Abstract
ObjectiveThe aim of this study is to develop a nomogram for prediction of pathologic complete remission (pCR) after preoperative chemoradiotherapy (CRT) for rectal cancer.MethodsmRNA expression levels of seven molecular markers [p53, p21, Ki-67, vascular endothelial growth factor (VEGF), CD133, CD24, CD44] were measured by reverse transcriptase polymerase chain reaction (RT-PCR) in 120 rectal cancers. Endoscopic findings of clinical complete remission (cCR) and biologic variables were used to construct nomogram in the training group (n=80), which was validated in the validation group (n=40).ResultsmRNA expression levels of four markers (p53, p21, Ki67, CD133) correlated with pCR (24/80, 30.0%) in the training group. Low expression of p53 and/or high expression of p21, Ki67 and CD133 showed greater pCR rate. pCR was shown in 18 (69.2%) of 26 cases showing endoscopic cCR in the training group. Higher pCR rate was demonstrated in lower tumor location than middle tumor (19/49, 38.8% vs. 5/31, 16.1%). A nomogram for prediction of pCR was developed from the multivariate prediction model using these six variables, which showed good discrimination ability in the training group [area under the curve (AUC)=0.945] and validation group (AUC=0.922). The calibration plot showed good agreement between actual and predicted pCR in both patient groups. ConclusionsNomogram for assessment of pCR can be useful for making treatment decisions after CRT according to predicted responses.
Highlights
Most expert groups and treatment guidelines have adopted preoperative chemoradiotherapy (CRT) as the preferred method to improve oncologic outcomes and allow performance of sphincter-preserving surgery through tumor downstaging in patients with advanced middle or low rectal cancer [1]
We demonstrated a scoring system based on IHC analysis of four tumor proteins (p53, vascular endothelial growth factor (VEGF), p21 and Ki67) that accurately predicted pathologic complete remission (pCR) in middle and low rectal cancer [8]
This study aimed to develop a nomogram for prediction of pCR after preoperative CRT in rectal cancer based on mRNA expression of molecular markers measured by reverse transcriptase polymerase chain reaction (RTPCR) and endoscopic findings
Summary
Most expert groups and treatment guidelines have adopted preoperative chemoradiotherapy (CRT) as the preferred method to improve oncologic outcomes and allow performance of sphincter-preserving surgery through tumor downstaging in patients with advanced middle or low rectal cancer [1]. A number of tumor proteins are being studied as candidate predictive markers for prediction of response to CRT in rectal cancer. These proteins can be assessed by immunohistochemical (IHC) analysis or reverse transcriptase polymerase chain reaction (RT-PCR). We demonstrated a scoring system based on IHC analysis of four tumor proteins (p53, VEGF, p21 and Ki67) that accurately predicted pCR in middle and low rectal cancer [8]. We validated the significance of these biomarkers and provide more quantitative data by RT-PCR for comprehensive analysis of potential predictive markers [9]
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