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Circulating tumor cells (CTCs) are present at extraordinarily low levels in the blood of patients with non-hematological cancers, but they provide a non-invasive source of cancer cells for potential diagnostic applications, as well as for understanding the process of blood-borne metastasis. We have developed and tested three generations of microfluidic devices for the isolation of CTCs, each with further improvements in automation, processing throughput, and downstream analytical capabilities. The CTC-iChip allows high throughput and high efficiency depletion of normal leukocytes through a microfluidic magnetophoresis device, revealing untagged CTCs. The unbiased isolation of CTCs irrespective of tumor epitopes, together with their presentation in a format where they can be readily manipulated, provides unique opportunities for their detailed molecular characterization. We have previously shown that rising or declining numbers of CTCs are well correlated with tumor progression or therapeutic response; that they can be used to monitor the prevalence of known clinically-relevant mutations; and that changes in their composition can be followed longitudinally during the course of targeted cancer therapies. Epithelial-to-mesenchymal transition (EMT) is evident among CTCs and evolves dynamically during the course of response or progression following cancer therapy. The heterogeneity of CTC populations is evident in single cell imaging analyses and sequencing studies, with implications for understanding the complexity of metastatic progression and therapeutic responses. Taken together, the application of novel bioengineering technologies to the isolation and analysis of CTCs across multiple different cancer types offers a unique window into the properties of cancer cells that invade into the bloodstream and give rise to metastases. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):PL06-04. Citation Format: Daniel A. Haber, Shyamala Maheswaran, Lecia Sequist, Min Yu, Emre Ozkumur, David Ting, David Miyamoto, Richard Lee, Ajay Shah, Aditya Bardia, Shannon Stott, Mehmet Toner. Molecular characterization of circulating tumor cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr PL06-04.

Background It is not known whether the addition of chemotherapy to radiation therapy improves outcomes in primary vaginal cancer. Here, we review clinical outcomes in patients with primary vaginal cancer treated with radiation therapy (RT) or concurrent chemoradiation therapy (CRT). Methods Seventy-one patients with primary vaginal cancer treated with definitive RT with or without concurrent chemotherapy at a single institution were identified and their records reviewed. A total of 51 patients were treated with RT alone; 20 patients were treated with CRT. Recurrences were analyzed. Overall survival (OS) and disease-free survival (DFS) rates were estimated using the Kaplan-Meier method. Cox regression analysis was performed. Results The median age at diagnosis was 61 years (range, 18–92 years) and the median follow-up time among survivors was 3.0 years. Kaplan-Meier estimates for OS and DFS differed significantly between the RT and CRT groups (3-yr OS = 56% vs. 79%, log-rank p = 0.037; 3-yr DFS = 43% vs. 73%, log-rank p = 0.011). Twenty-three patients (45%) in the RT group had a relapse at any site compared to 3 (15%) in the CRT group (p = 0.027). With regard to the sites of first relapse, 10 patients (14%) had local only, 4 (6%) had local and regional, 9 (13%) had regional only, 1 (1%) had regional and distant, and 2 (3%) had distant only relapse. On univariate analysis, the use of concurrent chemotherapy, FIGO stage, tumor size, and date of diagnosis were significant predictors of DFS. On multivariate analysis, the use of concurrent chemotherapy remained a significant predictor of DFS (hazard ratio 0.31 (95% CI, 0.10–0.97; p = 0.04)). Conclusions Vaginal cancer results in poor outcomes. Adequate radiation dose is essential to ensure curative management. Concurrent chemotherapy should be considered for vaginal cancer patients.

4566 Background: Cabo (XL184) is an oral inhibitor of MET and VEGFR2. In a randomized discontinuation trial of cabo 100mg daily, 76% of men with CRPC and bone metastases had partial or complete resolution of bone scan lesions as early as week (wk) 6. However, treatment was limited by adverse events (AEs), with dose reductions in 51% of patients (pts), and discontinuations in 10%. The current study was designed to determine the efficacy and tolerability of cabo at lower starting doses. Methods: An adaptive response scheme was used to determine the lowest active daily cabo dose among dose levels +1 (60mg), 0 (40mg), and -1 (20mg). The primary endpoint was wk 6 bone scan response (BSR) assessed with an automated FDA 510(k) approved computer-aided detection system. A ≥30% decrease in total bone scan lesion area (BSLA) was defined as a response. The first cohort was treated at dose level 0. The number of responses (≥8 vs.