# Utility of combined solid and liquid biopsy for molecular profiling in lung adenocarcinoma: Insights from a real-world case

## TL;DR

This case study shows how combining solid and liquid biopsies can improve treatment decisions for lung cancer by tracking genetic changes over time.

## Contribution

Demonstrates the added value of integrating solid and liquid biopsy data to detect emerging mutations and guide personalized therapy in lung adenocarcinoma.

## Key findings

- Liquid biopsy identified ROS1-CCDC6 fusion, leading to Crizotinib treatment initiation.
- Combined solid and liquid biopsy revealed EGFR p.L858R mutation, prompting dual therapy with Crizotinib and Gefitinib.
- Liquid biopsy detected a new TP53 mutation alongside persistent EGFR mutation, enabling targeted therapy restart for disease resolution.

## Abstract

Lung adenocarcinoma is a subtype of NSCLC that is often associated with poor prognosis. We present a case of metastatic lung adenocarcinoma in which comprehensive genomic profiling using both solid and liquid biopsies was employed to monitor disease progression and guide targeted therapy decisions. An initial liquid biopsy detected ROS1-CCDC6 gene fusion, and the patient was started on Crizotinib. Following disease progression, further genomic profiling using both solid tissue and cfDNA revealed the presence of a previously undetected classical mutation EGFR exon 21, p. L858R. Consequently, the treatment was adjusted to include both Crizotinib and Gefitinib. A 6-month follow-up showed relapse and extensive metastasis. A repeat liquid biopsy identified a newly acquired TP53 mutation (exon 7, p.R248Q) in addition to the persistent EGFR mutation. Restarting the targeted therapy led to complete metabolic resolution of the disease. This case highlights the utility of liquid biopsy when tissue biopsy is not feasible and underscores the importance of integrating both solid and liquid genomic data to capture a more comprehensive mutational landscape, including low-frequency or emerging variants, ultimately enabling more effective, individualized treatment strategies.

•Liquid biopsy in a metastatic lung adenocarcinoma patient detected ROS1-CCDC6 fusion; Crizotinib targeted therapy was given.•Solid+liquid biopsy after disease progression detected EGFR p.L858R; modified therapy with Crizotinib+Gefitinib was started.•Follow-up showed disease resolution, but new brain lesion was found. Targeted therapy was continued with radiation therapy.•Disease progression with multiple metastases was seen in follow-up. Liquid biopsy detected TP53 p.R248Q and EGFR p.L858R.•Targeted therapy was restarted, resulting in complete metabolic resolution of primary and metastatic lesions.

Liquid biopsy in a metastatic lung adenocarcinoma patient detected ROS1-CCDC6 fusion; Crizotinib targeted therapy was given.

Solid+liquid biopsy after disease progression detected EGFR p.L858R; modified therapy with Crizotinib+Gefitinib was started.

Follow-up showed disease resolution, but new brain lesion was found. Targeted therapy was continued with radiation therapy.

Disease progression with multiple metastases was seen in follow-up. Liquid biopsy detected TP53 p.R248Q and EGFR p.L858R.

Targeted therapy was restarted, resulting in complete metabolic resolution of primary and metastatic lesions.