Circulating Tumor DNA Testing Overcomes Limitations of Comprehensive Genomic Profiling from Tumor Tissue

Anivarya Kumar; Michelle Green; Julie Thacker; William Richard Jeck; John H Strickler

doi:10.1159/000529813

Circulating Tumor DNA Testing Overcomes Limitations of Comprehensive Genomic Profiling from Tumor Tissue

Case Rep Oncol. 2023 Apr 12;16(1):210-217. doi: 10.1159/000529813. eCollection 2023 Jan-Dec.

Authors

Anivarya Kumar¹, Michelle Green², Julie Thacker³, William Richard Jeck², John H Strickler⁴

Affiliations

¹ Duke University School of Medicine, Duke University, Durham, NC, USA.
² Department of Pathology, Duke University, Durham, NC, USA.
³ Division of Surgical Oncology, Department of Surgery, Duke University, Durham, NC, USA.
⁴ Division of Medical Oncology, Department of Medicine, Duke University, Durham, NC, USA.

Abstract

"Liquid biopsy" is an established technique for examining circulating tumor DNA (ctDNA) from a routine blood draw and detecting actionable biomarkers. Nonetheless, ctDNA testing is rarely utilized for patients with newly diagnosed metastatic colorectal cancer (CRC). We report a case in which ctDNA testing uncovered an actionable biomarker that was not detected by comprehensive genomic profiling of tumor tissue. An 81-year-old woman with a remote history of non-Hodgkin's lymphoma presented with primary masses in the ascending colon and sigmoid colon. The ascending colon and sigmoid colon tumors were classified as microsatellite stable (MSS) and mismatch repair proficient (pMMR), and both ctDNA and tissue next-generation sequencing (NGS) from the ascending colon mass were ordered. Because tissue NGS results indicated that the ascending colon tumor was MSS, palliative 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy was started. However, the ctDNA NGS results that arrived after the start of FOLFOX found high microsatellite instability (MSI-H) and mismatch repair deficiency (dMMR) disease with a serine/threonine-protein kinase B-Raf (BRAF ^V600E ) mutation. To treat both her MSS/pMMR ascending colon and sigmoid colon tumors and MSI-H/dMMR metastatic disease, the immunotherapy nivolumab was added to FOLFOX. After 8 months of combined nivolumab and chemotherapy, the patient's metastatic disease had a complete clinical response. This case highlights the complementary role of ctDNA testing for biomarker identification. By performing simultaneous ctDNA testing at the time of diagnosis, an actionable biomarker was discovered that significantly altered this patient's prognosis and treatment options. Orthogonal testing of key molecular alterations offers significant advantages for identifying actionable biomarkers and improving management of metastatic CRC.

Keywords: Circulating tumor DNA; Colorectal cancer; High microsatellite instability; Precision oncology.

Publication types

Case Reports

Grants and funding

No funding was received for this study.