Circulating Tumor DNA for Prediction of Complete Pathological Response to Neoadjuvant Radiochemotherapy in Locally...

Area of Science:

• Oncology
• Molecular Diagnostics
• Rectal Cancer Research

Background:

• Locally advanced rectal cancer treatment involves neoadjuvant chemoradiotherapy (nCRT) followed by surgery.
• Complete pathologic remission (pCR) occurs in ~30% of patients, prompting investigation into non-surgical options like 'watch and wait' (W&W).
• Predictive biomarkers for pCR are needed to guide treatment decisions and personalize care.

Purpose of the Study:

• To investigate the potential of monitoring circulating tumor DNA (ctDNA) changes during nCRT for predicting pCR in rectal cancer.
• To assess if ctDNA dynamics can identify patients achieving pCR and guide W&W strategies.

Main Methods:

• Prospective single-center NEORECT trial involving 40 rectal cancer patients.
• Plasma ctDNA collected before, during, and after nCRT, and before surgery.
• Next-generation sequencing (NGS) identified mutations in tissue; digital PCR (dPCR) quantified ctDNA.

Main Results:

• Identified three ctDNA patterns: increase, decrease, and absence.
• Undetectable ctDNA correlated with good response; tenfold increase linked to new metastases.
• ctDNA alone showed low specificity for pCR prediction and no significant correlation with long-term prognosis.

Conclusions:

• The NEORECT trial demonstrated the feasibility of ctDNA-based monitoring in rectal cancer patients undergoing nCRT.
• ctDNA's utility in predicting pCR for W&W strategies requires further research.
• Larger studies with multi-gene analysis and expanded clinical data are needed for improved prediction.