Brazilian study shows liquid biopsies can expedite lung cancer care

In Brazil, the early detection of genetic alterations in lung cancer through liquid biopsies could be a valuable tool for expediting diagnoses and guiding patient treatment. A study supported by FAPESP and published in the journal Molecular Oncology showed that it is possible to identify relevant mutations in blood samples from patients with non-small cell lung cancer (NSCLC) using a commercial multigene panel. Conducted at Hospital de Amor de Barretos, a national oncology reference center, the research evaluated the presence of circulating tumor DNA (ctDNA) in different patient groups, including asymptomatic individuals.

NSCLC accounts for about 85% of cases and is the most prevalent subtype. Within this subtype, there are different groups, such as adenocarcinoma and squamous cell carcinoma. Adenocarcinoma, in particular, is marked by mutations that have become targets of specific therapies, changing the course of treatment in recent years. Just over ten years ago, the median survival rate did not exceed eight months. Today, the scenario is different. There is talk of an overall survival rate of two to three years with targeted therapies, reaching up to ten years in some cases.

Adenocarcinoma is the lung cancer subtype that has benefited most from advances in genomics and is therefore the main focus of our study. Genes such as EGFR, ALK, and KRAS have what we call ‘actionability.’ This means that when we identify such an alteration in a patient, there’s a targeted drug capable of acting directly on it.” 

Letícia Ferro Leal, researcher, co-supervisor of the study

The study examined a total of 32 plasma samples from 30 patients. Most of the patients had not received any previous treatment, though previously treated patients and four participants in a lung cancer screening program were also included. The researchers then used a commercial panel designed for specific known mutations in adenocarcinoma to look for alterations in 11 genes related to tumor development. The performance of the technique was surprising: 65.6% of the samples had mutations, a rate that reached 87.5% among patients who had undergone therapy.

The most frequent mutations occurred in the TP53 (40.6%), KRAS (28.1%), and EGFR (12.5%) genes. TP53 is the most mutated gene in different types of cancer; however, there is still no specific drug for it. However, changes in EGFR and a specific KRAS mutation (p.G12C) can be treated – in the case of EGFR, with several drugs already approved in Brazil. One of these mutations, the EGFR p.T790M mutation linked to treatment resistance, was identified in one of the samples analyzed.

“This type of mutation can arise even in patients who initially respond well to treatment. However, it’s usually detected when the patient has already shown disease progression. The same occurs in patients with mutations in other genes, treated with other targeted therapies. It’s a major challenge in oncology,” says Leal.

One of the most striking findings of the study occurred in the screening group: an asymptomatic participant had a TP53 gene mutation six months before being diagnosed with cancer. According to the researchers, this finding demonstrates the potential of liquid biopsies as a complementary screening tool for high-risk populations, particularly smokers and former smokers.

Time is crucial

The researcher explains that, in clinical practice, the big difference in performing a liquid biopsy for lung cancer is time. While the conventional analysis of a tumor obtained by biopsy or surgery takes weeks due to the time required for sample collection, processing, pathology evaluation, and report release, the liquid biopsy process is considerably shorter.

“Time is a crucial factor when it comes to lung cancer. When we perform a tissue biopsy, we need to consider how long the patient waited to schedule the biopsy or surgery. Only after this waiting period does the time for sample processing and molecular analysis begin. In the best-case scenario, the report takes around two weeks from collection. With liquid biopsy, we can collect the sample at any time, and the results can be available in two days, allowing treatment to begin sooner,” explains the researcher.

In addition to speed and a reduced response time, the study revealed another benefit: the panel could detect ctDNA in frozen samples without requiring special tubes or immediate transport to specialized laboratories. This increases the likelihood that the method will be adopted by public health services, which do not always have the complex structure or equipment necessary for molecular testing.

Cost is still a barrier

Despite the promising results, Leal acknowledges that incorporating liquid biopsies into Brazil’s public health system faces significant barriers, particularly economic ones. The test used in the study costs around BRL 6,000 (approximately USD 1,110) per patient. While the price may decrease with increased competition among genetic sequencing companies, it is still too high for most of the population.

In the private sector, several targeted therapies are available through the National Supplementary Health Agency (ANS), which regulates health insurance companies. In the SUS (acronym for Sistema Único de Saúde, the national public health network), options are scarce and are restricted to a few referral centers, few of which can offer routine molecular testing. “Sometimes patients can afford the test but not the therapy, which can cost up to BRL 40,000 [USD 7,400] per month. That’s why there are still many cases of judicialization,” Leal comments.

Leal also points out that although the panel used by the researchers is highly sensitive – up to ten times more than some tumor tissue tests – a negative result does not rule out mutations. “If the liquid biopsy doesn’t detect any changes, it’s necessary to confirm with the tissue. We still can’t completely replace the conventional biopsy; these are complementary tests,” says the researcher. This is partly due to the difficulty of detecting mutations in the early stages of the disease when the volume of ctDNA is very small.

Despite these limitations, the researchers conclude that liquid biopsies have the potential to speed up diagnoses, guide treatment more accurately, and inform clinical decisions for patients with lung cancer. The study reinforces the feasibility of this strategy, its potential incorporation into hospital routines in Brazil, and its ability to benefit patients with both early- and advanced-stage tumors.

“Our work shows that it’s possible to detect several mutations at the same time, reduce response time, and use samples that don’t require special collection. This can accelerate the start of treatment and improve patient outcomes,” Leal summarizes. With the fall in sequencing costs and the expansion of testing availability, the expectation is that access to personalized medicine for lung cancer will become a reality in Brazil.