Introduction
Despite complete surgical resection survival in early stage non-small cell lung cancer (NSCLC) remains poor. Based on prior pre-clinical evaluations, we hypothesized that combined induction proteasome and histone deacetylase inhibitor therapy, followed by tumor resection, is feasible.
Methods
A phase I clinical trial using a two-staged multiple agent design of bortezomib and vorinostat as induction therapy followed by consolidative surgery in patients with NSCLC was performed. Standard toxicity and MTD were examined. Pre- and post-treatment tumor gene expression arrays were performed and analyzed. Pre- and post-treatment FDG-PET imaging was used to assess tumor metabolism. Finally, serum 20S proteasome levels were analyzed with ELISA, and selected intratumoral proteins were assessed via immunohistochemistry.
Results
Thirty-four patients were consented with 21 patients enrolling in the trial. One patient withdrew early secondary to disease progression. The MTD was bortezomib 1.3 mg/m2 and vorinostat 300 mg BID given. There were (2) grade III dose-limiting toxicities of fatigue and hypophosphatemia that were self-limited. There was no mortality. Thirty percent (6/20) of patients had greater than 60% histologic necrosis of their tumor following treatment, with two having ≥90% tumor necrosis. Tumor metabolism, 20S proteasome activity, and specific protein expression did not demonstrate consistent results. Gene expression arrays comparing pre- and post-therapy NSCLC specimens revealed robust intratumoral changes in specific genes.
Conclusions
Induction bortezomib and vorinostat therapy followed by surgery in patients with operable NSCLC is feasible. Correlative gene expression studies suggest new targets and cell signaling pathways that may be important in modulating this combined therapy.
EUS-FNA is a safe, relatively cost-effective, and accurate initial diagnostic modality for the diagnosis of lung lesions adjacent to the esophagus or invading the mediastinum. Although further randomized prospective trials are warranted, this modality should be considered as a first step in the diagnostic armamentarium in centrally located lung lesions.
Providing an adequate method of distance learning is a challenge faced by many multicenter residency programs. The delivery of live didactics over the Internet is a convenient means of providing a uniform and equivalent educational experience to residents at distant sites. An application called MedCast has been developed with use of existing technologies, without the need for costly commercial products or equipment. MedCast captures the presenter's computer screen and audio from a microphone source to produce a streaming video that is transmitted online and archived on a local server. Offsite residents can view broadcasts in real time or access archived conference sessions for later viewing. MedCast is available for download at no cost and offers several advantages, including a user-friendly graphical display interface, near-perfect preservation of image quality, and cost efficiency. Future plans include objective assessment of the efficacy of MedCast by comparing postlecture examinations to help evaluate for any differences between on- and offsite residents in terms of knowledge gained. A movie clip to supplement this article is available online at http://radiographics.rsnajnls.org/cgi/content/full/285085701/DC1.
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