How Liquid Biopsies Are Used in Cancer Treatment Selection
By Megan Roy, BSN, RN, OCN®
Biomarker testing is an essential tool when choosing the right treatment for many advanced solid cancers. However, tissue-based testing may take weeks to get results with a chance that not enough tissue was collected to complete the entire biomarker panel. Blood draw–based liquid biopsies may be a useful alternative to identify a tumor’s biomarker details and can be performed by testing for circulating tumor DNA (ctDNA).
CtDNA can be found (https://www.esmoopen.com/article/S2059-7029(21)00015-6/fulltext) when degrading or dying tumor cells are shed into a patient’s blood. Liquid biopsies usually return results within a week, and if they identify an actionable biomarker, treatment can begin right away.
Non-Small Cell Lung Cancer
Because non-small cell lung cancer (NSCLC) has U.S. Food and Drug Administration-approved targeted therapies in the first-line setting, the National Comprehensive Cancer Network recommends (https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf) broad biomarker testing for all nonsquamous NSCLC at the time of diagnosis. If a biopsy has insufficient tissue for testing, the patient will need another biopsy or liquid biopsy prior to starting treatment (https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21650). Eight biomarkers have an approved targeted drug: EGFR, ALK, ROS1, BRAF, RET, MET, NTRK, and KRAS. Biomarkers also help determine eligibility for clinical trials.
Breast Cancer
The NCCN guidelines (https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf) for breast cancer recommend using ctDNA testing for all patients with HR-positive, HER2-negative disease. If results are negative for PIK3CA, then breast tissue should be tested. Although emerging data suggest using ctDNA for other biomarkers, but NCCN does not currently recommend it (https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21650).
Prostate Cancer
The NCCN guidelines (https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf) for prostate cancer recommend testing ctDNA only when a biopsy is unsafe or not feasible. Targeted therapies are currently approved for MSI, BRCA1, and BRCA2 variants. Patients with BRCA1 or BRCA2 pathogenic variants may benefit (https://www.futuremedicine.com/doi/10.2217/fon-2019-0298) from PARP inhibitors. Additionally, some genomic alterations found on liquid biopsies can predict (https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21650) clinical outcomes.
Future Applications
CtDNA analysis may one day be used to predict a cancer’s response to immunotherapy. Zhang et al. studied (https://cancerdiscovery.aacrjournals.org/content/10/12/1842) 16 types of advanced solid cancers in 978 patients who were receiving immunotherapy. Prior to treatment, ctDNA analysis showed that patients with a higher variant allele frequency (how often the DNA alteration is noted in the sample) had poorer overall survival. On treatment, they found that a ctDNA analysis predicted early response to therapy when combined with radiographic measurements.
Currently, liquid biopsy application is largely limited to analyzing the presence of DNA, but it has potential for expansion because the biopsy fluids also contain ribonucleic acids, circulating tumor cells, extracellular vesicles, and tumor-educated platelets. Although those components are mainly of research interest at this time, they may have clinical application in the future (https://www.esmoopen.com/article/S2059-7029(21)00015-6/fulltext).
Approvals of tests using next-generation sequencing are a step forward in precision cancer care. Although liquid biopsies are still a relatively new diagnostic tool and their application limited, with advancements in technology and research continuously adding to the body of knowledge, their possibility to change the landscape of cancer care from screening and detection to treatment and monitoring is promising.