Background: We investigated the effect of equivalent weight loss, by a hypocaloric diet or mainly exercise, on inflammatory markers and adipokines in overweight postmenopausal women.Methods: Women were randomized to a diet (n ¼ 97), mainly exercise (n ¼ 98), or control group (n ¼ 48). Goal of both interventions was to lose 5 to 6 kg bodyweight by a hypocaloric diet or an exercise program (4 hours/week) combined with a small caloric intake restriction. Outcomes after 16 weeks included serum high-sensitive C-reactive protein (hsCRP), IL6, adiponectin, and leptin.Results: Both intervention groups achieved the target weight loss. Controls remained weight stable. Compared with control, hsCRP decreased with mainly exercise [treatment effect ratio (TER) ¼ 0.64] and borderline statistically significant with diet (TER ¼ 0.77). There was a suggestively larger effect of exercise,

We aimed to estimate the proportion of Dutch postmenopausal breast cancer cases in 2010 that is attributable to lifestyle-related risk factors. We calculated population attributable fractions (PAFs) of potentially modifiable risk factors for postmenopausal breast cancer in Dutch women aged >50 in 2010. First, age-specific PAFs were calculated for each risk factor, based on their relative risks for postmenopausal breast cancer (from meta-analyses) and age-specific prevalence in the population (from national surveys) around the year 2000, assuming a latency period of 10 years. To obtain the overall PAF, age-specific PAFs were summed in a weighted manner, using the age-specific breast cancer incidence rates (2010) as weights. 95 % confidence intervals for PAF estimates were derived by Monte Carlo simulations. Of Dutch women >40 years, in 2000, 51 % were overweight/obese, 55 % physically inactive (<5 days/week 30 min activity), 75 % regularly consumed alcohol, 42 % ever smoked cigarettes and 79 % had a low-fibre intake (<3.4 g/1000 kJ/day). These factors combined had a PAF of 25.7 % (95 % CI 24.2–27.2), corresponding to 2,665 Dutch postmenopausal breast cancer cases in 2010. PAFs were 8.8 % (95 % CI 6.3–11.3) for overweight/obesity, 6.6 % (95 % CI 5.2–8.0) for alcohol consumption, 5.5 % (95 % CI 4.0–7.0) for physical inactivity, 4.6 % (95 % CI 3.3–6.0) for smoking and 3.2 % (95 % CI 1.6–4.8) for low-fibre intake. Our findings imply that modifiable risk factors are jointly responsible for approximately one out of four Dutch postmenopausal breast cancer cases. This suggests that incidence rates can be lowered substantially by living a more healthy lifestyle.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-015-3447-7) contains supplementary material, which is available to authorized users.

The aim of this study was to determine the long-term effects of a weight loss intervention with or without an exercise component on body weight and physical activity.Women were randomized to diet (n = 97) or exercise (N = 98) for 16 weeks. During the intervention, both groups had achieved the set goal of 5–6 kg weight loss. All women were re-contacted twelve months after study cessation for follow-up where body weight and physical activity were measured (PASE questionnaire and ActiGraph accelerometer).At follow-up, body weight and physical activity (measured by the PASE questionnaire and accelerometer) were measured again. At follow-up, both mainly exercise (− 4.3 kg, p < 0.001) and diet (− 3.4 kg, p < 0.001) showed significantly reduced body weight compared to baseline. Both the mainly exercise and diet group were significantly more physically active at one year follow-up compared to baseline (PASE: + 33%, p < 0.001 and + 12%, p = 0.040, respectively; ActiGraph: + 16%, p = 0.012. and + 2.2%, p = 0.695 moderate-to-vigorous activity, respectively). Moreover, the increase in physical activity was statistically significantly when comparing exercise to diet (+ 0.6%, p = 0.035). ActiGraph data also showed significantly less sedentary time in mainly exercise group compared to baseline (− 2.1%, p = 0.018) and when comparing exercise to diet (− 1.8%, p = 0.023). No significant within group differences were found for the diet group.This study shows largely sustained weight loss one year after completing a weight loss program with and without exercise in overweight postmenopausal women. Although the mainly exercise group maintained more physically active compared to the diet group, maintenance of weight loss did not differ between groups.

BackgroundWe assessed the effect of equivalent weight loss with or without exercise on (intra-) abdominal fat in postmenopausal women in the SHAPE-2 study.MethodsThe SHAPE-2 study is a three-armed randomised controlled trial conducted in 2012–2013 in the Netherlands. Postmenopausal overweight women were randomized to a diet (n = 97), exercise plus diet (n = 98) or control group (n = 48). Both intervention groups aimed for equivalent weight loss (6–7%) following a calorie-restricted diet (diet group) or a partly supervised intensive exercise programme (4 h per week) combined with a small caloric restriction (exercise plus diet group). Outcomes after 16 weeks are amount and distribution of abdominal fat, measured by magnetic resonance imaging (MRI) with the use of the three-point IDEAL Dixon method.ResultsThe diet and exercise plus diet group lost 6.1 and 6.9% body weight, respectively. Compared to controls, subcutaneous and intra-abdominal fat reduced significantly with both diet (− 12.5% and − 12.0%) and exercise plus diet (− 16.0% and − 14.6%). Direct comparison between both interventions revealed that the reduction in subcutaneous fat was statistically significantly larger in the group that combined exercise with diet: an additional 10.6 cm2 (95%CI -18.7; − 2.4) was lost compared to the diet-only group. Intra-abdominal fat loss was not significantly larger in the exercise plus diet group (− 3.8 cm2, 95%CI -9.0; 1.3).ConclusionsWe conclude that weight loss of 6–7% with diet or with exercise plus diet reduced both subcutaneous and intra-abdominal fat. Only subcutaneous fat statistically significantly reduced to a larger extent when exercise is combined with a small caloric restriction.Trial registerNCT01511276 (clinicaltrials.gov), prospectively registered.Electronic supplementary materialThe online version of this article (10.1186/s12889-019-6510-1) contains supplementary material, which is available to authorized users.

Introduction Fibroblast activation protein (FAP) is highly overexpressed in stromal tissue of various cancers. While FAP has been recognized as a potential diagnostic or therapeutic cancer target for decades, the surge of radiolabeled FAP-targeting molecules has the potential to revolutionize its perspective. It is presently hypothesized that FAP targeted radioligand therapy (TRT) may become a novel treatment for various types of cancer. To date, several preclinical and case series have been reported on FAP TRT using varying compounds and showing effective and tolerant results in advanced cancer patients. Here, we review the current (pre)clinical data on FAP TRT and discuss its perspective towards broader clinical implementation.  Methods A PubMed search was performed to identify all FAP tracers used for TRT. Both preclinical and clinical studies were included if they reported on dosimetry, treatment response or adverse events. The last search was performed on July 22 2022. In addition, a database search was performed on clinical trial registries (date 15th of July 2022) to search for prospective trials on FAP TRT. Results In total, 35 papers were identified that were related to FAP TRT. This resulted in the inclusion of the following tracers for review: FAPI-04, FAPI-46, FAP-2286, SA.FAP, ND-bisFAPI, PNT6555, TEFAPI-06/07, FAPI-C12/C16, and FSDD. Conclusion To date, data was reported on more than 100 patients that were treated with different FAP targeted radionuclide therapies such as [177Lu]Lu-FAPI-04, [90Y]Y-FAPI-46, [177Lu]Lu-FAP-2286, [177Lu]Lu-DOTA.SA.FAPI and [177Lu]Lu-DOTAGA.(SA.FAPi)2. In these studies, FAP targeted radionuclide therapy has resulted in objective responses in difficult to treat end stage cancer patients with manageable adverse events. Although no prospective data is yet available, these early data encourages further research.

Background The BULLSEYE trial is a multicenter, open-label, randomized controlled trial to test the hypothesis if 177Lu-PSMA is an effective treatment in oligometastatic hormone-sensitive prostate cancer (oHSPC) to prolong the progression-free survival (PFS) and postpone the need for androgen deprivation therapy (ADT). The original study protocol was published in 2020. Here, we report amendments that have been made to the study protocol since the commencement of the trial. Changes in methods and materials Two important changes were made to the original protocol: (1) the study will now use 177Lu-PSMA-617 instead of 177Lu-PSMA-I&T and (2) responding patients with residual disease on 18F-PSMA PET after the first two cycles are eligible to receive additional two cycles of 7.4 GBq 177Lu-PSMA in weeks 12 and 18, summing up to a maximum of 4 cycles if indicated. Therefore, patients receiving 177Lu-PSMA-617 will also receive an interim 18F-PSMA PET scan in week 4 after cycle 2. The title of this study was modified to; “Lutetium-177-PSMA in Oligo-metastatic Hormone Sensitive Prostate Cancer” and is now partly supported by Advanced Accelerator Applications, a Novartis Company. Conclusions We present an update of the original study protocol prior to the completion of the study. Treatment arm patients that were included and received 177Lu-PSMA-I&T under the previous protocol will be replaced. Trial registration ClinicalTrials.gov NCT04443062. First posted: June 23, 2020.

Background: An inactive lifestyle is a risk factor for several types of cancer. A proposed pathway through which exercise influences cancer risk is via insulin. We aim to investigate the effect of a oneyear exercise intervention on insulin sensitivity, and the role of body fat in this association, in healthy, normal to overweight/ obese, postmenopausal women.Methods: In the Sex Hormones And Physical Exercise (SHAPE) study, 189 healthy, inactive and postmenopausal women [ages, 50-69 years; body mass index (BMI), 22-40 kg/m 2 ] were randomly assigned to a one-year aerobic and strength exercise intervention (150 min/wk), or a control group. Between-group differences in fasting insulin, glucose, and homeostatic model assessment of insulin resistance (HOMA2) over time were estimated using linear mixed models.Results: Follow-up measurements of insulin sensitivity were available for 181 (95.8%) and 182 (96.3%) women at 4 and 12

Purpose For prostate-specific membrane antigen-directed radioligand therapy (PSMA-RLT), [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T are the currently preferred compounds. Recent preclinical studies suggested ~30x higher kidney absorbed dose for [177Lu]Lu-PSMA-I&T compared to [177Lu]Lu-PSMA-617, which may lead to an increased risk of kidney toxicity. We performed two single-centre, prospective dosimetry studies with either [177Lu]Lu-PSMA-617 or [177Lu]Lu-PSMA-I&T, using an identical dosimetry protocol. We evaluated the absorbed doses of both 177Lu-labelled radioligands in human kidneys. Methods 3D SPECT/computed tomography (CT) imaging of the kidneys was performed after PSMA-RLT in cancer patients with PSMA-positive disease and an adequate glomerular filtration rate (≥50 mL/min). Ten metastatic hormone-sensitive prostate cancer patients (mHSPC) were treated with [177Lu]Lu-PSMA-617 and 10 advanced salivary gland cancer (SGC) patients were treated with [177Lu]Lu-PSMA-I&T. SPECT/CT imaging was performed at five timepoints (1 h, 24 h, 48 h, 72 h, and 168 h post-injection). In mHSPC patients, SPECT/CT imaging was performed after cycles 1 and 2 (cumulative activity: 9 GBq) and in SGC patients only after cycle 1 (activity: 7.4 GBq). Kidney absorbed dose was calculated using organ-based dosimetry. Results The median kidney absorbed dose was 0.49 Gy/GBq (range: 0.34–0.66) and 0.73 Gy/GBq (range: 0.42–1.31) for [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T, respectively (independent samples t test; P = 0.010). Conclusion This study shows that the kidney absorbed dose for [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T differs, with a ~1.5x higher median kidney absorbed dose for [177Lu]Lu-PSMA-I&T. This difference in the clinical setting is considerably smaller than observed in preclinical studies and may not hamper treatments with [177Lu]Lu-PSMA-I&T.