Circulating tumor DNA detection in lung cancer patients before and after surgery

Abstract

Circulating tumor DNA (ctDNA) in peripheral blood is a “liquid biopsy” that contains representative tumor information including gene mutations. Additionally, repeated ctDNA samples can be easily obtained to monitor response to treatment and disease progression, which may be especially valuable to lung cancer patients with tumors that cannot be easily biopsied or removed. To investigate the changes in ctDNA after surgical tumor resection, tumor and blood samples obtained before and after surgery were collected prospectively from 41 non-small lung cancer (NSCLC) patients. Somatic driver mutations in tumor DNA (tDNA) and pre- and post-op plasma ctDNA sample pairs were identified by targeted sequencing in several genes including EGFR, KRAS, and TP53 with an overall study concordance of 78.1% and sensitivity and specificity of 69.2% and 93.3%, respectively. Importantly, the frequency of 91.7% of ctDNA mutations decreased after surgery and these changes were observed as little as 2 days post-op. Moreover, the presence of ctDNA had a higher positive predictive value than that of six tumor biomarkers in current clinical use. This study demonstrates the use of targeted sequencing to reliably identify ctDNA changes in response to treatment, indicating a potential utility of this approach in the clinical management of NSCLC.

Circulating Tumor DNA Reveals Clinically Actionable Somatic Genome of Metastatic Bladder Cancer

“…As this was not accompanied by increased (or any) ctDNA in most instances, it suggests elevated nonmalignant cell death in the wake of systemic cytotoxic therapy. In pregnant women, fetal cfDNA is cleared rapidly from circulation after childbirth (43), and ctDNA levels reduce after surgery in patients with NSCLC and colorectal cancer (44,45). The same is likely true in patients with bladder cancer responding to chemotherapy.…”

Using plasma cell‐free DNA to monitor the chemoradiotherapy course of cervical cancer

“…Noninvasive biopsy provides a valuable way to monitor tumor treatment efficacy . As shown in Supporting Information Figure S5A, the amount of unanticipated points became less along treatment course from cfDNA1 to cfDNA3, indicating the overall pattern of cfDNA approached the reference genome, that is, the pattern of WBC, as treatment progressed.…”

Blood‐based circulating tumor DNA mutations as a diagnostic and prognostic biomarker for lung cancer

“…The results of the current study add to the body of evidence accumulating regarding the usefulness of ctDNA as a blood‐based diagnostic test. Although several studies have reported on the ability to detect genetic aberrations in the blood of patients with early‐stage lung cancer, to our knowledge the cohorts usually were small and assessments of clinical test performance were undertaken with respect to FFPE mutations rather than a clinical diagnosis of cancer …”

“…Although several studies have reported on the ability to detect genetic aberrations in the blood of patients with early-stage lung cancer, to our knowledge the cohorts usually were small and assessments of clinical test performance were undertaken with respect to FFPE mutations rather than a clinical diagnosis of cancer. 8 The diagnostic clinical test performance invariably varies with the methods used for DNA enrichment and the identification of genetic aberrations. COLD-PCR with high-resolution melt analysis has the advantage of being a readily available, low-cost method for the blood-based detection of cancer-related single-nucleotide variants, but Cancer April 15, 2020…”