Handbook of Targeted Cancer Therapy and Immunotherapy

96 Colorectal Cancer Several early studies by multiple groups had shown individual cfDNA markers or marker panels as well as methylation patterns to have the ability to distinguish patients with colorectal cancer (CRC) from benign or healthy controls. These early studies had also established good concordance with tissue molecular profiling (4,5). In a study where fresh frozen tissue and plasma samples obtained at the time of surgery from 29 CRC patients were analyzed with an 85 gene panel, median ctDNA levels of 14.2 and 8.94 ng/mL were noted in colon and rectal cancer patients, respectively, with 70% concordance between ctDNA and tissue molecular profile. The small number of rectal cancer patients in this study ( N = 10) had lower overall concordance (50%) with tissue profiles (6). Systematic reviews of literature published over the past two decades have noted other individual ctDNA markers such as septin 9 ( SEPT9 ), or marker panels, that have been studied for disease detection. Varying ranges of sensitivity (37%–96%) and specificity (79%–99%) among studies have excluded these markers as clinically useful screening tools but with potential for other applications such as disease monitoring with further validation (7). Methylation status of promoter regions of genes methylguanine methyltransferase ( MGMT ) and DNA excision repair pro tein ( ERCC-1 ) analyzed via liquid biopsy in 50 patients with rectal cancer compared to 43 patients with benign rectal lesions had also shown discriminatory potential with a specificity of 93% to 95% and sensitivity of approximately 60% (8). Petit et al. (7) from their systematic review concluded that methylated cfDNA may serve as a promising candidate for CRC detection. With the advent of next-generation sequencing (NGS), genomic profiling using various com mercially available liquid biopsy platforms has enabled serial analysis of ctDNA for prediction of survival outcomes and detection of disease recurrence. MRD is defined as minute amounts of can cer cells remaining during or after completion of therapy as detected by highly sensitive techniques. MRD can imply the presence of micrometastasis prior to clinical detection. Identification of ctDNA after definitive surgery in colon cancer patients has been associated with increased disease recur rence. In a study of 231 stage II colon cancer patients, ctDNA had been detected in 14/178 patients postoperatively who did not receive adjuvant therapy, and 11/14 (79%) patients had recurrence of disease at 27 months follow-up compared to a recurrence rate of 16/164 (9.8%) patients who did not have ctDNA present postoperatively (hazard ratio [HR] 18; 95% confidence interval [CI] 7.9–40;

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