Family caregiver constructs and outcome measures in neuro-oncology: A systematic review

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

Outpatient Palliative Care Service Involvement: A Five-Year Experience from a Tertiary Hospital in Switzerland

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

Limitation of life sustaining measures in neurocritical care: sex, timing, and advance directive

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. Key words: Redirection of Care, Palliation, Neurocritical Care, Sex Difference

Lenalidomide in cancer cachexia: a randomized trial of an anticancer drug applied for anti-cachexia

Background Cancer cachexia (CC) impacts quality of life, physical function, anticancer treatment response, and survival. Inflammation is a prominent pathomechanism of CC. This small-scale study sets out to investigate the immunomodulatory drug lenalidomide in inflammatory CC in a randomized, double-blind, placebo-controlled trial. Methods Patients with advanced solid malignancies, documented weight loss, no or unchanged anticancer treatment, and C-reactive protein > 30 mg/L were included. In a 2:2:1 randomization, patients received either lenalidomide 25 mg once daily or C-reactive protein-guided dose, starting with 5 mg lenalidomide once daily or placebo once a day for 8 weeks. Dose adaption and safety were assessed twice a week. Treatment response was defined as an increase of lean body mass of more than 2% in a lower lumbar computed tomography and an increase in dynamometer-assessed handgrip strength of 4 kg. Secondary endpoints included adverse events, C-reactive protein response, nutritional intake, and symptoms. Results Of 24 eligible patients, 16 were included (25% female). At baseline, the mean age was 67 (range 51–88) years, and mean body weight was 64.7 kg (range 39.8–87.2 kg). Five were diagnosed with mesothelioma, two with non-small-cell lung cancer, two with renal cell carcinoma, two with neuroendocrine tumours, and five with other malignancies. Mean survival was 43 days. Eleven adverse events (four of which were severe) were recorded with a probable link to study participation. Nine patients completed the study. No participant showed a treatment response. C-reactive protein-guided dosing did not result in lower doses of lenalidomide. Lean body mass decreased less in the treatment groups. For the lenalidomide and placebo groups respectively, handgrip strength decreased by 2.3 vs. 5.5 kg, nutritional intake decreased by 249 vs. 32 kcal/day, and C-reactive protein increased by 35 mg/dL vs. decreased by 17 mg/dL. The study was closed prematurely due to slow accrual and the need for concurrent anticancer treatments. Conclusions No treatment response on muscle mass and muscle strength was observed with lenalidomide. Because of several limiting factors, including low recruitment caused in part by an ambitious study design and concomitant anticancer treatment, this study did not generate adequate data to draw reliable conclusions

Prevalence and predictors for 72-h mortality after transfer to acute palliative care unit

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

Quality-of-life and toxicity in cancer patients treated with multiple courses of radiation therapy

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

Antidepressant drug use in glioblastoma patients: an epidemiological view.

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

Ist eine Handlungsempfehlung für den Einsatz von Ketamin / Esketamin zur Behandlung von Depression und Angst in der Palliative Care möglich?

Aufgrund der oft limitierten Lebenserwartung von Patientinnen und Patienten in der Palliative Care stellt sich insbesondere in Bezug auf die Behandlung möglicher psychischer Störungen wie Depression oder Angst die Herausforderung rasch wirksamer und möglichst einfach zu applizierender Medikamente. Ziel dieser Arbeit ist es, die aktuelle Literatur und ausgewählte Leitlinien in Hinblick auf Evidenz bezüglich Einsatz von Ketamin und Esketamin als Medikamente zur Behandlung von Depression und Angststörung bei palliativen Patientinnen und Patienten zu untersuchen

Acceptance of Digital Health Technologies in Palliative Care Patients

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

MiR-16-5p is frequently down-regulated in astrocytic gliomas and modulates glioma cell proliferation, apoptosis, and response to cytotoxic therapy

AIMS Aberrant expression of microRNAs (miRNAs) is frequent in various cancers including gliomas. We aimed to characterize the role of miR-16-5p as a candidate tumour suppressor miRNA in gliomas. METHODS Real-time PCR-based approaches were used for miRNA and mRNA expression profiling of glioma and non-neoplastic brain tissues as well as glioma cell lines. Protein levels were determined by Western blotting. In vitro analyses were performed following overexpression of miR-16-5p, trichostatin A treatment, and siRNA-mediated knock-down of HDAC3 in glioma cells. Effects of miR-16-5p on glioma cell viability, apoptosis and response to irradiation and temozolomide were assessed. RESULTS Expression of miR-16-5p was reduced relative to control brain tissue in isocitrate dehydrogenase (IDH)-mutant astrocytomas of World Health Organization (WHO) grades II, III, and IV, and a subset of IDH-wildtype glioblastomas WHO grade IV. MiR-16-5p expression was lower in IDH-mutant than in IDH-wildtype gliomas, and down-regulated in IDH-wildtype glioma lines. MiR-16-5p overexpression reduced expression of important cell cycle and apoptosis regulators in glioma cells, including CDK6, CDC25A, CCND3, CCNE1, WEE1, CHEK1, BCL2, and MCL1. In line, CDK6, WEE1, CHEK1, BCL2, and MCL1 transcript levels were increased in WHO grade III or IV gliomas. Trichostatin A treatment and HDAC3 knockdown in glioma cells induced miR-16-5p up-regulation and reduced expression of its targets. Moreover, miR-16-5p overexpression inhibited proliferation and induced apoptosis in various glioma cell lines and increased sensitivity of A172 glioma cells to irradiation and temozolomide. CONCLUSION Reduced expression of miR-16-5p contributes to glioma cell proliferation, survival, and resistance to cytotoxic therapy. This article is protected by copyright. All rights reserved