RESUMO

PURPOSE: To analyze the differences in toxicity and biochemical relapse-free survival with hypofractionated radiotherapy with three-dimensional radiotherapy (3D-CRT) or volumetric arc therapy (VMAT) for prostate cancer taking into account comorbidity measured using the Charlson Comorbidity Index (CCI). METHODS: From January 2011 to June 2016, 451 patients with prostate cancer were treated with 60 Gy (20 daily fractions). VMAT or 3D-CRT was used. Distribution by stage: 17% low-risk, 27.2% intermediate-risk; 39.2% high-risk, 16.6% very high-risk. Mean CCI was 3.4. RESULTS: With a median follow up of 51 months, most patients did not experience any degree of acute GI toxicity (80.9%) compared to 19.1%, who experienced some degree, mainly G-I /II. In the multivariate analysis, only technique was associated with acute GI toxicity ≥ G2. Patients treated with VMAT had greater acute GI toxicity compared with those who received 3D-CRT (23.9% vs. 13.5%, p = 0.005). With respect to acute GU toxicity, 72.7% of patients experienced some degree, fundamentally G-I/II. Neither age, CCI, nor androgen deprivation therapy (ADT) were associated with greater toxicity. Overall survival at 2, 5 and 7 years was 97%, 88% and 83% respectively. The only factor with statistical significance was CCI, with a greater number of events in individuals with a CCI ≥ 4 (p < 0.03). CONCLUSIONS: Hypofractionated radiotherapy for prostate cancer is an effective, well-tolerated treatment even for elderly patients with no associated comorbidity. Longer follow up is needed in order to report data on late toxicity.

Assuntos

RESUMO

The original article shows two mistakes, which are listed here.

RESUMO

Androgen deprivation treatment was the only treatment available for metastatic prostate cancer until recently, with docetaxel as the only treatment with a proven survival benefit in castration-resistant prostate cancer (CRPC). Several drugs have been approved in the castration-resistant disease (sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, radium-223). More recently, docetaxel and abiraterone have been moved to the hormone-sensitive disease setting, achieving better patient survival. The purpose of this article is to define the state of the art in the treatment of prostate carcinoma.

Assuntos

RESUMO

Despite the improvement provided by androgenic suppression in the treatment of prostate cancer, most of tumors develop resistance to castration. However, new therapies have demonstrated an increase in patient survival such as radium-223 (Ra-223), an alpha emitter and calcium mimetic with the capability of targeting osteoblastic metastatic lesions. According to results of the ALSYMPCA phase III trial, Ra-223 has demonstrated its activity by improving symptoms and survival of patients with metastatic castration-resistant prostate cancer (mCRPC), symptomatic bone metastases, and no known visceral metastatic disease, without interfering with subsequent treatments. This review examines the key evidence to establish the best patient selection criteria to use Ra-223, how to assess the response to treatment, treatment-related toxicity, and follow-up, but also current research regarding imaging techniques and biomarkers to assess the efficacy of Ra-223. Finally, we briefly describe the clinical trials that are currently ongoing with Ra-223.

Assuntos

RESUMO

PURPOSE: Androgen receptor (AR) splice variant 7 (AR-V7) has been related with both a higher risk of prostate cancer (PC) progression and differential responsiveness to hormonal agents versus chemotherapy. The objective of this study was to investigate the feasibility of a novel capillary nano-immunoassay in assessing AR-V7 in plasma from PC patients. METHODS: Patients with either localized or advanced PC were included in the study. Assessment of AR-V7 in plasma was performed through a capillary nano-immunoassay platform. Correlation with clinical data, stem cell biomarkers (such as CD133+), AR amplification and PTEN status was identified. RESULTS: The study included 72 PC patients. AR-V7 signal was detected in 21 (29%) patients: 17 (81%) had a Gleason score ≥7, 15 (71%) castration-resistant prostate cancer (CRPC), 18 (86%) metastatic disease and PSA (median) high than AR-V7 negative (p < 0.05). CD133 was expressed in 69 (96%) patients. The median CD133+ expression in circulating tumor cells CTCs was higher among the 21 AR-V7 positive cases versus AR-V7 negative (7 vs. 3). Androgen Receptor and PTEN fluorescence in situ hybridization (FISH) on CD133+ captured cells were performed: 37 cases showed ≥four CD133+ CTCs, of which 81% showed an increased AR copy number. This percentage was similar in both AR-V7-positive and AR-V7-negative patients. A total of 68% of the cases showed deletion of PTEN: 70% were ARV-7 positive vs. 67%, which were AR-V7 negative. CONCLUSIONS: Assessing the presence of AR-V7 in plasma from PC patients is feasible by a novel capillary nano-immunoassay. AR-V7 was observed in 29% of the tumors and is more frequent in aggressive tumors.

Assuntos

RESUMO

INTRODUCTION: Anthracyclines have various mechanisms of action that in the end lead to DNA double-strand breaks. Single-nucleotide polymorphisms (SNPs) in DNA repair genes may alter the protein function, affecting DNA repair proficiency and, therefore, the efficiency of DNA damaging chemotherapy. We have analysed whether SNPs in DNA repair genes (XRCC1, XRCC3 and XPD) could be useful to predict the response to anthracyclines in patients with early-stage breast cancer (EBC). METHODS: Peripheral blood samples from 150 patients with EBC were used for genotyping XRCC3Thr241Met, XRCC1Arg399Gln and XPDLys751Gln. Genotypes were correlated with survival outcomes. RESULTS: Eighty-four patients received treatment with chemotherapy regimens containing anthracyclines. In this group, patients with XRCC1Arg399Arg had a significant improvement in 5-year Disease Free Survival (DFS) compared with those with the Arg/Gln and Gln/Gln variants (84 vs 46 %, p = 0.026). In the multivariate analysis, XRCC1Arg399Arg was reported as an independent prognostic factor for DFS (HR 0.4, CI-95 % 0.2-0.9, p = 0.035). Patients with the XRCC3 Met241Met genotype presented better 5-year OS than those carrying the Thr/Thr and Met/Thr variants (100 vs 70 %, p = 0.030). A multivariate analysis for OS confirmed the independent prognostic value of XRCC3 Met241Met (HR 0.15, CI-95 % 0.02-0.90, p = 0.048). These differences were not significant when patients receiving other chemotherapy treatments, different from anthracyclines, were also considered (n = 150). XPDLys751Lys was associated with older age at diagnosis than the Lys/Gln and Gln/Gln genotypes (65 vs 58 years, p < 0.0001). CONCLUSIONS: XRCC3Thr241Met and XRCC1Arg399Gln may be predictive of survival outcome in EBC patients treated with anthracycline-based chemotherapy regimens.

Assuntos

RESUMO

Dengue fever recently reemerged in the Americas. Because vaccines are still under development, dengue prevention depends entirely on vector control. Since Aedes aegypti (Linnaeus, 1762) is the principal vector of this arbovirus, knowledge of the genetic structure of the insect is therefore required to maintain effective vector control strategies and to estimate levels of gene flow from which movement can be inferred. This preliminary study uses microsatellite and amplified fragment length polymorphism (AFLP) markers, to provide insights into genetic diversity of A. aegypti populations from different districts of two towns, located in the north-west of Mexico, Hermosillo and Guaymas. Although the microsatellites used were found to display limited polymorphism, they allowed discrimination between mosquitoes from the northern and the southern districts of Hermosillo. Using AFLP markers, clustering of individuals from the same town and from the same district was observed. Data from microsatellite and AFLP markers analysis both suggest that reinvasion of A. aegypti probably occurs from Guaymas to Hermosillo.

Assuntos