Wnt signaling reprograms metabolism in dental pulp stem cells.

Human dental pulp stem cells (DPSCs) can differentiate to a wide range of different cell lineages, and share some gene expression and functional similarities with pluripotent stem cells. The stemness of DPSCs can also be pharmacologically enhanced by the activation of canonical Wnt signaling. Here, we examined the metabolic profile of DPSCs during reprogramming linked to Wnt activation, by a short (48 hr) exposure to either the GSK3-β inhibitor BIO (6-bromoindirubin-3´-oxine) or human recombinant protein WNT-3A.

Calculation of absorbed dose in radiotherapy by solution of the linear Boltzmann transport equations.

Over the last decade, dose calculations which solve the linear Boltzmann transport equations have been introduced into clinical practice and are now in widespread use. However, knowledge in the radiotherapy community concerning the details of their function is limited. This review gives a general description of the linear Boltzmann transport equations as applied to calculation of absorbed dose in clinical radiotherapy.

Ototoxicity in locally advanced head and neck cancer patients treated with induction chemotherapy followed by intermediate or high-dose cisplatin-based chemoradiotherapy.

Background: This study evaluated ototoxicity in locally advanced head and neck cancer patients treated in the CONDOR study with docetaxel/cisplatin/5-fluorouracil (TPF) followed by conventional radiotherapy with concomitant cisplatin 100 mg/m on days 1, 22, and 43 (cis100+RT) versus accelerated radiotherapy with concomitant cisplatin weekly 40 mg/m (cis40+ART).

Methods: Sixty-two patients were treated in this study. Audiometry was performed at baseline, during TPF, before start of chemoradiotherapy, and 1, 4, 8, and 12 months after treatment.

Cabozantinib Versus Mitoxantrone-prednisone in Symptomatic Metastatic Castration-resistant Prostate Cancer: A Randomized Phase 3 Trial with a Primary Pain Endpoint.

Background: Bone metastases in patients with metastatic castration-resistant prostate cancer (mCRPC) are associated with debilitating pain and functional compromise.

Objective: To compare pain palliation as the primary endpoint for cabozantinib versus mitoxantrone-prednisone in men with mCRPC and symptomatic bone metastases using patient-reported outcome measures.

Design, Setting, And Participants: A randomized, double-blind phase 3 trial (COMET-2; NCT01522443) in men with mCRPC and narcotic-dependent pain from bone metastases who had progressed after treatment with docetaxel and either abiraterone or enzalutamide.

The impact of 2D cine MR imaging parameters on automated tumor and organ localization for MR-guided real-time adaptive radiotherapy.

2D cine MR imaging may be utilized to monitor rapidly moving tumors and organs-at-risk for real-time adaptive radiotherapy. This study systematically investigates the impact of geometric imaging parameters on the ability of 2D cine MR imaging to guide template-matching-driven autocontouring of lung tumors and abdominal organs. Abdominal 4D MR images were acquired of six healthy volunteers and thoracic 4D MR images were obtained of eight lung cancer patients.

Metabolic biomarkers of response to the AKT inhibitor MK-2206 in pre-clinical models of human colorectal and prostate carcinoma.

Background: AKT is commonly overexpressed in tumours and plays an important role in the metabolic reprogramming of cancer. We have used magnetic resonance spectroscopy (MRS) to assess whether inhibition of AKT signalling would result in metabolic changes that could potentially be used as biomarkers to monitor response to AKT inhibition.

Methods: Cellular and metabolic effects of the allosteric AKT inhibitor MK-2206 were investigated in HT29 colon and PC3 prostate cancer cells and xenografts using flow cytometry, immunoblotting, immunohistology and MRS.

Novel adaptive beam-dependent margins for additional OAR sparing.

Margins are employed in radiotherapy treatment planning to mitigate the dosimetric effects of geometric uncertainties for the clinical target volume (CTV). Unfortunately, whilst the use of margins can increase the probability that sufficient dose is delivered to the CTV, it can also result in delivering high dose of radiation to surrounding organs at risk (OARs). We expand on our previous work on beam-dependent margins and propose a novel adaptive margin concept, where margins are moulded away from selected OARs for better OAR-high-dose sparing, whilst maintaining similar dose coverage probability to the CTV.

Adopting Advanced Radiotherapy Techniques in the Treatment of Paediatric Extracranial Malignancies: Challenges and Future Directions.

Geometric uncertainties in radiotherapy are conventionally addressed by defining a safety margin around the radiotherapy target. Misappropriation of such margins could result in disease recurrence from geometric miss or unnecessary irradiation of normal tissue. Numerous quantitative organ motion studies in adults have been published, but the first paediatric-specific studies were only published in recent years.

Optimistic, realistic, and pessimistic illness perceptions; quality of life; and survival among 2457 cancer survivors: the population-based PROFILES registry.

Background: Threatening illness perceptions (IPs) have been associated with poorer health outcomes. However, to the authors' knowledge, it remains unclear whether threatening IPs that are consistent with disease severity are equally harmful. The aim of the current study was to: 1) identify subgroups of cancer survivors based on IPs and prognosis; and 2) assess the health-related quality of life (HRQOL) and survival associated with these subgroups.

A risk-based approach to identifying oligometastatic disease on imaging.

Recognition of <3 metastases in <2 organs, particularly in cancers with a known predisposition to oligometastatic disease (OMD) (colorectal, prostate, renal, sarcoma and lung), offers the opportunity to focally treat the lesions identified and confers a survival advantage. The reliability with which OMD is identified depends on the sensitivity of the imaging technique used for detection and may be predicted from phenotypic and genetic factors of the primary tumour, which determine metastatic risk. Whole-body or organ-specific imaging to identify oligometastases requires optimization to achieve maximal sensitivity.

Tumor to cervical spinal cord standardized uptake ratio (SUR) improves the reproducibility of F-FDG-PET based tumor segmentation in head and neck squamous cell carcinoma in a multicenter setting.

Background: In quantitative FDG-PET data analysis, normalization of the standardized uptake value (SUV) with an internal image-derived standard improves its reproducibility. In this study, the cervical spinal cord is proposed as an internal standard that is within the field of view of the radiotherapy planning PET/CT-scan in head and neck cancer. The aim is to evaluate if the tumor to cervical spinal cord standardized uptake ratio (SUR) can improve the reproducibility of a model to determine the metabolic tumor volume (MTV) on FDG-PET/CT in a multicenter setting.

IL-23 secreted by myeloid cells drives castration-resistant prostate cancer.

Patients with prostate cancer frequently show resistance to androgen-deprivation therapy, a condition known as castration-resistant prostate cancer (CRPC). Acquiring a better understanding of the mechanisms that control the development of CRPC remains an unmet clinical need. The well-established dependency of cancer cells on the tumour microenvironment indicates that the microenvironment might control the emergence of CRPC.

Clinicopathological characteristics and outcome of 31 patients with ETV6-NTRK3 fusion gene confirmed (mammary analogue) secretory carcinoma of salivary glands.

Objectives: In 2010, a new subtype of salivary gland cancer (SGC), (mammary analogue) secretory carcinoma (SC), was defined, characterized by the ETV6-NTRK3 fusion gene. As clinical behavior and outcome data of this histological subtype tumor are still sparse, we aimed to describe the clinicopathological course and outcome of a series of translocation positive SC patients.

Patient And Methods: We re-evaluated the pathological diagnosis of a subset of SGCs, diagnosed in 4 of 8 Dutch head and neck centers.

Geometric and dosimetric evaluations of atlas-based segmentation methods of MR images in the head and neck region.

Owing to its excellent soft-tissue contrast, magnetic resonance (MR) imaging has found an increased application in radiation therapy (RT). By harnessing these properties for treatment planning, automated segmentation methods can alleviate the manual workload burden to the clinical workflow. We investigated atlas-based segmentation methods of organs at risk (OARs) in the head and neck (H&N) region using one approach that selected the most similar atlas from a library of segmented images and two multi-atlas approaches.

Super-resolution T2-weighted 4D MRI for image guided radiotherapy.

Background And Purpose: The superior soft-tissue contrast of 4D-T2w MRI motivates its use for delineation in radiotherapy treatment planning. We address current limitations of slice-selective implementations, including thick slices and artefacts originating from data incompleteness and variable breathing.

Materials And Methods: A method was developed to calculate midposition and 4D-T2w images of the whole thorax from continuously acquired axial and sagittal 2D-T2w MRI (1.

Review of Real-Time 3-Dimensional Image Guided Radiation Therapy on Standard-Equipped Cancer Radiation Therapy Systems: Are We at the Tipping Point for the Era of Real-Time Radiation Therapy?

Purpose: To review real-time 3-dimensional (3D) image guided radiation therapy (IGRT) on standard-equipped cancer radiation therapy systems, focusing on clinically implemented solutions.

Methods And Materials: Three groups in 3 continents have clinically implemented novel real-time 3D IGRT solutions on standard-equipped linear accelerators. These technologies encompass kilovoltage, combined megavoltage-kilovoltage, and combined kilovoltage-optical imaging.

Dosimetric comparison of five different techniques for craniospinal irradiation across 15 European centers: analysis on behalf of the SIOP-E-BTG (radiotherapy working group).

Purpose: Conventional techniques (3D-CRT) for craniospinal irradiation (CSI) are still widely used. Modern techniques (IMRT, VMAT, TomoTherapy, proton pencil beam scanning [PBS]) are applied in a limited number of centers. For a 14-year-old patient, we aimed to compare dose distributions of five CSI techniques applied across Europe and generated according to the participating institute protocols, therefore representing daily practice.

Nationwide trends in the incidence and outcome of patients with gastrointestinal stromal tumour in the imatinib era.

Background: The incidence, treatment and outcome of patients with newly diagnosed gastrointestinal stromal tumour (GIST) were studied in an era known for advances in diagnosis and treatment.

Methods: Nationwide population-based data were retrieved from the Netherlands Cancer Registry. All patients with GIST diagnosed between 2001 and 2012 were included.

Comparison of six fit algorithms for the intra-voxel incoherent motion model of diffusion-weighted magnetic resonance imaging data of pancreatic cancer patients.

The intravoxel incoherent motion (IVIM) model for diffusion-weighted imaging (DWI) MRI data bears much promise as a tool for visualizing tumours and monitoring treatment response. To improve the currently poor precision of IVIM, several fit algorithms have been suggested. In this work, we compared the performance of two Bayesian IVIM fit algorithms and four other IVIM fit algorithms for pancreatic cancer imaging.

Prognostic relevance of distant metastases versus locally advanced disease in soft tissue sarcomas: An EORTC-STBSG database study.

Introduction: In patients with advanced soft tissue sarcoma (STS) treated with chemotherapy, WHO performance status, histologic subtype and histologic grade are known prognostic factors. Although the difference between the subgroups: locally advanced disease only, metastatic disease only and both local and metastatic disease is easily made, its prognostic relevance is thus far unknown. The aim of this EORTC database study was to study the difference in prognosis between these subgroups in patients receiving first-line chemotherapy for advanced STS.

The effect of FASN inhibition on the growth and metabolism of a cisplatin-resistant ovarian carcinoma model.

Overexpression of fatty acid synthase (FASN), a key regulator of the de novo synthesis of fatty acids, has been demonstrated in a variety of cancers and is associated with poor prognosis and increased multidrug resistance. Inhibition of FASN with the anti-obesity drug orlistat has been shown to have significant anti-tumourigenic effects in many cancers, notably breast and prostate. In our study, we investigated whether FASN inhibition using orlistat is an effective adjunctive treatment for ovarian cancers that have become platinum resistant using a cisplatin-resistant ovarian tumour xenograft model in mice.

Automatic online and real-time tumour motion monitoring during stereotactic liver treatments on a conventional linac by combined optical and sparse monoscopic imaging with kilovoltage x-rays (COSMIK).

The purpose of this study was to develop, validate and clinically demonstrate fully automatic tumour motion monitoring on a conventional linear accelerator by combined optical and sparse monoscopic imaging with kilovoltage x-rays (COSMIK). COSMIK combines auto-segmentation of implanted fiducial markers in cone-beam computed tomography (CBCT) projections and intra-treatment kV images with simultaneous streaming of an external motion signal. A pre-treatment CBCT is acquired with simultaneous recording of the motion of an external marker block on the abdomen.