Dynamical systems model of ctDNA, tumor, and inflammation. (A) Qualitative schematic of the tumor burden (represented as B), surrounded by inflammation (represented as I), and ctDNA in the peripheral blood. (B) Compartment model schematic, including ctDNA (represented as Z). (C) Model kinetics inferred from a patient with MTV+/ctDNA+ undergoing CAR T-cell therapy with ctDNA measurements (dots). The curve represents the modeled (fitted) ctDNA compartment dynamics. (D) Inferred model kinetics of MTV (I + B, solid line) and tumor alone (B, dashed) of the same patient. MTV is measured from the PET scan at day 30 (red dot). This modeling successfully captures disease progression, although delayed compared with the actual clinical progression because of the tumor burden. (E) and (F) Inferred model kinetics for a patient who was tested MTV+/ctDNA– on day 30 and after. Here, the MTV eventually consists entirely of inflammation and is still undetectable at day 365, in line with the cDNA kinetics and the end point of complete response. LoD, estimated level of detection of 1 mL.