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.

Digoxin treatment does not reinduce radioiodine uptake in radioiodine refractory non-medullary thyroid carcinoma.

Objective: Patients with non-medullary thyroid carcinoma (NMTC) that are refractory to radioactive iodine (RAI) have a poor prognosis. Strategies for restoring the ability to take up iodine, so-called redifferentiation, are promising but not suitable for all patients. Preclinical studies, in human cell lines just as in a murine model, have shown that the cardiac glycoside digoxin restored RAI uptake.

European experience with the Afirma Gene Expression Classifier for indeterminate thyroid nodules: A clinical utility study in the Netherlands.

Background: The Gene Expression Classifier (GEC) and Genomic Sequencing Classifier (GSC) were developed to improve risk stratification of indeterminate nodules. Our aim was to assess the clinical utility in a European population with restrictive diagnostic workup.

Methods: Clinical utility of the GEC was assessed in a prospective multicenter cohort of 68 indeterminate nodules.

Precision oncology using organoids of a secretory carcinoma of the salivary gland treated with TRK-inhibitors.

The use of anticancer drugs targeting specific molecular tumor characteristics is rapidly increasing in clinical practice, but selecting patients to benefit from these remains a challenge. It has been suggested that organoid cultures would be ideally suited to test drug responses in vitro. Here we describe and characterize in depth a case of ETV6-NTRK3 gene fusion-positive secretory carcinoma of the salivary glands and corresponding organoid cultures that responded and subsequently acquired resistance to TRK targeting therapy with larotrectinib.

Development and characterization of patient-derived salivary gland cancer organoid cultures.

Objective: Three-dimensional organoid cell cultures have been established for a variety of human cancers. For most rare cancers, including salivary gland cancer (SGC), these models are lacking, despite the great unmet need to study cancer biology in these diseases. Therefore, we aimed to develop patient-derived organoid (PDO) models for different subtypes of SGC.

[F]FDG Uptake and Expression of Immunohistochemical Markers Related to Glycolysis, Hypoxia, and Proliferation in Indeterminate Thyroid Nodules.

Purpose: The current study explored the association between 2-[F]fluoro-2-deoxy-D-glucose ([F]FDG) uptake and the quantitative expression of immunohistochemical markers related to glucose metabolism, hypoxia, and cell proliferation in benign and malignant thyroid nodules of indeterminate cytology.

Procedures: Using a case-control design, 24 patients were selected from participants of a randomized controlled multicenter trial (NCT02208544) in which [F]FDG-PET/CT and thyroid surgery were performed for Bethesda III and IV nodules. Three equally sized groups of [F]FDG-positive malignant, [F]FDG-positive benign, and [F]FDG-negative benign nodules were included.

Identification of Fusion Genes and Targets for Genetically Matched Therapies in a Large Cohort of Salivary Gland Cancer Patients.

Salivary gland cancer (SGC) is a rare cancer for which systemic treatment options are limited. Therefore, it is important to characterize its genetic landscape in search for actionable aberrations, such as gene fusions. This research aimed to identify these actionable aberrations by combining NGS-based analysis of RNA (gene fusions) and DNA (single and multiple nucleotide variants, copy number variants, microsatellite instability and tumor mutational burden) in a large cohort of SGC patients.

High-Accuracy Nodal Staging of Head and Neck Cancer With USPIO-Enhanced MRI: A New Reading Algorithm Based on Node-to-Node Matched Histopathology.

Objectives: Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) is a potential diagnostic tool for lymph node assessment in patients with head and neck cancer. Validation by radiologic-pathologic correlation is essential before the method is evaluated in clinical studies. In this study, MRI signal intensity patterns of lymph nodes are correlated to their histopathology to develop a new USPIO-enhanced MRI reading algorithm that can be used for nodal assessment in head and neck cancer patients.

Thermal Effects of CO, KTP, and Blue Lasers with a Flexible Fiber Delivery System on Vocal Folds.

Objective: To determine the differences in thermal effects on vocal folds between four fiber-routed lasers.

Methods: In this experimental laboratory study the thermal effects of an AcuPulse Duo CO (CO AP), UltraPulse Duo CO (CO UP), KTP, and Blue laser were analyzed using a Schlieren technique on a human tissue mimicking gel model. Power, laser duration, laser fiber distance to tissue and mode (continuous wave [CW] vs pulsed [P] modes) were evaluated in varying combinations in order to compare the effects of the tested lasers and to explore the individual effect on thermal expansion and incision depth of each setting.

Validation of In Vivo Nodal Assessment of Solid Malignancies with USPIO-Enhanced MRI: A Workflow Protocol.

Background: In various cancer types, the first step towards extended metastatic disease is the presence of lymph node metastases. Imaging methods with sufficient diagnostic accuracy are required to personalize treatment. Lymph node metastases can be detected with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI), but this method needs validation.

Results of histopathological revisions of major salivary gland neoplasms in routine clinical practice.

Aims: Salivary gland neoplasms are rare and are characterised by overlapping histopathological aspects. Therefore, the assessment of the correct histopathological diagnosis can be challenging. This study evaluated the frequency of pathology consultations and revisions for salivary gland neoplasms during routine clinical practice in the Netherlands.

[F]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules: a blinded, randomised controlled multicentre trial.

Purpose: To assess the impact of an [F]FDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with indeterminate cytology.

Methods: In this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent [F]FDG-PET/CT and were randomised to an [F]FDG-PET/CT-driven or diagnostic surgery group. In the [F]FDG-PET/CT-driven group, management was based on the [F]FDG-PET/CT result: when the index nodule was visually [F]FDG-positive, diagnostic surgery was advised; when [F]FDG-negative, active surveillance was recommended.

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.

Validation of the Milan System for Reporting Salivary Gland Cytopathology and the diagnostic accuracy of FNA cytology for submandibular gland lesions.

Background: The Milan System for Salivary Gland Cytopathology (MSRSGC) is a categorical system for salivary gland fine-needle aspiration cytopathology (FNAC) developed to aid clinicians in the management of salivary gland lesions. This classification is widely studied and validated, especially in cohorts that consist of mostly parotid gland lesions. However, only sparse literature describes the use of this classification for submandibular gland lesions in particular.

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.

IGF2 is a potential factor in RAI-refractory differentiated thyroid cancer.

Differentiated thyroid cancer (DTC) is the most frequent endocrine tumor with a good prognosis after primary treatment in most cases. By contrast, 30-40% of patients with metastatic DTC are unresponsive to I radioactive iodide (RAI) treatment due to tumor dedifferentiation. Currently, underlying molecular mechanisms of dedifferentiation remain elusive and predictive biomarkers are lacking.

Accuracy of parotid gland FNA cytology and reliability of the Milan System for Reporting Salivary Gland Cytopathology in clinical practice.

Background: Differentiating between malignant and benign salivary gland tumors with fine-needle aspiration cytology (FNAC) can be challenging. This study was aimed at testing the validity of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and at assessing possible differences in the sensitivity and specificity of parotid gland FNAC between dedicated head and neck (H&N) centers, subdivided into head and neck oncology centers (HNOCs) and head and neck oncology affiliated centers (HNOACs), and general hospitals (GHs).

Methods: The Dutch Pathology Registry (PALGA) database was searched for patients who had undergone a salivary gland resection between January 1, 2006, and January 1, 2017, and had a preoperative FNAC result.

Novel Diagnostic Approaches for Assessment of the Clinically Negative Neck in Head and Neck Cancer Patients.

In head and neck cancer, the presence of nodal disease is a strong determinant of prognosis and treatment. Despite the use of modern multimodality diagnostic imaging, the prevalence of occult nodal metastases is relatively high. This is why in clinically node negative head and neck cancer the lymphatics are treated "electively" to eradicate subclinical tumor deposits.

Myotonic dystrophy and recurrent pleomorphic adenomas: Case report and association hypothesis.

We report a case of a patient with concurrent myotonic dystrophy and recurrent pleomorphic adenoma and hypothesize the association between both diseases. A 58-year-old man with classic myotonic dystrophy type 1 was diagnosed with pleomorphic adenoma. Appropriate treatment was commenced.

Assessment of surgical tumor-free resection margins in fresh squamous-cell carcinoma resection specimens of the tongue using a clinical MRI system.

Background: Current intraoperative methods of visual inspection and tissue palpation by the surgeon, and frozen section analysis cannot reliably prevent inadequate surgical margins in patients treated for oral squamous-cell carcinoma (OSCC). This study assessed feasibility of MRI for the assessment of surgical resection margins in fresh OSCC specimens.

Methods: Ten consecutive tongue specimens containing OSCC were scanned using 3 T clinical whole-body MRI.