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    ABSTRACT: With seven targeted agents, directed against the VEGF/VEGF receptor (VEGFR) axis or the mTOR pathway, approved for the treatment of metastatic renal cell carcinoma and more active agents in advanced phase of clinical testing, questions have arisen with regard to their optimal use, either in combination or in sequence. One of the most compelling (and debated) issues is whether continued VEGF/VEGFR inhibition with agents hitting the same targets (TKI-TKI) affords better results than switching mechanisms of action by alternating VEGFR and mTOR inhibition (TKI-mTOR). In this article, the authors review the (little) available evidence coming from randomized Phase III clinical trials and try to fill in the (many) remaining gaps using evidence from small-size, single-arm Phase II studies and retrospective series, as well as reviewing preclinical evidence supporting either strategy.
    Expert Review of Anti-infective Therapy 12/2012; 12(12):1545-57. DOI:10.1586/era.12.149 · 2.25 Impact Factor
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    ABSTRACT: Neoadjuvant approaches in renal cell carcinoma are currently under investigation, following the demonstration of targeted therapy efficacy in the metastatic setting. It raises the issues of downsizing locally advanced or nonresectable tumor and offering organ-sparing surgery, saety and its potential role in early micrometastatic disease. Relevant studies of the neoadjuvant setting in renal cell carcinoma with targeted therapies were identified from the literature, clinical trial databases and conference abstracts. To date, a neoadjuvant approach appears feasible in terms of saety. Currently available drugs do not achieve major tumor downsizing with primary tumor diameters response rate of 10%. Neoadjuvants should only be considered in clinical trials or as a litmus test in locally advanced patients.
    Expert Review of Anti-infective Therapy 12/2012; 12(12):1559-69. DOI:10.1586/era.12.142 · 2.25 Impact Factor
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    ABSTRACT: Background and purpose: To analyze the location of metastatic lymph nodes in seminoma patients relative to vascular and bony anatomy and conventional radiation fields. Materials and methods: Cross-sectional scans of 90 seminoma patients with infradiaphragmatic adenopathy were analyzed. The position of each node respective to vascular anatomy was transferred to a standardized template. Conventional radiation fields were overlaid on the template and locations of metastatic nodes were assessed. Results: One hundred and forty-five nodes were radiographically positive. Eighty-four percent, 9%, and 7% of nodes were located in the para-aortic, common iliac, and pelvic regions, respectively. Ninety-nine percent of nodes were within a 2.5 cm lateral and 2.1cm anterior expansion of the aorta inferior to T12/L1. No radiographically positive nodes were identified within the renal hilum or superior to L1 in left-sided seminomas. For right-sided seminomas, no radiographically positive nodes were superior to L2. Three percent of all radiographically positive nodes would have been located outside of conventional and modified fields. Conclusions: Infradiaphragmatic nodal metastases from a contemporary cohort of seminoma patients localized to a smaller area than is targeted by conventional radiation fields. Modified treatment fields based on vascular, rather than bony, anatomy are smaller and may allow for a significant decrease in normal tissue irradiation and toxicity.
    Radiotherapy and Oncology 01/2013; 106(1). DOI:10.1016/j.radonc.2012.12.002 · 4.36 Impact Factor
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