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Immune and BRAF-targeted therapies have changed the therapeutic scenario of advanced melanoma, turning the clinical decision-making a challenging task. This Bayesian network meta-analysis assesses the role of immunotherapies and targeted therapies for advanced melanoma. We retrieved randomized controlled trials testing immune, BRAF-or MEK-targeted therapies for advanced melanoma from electronic databases. A Bayesian network model compared therapies using hazard ratio (HR) for overall survival (OS), progression-free survival (PFS), and odds ratio (OR) for response rate (RR), along with 95% credible intervals (95% CrI), and probabilities of drugs outperforming others. We assessed the impact of PD-L1 expression on immunotherapy efficacy. Sixteen studies evaluating eight therapies in 6849 patients were analyzed. For OS, BRAF-MEK combination and PD-1 single agent ranked similarly and outperformed all other treatments. For PFS, BRAF-MEK combination surpassed all other options, including CTLA-4-PD-1 dual blockade hazard ratio (HR: 0.56; 95% CrI: 0.33-0.97; probability better 96.2%), whereas BRAF single agent ranked close to CTLA-4-PD-1 blockade.

There is strong evidence that enzalutamide outperforms AA with prednisone in terms of radiographic PFS and PSA progression and PSA response rate but not OS in the pre and post-docetaxel settings. These results may further guide clinicians in making treatment recommendations for patients with advanced prostate cancer. Prostate 77: 639-646, 2017. © 2017 Wiley Periodicals, Inc.

returning of cardiac functions to baseline he was re-challenged with second dose of nivolumab. Patient again developed decomensated CHF with ejection fraction of 30-40%. Subsequent therapy was aborted. Patient continues to have stable disease off therapy for the past 8 months. Our second patient developed moderate to severe pericardial effusion after fifth dose of nivolumab. Pericardial fluid cytology was negative for malignancy and CT scans showed stable visceral metastatic disease. He is currently off therapy and will get a prolonged 8 week steroid taper. Our literature review revealed only nineteen documented cases of immune checkpoint mediated cardiotoxicity. Seventeen of the 19 patients had metastatic melanoma; the remaining two had non-small cell lung cancer (one adenocarcinoma and one squamous cell). Six of the 19 patients developed cardiotoxicity within five weeks of treatment initiation. One of the patients developed biopsy confirmed immune mediated cardiotoxicity 31 weeks after initiation of treatment. Seven patients were treated with ipilimumab alone, four with nivolumab, one with pembrolizumab and the remaining seven patients received a combination of PD1/PDL-1 and CTLA-4 antibody either sequentially or concurrently. Six out of 19 patients died from toxicity of the respective drugs. Conclusion: Immune checkpoint associated cardiotoxicity is rare but well defined in literature. Patients can present with decompensated heart failure, arrhythmia or pericardial effusions. Early recognition, prolonged steroid taper and optimization of cardiac function with diuretics, ACE inhibitors and beta blockade are critical steps for the successful management.

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Distribution forecast can quantify forecast uncertainty and provide various forecast scenarios with their corresponding estimated probabilities. Accurate distribution forecast is crucial for planning -for example when making production capacity or inventory allocation decisions. We propose a practical and robust distribution forecast framework that relies on backtest-based bootstrap and adaptive residual selection. The proposed approach is robust to the choice of the underlying forecasting model, accounts for uncertainty around the input covariates, and relaxes the independence between residuals and covariates assumption. It reduces the Absolute Coverage Error by more than 63% compared to the classic bootstrap approaches and by 2% − 32% compared to a variety of State-of-the-Art deep learning approaches on in-house product sales data and M4-hourly competition data.