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

ABSTRACT

Introduction

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.

Areas covered

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), K^trans, SUV_max, 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.

Expert opinion

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.

KEYWORDS:

• Rectal cancer
• chemoradiotherapy
• response prediction
• magnetic resonance imaging
• positron emission tomography
• circulating tumor cells
• circulating tumor nucleic acid

Article highlights

• This review examines the value of functional imaging (diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE) MRI, and PET) and liquid biomarkers (circulating tumor cells and circulating tumor nucleic acid) in the prediction of chemoradiotherapy response in rectal cancer.

• This review discusses how imaging and liquid biomarkers can be used to stratify patients for personalized treatment strategies such as ‘watch-and-wait,’ biology-guided adaptive radiotherapy, and total neoadjuvant therapy.

• The most promising imaging biomarkers for response prediction are ADC (DWI MRI) and SUV_max (PET). The value of DCE MRI for response prediction is less certain.

• The presence of circulating tumor cells and circulating tumor DNA after CRT has been correlated with poorer response and outcomes.

• New imaging systems such as MRI-Linac and hybrid MRI-PET are discussed.

• Further steps needed for clinical translation of imaging and liquid biomarkers include multicenter clinical and technical validation, and incorporation of biomarkers into prospective treatment stratification studies.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737140.2022.2114457

Additional information

Funding

The authors have no funding to report.