Effective Cancer Genotyping-Many Means to One End

Abstract

Precision cancer medicine requires effective genotyping of every patient's tumor to optimally design treatment plans. Despite its imperfect sensitivity, the rapidity and convenience of cell-free DNA sequencing makes it an essential complement to tumor genotyping, which, when used appropriately, can aid the pursuit of effective genotyping for all patients.See related article by Leighl et al., p. 4691.

Figure. Achieving effective cancer genotyping:

The availability of convenient plasma NGS assays with a high positive predictive value (PPV) means that, today, no patients with advanced NSCLC should receive no molecular testing or PD-L1 testing only (red). However, the limitations of our genotyping assays must be recognized if we wish to avoid incomplete genotyping (yellow). Targeted assays for common driver mutations (e.g. EGFR, ALK) can take time and exhaust tissue, making it harder to then test for rarer driver mutations if negative, while cfDNA analysis has imperfect sensitivity such that targetable driver mutations can be missed. These more limited assays can be useful if positive, but further testing must be pursued if they are negative. To offer our patients effective genotyping (green), the most reliable approaches either involve a panel-based assay tested on a high-quality tissue biopsy, or cfDNA analysis first, followed by reflex to tumor genotyping if the “liquid biopsy” is negative for a targetable driver mutation.