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).

Shared decision-making performance of general practice residents: an observational study combining observer, resident, and patient perspectives.

BACKGROUND: Shared decision making (SDM) is considered fundamental to person-centred care. However, applying SDM may be a challenge for residents in general practice, since it is a complex competence that requires the integration of knowledge and skills from several competency domains. OBJECTIVE: To support learning of SDM during medical residency, we aimed to gain insight in Dutch residents' observed and perceived SDM performance in general practice. METHODS: We evaluated residents' SDM performance from an observer, resident, and patient perspective. Consultations of first- and third-year residents were recorded. Trained observers used the validated Observing Patient Involvement (OPTION5) scale to assess observed SDM performance of residents in 98 actual recorded consultations. Perceived SDM performance was evaluated by residents and patients completing validated SDM questionnaires, supplemented with questions about (the context of) the consultation and perceived relevance of SDM immediately after the consultation. The data were analysed using descriptive statistics (mean, SD, minimums, and maximums) and explorative bivariate analyses. RESULTS: The residents' observed mean SDM performance was 19.1 (range, 0-100, SD = 10.9), mean resident self-reported SDM performance was 56.9 (range, 0-100, SD = 18.5), and mean patient-reported SDM performance was 73.3 (range, 0-100, SD = 26.8). We found a significant and positive correlation between observed SDM performance and residents' perceived relevance of SDM for the consultation (t = 4.571, P ≤ 0.001) and the duration of the consultation (r = 0.390, P ≤ 0.001). CONCLUSIONS: This study showed that there is room for increasing awareness of the potential incongruence between observed and perceived SDM performance during medical residency, in order to facilitate the implementation of SDM in clinical practice.

THE PROBLEM: Shared decision making is an important process in which healthcare professional and patient work together to reach a decision on how to solve a health problem. This decision should include patients' needs and what matters most to them. We investigated if consultations between general practitioners in training (i.e. residents) and their patients demonstrate shared decision making. The research methods: We asked the residents and patients to respond to questions on their experience of shared decision making right after the consultation. We recorded 98 consultations of residents with their patients. Two researchers rated to what extent residents demonstrated shared decision-making behaviours during these consultations. THE RESULTS: The patients reported more shared decision making than the residents (patients: 73 versus residents: 57 on a 0­100 scale). The researchers observed low levels of SDM during the consultations (19 on a 0­100 scale). Our conclusion: Residents should be aware that shared decision making does not yet frequently occur in practice. To improve the extent to which residents share decisions with their patients in general practice, residents should learn why, when, and how to involve patients in decision making during consultations.

Molecular imaging as biomarker for treatment response and outcome in breast cancer.

Molecular imaging, such as positron emission tomography (PET), is increasingly used as biomarker to predict and assess treatment response in breast cancer. The number of biomarkers is expanding with specific tracers for tumour characteristics throughout the body and this information can be used to aid the decision-making process. These measurements include metabolic activity using [18F]fluorodeoxyglucose PET ([18F]FDG-PET), oestrogen receptor (ER) expression using 16α-[18F]Fluoro-17ß-oestradiol ([18F]FES)-PET and human epidermal growth factor receptor 2 (HER2) expression using PET with radiolabelled trastuzumab (HER2-PET). In early breast cancer, baseline [18F]FDG-PET is frequently used for staging, but limited subtype-specific data reduce its usefulness as biomarker for treatment response or outcome. Early metabolic change on serial [18F]FDG-PET is increasingly used in the neo-adjuvant setting as dynamic biomarker to predict pathological complete response to systemic therapy, potentially allowing de-intensification or step-up intensification of treatment. In the metastatic setting, baseline [18F]FDG-PET and [18F]FES-PET can be used as biomarker to predict treatment response, in triple-negative and ER-positive breast cancer, respectively. Metabolic progression on repeated [18F]FDG-PET appears to precede progressive disease on standard evaluation imaging; however, subtype-specific studies are limited and more prospective data are needed before implementation in clinical practice. Even though (repeated) [18F]FDG-PET, [18F]FES-PET and HER2-PEt all show promising results as biomarkers to predict therapy response and outcome, for eventual integration into clinical practice, future studies will have to clarify at what timepoint this integration has to optimally take place.

PD-L1 blockade in combination with carboplatin as immune induction in metastatic lobular breast cancer: the GELATO trial.

Invasive lobular breast cancer (ILC) is the second most common histological breast cancer subtype, but ILC-specific trials are lacking. Translational research revealed an immune-related ILC subset, and in mouse ILC models, synergy between immune checkpoint blockade and platinum was observed. In the phase II GELATO trial ( NCT03147040 ), patients with metastatic ILC were treated with weekly carboplatin (area under the curve 1.5 mg ml-1 min-1) as immune induction for 12 weeks and atezolizumab (PD-L1 blockade; triweekly) from the third week until progression. Four of 23 evaluable patients had a partial response (17%), and 2 had stable disease, resulting in a clinical benefit rate of 26%. From these six patients, four had triple-negative ILC (TN-ILC). We observed higher CD8+ T cell infiltration, immune checkpoint expression and exhausted T cells after treatment. With this GELATO trial, we show that ILC-specific clinical trials are feasible and demonstrate promising antitumor activity of atezolizumab with carboplatin, particularly for TN-ILC, and provide insights for the design of highly needed ILC-specific trials.

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).