SPATIAL-CONTINUUM: The In Silico Sanctuary Digital Twin Nature Comms Companion

Biophysical Reaction-Diffusion & Evolutionary Game Engine for Post-ADAURA Sanctuary Dynamics • Luca Celebrano

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Simulated Timeline
Day 0 (0.0 Yrs)
Tumor Burden V(t)
100.0% (1000 mm³)
Continuum Resistance Index (CRI)
0.12 [Low Risk]
Sanctuary Surface Area
34.2% (Sub-therapeutic)
Phenotype Ratio (S : P : R)
88% : 10% : 2%

2D Radial Reaction-Diffusion & Cellular Architecture (500 μm Cord)

Microenvironment Probe:
Hover mouse over cord to inspect local microenvironment...
Sensitive (S) [EGFRmut, Osimertinib-Killable]
Plastic (P) [DTP, AXL/ZEB1 Niche]
Resistant (R) [C797S / MET amp]
⚡ Capillary Core (r=0)

PDE Radial Drug Gradient C(r) vs Sanctuary Window

D = 85 μm²/s • IFP = 18 mmHg

5-Year Longitudinal Recurrence Trial V(t)

● ADAURA (Stop Yr 3) ● SG-ADAURA (Adaptive)

Evolutionary Replicator Phase Simplex (S-P-R Attractor)

3x3 Game Payoff Trajectory
Select Therapeutic Regimen:
Standard ADAURA Continuous 80mg
Daily Osimertinib 36 months → Cessation → Sanctuary-driven explosive recurrence flare.
SG-ADAURA Protocol Adaptive (CRI-Guided)
CRI-monitored pulsed dosing: preserves sensitive competitors, suppressing resistant expansion.
Metronomic Maintenance Low-Dose 40mg
Continuous sub-maximal dosing. Flattens vascular peak but risks intermediate sanctuary niche.
Drug Diffusivity (Deff) 85 μm²/s
Capillary Permeability (Pv) 1.00
Tumor Interstitial Pressure (IFP) 18 mmHg
Plasticity Transition (μS→P) 0.035 /day
Cost of Resistance (cR) 15% penalty
Planned ADAURA Cessation 36 Months
Clinical Benchmark Scenarios:
The Spatial Invariant: Whenever high interstitial fluid pressure impedes convective penetration, sub-lethal concentrations (0.15 – 0.65 C₀) create an inevitable evolutionary sanctuary breeding genetic resistance.