A humanized orthotopic tumor microenvironment alters the bone metastatic tropism of prostate cancer cells.

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men, and bone is the most frequent site of metastasis. The tumor microenvironment (TME) impacts tumor growth and metastasis, yet the role of the TME in PCa metastasis to bone is not fully understood. We used a tissue-engineered xenograft approach in NOD-scid IL2Rγ (NSG) mice to incorporate two levels of humanization; the primary tumor and TME, and the secondary metastatic bone organ.

Radiation and Androgen Deprivation Therapy With or Without Docetaxel in the Management of Nonmetastatic Unfavorable-Risk Prostate Cancer: A Prospective Randomized Trial.

Purpose: Although docetaxel is not recommended when managing men with unfavorable-risk prostate cancer (PC) given negative or inconclusive results from previous randomized trials, unstudied benefits may exist.

Methods: Between September 21, 2005, and January 13, 2015, we randomly assigned 350 men 1:1 with T1c-4N0M0 unfavorable-risk PC to receive radiation therapy (RT) and androgen deprivation therapy (ADT) plus docetaxel (60 mg/m once every 3 weeks for three cycles before RT and 20 mg/m once weekly during RT) versus ADT + RT. We evaluated the treatment effect of adding docetaxel to ADT + RT on the primary end point of overall survival (OS) and the incidence of RT-induced cancers and explored whether the impact of the treatment effect on OS differed within prostate-specific antigen (PSA) subgroups (< 4, > 20 4-20 ng/mL) using the interaction test for heterogeneity adjusted for age and PC prognostic factors.

Voxel-based supervised machine learning of peripheral zone prostate cancer using noncontrast multiparametric MRI.

Purpose: The aim of this study was to develop and assess the performance of supervised machine learning technique to classify magnetic resonance imaging (MRI) voxels as cancerous or noncancerous using noncontrast multiparametric MRI (mp-MRI), comprised of T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and advanced diffusion tensor imaging (DTI) parameters.

Materials And Methods: In this work, 191 radiomic features were extracted from mp-MRI from prostate cancer patients. A comprehensive set of support vector machine (SVM) models for T2WI and mp-MRI (T2WI + DWI, T2WI + DTI, and T2WI + DWI + DTI) were developed based on novel Bayesian parameters optimization method and validated using leave-one-patient-out approach to eliminate any possible overfitting.

The Membrane Protein Sortilin Can Be Targeted to Inhibit Pancreatic Cancer Cell Invasion.

Pancreatic cancer has a dismal prognosis, and there is no targeted therapy against this malignancy. The neuronal membrane protein sortilin is emerging as a regulator of cancer cell development, but its expression and impact in pancreatic cancer are unknown. This study found that sortilin expression was higher in pancreatic cell lines versus normal pancreatic ductal epithelial cells, as shown by Western blot analysis and mass spectrometry.

Tumour innervation and neurosignalling in prostate cancer.

Prostate cancer progression has been shown to be dependent on the development of autonomic nerves into the tumour microenvironment. Sympathetic nerves activate adrenergic neurosignalling that is necessary in early stages of tumour progression and for initiating an angiogenic switch, whereas parasympathetic nerves activate cholinergic neurosignalling resulting in tumour dissemination and metastasis. The innervation of prostate cancer seems to be initiated by neurotrophic growth factors, such as the precursor to nerve growth factor secreted by tumour cells, and the contribution of brain-derived neural progenitor cells has also been reported.

Multi-observer contouring of male pelvic anatomy: Highly variable agreement across conventional and emerging structures of interest.

Introduction: This study quantified inter-observer contouring variations for multiple male pelvic structures, many of which are of emerging relevance for prostate cancer radiotherapy progression and toxicity response studies.

Methods: Five prostate cancer patient datasets (CT and T2-weighted MR) were distributed to 13 observers for contouring. CT structures contoured included the clinical target volume (CTV), seminal vesicles, rectum, colon, bowel bag, bladder and peri-rectal space (PRS).

Characterization of prostate cancer using diffusion tensor imaging: A new perspective.

Purpose: This study is aimed at evaluating the potential role of quantitative magnetic resonance diffusion tensor imaging (DTI) and tractography parameters in the detection and characterization of peripheral zone prostate cancer with a particular attention for fiber tract density.

Materials And Methods: DTI was acquired from eleven high risk, transrectal ultrasound (TRUS)-guided biopsy proven prostate cancers with perineural invasion (histological Gleason score ≥ 7) on a 3 T magnet. Twenty parameters derived from DTI were quantified in cancer and healthy regions of the prostate.

Prostate-Specific Membrane Antigen Positron Emission Tomography-Computed Tomography for Prostate Cancer: Distribution of Disease and Implications for Radiation Therapy Planning.

Purpose: To explore the prostate-specific membrane antigen (PSMA)-avid distribution of prostate cancer (PC) on positron emission tomography (PET), both at the time of initial diagnosis and at the time of relapse after definitive local treatment.

Methods And Materials: A total of 179 PSMA PET scans in patients with nil or ≤3 lesions on conventional imaging were retrospectively categorized into 3 subgroups: group A, high-risk PC with no prior definitive therapy (n=34); group B, prior prostatectomy (n=75); and group C, prior radiation therapy (n=70). The numbers and locations of the PSMA-avid lesions were mapped.

Spinal Cord Injuries and Nerve Dependence in Prostate Cancer.

Nerves are emerging as drivers of tumorigenesis, as demonstrated in the mouse where denervation suppresses prostate cancer; however, clinical evidence is needed. Patients with spinal cord injuries (SCIs) resulting in functional denervation of the prostate have a lower incidence of prostate cancer. This may constitute a clinical evidence for nerve dependence in human prostate tumorigenesis.

Tissue engineering and regenerative medicine in musculoskeletal oncology.

Currently used surgical techniques to reconstruct tissue defects after resection of musculoskeletal tumours are associated with high complication rates. This drives a strong demand for innovative therapeutic concepts that are able to improve the clinical outcomes of patients suffering from bone and soft tissue tumours. Tissue engineering and regenerative medicine (TE&RM) provides a technology platform based on biochemical, molecular, cellular and biomaterials modules to selectively direct tissue healing processes for improved defect regeneration.

Dosimetry, clinical factors and medication intake influencing urinary symptoms after prostate radiotherapy: An analysis of data from the RADAR prostate radiotherapy trial.

Purpose/objective: To identify dosimetry, clinical factors and medication intake impacting urinary symptoms after prostate radiotherapy.

Material And Methods: Data describing clinical factors and bladder dosimetry (reduced with principal component (PC) analysis) for 754 patients treated with external beam radiotherapy accrued by TROG 03.04 RADAR prostate radiotherapy trial were available for analysis.

Impact of treatment planning and delivery factors on gastrointestinal toxicity: an analysis of data from the RADAR prostate radiotherapy trial.

Background: To assess the impact of incremental modifications of treatment planning and delivery technique, as well as patient anatomical factors, on late gastrointestinal toxicity using data from the TROG 03.04 RADAR prostate radiotherapy trial.

Methods: The RADAR trial accrued 813 external beam radiotherapy participants during 2003-2008 from 23 centres.

Wellbeing during Active Surveillance for localised prostate cancer: a systematic review of psychological morbidity and quality of life.

Background: Active Surveillance (AS) is recommended for the treatment of localised prostate cancer; however this option may be under-used, at least in part because of expectations of psychological adverse events in those offered or accepting AS.

Objective: (1) Determine the impact on psychological wellbeing when treated with AS (non-comparative studies). (2) Compare AS with active treatments for the impact on psychological wellbeing (comparative studies).

Do women have a role in early detection of prostate cancer? - Lessons from a qualitative study.

Background: Prostate cancer is the most common internal cancer in Australian men; more than 3000 men die annually from it. Public awareness of prostate cancer is an important factor in early detection and treatment. Women are known to act as 'health managers' for their families and may have a role to play in early detection.

Telling their stories, telling our stories: physicians' experiences with patients who decide to forgo or stop treatment for cancer.

There is currently very little research on how physicians respond to patients with cancer who decide to forgo or stop medically recommended "curative" therapy. The purpose of this article is to report on a qualitative study with 12 oncology specialists in Israel and Australia that addresses this question. The findings indicate that physicians tend to construct patients and their decisions in terms of mutually exclusive categories that focus on curability of the disease, rationality of the patient's decision, and patients' personal attributes.

Tirapazamine, Cisplatin, and Radiation versus Fluorouracil, Cisplatin, and Radiation in patients with locally advanced head and neck cancer: a randomized phase II trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02).

Purpose: To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma (SCC) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial.

Patients And Methods: One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were randomized to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either cisplatin (75 mg/m(2)) plus tirapazamine (290 mg/m(2)/d) on day 2 of weeks 1, 4, and 7, and tirapazamine alone (160 mg/m(2)/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS), or cisplatin (50 mg/m(2)) on day 1 and infusional fluorouracil (360 mg/m(2)/d) on days 1 through 5 of weeks 6 and 7 (chemoboost).

Results: Three-year failure-free survival rates were 55% with TPZ/CIS (95% CI, 39% to 70%) and 44% with chemoboost (95% CI, 30% to 60%; log-rank P = .

Dosimetric intercomparison for two Australasian clinical trials using an anthropomorphic phantom.

Introduction: Many different factors can affect the accurate delivery of dose to the clinical target volume in radiotherapy. This is particularly important in the context of multicenter clinical trials where different equipment and techniques may be used for supposedly identical treatments. A dosimetric intercomparison employing an anthropomorphic phantom (level III dosimetric intercomparison) can be used to check many of the factors that could affect treatment by mimicking the radiotherapy pathway of a patient as closely as possible.