Abstract 451P
Background
For locally advanced rectal cancer (LARC) patients who achieved complete clinical response (cCR) after neoadjuvant chemoradiotherapy (nCRT), a “Watch & Wait” (W&W) approach is adopted to improve quality of life. However, W&W may increase the recurrence risk of those who are not pathological complete response (non-pCR). Cell-free DNA (cfDNA) end motifs have been used in cancer detection. But its utility in predicting pCR status has not been reported. In this study, we explored the potential of cfDNA end motif profile in the prediction of pathological response in LARC patients.
Methods
We recruited 119 LARC patients (cT3-4/N0-2, M0) who received nCRT plus total mesorectal excision (TME) from February, 2016 to October, 2017. Plasma samples at baseline, during and after nCRT were collected and applied to deep targeted-panel sequencing covering 422 genes. Frequencies of 4096 6-mer 5'-end motifs during and after nCRT were calculated and used as input to construct an elastic-net logistic regression model to predict pCR status. Its predictive performance was evaluated by internal 5-fold cross validation and 30-time repeats.
Results
Among 119 patients, 103 patients completed all sample collection and were included. The out-of-sample validation AUC of the motif model for predicting pCR status was 0.95±0.02 (mean ± standard deviation). With Youden index as cut off, the sensitivity and specificity for predicting non-pCR were 0.95±0.05 and 0.85±0.04, and accuracy was 0.93±0.03. The AUC of MRI-based tumor regression grade (mTRG) was 0.72 with a maximum accuracy of 0.74. Particularly, the end motif based classifier maintained good predictive ability for patients whose circulating tumor DNA (ctDNA) was undetectable during and after nCRT (n=74). The out-of-sample AUC of the model was 0.94±0.02 and sensitivity and specificity for predicting non-pCR were 0.89±0.07 and 0.88±0.06, and the accuracy was 0.89±0.03.
Conclusions
cfDNA 5'-end motif profile has a potential to predict pathological response after nCRT. The model based on the 5'-end motif profile shows superior predictive performance compared to MRI, therefore, may improve the selection of patients for W&W approach.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Fudan University Shanghai Cancer Center.
Funding
National Natural Science Foundation of China (No. 81773357).
Disclosure
All authors have declared no conflicts of interest.