TORONTO, May 19th, 2022 – Nearly one-third of non-small cell lung cancer (NSCLC) cases are diagnosed as inoperable localized diseases without surgical options. On top of that, there is no reliable clinical indicator to accurately assess the treatment response of definitive chemoradiotherapy (CRT) in these patients. Despite intensive CRT treatment, the inoperable localized NSCLC patients suffer from poor prognosis, with a 5-year survival rate of only 10-20%. Some recent clinical studies demonstrated sustained survival benefits of durvalumab consolidation treatment after CRT. However, finding an effective biomarker to direct treatment after CRT is still challenging.

A recent prospective study published in the journal of Molecular Cancer led by the Chinese Academy of Medical Sciences and Geneseeq Technology Inc., demonstrated the time-dependent clinical utility of circulating tumor DNA (ctDNA) to detect the minimal residual disease (MRD) and predict prognosis in CRT-treated inoperable localized NSCLC patients.

This study recruited 59 NSCLC patients who received CRT or radiotherapy (CRT/RT) at the Cancer Hospital of the Chinese Academy of Medical Sciences from May 2018 to November 2020. Their serial plasma samples were collected at baseline, the fourth week in the middle of CRT/RT, one month after and three months after CRT/RT, and during disease progression. The samples underwent RadiotronTM Panel (474 cancer-related genes) broad panel-next generation sequencing. The clinical utility of different ctDNA time points and the dynamic changes of ctDNA were explored to estimate their prognostic potentials. The results were then validated using an independent cohort of 20 inoperable localized NSCLC treated with definitive CRT.

Intriguingly, baseline ctDNA was positively related to disease stage, tumor size, and regional metastasis, but was not a promising prognostic biomarker for CRT/RT-treated localized NSCLC patients. On the other hand, ctDNA collected during/after treatment demonstrated a significant correlation with prognosis.

Notably, ctDNA detection at one month after CRT/RT exhibited a superior capacity for estimating both disease progression (p<0.0001) and overall survival (p=0.0016), and this result was further validated using the external patient cohort. The dynamic changes of ctDNA, especially the clearance of ctDNA at the last surveillance, were strongly associated with clinical outcomes. These results indicate that serial ctDNA collected at different time points could have distinct clinical utility, balanced by false positivity at early ctDNA time points due to CRT-induced tumor death and diminished clinical values at later ctDNA time points.

“ctDNA shedding during and after CRT exhibits a dynamic pattern, and it is imperative to select the proper ctDNA time point for early and reliable estimation of prognosis and timely adjustment of treatment regimens for inoperable localized NSCLC”, says Dr. Qiuxiang Ou, author and Senior Principle Investigator of Geneseeq Research Institute.