95P - Baseline-informed longitudinal monitoring of lung cancer by cell-free DNA methylation profiles

Background

Lung cancer remains a formidable challenge in oncology, necessitating innovative approaches for effective monitoring and management. Circulating cell-free DNA (cfDNA) methylation dynamics offer a promising avenue for non-invasive monitoring of tumor evolution. Our study aims to development of longitudinal monitoring strategy implementing cfDNA epigenetic profiles for precise tracking of lung cancer progression.

Methods

We conducted a prospective cohort study involving 18 NSCLC with Cadonilimab (PD-1/CTLA-4 bispecific antibody) plus chemotherapy, where serial blood samples were collected longitudinally throughout the disease course. Utilizing PredicineALERT^TM, a whole DNA methylome panel assay, we comprehensively investigated cfDNA methylation dynamic patterns including differentially methylated fragments and tissue-of-origin deconvolution. These features were integrated to enable the identification of key biomarkers indicative of disease progression.

Results

In this ongoing study, our results demonstrated the significantly correlation between cfDNA methylation score and tumor burden measured by sum of longest diameters of lesion at baseline (Pearson’s cor = 0.52, P-value = 0.03). The alterations of methylation score from baseline to C3D1 matched with clinical Response Evaluation Criteria in Solid Tumors. In details, all of 9 patients with partial response showed the decreased differentially methylated fragment (DMF) score (-62.8%, 95% CI [-83.5%, -42.1%]). We observed 2 of patients with stable disease which showed substantial increases in DMF (> 20%), suggesting potential treatment resistance. After evaluating the baseline-informed DMF and the proportion of lung cells derived fragments, the results illustrated concordance of DNA fragment-level alterations with tumor size changes in longitudinal timepoints.

Conclusions

Our study highlights the strategy of efficacy response monitoring by leveraging cfDNA methylation dynamic profiles. This approach holds promise for optimizing patient care and improving clinical outcomes in lung cancer management through liquid biopsy technology.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.