Predictive value of circulating methylated Septin 9 for pathologic complete response to neoadjuvant chemoradiation therapy in locally advanced rectal cancer.

e15649 Background: Prediction of pathologic complete response (pCR) after neoadjuvant radio-chemotherapy (nCRT) is of great importance for locally advanced rectal cancer (LARC) since it provides the basis for selection of patients appropriate for non-operative management. Unfortunately, there is a lack of significant biomarkers that can predict pCR with sufficient accuracy. Circulating methylated Septin 9 (mSEPT9) is detected in around 70% of patients with early colorectal cancer, but whether it has applicable clinical value in predicting response to nCRT has remained unaddressed. The primary objective was to examine the connection between baseline mSEPT9 and tumor response to nCRT of LARC and whether mSEPT9 blood test can be used as an early predictor of pCR achievement. Methods: Consecutive patients with cT 3-4 N x M 0 staged rectal carcinoma who underwent 5-FU-based nCRT followed by radical surgery between February 2019 and October 2022 were retrospectively enrolled from the database of The First Affiliated Hospital of Nankai University. The level of mSEPT9 was detected at baseline from venous blood samples with pCR technique. Collection of demographic and other clinical-pathological data included patient gender, age, cTNM and ypTNM stage, pathology, distance from anal verge, hemoglobin, serum CEA and CA-199, treatment regimens, and data from imaging tests. mSEPT9, along with other baseline characteristics, were compared between pCR group and non-pCR group using the Chi-square test or Fisher’s exact test with P < 0.05 considered significant. Multivariate logistic regression was then performed to assess the effect of mSEPT9 status on pCR, controlling for predetermined mediating and confounding variables, and the prediction efficiency was assessed using the receiver operating characteristic curve (ROC). Results: Of the 87 LARC patients included, 30 (34.5%) patients had a negative mSEPT9 blood test at baseline, and 57 (65.5%) were mSEPT9 positive. pCR was achieved in 14 patients at a total pCR rate of 16.1%. Patients who showed a negative mSEPT9 at baseline had a significantly higher rate of pCR than those who were mSEPT positive (40.0% vs. 3.5%, P < 0.05). But none of the other pretreatment clinical variables were significantly correlated with the likelihood of pCR in univariate analysis. Multivariate logistic regression revealed that only negative baseline mSEPT9 was an independent predictive factor for pCR (β-coefficient [SE], 2.909 [0.811]; P = .000). ROC curve was drawn, and the area under ROC curve value was 0.805 (95% Cl = 0.683 to 0.928), with a sensitivity of 85.7% and specificity of 75.3%. Conclusions: Our results showed that a negative mSEPT9 blood test at baseline had a predictive potential for pCR and may serve as an ancillary aid for individualized therapeutic decisions in patients with LARC.