A cumulative cold dosimetry model for cryoablation: from geometry to dose-time planning

Abstract

Abstract Purpose To propose a cumulative cold dose (CCD) model integrating spatial, temporal, and biological dosimetry for cryoablation protocol optimization. Methods Systematic searches identified studies reporting freeze duration effects, cell-type-specific lethal thresholds, lethal isotherm ratio, or protocol-stratified outcomes. CCD was defined as the total time tissue is held at or below its cell-type-specific lethal threshold across all freeze cycles, targeting ≥ 80% cell death probability per point. Isotherm geometry was modeled across three cryoablation systems, four ice ball sizes (25–40 mm), and four power levels (40–100%). Results A total of 43 studies met inclusion criteria (24 in vitro, 9 in vivo, 7 clinical, 3 reviews). Freeze duration independently determined cell death: marginal zone cell death nearly doubled (42.5% to 84.8%) extending exposure from 60 to 120 s; double cycling raised renal cell lethality from 22 to 62% at − 10 °C and from 63 to 89% at − 15 °C. Minimum CCD estimates were 120 s single-cycle, 50 s per cycle double-cycle, and 31 s per cycle triple-cycle, independent of tissue type or system. For cold-sensitive tissues, double-cycle protocols maintained adequate CCD at all power levels (50–125 s/cycle). For cold-resistant phenotypes, most configurations required escalation to triple-cycle protocols (31–79 s/cycle) or multi-probe overlap. Conclusion CCD provides a model for transitioning cryoablation from geometry-driven to dose-time-driven planning; its clinical validity remains to be established through prospective thermometry-correlated outcomes research.