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

Nannan Guo, Feng Lou, Yongfu Ma, Jie Li, Bo Yang, Wei Chen et al. · 2016 · 122 citationsRead the paper

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.

What the full text shows

Working prototype
  • Mutation frequency of ctDNA decreased after surgery. — 91.7% of mutations decreased (NSCLC patients, observed as early as 2 days post-op)
  • Concordance between tDNA and plasma ctDNA mutations. — 78.1% concordance, 69.2% sensitivity, 93.3% specificity (41 NSCLC patients)
  • Positive Predictive Value (PPV) for cancer detection using ctDNA. — 94.7% PPV (41 NSCLC patients)
  • Average plasma ctDNA mutation frequency change post-surgery. — 8.88% pre-op to 0.28% post-op (Across all genes with mutations)
  • ctDNA detection compared to six clinical tumor protein biomarkers. — Higher detection rate and higher PPV than biomarkers (Pre-surgery plasma samples)
  • Cell-free DNA (cfDNA) concentration change after surgery. — Increased in 73.2% of patients (avg. 0.329 ng/μl increase) (41 NSCLC patients)
Setup
41 non-small cell lung cancer (NSCLC) patients; samples collected 0-13 days pre-op and 2-10 days post-op.
How
Targeted next-generation sequencing (Ion Proton) was used to identify somatic mutations in a 50-gene panel from matched tumor tissue (tDNA) and plasma (ctDNA) samples. Pre- and post-operative blood samples were compared to monitor changes in mutation frequency.
Limitations
Detection limit of 0.1% variant frequency may miss low-level ctDNA (estimated at 0.02%-0.1% of total circulating DNA). · Small sample size (41 patients). · Targeted sequencing cannot distinguish if mutations originate from primary or metastatic tumors.

Summarized by Gemma 4 from the open-access full text · 3 Oct 2026. Read it