Blood-derived dendritic cell vaccinations induce immune responses that correlate with clinical outcome in patients with chemo-naive castration-resistant prostate cancer.

Background: Clinical benefit of cellular immunotherapy has been shown in patients with castration-resistant prostate cancer (CRPC). We investigated the immunological response and clinical outcome of vaccination with blood-derived CD1c myeloid dendritic cells (mDCs; cDC2) and plasmacytoid DCs (pDCs).

Methods: In this randomized phase IIa trial, 21 chemo-naive CRPC patients received maximally 9 vaccinations with mature mDCs, pDCs or a combination of mDCs plus pDCs.

Surveillance of Women with the BRCA1 or BRCA2 Mutation by Using Biannual Automated Breast US, MR Imaging, and Mammography.

Purpose To evaluate a multimodal surveillance regimen including yearly full-field digital (FFD) mammography, dynamic contrast agent-enhanced (DCE) magnetic resonance (MR) imaging, and biannual automated breast (AB) ultrasonography (US) in women with BRCA1 and BRCA2 mutations. Materials and Methods This prospective multicenter trial enrolled 296 carriers of the BRCA mutation (153 BRCA1 and 128 BRCA2 carriers, and 15 women with first-degree untested relatives) between September 2010 and November 2012, with follow-up until November 2015. Participants underwent 2 years of intensified surveillance including biannual AB US, and routine yearly DCE MR imaging and FFD mammography.

Time to enhancement derived from ultrafast breast MRI as a novel parameter to discriminate benign from malignant breast lesions.

Objectives: To investigate time to enhancement (TTE) as novel dynamic parameter for lesion classification in breast magnetic resonance imaging (MRI).

Methods: In this retrospective study, 157 women with 195 enhancing abnormalities (99 malignant and 96 benign) were included. All patients underwent a bi-temporal MRI protocol that included ultrafast time-resolved angiography with stochastic trajectory (TWIST) acquisitions (1.

Prophylactic vaccines are potent activators of monocyte-derived dendritic cells and drive effective anti-tumor responses in melanoma patients at the cost of toxicity.

Dendritic cell (DC)-based immunotherapy is explored worldwide in cancer patients, predominantly with DC matured with pro-inflammatory cytokines and prostaglandin E2. We studied the safety and efficacy of vaccination with monocyte-derived DC matured with a cocktail of prophylactic vaccines that contain clinical-grade Toll-like receptor ligands (BCG, Typhim, Act-HIB) and prostaglandin E2 (VAC-DC). Stage III and IV melanoma patients were vaccinated via intranodal injection (12 patients) or combined intradermal/intravenous injection (16 patients) with VAC-DC loaded with keyhole limpet hemocyanin (KLH) and mRNA encoding tumor antigens gp100 and tyrosinase.

Effective Clinical Responses in Metastatic Melanoma Patients after Vaccination with Primary Myeloid Dendritic Cells.

Purpose: Thus far, dendritic cell (DC)-based immunotherapy of cancer was primarily based on in vitro-generated monocyte-derived DCs, which require extensive in vitro manipulation. Here, we report on a clinical study exploiting primary CD1c(+) myeloid DCs, naturally circulating in the blood.

Experimental Design: Fourteen stage IV melanoma patients, without previous systemic treatment for metastatic disease, received autologous CD1c(+) myeloid DCs, activated by only brief (16 hours) ex vivo culture and loaded with tumor-associated antigens of tyrosinase and gp100.

Intranodal vaccination with mRNA-optimized dendritic cells in metastatic melanoma patients.

Autologous dendritic cell (DC) therapy is an experimental cellular immunotherapy that is safe and immunogenic in patients with advanced melanoma. In an attempt to further improve the therapeutic responses, we treated 15 patients with melanoma, with autologous monocyte-derived immature DC electroporated with mRNA encoding CD40 ligand (CD40L), CD70 and a constitutively active TLR4 (caTLR4) together with mRNA encoding a tumor-associated antigen (TAA; respectively gp100 or tyrosinase). In addition, DC were pulsed with keyhole limpet hemocyanin (KLH) that served as a control antigen.

A novel approach to contrast-enhanced breast magnetic resonance imaging for screening: high-resolution ultrafast dynamic imaging.

Objectives: The use of breast magnetic resonance imaging (MRI) as screening tool has been stalled by high examination costs. Scan protocols have lengthened to optimize specificity. Modern view-sharing sequences now enable ultrafast dynamic whole-breast MRI, allowing much shorter and more cost-effective procedures.

Evaluation of the effect of computer-aided classification of benign and malignant lesions on reader performance in automated three-dimensional breast ultrasound.

Rationale And Objectives: To investigate the effect of a newly developed computer-aided diagnosis (CAD) system on reader interpretation of breast lesions in automated three-dimensional (3D) breast ultrasound.

Materials And Methods: A CAD system was developed to differentiate malignant lesions from benign lesions including automated lesion segmentation in three dimensions; extraction of lesion features such as spiculation, margin contrast, and posterior acoustic behavior; and a classification stage. Eighty-eight patients with breast lesions were included for an observer study: 47 lesions were malignant and 41 were benign.

Automated characterization of breast lesions imaged with an ultrafast DCE-MR protocol.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast has become an invaluable tool in the clinical work-up of patients suspected of having breast carcinoma. The purpose of this study is to introduce novel features extracted from the kinetics of contrast agent uptake imaged by a short (100 s) view-sharing MRI protocol, and to investigate how these features measure up to commonly used features for regular DCE-MRI of the breast. Performance is measured with a computer aided diagnosis (CADx) system aimed at distinguishing benign from malignant lesions.

Computer-aided detection of cancer in automated 3-D breast ultrasound.

Automated 3-D breast ultrasound (ABUS) has gained a lot of interest and may become widely used in screening of dense breasts, where sensitivity of mammography is poor. However, reading ABUS images is time consuming, and subtle abnormalities may be missed. Therefore, we are developing a computer aided detection (CAD) system to help reduce reading time and prevent errors.

One-day core needle biopsy in a breast clinic: 4 years experience.

Many attempts have been made to combine the high diagnostic accuracy and conclusive rate of core needle biopsy (CNB) with the speed of fine needle aspiration cytology in evaluation of solid breast lesions. Multiple hybrid techniques have been developed to achieve this. We describe a cohort of patients for whom we used a relatively new, accelerated method of CNB processing, allowing for a definitive diagnosis the same day.

Computer-aided detection of masses at mammography: interactive decision support versus prompts.

Purpose: To compare effectiveness of an interactive computer-aided detection (CAD) system, in which CAD marks and their associated suspiciousness scores remain hidden unless their location is queried by the reader, with the effect of traditional CAD prompts used in current clinical practice for the detection of malignant masses on full-field digital mammograms.

Materials And Methods: The requirement for institutional review board approval was waived for this retrospective observer study. Nine certified screening radiologists and three residents who were trained in breast imaging read 200 studies (63 studies containing at least one screen-detected mass, 17 false-negative studies, 20 false-positive studies, and 100 normal studies) twice, once with CAD prompts and once with interactive CAD.

Targeting CD4(+) T-helper cells improves the induction of antitumor responses in dendritic cell-based vaccination.

To evaluate the relevance of directing antigen-specific CD4(+) T helper cells as part of effective anticancer immunotherapy, we investigated the immunologic and clinical responses to vaccination with dendritic cells (DC) pulsed with either MHC class I (MHC-I)-restricted epitopes alone or both MHC class I and II (MHC-I/II)-restricted epitopes. We enrolled 33 stage III and IV HLA-A*02:01-positive patients with melanoma in this study, of whom 29 were evaluable for immunologic response. Patients received intranodal vaccinations with cytokine-matured DCs loaded with keyhole limpet hemocyanin and MHC-I alone or MHC-I/II-restricted tumor-associated antigens (TAA) of tyrosinase and gp100, depending on their HLA-DR4 status.

Vaccination with mRNA-electroporated dendritic cells induces robust tumor antigen-specific CD4+ and CD8+ T cells responses in stage III and IV melanoma patients.

Purpose: Electroporation of dendritic cells (DC) with mRNA encoding tumor-associated antigens (TAA) has multiple advantages compared to peptide loading. We investigated the immunologic and clinical responses to vaccination with mRNA-electroporated DC in stage III and IV melanoma patients.

Experimental Design: Twenty-six stage III HLA*02:01 melanoma patients scheduled for radical lymph node dissection (stage III) and 19 melanoma patients with irresectable locoregional or distant metastatic disease (referred to as stage IV) were included.

18F-2-deoxy-2-fluoro-D-glucose positron emission tomography, computed tomography, and magnetic resonance imaging for the detection of experimental colorectal liver metastases.

During the treatment of colorectal liver metastases, evaluation of treatment efficacy is of the utmost importance for decision making. The aim of the present study was to explore the ability of preclinical imaging modalities to detect experimental liver metastases. Nine male Wag/Rij rats underwent a laparotomy with intraportal injection of CC531 tumor cells.

Computer-aided lesion diagnosis in automated 3-D breast ultrasound using coronal spiculation.

A computer-aided diagnosis (CAD) system for the classification of lesions as malignant or benign in automated 3-D breast ultrasound (ABUS) images, is presented. Lesions are automatically segmented when a seed point is provided, using dynamic programming in combination with a spiral scanning technique. A novel aspect of ABUS imaging is the presence of spiculation patterns in coronal planes perpendicular to the transducer.

Early identification of antigen-specific immune responses in vivo by [18F]-labeled 3'-fluoro-3'-deoxy-thymidine ([18F]FLT) PET imaging.

Current biomarkers are unable to adequately predict vaccine-induced immune protection in humans with infectious disease or cancer. However, timely and adequate assessment of antigen-specific immune responses is critical for successful vaccine development. Therefore, we have developed a method for the direct assessment of immune responses in vivo in a clinical setting.

MR-guided breast biopsy at 3T: diagnostic yield of large core needle biopsy compared with vacuum-assisted biopsy.

Objective: The purpose of this study was to evaluate two MR-guided biopsy techniques at 3 T, large core needle breast biopsy (LCNB) and vacuum-assisted breast biopsy (VAB) and to compare the diagnostic yield and rate of complications to determine the optimal biopsy technique at 3 T.

Methods: 55 LCNB and 64 VAB were consecutively performed. Benign biopsy results were verified by retrospective correlation of histology, with pre-interventional, post-interventional MRI studies and follow-up and were classified as representative or non-representative.

Route of administration modulates the induction of dendritic cell vaccine-induced antigen-specific T cells in advanced melanoma patients.

Purpose: It is unknown whether the route of administration influences dendritic cell (DC)-based immunotherapy. We compared the effect of intradermal versus intranodal administration of a DC vaccine on induction of immunologic responses in melanoma patients and examined whether concomitant administration of interleukin (IL)-2 increases the efficacy of the DC vaccine.

Experimental Design: HLA-A2.

MRI-guided breast biopsy at 3T using a dedicated large core biopsy set: feasibility and initial results.

Objective: The increasing importance of breast MRI in the diagnostic processes concerning breast cancer yield often lesions that are visible on MRI only. To assess the nature of these lesions, pathologic analysis is necessary. Therefore, MR-guided biopsy should be available.

Using computer-aided detection in mammography as a decision support.

Objective: To evaluate an interactive computer-aided detection (CAD) system for reading mammograms to improve decision making.

Methods: A dedicated mammographic workstation has been developed in which readers can probe image locations for the presence of CAD information. If present, CAD findings are displayed with the computed malignancy rating.

The diagnostic hurdle of an elderly male with bone pain: how 18F-FDG-PET led to diagnosis of a leiomyosarcoma of the adrenal gland.

It is uncommon for patients to present with bone metastases while the primary tumor is still unknown. The case of a patient with bone metastases as primary presentation of leiomyosarcoma, who was diagnosed after a 18F-FDG PET-CT and a CT-guided biopsy of the adrenal gland is described. If after routine physical, laboratory and radiological investigations no diagnosis can be made, 18F-FDG PET should be added to the conventional work-up of patients with unknown primary cancer.

Commonly used imaging techniques for diagnosis and staging.

Imaging plays a vital role in the management of patients with cancer. Not only is it important for diagnosis, indicating sites of abnormality, and guiding biopsies, but it is also crucial in assessing disease extent and thereby determining treatment. In this review, conventional imaging techniques such as ultrasound, computed tomography, magnetic resonance imaging, and [18F]fluorodeoxyglucose-positron emission tomography are described, with attention to their mechanisms of action, and their strengths and weaknesses in diagnosis and staging of tumors.