Circulating Tumor DNA As A MRD Assessment And Recurrence Risk In Patients Undergoing Curative Intent Resection With Or Without Adjuvant Chemotherapy In Colorectal Cancer: A Meta-analysis

Abstract

PURPOSE: Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for Minimal residual disease (MRD) in CRC patients. Recent studies have shown that the ability to detect MRD using ctDNA assay after curative-intent surgery will change how to assess recurrence risk and patient selection for adjuvant chemotherapy. METHODS: We performed a meta-analysis of post-operative ctDNA in Stage I-IV (oligometastatic) CRC patients after curative-intent resection. We included 23 studies representing 3,568 patients with evaluable ctDNA in CRC patients post-curative intent surgery. Data were extracted from each study to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. RESULTS: The pooled hazard ratio (HR) for recurrence-free survival (RFS) in post-surgical ctDNA positive versus negative patients in all stages was 7.27 (95% CI 5.49-9.62) p <0.00001. Subgroup analysis revealed pooled HR of 8.14 (95% CI 5.60-11.82) and 4.83 (95% CI 3.64-6.39) for stage I-III and IV CRC, respectively. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA positive versus negative patients in all stages was 10.59 (95% CI 5.59-20.06) p <0.00001. The subgroup analysis based on the ctDNA method showed a pooled HR of 8.66 (95% CI 6.38-11.75) and 3.76 (95% CI 2.58-5.48) for tumor-informed and tumor-agnostic, respectively. CONCLUSION: Our analysis emphasizes that post-operative ctDNA is a strong prognostic marker of RFS. Based on our results, ctDNA can be a significant and independent predictor of RFS. This real-time assessment of treatment benefits using ctDNA can be used as a surrogate endpoint for the development of novel drugs in the adjuvant setting.

Mechanisms of Action and Limitations of Monoclonal Antibodies and Single Chain Fragment Variable (scFv) in the Treatment of Cancer

“…Some mAbs approved by the FDA act by blocking signaling pathways, such as Cetuximab and Panitumumab. Cetuximab was able to bind to EGFR and competitively inhibited the binding to the epidermal growth factor (EGF) and other ligands, which blocked the phosphorylation of EGFR induced by ligands and mitigated the activation of the signaling pathways related to cancer development [72] (Figure 1A). Panitumumab is an antagonist and induces the internalization of EGFR.…”