Liquid biopsy for assessment of RFS (recurrence-free survival) in NSCLC (non-small cell lung cancer) patients post-treatment through circulating tumour DNA detection: A meta-analysis

Abstract

Background: One of the main techniques for diagnosing lung cancer is still tissue biopsy. The more recent liquid biopsy technique includes the assessment of fragments of cfDNA, ctDNA, and CTCs, which are released by tumour cells and act as biomarkers. After compiling information from the existing literature, we conducted a statistical analysis to evaluate the prognosis and recurrence of NSCLC post-treatment using ctDNA levels.

Method: Based on predefined inclusion and exclusion criteria, published studies between 2000 and 2022 from electronic databases with statistical data on ctDNA levels for NSCLC were included. Then, using PRISMA guidelines, we carried out a systematic review of those studies.

Result: A total of 7 studies were included in the analysis, and we found a correlation of ctDNA levels for determination of prognosis and recurrence after treatment in NSCLC. Meta-analysis was performed using RevMan version 5.4. A P-value of less than 0.05 was considered significant. Studies were divided into three groups: <1 week post-surgery, one week to 3 months post-surgery, and > three months post-surgery. Analysis showed that in <1-week post-surgery group, ctDNA-negative post-treatment detection had an HR of 4.85 (95 % CI: 2.41 to 9.77; p=<0.0001, I2 = 0 %) for recurrence-free survival compared to ctDNA-positive post-treatment detection. Similar findings were obtained for one week to 3 months and > three months group, with HR of 5.27 (95 % CI: 3.62 to 7.67; p=<0.00001, I2 = 11 %) and HR of 6.62 (95 % CI: 2.85 to 15.35; p=<0.0001, I2 = 64 %) respectively.

Conclusion: According to our meta-analysis, patients with NSCLC who were ctDNA negative after surgery had a significantly longer recurrence-free survival than those who were ctDNA positive. As a result, liquid biopsy used to measure ctDNA levels is a useful non-invasive technique to assess the prognosis in such patients. The early detection of recurrence may also allow timely therapeutic intervention, leading to better outcomes.

Keywords: Liquid biopsy; Minimal residual disease (MRD); Non-small cell lung cancer prognosis after treatment; Recurrence-free survival in non-small cell lung cancer patients; ctDNA; ctDNA detection.

Fig. 1

PRISMA flow diagram of search strategy for included studies.

Fig. 2

Random-effect Forest plot showing the relationship of recurrence-free survival in ctDNA-negative compared to ctDNA-positive at less than one-week post-treatment.

Fig. 3

Random-effect Forest plot showing the relationship of recurrence-free survival in ctDNA-negative compared to ctDNA-positive at less than one-week post-treatment.

Fig. 4

Random-effect Forest plot showing the relationship of recurrence-free survival in ctDNA-negative compared to ctDNA-positive more than three months post-treatment.