Clinical utility of circulating tumor DNA as a biomarker for relapse detection and therapy monitoring: case reports

Background:

Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for minimal residual disease assessment, therapy response monitoring and detection of recurrence in cancer. Previously we reported the clinical performance of a bespoke, multiplex PCR, WES-based assay (Signatera™RUO) for ctDNA assessment in various solid tumors. We present two case studies to demonstrate the utility of serial ctDNA analysis by the bespoke assay for recurrence detection and therapy monitoring.

Case 1: A 56-year-old male, with a recent diagnosis of T2N1M0 pancreatic adenocarcinoma underwent Whipple resection (March 2018). Pre-surgical ctDNA status was positive. Adjuvant chemotherapy was administered (FOLFIRINOX; May–October 2018) and the patient was ctDNA negative at seven post-surgical timepoints (March–September 2018). Radiation/oral chemotherapy (capecitabine) were started in November 2018. Following a positive ctDNA result (November 2018), biopsy and imaging performed in December 2018 confirmed metastasis to the liver. The patient remained ctDNA positive at four subsequent timepoints (December 2018–March 2019).

Case 2: A 77-year-old female was diagnosed with metastatic stage IV lung adenocarcinoma (September 2016). An EGFR mutation (p.E746_A750DEL) was identified and treatment with erlotinib was initiated. The patient was ctDNA positive in October 2017 and April 2018. A PET/CT scan (August 2018) revealed a right pulmonary juxta hilar mass; patient remained ctDNA positive in August 2018. Abnormal imaging and identification of an erlotinib-resistant mutation resulted in a therapy switch to osimertinib (September 2018). Minor decrease in midlung masses was observed by CT imaging (October 2018); lung nodules and bone metastasis remained unchanged. The patient was ctDNA negative in November 2018 and February 2019.

Conclusions:

These cases demonstrate the potential use of ctDNA as an informative biomarker for recurrence detection (case 1; ctDNA detected 1.5 months ahead of clinical recurrence) and monitoring therapy response (case 2; ctDNA negative status indicative of response to osimertinib) in clinical practice.