Circulating Tumor DNA Sequencing for Early Diagnosis and Detection of Treatment Response, Minimal Residual Disease, and Recurrence in Gastroesophageal Cancer.

Gastroesophageal cancers (GEC) have high mortality rates with poor prognosis, especially at late stages. This is partly due to unspecific symptoms at early stages, early treatment resistance, and recurrence after curative-intent treatment. Circulating tumor DNA (ctDNA) has gained attention for early cancer diagnosis and longitudinal monitoring. This narrative review summarizes the recent developments of genomic ctDNA analysis for early GEC diagnosis and longitudinal monitoring across 57 relevant studies. For early diagnosis, several studies combined genomic ctDNA analysis with other ctDNA approaches or serum biomarkers. These approaches achieved high sensitivities and specificities in cancer detection within GEC while accurately predicting the tissue of origin, The use of genomic ctDNA analysis has also been studied for longitudinal monitoring of GEC patients during and after various treatment regimens. Studies have shown that ctDNA dynamics is highly consistent with treatment response and disease progression. CtDNA could frequently detect disease progression before conventional methods, thereby displaying its potential application in longitudinal monitoring. Genomic ctDNA analysis could also detect recurrence after curative-intent treatment and, in many cases, before clinical detection. However, ctDNA has low abundance in total cell-free DNA during low-burden disease. Additionally, methodological variation in ctDNA processing and quantification complicates interpretation across studies.