A study conducted in Brazil has investigated the early detection of genetic alterations in lung cancer through liquid biopsies. The research, supported by FAPESP and published in Molecular Oncology, indicated the feasibility of identifying mutations in blood samples from patients with non-small cell lung cancer (NSCLC) using a commercial multigene panel. This method aims to accelerate diagnoses and inform patient treatment strategies. A study conducted in Brazil has investigated the early detection of genetic alterations in lung cancer through liquid biopsies. The research, supported by FAPESP and published in Molecular Oncology, indicated the feasibility of identifying mutations in blood samples from patients with non-small cell lung cancer (NSCLC) using a commercial multigene panel. This method aims to accelerate diagnoses and inform patient treatment strategies. The study, performed at Hospital de Amor de Barretos, a national oncology center, evaluated circulating tumor DNA (ctDNA) in various patient cohorts, including individuals without symptoms. NSCLC accounts for approximately 85% of lung cancer cases. Within this subtype, adenocarcinoma often presents mutations that are targets for specific therapies, which have reportedly increased median survival rates from under eight months to two to three years, and up to ten years in certain cases. Genes such as EGFR, ALK, and KRAS are associated with "actionability," meaning identified alterations may correspond to available targeted drug treatments.
Research Methodology and Findings
The study analyzed 32 plasma samples from 30 patients. This group included individuals who had not received prior treatment, previously treated patients, and four participants from a lung cancer screening program. Researchers utilized a commercial panel designed to detect specific known mutations in adenocarcinoma across 11 genes linked to tumor development. Mutations were detected in 65.6% of the samples, with this rate increasing to 87.5% among patients who had undergone therapy.
The most frequently identified mutations were in the TP53 gene (40.6%), KRAS gene (28.1%), and EGFR gene (12.5%). While TP53 is commonly mutated in various cancers, no specific drug is currently available for it. However, alterations in EGFR and a specific KRAS mutation (p.G12C) can be treated; several EGFR-targeting drugs are approved in Brazil. The EGFR p.T790M mutation, associated with treatment resistance, was also identified in one sample. This type of mutation can develop in patients who initially respond to treatment.
A finding in the screening group involved an asymptomatic participant who presented a TP53 gene mutation six months prior to a cancer diagnosis. This observation suggests a potential role for liquid biopsies as a complementary screening tool for high-risk populations, such as smokers and former smokers.
Advantages and Challenges
Liquid biopsies offer a time advantage in clinical practice compared to conventional tumor tissue analysis. Tissue biopsies typically require weeks for sample collection, processing, pathology review, and report generation. In contrast, liquid biopsy results can potentially be available within two days, facilitating earlier initiation of treatment. Another aspect of the study was the panel's ability to detect ctDNA in frozen samples, eliminating the need for specialized tubes or immediate transport to specific laboratories. This factor may support its adoption by public health services, which may lack complex infrastructure for molecular testing.
Despite these findings, the integration of liquid biopsies into Brazil's public health system faces economic challenges. The test used in the study has a cost of approximately BRL 6,000 (USD 1,110) per patient. While increased competition among genetic sequencing companies may reduce costs, the current price is a barrier for many individuals. In the private sector, several targeted therapies are accessible via the National Supplementary Health Agency (ANS), whereas the public health system (SUS) has limited options and molecular testing availability, often leading to judicialization for treatment access.
Limitations
The study noted that a negative liquid biopsy result does not exclude the presence of mutations. In such cases, confirmation with a tissue biopsy is required, as liquid biopsies are considered complementary to conventional methods. This is partly due to the difficulty of detecting mutations in early disease stages where ctDNA volume may be minimal. The researchers conclude that liquid biopsies could expedite diagnoses, guide treatment, and inform clinical decisions for lung cancer patients. The study supports the feasibility of this strategy and its potential incorporation into Brazilian hospital routines, benefiting patients with both early and advanced-stage tumors. The expectation is that reduced sequencing costs and expanded testing availability will increase access to personalized medicine for lung cancer in Brazil.