BACKGROUND AND PURPOSE:External beam radiotherapy (EBRT) is a well-established and effective intervention for pain palliation in patients with bone metastases. Variability in trial endpoints, however, has limited comparability and synthesis of available evidence. To address this, the International Bone Metastases Consensus Working Party published endpoint guidelines in 2002 and updated them in 2012. This study aims to review, re-evaluate, and update the existing consensus to reflect contemporary clinical practice and technological advances. MATERIALS AND METHODS:A modified Delphi process was undertaken, informed by a systematic literature review and post-2012 guideline publications. An electronic survey was distributed to previous contributors and internationally recognized bone EBRT experts. In Phase I, statements achieving ≥ 75 % agreement were accepted. Items not reaching consensus were refined by the Working Party, discussed by a core panel of eight experts, and recirculated in Phase II. Descriptive statistics summarized response rates and agreement levels. RESULTS:Of 125 experts invited, 58 participated in Phase I, and 44 in Phase II. Consensus was achieved for 38 out of 49 statements (78%), including 18 new or revised items. Key recommendations addressed eligibility criteria for trial enrolment, standardized pain and analgesic assessments, specification of radiation techniques and dose schedules, follow-up intervals, assessment timing and modalities, and incorporation of cost-effectiveness analyses. CONCLUSION:This updated consensus provides a contemporary, standardized framework for EBRT trial design and reporting in bone metastases. Adoption will improve cross-study comparability and guide future research priorities. Regular updates are planned to ensure alignment with evolving clinical practice and technology.

Background: Palliative sedation has major clinical, social and ethical implications. Vicariously witnessing suffering in others is known to be distressing. However, little is understood about how palliative sedation is experienced by relatives and health care professionals. Objectives: To explore the experiences of relatives and health care professionals with palliative sedation. Design: A qualitative design with thematic framework analysis of data collected in semistructured interviews. Setting/participants: Research was conducted in seven specialist in-patient palliative care services in Belgium, Germany, Italy, the Netherlands, and Spain. A bereaved relative and health care provider linked to a deceased patient with cancer who had palliative sedation was recruited. Measurements: We coded transcripts and characterized factors that arose during the process of palliative sedation. Results: We interviewed 66 people (33 relatives and 33 health care professionals) linked to 33 deceased patients. Three main themes were identified: (1) Understanding the aim of palliative sedation among relatives and health care professionals such as to alleviate suffering, dying with dignity, (2) Palliative sedation is a complex process, accompanied by many uncertainties, which can cause distress for both relatives and health care providers such as eligibility of the patient, when to start or the effectiveness of palliative sedation, (3) Sedation involves a period of intense family communication, collaboration, and caregiving with heightened mixed emotions. Opportunities to say goodbye before starting palliative sedation were important. Conclusion: Relatives and health care professionals focused on the effectiveness of palliative sedation in alleviating suffering and offering a dignified death. It was described as complex, with mixed experiences of relief and distress.

ObjectivesThis study aims to provide an in-depth understanding of the content and process of decision-making about palliative sedation for existential suffering (PS-ES) as perceived by Belgian palliative care physicians. MethodsThis Belgian nationwide qualitative study follows a grounded theory approach. We conducted semistructured interviews with 25 palliative care physicians working in 19 Belgian hospital-based palliative care units and 4 stand-alone hospices. We analyzed the data using the Qualitative Analysis Guide of Leuven, and we followed the Consolidated Criteria for Reporting Qualitative Research Guidelines (COREQ). ResultsAnalysis of the data identified several criteria that physicians apply in their decision-making about PS-ES, namely, the importance of the patient's demand, PS-ES as a last resort option after all alternatives have been applied, the condition of unbearable suffering combined with other kinds of suffering, and the condition of being in a terminal stage. Regarding the process of decision-making itself, physicians refer to the need for multidisciplinary perspectives supported by an interpretative dialogue with the patient and all other stakeholders. The decision-making process involves a specific temporality and physicians' inner conviction about the need of PS-ES. Significance of resultsBelgian palliative care physicians are not sure about the criteria regarding decision-making in PS-ES. To deal with complex existential suffering in end-of-life situations, they stress the importance of participation by all stakeholders (patient, relatives, palliative care team, other physicians, nurses, social workers, physiotherapists, occupational therapists, chaplains, etc.) in the decision-making process to prevent inadequate decisions being made.

BACKGROUND:The European Association for Palliative Care (EAPC) acknowledges palliative sedation as an important, broadly accepted intervention for patients with life-limiting disease experiencing refractory symptoms. The EAPC therefore developed 2009 a framework on palliative sedation. A revision was needed due to new evidence from literature, ongoing debate and criticism of methodology, terminology and applicability.AIM:To provide evidence- and consensus-based guidance on palliative sedation for healthcare professionals involved in end-of-life care, for medical associations and health policy decision-makers.DESIGN:Revision between June 2020 and September 2022 of the 2009 framework using a literature update and a Delphi procedure.SETTING:European.PARTICIPANTS:International experts on palliative sedation (identified through literature search and nomination by national palliative care associations) and a European patient organisation.RESULTS:A framework with 42 statements for which high or very high level of consensus was reached. Terminology is defined more precisely with the terms suffering used to encompass distressing physical and psychological symptoms as well as existential suffering and refractory to describe the untreatable (healthcare professionals) and intolerable (patient) nature of the suffering. The principle of proportionality is introduced in the definition of palliative sedation. No specific period of remaining life expectancy is defined, based on the principles of refractoriness of suffering, proportionality and independent decision-making for hydration. Patient autonomy is emphasised. A stepwise pharmacological approach and a guidance on hydration decision-making are provided.CONCLUSIONS:This is the first framework on palliative sedation using a strict consensus methodology. It should serve as comprehensive and soundly developed information for healthcare professionals.

BackgroundPalliative sedation refers to the proportional use of titrated medication which reduces consciousness with the aim of relieving refractory suffering related to physical and psychological symptoms and/or existential distress near the end of life. Palliative sedation is intended to be an end of life option that enables healthcare professionals to provide good patient care but there remains controversy on how it is used. Little is known about decision-making processes regarding this procedure. The aim of this study was to explore decision-making processes in palliative sedation based on the experiences and perceptions of relatives and healthcare professionals.MethodsWe conducted a qualitative interview study with dyads (a bereaved relative and a healthcare professional) linked to 33 deceased patient with cancer who had palliative sedation, in seven in-patient palliative care settings in five countries (Belgium, Germany, Italy, the Netherlands, and Spain). A framework analysis approach was used to analyse the data.ResultsTwo main themes are defined: 1) Decision-making about palliative sedation is a complex iterative process, 2) Decision-making is a shared process between the patient, healthcare professionals, and relatives. Decision-making about palliative sedation appears to follow an iterative process of shared information, deliberation, and decision-making. The patient and healthcare professionals are the main stakeholders, but relatives are involved and may advocate for, or delay, the decision-making process. Starting palliative sedation is reported to be an emotionally difficult decision for all parties.ConclusionsAs decision-making about palliative sedation is a complex and iterative process, patients, relatives and healthcare professionals need time for regular discussions. This requires a high level of engagement by healthcare professionals, that takes into account patients' wishes and needs, and helps to facilitate decision-making.

Abstract Background Palliative sedation involves the intentional proportional lowering of the level of consciousness in patients with life-limiting disease who are experiencing refractory suffering. The efficacy of palliative sedation needs to be monitored to ensure patient comfort. The aim of this study was to evaluate the efficacy using discomfort levels combined with sedation/agitation levels. Methods In this prospective observational study, adult patients with advanced malignancies were recruited from hospice units, palliative care units, and hospital wards in five European countries. Health care professionals used proxy observations of discomfort levels (Discomfort Scale-Dementia of Alzheimer Type, range 0–27) and sedation/agitation levels (Richmond Agitation-Sedation Scale modified for palliative care inpatients), range − 5 to + 4) to evaluate the efficacy of palliative sedation. Results In 78 participants, discomfort levels were monitored during palliative sedation. The mean discomfort score before start was 9.4 points (95% CI 8.3–10.5), which showed a significant decrease of 6.0 points (95% CI 4.8–7.1) after start of sedation for the total sedation period. In the multivariable analysis, no significant factors influencing baseline discomfort levels were identified. The discomfort and depth of sedation scores were found to be positively correlated, with an r of 0.72 (95% CI 0.61–0.82). The internal consistency of the discomfort scale was good (0.83), but the “Noisy breathing” item was less informative of the total discomfort score. Conclusions The efficacy of palliative sedation can be evaluated by measuring discomfort levels combined with sedation/agitation levels. The measurement of discomfort levels might provide a more specific and detailed evaluation of adequate sedation. Trial registration This study is registered at ClinicalTrials.gov since January 22, 2021, registration number: NCT04719702.

BACKGROUND AND OBJECTIVE:The 30-day expected mortality rate is frequently used as a metric to determine which patients benefit from palliative radiation treatment (RT). We conducted a narrative review to examine whether its use as a metric might be appropriate for patient selection.METHODS:A literature review was conducted to identify relevant studies that highlight the benefits of palliative RT in timely symptom management among patients with a poor performance status, the accuracy of predicting survival near the end of life and ways to speed up the process of RT administration through rapid response clinics.KEY CONTENT AND FINDINGS:Several trials have demonstrated substantial response rates for pain and/or bleeding by four weeks and sometimes within the first two weeks after RT. Models of patient survival have limited accuracy, particularly for predicting whether patients will die within the next 30 days. Dedicated Rapid Access Palliative RT (RAPRT) clinics, in which patients are assessed, simulated and treated on the same day, reduce the number of patient visits to the radiation oncology department and hence the burden on the patient as well as costs.CONCLUSIONS:Single-fraction palliative RT should be offered to eligible patients if they are able to attend treatment and could potentially benefit from symptom palliation, irrespective of predicted life expectancy. We discourage the routine use of the 30-day mortality as the only metric to decide whether to offer RT. More common implementation of RAPRT clinics could result in a significant benefit for patients of all life expectancies, but particularly those having short ones.

Radiotherapy is an important treatment modality for pain control in patients with bone metastases. Stereotactic body radiation therapy (SBRT), which allows delivering a much higher dose per fraction while sparing critical structures compared to conventional external beam radiotherapy (cEBRT), has become more widely used, especially in the oligometastatic setting. Randomized controlled trials (RCTs) comparing the pain response rate of SBRT and cEBRT for bone metastases have shown conflicting results, as have four recent systematic reviews with meta-analyses of these trials. Possible reasons for the different outcomes between these reviews include differences in methodology, which trials were included, and the endpoints examined and how they were defined. We suggest ways to improve analysis of these RCTs, particularly performing an individual patient-level meta-analysis since the trials included heterogeneous populations. The results of such studies will help guide future investigations needed to validate patient selection criteria, optimize SBRT dose schedules, include additional endpoints (such as the time to onset of pain response, durability of pain response, quality of life (QOL), and side effects of SBRT), and better assess the cost-effectiveness and trade-offs of SBRT compared to cEBRT. An international Delphi consensus to guide selection of optimal candidates for SBRT is warranted before more prospective data is available.

Palliative sedation involves the intentional lowering of consciousness at the end of life. It can be initiated to relieve a patient’s burden caused by refractory symptoms at the end of life. The impact of palliative sedation needs to be clinically monitored to adjust the proper dose and regimen of sedative medication to ensure that patients are at ease and comfortable at the end of their lives. Although there is consensus among health care professionals and within guidelines that efficacy of palliative sedation needs to be closely monitored, there is no agreement about how, when, and by whom, this monitoring should be performed. The aim of this study is to evaluate the effects of palliative sedation by measuring the discomfort levels and sedation/agitation levels of the patients at regular timepoints. In addition, the clinical trajectories of those patients receiving palliative sedation will be monitored and recorded. The study is an international prospective non-experimental observational multicentre study. Patients are recruited from in-patient palliative care settings in Belgium, Germany, Italy, Spain and the Netherlands. Adult patients with advanced cancer are monitored by using proxy observations of discomfort (DS-DAT) and depth of sedation/agitation levels (RASS-PAL) during palliative sedation. After the palliative sedation period, the care for the specific participant case is evaluated by one of the attending health care professionals and one relative via a questionnaire. This study will be the first international prospective multicenter study evaluating the clinical practice of palliative sedation including observations of discomfort levels and levels of sedation. It will provide valuable information about the practice of palliative sedation in European countries in terminally ill cancer patients. Results from this study will facilitate the formulation of recommendations for clinical practice on how to improve monitoring and comfort in patients receiving palliative sedation. This study is registered at Clinicaltrials.gov since January 22, 2021, registration number: NCT04719702.

Inmaculada Navarro-Domenech, Tara Behroozian, Peter Hoskin, Candice Johnstone, Abram Recht, Johan Menten, Eva Oldenburger, Yvette M. van der Linden, Joanne M. van der Velden, Quynh-Nhu Nguyen, Charles B. Simone II, Peter Johnstone, Stephen Lutz, Lauren Milton, Nicolaus Andratschke, Jonas Willmann, Joanna Kazmierska, Mateusz Spałek, Gustavo N. Marta, Edward Chow, Srinivas Raman

Background Palliative sedation is a commonly accepted medical practice. This study aims to clarify how palliative sedation is regulated in various countries and whether this may impact its practice. Methods An online survey requesting regulations on palliative sedation was conducted in Belgium, Germany, Hungary, Italy, The Netherlands, Spain, Romania and the UK. Purposive sampling strategy was used to identify clinicians from different medical fields and legal experts for each country. Regulations were analyzed using the principles of the European Association for Palliative Care Framework on palliative sedation. Country reports describing how palliative sedation is regulated were elaborated. Results One hundred and thirty-nine out of 223 (62%) participants identified 31 laws and other regulations affecting palliative sedation. In Spain, 12 regional laws recognize palliative sedation as a right of the patient at the end of life when there are refractory symptoms. In Italy, the law of informed consent and advance directives specifically recognizes the doctor can use deep sedation when there are refractory symptoms. There are also general medical laws that, while not explicitly referring to palliative sedation, regulate sedation-related principles: the obligation of doctors to honour advance directives, informed consent, the decision-making process and the obligation to document the whole process. In Germany, the Netherlands and the UK, palliative sedation is also regulated through professional guidelines that are binding as good practice with legal significance. Conclusions Palliative sedation is considered in the general law of medical practice, in laws regarding the patient's autonomy, and through professional guidelines.

In 2009, the European Association for Palliative Care (EAPC) developed a framework on palliative sedation, acknowledging this practice as an important and ethically acceptable intervention of last resort for terminally ill patients experiencing refractory symptoms. Before and after that, other guidelines on palliative sedation have been developed in Europe with variations in terminology and concepts. As part of the Palliative Sedation project (Horizon 2020 Funding No. 825700), a revision of the EAPC framework is planned. The aim of this article is to analyze the most frequently used palliative sedation guidelines as reported by experts from eight European countries to inform the discussion of the new framework. The three most reported documents per country were identified through an online survey among 124 clinical experts in December 2019. Those meeting guideline criteria were selected. Their content was assessed against the EAPC framework on palliative sedation. The quality of their methodology was evaluated with the Appraisal Guideline Research and Evaluation (AGREE) II instrument. Nine guidelines were included. All recognize palliative sedation as a last-resort treatment for refractory symptoms, but the criterion of refractoriness remains a matter of debate. Most guidelines recognize psychological or existential distress as (part of) an indication and some make specific recommendations for such cases. All agree that the assessment should be multiprofessional, but they diverge on the expertise required by the attending physician/team. Regarding decisions on hydration and nutrition, it is proposed that these should be independent of those for palliative sedation, but there is no clear consensus on the decision-making process. Several weaknesses were highlighted, particularly in areas of rigor of development and applicability. The identified points of debate and methodological weaknesses should be considered in any update or revision of the guidelines analyzed to improve the quality of their content and the applicability of their recommendations.

ObjectivesPalliative sedation for existential suffering (PS-ES) is considered a controversial practice to control refractory suffering at the end of life. This study aims to explore Belgian palliative care physicians’ perceptions regarding the ethics of PS-ES.MethodsThis nationwide qualitative study follows a Grounded Theory approach. We conducted semistructured interviews with 25 palliative care physicians working in 23 Belgian hospitals and hospices (Flanders, Brussels, Wallonia). We analysed the data using the Qualitative Analysis Guide Of Leuven and we followed the Consolidated Criteria for Reporting Qualitative Research guidelines.ResultsThe data revealed that Belgian palliative care physicians have difficulty characterising ES and distinguishing it from other types of suffering. They express mixed attitudes towards PS-ES and employ a wide range of ethical arguments in favour and against it, which are mainly linked to the four principles of biomedical ethics.ConclusionSince there is a lack of consensus among Belgian palliative care physicians about PS-ES, further research is needed to clarify their attitudes. A better understanding of physicians’ underlying presuppositions can provide more insight into their perceptions of ES and PS-ES and provide further insight for establishing good practices in ES management at the end of life.

Background. The involvement of patients in decision making about their healthcare plans is being emphasized. In the context of palliative sedation, it is unclear how these decisions are made and who are involved in. The aim of the study is to understand how this decision-making is taken. Method. Information from a systematic review on clinical aspects of palliative sedation prospective studies were included. PubMed, CINAHL, Cochrane, MEDLINE, and EMBASE were searched (January 2014–December 2019). Data extraction and analysis regarded: (a) When and by whom the decision-making process is initiated; (b) patient involvement; (c) family involvement and (d) healthcare involvement. Results. Data about decision making were reported in 8/10 included articles. Palliative sedation was reported in 1137 patients (only 16 of them were non-cancer). Palliative sedation was introduced by the palliative care team during the disease process, at admission, or when patients experienced refractory symptoms. Only two studies explicitly mentioned the involvement of patients in decision making. Co-decision between families and the regular health care professionals was usual, and the health care professionals involved had been working in palliative care services. Conclusion. Patient participation in decision making appeared to be compromised by limited physical or cognitive capacity and family participation is described. The possibility of palliative sedation should be discussed earlier in the disease process.

Recently published ESTRO ACROP guidelines summarize the latest clinical landscape in radiotherapy management of uncomplicated bone metastases, and recommend that a single 8 Gy fraction should be utilized for palliative treatment [ [1] van der Velden J. Willmann J. Spałek M. Oldenburger E. Brown S. Kazmierska J. et al. ESTRO ACROP guidelines for external beam radiotherapy of patients with uncomplicated bone metastases. Radiother Oncol. 2022; Abstract Full Text Full Text PDF Scopus (1) Google Scholar ]. This recommendation is supported by multiple systematic reviews on the efficacy of single fraction conventional radiotherapy (SFRT) versus multiple fraction conventional radiotherapy (MFRT), which have been conducted and updated regularly over the past two decades [ 2 Chow E. Harris K. Fan G. Tsao M. Sze W.M. Palliative radiotherapy trials for bone metastases: a systematic review. J Clin Oncol. 2007; 25: 1423-1436 Crossref PubMed Scopus (695) Google Scholar , 3 Chow E. Zeng L. Salvo N. Dennis K. Tsao M. Lutz S. Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin oncology. 2012; 24: 112-124 Abstract Full Text Full Text PDF PubMed Scopus (455) Google Scholar , 4 Rich S.E. Chow R. Raman S. Zeng K.L. Lutz S. Lam H. et al. Update of the systematic review of palliative radiation therapy fractionation for bone metastases. Radiother Oncol. 2018; 126: 547-557 Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar ]. The most recent systematic review was published in 2018 by Rich et al. [ [4] Rich S.E. Chow R. Raman S. Zeng K.L. Lutz S. Lam H. et al. Update of the systematic review of palliative radiation therapy fractionation for bone metastases. Radiother Oncol. 2018; 126: 547-557 Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar ], reporting on 29 randomized controlled trials. In line with systematic review best practices, we endeavored to update the 2018 review. However, when searching the literature across several databases (Ovid MEDLINE, Embase, Cochrane Central and APA PsychInfo from 2017 to April 21st, 2022) and ClinicalTrials.gov, no new or ongoing randomized controlled trials (RCTs) were identified.

Background Patients at the end-of-life may experience refractory symptoms of which pain, delirium, vomiting and dyspnea are the most frequent. Palliative sedation can be considered a last resort option to alleviate one or more refractory symptoms. There are only a limited number of (qualitative) studies exploring the experiences of relatives of sedated patients and their health care professionals (HCPs). The aims of this study protocol are: 1) to elicit the experiences of bereaved relatives and health care professionals of patients treated with palliative sedation and 2) to explore the understanding of the decision-making process to start palliative sedation across care settings in 5 European countries. Methods This study protocol is part of the larger HORIZON 2020 Palliative Sedation project. Organisational case study methodology will be used to guide the study design. In total, 50 cases will be conducted in five European countries (10 per country). A case involves a semi-structured interview with a relative and an HCP closely involved in the care of a deceased patient who received some type of palliative sedation at the end-of-life. Relatives and health care professionals of deceased patients participating in a linked observational cohort study of sedated patients cared for in hospital wards, palliative care units and hospices will be recruited. The data will be analyzed using a framework analysis approach. The first full case will be analyzed by all researchers after being translated into English using a pre-prepared code book. Afterwards, bimonthly meetings will be organized to coordinate the data analysis. Discussion The study aims to have a better understanding of the experiences of relatives and professional caregivers regarding palliative sedation and this within different settings and countries. Some limitations are: 1) the sensitivity of the topic may deter some relatives from participation, 2) since the data collection and analysis will be performed by at least 5 different researchers in 5 countries, some differences may occur which possibly makes it difficult to compare cases, but using a rigorous methodology will minimize this risk.

Patients with a benign meningioma often have a long survival following the treatment of their meningioma. Since radiotherapy is frequently part of the treatment, long-term side effects are of considerable concern. A controversial long-term side effect of radiotherapy is stroke. Due to its severity, it is important to know the frequency of this side effect. The aim of this study was to assess the stroke incidence and risk factors among patients receiving radiotherapy for their benign meningioma. We performed a retrospective database study of patients who underwent primary or adjuvant radiotherapy for their benign meningioma at University Hospitals Leuven from January 2003 to December 2017. We included 169 patients with a median age of 51 years (range 22–84). Every patient received fractionated radiotherapy using photons with a median dose of 56 Gy (range 54–56) in fractions of 2 Gy (range 1.8–2). The median follow-up was 5.3 years (range 0.1–14). The cumulative stroke incidence function showed an incidence of 11.6% after 9 years of follow-up, translating to a stroke incidence per year of 1.29%. We found two significant risk factors for stroke: medically treated arterial hypertension (p = 0.005) and history of previous stroke or transient ischemic attack (p < 0.001). 5-year local control and overall survival rates were respectively 97.4% and 91.2%. Other late grade III/IV toxicities occurred in 16.0% (27/169) of patients. Our study shows a higher incidence of stroke in patients who received radiotherapy for their benign meningioma compared to the general population.