Abstract

Abstract Background: Approximately 10% to 15% have residual disease after surgery in patients with stage II CRC. Identification of this high-risk population and treatment with ACT could potentially reduce their risk of recurrence. However, the relative contribution of the factors used to define high risk stage II disease needs better understanding, although post-surgical ctDNA has been studied as a marker for an elevated risk of recurrence in stage I-III colorectal cancer. Methods: Individual data from 3 early colorectal cancer clinical studies(Tie, 2016;Reinert, 2019; Chen, 2021) that included information on high-risk factors and post-surgical ctDNA status were collected and reanalysed for 595 patients with or without ACT. Results: In stage II CRC patients with ctDNA-negative not treated with ACT form the Tie cohort, with high-risk status (n=42) showed a significantly reduced recurrence-free survival (RFS) compared to those with low-risk status(n=122) [HR, 3.283; 95%CI, 1.398 to 14.18; P = 0.0116], but in the ctDNA-negative patients with high-risk status, ACT (n=32) or not did not affect the RFS(P=0.1758). It meant false negatives of ctDNA made for bias of survival analysis results. Interestingly, in other two cohorts of stage II CRC patients with ctDNA-negative not treated with ACT, high-risk status showed no difference in RFS compared to low-risk status (p=0.3429 and 0.3173, respectively). In addition to the low sample size, the contribution of defined high-risk factors in prognosis was worth exploring which meant pseudo high-risk status also affect survival analysis results. And there were big differences in the high-risk factors included in the three cohorts especially in ctDNA-negative patients, such as the proportion of lymph nodes (LN) yield <12 seemed higher in Tie cohort. Conclutions: It was not enough to predict recurrence depend on ctDNA status alone for stage II CRC. Different risk factors might have different prognostic weights so that different combinations of post-surgical ctDNA status and risk factors might be used to make more accurate ACT decision. Citation Format: Xie Gui Yuan, Liu Miao, Huang Meng Li. Combine high risk factors with circulating tumor DNA (ctDNA) to assist adjuvant chemotherapy (ACT) decision in Stage II colorectal cancer (CRC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5115.

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