What should I pay attention to when using liquid biopsies for genetic testing for lung cancer patients?

With the rise of targeted therapies and cancer immunotherapy, genetic testing of tumors before treatment is becoming increasingly important.
Taking non-small cell lung cancer (NSCLC) as an example, more than a dozen targeted therapies have been approved for the treatment of patients with advanced NSCLC, and understanding whether patients carry EGFR and ALC gene variants has become one of the important factors in determining their suitability for immunosuppressant therapy.
guidelines recommend genetic testing of tumors in NSCLC patients as part of treatment decisions.
genetic testing of circulating tumor DNA (ctDNA) in patients' blood can identify genetic variants that drive cancer progression, guiding targeted individualized therapy options.
last month, the FDA approved a pan-tumor liquid biopsy test based on next-generation sequencing technology (NGS) developed by Goodant Health and Roche's Foundation Medicine.
, however, with the rise of ctDNA-based genetic testing in the blood, how to integrate these innovative tests into the traditional diagnosis and treatment of NSCLC patients is a challenge for clinicians.
advantages and disadvantages of liquid biopsies compared to traditional tissue biopsies? Under what circumstances should I choose an tissue biopsy or a liquid biopsy? How do I evaluate the results of a liquid biopsy and make follow-up tests and therapies? These issues are discussed today in an article published today in The Reviews Clinical Oncolgy.
When detecting tumors in NSCLC patients based on plasma ctDNA and tumor tissue-based genetic testing, liquid biopsies based on ctDNA in plasma provide a simpler non-invasive detection method than gene testing based on tumor tissue.
blood samples are easier to obtain than those requiring a biopsy oncology, but the process of extracting DNA fragments requires fewer steps.
, however, traditional tissue biopsies also have a unique advantage.
in the process of genetic testing based on tumor tissue, testers will first evaluate the resulting tissue samples to determine whether they are large enough for genetic testing.
this assessment step ensures that genetic testing based on tissue samples is highly sensitive.
and the liquid biopsy did not contain a step to determine the presence of ctDNA and ctDNA levels in the blood sample before testing.
this means that the sensitivity of the liquid biopsy is lower.
from the point of view of the specificity of the test, the tumor tissue and the genetic test based on ctDNA in the blood are highly specific.
in liquid biopsies, certain genetic variants carried by white blood cells can lead to false positive results.
The authors of the strategy paper on selecting gene testing based on plasma ctDNA or tumor tissue in clinical practice say that NSCLC's treatment guidelines currently recommend the detection of multiple genetic variants in tumor samples, but do not provide more detailed guidance on whether to use plasma samples or tumor tissue for genetic testing.
, the authors of the paper propose a process for genetic testing selection based on the patient's condition, based on the different characteristics of the two types of testing (see figure below).
's strategy for genetic testing in patients with late NSCLC (Source: Resources, Pharmaceutical Mingkang content team drawing) Specifically, the use of plasma ctDNA-based liquid biopsies is a very intuitive and compelling first choice if there are no samples of tumor tissue that can be used for genetic testing.
At the same time, doctors should strive to obtain samples of tumor tissue that can be genetically tested, as the sensitivity of liquid biopsies is not very high, and when liquid biopsies are negative, genetic testing based on tissue samples is still required.
when tumor tissue samples are present, but it is not certain that they meet the criteria for genetic testing, it makes strong sense to conduct both liquid biopsies and tumor tissue-based genetic testing.
because published literature suggests that in this case, genetic testing based on tumor tissue is 18-28% likely to fail.
depending on the tumor load of the tissue, doctors can choose to perform a liquid biopsy or a genetic test based on the tumor tissue.
, if the tumor load is high and the level of release of ctDNA is expected to be high, a liquid biopsy may be performed first.
, if the tumor load is low and the expected level of ctDNA release is not significant, you can choose to conduct genetic testing based on tumor tissue first.
if tumor tissue samples meet the criteria for genetic testing, using them for genetic testing remains the most reliable way to understand tumor genotypes.
, however, doctors may need to start treatment as soon as possible because the genetic testing process based on tumor tissue takes a long time, at which point a fluid biopsy may be available at the same time.
's interpretation of ctDNA-based genetic test results is currently a challenge for clinicians, as NGS-based liquid biopsies may find dozens or even hundreds of genetic variants at once.
authors argue that regardless of the liquid biopsy used, the interpretation of the results can use some of the following strategies: 1. If ctDNA-based testing is used to detect targeted driver gene mutations, appropriate targeted therapies are chosen for treatment.
2. If no genetic mutations are found, seek genetic testing based on tumor tissue in an effort to detect the genetic mutations that drive them.
this is due to the possibility that a liquid biopsy may produce false negative results.
It's worth noting that several studies have shown that patients who can't detect ctDNA in the blood have relatively better prognosis, and that cancer may progress more slowly in these patients, so it may be more acceptable to wait in this subset of patients for genetic test results based on tumor tissue before starting initial treatment.
3. If sore cell mutations are found, but no targeted drive gene mutations are found, genetic testing based on tumor tissue should still be sought to identify specific drive gene mutations that may be missed.
is due to mutations in somater cell genes detected in liquid biopsies that may be due to genetic mutations carried by white blood cells in the blood.
in an era of ever-expanding treatment options for NSCLC, oncologists need the flexibility to choose individual therapies to find the best outcome for their patients.
genetic testing of tumors is undoubtedly a powerful tool in the selection of therapies.
liquid biopsy based on ctDNA in plasma may not completely replace genetic testing based on tumor tissue, but it allows more patients to perform genetic testing.
, guardant Health and Foundation Medicine's pan-tumor genetic testing has been approved by the FDA.
, these liquid biopsies based on NGS technology are not perfect, strategies to further optimize them have taken shape.
the authors hope that integrating this new technology into clinical practice will enable all patients with advanced NSCLC to obtain effective genetic testing.
References: ( 1 ) Aggarwal et al., (2020). Strategies for the successful practice of plasma-based NSCLC genotyping in clinical practice. Nature Reviews Clinical Oncology, x follow Medicinal Conde WeChat Public No