EQD2 In modern cervix HDR brachytherapy: Clinical utility, sources of uncertainty, and interpretation.

Equivalent dose in 2 Gy fractions remains the operational reporting standard for cervical cancer HDR brachytherapy outcomes. Coverage goals, dose constraints, and the evidence linking volumetric dose parameters to local control and late morbidity were all derived within this framework. At the same time, EQD2 in cervix HDR brachytherapy is influenced by four recurring operational domains of uncertainty. First, steep near-source dose gradients amplify the biological consequence of geometric and contouring uncertainty through the nonlinear EQD2 transform, so small spatial errors can produce disproportionately large biological differences. Second, source decay prolongs delivery across the exchange cycle by up to 2.3-fold, while repair kinetics for late-responding pelvic organs at risk remain incompletely defined, making time-corrected biological dose inherently model-dependent. Third, large per-fraction doses place biological conversion in a regime where standard linear-quadratic assumptions are less secure: the most probable cervical tumor α/β derived from in vitro data is below the conventional assumption, and reported deviations in converted prescription dose can reach 10 Gy for common HDR schedules. Fourth, inter-fraction applicator reinsertion, organ filling, tissue deformation, and packing shift pelvic OARs relative to the high-dose region, so cumulative D2cc represents repeated sampling of near-maximum sub-volumes rather than a voxelwise dose history. Across these domains, the dose calculation algorithm adds a further layer of complexity, because published clinical thresholds were calibrated in the TG-43 framework. The literature does not support abandoning current EQD2-based constraints. Instead, current coverage goals and OAR constraints should remain the primary clinical reference while the delivery and accumulation factors that affect their interpretation are reported more explicitly.