Integrated circulating tumour DNA and cytokine analysis for therapy monitoring of ALK-rearranged lung adenocarcinoma.
Br J Cancer
; 129(1): 112-121, 2023 07.
Article
in En
| MEDLINE
| ID: mdl-37120670
ABSTRACT
BACKGROUND:
Detection of circulating tumour DNA (ctDNA) in biological fluids is a minimally invasive alternative to tissue biopsy for therapy monitoring. Cytokines are released in the tumour microenvironment to influence inflammation and tumorigenic mechanisms. Here, we investigated the potential biomarker utility of circulating cytokines vis-à-vis ctDNA in ALK-rearranged+ lung adenocarcinoma (ALK + NSCLC) and explored the optimal combination of molecular parameters that could indicate disease progression.METHODS:
Longitudinal serum samples (n = 296) were collected from ALK + NSCLC patients (n = 38) under tyrosine kinase inhibitor (TKI) therapy and assayed to quantify eight cytokines IFN-γ, IL-1ß, IL-6, IL-8, IL-10, IL-12p70, MCP1 and TNF-α. Generalised linear mixed-effect modelling was performed to test the performance of different combinations of cytokines and previously determined ctDNA parameters in identifying progressive disease.RESULTS:
Serum IL-6, IL-8 and IL-10 were elevated at progressive disease, with IL-8 having the most significant impact as a biomarker. Integrating changes in IL-8 with ctDNA parameters maximised the performance of the classifiers in identifying disease progression, but this did not significantly outperform the model based on ctDNA alone.CONCLUSIONS:
Serum cytokine levels are potential disease progression markers in ALK + NSCLC. Further validation in a larger and prospective cohort is necessary to determine whether the addition of cytokine evaluation could improve current tumour monitoring modalities in the clinical setting.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Non-Small-Cell Lung
/
Circulating Tumor DNA
/
Adenocarcinoma of Lung
/
Lung Neoplasms
Type of study:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Br J Cancer
Year:
2023
Type:
Article
Affiliation country:
Germany