Continuity of care for patients with de novo metastatic cancer during the COVID-19 pandemic: A population-based observational study.

During the COVID-19 pandemic recommendations were made to adapt cancer care. This population-based study aimed to investigate possible differences between the treatment of patients with metastatic cancer before and during the pandemic by comparing the initial treatments in five COVID-19 periods (weeks 1-12 2020: pre-COVID-19, weeks 12-20 2020: 1st peak, weeks 21-41 2020: recovery, weeks 42-53 2020: 2nd peak, weeks 1-20 2021: prolonged 2nd peak) with reference data from 2017 to 2019. The proportion of patients receiving different treatment modalities (chemotherapy, hormonal therapy, immunotherapy or targeted therapy, radiotherapy primary tumor, resection primary tumor, resection metastases) within 6 weeks of diagnosis and the time between diagnosis and first treatment were compared by period. In total, 74,208 patients were included. Overall, patients were more likely to receive treatments in the COVID-19 periods than in previous years. This mainly holds for hormone therapy, immunotherapy or targeted therapy and resection of metastases. Lower odds were observed for resection of the primary tumor during the recovery period (OR 0.87; 95% CI 0.77-0.99) and for radiotherapy on the primary tumor during the prolonged 2nd peak (OR 0.84; 95% CI 0.72-0.98). The time from diagnosis to the start of first treatment was shorter, mainly during the 1st peak (average 5 days, p < .001). These findings show that during the first 1.5 years of the COVID-19 pandemic, there were only minor changes in the initial treatment of metastatic cancer. Remarkably, time from diagnosis to first treatment was shorter. Overall, the results suggest continuity of care for patients with metastatic cancer during the pandemic.

Trajectories of health-related quality of life and symptom burden in patients with advanced cancer towards the end of life: Longitudinal results from the eQuiPe study.

BACKGROUND: Support for health-related quality of life (HRQOL) is an essential part of cancer care in the final stages of life, yet empirical guidance regarding HRQOL and symptom trajectories is lacking. AIM: To assess the change in HRQOL and symptom burden in the last year of life in patients with advanced cancer and its association with health care-related factors, cancer-specific treatment, and comorbidity. METHODS: A prospective, multicenter, observational study in patients with advanced cancer (eQuiPe). Three monthly questionnaires included European Organization for Research and Treatment of Cancer Quality of Life-C30 and reported continuity of care. Multivariable mixed-effects analysis was used to assess the association between HRQOL and health care-related factors. RESULTS: A total of 762 deceased patients were included with a mean age of 66 (SD, 10) years and 52% were male. The most common primary tumors were lung (29%), colorectal (20%), and breast cancer (13%). Mean overall HRQOL decreased in the last 9 months of life, with the greatest decrease in the last 3 months (ß -16.2). Fatigue, pain, appetite loss, dyspnea, constipation, and nausea worsened significantly in the last year of life. Multimorbidity (ß -7.5) and a better reported continuity of care (ß 0.7) were both significantly associated with the trajectory of HRQOL. CONCLUSION: Mean overall HRQOL begins to decline 9 months before death, highlighting the need for early identification and (re)assessment of different symptoms as aspects of HRQOL follow different trajectories. Multimorbidity and reported continuity of care may be associated with the trajectory of HRQOL.

Decline in Smartphone-Assessed Physical Activity Level is Associated With Clinical Outcomes in Phase I/II Clinical Cancer Trials.

BACKGROUND: A decline in physical function may be an early predictor for complications of cancer treatment. This study examined whether repeated objective smartphone measurements of physical activity and exercise capacity in patients with cancer are feasible during early-phase clinical trials (EPCTs) and whether a decline in physical function is associated with clinical outcomes. METHODS: Physical activity (steps/day) and exercise capacity (6-minute walk test [6MWT]) were measured with a smartphone before EPCT start (T0) and after 4 weeks (T1) and 8 weeks (T2). Univariable logistic regression analyzed associations between a decline in step count (≥20%), 6MWT distance (≥10%), or deterioration of ECOG performance status (PS) and trial discontinuation at 8 weeks and 90 days. Cox proportional hazards models were used to examine associations with progression-free survival (PFS) and overall survival (OS), adjusting for trial phase (I vs II), cancer type (hematologic malignancy vs solid tumor), and PS (0 vs ≥1). RESULTS: Among 117 included patients, valid step count and 6MWT measurements were available for 96.6% and 76.7% of patients at T0, 74.4% and 53.3% at T1, and 89.7% and 54.4% at T2, respectively. Patients experiencing step count decline between T0 and T1 had higher odds of trial discontinuation at 8 weeks (odds ratio, 8.67; 95% CI, 1.94-61.43), and decline between T1 and T2 was associated with discontinuation at 90 days (odds ratio, 5.20; 95% CI, 1.43-21.14). Step count decline was significantly associated with shorter PFS (hazard ratio, 3.54; 95% CI, 2.06-6.08) and OS (hazard ratio, 2.31; 95% CI, 1.26-4.23). Declines in 6MWT distance or deterioration in ECOG PS were not associated with trial discontinuation or survival. CONCLUSIONS: Repeated smartphone measurements of physical activity are feasible in patients participating in EPCTs. Additionally, physical activity decline is significantly associated with trial discontinuation, PFS, and OS. Hence, we envision that objective smartphone measurements of physical activity will contribute to optimal treatment development for patients with cancer.

Reduction in potentially inappropriate end-of-life hospital care for cancer patients during the COVID-19 pandemic: A retrospective population-based study.

BACKGROUND: The COVID-19 pandemic impacted cancer diagnosis and treatment. However, little is known about end-of-life cancer care during the pandemic. AIM: To investigate potentially inappropriate end-of-life hospital care for cancer patients before and during the COVID-19 pandemic. DESIGN: Retrospective population-based cohort study using data from the Netherlands Cancer Registry and the Dutch National Hospital Care Registration. Potentially inappropriate care in the last month of life (chemotherapy administration, >1 emergency room contact, >1 hospitalization, hospitalization >14 days, intensive care unit admission or hospital death) was compared between four COVID-19 periods and corresponding periods in 2018/2019. PARTICIPANTS: A total of 112,919 cancer patients (⩾18 years) who died between January 2018 and May 2021 were included. RESULTS: Fewer patients received potentially inappropriate end-of-life care during the COVID-19 pandemic compared to previous years, especially during the first COVID-19 peak (22.4% vs 26.0%). Regression analysis showed lower odds of potentially inappropriate end-of-life care during all COVID-19 periods (between OR 0.81; 95% CI 0.74-0.88 and OR 0.92; 95% CI 0.87-0.97) after adjustment for age, sex and cancer type. For the individual indicators, fewer patients experienced multiple or long hospitalizations, intensive care unit admission or hospital death during the pandemic. CONCLUSIONS: Cancer patients received less potentially inappropriate end-of-life care during the COVID-19 pandemic. Because several factors may have contributed, it is unclear whether this reflects better quality care. However, these findings raise important questions about what pandemic-induced changes in care practices can help provide appropriate end-of-life care for future patients in the context of increasing patient numbers and limited resources.

Are specialist-provided end-of-life scenarios key to initiation of advance care planning in primary care? A mixed-methods study.

OBJECTIVES: Specialist-provided end-of-life scenarios (SP-EOLS) may improve advance care planning (ACP) implementation in primary care by helping overcome barriers such as uncertain prognosis and poor interprofessional collaboration. We aimed to explore the current use and potential impact of SP-EOLS on ACP in Dutch primary care. METHODS: We performed a mixed-methods study. From patients discussed in a hospital-based academic palliative care multidisciplinary team meeting between 2016 and 2019 and died, we collected primary care electronic medical records data on SP-EOLS, actual EOLS, and ACP initiation and applied descriptive and comparative analyses. Subsequently, we interviewed general practitioners (GPs) and thematically analyzed the transcripts. RESULTS: In 69.7% of 66 reviewed patient files, SP-EOLS were found. In patients whose GP had received SP-EOLS, ACP conversations were more often reported (92.0 vs. 61.0%, p = 0.006). From 11 GP interviews, we identified 4 themes: (1) SP-EOLS guide GPs, patients, and relatives when dealing with an uncertain future perspective; (2) SP-EOLS provide continuity of care between primary and secondary/tertiary care; (3) SP-EOLS should be tailored to the individual patient; and (4) SP-EOLS need to be personalized and uniformly transferred to GPs. SIGNIFICANCE OF RESULTS: SP-EOLS may facilitate ACP conversations by GPs. They have the potential to help overcome existing barriers to ACP implementation by providing guidance and supporting interprofessional collaboration. Future research should focus on improving SP-EOLS and tailor them to the needs of all end users, focusing on improving their effect on ACP conversations.

The clinical practice of palliative sedation in patients dying from COVID-19: a retrospective chart review.

BACKGROUND: Clinical experts experienced challenges in the practice of palliative sedation (PS) during the COVID-19 pandemic. Rapid deterioration in patients' situation was observed while the indications for starting PS seemed to differ compared to other terminal patients. It is unclear to which extent clinical trajectories of PS differ for these COVID patients compared to regular clinical practice of PS. OBJECTIVES: To describe the clinical practice of PS in patients with COVID versus non-COVID patients. METHODS: A retrospective analysis of data from a Dutch tertiary medical centre was performed. Charts of adult patients who died with PS during hospitalisation between March '20 and January '21 were included. RESULTS: During the study period, 73 patients received PS and of those 25 (34%) had a COVID infection. Refractory dyspnoea was reported as primary indication for starting PS in 84% of patients with COVID compared to 33% in the other group (p < 0.001). Median duration of PS was significantly shorter in the COVID group (5.8 vs. 17.1 h, p < 0.01). No differences were found for starting dosages, but median hourly dose of midazolam was higher in the COVID group (4.2 mg/hr vs. 2.4 mg/hr, p < 0.001). Time interval between start PS and first medication adjustments seemed to be shorter in COVID patients (1.5 vs. 2.9 h, p = 0.08). CONCLUSION: PS in COVID patients is characterized by rapid clinical deterioration in all phases of the trajectory. What is manifested by earlier dose adjustments and higher hourly doses of midazolam. Timely evaluation of efficacy is recommended in those patients.

Monitoring the clinical practice of palliative sedation (PALSED) in patients with advanced cancer: an international, multicentre, non-experimental prospective observational study protocol.

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.

Dyadic coping and its association with emotional functioning in couples confronted with advanced cancer: Results of the multicenter observational eQuiPe study.

OBJECTIVE: How patients and their partners cope with advanced cancer as a couple, may impact their emotional functioning (EF). The aim of this study was to assess dyadic coping (DC) of couples confronted with advanced cancer and its association with EF. METHODS: Actor-partner interdependence models were used to analyze baseline data of 566 couples facing advanced cancer participating in an observational study on quality of care and life. Measures included the DC Inventory and the European Organization for Research and Treatment of Cancer quality of life questionnaire (EOQLQ-C30). RESULTS: Negative DC (mean 86-88) was most often used and common DC (both mean 66) was least often used. We found small to moderate interdependence (r = 0.27-0.56) between patients' and partners' DC perceptions. Compared to partners, patients were more satisfied with their DC (p < 0.001). Partners' satisfaction with DC was positively associated with their own (B = 0.40, p < 0.001) and patients' (B = 0.23, p = 0.04) EF. We found positive actor (patients B = 0.37 B = 0.13, p = 0.04) and partner (both B = 0.17, p < 0.05) associations for negative DC in patients and partners. Partners' supportive DC was negatively associated with patients (B = -0.31, p = 0.03) and partners' EF (B = -0.34, p = 0.003). CONCLUSIONS: This study highlight the importance of DC (especially from the partners' perspective) for EF in advanced cancer but also identifies differences in the experience of patients and their partners. Future research is needed to understand the mechanisms of such relations and the common and unique support options that may facilitate adjustment in patients with advanced cancer and their partners.

Emotional functioning during bereavement after the death of patients with advanced cancer and associated factors.

OBJECTIVE: The death of a loved one is considered to be the most stressful of all life events. However, the impact of bereavement on quality of life varies between individuals. The aim of our study was to assess emotional functioning (EF), which is a domain of quality of life, of bereaved relatives after the death of their loved one and its associated factors. METHOD: A prospective, longitudinal, multicenter, observational study on quality of care and quality of life of patients with advanced cancer and their relatives was conducted (eQuiPe). The association between EF of relatives during bereavement and the following factors was investigated: gender, type of relationship, educational level, pre-bereavement emotional and social functioning and global quality of life, social support pre- and during bereavement, anticipatory complicated grief, support of healthcare professionals during bereavement, age of patient and bereaved relative and duration of survival after primary cancer diagnosis. RESULTS: 150 bereaved relatives completed the bereavement questionnaire. In 41% of the bereaved relatives EF was ≤71, indicating clinically relevant low EF. Multivariable logistic regression showed that females experienced more often emotional problems (OR = 2.82). Emotional functioning pre-bereavement (OR = 0.96) and social support during bereavement (OR = 0.97) were associated with low EF during bereavement. CONCLUSIONS: Almost half of the bereaved relatives of patients with advanced cancer experienced low EF and this was associated with low EF pre-bereavement and low social support during bereavement. Support for relatives should be initiated before the patient's death. Future research is needed to investigate the impact of such support on relatives' wellbeing during bereavement.

Oncologist responses to advanced cancer patients' lived illness experiences and effects: an applied conversation analysis study.

BACKGROUND: An advanced cancer patient's life is often disturbed by fear of cancer recurrence, cancer progress, approaching suffering, and fear of dying. Consequently, the role of the medical oncologist is not only to provide best quality anti-cancer treatment, but also to address the impact of disease and treatment on a patient's life, the lived illness experience. We aimed to gain insights into whether and how medical oncologists working at an outpatient clinic identify and explore lived illness experiences raised by patients with advanced cancer, and how this influences patients' responses. METHODS: Conversation Analysis was applied to analyse 16 verbatim transcribed audio-recorded consultations. RESULTS: We identified 37 fragments in which patients expressed a lived experience from 11 of the 16 consultations. We found differing responses from different oncologists. Patients continued talking about their lived experiences if the listener produced a continuer such as humming or tried to capture the experience in their own words. In contrast, a response with optimistic talking or the presentation of medical evidence prevented patients from further unfolding the experience. In consultations in which the lived illness experience was most extensively unfolded, medical oncologists and patients could constantly see each other's facial expressions. CONCLUSIONS: When a patient with advanced cancer spontaneously introduces a lived illness experience, it helps to identify and explore it when the medical oncologist produces a continuer or tries to capture this experience in their own words. Our findings can be implemented in training sessions, followed by frequent reinforcement in daily care.

Timely identification of patients in need of palliative care using the Double Surprise Question: A prospective study on outpatients with cancer.

BACKGROUND: The Surprise Question ("Would I be surprised if this patient were to die within the next 12 months?") is widely used to identify palliative patients, though with low predictive value. To improve timely identification of palliative care needs, we propose an additional Surprise Question ("Would I be surprised if this patient is still alive after 12 months?") if the original Surprise Question is answered with "no." The combination of the two questions is called the Double Surprise Question. AIM: To examine the prognostic accuracy of the Double Surprise Question in outpatients with cancer. DESIGN: A prospective study. PARTICIPANTS: Twelve medical oncologists completed the Double Surprise Question for 379 patients. RESULTS: In group 1 (original Surprise Question "yes": surprised if dead) 92.1% (176/191) of the patients were still alive after 1 year, in group 2a (original and additional Surprise Question "no": not surprised if dead and not surprised if alive) 60.0% (63/105), and in group 2b (original Surprise Question "no," additional Surprise Question "yes": surprised if alive) 26.5% (22/83) (p < 0.0001). The positive predictive value increased by using the Double Surprise Question; 74% (61/83) vs 55% (103/188). Anticipatory palliative care provision and Advance Care Planning items were most often documented in group 2b. CONCLUSIONS: The Double Surprise Question is a promising tool to more accurately identify outpatients with cancer at risk of dying within 1 year, and therefore, those in need of palliative care. Studies should reveal whether the implementation of the Double Surprise Question leads to more timely palliative care.

Experiences of bereaved family caregivers with shared decision making in palliative cancer treatment: a qualitative interview study.

BACKGROUND: Patients with incurable cancer face complex medical decisions. Their family caregivers play a prominent role in shared decision making processes, but we lack insights into their experiences. In this study, we explored how bereaved family caregivers experienced the shared decision making process. METHODS: We performed a qualitative interview study with in-depth interviews analysed with inductive content analysis. We used a purposive sample of bereaved family caregivers (n = 16) of patients with cancer treated in a tertiary university hospital in the Netherlands. RESULTS: Four themes were identified: 1. scenarios of decision making, 2. future death of the patient 3. factors influencing choices when making a treatment decision, and 4. preconditions for the decision making process. Most family caregivers deferred decisions to the patient or physician. Talking about the patient's future death was not preferred by all family caregivers. All family caregivers reported life prolongation as a significant motivator for treatment, while the quality of life was rarely mentioned. A respectful relationship, close involvement, and open communication with healthcare professionals in the palliative setting were valued by many interviewees. Family caregivers' experiences and needs seemed to be overlooked during medical encounters. CONCLUSIONS: Family caregivers of deceased patients with cancer mentioned life prolongation, and not quality of life, as the most important treatment aim. They highly valued interactions with the medical oncologist and being involved in the conversations. We advise medical oncologists to take more effort to involve the family caregiver, and more explicitly address quality of life in the consultations.

A review of factors explaining variability in fentanyl pharmacokinetics; focus on implications for cancer patients.

Fentanyl is a strong opioid that is available for various administration routes, and which is widely used to treat cancer-related pain. Many factors influence the fentanyl pharmacokinetics leading to a wide inter- and intrapatient variability. This systematic review summarizes multiple studied factors that potentially influence fentanyl pharmacokinetics with a focus on implications for cancer patients. The use of CYP3A4 inhibitors and inducers, impaired liver function, and heating of the patch potentially influence fentanyl pharmacokinetics in a clinically relevant way. In elderly patients, current data suggest that we should carefully dose fentanyl due to alterations in absorption and metabolism. The influence of BMI and gender on fentanyl pharmacokinetics is questionable, most probably due to a large heterogeneity in the published studies. Pharmacogenetics, e.g. the CYP3A5*3 gene polymorphism, may influence fentanyl pharmacokinetics as well, although further study is warranted. Several other factors have been studied but did not show significant and clinically relevant effects on fentanyl pharmacokinetics. Unfortunately, most of the published papers that studied factors influencing fentanyl pharmacokinetics describe healthy volunteers instead of cancer patients. Results from the studies in volunteers may not be simply extrapolated to cancer patients because of multiple confounding factors. To handle fentanyl treatment in a population of cancer patients, it is essential that physicians recognize factors that influence fentanyl pharmacokinetics, thereby preventing potential side-effects and increasing its efficacy.

Treatment with subcutaneous and transdermal fentanyl: results from a population pharmacokinetic study in cancer patients.

PURPOSE: Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the pharmacokinetics of subcutaneous and transdermal fentanyl. Furthermore, we evaluated rotations from the subcutaneous to the transdermal route. METHODS: Fifty-two patients treated with subcutaneous and/or transdermal fentanyl for moderate to severe cancer-related pain participated. A population pharmacokinetic model was developed and evaluated using non-linear mixed-effects modelling. For rotations from subcutaneous to transdermal fentanyl, a 1:1 dose conversion ratio was used while the subcutaneous infusion was continued for 12 h (with a 50 % tapering after 6 h). A 6-h scheme with 50 % tapering after 3 h was simulated using the final model. RESULTS: A one-compartment model with first-order elimination and separate first-order absorption processes for each route adequately described the data. The estimated apparent clearance of fentanyl was 49.6 L/h; the absorption rate constant for subcutaneous and transdermal fentanyl was 0.0358 and 0.0135 h(-1), respectively. Moderate to large inter-individual and inter-occasion variability was found. Around rotation from subcutaneous to transdermal fentanyl, measured and simulated plasma fentanyl concentrations rose and increasing side effects were observed. CONCLUSIONS: We describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice. Further research is warranted to study the optimal scheme for rotations from the subcutaneous to the transdermal route.

Relatives' Unmet Needs in the Last Year of Life of Patients With Advanced Cancer: Results of a Dutch Prospective, Longitudinal Study (eQuiPe).

Objective(s): Unmet needs of relatives of patients with advanced cancer not only reduce their own health-related quality of life, but may also negatively affect patients' health outcomes. The aim of this study was to assess changes in relatives' unmet needs of patients with advanced cancer in the last year of life and to identify differences in unmet needs by gender and type of relationship. Methods: Relatives of patients with advanced cancer in the Netherlands were included in a prospective, longitudinal, observational study. Relatives' unmet needs were measured every 3 months with an adapted version of the Problems and Needs in Palliative Care (PNPC) questionnaire Caregiver form (44 items, 12 domains). Questionnaires completed in the patients' last year of life were analyzed. Change of unmet needs in the last year, and differences in unmet needs by gender and type of relationship were analyzed. Results: A total of 409 relatives were included with a median of 4 unmet needs in the patient's last year. Unmet needs were most prevalent at all time points during the last year in the domains "caring for the patient" (highest need = 35%) and "psychological issues" (highest need = 40%). The number of unmet needs of relatives did not change significantly during the last year of life (P=.807). There were no significant differences in the number of unmet needs between male and female partners and between partners and other relatives. Conclusion: The most unmet needs for relatives were in the domains "caring for the patient" and "psychological issues." Professional support should focus on these items. Within these domains, it seems especially important that relatives get more knowledge and support about what scenarios to expect and how to deal with them.

Whole-Body HER2 Heterogeneity Identified on HER2 PET in HER2-Negative, -Low, and -Positive Metastatic Breast Cancer.

Understanding which patients with human epidermal growth factor receptor 2 (HER2)-negative or -low metastatic breast cancer (MBC) benefit from HER2-targeted strategies is urgently needed. We assessed the whole-body heterogeneity of HER2 expression on 89Zr-trastuzumab PET (HER2 PET) and the diagnostic performance of HER2 PET in a large series of patients, including HER2-negative and -low MBC. Methods: In the IMPACT-MBC study, patients with newly diagnosed and nonrapidly progressive MBC of all subtypes were included. Metastasis HER2 status was determined by immunohistochemistry and in situ hybridization.89Zr-trastuzumab uptake was quantified as SUVmax and SUVmean HER2 immunohistochemistry was related to the quantitative 89Zr-trastuzumab uptake of all metastases and corresponding biopsied metastasis, uptake heterogeneity, and qualitative scan evaluation. A prediction algorithm for HER2 immunohistochemistry positivity based on uptake was developed. Results: In 200 patients, 89Zr-trastuzumab uptake was quantified in 5,163 metastases, including 186 biopsied metastases. With increasing HER2 immunohistochemistry status, uptake was higher (geometric mean SUVmax of 7.0, 7.6, 7.3, and 17.4 for a HER2 immunohistochemistry score of 0, 1, 2, or 3+, respectively; P < 0.001). High uptake exceeding 14.6 (90th percentile) was observed in one third of patients with a HER2-negative or -low metastasis biopsy. The algorithm performed best when lesion site and size were incorporated (area under the curve, 0.86; 95% CI, 0.79-0.93). Conclusion: HER2 PET had good diagnostic performance in MBC, showing considerable whole-body HER2 heterogeneity and uptake above background in HER2-negative and -low MBC. This provides novel insights into HER2-negative and -low MBC compared with standard HER2 immunohistochemistry on a single biopsy.

Correlation between Histopathological Prognostic Tumor Characteristics and [18F]FDG Uptake in Corresponding Metastases in Newly Diagnosed Metastatic Breast Cancer.

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 (SUVmax) 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 SUVmax 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 SUVmax 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 SUVmax 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).

Quality of care and quality of life as experienced by patients with advanced cancer of a rare tumour type: results of the multicentre observational eQuiPe study.

PURPOSE: Patients with a rare cancer face difficulties during their disease trajectory, such as delayed diagnosis and lack of expert care. However, little is known about their perceived quality of care (QoC) and quality of life (QoL) in the advanced disease stage. We aimed to assess the QoC and QoL as experienced by patients with advanced rare cancers compared to patients with advanced common cancers. METHODS: In this cross-sectional study, baseline data of patients with advanced cancer from the multicentre, longitudinal, observational eQuipe study were analysed. Multivariable linear regression analyses were conducted to assess differences in experienced QoC (continuity of care, continuity of information, and satisfaction with care) and QoL (functioning, symptoms, overall QoL, and social wellbeing) between advanced rare and common cancer patients. RESULTS: Of the 1087 included patients, 106 (9.8%) had a rare cancer type. In comparison to patients with advanced common cancers, patients with advanced rare cancers experienced significantly lower continuity of care (77.8 vs. 71.1 respectively, p = 0.011) and social functioning (78.8 vs. 72.6 respectively, p = 0.012). No differences were found regarding continuity of information, satisfaction with care, overall QoL, and social wellbeing. CONCLUSIONS: Patients with advanced rare cancers experience less continuity of care, and the impact of the disease on social and family life seems higher compared to patients with advanced common cancers. IMPLICATIONS FOR CANCER SURVIVORS: To enhance the QoC and QoL of patients with advanced rare cancers, supportive care should mainly focus on improving continuity of care and patients' social functioning.

Clinical Validity of 16α-[18F]Fluoro-17ß-Estradiol Positron Emission Tomography/Computed Tomography to Assess Estrogen Receptor Status in Newly Diagnosed Metastatic Breast Cancer.

PURPOSE: Determining the estrogen receptor (ER) status is essential in metastatic breast cancer (MBC) management. Whole-body ER imaging with 16α-[18F]fluoro-17ß-estradiol positron emission tomography ([18F]FES-PET) is increasingly used for this purpose. To establish the clinical validity of the [18F]FES-PET, we studied the diagnostic accuracy of qualitative and quantitative [18F]FES-PET assessment to predict ER expression by immunohistochemistry in a metastasis. METHODS: In a prospective multicenter trial, 200 patients with newly diagnosed MBC underwent extensive workup including molecular imaging. For this subanalysis, ER expression in the biopsied metastasis was related to qualitative whole-body [18F]FES-PET evaluation and quantitative [18F]FES uptake in the corresponding metastasis. A review and meta-analysis regarding [18F]FES-PET diagnostic performance were performed. RESULTS: Whole-body [18F]FES-PET assessment predicted ER expression in the biopsied metastasis with good accuracy: a sensitivity of 95% (95% CI, 89 to 97), a specificity of 80% (66 to 89), a positive predictive value (PPV) of 93% (87 to 96), and a negative predictive value (NPV) of 85% (72 to 92) in 181 of 200 evaluable patients. Quantitative [18F]FES uptake predicted ER immunohistochemistry in the corresponding metastasis with a sensitivity/specificity of 91%/69% and a PPV/NPV of 90%/71% in 156 of 200 evaluable patients. For bone metastases, PPV/NPV was 92%/81%. Meta-analysis with addition of our data has increased diagnostic performance and narrowed the 95% CIs compared with previous studies with a sensitivity/specificity of both 86% (81 to 90 and 73 to 93, respectively). CONCLUSION: In this largest prospective series so far, we established the clinical validity of [18F]FES-PET to determine tumor ER status in MBC. In view of the high diagnostic accuracy of qualitatively assessed whole-body [18F]FES-PET, this noninvasive imaging modality can be considered a valid alternative to a biopsy of a metastasis to determine ER status in newly MBC (ClinicalTrials.gov identifier: NCT01957332).