A randomized phase II trial on the addition of dutasteride to combined androgen blockade therapy versus combined androgen blockade therapy alone in patients with advanced or metastatic salivary duct carcinoma - the DUCT study protocol.

Background: Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer, frequently associated with incurable recurrences and distant metastases (R/M). Proliferation of SDC relies on androgen receptor (AR) signalling, prompting the use of combined androgen blockade (CAB, i.e.

Exploring immune status in peripheral blood and tumor tissue in association with survival in patients with multi-organ metastatic colorectal cancer.

Colorectal cancer (CRC) raises considerable clinical challenges, including a high mortality rate once the tumor spreads to distant sites. At this advanced stage, more accurate prediction of prognosis and treatment outcome is urgently needed. The role of cancer immunity in metastatic CRC (mCRC) is poorly understood.

Bayesian federated inference for estimating statistical models based on non-shared multicenter data sets.

Identifying predictive factors for an outcome of interest via a multivariable analysis is often difficult when the data set is small. Combining data from different medical centers into a single (larger) database would alleviate this problem, but is in practice challenging due to regulatory and logistic problems. Federated learning (FL) is a machine learning approach that aims to construct from local inferences in separate data centers what would have been inferred had the data sets been merged.

A powerful global test for spliceQTL effects.

Statistical methods to test for effects of single nucleotide polymorphisms (SNPs) on exon inclusion exist but often rely on testing of associations between multiple exon-SNP pairs, with sometimes subsequent summarization of results at the gene level. Such approaches require heavy multiple testing corrections and detect mostly events with large effect sizes. We propose here a test to find spliceQTL (splicing quantitative trait loci) effects that takes all exons and all SNPs into account simultaneously.

Estimation and expected sample size in Simon's two-stage designs that stop as early as possible.

In early phase clinical studies in oncology, Simon's two-stage designs are widely used. The trial design could be made more efficient by stopping early in the second stage when the required number of responses is reached, or when it has become clear that this target can no longer be met (a form of non-stochastic curtailment). Early stopping, however, will affect proper estimation of the response rate.

Excessive toxicity of cabozantinib in a phase II study in patients with recurrent and/or metastatic salivary gland cancer.

Aim: Because the tyrosine kinases c-MET and vascular endothelial growth factor receptors (VEGFR) are often overexpressed in salivary gland cancer (SGC), this study evaluated the efficacy and safety of cabozantinib in patients with recurrent/metastatic (R/M) SGC.

Patients And Methods: A single-centre phase II study was conducted. Patients with immunohistochemical c-MET-positive R/M SGC were included in three cohorts: adenoid cystic carcinoma (ACC); salivary duct carcinoma (SDC) and other miscellaneous SGCs.

Update to a randomized controlled trial of lutetium-177-PSMA in Oligo-metastatic hormone-sensitive prostate cancer: the BULLSEYE trial.

Background: The BULLSEYE trial is a multicenter, open-label, randomized controlled trial to test the hypothesis if Lu-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.

Differences in the number of de novo mutations between individuals are due to small family-specific effects and stochasticity.

The number of de novo mutations (DNMs) in the human germline is correlated with parental age at conception, but this explains only part of the observed variation. We investigated whether there is a family-specific contribution to the number of DNMs in offspring. The analysis of DNMs in 111 dizygotic twin pairs did not identify a substantial family-specific contribution.

Predictive and Prognostic Biomarker Identification in a Large Cohort of Androgen Receptor-Positive Salivary Duct Carcinoma Patients Scheduled for Combined Androgen Blockade.

Patients suffering from recurrent or metastatic (R/M) salivary duct carcinoma (SDC) are often treated with combined androgen blockade (CAB). However, CAB frequently fails, resulting in a worse prognosis. Therefore, biomarkers that can predict treatment failure are urgently needed.

Two-Stage Testing for Epistasis: Screening and Verification.

Undiscovered gene-to-gene interaction (epistasis) is a possible explanation for the "missing heritability" of complex traits and diseases. On a genome-wide scale, screening for epistatic effects among all possible pairs of genetic markers faces two main complications. Firstly, the classical statistical methods for modeling epistasis are computationally very expensive, which makes them impractical on such large scale.

Flexible modelling of risk factors on the incidence of pneumonia in young children in South Africa using piece-wise exponential additive mixed modelling.

Introduction: Recurrent episodes of pneumonia are frequently modeled using extensions of the Cox proportional hazards model with the underlying assumption of time-constant relative risks measured by the hazard ratio. We aim to relax this assumption in a study on the effect of factors on the evolution of pneumonia incidence over time based on data from a South African birth cohort study, the Drakenstein child health study.

Methods: We describe and apply two models: a time-constant and a time-varying relative effects model in a piece-wise exponential additive mixed model's framework for recurrent events.

Prognostic value of PSMA, c-MET and E-cadherin in salivary duct carcinoma.

Objectives: Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer. Androgen receptor (AR) (96%) and HER2 (29-46%) expression, and a high propensity for regional lymph node metastases are hallmarks of the disease. We hypothesized that c-MET, E-cadherin, PSMA tumor and PSMA neovascular expression may be prognostic factors in SDC.

Lutetium-177-PSMA-I&T as metastases directed therapy in oligometastatic hormone sensitive prostate cancer, a randomized controlled trial.

Background: In recent years, there is increasing evidence showing a beneficial outcome (e.g. progression free survival; PFS) after metastases-directed therapy (MDT) with external beam radiotherapy (EBRT) or targeted surgery for oligometastatic hormone sensitive prostate cancer (oHSPC).

Mutational spectrum and dynamics of clonal hematopoiesis in anemia of older individuals.

Anemia is a major and currently poorly understood clinical manifestation of hematopoietic aging. Upon aging, hematopoietic clones harboring acquired leukemia-associated mutations expand and become detectable, now referred to as clonal hematopoiesis (CH). To investigate the relationship between CH and anemia of the elderly, we explored the landscape and dynamics of CH in older individuals with anemia.

Thermal distribution, physiological effects and toxicities of extracorporeally induced whole-body hyperthermia in a pig model.

Background: Extracorporeally induced whole-body hyperthermia (eWBH) might be a beneficial treatment in cancer patients. Objectives of this pig study were to assess thermal distribution, (patho-)physiological effects, and safety of eWBH with a new WBH device.

Methods: Fourteen healthy adult pigs were anesthetized, mechanically ventilated, and cannulated; 12 were included in the analysis.

Ga-PSMA-HBED-CC PET/CT imaging for adenoid cystic carcinoma and salivary duct carcinoma: a phase 2 imaging study.

: Treatment options for recurrent and/or metastatic (R/M) adenoid cystic carcinoma (ACC) and salivary duct carcinoma (SDC), major subtypes of salivary gland cancer, are limited. Both tumors often show overexpression of prostate-specific membrane antigen (PSMA). In prostate cancer, PSMA-ligands labeled with Ga or Lu are used for imaging and therapy, respectively.

Methotrexate plus or minus cetuximab as first-line treatment in a recurrent or metastatic (R/M) squamous cell carcinoma population of the head and neck (SCCHN), unfit for cisplatin combination treatment, a phase Ib-randomized phase II study Commence.

Background: Methotrexate in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) has limited progression-free survival (PFS) benefit. We hypothesized that adding cetuximab to methotrexate improves PFS.

Methods: In the phase-Ib-study, patients with R/M SCCHN received methotrexate and cetuximab as first-line treatment.

Estimating the age at onset distribution of the asymptomatic stage of a genetic disease based on pedigree data.

Information on the age at onset distribution of the asymptomatic stage of a disease can be of paramount importance in early detection and timely management of that disease. However, accurately estimating this distribution is challenging, because the asymptomatic stage is difficult to recognize for the patient and is often detected as an incidental finding or in case of recommended screening; the age at onset is often interval-censored. In this paper, we propose a method for the estimation of the age at onset distribution of the asymptomatic stage of a genetic disease based on ascertained pedigree data that take into account the way the data are ascertained to overcome selection bias.

Self-management program improves participation in patients with neuromuscular disease: A randomized controlled trial.

Objective: To investigate the effectiveness of Energetic, a self-management group program combining aerobic training, energy conservation management, and relapse prevention to improve social participation in patients with neuromuscular disease (NMD) and chronic fatigue.

Methods: In this multicenter, assessor-blinded, 2-armed randomized controlled trial with repeated measurements, 53 patients with various types of NMD and chronic fatigue were randomly allocated to Energetic, a 4-month group intervention, or to usual care. The primary endpoint was social participation assessed with the Canadian Occupational Performance Measure (COPM) performance scale immediately postintervention.

Prospective Study of Drug-induced Interstitial Lung Disease in Advanced Breast Cancer Patients Receiving Everolimus Plus Exemestane.

Background: Everolimus-related interstitial lung disease (ILD) (also: pneumonitis) poses a difficulty for physicians, as it is hard to discriminate ILD from other causes of respiratory symptoms and to decide on safe treatment continuation.

Objective: We investigated the capability of pulmonary function tests (PFT), plasma biomarkers, everolimus pharmacokinetics, and FDG-PET to discriminate between everolimus-related ILD and other causes of respiratory problems and to predict the severity of ILD.

Patients And Methods: Women starting treatment with everolimus plus exemestane for advanced breast cancer were included.

Prophylactic antibiotics reduce hospitalisations and cost in locally advanced head and neck cancer patients treated with chemoradiotherapy: A randomised phase 2 study.

Background: Platinum-based chemoradiotherapy for locally advanced head and neck cancer (LAHNC) induces a high rate of acute toxicity, including dysphagia and aspiration pneumonia. We hypothesised that prophylactic antibiotics can prevent pneumonia and hospitalisations and can be cost-effective.

Patient And Methods: In this multicentre randomised trial, patients with LAHNC treated with chemoradiotherapy received prophylactic amoxicillin/clavulanic acid from day 29 after the start of treatment until 14 days after completion of chemoradiotherapy or standard care without prophylaxis.

Renal imaging in 199 Dutch patients with Birt-Hogg-Dubé syndrome: Screening compliance and outcome.

Birt-Hogg-Dubé syndrome is associated with an increased risk for renal cell carcinoma. Surveillance is recommended, but the optimal imaging method and screening interval remain to be defined. The main aim of our study was to evaluate the outcomes of RCC surveillance to get insight in the safety of annual US in these patients.

Everolimus Exposure and Early Metabolic Response as Predictors of Treatment Outcomes in Breast Cancer Patients Treated with Everolimus and Exemestane.

Background: Treating breast cancer patients with everolimus and exemestane can be challenging due to toxicity and suboptimal treatment responses.

Objective: We investigated whether everolimus exposure and early metabolic response are predictors for toxicity and effectiveness in these patients.

Patients And Methods: We performed pharmacokinetic assessments 14 and 35 days after starting treatment.

Phenotype-genotype relations in facioscapulohumeral muscular dystrophy type 1.

To determine how much of the clinical variability in facioscapulohumeral muscular dystrophy type 1 (FSHD1) can be explained by the D4Z4 repeat array size, D4Z4 methylation and familial factors, we included 152 carriers of an FSHD1 allele (23 single cases, 129 familial cases from 37 families) and performed state-of-the-art genetic testing, extensive clinical evaluation and quantitative muscle MRI. Familial factors accounted for 50% of the variance in disease severity (FSHD clinical score). The explained variance by the D4Z4 repeat array size for disease severity was limited (approximately 10%), and varied per body region (facial muscles, upper and lower extremities approximately 30%, 15% and 3%, respectively).

Estimating the penetrance of pathogenic gene variants in families with missing pedigree information.

Accurate assessment of the age-dependent disease risk conferred by germline variants in disease susceptibility genes is often hampered by the way the data are collected. Cohort-based data sets frequently contain an overrepresentation of patients (i.e.