Correlation between progression‐free survival, tumor burden, and circulating tumor DNA in the initial diagnosis of advanced‐stage EGFR‐mutated non‐small cell lung cancer

Abstract

BackgroundThis study was conducted to identify whether the presence of circulating tumor DNA (ctDNA) in plasma before treatment with EGFR‐tyrosine kinase inhibitors (TKIs) is associated with clinical outcomes.MethodsFifty‐seven pairs of tissues and plasma samples were obtained from patients with NSCLC adenocarcinoma harboring activating EGFR mutations before the administration of EGFR‐TKI treatment. ctDNA mutation was identified using the PANAMutyper EGFR mutation kit. Both qualitative and quantitative analyzes of the data were performed.ResultsConcordance rates with tissue biopsy were 40.4% and 59.6% for the qualitative and quantitative methods, respectively. Bone metastasis showed a statistically significant correlation with ctDNA detection (odds ratio 3.985, 95% confidence interval [CI] 1.027–15.457; P = 0.046). Progression‐free survival (PFS) was significantly shorter in the group detected with ctDNA than in the undetected ctDNA group (median PFS 9.8 vs. 20.7 months; hazard ratio [HR] 2.30, 95% CI 1.202–4.385; P = 0.012). Detection of ctDNA before treatment with EGFR‐TKIs (HR 2.388, 95% CI 1.138–5.014; P = 0.021) and extra‐thoracic lymph node metastasis (HR 13.533, 95% CI 2.474–68.747; P = 0.002) were independently associated with PFS. Six of 11 patients (45.5%) monitored by serial sampling showed a dynamic change in ctDNA prior to disease progression.ConclusionQuantitative testing can increase the sensitivity of the ctDNA detection test. Patients with detectable ctDNA had significantly shorter PFS after receiving EGFR‐TKIs than those with undetectable ctDNA. Tumor burden may be associated with plasma ctDNA detection. A shorter PFS was associated with detection of ctDNA and extra‐thoracic lymph node metastasis. Dynamic changes in the ctDNA level may help predict clinical outcomes.

Baseline Plasma EGFR Circulating Tumour DNA Levels in a Pilot Cohort of EGFR-Mutant Limited-Stage Lung Adenocarcinoma Patients Undergoing Radical Lung Radiotherapy

“…Univariate analyses of our results showed a negative correlation between a detectable baseline plasma EGFR ctDNA and PFS. This result is consistent with some reports performed in metastatic NSCLC patients [21][22][23][24][25]. Given that ctDNA values are correlated with tumour burden, we speculate that these patients with radiological local disease but detectable baseline plasma EGFR ctDNA may harbour a higher systemic burden and do poorly despite local radical treatment.…”

Clinicopathological parameters for circulating tumor DNA shedding in surgically resected non-small cell lung cancer with EGFR or KRAS mutation

“…In advanced NSCLC, ctDNA detection is related to tumor burden as well as extrathoracic lymph node and bone metastasis [24]. In early-stage NSCLC, Abbosh et al showed that nonadenocarcinoma histology, lymphovascular invasion, and high Ki-67 proliferation index were…”

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

“…Currently, a number of studies have shown that a high concentration of cfDNA at baseline represents a negative prognostic factor in terms of PFS and OS, irrespectively of patient characteristics like age and smoking habits, treatments and tumor histological type [13,[30][31][32][33]. In this regard, Cargnin et al performed a systematic review and meta-analysis to evaluate the impact of baseline cfDNA levels on the progression and survival of lung cancer patients.…”