Fig. 4
Examples of the longitudinal dynamics of ctDNA. Time is measured from study enrollment or start of treatment if the patient was enrolled during treatment. Inverted triangles indicate the radiologic response, a partial response as blue, stable disease as green and progressive disease as orange. Each treatment is shaded in different colors. Measurable lesions are plotted in dotted lines to the right y-axis. (A) Patient M019 was diagnosed with bone metastasis and regional lymph node metastasis after a disease-free interval of 61 months. The ctDNA eVAF decreased in this case after a partial response to a 1st line palliative therapy. An abrupt rise and additional ctDNA detection were noted at the 6th serial follow-up, showing a lead time of 8 months before a liver metastasis was radiologically detected. (B) Patient M015 had a locoregional recurrence along with bone metastasis at baseline. PIK3CA mutation eVAF increased as peritoneal seeding progressed. This metastasis was not detected by primary or metastatic tissue targeted sequencing. (C) Patient M005 initially had a bone metastasis but was ctDNA-negative at enrollment. However, as a liver metastasis progressed two PIK3CA mutations were detected by ctDNA. (D) Patient M039 was identified as having mediastinal lymph nodes and pleural metastasis at baseline. During a 1st line treatment, a liver metastasis was identified and progressed along with PIK3CA ctDNA eVAF changes.
