To switch or not to switch? A real-life experience using dexamethasone in combination with abiraterone

The recently published phase II prospective SWITCH trial evaluated whether patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate could benefit from a 'steroid switch' from prednisone to dexamethasone. A total of 26 patients, both chemonaive (14 patients) or pretreated with docetaxel (12 patients), with biochemical and/or limited radiological progression, were enrolled in this trial. Primary endpoint was prostate specific antigen (PSA) 30 defined as the proportion of patients with a PSA level decline 30% or more after 6 weeks of treatment with abiraterone acetate + dexamethasone. Secondary endpoints were: a PSA50 rate (defined as the proportion of patients with PSA decline of 50% or more after 12 weeks on abiraterone acetate + dexamethasone), biochemical and radiological progression-free survival (bPFS and rPFS, respectively), benefit from subsequent treatment and identification of biomarkers of response. Primary endpoint was reached in 46.2% of patients (12 patients), and two patients had an objective partial response on computed tomography scan. Median bPFS and rPFS were 5.3 months and 11.8 months. We present a case series of 11 patients who were consecutively treated with a steroid switch at our institution from January 2016 to August 2018 to investigate if this strategy could be used in a 'real-life' setting. We observed a PSA30 response in two patients (18%), median bPFS was 4.77 months (95% confidence interval [CI] 2.5-14.6) and median rPFS was 7.2 months (95% CI 3.8-15.5). Seven patients had a radiological stable disease as best response to steroid switch. Three patients were being still treated with abiraterone acetate + dexamethasone at data cut-off time. Our case series confirms that switching from prednisone to dexamethasone during abiraterone acetate treatment produces biochemical and radiological responses in both a predocetaxel and a postdocetaxel setting, providing a clinical benefit in mCRPC patients. However, to date, there is no clear indication as to which patient could benefit most from this kind of strategy

Current Treatment Options for Metastatic Hormone-Sensitive Prostate Cancer

The possible treatments options for metastatic hormone-sensitive prostate cancer (mHSPC) have dramatically increased during the last years. The old backbone, which androgen-deprivation therapy (ADT) is the exclusive approach for hormone-na\uefve patients, has been disrupted. Despite the fact that several high-quality, randomized, controlled phase 3 trials have been conducted in this setting, no direct comparison is currently available among the different strategies. Inadequate power, absence of preplanning and small sample size frequently affect the subgroup analyses according to disease volume or patient's risk. The choice between ADT alone and ADT combined with docetaxel, abiraterone acetate, enzalutamide, apalutamide or radiotherapy to the primary tumor remains challenging. Factors that are related to the tumor, patient or drug side effects, currently guide these clinical decisions. This comprehensive review aims to indirectly compare the phase 3 trials in the mHSPC setting, in order to extrapolate data useful for treatment selection, providing also perspectives on future biomarkers

Role of Circulating Tumor Cells (CTC), Androgen Receptor Full Length (AR-FL) and Androgen Receptor Splice Variant 7 (AR-V7) in a Prospective Cohort of Castration-Resistant Metastatic Prostate Cancer Patients

Circulating tumor cells (CTC), androgen receptor full-length (AR-FL), and androgen receptor splice variant 7 (AR-V7) are prognostic in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). AR-V7 seems to predict resistance to androgen-receptor signaling inhibitors (ARSi)

BRCA Mutations in Prostate Cancer: Prognostic and Predictive Implications

Despite chemotherapy and novel androgen-receptor signalling inhibitors (ARSi) have been approved during the last decades, metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with poor clinical outcomes. Several studies found that germline or acquired DNA damage repair (DDR) defects affect a high percentage of mCRPC patients. Among DDR defects, BRCA mutations show relevant clinical implications. BRCA mutations are associated with adverse clinical features in primary tumors and with poor outcomes in patients with mCRPC. In addition, BRCA mutations predict good response to poly-ADP ribose polymerase (PARP) inhibitors, such as olaparib, rucaparib, and niraparib. However, concerns still remain on the role of extensive mutational testing in prostate cancer patients, given the implications for patients and for their progeny. The present comprehensive review attempts to provide an overview of BRCA mutations in prostate cancer, focusing on their prognostic and predictive roles

Exploiting exciton-exciton interactions in semiconductor quantum dots for quantum-information processing

We propose an all-optical implementation of quantum-information processing in semiconductor quantum dots, where electron-hole excitations (excitons) serve as the computational degrees of freedom (qubits). We show that the strong dot confinement leads to an overall enhancement of Coulomb correlations and to a strong renormalization of the excitonic states, which can be exploited for performing conditional and unconditional qubit operations.Comment: 5 pages revtex, 2 encapsulated postscript figures. Accepted for publication in Phys. Rev. B (Rapid Communication

Exact entanglement entropy of the XYZ model and its sine-Gordon limit

We obtain the exact expression for the Von Neumann entropy for an infinite bipartition of the XYZ model, by connecting its reduced density matrix to the corner transfer matrix of the eight vertex model. Then we consider the anisotropic scaling limit of the XYZ chain that yields the 1+1 dimensional sine-Gordon model. We present the formula for the entanglement entropy of the latter, which has the structure of a dominant logarithmic term plus a constant, in agreement with what is generally expected for a massive quantum field theory.Comment: 13 pages, 1 figure - v2: typos corrected - v3: some references and comments of sine-Gordon result added - v4: typos correcte

Abordagens Terapêuticas Atuais para a Obesidade: Uma Análise da Literatura

This article provides a comprehensive analysis of current therapeutic approaches for obesity, exploring behavioral interventions, lifestyle modifications, pharmacological options, and bariatric surgery. Through a systematic literature review, the study highlights the ongoing efficacy of behavioral interventions, the diversity of promising pharmacological agents, and the long-term benefits of bariatric surgery. The review also emphasizes the importance of combined therapy and individualized treatment to optimize outcomes. Together, the findings offer a comprehensive insight into available strategies, informing clinical practice and guiding future research in obesity management.Este artigo apresenta uma análise abrangente das abordagens terapêuticas atuais para a obesidade, explorando intervenções comportamentais, modificações no estilo de vida, opções farmacológicas e cirurgia bariátrica. Utilizando uma revisão sistemática da literatura, o estudo destaca a eficácia contínua das intervenções comportamentais, a diversidade de agentes farmacológicos promissores e os benefícios a longo prazo da cirurgia bariátrica. A revisão também enfatiza a importância da terapia combinada e da individualização do tratamento para otimizar resultados. Em conjunto, os resultados oferecem uma visão abrangente das estratégias disponíveis, informando a prática clínica e direcionando futuras pesquisas na gestão da obesidade

Case report: Pembrolizumab plus Axitinib related hypothyroid myopathy in two kidney cancer patients

The first-line therapy in advanced kidney cancer has changed in recent years due to the introduction of combinations of tyrosine kinase inhibitors (TKIs) of vascular endothelial growth factor receptors (VEGFR) and immune checkpoint inhibitors (ICIs). Although immune-related adverse events are well-known, in the case of combination treatments, the determination of which drug is related to an adverse event may be challenging. We reported two cases of patients who developed muscle enzyme elevation in association with hypothyroidism during therapy with pembrolizumab plus axitinib for metastatic kidney cancer. The myopathy rapidly resolved after hormone replacement therapy with levothyroxine. Hypothyroid myopathy is a scarcely known and underreported adverse event. This adverse event may be relevant in the differential diagnosis with immune-related myositis, which has an autoimmune pathogenesis and a potentially fatal course