PMC9795219_01
CT scan results. CT scan 20 days prior to right hemicolectomy did not show any evidence of metastatic disease (top panel). Rising ctDNA levels prompted a CT scan on post-operative day 155, which revealed a 2.4 x 1.8 cm ill-defined hypoattenuating lesion in the right hepatic lobe, as well as 0.8 cm and 0.4 cm nodules in the left hepatic lobe (red arrows, middle panel). An interval CT scan after two cycles of chemotherapy showed response of all hepatic lesions (red arrows, bottom panel).
fonc-12-1074786-g001.jpg
PMC9795219_01_fonc-12-1074786-g001.jpg
f1
An initial right hepatic lobe lesion noted on CT ( Figure 1 ) and PET-scan was later confirmed to represent a benign hemangioma based on follow up magnetic resonance imaging (MRI). This rapid rise in ctDNA level prompted a CT scan of the chest, abdomen, and pelvis with contrast that detected a 2.4 x 1.8 cm ill-defined hypoattenuating lesion in the right hepatic lobe, as well as 0.8 cm and 0.4 cm nodules in the left hepatic lobe, concerning for oligometastatic disease ( Figure 1 ). Interval imaging after two cycles of chemotherapy showed a response of all hepatic lesions, with ctDNA level cleared to undetectable (0.00 MTM/mL) ( Figure 1 ;  Figure 2A ).
ctDNA dynamics throughout the clinical course. (A) Overview plot depicting composite ctDNA changes as measured in MTM/mL, along with radiographic imaging and therapeutic interventions. (B) Changes in levels of patient-specific variants identified and tracked using Signatera  Molecular Residual Disease Test. ctDNA, circulating tumor DNA; MTM/mL, mean tumor molecules per milliliter of plasma.
fonc-12-1074786-g002.jpg
PMC9795219_01_fonc-12-1074786-g002.jpg
f2
At the time of diagnosis, the patient had undetectable carcinoembryonic antigen (CEA) levels ( Figure 2A ). The patient's ctDNA level, measured using the assay described above, 25 days after surgery was 0.42 MTM/mL, with repeat ctDNA analysis six weeks after surgery indicating persistently low-level positive ctDNA at 0.55 MTM/mL ( Figure 2A ). Longitudinal ctDNA monitoring revealed an ongoing increase to 10.96 MTM/mL five months after surgery ( Figures 2A, B ). A ctDNA level after the first cycle of FOLFOXIRI-Bev decreased to 0.04 MTM/mL ( Figure 2A ). Interval imaging after two cycles of chemotherapy showed a response of all hepatic lesions, with ctDNA level cleared to undetectable (0.00 MTM/mL) ( Figure 1 ;  Figure 2A ). The patient's ctDNA level remained undetectable (0.00 MTM/mL) ( Figures 2A, B ) throughout the remainder of his adjuvant treatment course. Of note, the patient's CEA levels remained within normal limits (<=3.0 ng/mL per institutional assay) throughout his disease course, from diagnosis to recurrence to post-treatment monitoring ( Figure 2A ).