Circulating Tumor Cells Analyses and Molecular Profiling for Patients Receiving Radiation Therapy

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Circulating Tumor Cells Analyses and Molecular Profiling for Patients Receiving Radiation Therapy ABSTRACT We propose to develop a circulating tumor cell (CTC) assay with unique features and efficacy superior to currently available CTC assays. CTC assays have attracted intense recent attention because of the potential to serially interrogate the biology of solid tumors with minimal risk. The resulting information obtained, including genetic information predicting response to targeted therapy, may inform the clinical management of patients receiving radiation therapy (RT), thus “personalizing treatment” in ways previously unachievable. We propose to study non-small cell lung cancer (NSCLC) and melanoma, two solid tumors of strategic importance and for which we have protocols rapidly accruing patients. These disease sites represent high priority for RT treatment in our investigational clinical trials and represent examples of respectively, epithelial and non-epithelial tumors. We have achieved preliminary data that suggests our approach successfully detects CTCs in patients for whom the current FDA-approved CTC assay is ineffective. Key questions regarding CTC analyses remain, the answers to which would inform how best to incorporate these assays into standard radiation oncology practice. These questions include: (1) Can CTCs be detected in a range of solid tumors undergoing radiation therapy (RT) or other forms of treatment? (2) Do CTC counts give lead-time notice of disease recurrence or progression? (3) Can the genetic background of the identified CTCs be elucidated and does it change over time and after treatment? We will employ a CTC detection method that relies on the elevated telomerase activity in almost all tumors, a hallmark of cancer, which is impervious to limitations posed by the lack of surface expression of tumor markers. In Specific Aim 1 we will track CTC counts in patients with a range of presentations of localized NSCLC undergoing RT to test whether CTC analysis can give lead time notice of tumor recurrence. Aim 2 will test whether CTC analysis is effective in melanoma patients undergoing treatment, including radiation and immunotherapy. For Aim 3, we will test whether the genetic profile of CTCs changes after treatment, including DNA mutations that predict for response to biologically targeted agents. Our successful accomplishment of these scientific aims will illuminate the potential usefulness of CTC assays for a wide range of patients receiving RT and other anticancer treatment.