Nipple-sparing mastectomy in women at high risk of developing breast cancer.

Nipple-sparing mastectomy is a valuable addition to the options available for women at high risk of developing breast cancer. In this review, we summarize current knowledge about the high-risk genes, , and and the associated guidelines with regard to risk-reducing surgery. We consider other genetic risks and high-risk lesions.

Positron Emission Tomography/Computed Tomography with Zr-girentuximab Can Aid in Diagnostic Dilemmas of Clear Cell Renal Cell Carcinoma Suspicion.

Unlabelled: Based on the high expression of carbonic anhydrase IX (CAIX) in 95% of clear cell renal cell carcinoma (ccRCC), the anti-CAIX monoclonal antibody girentuximab can be used for the detection of ccRCC. This clinical study explores the value of Zr-labeled girentuximab positron emission tomography/computed tomography (PET/CT) imaging in diagnostic challenges regarding ccRCC. PET/CT imaging was performed 4 or 5 d after injection of Zr-girentuximab in patients with a primary renal mass (n=16) or a history of ccRCC (n=14).

Tumor-targeted Dual-modality Imaging to Improve Intraoperative Visualization of Clear Cell Renal Cell Carcinoma: A First in Man Study.

Intraoperative imaging with antibodies labeled with both a radionuclide for initial guidance and a near-infrared dye for adequate tumor delineation may overcome the main limitation of fluorescence imaging: the limited penetration depth of light in biological tissue. In this study, we demonstrate the feasibility and safety of intraoperative dual-modality imaging with the carbonic anhydrase IX (CAIX)-targeting antibody In-DOTA-girentuximab-IRDye800CW in clear cell renal cell carcinoma (ccRCC) patients. A phase I protein dose escalation study was performed in patients with a primary renal mass who were scheduled for surgery.

Update on Systemic Prostate Cancer Therapies: Management of Metastatic Castration-resistant Prostate Cancer in the Era of Precision Oncology.

Context: Introduction of novel agents for the management of advanced prostate cancer provides a range of treatment options with notable benefits for men with metastatic castration-resistant prostate cancer (mCRPC). At the same time, understanding of optimal patient selection, effective sequential use, and development of resistance patterns remains incomplete.

Objective: To review current systemic therapies and recent advances in drug development for mCRPC and strategies to aid in patient selection and optimal sequencing.

Effects of Synchrotron X-Ray Micro-beam Irradiation on Normal Mouse Ear Pinnae.

Purpose: To analyze the effects of micro-beam irradiation (MBI) on the normal tissues of the mouse ear.

Methods And Materials: Normal mouse ears are a unique model, which in addition to skin contain striated muscles, cartilage, blood and lymphatic vessels, and few hair follicles. This renders the mouse ear an excellent model for complex tissue studies.

Correction to: Dosimetry in clinical radionuclide therapy: the devil is in the detail.

The above article which was published in Volume 44/ Issue 12 has incorrect page numbers. Instead of 1-3, it should have been 2137-2139.

Bone lesion absorbed dose profiles in patients with metastatic prostate cancer treated with molecular radiotherapy.

Objective: The aim of this study was to calculate the range of absorbed doses that could potentially be delivered by a variety of radiopharmaceuticals and typical fixed administered activities used for bone pain palliation in a cohort of patients with metastatic castration-resistant prostate cancer (mCRPC). The methodology for the extrapolation of the biodistribution, pharmacokinetics and absorbed doses from a given to an alternative radiopharmaceutical is presented.

Methods: Sequential single photon emission CT images from 22 patients treated with 5 GBq of Re-HEDP were used to extrapolate the time-activity curves for various radiopharmaceuticals.

Circulating Tumor Cell Number as a Response Measure of Prolonged Survival for Metastatic Castration-Resistant Prostate Cancer: A Comparison With Prostate-Specific Antigen Across Five Randomized Phase III Clinical Trials.

Purpose Measures of response that are clinically meaningful and occur early are an unmet need in metastatic castration-resistant prostate cancer clinical research and practice. We explored, using individual patient data, week 13 circulating tumor cell (CTC) and prostate-specific antigen (PSA) response end points in five prospective randomized phase III trials that enrolled a total of 6,081 patients-COU-AA-301, AFFIRM, ELM-PC-5, ELM-PC-4, and COMET-1- ClinicalTrials.Gov identifiers: NCT00638690, NCT00974311, NCT01193257, NCT01193244, and NCT01605227, respectively.

Neutrophil-lymphocyte ratio kinetics in patients with advanced solid tumours on phase I trials of PD-1/PD-L1 inhibitors.

Background: Although the neutrophil-lymphocyte ratio (NLR) is prognostic in many oncological settings, its significance in the immunotherapy era is unknown. Mechanistically, PD-1/PD-L1 inhibitors may alter NLR. We sought to characterise NLR kinetics in patients with advanced solid tumours treated with PD-1/PD-L1 inhibitors.

Magnetic resonance imaging in precision radiation therapy for lung cancer.

Radiotherapy remains the cornerstone of curative treatment for inoperable locally advanced lung cancer, given concomitantly with platinum-based chemotherapy. With poor overall survival, research efforts continue to explore whether integration of advanced radiation techniques will assist safe treatment intensification with the potential for improving outcomes. One advance is the integration of magnetic resonance imaging (MRI) in the treatment pathway, providing anatomical and functional information with excellent soft tissue contrast without exposure of the patient to radiation.

Defining Genome-Wide Expression and Phenotypic Contextual Cues in Macrophages Generated by Granulocyte/Macrophage Colony-Stimulating Factor, Macrophage Colony-Stimulating Factor, and Heat-Killed Mycobacteria.

Heat-killed (HK) (NCTC13365) is currently being evaluated in the clinic as an immunotherapeutic agent for cancer treatment. Yet, the molecular underpinnings underlying immunomodulatory properties of HK are still largely undefined. To fill this void, we sought to perform immunophenotyping, chemokine/cytokine release analysis and genome-wide characterization of monocyte-derived macrophages (MDM) in which monocytes were originally isolated from healthy donors and differentiated by HK (Mob-MDM) relative to macrophage colony-stimulating factor (M-MDM) and granulocyte/macrophage colony-stimulating factor (GM-MDM).

Immunomodulatory effects of heat-killed Mycobacterium obuense on human blood dendritic cells.

Heat-killed (HK) Mycobacterium obuense is a novel immunomodulator, currently undergoing clinical evaluation as an immunotherapeutic agent in the treatment of cancer. Here, we examined the effect of in vitro exposure to HK M. obuense on the expression of different categories of surface receptors on human blood myeloid (m) and plasmacytoid (p) DCs.

The Role of Hypofractionated Radiotherapy in Prostate Cancer.

Purpose Of Review: It is now accepted that prostate cancer has a low alpha/beta ratio, establishing a strong basis for hypofractionation of prostate radiotherapy. This review focuses on the rationale for hypofractionation and presents the evidence base for establishing moderate hypofractionation for localised disease as the new standard of care. The emerging evidence for extreme hypofractionation in managing localized and oligometastatic prostate cancer is reviewed.

Clinical Outcomes from Androgen Signaling-directed Therapy after Treatment with Abiraterone Acetate and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.

Unlabelled: In the COU-AA-302 trial, abiraterone acetate plus prednisone significantly increased overall survival for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Limited information exists regarding response to subsequent androgen signaling-directed therapies following abiraterone acetate plus prednisone in patients with mCRPC. We investigated clinical outcomes associated with subsequent abiraterone acetate plus prednisone (55 patients) and enzalutamide (33 patients) in a post hoc analysis of COU-AA-302.

A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases.

Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer.

Pre-clinical quantitative imaging and mouse-specific dosimetry for In-labelled radiotracers.

Background: Accurate quantification in molecular imaging is essential to improve the assessment of novel drugs and compare the radiobiological effects of therapeutic agents prior to in-human studies. The aim of this study was to investigate the challenges and feasibility of pre-clinical quantitative imaging and mouse-specific dosimetry of In-labelled radiotracers. Attenuation, scatter and partial volume effects were studied using phantom experiments, and an activity calibration curve was obtained for varying sphere sizes.

Phase I/II trials of Re-HEDP in metastatic castration-resistant prostate cancer: post-hoc analysis of the impact of administered activity and dosimetry on survival.

Purpose: To investigate the role of patient-specific dosimetry as a predictive marker of survival and as a potential tool for individualised molecular radiotherapy treatment planning of bone metastases from castration-resistant prostate cancer, and to assess whether higher administered levels of activity are associated with a survival benefit.

Methods: Clinical data from 57 patients who received 2.5-5.

Subsequent Chemotherapy and Treatment Patterns After Abiraterone Acetate in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.

Background: Treatment patterns for metastatic castration-resistant prostate cancer (mCRPC) have changed substantially in the last few years. In trial COU-AA-302 (chemotherapy-naïve men with mCRPC), abiraterone acetate plus prednisone (AA) significantly improved radiographic progression-free survival and overall survival (OS) when compared to placebo plus prednisone (P).

Objective: This post hoc analysis investigated clinical responses to docetaxel as first subsequent therapy (FST) among patients who progressed following protocol-specified treatment with AA, and characterized subsequent treatment patterns among older (≥75 yr) and younger (<75 yr) patient subgroups.

ESMO consensus guidelines for the management of patients with metastatic colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and specialist cancer centres, and the emergence over the same time period not only of improved imaging techniques but also prognostic and predictive molecular markers.