Revolutionary Blood Test for Lung Cancer Detection and Treatment: Longmerker Study Results

The treatment plan for metastatic lung cancer depends, among other things, on the presence of certain genetic abnormalities in the tumor. With the help of a new blood test, in 50% of cases where a mutation is found in the tumor biopsy, this mutation is also found in the blood. This test even detects additional mutations. So the technology seems to be very relevant in the screening process for lung cancer detection. Its application also means that the patient’s treatment can start more quickly.

Eight years ago, research began on whether lung cancer can be diagnosed without the use of lung biopsies liquid biopsy. “Lung biopsy is a stressful procedure for the patient,” says Volkher Scharnhorst, head of the general clinical laboratory at Catharina Hospital Eindhoven and professor of clinical chemistry at Eindhoven University of Technology. “It is not always able to collect enough tissue for analysis the first time, so the patient has to go through the procedure again.”

Hence the idea that it should also be possible to reach the diagnosis through a blood test, with a liquid biopsy. “It was already known that cell-free DNA from the fetus circulates in the blood of pregnant women,” says Scharnhorst. “If this can be used for fetal genotyping – we thought – it should be also possible with mutated DNA in lung cancer.” This particularly applies to mutations in circulating tumor cell-free DNA (ctDNA) and the tumor markers that are produced in relatively high concentrations. with tumor cells.

Pulmonary symptom monitoring

That idea was the starting point for Longmerker’s study. The foundation for this was laid with the establishment of the droplet digital polymerase chain reactiontechnique (ddPCR). A clinical study, in which 6 hospitals were involved, investigated what the the clinical value of ddPCR in the diagnosis of lung cancer and whether information from liquid biopsies can be used for the diagnosis and staging of lung cancer.

“The research on this lasted from 2017 to 2021,” said Scharnhorst. “At that time, 1,100 patients with suspected lung cancer were brought in to receive additional blood.” The blood was used to detect driver mutations by ctDNA-ddPCR EGFR, KRAS in BRAF trace down. The results showed that in front indeed mutation detection in this way has additional diagnostic value. The number of mutations detected was increased by 17% using ctDNA-ddPCR and, if negative, tDNA NGS. It also turned out that ctDNA-ddPCR made tDNA-NGS useless in 40% of cases. “An important decision,” says Scharnhorst, “because while tDNA-NGS has an average turnaround time of 2 weeks, tDNA-ddPCR results are often available within a day. This means that the tests will be completed in 3 days and a treatment plan can already be drawn up. That is a huge time saver for the patient. “

The Lung Markers study also investigated whether the protein markers CA125, CA15.3, CEA, CYFRA 21-1, HE4 NSE, ProGRP and SCCA can be used to differentiate the subtypes of non-small cell lung cancer and small cell (NSCLC and SCLC). respectively). To this end, information from the liquid biopsies was combined in decision support algorithms. “It turns out that it really is possible,” says Scharnhorst. “We were able to identify two-thirds of NSCLC patients and 50% of SCLC patients with the algorithms.”

Long man 2

As a follow-up, the Lungmerker 2 study was recently initiated. This explores the question of which markers can be analyzed for circulating tumor cells. This is done in collaboration with the Eindhoven University of Technology and the Máxima Medical Center in the Clinical Chemistry Knowledge Center Eindhoven. The lung markers group will conduct a retrospective study of whether the integration of CT scan results leads to further development of the decision support algorithms.

The question of whether it is possible to predict the first tumor response shortly after the start of the treatment and the tumor response 6 months after the first treatment is also being investigated. If this is indeed possible, it could mean that patients who do not respond to treatment are quickly identified and therefore quickly switched to another treatment.

Differences in time to diagnosis

According to the guidelines, patients should receive a definitive diagnosis within 5 weeks. A recent study¹ which is part of the Lungmerker study shows that this period is indeed achieved in the majority of patients. But in patients early stage and patients without lung cancer, it took much longer than for advanced lung cancer and in some cases multiple biopsy procedures were also required.

“There are several reasons for these differences,” says Scharnhorst. “If there is metastatic cancer, there is more tumor tissue present. At an early stage it is not always possible to perform a successful biopsy or surgery is performed immediately and surgical material is sent for analysis. Preparation in the operating room takes longer than taking a biopsy in the treatment room. And in the case of an undefined area of ​​the lung, the diagnosis ‘no lung cancer’ will only be made if no substrate is found again. “

Determination of position

The conclusion of the study is that new methods such as liquid biopsy and AI can lead to more timely lung cancer care, less invasive procedures and less variability in the diagnostic process of different patients, and therefore can play a positive role take in making a definitive diagnosis for every patient.

“The current position in the guidelines is that ctDNA analysis can be used to create a treatment plan,” says Scharnhorst. “But there are practical objections. First, it is a complicated method. His application requires a laboratory that has the right facilities: special equipment with which the team must become familiar. It also requires knowledge of the pathologists. But in addition, agreements must be made about the repayment. And the latter is still a problem, because health insurers are not very inclined to spend the money for it. However, there are certainly enough reasons to use it as the first standard molecular method. It costs money, but these costs are nothing compared to the costs of treating patients with lung cancer. In addition, as I have already said, it saves on heavy research and means that the process of diagnosis and design of a treatment plan is accelerated. It’s time to really build it on a bigger scale.”

Reference:

1. Genet S, Visser E, Youssef-El Soud M, et al. Strengths and challenges in current lung cancer care: Time and study methods in six Dutch hospitals. Lung cancer. 2024; 189: 107477.