PMC7446309_01
(A) Timeline depicting changes in tumoral size, treatment lines, and progression of disease events. (B) Next-generation sequencing (NGS) of circulating tumor DNA depicting somatic mutation burden of primary and acquired mutations. The tumor response mapping illustrates the mutant allele percentage (percent cell-free DNA [cfDNA]) of observed somatic variants at each sample submission time point. The somatic alteration burden value refers to the maximum percentage cfDNA detected at each time point and has been used to illustrate how tumor progeny is responding to the selective pressure of treatment. Note that this graph depicts each variant allele's frequency complementarily, meaning that the percentage shown corresponds to the sum of all variant alleles' frequency at a given time point. (C) Illustration of NGS selectively highlighting molecular response of CCDC6-RET fusion and TP53 to cabozantinib.
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A CT scan 4 months later showed partial response (Fig 1A). Repeat ctDNA NGS no longer detected the T790M mutation but presented new mutations in PIK3CA (G118D, 0.7%) and TP53 (H193L, 0.4%) as well as a CCDC6-RET rearrangement with a frequency of 0.1% (Fig 1C). A new evaluation of ctDNA NGS still did not detect EGFR T790M mutation but showed an increase in the frequency of CCDC6-RET rearrangement from 0.1% to 0.4% (Fig 1C). Evaluation of ctDNA NGS detected additional increase in the frequency of CCDC6-RET rearrangement to 0.7% (Fig 1C). After 2 months of treatment, ctDNA NGS detected a lower level of CCDC6-RET rearrangement (0.08%; Fig 1C).