit from outpatient palliative care services, which symptoms are addressed most, and which support services are installed in this early phase of disease., Methods: We retrospectively analyzed the entire patient collective of a recently developed palliative care outpatient clinic within the leading university hospital in Switzerland for a period of five years. Sociodemographics, symptoms, and information on disease as well as patient-reported outcomes were retrieved from the electronic patient files. Demographic and clinical data were analyzed by descriptive statistics between groups and survival was analyzed by means of Kaplan-Meier estimates and log-rank test., Results: We report on 642 consultations of 363 patients between 2016 and 2020. Patients had a mean of 1.8 visits (range 1-10), with n  = 340 patients (93.7%) of patients suffering from an oncological disease. Overall symptom load was high, with n  = 401 (73.7%) of patient-reported outcomes reporting two or more symptoms. Distress levels of 5 or higher were reported in n  = 78 (30.4%) of available patient-reported outcomes. Independent of the origin of primary disease and the length of the disease trajectory, patients were referred to the palliative care service in median only four months before death., Conclusion: We identify high symptom load and distress in the outpatient palliative patient population. Patients benefitted from supportive medication, improvement of ambulatory support systems and advance care planning, and more than one-third of patients remained in follow-up, indicating a good acceptance of the service. Overcoming the overall late referral could, however, further increase the quality of life at earlier stages of disease., Competing Interests: No competing financial interests exist., (© Dorothea Rebekka Birkner et al., 2024; Published by Mary Ann Liebert, Inc.)

Introduction and Background: While recurrent glioblastoma patients are often treated with re-irradiation, there is limited data on the use of re-irradiation in the setting of bevacizumab (BEV), temozolomide (TMZ) re-challenge, or immune checkpoint inhibition (ICI). We describe target delineation in patients with prior anti-angiogenic therapy, assess safety and efficacy of re-irradiation, and evaluate patterns of recurrence., Materials and Methods: Patients with a histologically confirmed diagnosis of glioblastoma treated at a single institution between 2013 and 2021 with re-irradiation were included. Tumor, treatment and clinical data were collected. Logistic and Cox regression analysis were used for statistical analysis., Results: One hundred and seventeen recurrent glioblastoma patients were identified, receiving 129 courses of re-irradiation. In 66 % (85/129) of cases, patients had prior BEV. In the 80 patients (62 %) with available re-irradiation plans, 20 (25 %) had all T2/FLAIR abnormality included in the gross tumor volume (GTV). Median overall survival (OS) for the cohort was 7.3 months, and median progression-free survival (PFS) was 3.6 months. Acute CTCAE grade ≥ 3 toxicity occurred in 8 % of cases. Concurrent use of TMZ or ICI was not associated with improved OS nor PFS. On multivariable analysis, higher KPS was significantly associated with longer OS (p < 0.01). On subgroup analysis, patients with prior BEV had significantly more marginal recurrences than those without (26 % vs. 13 %, p < 0.01)., Conclusion: Re-irradiation can be safely employed in recurrent glioblastoma patients. Marginal recurrence was more frequent in patients with prior BEV, suggesting a need to consider more inclusive treatment volumes incorporating T2/FLAIR abnormality., Competing Interests: CH has received research support through the “Filling the Gap” Program of the University of Zurich. CH has received honoraria from Vifor. DAR has received research support through DFCI from Acerta Phamaceuticals; Agenus; Bristol-Myers Squibb; Celldex; EMD Serono; Enterome; Epitopoietic Research Corporation; Incyte; Inovio; Insightec; Merck; Novartis; Omniox; Tragara. DAR has received advisory fees from Agios; AnHeart Therapeutics; Avita Biomedical, Inc., Bristol Myers Squibb; Boston Biomedical; CureVac AG; Del Mar Pharma; DNAtrix; Hoffman-LaRoche, Ltd; Imvax; Janssen; Kiyatec; Medicenna Therapeutics; Neuvogen; Novartis; Novocure; Pyramid; Sumitomo Dainippon Pharma; Vivacitas Oncology, Inc Y-mabs Therapeutics. DAR has received Honoraria from Abbvie; Advantagene; Agenus; Agios; Amgen; Avita Biomedical, Inc., Bayer; Boston Biomedical; Boehringer Ingelheim; Bristol-Myers Squibb; Celldex; Deciphera; DelMar; Ellipses Pharma; EMD Serono; Genenta; Genentech/Roche; Imvax; Inovio; Kintara; Kiyatec; Medicenna Biopharma, Inc.; Merck; Merck KGaA; Monteris; Neuvogen; Novartis; Novocure; Oncorus; Oxigene; Regeneron; Stemline; Sumitono Dainippon Pharma; Taiho Oncology, Inc. NA reports personal fees from AstraZeneca; Debiopharm; ViewRay; BrainLab. NA received research grants from ViewRay. MG has received research support from ViewRay; AstraZeneca. MG is the current President-elect of ESTRO. MW has received research grants from Versameb; Quercis. MW has received consulting fees from Bayer; Curevac; Medac; Novocure; Philogen; Roche; Sandoz. MW has received honoraria from Novartis. MV holds a board role at Orbus. PY has received research grants from Astra Zeneca/Medimmune; Black Diamond; Beigene; Celgene; Chimerix; Eli Lily; Erasca; Genentech/Roche; Kazia; MediciNova; Merck; Novartis; Nuvation Bio; Puma, Servier; Vascular Biogenics; VBI Vaccines. PY has received consulting fees from Astra Zeneca, Bayer; Black Diamond; Boehringer Ingelheim; Boston Pharmaceuticals; Celularity; Chimerix; Day One Bio; Genenta; Glaxo Smith Kline; Karyopharm; Merck, Mundipharma; Novartis; Novocure; Nuvation Bio; Prelude Therapeutics; Sapience; Servier; Sagimet; Vascular Biogenics; VBI Vaccines. PY holds board positions at Novocure; Day One Bio.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Consumption of animal-sourced food is an important factor in broadening the diet of early hominins, promoting brain and body growth, and increasing behavioural complexity. However, whether early hominins obtained animal food by scavenging or hunting large mammals remains debated. Sabre-toothed felids have been proposed to facilitate the expansion of early Homo out of Africa into Europe 1.4-0.8 Ma by creating a niche for scavengers in Eurasia as the carcasses abandoned by these felids still contained abundant edible resources. In contrast, it has been argued that the niche for a large scavenger was already occupied in Eurasia by the giant hyena, preventing hominins from utilising this resource. This study shows that sabre-toothed felids generated carcasses rich in edible resources and that hominins were capable of competing with giant hyenas for this resource. The simulation experiments showed that maintaining an optimum group size is essential for the success of the hominin scavenging strategy. Early hominins could outcompete giant hyenas only if they could successfully dispute carcasses with them. Thus, in the presence of a strong competitor, passive scavenging is essentially the same as confrontational scavenging., (© 2023. Springer Nature Limited.)

Background and Introduction: The place of last care carries importance for patients at the end of life. It is influenced by the realities of the social welfare and healthcare systems, cultural aspects, and symptom burden. This study aims to investigate the place of care trajectories of patients admitted to an acute palliative care unit., Materials and Methods: The medical records of all patients hospitalized on our acute palliative care unit in 2019 were assessed. Demographic, socio-economic and disease characteristics were recorded. Descriptive and inferential statistics were used to identify determinants for place of last care., Results: A total of 377 patients were included in this study. Median age was 71 (IQR, 59-81) years. Of these patients, 56% (n = 210) were male. The majority of patients was Swiss (80%; n = 300); about 60% (n = 226) reported a Christian confession; and 77% had completed high school or tertiary education. Most patients (80%, n = 300) had a cancer diagnosis. The acute palliative care unit was the place of last care for 54% of patients. Gender, nationality, religion, health insurance, and highest level of completed education were no predictors for place of last care, yet previous outpatient palliative care involvement decreased the odds of dying in a hospital (OR, 0.301; 95% CI, 0.180-0.505; p-value < 0.001)., Conclusion: More than half of patients admitted for end-of-life care died on the acute palliative care unit. While socio-economic factors did not determine place of last care, previous involvement of outpatient palliative care is a lever to facilitate dying at home., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Large scale databases are critical for helping scientists decipher long-term patterns in human evolution. This paper describes the conception and development of such a research database and illustrates how big data can be harnessed to formulate new ideas about the past. The Role of Culture in Early Expansions of Humans (ROCEEH) is a transdisciplinary research center whose aim is to study the origins of culture and the multifaceted aspects of human expansions across Africa and Eurasia over the last three million years. To support its research, the ROCEEH team developed an online tool named the ROCEEH Out of Africa Database (ROAD) and implemented its web-based applications. ROAD integrates geographical data as well as archaeological, paleoanthropological, paleontological and paleobotanical content within a robust chronological framework. In fact, a unique feature of ROAD is its ability to dynamically link scientific data both spatially and temporally, thereby allowing its reuse in ways that were not originally conceived. The data stem from published sources spanning the last 150 years, including those generated by the research team. Descriptions of these data rely on the development of a standardized vocabulary and profit from online explanations of each table and attribute. By synthesizing legacy data, ROAD facilitates the reuse of heritage data in novel ways. Database queries yield structured information in a variety of interoperable formats. By visualizing data on maps, users can explore this vast dataset and develop their own theories. By downloading data, users can conduct further quantitative analyses, for example with Geographic Information Systems, modeling programs and artificial intelligence. In this paper, we demonstrate the innovative nature of ROAD and show how it helps scientists studying human evolution to access datasets from different fields, thereby connecting the social and natural sciences. Because it permits the reuse of "old" data in new ways, ROAD is now an indispensable tool for researchers of human evolution and paleogeography., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kandel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Median survival with glioblastoma remains in the range of 12 months on population levels. Only few patients survive for more than 5 years. Patient and disease features associated with long-term survival remain poorly defined., Methods: European Organization for Research and Treatment of Cancer (EORTC) 1419 (ETERNITY) is a registry study supported by the Brain Tumor Funders Collaborative in the US and the EORTC Brain Tumor Group. Patients with glioblastoma surviving at least 5 years from diagnosis were identified at 24 sites in Europe, US, and Australia. In patients with isocitrate dehydrogenase (IDH) wildtype tumours, prognostic factors were analysed using the Kaplan-Meier method and the Cox proportional hazards model. A population-based reference cohort was obtained from the Cantonal cancer registry Zurich., Results: At the database lock of July 2020, 280 patients with histologically centrally confirmed glioblastoma (189 IDH wildtype, 80 IDH mutant, 11 incompletely characterised) had been registered. In the IDH wildtype population, median age was 56 years (range 24-78 years), 96 patients (50.8%) were female, 139 patients (74.3%) had tumours with O 6 -methylguanine DNA methyltransferase (MGMT) promoter methylation. Median overall survival was 9.9 years (95% confidence interval [95% CI] 7.9-11.9). Patients without recurrence experienced longer median survival (not reached) than patients with one or more recurrences (8.92 years) (p < 0.001) and had a high rate (48.8%) of MGMT promoter-unmethylated tumours., Conclusions: Freedom from progression is a powerful predictor of overall survival in long-term survivors with glioblastoma. Patients without relapse often have MGMT promoter-unmethylated glioblastoma and may represent a distinct subtype of glioblastoma., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C.H. has received a research grant for protected time by the Filling the Gap foundation and honoraria for lecture from Vifor; E.L.R. has received honoraria for lectures or advisory board from Bayer, Janssen, Leo Pharma, Pierre Fabre, Seattle Genetics; J.C. has received research funding from Servier and Merck and consultant for Servier; R.S. reports consultation for Bayer, Astra Zeneca; W.W. reports consultation for Apogenix, Astra Zeneca, Bayer, Enterome, Medac, MSD and Roche/Genentech with honoraria paid to the Medical Faculty at the University of Heidelberg; F.D. has received honoraria for lectures or advisory board participation from Novocure; P.R. has received honoraria for lectures or advisory board participation from Bristol-Myers Squibb, Boehringer Ingelheim, Debiopharm, Merck Sharp and Dohme, Midatech, Novocure, QED, and Roche and research support from Merck Sharp and Dohme and Novocure; P.H. has received honoraria for lectures or advisory board participation or consulting from Bayer, Lilly, medac, Novartis, Novocure and Seagen; A.H. has received honoraria for lectures, consultation or advisory board participation from Novocure and Novartis; G.L. has received funding for a consulting or advisory role from Bayer, AbbVie, Orbus Therapeutics, BrainFarm, Health4U, Novartis, Braun and Janssen, and funding for travel from Roche, Bayer, and Ipsen; D.K. has received honoraria for lectures, consultation or advisory board participation from Novocure and BrainLab; M.G. reports honoraria from Roche, Novartis, UCB, AbbVie, Daiichi Sankyo, Novocure, Seagen, Bayer, Janssen-Cilag, Medac, Merck, Kyowa Kirin, travel support from Novocure and Medac, research grant from Novocure; D.R. reports support from Agenus, Agios; AnHeart Therapeutics, Avita Biomedical, Inc., Blue Rock Therapeutics, Bristol Myers Squibb, Boston Biomedica, CureVac AG, Del Mar Pharma, DNAtrix, Enterome, Hoffman-LaRoche, Ltd, Imvax, Janssen, Kiyatec, Medicenna Therapeutics, Neuvogen, Novartis, Novocure, Pyramid Bio, Sumitomo Dainippon Pharma. Vivacitas Oncology, Inc, Y-mabs Therapeutics; M.v.d.B has received honoraria for consultancy from Genenta, Servier, Astra Zeneca, Boehringer-Ingelheim, Carthera, Nerviano, Chimerix, Roche, Fore Biotherapeutics, Menarini-Stemline, Incyte and Sumitomo Pharma Oncology; F.L. received research funding from the Fonds Erasme; U.H. reports honoraria for lectures and and/or advisory board participation from Medac, Janssen, Bayer; E.R. reports travels grants BMS, Pfizer, MSD, Sanofi, Roche, Karyo labs Honorarium MSD, Servier; AF.C. received honoraria for lectures and/or advisory board participation from Gilead, Novartis; R.Ru. has received honoraria for lectures or consultation or advisory board from UCB, Novocure, Bayer, Genenta; M.P. has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals; P.W. has received research support from Astra Zeneca/Medimmune, Beigene, Celgene, Chimerix, Eli Lily, Genentech/Roche, Kazia, MediciNova, Merck, Novartis, Nuvation Bio, Puma, Servier, Vascular Biogenics, VBI Vaccines and honoraria for advisory board participation or serving on data safety monitoring board from Astra Zeneca, Bayer, Black Diamond, Celularity, Chimerix, Day One Bio, Genenta, Novartis, Prelude Therapeutics, Sapience, Servier, Sagimet, Vascular Biogenics, VBI Vaccines; MW has received research grants from Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Bayer, Medac, Merck (EMD), Novartis, Orbus, and Philogen. All remaining authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Introduction: Definitive surgical, oncological and radio-oncological treatment may result in significant morbidity and acute mortality. Mortality during or shortly after treatment in patients undergoing curative radio-(chemo)-therapy has not been studied systematically. We reviewed all curative radio-(chemo-)therapies at a large comprehensive cancer center over the last decade., Materials and Methods: The institutional record was screened for patients who received curative-intent radio-(chemo-)therapy and deceased during or within 30 days after radiotherapy. Curative therapy was defined as prescribed dosage of EQD2 ≥ 50 Gy for radiotherapy alone and EQD2 ≥ 40 Gy for radiochemotherapies. Data on demographics, disease and treatment were assembled and assessed., Results: Of 15,255 radiotherapy courses delivered at our center, 8,515 (56%) were performed with curative-intent. During or within 30 days after radio-(chemo-)therapy, 78 patients died (0.9% of all curative-intent courses). Median age of the deceased patients was 70 (IQR, 62-78) years, and 36% (28/78) were female. Median pre-therapeutic ECOG-PS was 1 (IQR, 0-2) and Charlson-Comorbidity-Index was 3+ (IQR, 2-3+). The most common primary malignancies were head and neck cancer (33/78; 42%) and central nervous system tumors (13/78; 17%). Peritherapeutic mortality varied by primary tumor, with the highest prevalence observed in head and neck and gastrointestinal cancer patients with 2.9% (33/1,144) and 2.4% (8/332), respectively. Among patients with known cause of death (34/78; 44%), tumor progression (12/34; 35%) and pulmonary complications/causes (11/34; 35%) were most common. On multivariable regression analysis, a worse ECOG-PS was associated with a relatively earlier peri -radiotherapeutic death (p = 0.014)., Conclusion: Mortality during or within 30 days of curative-intent radio-(chemo-)therapy was low, yet highest for head and neck (2.9%) and gastrointestinal tumor (2.4%) patients. Reasons for these findings include rapid tumor progression in some cancers, good patient selection, with ECOG-PS being most useful and predictive for avoiding early mortality. Future research should help refine predictors for peri -RT mortality., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: STL received a research grant from Varian, honoraria from Varian, and her husband is employed at Varian. PB cited research grants to the institution from ViewRay Inc. (Mountain View, CA, USA). NA has received grants from ViewRay Inc. and BrainLab and personal fees from AstraZeneca, Debiopharm, ViewRay and BrainLab, and non-financial support from ViewRay, all outside of the submitted work. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

AbstractGlioma patients carry the burden of having both a progressive neurological disease and cancer, and may face a variety of symptoms, including depression and anxiety. These symptoms are highly prevalent in glioma patients (median point prevalence ranging from 16-41% for depression and 24-48% for anxiety when assessed by self-report questionnaires) and have a major impact on health-related quality of life and even overall survival time. A worse overall survival time for glioma patients with depressive symptoms might be due to tumor progression and/or its supportive treatment causing depressive symptoms, an increased risk of suicide or other (unknown) factors. Much is still unclear about the etiology of depressive and anxiety symptoms in glioma. These psychiatric symptoms often find their cause in a combination of neurophysiological and psychological factors, such as the tumor and/or its treatment. Although these patients have a particular idiosyncrasy, standard treatment guidelines for depressive and anxiety disorders apply, generally recommending psychological and pharmacological treatment. Only a few nonpharmacological trials have been conducted evaluating the efficacy of psychological treatments (eg, a reminiscence therapy-based care program) in this population, which significantly reduced depressive and anxiety symptoms. No pharmacological trials have been conducted in glioma patients specifically. More well-designed trials evaluating the efficacy of nonpharmacological treatments for depressive and anxiety disorders in glioma are urgently needed to successfully treat psychiatric symptoms in brain tumor patients and to improve (health-related) quality of life., Competing Interests: None of the authors declares a conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

End-of-Life Dreams and Visions Abstract: End-of life dreams and visions (ELDVs) or so-called death bed phenomena are transcendent experiences at the end of life that can be visual, auditory and/or kinesthetic, and often include visions of (deceased) loved ones, close friends or perceptions of places, travels, bright lights, or music. ELDVs typically occur weeks to hours prior to death and may comfort the dying and prepare spiritually for the end of life. Such experiences are frequently reported by dying individuals, the prevalence varying between 30 and 80%, but in the clinical context ELDVs are usually neglected, but interpreted and treated as pathological changes in the brain that result in, and from, delirium. This article tries to enlighten the occurrence, the contents and meanings of ELDVs in dying persons as opposed to delirium and night dreams using findings from the literature and from clinical observations. Implications of these conclusions for palliative care and the therapeutic relevance of ELDVs when taking care of dying individuals and their loved ones will also be discussed.

Background: This systematic review provides updated insights, from the published literature in the past 5 years, based on the 2017 European Association of Neuro-Oncology (EANO) guidelines for palliative care in adults with malignant brain tumors. It provides an overview of palliative care options, including during the end-of-life phase for patients with malignant brain tumors., Methods: A systematic literature search was conducted from 2016 to 2021 focusing on four main topics: (1) symptom management, (2) caregiver needs, (3) early palliative care, and (4) care in the end-of-life phase. An international panel of palliative care experts in neuro-oncology synthesized the literature and reported the most relevant updates. A total of 140 articles were included., Results: New insights include that: Hippocampal avoidance and stereotactic radiosurgery results in a lower risk of neurocognitive decline in patients with brain metastases; levetiracetam is more efficacious in reducing seizures than valproic acid as first-line monotherapy antiseizure drug (ASD) in glioma patients; lacosamide and perampanel seem well-tolerated and efficacious add-on ASDs; and a comprehensive framework of palliative and supportive care for high-grade glioma patients and their caregivers was proposed. No pharmacological agents have been shown in randomized controlled trials to significantly improve fatigue or neurocognition., Conclusions: Since the 2017 EANO palliative care guidelines, new insights have been reported regarding symptom management and end-of-life care, however, most recommendations remain unchanged. Early palliative care interventions are essential to define goals of care and minimize symptom burden in a timely fashion. Interventional studies that address pain, fatigue, and psychiatric symptoms as well as (the timing of) early palliative care are urgently needed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To summarize the available literature on using machine learning (ML) for palliative care practice as well as research and to assess the adherence of the published studies to the most important ML best practices. Methods: The MEDLINE database was searched for the use of ML in palliative care practice or research, and the records were screened according to PRISMA guidelines. Results: In total, 22 publications using machine learning for mortality prediction (n = 15), data annotation (n = 5), predicting morbidity under palliative therapy (n = 1), and predicting response to palliative therapy (n = 1) were included. Publications used a variety of supervised or unsupervised models, but mostly tree-based classifiers and neural networks. Two publications had code uploaded to a public repository, and one publication uploaded the dataset. Conclusions: Machine learning in palliative care is mainly used to predict mortality. Similarly to other applications of ML, external test sets and prospective validations are the exception.

During the Early to Middle Pleistocene, Java was inhabited by hominid taxa of great diversity. However, their seasonal dietary strategies have never been explored. We undertook geochemical analyses of orangutan (Pongo sp.), Homo erectus and other mammalian Pleistocene teeth from Sangiran. We reconstructed past dietary strategies at subweekly resolution and inferred seasonal ecological patterns. Histologically controlled spatially resolved elemental analyses by laser-based plasma mass spectrometry confirmed the preservation of authentic biogenic signals despite the effect of spatially restricted diagenetic overprint. The Sr/Ca record of faunal remains is in line with expected trophic positions, contextualizing fossil hominid diet. Pongo sp. displays marked seasonal cycles with ~3 month-long strongly elevated Sr/Ca peaks, reflecting contrasting plant food consumption presumably during the monsoon season, while lower Sr/Ca ratios suggest different food availability during the dry season. In contrast, omnivorous H. erectus shows low and less accentuated intra-annual Sr/Ca variability compared to Pongo sp., with δ 13 C data of one individual indicating a dietary shift from C 4 to a mix of C 3 and C 4 plants. Our data suggest that H. erectus on Java was maximizing the resources available in more open mosaic habitats and was less dependent on variations in seasonal resource availability. While still influenced by seasonal food availability, we infer that H. erectus was affected to a lesser degree than Pongo sp., which inhabited monsoonal rain forests on Java. We suggest that H. erectus maintained a greater degree of nutritional independence by exploiting the regional diversity of food resources across the seasons., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Accurate prediction of survival is important to facilitate clinical decision-making and improve quality of care at the end of life. While it is well documented that survival prediction poses a challenge for treating physicians, the need for clinically valuable predictive factors has not been met. This study aims to quantify the prevalence of patient transfer 72 h before death onto the acute palliative care unit in a tertiary care center in Switzerland, and to identify factors predictive of 72-h mortality., Methods: All patients hospitalized between January and December 2020 on the acute palliative care unit of the Competence Center Palliative Care of the Department of Radiation Oncology at the University Hospital Zurich were assessed. Variables were retrieved from the electronic medical records. Univariable and multivariable logistic regressions were used to identify predictors of mortality., Results: A total of 398 patients were screened, of which 188 were assessed. Every fifth patient spent less than 72 h on the acute palliative care unit before death. In multivariable logistic regression analysis, predictors for 72-h mortality after transfer were no prior palliative care consult (p = 0.011), no advance care directive (p = 0.044), lower performance status (p = 0.035), lower self-care index (p = 0.003), and lower blood albumin level (p = 0.026)., Conclusion: Late transfer to the acute palliative care unit is not uncommon, which can cause additional distress to patients and caretakers. Though clinically practical short-term survival predictors remain largely unidentified, early integration of palliative care should be practiced more regularly in patients with life-limiting illness., (© 2022. The Author(s).)

Purpose: There is limited information on treatment recommendations for glioblastoma patients with poor performance status. Here, we aim to evaluate the association of radiotherapy on survival in glioblastoma patients presenting with poor postoperative performance status in first-line setting., Methods: We retrospectively analyzed data of 93 glioblastoma patients presenting with poor postoperative performance status (ECOG 2-4) at the University Hospital Zurich, Switzerland, in the years 2005-2019. A total of 43 patients received radiotherapy with or without systemic therapy in the first-line setting, whereas 50 patients received no additive local or systemic treatment after initial biopsy or resection. Overall survival was calculated from primary diagnosis and from the end of radiotherapy. In addition, factors influencing survival were analyzed., Results: Median overall survival from primary diagnosis was 6.2 months in the radiotherapy group (95% CI 6.2-14.8 weeks, range 2-149 weeks) and 2.3 months in the group without additive treatment (95% CI 1.3-7.4 weeks, range 0-28 weeks) (p < 0.001). This survival benefit was confirmed by landmark analyses. Factors associated with overall survival were extent of resection and administration of radiotherapy with or without systemic treatment. Median survival from end of radiotherapy was 3 months (95% CI 4.3-21.7 weeks, range 0-72 weeks), with 25.6% (n = 11) early termination of treatment and 83.7% (n = 36) requiring radiotherapy as in-patients. Performance status improved in 27.9% (n = 12) of patients after radiotherapy., Conclusion: In this retrospective single-institution analysis, radiotherapy improved overall survival in patients with poor performance status, especially in patients who were amendable to neurosurgical resection., (© 2021. The Author(s).)

Background: As a first step to reach consensus on the key constructs and outcomes in neuro-oncology caregiver research, we performed a systematic review to evaluate the constructs that are being evaluated in research studies and how these have been assessed., Methods: All peer-reviewed publications with primary data reporting on outcomes of family caregivers of adult primary brain tumor patients were eligible. Electronic databases PubMed/Medline, Embase, Web of Science, Emcare, Cochrane Library, and PsycINFO were searched up to September 2021. Using Covidence, title and abstract screening, full-text review, and data extraction were done by two researchers independently, with a third guiding consensus. Constructs as reported in each study, and how these were assessed were the primary result., Results: Searches yielded 1090 unique records, with 213 remaining after title/abstract screening. Of these, 157 publications met inclusion criteria, comprising 120 unique studies. These originated from 18 countries and were published between 1996 and 2022. Most were observational (75%) cross-sectional (61%) studies, reporting on quantitative methods (62%). Twenty-seven different constructs were assessed and mapped along the Caregiver Health Model (CGHM) categories, namely, caregiver health, needs, tasks, beliefs and attitudes, and environment. Seventeen questionnaires were used >2 times to measure the same construct, with the vast majority of questionnaires only used across one or two studies., Conclusions: Neuro-oncology caregiving research is a field gaining traction, but lags behind in clear definition of key constructs, and consistency in assessment of these constructs. Developing consensus or guidance will improve comparability of studies, meta-analyses, and advance the science more quickly., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

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., Methods: 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  < .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  = .017) while there were no associations with hematologic toxicity, fatigue, or psychiatric adverse events., Conclusions: LEV is not associated with reduced tolerability of chemoradiotherapy in patients with glioblastoma regarding hematologic toxicity and fatigue. Antiemetic properties of LEV may be beneficial during maintenance temozolomide., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Cancer burdens not only the patients themselves but also their personal environment. A few studies have already focused on the mental health and personal needs of caregivers of patients. The purpose of this retrospective analysis was to further assess the emotional burden and unmet needs for support of caregivers in a population of brain metastasis patients. In the time period 2013-2020, we identified 42 informal caregivers of their respective patients after palliative radiation treatment for brain metastases. The caregivers completed two standardized questionnaires about different treatment aspects, their emotional burden, and unmet needs for support. Involvement of psycho-oncology and palliative care was examined in a chart review. The majority of the caregivers (71.4%, n = 30) suffered from high emotional burden during cancer treatment of their relatives and showed unmet needs for emotional and psychosocial support, mostly referring to information needs and the involvement in the patient's treatment decisions. Other unmet needs referred to handling personal needs and fears of dealing with the sick cancer patient in terms of practical care tasks and appropriate communication. Palliative care was involved in 30 cases and psycho-oncology in 12 cases. There is a high need for emotional and psychosocial support in informal caregivers of cancer patients. There might still be room for an improvement of psychosocial and psycho-oncological support. Care planning should cater to the emotional burden and unmet needs of informal caregivers as well. Further prospective studies in larger samples should be performed in order to confirm this analysis.

Introduction and Background: Choosing the right treatment for the right patient in a setting of metastatic cancer disease remains a challenge. To facilitate clinical decision-making, predictive tools have been developed to personalize treatment. Here, we aim to assess the use of the recently proposed "METSSS score" as a prognostic tool for overall survival of cancer patients after palliative radiotherapy in the last phase of life., Methods: All patients treated with palliative radiotherapy at the end-of-life at the Department of Radiation Oncology of the University Hospital Zurich between January 2010 and December 2019 were included in this study. Data on demographics, diagnosis, treatment and comorbidities was extracted from the treatment planning and the electronical medical records system. To statistically assess the validity of the "METSSS score", the mortality risk score was calculated, followed by stratification of all patients to prognostic risk groups. The prediction of the 1-year overall survival estimates was subsequently calculated., Results: Over the past decade, 274 patients have received palliative radiotherapy during the end-of-life period. One third of patients was female (34%, n = 93). The most frequent primary tumor was lung cancer (n = 121, 44%), and 55% of patients (n = 152) had no comorbidities according to the Charlson-Deyo comorbidity index. The most common radiotherapy site was the brain and eye region (42%, n = 115). The median actual overall survival of all patients was 40 days from the start of radiotherapy. The "METSSS score" survival model predicted that 269 patients (98.1%) belong into the high-risk, four patients (1.5%) into the medium-risk, and one patient (0.4%) into the low-risk group. The predicted median 1-year overall survival was 10%., Discussion: The METSSS score correctly predicted the survival of our end-of-life patient cohort by assigning them into the highest risk category, and it can therefore serve as a decision-making tool when assigning patient to symptomatic radiotherapy., Competing Interests: NA received research support from ViewRay, BrainLab, SNF, the Swiss Cancer League, the Staffanini Foundation, and received honoraria from ViewRay, AstraZeneca, BrainLab, and Debiopharm., (© 2022 The Authors.)

Objectives: Virtual reality (VR) opens a variety of therapeutic options to improve symptom burden in patients with advanced disease. Until to date, only few studies have evaluated the use of VR therapy in the context of palliative care. This case series aims to evaluate the feasibility and acceptability of VR therapy in a population of palliative care patients., Methods: In this single-site case series, we report on six palliative care patients undergoing VR therapy. The VR therapy consisted of a one-time session ranging between 20 to 60 minutes depending on the patient's needs and the content chosen for the VR sessions. A semi-structured survey was conducted and the Edmonton Symptom Assessment System (ESAS) and the Distress Thermometer were performed pre- and post-intervention., Results: Overall, VR therapy was well accepted by all patients. Five out of six patients reported having appreciated VR therapy. There were individual differences of perceived effects using VR therapy. The semi-structured survey revealed that some patients felt a temporary detachment from their body and that patients were able to experience the VR session as a break from omnipresent worries and the hospital environment ("I completely forgot where I am"). There was a considerable reduction in the total ESAS score post-treatment (T0 ESAS Tot  = 27.2; T1 ESAS Tot  = 18.8) and a slightly reduction in distress (T0 DT Tot  = 4.4; T1 DT Tot  = 3.8). However, two patients were more tired after the intervention.Significance of Results: Our preliminary results demonstrate that VR therapy is acceptable, feasible and safe for use within a palliative care population and appears to be a viable treatment option. Clinical trials are both warranted and necessary to confirm any therapeutic effects of VR therapy, as is the need to tailor VR systems better for use in palliative care settings.

Background: Treatment of metastatic cancer patients with multiple repeat courses of radiotherapy has become more frequent due to their improved overall survival. However, very little is known about their long-term outcome. This analysis reports on the quality-of-life, hematologic toxicity, patient-reported experiences and satisfaction, and psychological distress of cancer patients treated with multiple repeat radiotherapy., Methods: All patients treated with ≥5 courses of radiotherapy between 2011 and 2019 at the Department of Radiation Oncology, University Hospital Zurich (USZ) were screened for this study. A course of radiotherapy was defined as all treatment sessions to one anatomical site under one medical indication. All patients completed two questionnaires: EORTC QLQ-C30 questionnaire for quality-of-life and a questionnaire evaluating psychological distress and patient-reported experiences. Hematologic toxicities were assessed via a recent blood sample., Results: Of n = 33 patients treated with ≥5 radiotherapy courses and being alive, 20 (60.6%) participated in this study. The most common primary tumor was non-small cell lung cancer (n = 14, 42.4%). The most common sites of irradiation were brain (n = 78, 37.1%) and bone metastases (n = 59, 28.1%). All participating patients reported that they had experienced a subjective benefit from multiple repeat radiotherapy and denied increased side effects in later radiotherapy courses. Yet, 45% (n = 9) of the patients reported an increase of psychological distress with increasing numbers of radiotherapy treatments. While global health status was stable, patients having received multiple repeat radiotherapy reported increased fatigue (p = <0.006). Blood analysis showed significantly reduced hemoglobin and lymphocyte levels compared to the healthy population (p = <0.03)., Discussion and Conclusion: Patient-reported experiences and satisfaction of long-term cancer patients treated with multiple repeat radiotherapy are positive. However, increased levels of fatigue and significantly reduced hemoglobin and lymphocyte levels were observed. These data indicate the need to further investigate the effects of multiple courses of radiotherapy in chronic cancer patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Pro-tumorigenic electrochemical synapses between neurons and brain tumour cells in preclinical studies suggest unfavourable effects of epilepsy on patient survival. We investigated associations of epilepsy and survival in three cohorts of brain tumour patients (meningioma, glioblastoma and brain metastases). Cohorts were segregated into three groups for comparative analyses: (i) no epilepsy; (ii) epilepsy without status epilepticus; and (iii) status epilepticus. Status epilepticus was considered a surrogate of extensive neuronal hyperexcitability. The main outcome was progression-free survival (meningioma) and overall survival (glioblastoma and brain metastases), adjusted for established prognostic factors and onset of epilepsy by time-dependent multivariate Cox modelling. The primary analysis population comprised 1792 patients (742 meningioma, 249 glioblastoma, 801 brain metastases). Epilepsy was associated with favourable prognostic factors. However, on multivariate analyses, status epilepticus was associated with inferior overall survival of patients with glioblastoma [status epilepticus versus no epilepsy multivariate hazard ratio (HR) 3.72, confidence interval (CI) 1.78-7.76, P < 0.001] and brain metastases (status epilepticus versus no epilepsy HR 2.30, CI 1.10-4.79, P = 0.026). Among brain metastases patients, but not among patients with meningioma or glioblastoma, epilepsy was similarly associated with inferior overall survival (epilepsy versus no epilepsy HR 2.16, CI 1.60-2.93, P < 0.001). We conclude that epilepsy may convey inferior survival of patients with malignant brain tumours., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction and Background: As cancer is developing into a chronic disease due to longer survival, continuity and coordination of oncological care are becoming more important for patients. As radiation oncology departments are an integral part of cancer care and as repeat irradiation becomes more commonplace, the relevance of continuity and coordination of care in operating procedures is increasing. This study aims to perform a single-institution analysis of cancer patients in which continuity and coordination of care matters most, namely the highly selected group with multiple repeat course radiotherapy throughout their chronic disease., Materials and Methods: All patients who received at least five courses of radiotherapy at the Department of Radiation Oncology at the University Hospital Zurich from 2011 to 2019 and who were alive at the time of the initiation of this project were included into this study. Patient and treatment characteristics were extracted from the hospital information and treatment planning systems. All patients completed two questionnaires on continuity of care, one of which was designed in-house and one of which was taken from the literature., Results: Of the 33 patients identified at baseline, 20 (60.6%) participated in this study. A median of 6 years (range 3-13) elapsed between the first and the last visit at the cancer center. The median number of involved primary oncologists at the radiation oncology department was two (range 1-5). Fifty-seven percent of radiation therapy courses were preceded by a tumor board discussion. Both questionnaires showed high levels of experienced continuity of care. No statistically significant differences in experienced continuity of care between groups with more or less than two primary oncologists was found., Discussion and Conclusion: Patients treated with multiple repeat radiation therapy at our department over the past decade experienced high levels of continuity of care, yet further efforts should be undertaken to coordinate care among oncological disciplines in large cancer centers through better and increased use of interdisciplinary tumor boards., (© 2021. The Author(s).)

Palliative Care in Neurology Abstract. Neurology as a discipline clearly overlaps with palliative care. Nevertheless, an early integration of palliative care accompanying neurological treatment rarely takes place, and there are still misunderstandings with regard to the timing of the inclusion of palliative care and its role beyond pure end-of-life care and hospice care. A further expansion and use of synergies should become an integral part of both disciplines in the coming years, and training should focus on appropriate training, especially for our young medical colleagues.

Background: Radiotherapy plays an important role for symptom control in advanced stage cancer patients. Yet patients need to be carefully selected, and its use and benefits must be weighed against time spent under treatment and patient priorities in the last phase of life. In this study, we assess prevalence, indications and outcomes of radiotherapy close to death., Methods: We screened all radiotherapy treatments performed at the Department of Radiation Oncology of the University Hospital Zurich between January 2010 and December 2019 to identify those which occurred near patients' end-of-life. Analyzed data was extracted from the database of the Comprehensive Cancer Center Zurich, the treatment planning system Aria® and the electronical medical records system KISIM®., Results: Within 60 days of death, 377 radiotherapy courses were prescribed to 280 patients, which constitutes 3.4% of all radiotherapy courses administered over the last decade at our department. Within 60-31, 30-8, and 7-0 days to death 164, 159, and 54 radiotherapy courses were prescribed, respectively. The most frequent treatment sites were brain (N = 122, 32%) and bone (N = 119, 32%), and there was no statistically significant difference in treatment site between the three sub-groups. The most common regimen was 10x3Gy (N = 130, 35%) in all three sub-groups (p = 0.23). Radiotherapy finished more than one week before death was associated with high completion rates (>80%) and treatment benefit (>55%)., Conclusion: Patient selection and survival prognostication remains challenging for radiation oncologists. While radiotherapy achieved high completion and success rates until one week before death, treatment within one week of death should be restricted to carefully selected patients or avoided altogether., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Understanding hominin expansions requires the comprehension of movement processes at different scales. In many models of hominin expansion these processes are viewed as being determined by large-scale effects, such as changes in climate and vegetation spanning continents and thousands or even millions of years. However, these large-scale patterns of expansions also need to be considered as possibly resulting from the accumulation of small-scale decisions of individual hominins. Moving on a continental scale may for instance involve crossing a water barrier. We present a generalized agent-based model for simulating the crossing of a water barrier where the agents represent the hominin individuals. The model can be configured to represent a variety of movement modes across water. Here, we compare four different behavioral scenarios in conjunction with a set of water barrier configurations, in which agents move in water by either paddling, drifting, swimming or rafting. We introduce the crossing-success-rate (CSR) to quantify the performance in water crossing. Our study suggests that more focus should be directed towards the exploration of behavioral models for hominins, as directionality may be a more powerful factor for crossing a barrier than environmental opportunities alone. A prerequisite for this is to perceive the opposite shore. Furthermore, to provide a comprehensive understanding of hominin expansions, the CSR allows for the integration of results obtained from small-scale simulations into large-scale models for hominin expansion., Competing Interests: The authors have declared that no competing interest exist.

Objective: Delirium is a frequent complication in advanced cancer patients, among whom it is frequently underdiagnosed and inadequately treated. To date, evidence on risk factors and the prognostic impact of delirium on outcomes remains sparse in this patient population., Method: In this prospective observational cohort study at a single tertiary-care center, 1,350 cancer patients were enrolled. Simple and multiple logistic regression models were utilized to identify associations between predisposing and precipitating factors and delirium. Cox proportional-hazards models were used to estimate the effect of delirium on death rate., Results: In our patient cohort, the prevalence of delirium was 34.3%. Delirium was associated inter alia with prolonged hospitalization, a doubling of care requirements, increased healthcare costs, increased need for institutionalization (OR 3.22), and increased mortality (OR 8.78). Predisposing factors for delirium were impaired activity (OR 10.82), frailty (OR 4.75); hearing (OR 2.23) and visual impairment (OR 1.89), chronic pneumonitis (OR 2.62), hypertension (OR 1.46), and renal insufficiency (OR 1.82). Precipitating factors were acute renal failure (OR 7.50), pressure sores (OR 3.78), pain (OR 2.86), and cystitis (OR 1.32). On multivariate Cox regression, delirium increased the mortality risk sixfold (HR 5.66). Age ≥ 65 years and comorbidities further doubled the mortality risk of delirious patients (HR 1.77; HR 2.05)., Significance of Results: Delirium is common in cancer patients and associated with increased morbidity and mortality. Systematically categorizing predisposing and precipitating factors might yield new strategies for preventing and managing delirium in cancer patients.

Objectives: Patients with terminal illness are at high risk of developing delirium, in particular, those with multiple predisposing and precipitating risk factors. Delirium in palliative care is largely under-researched, and few studies have systematically assessed key aspects of delirium in elderly, palliative-care patients., Methods: In this prospective, observational cohort study at a tertiary care center, 229 delirious palliative-care patients stratified by age: <65 (N = 105) and ≥65 years (N = 124), were analyzed with logistic regression models to identify associations with respect to predisposing and precipitating factors., Results: In 88% of the patients, the underlying diagnosis was cancer. Mortality rate and median time to death did not differ significantly between the two age groups. No inter-group differences were detected with respect to gender, care requirements, length of hospital stay, or medical costs. In patients ≥65 years, exclusively predisposing factors were relevant for delirium, including hearing impairment [odds ratio (OR) 3.64; confidence interval (CI) 1.90-6.99; P < 0.001], hypertension (OR 3.57; CI 1.84-6.92; P < 0.001), and chronic kidney disease (OR 4.84; CI 1.19-19.72; P = 0.028). In contrast, in patients <65 years, only precipitating factors were relevant for delirium, including cerebral edema (OR 0.02; CI 0.01-0.43; P = 0.012)., Significance of Results: The results of this study demonstrate that death in delirious palliative-care patients occurs irrespective of age. The multifactorial nature and adverse outcomes of delirium across all age in these patients require clinical recognition. Potentially reversible factors should be detected early to prevent or mitigate delirium and its poor survival outcomes.

We report on a patient suffering from seizures caused by cerebral metastases of adenocarcinoma of the lung. Initially, the patient was treated effectively with oral levetiracetam. As the disease progressed, oral intake was no longer possible. Since levetiracetam had controlled the patient's seizures well, the medication delivery mode was switched first to intravenous application, followed by a return to oral administration. After further deterioration, subcutaneous levetiracetam application was used to control epileptic symptoms while avoiding the sedating effects of subcutaneous midazolam. Subcutaneous levetiracetam allowed for stable seizure control in the end-of-life situation. Serum levels of levetiracetam were assessed for all application conditions and demonstrate that therapeutic drug levels can be reached by subcutaneous application. This report from a tertiary care center in Switzerland adds to the sparse but growing evidence base for the use of subcutaneous levetiracetam to manage seizures in palliative and end-of-life care., Competing Interests: No competing financial interests exist., (© Sophia Westphal et al., 2021; Published by Mary Ann Liebert, Inc.)

Objective: The management of brain tumour patients who would like to resume driving is complex, and needs multidisciplinary input and a consensus among treating physicians. The Swiss Neuro-Oncology Society (SwissNOS) and the Swiss Society for Legal Medicine (SGRM) aim to provide guidance on how to assess “fitness-to-drive” of glioblastoma patients and to harmonise the relevant procedures in Switzerland., Methods: At several meetings, Swiss neuro-oncologists discussed common practices on how to advise patients with a stable, i.e., non-progressive, glioblastoma, who wish to resume driving after the initial standard tumour treatment. All participants of the SwissNOS meetings were invited twice to return a questionnaire (modified Delphi process) on specific tools/procedures they commonly use to assess “fitness-to-drive” of their patients. Answers were analysed to formulate a tentative consensus for a structured and reasonable approach., Results: Consensus on minimum requirements for a “fitness-to-drive” programme for glioblastoma patients could be reached among Swiss neuro-oncologists. The recommendations were based on existing guidelines and expert opinions regarding patients with seizures, visual disturbances, cognitive impairment or focal deficits for safe driving. At this point in time, the Swiss neuro-oncologists agreed on the following requirements for glioblastoma patients after the initial standard therapy and without a seizure for at least 12 months: (1) stable cranial magnetic resonance imaging (MRI) according to Response Assessment in Neuro-Oncology (RANO) criteria, to be repeated every 3 months; (2) thorough medical history, including current or new medication, a comprehensive neurological examination at baseline (T0) and every 3 months thereafter, optionally an electrocencephalogram (EEG) at baseline; (3) ophthalmological examination including visual acuity and intact visual fields; and (4) optional neuropsychological assessment with a focus on safe driving. Test results have to be compatible with safe driving at any time-point. Patients should be informed about test results and optionally sign a document., Conclusions: We propose regular thorough clinical neurological examination and brain MRI, optional EEG, neuropsychological and visual assessments to confirm “fitness-to-drive” for glioblastoma patients after initial tumour-directed therapy. The proposed “fitness-to-drive” assessments for glioblastoma patients serves as the basis for a prospective Swiss Pilot Project GLIODRIVE (BASEC ProjectID 2020-00365) to test feasibility, adherence and safety in a structured manner for patients who wish to resume driving. Research will focus on confirming the usefulness of the proposed tools in predicting “fitness-to-drive” and match results with events obtained from the road traffic registry (Strassenverkehrsamt).

Patient-reported outcomes (PROs) are important tools in patient-centred medicine and allow for individual assessment of symptom burden and aspects of patients' quality of life. While sex and gender differences have emerged in preclinical and clinical medicine, these differences are not adequately represented in the development and use of patient-reported outcome measures. However, even in personalised approaches, undesirable biases may occur when samples are unbalanced for certain characteristics, such as sex or gender. This review summarises the current status of the literature and trends in PROs with a focus on sex and gender aspects., Competing Interests: Competing interests: None declared., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Background: O6-methylguanine DNA-methyl transferase (MGMT) promoter methylation status is predictive for alkylating chemotherapy, but there are non-benefiting subgroups., Methods: This is the long-term update of NOA-08 (NCT01502241), which compared efficacy and safety of radiotherapy (RT, n = 176) and temozolomide (TMZ, n = 193) at 7/14 days in patients >65 years old with anaplastic astrocytoma or glioblastoma. DNA methylation patterns and copy number variations were assessed in the biomarker cohort of 104 patients and in an independent cohort of 188 patients treated with RT+TMZ-containing regimens in Heidelberg., Results: In the full NOA-08 cohort, median overall survival (OS) was 8.2 [7.0-10.0] months for TMZ treatment versus 9.4 [8.1-10.4] months for RT; hazard ratio (HR) = 0.93 (95% CI: 0.76-1.15) of TMZ versus RT. Median event-free survival (EFS) [3.4 (3.2-4.1) months vs 4.6 (4.2-5.0) months] did not differ, with HR = 1.02 (0.83-1.25). Patients with MGMT methylated tumors had markedly longer OS and EFS when treated with TMZ (18.4 [13.9-24.4] mo and 8.5 [6.9-13.3] mo) versus RT (9.6 [6.4-13.7] mo and 4.8 [4.3-6.2] mo, HR 0.44 [0.27-0.70], P < 0.001 for OS and 0.46 [0.29-0.73], P = 0.001 for EFS). Patients with glioblastomas of the methylation classes receptor tyrosine kinase I (RTK I) and mesenchymal subgroups lacked a prognostic impact of MGMT in both cohorts., Conclusion: MGMT promoter methylation is a strong predictive biomarker for the choice between RT and TMZ. It indicates favorable long-term outcome with initial TMZ monotherapy in patients with MGMT promoter-methylated tumors primarily in the RTK II subgroup., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Delirium is a common complication in palliative care patients, especially in the terminal phase of the illness. To date, evidence regarding risk factors and prognostic outcomes of delirium in this vulnerable population remains sparse., Method: In this prospective observational cohort study at a tertiary care center, 410 palliative care patients were included. Simple and multiple logistic regression models were used to identify associations between predisposing and precipitating factors and delirium in palliative care patients., Results: The prevalence of delirium in this palliative care cohort was 55.9% and reached 93% in the terminally ill. Delirium was associated with prolonged hospitalization (p < 0.001), increased care requirements (p < 0.001) and health care costs (p < 0.001), requirement for institutionalization (OR 0.11; CI 0.069-0.171; p < 0.001), and increased mortality (OR 18.29; CI 8.918-37.530; p < 0.001). Predisposing factors for delirium were male gender (OR 2.19; CI 1.251-3.841; p < 0.01), frailty (OR 15.28; CI 5.885-39.665; p < 0.001), hearing (OR 3.52; CI 1.721-7.210; p < 0.001), visual impairment (OR 3.15; CI 1.765-5.607; p < 0.001), and neoplastic brain disease (OR 3.63; CI 1.033-12.771; p < 0.05). Precipitating factors for delirium were acute renal failure (OR 6.79; CI 1.062-43.405; p < 0.05) and pressure sores (OR 3.66; CI 1.102-12.149; p < 0.05)., Significance of Results: Our study identified several predisposing and precipitating risk factors for delirium in palliative care patients, some of which can be targeted early and modified to reduce symptom burden.

Purpose: Little is known about efficacy and toxicity of radiation therapy in the elderly, as the vast majority of prospective trials excluded patients aged over 70 years. The aim of this study was to investigate the outcome of radiation therapy in a group of so-called oldest old cancer patients (≥85 years)., Materials and Methods: We retrospectively reviewed data from patients aged ≥85 years, treated between 2010 and 2015 for any tumor histology at the University Hospital Zurich, Switzerland. Overall survival (OS), relapse-free survival (RFS), performance status (ECOG), Charlson comorbidity index (CCI) and treatment tolerance were assessed., Results: We identified and included 100 patients with a mean age of 88 years (range: 85-102 years). Most patients received a curative-intent treatment (n = 64, 64%). About one third received palliative radiation therapy for symptomatic metastatic disease (n = 36, 36%). Curative treatment was well tolerated, with no high-grade acute toxicities (≥grade 4). Median OS was 52.6 and 13.1 months for the curative and palliative treated patient groups, respectively. 5‑year OS for all patients was 39.5% (95% CI: 23.6-54.5%). The Charlson comorbidity index (CCI) had a predictive value for overall survival (CCI > 10, p = 0.0001) in the curative group., Conclusion: The number of older cancer patients will increase considerably in the next decades because of demographic changes. Our analysis supports the notion that radiation therapy for this patient group of oldest old cancer patients is feasible in general. Treatment decisions should not be based on chronological age but rather on comorbidities and functional status.

In recent years, research on artificial intelligence (AI) in medicine has seen great advances, especially with regards to the detection of diseases [...].

Purpose: Gliomas are primary brain tumors with a life-limiting course of disease, and the last weeks of life are often characterized by neurological deficits that affect communication and personality. End-of-life treatment in this patient group therefore requires specific approaches. To date, little data is available on patients' and caregivers' needs and experiences in the last phase of the disease., Methods: In this observational study, relatives of patients treated at the University Hospital Zurich, Switzerland and deceased 2015-2017 due to glioma progression were contacted to complete a structured questionnaire assessing caregivers experience within the last weeks of the disease., Results: The survey was sent to 120 relatives of deceased patients with a glioma (WHO grades II-IV) (median patient age: 62 years; 73.8% male). Forty-three questionnaires were returned (37.7%). Approximately half of the patients were taken care of at home in the last 4 weeks of the disease, mainly with the assistance of in-home nursing care, of which eventually 14 patients (63.6%) died at home. While caregivers reported high satisfaction with medical and nursing care, psychological support was rated average to poor on a 10-point scale. Free comment fields were used widely, revealing open questions and needs of the relatives., Conclusions: This study illustrates the need for a more patient-centered end-of-life care including higher psychological support mechanisms, and a higher inclusion and consideration of relatives and caregivers into the care focus. Earlier discussion of end-of-life preferences could prevent hospitalizations in the last phase of life and could improve patients' and caregivers' quality of life.

Background: Antidepressant drugs have shown antitumor activity in preclinical glioblastoma studies. Antidepressant drug use, as well as its association with survival, in glioblastoma patients has not been well characterized on a population level., Methods: Patient characteristics, including the frequency of antidepressant drug use, were assessed in a glioblastoma cohort diagnosed in a 10-year time frame between 2005 and 2014 in the Canton of Zurich, Switzerland. Cox proportional hazards regression models were applied for multivariate analysis. Kaplan-Meier survival curves were used to estimate overall survival (OS) data and the log-rank test was performed for comparisons., Results: A total of 404 patients with isocitrate dehydrogenase wild-type glioblastoma were included in this study. Sixty-five patients (16.1%) took antidepressant drugs at some point during the disease course. Patients were most commonly prescribed selective serotonin reuptake inhibitors at any time (N = 46, 70.8%). Nineteen patients (29.2%) were on antidepressant drugs at the time of their tumor diagnosis. No differences were observed in OS between those patients who had taken antidepressants at some point in their disease course and those who had not ( P  = .356). These data were confirmed in a multivariate analysis including age, Karnofsky Performance Scale (KPS), sex, extent of resection, O 6 -methylguanine DNA methyltransferase ( MGMT ) promoter methylation status, and first-line treatment as cofounders ( P  = .315). Also, there was no association of use of drugs modulating voltage-dependent potassium channels (citalopram; escitalopram) with survival ( P  = .639)., Conclusions: This signal-seeking study does not support the hypothesis that antidepressants have antitumor efficacy in glioblastoma on a population level., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)