68Ga-PSMA PET/CT for Response Assessment and Outcome Prediction in Metastatic Prostate Cancer Patients Treated with Taxane-Based Chemotherapy.

We aimed to evaluate the role of PET targeting the prostate-specific membrane antigen (PSMA) for response assessment in metastatic prostate cancer (PCa) patients treated with taxane-based chemotherapy (docetaxel or cabazitaxel) and its predictive value on patient outcome. Methods: We retrospectively evaluated 37 patients with metastatic hormone-sensitive PCa or metastatic castration-resistant PCa (mCRPC) who underwent 68Ga-PSMA-11 PET/CT at baseline and after the last cycle of taxane-based chemotherapy (docetaxel or cabazitaxel) without treatment modification between scans. Biochemical response (BR) was defined as an undetectable or at least 50% decreased level of prostate-specific antigen, compared with baseline. Associations between BR and different PET parameters were tested. A cutoff of at least a 30% decrease in PSMA total tumor volume (PSMA-TV) was used to define a PSMA response (PSMA-R) versus a PSMA nonresponse (PSMA-NR). Correlations between PSMA PET/CT response and BR were evaluated using the ϕ-coefficient. Associations between PET response and overall survival (OS) was tested using Cox regression and the Kaplan-Meier method. Results: Our cohort comprised 8 (22%) metastatic hormone-sensitive PCa and 29 (78%) mCRPC patients. Twenty-one patients received docetaxel treatment, and 16 received cabazitaxel (median, 6 cycles; interquartile range, 5-8 cycles). BR was found in 18 of 37 patients. Using PSMA total tumor volume, PSMA PET/CT response was concordant with BR in 35 of 37 patients (ϕ = 0.89, P < 0.0001). Eighteen of 37 patients had PSMA-R (6, complete response; 12, partial response), and 19 had PSMA-NR (17, progressive disease; 2, stable disease). After a median follow-up of 23 mo, there was a statistically significant longer OS for PSMA-R than for PSMA-NR (median OS not reached vs. 12 mo, respectively; hazard ratio, 0.10; 95% CI, 0.03-0.39; P = 0.001) for the entire population. Among the mCRPC subgroup, differences in OS were also observed (median, 22 vs. 12 mo, respectively; hazard ratio, 0.22; 95% CI, 0.06-0.82; P = 0.023), with a 12-mo OS rate of 100% for PSMA-R and 52% for PSMA-NR (P = 0.011). Conclusion: This retrospective analysis suggests that 68Ga-PSMA-11 PET/CT is a promising imaging modality for assessing response to taxane-based chemotherapy in metastatic PCa. Changes in PSMA expression might be used as a predictive biomarker for OS to help tailor individual therapy and select eligible patients for clinical trials.

Do recent immigrants have similar obstetrical care and perinatal complications as long-term residents? A retrospective exploratory cohort study in Brussels.

PURPOSE: Recent immigrants (RIs) face various barriers affecting quality of care. The main research question assessed whether perinatal complications (during pregnancy, labour, delivery and neonatal period) were similar in RIs to those in long-term residents (LTRs). The secondary question assessed whether prenatal and perinatal care was similar in the two groups. METHODS: This is a monocentric observational study, carried out in Brussels between November 2016 and March 2017 (n=1365). We surveyed 892 pregnant women during prenatal consultations and immediate postpartum period in order to identify RIs of less than 3 years (n=230, 25%) and compared them with LTRs (n=662). Sociodemographic data, baseline health status, prenatal care, obstetrical and neonatal complications were compared between these two groups. Multivariable binary logistic regression was conducted to examine the occurrence of perinatal complications (during pregnancy, labour and delivery, and neonatal period) between RIs and LTRs after adjustment for potential confounders. RESULTS: RIs were living more frequently in precarious conditions. RIs were younger (p<0.001) and had a lower body mass index (p<0.001) than LTRs. Prenatal care was often delayed in RIs, resulting in fewer evaluations during the first trimester (p<0.001). They had a lower prevalence of gestational diabetes mellitus (p<0.05) and less complications during the pregnancy even after adjustment for confounding factors. Similar obstetrical care during labour and delivery occurred. After adjustment for confounding factors, no differences in labour and delivery complications were observed. Although RIs' newborns had a lower umbilical cord blood pH (<0.05), a lower 1 min of life Apgar score (p<0.01) and more frequently required respiratory assistance (p<0.05), no differences in the composite endpoint of neonatal complications were observed. No increase in complications in the RI group was detected whatever the considered period. CONCLUSION: RIs had less optimal prenatal care but this did not result in more obstetrical and perinatal complications.

Assessment of bone quality with trabecular bone score in type 2 diabetes mellitus: A study from the FRISBEE cohort.

OBJECTIVE: The purpose of our study was to compare bone mineral density (BMD) and trabecular bone score (TBS) values between patients with type 2 diabetes (T2D) and control subjects with similar FRAX scores in order to evaluate TBS as an additional tool for assessing fracture risk in diabetic subjects. METHODS: A cross-sectional analysis was performed using BMD results from 260 subjects participating in the FRISBEE study (Fracture RISk Brussels Epidemiological Enquiry), an ongoing prospective epidemiological study in a population-based cohort (Brussels, Belgium) of 3560 postmenopausal women aged 60-85 years. TBS measurement was possible in 1108 subjects from the FRISBEE cohort. Among these 1108 subjects, 65 had known T2D at inclusion. For each diabetic case we selected 3 controls from our database. (n = 195). Diabetic subjects and controls were matched for age and baseline FRAX score for major osteoporotic fractures. RESULTS: BMD (g/cm2 ) tended to be higher in T2D than in control subjects, significantly so at the total hip 0.90 ± 0.13 versus 0.87 ± 0.12 (P = 0.015). On the contrary, TBS was significantly lower in the T2D group (mean = 1.19 ± 0.17) compared with the control group (mean = 1.27 ± 0.13) (P = 0.005). Mean TBS remained significantly lower in T2D (1.22 ± 0.17) compared with the control group (1.27 ± 0.13) (P = 0.02) after adjustment for body mass index. CONCLUSION: Our data suggest that TBS complements BMD at the total hip, in demonstrating the "diabetes-associated bone disease".

Circulating tumor DNA in early response assessment and monitoring of advanced colorectal cancer treated with a multi-kinase inhibitor.

Predictive biomarkers are eagerly awaited in advanced colorectal cancer (aCRC). Targeted sequencing performed on tumor and baseline plasma samples in 20 patients with aCRC treated with regorafenib identified 89 tumor-specific mutations of which ≥50% are also present in baseline plasma. Droplet digital PCR (ddPCR) assays were optimized to monitor circulating tumor DNA (ctDNA) levels in plasmatic samples collected throughout the treatment course and showed the importance of using the absolute value for ctDNA rather than the mutant/wild type ratio in monitoring the therapy outcome. High baseline cell free DNA (cfDNA) levels are associated with shorter overall survival (OS) (HR 7.38, P=0.001). An early increase (D14) in mutated copies/mL is associated with a significantly worse PFS (HR 6.12, P=0.008) and OS (HR 8.02, P=0.004). These data suggest a high prognostic value for early ctDNA level changes and support the use of blood-born genomic markers as a tool for treatment.

Cardiac assessment of early breast cancer patients 18 years after treatment with cyclophosphamide-, methotrexate-, fluorouracil- or epirubicin-based chemotherapy.

BACKGROUND: Epirubicin-based chemotherapy improves the outcome of early breast cancer (BC) patients. However, cardiotoxicity remains an important side effect. METHODS: We re-consented node-positive BC patients enrolled in a phase III trial between 1988 and 1996 which compared six cycles of oral cyclophosphamide, methotrexate, fluorouracil (CMF) versus two epirubicin-cyclophosphamide regimens differing by the anthracycline cumulative dose [standard-dose epirubicin and cyclophosphamide (SDE) (8 × 60 mg/m(2)) and higher-dose epirubicin and cyclophosphamide (HDE) (8 × 100 mg/m(2))]. Eligible patients were those who were alive and free of disease and had no contra-indications to the proposed tests (cardiac evaluation). Cardiotoxicity was defined as asymptomatic systolic dysfunction (left ventricular ejection fraction (LVEF)< 50%, New York Heart Association (NYHA) Class I) or symptomatic heart failure (NYHA Class II-IV). Differences in cardiotoxicity between CMF and SDE/HDE were assessed using chi-square and Fisher Exact tests for binary variables and t-test and Wilcoxon test for continuous variables. RESULTS: Among the 777 patients, 20 cases of CHF were reported (CMF = 1, SDE = 5, HDE = 14; p < 0.001). Between September 2010 and June 2013, 82 patients (30%) out of 269 eligible patients accepted to participate in this substudy. Median follow-up was 18 years (range 15-24). Epirubicin-treated patients had significantly higher heart rate, more abnormal echocardiograms and LVEF by magnetic resonance imaging (MRI) compared to CMF-treated ones. A trend towards higher BNP was also observed in the SDE/HDE group (P = 0.08). No differences were observed in LVEF assessed by echocardiogram or troponin T levels. CONCLUSIONS: Participation rate in this substudy was lower than expected highlighting the complexity of re-calling patients several years after the initial BC diagnosis. After 18 years, epirubicin-treated patients had a lower LVEF by MRI, more abnormal echocardiograms, higher heart rates compared to patients treated with CMF. However, no major delayed cardiotoxicity was observed.

Regorafenib assessment in refractory advanced colorectal cancer: RegARd-C study protocol.

INTRODUCTION: Regorafenib was recently approved for patients with pretreated advanced colorectal cancer (aCRC), despite a moderate improvement of the patients' outcome, and significant toxicities. Based on previous studies showing that early fluorodeoxyglucose-positron emission tomography (FDG-PET)-based metabolic response assessment (MRA) might adequately select patients unlikely to benefit from treatment, the RegARd-C trial uses early MRA to identify likely non-responders to regorafenib in a population of patients with aCRC and guide a comprehensive evaluation of genomic and epigenetic determinants of resistance to treatment. METHODS AND ANALYSIS: RegARd-C is a multicentric prospective study. Its primary objective is to identify non-benefitters from regorafenib given at 160 mg/day, 3 weeks out of 4 in a population of patients with pretreated aCRC. Baseline PET is repeated at day 14 of the first treatment course. MRA is blinded for the investigators. Overall survival (OS) is the primary end point and will be correlated with metabolic parameters and (epi)genetic alterations assessed from tumour and serial blood samples. A target sample size of 105 evaluable patients (70 as derivation set and 35 as validation set), is considered as sufficient to validate an expected HR for OS of metabolic responders compared to metabolic non-responders significantly <1 (with 80% power and 1-sided 5% α in case of a true HR≤0.59 and a responders rate of 47%). ETHICS AND DISSEMINATION: The study was approved by the Institut Jules Bordet's competent ethics committee and complies with the Helsinki declaration or the Belgian laws and regulations, whichever provides the greatest protection for the patient, and follows the International Conference on Harmonisation E 6 (R1) Guideline for Good Clinical Practice, reference number CPMP/ICH/135/95. The protocol and the trials results, even inconclusive, will be presented at international oncology congresses, and published in peer-reviewed journals. Genomic and epigenetic data will be made available in public open data sets. TRIAL REGISTRATION NUMBERS: EudraCT number: 2012-005655-16; ClinicalTrials.gov number: NCT01929616.

Sleep efficiency during sleep studies: results of a prospective study comparing home-based and in-hospital polysomnography.

To date, the clinical use of unattended home-based polysomnography (PSG) is not recommended. To assess whether sleep efficiency is better at home, we have performed a prospective, crossover, single-blind study comparing unattended home- versus attended in-hospital PSG in a population referred for high clinical suspicion of obstructive sleep apnoea syndrome (OSA). Within 2 weeks, all the patients underwent both PSG performed by the same sleep technician, which were analysed by another blinded technician. Payments for each procedure were also calculated. Sixty-six patients (mean age: 49±13 years; mean body mass index: 30±7; mean Epworth Sleepiness Scale: 10±5) were included. The quality of recordings was poor in 1.5% of the attended PSG versus 4.7% for unattended PSG (P=0.36). Sleep efficiency at home was better (82% versus 75%, P<0.001), and sleep duration longer (412 min versus 365 min, P<0.001). Sleep latency was also shorter at home (28 min versus 45 min, P=0.004), and patients spent more time in rapid eye movement sleep (19% versus 16%, P=0.006). Apnoea-hypopnoea index (23 versus 26, P=0.08) was similar at home and in the sleep lab. Sixty-seven per cent of patients preferred home-based PSG. PSG payment was also lower at home (268 Euros versus 1057 Euros). We conclude that home-based PSG is associated with a better sleep efficiency. It also appears as feasible and reliable in patients with high preclinical suspicion for OSA. It is also more comfortable for the patients whose sleep efficiency is better and allows cost saving related to the absence of hospitalization.

Predicting febrile neutropenic patients at low risk using the MASCC score: does bacteremia matter?

BACKGROUND: Febrile neutropenic cancer patients represent a heterogeneous population with a limited proportion at risk of serious medical complications. The Multinational Association for Supportive Care in Cancer (MASCC) score has been developed and validated for identifying low-risk patients at the onset of febrile neutropenia. Since bacteremia, although not documented at baseline, is a predictor of pejorative outcome, the purpose of this study was to investigate the possible interaction between the MASCC score and bacteremic status and to assess whether, assuming that bacteremic status could be predicted at onset of febrile neutropenia, adding bacteremia as a covariate in a risk model would improve the accuracy of low-risk patients identification. METHODS: Two consecutive multicentric observational studies were carried out from 1994 till 2005 involving 2,142 febrile neutropenic patients. The study data bases were retrospectively used for the present analysis. RESULTS: A predictive value was found for the MASCC score in all strata obtained by stratification for the bacteremic status with odds ratios for successful outcome being, in patients with a score ≥21, respectively, 6.06 (95%CI: 4.51-8.15), 3.42 (95%CI: 1.95-5.98), and 6.04 (95%CI: 3.01-12.09) in patients without bacteremia, gram-positive bacteremia, and gram-negative bacteremia. No interaction between the MASCC score and the bacteremic status was present. A clinical prediction rule integrating the MASCC score and the bacteremic status was not helpful in improving the identification of low-risk patients. This rule may then be used in a general population of patients with febrile neutropenia without having concerns for a lower predictive value in bacteremic patients. CONCLUSIONS: Our results suggest that the knowledge, provided we could find a model to predict it at fever onset, of a bacteremic etiology of the fever would be of little additional value to the MASCC score when attempting to identify low-risk patients.