Comprehensive genetic profiling using tissue and blood in locally advanced tumors

Abstract

Comprehensive genomic profiling (CGP) aims to assist clinicians with the diagnosis, treatment decisions and early detection of recurrence in patients with cancer. CGP using tumor tissue is widely implemented, whereas circulating tumor DNA (ctDNA) analysis is a noninvasive method that uses peripheral blood. This pilot study included eight patients with locally advanced tumors (two each of breast, lung, pancreatic, and head and neck cancers). The concordance of somatic variants with tumor tissues and paired ctDNA from pre‑ and post‑resection samples was evaluated. This study demonstrated that the overall concordance rate in all genes between tissue and postoperative blood was high (94.2%), but the concordance rate in genes with somatic variants was low (4.76%). In patient 8 with head and neck cancer, the MAP2K1 variant was concordant between the tissue and blood after surgery. The patient was found to have a small lung tumor at 10 months after surgery, indicating recurrence in the lung. In patient 6 with pancreas cancer, the TP53 variant was concordant between the blood before and after surgery, but no recurrence was observed. In patient 5 with pancreas cancer, recurrence was identified; however, the somatic variants were not concordant between the tissue and blood. Furthermore, a case, such as patient 8, of recurrence with somatic variants matching the tissue and postoperative blood was encountered, suggesting that detecting a somatic variant in postoperative ctDNA matching the same variant in the tissue may predict recurrence. However, since the major limitation of this study was the limited sample size, subsequent studies with larger sample sizes and more extensive research designs are warranted. The study was entered in the Japan Registry of Clinical Trials (April 10, 2023; no. 072230003).

Keywords: biomarker; circulating tumor DNA; comprehensive genomic profiling; liquid biopsy; precision medicine.

Figure 1.

Study design and clinical course of the cases. (A) Blood samples were obtained before surgery and 1 and 2 months after surgery. A tissue sample was obtained during surgery. All samples were analyzed using Genexus-NGS (OPA for blood and OCAv3 for tissue samples). (B-D) Clinical information and somatic variants of (B) patient 5, (C) patient 6 and (D) patient 8. The CT image on the upper right in B shows the recurrence (yellow arrows) in the abdomen at nine months postoperatively. M, month(s); y.o., years old; NGS, next-generation sequencing; ctDNA, circulating tumor DNA; RT, radiation therapy; Pre ope, preoperative; OCAv3, Genexus Oncomine Comprehensive Assay v3; OPA, Genexus Oncomine Precision Assay; TS-1, tegafur/gimeracil/oteracil.