Androgenic suppression combined with radiotherapy for the treatment of prostate adenocarcinoma: a systematic review.

BACKGROUND: Locally advanced prostate cancer is often associated with elevated recurrence rates. Despite the modest response observed, external-beam radiotherapy has been the preferred treatment for this condition. More recent evidence from randomised trials has demonstrated clinical benefit with the combined use of androgen suppression in such cases. The aim of this meta-analysis is to compare the combination of distinct hormone therapy modalities versus radiotherapy alone for overall survival, disease-free survival and toxicity. METHODS: Databases (MEDLINE, EMBASE, LILACS, Cochrane databases and ClinicalTrials.gov) were scanned for randomised clinical trials involving radiotherapy with or without androgen suppression in local prostate cancer. The search strategy included articles published until October 2011. The studies were examined and the data of interest were plotted for meta-analysis. Survival outcomes were reported as a hazard ratio with corresponding 95% confidence intervals. RESULTS: Data from ten trials published from 1988 to 2011 were included, comprising 6555 patients. There was a statistically significant advantage to the use of androgen suppression, in terms of both overall survival and disease free survival, when compared to radiotherapy alone. The use of long-term goserelin (up to three years) was the strategy providing the higher magnitude of clinical benefit. In contrast to goserelin, there were no trials evaluating the use of other luteinizing hormone-releasing hormone (LHRH) analogues as monotherapy. Complete hormonal blockade was not shown to be superior to goserelin monotherapy. CONCLUSIONS: Based on the findings of this systematic review, the evidence supports the use of androgen suppression with goserelin monotherapy as the standard treatment for patients with prostate cancer treated with radiotherapy, which are at high risk of recurrence or metastases.

Myosteatosis in a systemic inflammation-dependent manner predicts favorable survival outcomes in locally advanced esophageal cancer.

Increased adiposity and its attendant metabolic features as well as systemic inflammation have been associated with prognosis in locally advanced esophageal cancer (LAEC). However, whether myosteatosis and its combination with systemic inflammatory markers are associated with prognosis of esophageal cancer is unknown. Our study aimed to investigate the influence of myosteatosis and its association with systemic inflammation on progression-free survival (PFS) and overall survival (OS) in LAEC patients treated with definitive chemoradiotherapy (dCRT). We retrospectively gathered information on 123 patients with LAEC submitted to dCRT at the University of Campinas Hospital. Computed tomography (CT) images at the level of L3 were analyzed to assess muscularity and adiposity. Systemic inflammation was mainly measured by calculating the neutrophil-to-lymphocyte ratio (NLR). Median PFS for patients with myosteatosis (n = 72) was 11.0 months vs 4.0 months for patients without myosteatosis (n = 51) (hazard ratio [HR]: 0.53; 95% confidence interval [CI], 0.34-0.83; P = .005). Myosteatosis was also independently associated with a favorable OS. Systemic inflammation (NLR > 2.8) was associated with a worse prognosis. The combination of myosteatosis with systemic inflammation revealed that the subgroup of patients with myosteatosis and without inflammation presented less than half the risk of disease progression (HR: 0.47; 95% CI: 0.26-0.85; P = .013) and death (HR: 0.39; 95% CI, 0.21-0.72; P = .003) compared with patients with inflammation. This study demonstrated that myosteatosis without systemic inflammation was independently associated with favorable PFS and OS in LAEC patients treated with dCRT.

Chagasic Megaesophagus-Associated Carcinoma: Clinical Pattern and Outcomes.

PURPOSE: Approximately 4% to 10% of patients diagnosed with Chagas-induced megaesophagus disease develop esophageal carcinoma. However, the natural history and clinical pattern of this entity are not well described. METHODS: Herein, we retrospectively analyzed 593 patients with esophageal carcinoma treated at a single Brazilian institution. We identified 32 patients with Chagas disease, of whom 11 had megaesophagus. The epidemiologic profile and oncological treatment outcomes were evaluated. RESULTS: Although baseline characteristics were similar among the three groups, patients with Chagas megaesophagus-associated carcinoma (CMAC) presented with a lower rate of smoking. This factor reinforced the concept that achalasia is the predominant risk factor for cancer development. The CMAC group had a higher rate of tumor in situ (two of 11 patients) compared with the other groups. These patients were treated with endoscopic resection, and no recurrence was detected. Eight of 11 patients with CMAC were diagnosed with locally advanced disease. Patients with locally advanced CMAC presented with a median progression-free survival of 7.8 months and a median overall survival of 9.1 months. CONCLUSION: If CMAC is not promptly detected, it has a dismal prognosis, indicating that a high index of suspicion of esophageal carcinoma is required for patients with Chagasic megaesophagus. Additional studies are needed to improve the surveillance and treatment approaches for this neglected disease.

Gemcitabine-related thrombotic microangiopathy: a single-centre retrospective series.

INTRODUCTION: Thrombotic microangiopathy (TMA) has been reported as a complication of chemotherapy. Many antineoplastic agents have been linked to TMA, gemcitabine being one of the most frequently cited as related to this syndrome. METHODS: A retrospective search for chemotherapy-induced TMA cases among gemcitabine users in a single oncology centre from January 2009 to September 2012 was performed. RESULTS: Three cases of gemcitabine-induced TMA were reported, from a total of 264 patients (incidence: 1·13%) who received the drug. From the three cases reported, two (66%) patients died as a consequence of the syndrome. DISCUSSION: These findings are compatible with previous analyses, which report an incidence of gemcitabine-associated TMA ranging from 0·008 to 2·2% and mortality rates from 15 to 90%. Unlike previously reported, however, cumulative dose was not predictive of risk. CONCLUSION: Gemcitabine-induced TMA is an underdiagnosed condition characterized by high mortality rates. Attention should be called for a higher level of awareness to provide early diagnosis and proper treatment.

Addition of bevacizumab to chemotherapy in advanced non-small cell lung cancer: a systematic review and meta-analysis.

INTRODUCTION: Recently, studies have demonstrated that the addition of bevacizumab to chemotherapy could be associated with better outcomes in patients with advanced non-small cell lung cancer (NSCLC). However, the benefit seems to be dependent on the drugs used in the chemotherapy regimens. This systematic review evaluated the strength of data on efficacy of the addition of bevacizumab to chemotherapy in advanced NSCLC. METHODS: PubMed, EMBASE, and Cochrane databases were searched. Eligible studies were randomized clinical trials (RCTs) that evaluated chemotherapy with or without bevacizumab in patients with advanced NSCLC. The outcomes included overall survival (OS), progression-free survival (PFS), response rate (RR), toxicities and treatment related mortality. Hazard ratios (HR) and odds ratios (OR) were used for the meta-analysis and were expressed with 95% confidence intervals (CI). RESULTS: We included results reported from five RCTs, with a total of 2,252 patients included in the primary analysis, all of them using platinum-based chemotherapy regimens. Compared to chemotherapy alone, the addition of bevacizumab to chemotherapy resulted in a significant longer OS (HR 0.89; 95% CI 0.79 to 0.99; p = 0.04), longer PFS (HR 0.73; 95% CI 0.66 to 0.82; p<0.00001) and higher response rates (OR 2.34; 95% CI 1.89 to 2.89; p<0.00001). We found no heterogeneity between trials, in all comparisons. There was a slight increase in toxicities in bevacizumab group, as well as an increased rate of treatment-related mortality. CONCLUSIONS: The addition of bevacizumab to chemotherapy in patients with advanced NSCLC prolongs OS, PFS and RR. Considering the toxicities added, and the small absolute benefits found, bevacizumab plus platinum-based chemotherapy can be considered an option in selected patients with advanced NSCLC. However, risks and benefits should be discussed with patients before decision making.