Abstract
Changes in circulating free DNA concentrations have been correlated with chemotherapeutic effects in solid tumors. The present study was designed to determine and compare the changes in circulating free mitochondrial DNA (mtDNA) concentrations prior to and following erlotinib treatment, as well as the potential prognostic value of plasma mtDNA. Patients with adenocarcinoma of the lung who were to receive erlotinib treatment were enrolled in the present study once informed consent had been obtained. Patient plasma samples were collected immediately prior to starting erlotinib treatment, on days 15 and 29 following the initiation of erlotinib treatment and also when the patient’s disease had progressed. The most common erlotinib treatment response was a partial response (PR), achieved in 26 (49.1%) of the 53 enrolled patients, followed by stable disease (SD) in 13 patients (24.5%) and progressive disease (PD) in 14 patients (26.4%). Plasma mtDNA concentrations were significantly decreased on day 15 compared with day 0 in the patients with PD (P=0.028) or in those patients without a response to erlotinib treatment (SD and PD; P=0.007). Plasma mtDNA concentrations were similar or elevated on day 15 compared with day 0 in the patients with a PR (P=0.808). The concentration of plasma mtDNA did not correlate with progression-free survival (PFS). Tumor epidermal growth factor receptor (EGFR) mutation status (activating mutations in 16 patients and wild-type in 14 patients) did not correlate with the concentration of plasma mtDNA (P=0.951). Plasma mtDNA levels did not correlate with the PFS of the patients when they received erlotinib treatment. The plasma mtDNA levels were decreased on day 15 in those patients who had disease progression following erlotinib treatment. These results demonstrate that plasma mtDNA is of weak clinical utility as a screening, diagnostic or prognostic tool in lung cancer patients.
Highlights
Lung cancer is the leading cause of cancer‐associated mortality worldwide, and non‐small cell lung cancer (NSCLC) accounts for >80% of all cases
E‐mail: ymchen@vghtpe.gov.tw disease progression following erlotinib treatment. These results demonstrate that plasma mitochondrial DNA (mtDNA) is of weak clinical utility as a screening, diagnostic or prognostic tool in lung cancer patients
The present study investigated whether plasma mtDNA concentrations in lung cancer patients with adenocarcinoma were altered during treatment with erlotinib, an epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI), and whether this change has the potential to be used as a predictor of treatment response
Summary
Lung cancer is the leading cause of cancer‐associated mortality worldwide, and non‐small cell lung cancer (NSCLC) accounts for >80% of all cases. The presence of circulating free DNA in the plasma of patients with malignant neoplasms has been a well‐established concept for >30 years. Studies have been undertaken to analyze the plasma circulating free DNA concentrations, together with the genetic and epigenetic alterations of the tumor DNA of patients who suffer from numerous types of cancer, including colon, breast, prostate and germ cell tumors [4,5,6]. The present study investigated whether plasma mtDNA concentrations in lung cancer patients with adenocarcinoma were altered during treatment with erlotinib, an epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI), and whether this change has the potential to be used as a predictor of treatment response
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