Use of circulating tumor DNA levels to gauge necessity of surgery for patients undergoing trimodality therapy for esophageal cancer.
TPS214 Background: Up to 40% of patients receiving neoadjuvant esophageal chemoradiotherapy (CRT) are found to have no evidence of malignancy post-operatively. Given this, a sensitive and specific biomarker is needed, as reliable identification of complete responders may spare patients the morbidity and mortality of esophagectomies. Recent work with circulating tumor DNA (ctDNA) collected from the plasma of cancer patients indicates tumors routinely shed large amounts of DNA into the blood. This ctDNA can be systematically analyzed, quantification of which has been correlated with local and systemic disease burden. To further increase the specificity of analysis, the somatic mutations that arose in the tumor can be detected in ctDNA via targeted and whole genome sequencing. However, information on the feasibility of using ctDNA quantification as a biomarker for neoadjuvant response assessment is lacking. We hypothesize that quantification of ctDNA throughout trimodality therapy can be of practical use in the non-invasive monitoring of treatment response. The overall goal of this pilot project is to assess the feasibility and predictive utility of incorporating a sensitive, patient and tumor specific, plasma ctDNA quantification assay to more reliably identify complete responders following CRT. The long-term goal of this proposal is to apply these methods into prospective clinical trials for personalization of therapy by identifying neoadjuvant complete responders who may benefit from non-operative therapy. Methods: Pilot/feasibility study to evaluate the correlation between plasma ctDNA levels and pathologic treatment response. Plasma samples at different treatment time points (pre-CRT, during CRT, immediately pre-op and post-op) will be collected from 28 patients receiving pre-operative CRT followed by surgery for esophageal cancer. Patient-specific mutations will be identified through whole exome sequencing of paraffin-embedded pre-treatment biopsies. SafeSeqS PCR primers will be designed per patient for targeting of tumor mutations. Plasma-derived ctDNA will be assayed using the patient-specific SafeSeqS approach for each time point in triplicate.