Management of castrate resistant prostate cancer-recent advances and optimal sequence of treatments.

Until 2010, chemotherapy with docetaxel was the only approved agent for treatment of metastatic castrate resistant prostate cancer (mCRPC). Since then, the therapeutic landscape of mCRPC has changed rapidly. Multiple novel agents have received regulatory approval after demonstrating improved overall survival in separate randomized Phase 3 studies. These include immunotherapeutic agent sipuleucel-T, androgen axis inhibitors abiraterone and enzalutamide, and a novel microtubule inhibitor cabazitaxel. More recently, radium-223, a bone-targeting alpha emitting radiopharmaceutical, was reported to improve skeletal related events, as well as overall survival in a Phase 3 randomized study. Additionally, there are several promising agents in the advanced stages of clinical development. Here, we describe the agents recently shown to improve overall survival, and those that have reached the advanced stages of development in Phase 3 clinical trials. We will also propose a strategy for optimal sequencing of these agents in the treatment of mCRPC.

Breast MRI background parenchymal enhancement as an imaging bridge to molecular cancer sub-type.

PURPOSE: To evaluate the distribution of MRI breast parenchymal enhancement (BPE) among different breast cancer subtypes searching for any significant difference in terms of immunohistochemical and receptorial patterns (Estrogen Receptor -ER, Progesterone Receptor - PR, Human Epidermal Growth Factor Receptor 2 - HER2). METHODS: 82 consecutive patients affected by breast cancer underwent breast DCE-MRI. Two radiologists retrospectively evaluated all subtracted MR enhanced images for classifying BPE. ER, PR and HER2 expression was assessed by immunohistochemical analysis. ER and PR status was evaluated using Allred score (positive values: score ≥3). The intensity of the cerbB-2 staining was scored as 0, 1+, 2+, or 3+ (positive values: ≥ 3+; negative:0 and 1+; 2+ value assessed with silver in-situ hybridization). Patients were classified into five categories based on cancer subtypes: Luminal A, Luminal B HER2 negative, Luminal B HER2 positive, HER2 positive non luminal, triple negative. The χ2 test was used for evaluating the significance of BPE type distribution into the five groups of tumor subtypes and the distribution of the five breast cancer subtypes among every single BPE type. The correlation of BPE with factors such as age, menopausal status and lesion diameter was investigated using multivariate regression analysis and logistic regression. Cohen's kappa statistics was used in order to assess inter-observer agreement for classifying BPE. RESULTS: 6/82 cases were Luminal A-like (7.3%), 42/82 Luminal B-like (HER2-) (51.2%), 12/82 Luminal B-like (HER2+) (14.6%), 4/82 Non Luminal (HER+) (4.9%), 18/82 Triple Negative (ductal) (22%). 16/82 cases showed minimal BPE, 28/82 mild BPE, 22/82 moderate BPE, 16/82 marked BPE. Mild BPE pattern was significantly more prevalent (p = 0.0001) than other BPE types only in the luminal B (HER-) tumors. Moderate and marked BPE prevailed over minimal and mild, in triple negatives. Among all patients with mild BPE, luminal B (HER2-) tumors were significantly higher (p = 0.0001). Among all patients with marked BPE, triple negative subtypes were significantly higher (p = 0.0074). No significant confounder to BPE qualitative evaluation was found (p = 0.39). The inter-rater agreement in evaluating BPE patterns on MRI was almost perfect with Cohen's k = 0.83. CONCLUSIONS: BPE could play a crucial role as an imaging bridge to molecular breast cancer subtype allowing an additional risk stratification in the field of breast MRI and targeted screening tests. Luminal B (HER2-) tumors could prevail in case of mild BPE on CE-MRI examinations and TN tumors in patients with marked BPE. Further studies on larger series are needed to confirm this hypothesis.

Uremic lung: The "calcified cauliflower" sign in the end stage renal disease.

Metastatic pulmonary calcification (MPC) is a rare pathological condition consisting of lung calcium salt deposits which commonly occurs in patients affected by chronic kidney disease probably for some abnormalities in calcium and phosphate metabolism. CT represents the technique of choice for detecting MPC findings including ground glass opacities and partially calcified nodules or consolidations. We present a case of MCP in a patient affected by hepato-renal autosomic-dominant polycystic disease; chest CT revealed extensive lobar-segmental parenchymal calcification with a peculiar cauliflower shape which we called "calcified cauliflower" sign. The "calcified cauliflower" sign can be reported as a new CT pattern of uremic lung that needs to be identified for a correct diagnosis and patient management.