Tissue biopsies remain the gold standard for genomic testing; however, alternative sources of tumor material, such as blood, saliva and urine, have been actively investigated in the past several years with the goal of providing biopsy surrogates that can provide rapid, accurate detection of genomic alterations through noninvasive procedures.
Liquid biopsies are based on the premise that tumor material is shed from a tumor in the form of circulating tumor cells or cell-free DNA (cfDNA) into the circulation of the patient. Studies have demonstrated genomic testing with advanced technology can detect the same genomic alterations in the shed material pulled out of bodily fluids as captured to sampling the actual tumor site.
Several advantages of liquid biopsies exist (Figure 4):
- Liquid biopsies may provide a more complete assessment of the tumor landscape compared with single-site (traditional) tumor sampling, because tumor material shed into the bloodstream may be from the primary and/or metastatic sites.
- Serial sampling through liquid biopsies is a cost-effective approach to capture the acquisition of resistance mutations in real time, and studies have shown serial sampling may detect resistance mutations up to 16 weeks before finding progression through traditional monitoring platforms (CT/PET scans).
- Liquid biopsies provide a safe, noninvasive alternative to obtaining tumor material when the patient status or location of tumor limits feasibility of invasive procedures.
- EGFR-mutated lung cancer is currently the only tumor type in which monitoring treatment response through liquid or tumor biopsies is considered standard of care.
- Appearance of the EGFR T790M mutation in patients with lung cancer, in either tumor or liquid biopsy, prompts the switching of therapies to osimertinib (Tagrisso, AstraZeneca), a targeted therapy developed to selectively inhibit T790M, the most common resistance mechanism in lung cancer patients treated with first-generation EGFR inhibitors (eg, erlotinib [Tarceva; Genentech, Astellas]).
Figure 4. Tissue vs. liquid biopsies.
Status of liquid biopsies in clinical practice
- Outside of lung cancer, liquid biopsies and genomic testing may be used as an alternative when tumor tissue is not available and selection of targeted therapy is dependent on genetic results.
- The evidence for liquid biopsies demonstrates significant discordance between tissue- and liquid-based testing; therefore, currently, a negative result by liquid biopsy is not considered actionable, and retrieval of tissue sample is strongly encouraged.
- The use of genomic testing of liquid biopsies to monitor disease progression remains exploratory for other tumor types; however, several studies have shown quantitative measurement of mutations detected in cfDNA, particularly in patients receiving targeted therapies, may indicate disease progression and acquisition of resistance mutations.
- BRCA1 reversions in ovarian cancers receiving platinum- or PARP-based treatment
- ESR1 mutations in breast cancer patients receiving aromatase inhibitors
- Presence of cfDNA may indicate manifestation of metastatic disease.
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