Using Liquid Biopsy to Predict Relapse After Radiotherapy in Squamous Cell Head-Neck and Esophageal Cancer

Circulating cell-free DNA (cfDNA) in the blood of cancer patients contains tumor-specific mutated genes and viral genome that can be identified and quantified as 'tumor-specific cfDNA' (circulating tumor DNA, ctDNA). Various technologies are available that offer reliable detection of ctDNA at a low concentration. Quantitative and qualitative analysis of ctDNA may be of prognostic and predictive value in oncology. Here, we present concisely the experience on the assessment of ctDNA levels and kinetics during therapy in the outcome of radiotherapy (RT) and chemo-radiotherapy (CRT) in squamous cell head-neck cancer and esophageal squamous cell cancer patients. The levels of circulating viral (human papilloma virus or Epstein-Barr) ctDNA, and levels of total, mutated or methylated ctDNA at diagnosis are linked with tumor burden and clinical aggressiveness, and may be of prognostic or even predictive value of RT/CRT efficacy. Persistent ctDNA levels after therapy seem to predict high rates of tumor relapse several months before radiological documentation. This can prove of value for the identification of subgroups of patients who could benefit from RT dose-escalation or consolidation chemotherapy and immunotherapy, a hypothesis that should be tested in clinical trials.