Effective tumor kinetics inferred from single routine H&E biopsies enable counterfactual virtual radiotherapy trials
- 1University of Salzburg
Abstract
Routine H&E-histopathology captures spatial snapshots of tumor ecosystems, yet computational pathology largely treats them as textures without explicit links to underlying kinetics. We show that patient-specific parameters of a mechanistic reaction-diffusion model can be inferred from a single biopsy. Cell-nucleus point patterns are fitted jointly to the analytical two-point correlation function and power spectral density, recovering patient-specific mechanistic proliferation and diffusion rates across eleven multicenter cohorts. Derived dispersion length and front velocity define mechanistic phenotypes stratifying progression-free and overall survival and adding information independent of routine covariates. We illustrate counterfactual radiotherapy simulations in glioblastoma and show that a virtual clinical trial deescalating histology-calibrated faster-growing tumors to hypofractionation while dose-intensifying slower-growing tumors adds 96.7 days of restricted mean progression-free in silico survival over standard of care (permutation p < 0.001 against random allocation to the same arms). This provides a low-barrier transition from routine histopathology to mechanistically interpretable model-based forward simulations.
Related
- How Effective Is Saline Solution Infiltration During Coaxial Needle Withdrawal in Reducing the Incidence of Pneumothorax in CT-Guided Lung Biopsies?
- Direct Amplification-Free Nanopore Sequencing of Leishmania from Cutaneous Biopsies
- Endometrial evolution assessment using a high-resolution mini-hysteroscope for virtual biopsies
- Collapsing Glomerulopathy Encountered in Time Zero Kidney Allograft Biopsies
- Transcriptomic Reproducibility in Endometrial Biopsies: Evidence Across Cycles and Tissue Regions in Hormonal Replacement Therapy Endometrial Preparation Protocols
BibTeX
@misc{schlicke2026effective,
title = {{Effective tumor kinetics inferred from single routine H&E biopsies enable counterfactual virtual radiotherapy trials}},
author = {P. Schlicke and C. Ercan and S. Ranjbar and A. N. Seldomridge and S. Aggarwal and A. Mehta and T. P. Sainz and M. U. Zahid and P. Fang and V. A. Hofmann and S. Pasetto and T. Cisneros Napravnik and N. Puebla-Osorio and C. Kuttler and A. Klopp and L. Colbert and A. M. Holder and R. Weiser and S. H. Lin and C. A. Torres-Cabala and F. Vega and Y. Yuan and H. Enderling},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.26362768},
url = {https://www.medrxiv.org/content/10.64898/2026.09.10.26362768v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Effective tumor kinetics inferred from single routine H&E biopsies enable counterfactual virtual radiotherapy trials
AU - P. Schlicke
AU - C. Ercan
AU - S. Ranjbar
AU - A. N. Seldomridge
AU - S. Aggarwal
AU - A. Mehta
AU - T. P. Sainz
AU - M. U. Zahid
AU - P. Fang
AU - V. A. Hofmann
AU - S. Pasetto
AU - T. Cisneros Napravnik
AU - N. Puebla-Osorio
AU - C. Kuttler
AU - A. Klopp
AU - L. Colbert
AU - A. M. Holder
AU - R. Weiser
AU - S. H. Lin
AU - C. A. Torres-Cabala
AU - F. Vega
AU - Y. Yuan
AU - H. Enderling
PY - 2026
DA - 2026/09/10
PB - medRxiv
DO - 10.64898/2026.09.10.26362768
UR - https://www.medrxiv.org/content/10.64898/2026.09.10.26362768v1
AB - Routine H&E-histopathology captures spatial snapshots of tumor ecosystems, yet computational pathology largely treats them as textures without explicit links to underlying kinetics. We show that patient-specific parameters of a mechanistic reaction-diffusion model can be inferred from a single biopsy. Cell-nucleus point patterns are fitted jointly to the analytical two-point correlation function and power spectral density, recovering patient-specific mechanistic proliferation and diffusion rates across eleven multicenter cohorts. Derived dispersion length and front velocity define mechanistic phenotypes stratifying progression-free and overall survival and adding information independent of routine covariates. We illustrate counterfactual radiotherapy simulations in glioblastoma and show that a virtual clinical trial deescalating histology-calibrated faster-growing tumors to hypofractionation while dose-intensifying slower-growing tumors adds 96.7 days of restricted mean progression-free in silico survival over standard of care (permutation p < 0.001 against random allocation to the same arms). This provides a low-barrier transition from routine histopathology to mechanistically interpretable model-based forward simulations.
ER -