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Mitigating the Stage-Cliff: Continuous Spatial Validation of the Ghartey Scalar Model in the METABRIC Cohort

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Preprints.org
DOI
10.20944/preprints202605.0659.v1

Background: Categorical TNM staging evaluates anatomical mass in a vacuum, creating artificial prognostic "cliffs" and ignoring cellular kinetics. The Ghartey et al Frugal Scalar Model introduced a kinetic paradigm to oncology—1 / ([Mass] x [Velocity]) —demonstrating that multiplying mass by proliferative velocity significantly improves prognostication. However, its initial iterations remained mathematically constrained by ordinal stage approximations. This study aims to evaluate the Ghartey Scalar against baseline TNM staging and computationally validate the integration of continuous spatial mass to mitigate these categorical limitations. Methods: Clinical data and exact continuous tumor dimensions (mm) were extracted from the METABRIC breast cancer cohort (N = 1,300). Model discrimination and probabilistic calibration were evaluated strictly against 5-year Disease-Specific Survival (DSS, 240 events). Traditional TNM staging was compared against the Ghartey et al Frugal Scalar Model, as well as continuous 1-Dimensional (winsorized diameter) and 3-Dimensional (log-volume) spatial derivatives. Model stability was verified via nonparametric bootstrapping (1,000 resamples). Results: The continuous 1-D Scalar definitively outperformed traditional categorical TNM staging, achieving an AUROC of 0.7364 and a Brier score of 0.1358. To evaluate clinical triage utility within the cohort (N=1,300; 240 events), a "Kinetic Maximum" threshold for early-stage disease was established using the largest, fastest-growing tumor within the Stage I boundary (RSD=1.0, Diameter=2.0 cm, Velocity=3.5; TmdRxResCoef (%) cut off = 14.28%). At 5 years, this threshold demonstrated a Negative Predictive Value (NPV) of 89.3% and a Sensitivity of 75.8% for predicting disease-specific death. Furthermore, longitudinal analysis out to 10 years revealed a significant stage-migration effect, as the Positive Predictive Value (PPV) of the Red Zone increased from 32.8% to 46.0%, confirming that the scalar successfully flags intrinsic biologic momentum prior to delayed clinical failure. Conclusion: Substituting ordinal tumor stage with exact continuous spatial dimensions entirely eliminates the stage-cliff. The Ghartey Frugal Scalar provides an exceptionally safe exclusionary triage threshold (NPV ~90%) while isolating high-velocity phenotypes that require immediate systemic velocity-braking.

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