Head and neck squamous cell carcinoma (HNSCC) is a deadly disease which in many cases is managed with a combination of radiation and chemotherapy. Unfortunately, the ability to monitor treatment response in real time is limited. Thus, truly individualized therapy remains an unrealized goal. We have previously investigated the possibility of combining advanced imaging using magnetic resonance imaging (MRI) combined with the analysis of circulating tumor cells to classify response in HNSCC as part of a prospective trial (PREDICT-HN). An adaption of the methodology from that trial is described herein in hopes of allowing for recapitulation and further development of this exciting methodology.