Longitudinal circulating tumor DNA monitoring in predicting response to short-course radiotherapy followed by neoadjuvant chemotherapy and camrelizumab in locally advanced rectal cancer: data from a Phase Ⅲ clinical trial (UNION)

Zhenyu Lin ¹, Menglan Zhai ¹, Haihong Wang ¹

⁰Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Hubei Key Laboratory of Precision Radiation Oncology, Wuhan, 430022, China.

Cancer Letters +

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January 4, 2025

View abstract on PubMed

Summary

Circulating tumor DNA (ctDNA) minimal residual disease (MRD) monitoring shows promise in predicting treatment response for locally advanced rectal cancer (LARC). ctDNA negativity after short-course chemoradiotherapy (CRT) significantly correlates with pathological complete response.

Area Of Science

Oncology
Molecular Diagnostics
Gastrointestinal Cancer Research

Background

Locally advanced rectal cancer (LARC) treatment involves neoadjuvant therapy (NAT) followed by surgery.
Comparing short-course and long-course chemoradiotherapy (CRT) efficacy is crucial.
Minimal residual disease (MRD) assessment aids in treatment response evaluation.

Purpose Of The Study

To evaluate circulating tumor DNA (ctDNA)-based MRD in comparing short-course vs. long-course CRT for LARC.
To assess the predictive value of ctDNA-MRD for pathological complete response (pCR).
To develop a predictive model for pCR/non-pCR in LARC patients.

Main Methods

Multicenter phase III clinical trial involving 79 LARC patients.
Collection and analysis of 244 plasma samples during NAT.
Targeted deep sequencing using a novel ctDNA-MRD panel.

Main Results

ctDNA levels significantly decreased during NAT.
Short-course radiotherapy (shortRT) significantly increased microsatellite instability compared to long-course.
ctDNA negativity/low levels and clearance after shortRT significantly correlated with pCR.
A combined ctDNA-MRD and CEA model outperformed individual predictors for pCR.

Conclusions

ctDNA-based MRD assessment is a valuable tool for monitoring LARC treatment response.
ShortRT shows distinct molecular changes compared to long-course CRT.
Personalized treatment strategies for LARC can be enhanced by ctDNA-MRD monitoring.

Keywords:

Circulating tumor DNA Locally advanced rectal cancer Minimal residual disease Pathologic complete response Short-course radiotherapy