Challenges and controversies patients and (health care) professionals experience in managing vaginal, vulvar, penile or anal cancer: The SILENCE study.

Objective: Patients with vaginal, vulvar, penile or anal cancer experience deteriorated psychosocial functioning and decreased Quality of Life (QoL). The aims of this study were to explore (1) the challenges and controversies patients experience in managing vaginal, vulvar, penile or anal cancer; their unmet needs; and how this affects their psychosocial functioning and (2) the gaps health care professionals (HCPs) experience in providing psychosocial support and potential improvements in care.

Methods: Semi-structured interviews with patients with vaginal, vulvar, penile or anal cancer and with HCPs were conducted.

Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma (CHOPIN): study protocol for a phase Ib/randomized phase II trial.

Background: While immune checkpoint inhibition (ICI) has revolutionized the treatment of metastatic cutaneous melanoma, no standard treatments are available for patients with metastatic uveal melanoma (UM). Several locoregional therapies are effective in the treatment of liver metastases, such as percutaneous hepatic perfusion with melphalan (M-PHP). The available literature suggests that treatment with ICI following locoregional treatment of liver UM metastases can result in clinical response.

T cells expanded from renal cell carcinoma display tumor-specific CD137 expression but lack significant IFN-γ, TNF-α or IL-2 production.

Metastatic renal cell carcinoma (RCC) has a poor prognosis. Recent advances have shown beneficial responses to immune checkpoint inhibitors, such as anti-PD-1/PD-L1 antibodies. As only a subset of RCC patients respond, alternative strategies should be explored.

Delta-Like Ligand-Notch1 Signaling Is Selectively Modulated by HPV16 E6 to Promote Squamous Cell Proliferation and Correlates with Cervical Cancer Prognosis.

Human papillomavirus (HPV) drives high-grade intraepithelial neoplasia and cancer; for unknown reasons, this occurs most often in the cervical transformation zone. Either mutation or HPV E6-driven inhibition of Notch1 can drive neoplastic development in stratified squamous epithelia. However, the contribution of Notch1 and its Delta-like ligands (DLL) to site susceptibility remains poorly understood.

Adenocarcinoma of the Uterine Cervix Shows Impaired Recruitment of cDC1 and CD8 T Cells and Elevated β-Catenin Activation Compared with Squamous Cell Carcinoma.

Purpose: Adenocarcinoma of the uterine cervix is the second most common type of cervical cancer after squamous cell carcinoma (SCC). Although both subtypes are treated similarly, patients with adenocarcinoma have a worse prognosis. In this study, immunologic features of the tumor microenvironment in these two subsets were pursued with potential therapeutic implications.

Repeatability of arterial input functions and kinetic parameters in muscle obtained by dynamic contrast enhanced MR imaging of the head and neck.

Background: Quantification of pharmacokinetic parameters in dynamic contrast enhanced (DCE) MRI is heavily dependent on the arterial input function (AIF). In the present patient study on advanced stage head and neck squamous cell carcinoma (HNSCC) we have acquired DCE-MR images before and during chemo radiotherapy. We determined the repeatability of image-derived AIFs and of the obtained kinetic parameters in muscle and compared the repeatability of muscle kinetic parameters obtained with image-derived AIF's versus a population-based AIF.

A prediction model relating the extent of intraoperative fascia preservation to erectile dysfunction after nerve-sparing robot-assisted radical prostatectomy.

Robot-assisted radical prostatectomy (RARP) is performed in patients with prostate cancer. Unfortunately, 10-46% of patients may still suffer from limited erectile function (EF) after RARP. This study aimed to develop a prediction model based on the extent of fascia preservation (FP) and postoperative EF after RARP.

Incidence of small bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy.

Background And Study Aims: Lynch syndrome (LS) patients have an increased risk of small bowel cancer. The question is whether surveillance will lead to early detection of (pre)malignant lesions. We recently reported on prevalence of small bowel neoplasia (SBN) in LS patients as assessed by video capsule endoscopy (VCE).

Increased levels of choline metabolites are an early marker of docetaxel treatment response in BRCA1-mutated mouse mammary tumors: an assessment by ex vivo proton magnetic resonance spectroscopy.

Background: Docetaxel is one of the most frequently used drugs to treat breast cancer. However, resistance or incomplete response to docetaxel is a major challenge. The aim of this study was to utilize MR metabolomics to identify potential biomarkers of docetaxel resistance in a mouse model for BRCA1-mutated breast cancer.

Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy.

Objective: The aim was to determine the prevalence of small-bowel neoplasia in asymptomatic patients with Lynch syndrome (LS) by video capsule endoscopy (VCE).

Design: After obtaining informed consent, asymptomatic proven gene mutation carriers aged 35-70 years were included in this prospective multicentre study in the Netherlands. Patients with previous small-bowel surgery were excluded.

Pharmacokinetics, brain delivery, and efficacy in brain tumor-bearing mice of glutathione pegylated liposomal doxorubicin (2B3-101).

Brain cancer is a devastating disease affecting many people worldwide. Effective treatment with chemotherapeutics is limited due to the presence of the blood-brain barrier (BBB) that tightly regulates the diffusion of endogenous molecules but also xenobiotics. Glutathione pegylated liposomal doxorubicin (2B3-101) is being developed as a new treatment option for patients with brain cancer.

Critical appraisal of translational research models for suitability in performance assessment of cancer centers.

Background: Translational research is a complex cumulative process that takes time. However, the operating environment for cancer centers engaged in translational research is now financially insecure. Centers are challenged to improve results and reduce time from discovery to practice innovations.

Non-invasive longitudinal imaging of tumor progression using an (111)indium labeled CXCR4 peptide antagonist.

The chemokine receptor 4 (CXCR4) is a biomarker that is over-expressed in ductal carcinoma in situ (DCIS). Hence, CXCR4-targeted (molecular) imaging approaches may have diagnostic value in such a challenging, premalignant lesion. The indium labeled CXCR4 peptide-antagonist, (111)In-DTPA-Ac-TZ14011, was used to visualize CXCR4-expression in a mammary intraepithelial neoplastic outgrowth (MIN-O) mouse tumor model resembling human DCIS.

Mimicking homeostatic proliferation in vitro generates T cells with high anti-tumor function in non-lymphopenic hosts.

CD8(+) T cells undergoing homeostatic proliferation (HP) in a lymphopenic environment acquire a central memory-like phenotype (CD44(+) CD62L(+) Ly6c(+)). Such cells are readily functional in vitro, with a strong capacity to secrete IFNγ and IL-2 and to lyse target cells upon antigen recognition. In vivo, these memory-like T cells display potent anti-tumor reactivity.

Radioactive seed localization of breast lesions: an adequate localization method without seed migration.

Preoperative localization is important to optimize the surgical treatment of breast lesions, especially in nonpalpable lesions. Radioactive seed localization (RSL) using iodine-125 is a relatively new approach. To provide accurate guidance to surgery, it is important that the seeds do not migrate after placement.

Overall survival and PD-L1 expression in metastasized malignant melanoma.

Background: Cancers are known to elude the immune system, for example, by MHC loss, FAS up-regulation, or increased secretion of TGF-beta. Recently, ligands of coinhibitory receptors like programmed cell death ligand-1 (PD-L1, B7-H1) have come to attention for their role in tumor immune escape. Various tumors have been tested for PD-L1 expression, and conflicting results were obtained regarding its correlative impact on patient survival.

Magnetic resonance imaging response monitoring of breast cancer during neoadjuvant chemotherapy: relevance of breast cancer subtype.

Purpose: To evaluate the relevance of breast cancer subtypes for magnetic resonance imaging (MRI) markers for monitoring of therapy response during neoadjuvant chemotherapy (NAC).

Patients And Methods: MRI examinations were performed in 188 women before and during NAC. MRI interpretation included lesion morphology at baseline, changes in morphology, size, and contrast uptake kinetics (initial and late enhancement).

The effects of muscle exercise and bed rest on [18F]methylcholine PET/CT.

Purpose: This study evaluated the impact of limited and strenuous physical exercise on [(18)F]methylcholine uptake in muscle.

Methods: Ten consecutive patients participated, three of whom had strict bed rest, three were allowed to walk around and four performed strenuous single arm exercise by lifting a 7.5-kg weight.

Regular surveillance for Li-Fraumeni Syndrome: advice, adherence and perceived benefits.

Li Fraumeni Syndrome (LFS) is a hereditary cancer syndrome characterized by a high risk of developing various types of cancer from birth through late adulthood. Clinical benefits of surveillance for LFS are limited. The aim of this study is to investigate which advice for regular surveillance, if any, is given to high risk LFS individuals, adherence to that advice, and any psychological gain or burden derived from surveillance.

On the feasibility of MRI-guided navigation to demarcate breast cancer for breast-conserving surgery.

Purpose: The aim of this study was to investigate the feasibility of image-guided navigation approaches to demarcate breast cancer on the basis of preacquired magnetic resonance (MR) imaging in supine patient orientation.

Methods: Strategies were examined to minimize the uncertainty in the instrument-tip position, based on the hypothesis that the release of instrument pressure returns the breast tissue to its predeformed state. For this purpose, four sources of uncertainty were taken into account: (1) U(ligaments): Uncertainty in the reproducibility of the internal mammary gland geometry during repeat patient setup in supine orientation; (2) U(r_breathing): Residual uncertainty in registration of the breast after compensation for breathing motion using an external marker; (3) U(reconstruction): Uncertainty in the reconstructed location of the tip of the needle using an optical image-navigation system (phantom experiments, n = 50); and (4) U(deformation): Uncertainty in displacement of breast tumors due to needle-induced tissue deformations (patients, n = 21).

RNA interference targeting programmed death receptor-1 improves immune functions of tumor-specific T cells.

Adoptive cell transfer (ACT), either using rapidly expanded tumor infiltrating lymphocytes or T-cell receptor transduced peripheral blood lymphocytes, can be considered one of the most promising approaches in cancer immunotherapy. ACT results in the repopulation of the host with high frequencies of tumor-specific T cells; however, optimal function of these cells within the tumor micro-environment is required to reach long-term tumor clearance. We and others have shown that ongoing anti-tumor immune responses can be impaired by the expression of ligands, such as PD-L1 (B7-H1) on tumor cells.

Psychosocial impact of Von Hippel-Lindau disease: levels and sources of distress.

Von Hippel-Lindau disease (VHL) is a hereditary tumor susceptibility syndrome, characterized by an increased risk of developing multiple benign and malignant tumors at various sites and ages with limited preventive options. This study evaluates the prevalence of distress among VHL family members and factors associated significantly with such distress. Forty-eight families with a VHL mutation were identified via the nine family cancer clinics in the Netherlands.

Toward visualization of nanomachines in their native cellular environment.

The cellular nanocosm is made up of numerous types of macromolecular complexes or biological nanomachines. These form functional modules that are organized into complex subcellular networks. Information on the ultra-structure of these nanomachines has mainly been obtained by analyzing isolated structures, using imaging techniques such as X-ray crystallography, NMR, or single particle electron microscopy (EM).

Automatic prostate localization on cone-beam CT scans for high precision image-guided radiotherapy.

Purpose: Previously, we developed an automatic three-dimensional gray-value registration (GR) method for fast prostate localization that could be used during online or offline image-guided radiotherapy. The method was tested on conventional computed tomography (CT) scans. In this study, the performance of the algorithm to localize the prostate on cone-beam CT (CBCT) scans acquired on the treatment machine was evaluated.

Automatic localization of the prostate for on-line or off-line image-guided radiotherapy.

Purpose: With higher radiation dose, higher cure rates have been reported in prostate cancer patients. The extra margin needed to account for prostate motion, however, limits the level of dose escalation, because of the presence of surrounding organs at risk. Knowledge of the precise position of the prostate would allow significant reduction of the treatment field.