Predicting neoadjuvant chemoradiotherapy response with functional imaging and liquid biomarkers in locally advanced rectal cancer

Noninvasive predictive quantitative biomarkers are required to guide treatment individualization in patients with locally advanced rectal cancer (LARC) in order to maximize therapeutic outcomes and minimize treatment toxicity. Magnetic resonance imaging (MRI), positron emission tomography (PET), and blood biomarkers have the potential to predict chemoradiotherapy (CRT) response in LARC.This review examines the value of functional imaging (MRI and PET) and liquid biomarkers (circulating tumor cells (CTCs) and circulating tumor nucleic acid (ctNA)) in the prediction of CRT response in LARC. Selected imaging and liquid biomarker studies are presented and the current status of the most promising imaging (apparent diffusion coefficient (ADC), Ktrans, SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) and liquid biomarkers (CTCs, ctNA) is discussed. The potential applications of imaging and liquid biomarkers for treatment stratification and a pathway to clinical translation are presented.Functional imaging and liquid biomarkers provide novel ways of predicting CRT response. The clinical and technical validation of the most promising imaging and liquid biopsy biomarkers in multicenter studies with harmonized acquisition techniques is required. This will enable clinical trials to investigate treatment escalation or de-escalation pathways in rectal cancer.