Background: In metastatic breast cancer (MBC), [¹⁸F]fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]FDG-PET/CT) can be used for staging. We evaluated the correlation between BC histopathological characteristics and [¹⁸F]FDG uptake in corresponding metastases. Patients and Methods: Patients with non-rapidly progressive MBC of all subtypes prospectively underwent a baseline histological metastasis biopsy and [¹⁸F]FDG-PET. Biopsies were assessed for estrogen, progesterone, and human epidermal growth factor receptor 2 (ER, PR, HER2); Ki-67; and histological subtype. [¹⁸F]FDG uptake was expressed as maximum standardized uptake value (SUV_max) and results were expressed as geometric means. Results: Of 200 patients, 188 had evaluable metastasis biopsies, and 182 of these contained tumor. HER2 positivity and Ki-67 ≥ 20% were correlated with higher [¹⁸F]FDG uptake (estimated geometric mean SUV_max 10.0 and 8.8, respectively; p = 0.0064 and p = 0.014). [¹⁸F]FDG uptake was lowest in ER-positive/HER2-negative BC and highest in HER2-positive BC (geometric mean SUV_max 6.8 and 10.0, respectively; p = 0.0058). Although [¹⁸F]FDG uptake was lower in invasive lobular carcinoma (n = 31) than invasive carcinoma NST (n = 146) (estimated geometric mean SUV_max 5.8 versus 7.8; p = 0.014), the metastasis detection rate was similar. Conclusions: [¹⁸F]FDG-PET is a powerful tool to detect metastases, including invasive lobular carcinoma. Although BC histopathological characteristics are related to [¹⁸F]FDG uptake, [¹⁸F]FDG-PET and biopsy remain complementary in MBC staging (NCT01957332).

Background: 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. Methods: 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. Discussion: 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. Trial registration: This study is registered at Clinicaltrials.gov since January 22, 2021, registration number: NCT04719702.

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.

The transdermal fentanyl patch is widely used to treat cancer-related pain despite its wide inter- and intrapatient variability in pharmacokinetics. The aim of this study was to investigate whether smoking and body size (i.e. body mass index) influence fentanyl exposure in patients with cancer. These are factors that typically change during treatment and disease trajectories. We performed an explorative cohort study in patients with cancer using transdermal fentanyl patches (Durogesic^®), by taking a blood sample for pharmacokinetic analysis one day after applying a patch in patients with a stable fentanyl dose. A total of 88 patients were evaluable. Although no statistically significant difference was found, the plasma concentrations of non-smokers was 28% (95% CI [-14%; +89-%]) higher than those of smokers normalizing for a dose of 25μg/min. Patients with a low BMI (< 20 kg/m2) had almost similar (10% (95% CI [-39%; +97%]) higher) plasma concentrations compared to patients with a high BMI (> 25 kg/m2). A wider variation in fentanyl plasma concentrations was found in this study than anticipated. Due to this variation, studies in larger patient cohorts are needed to further investigate the effect of smoking on plasma concentration of fentanyl and thereby clarify the clinical significance of our findings.