Personalized Approach to Tissue and Liquid Biopsy after Failure of First-Line EGFR-TKIs: Is There an Issue When Tissue Is Not the Issue? A Case Series

Traditionally, tissue availability from rebiopsy is a prerequisite for adequate sequencing of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in therapy for advanced-stage lung cancer. Tissue biopsy truly is the gold standard for genetic analyses, but in some cases, such as with inadequate localization of the lesion or a patient’s inadequate performance status, comorbidities, or unwillingness to undergo an invasive procedure, liquid biopsy-based ctDNA analysis can be a noninvasive alternative approach. However, in some cases the gold standard might not shine that much. It is known that tumor heterogeneity or an inadequate amount of tissue might significantly interfere with the results of testing. In this paper, we present cases of patients with a negative tissue biopsy but a positive liquid biopsy which identified coexisting T790M mutation. These results enabled adequate sequencing and treatment with third-line EGFR-TKIs. Such possibilities stress the need to individualize testing for driver mutations in cases where it is clinically highly indicated.