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Ductal carcinoma in situ (DCIS) simulation -- extended results

Agent-based simulation of ductal carcinoma in situ (DCIS), a type of breast cancer that is constrained to growth in the breast duct lumen by a basement membrane. Shown here: a simulation of 45 days' growth in a 1.5 mm length of duct.

The mechanical and population dynamic parameters have been calibrated to patient-specific immunohistochemistry and other histologic measurements.

Dark circles: cell nuclei
Green cells: proliferating cells (Ki-67 positive; S, G2, M, or G1)
Red cells: apoptosis cells (cleaved Caspase-3 positive)
Pale blue cells: quiescent cells (G0)
Dark grey cells: necrotic cells prior to lysis
Debris in centre of duct: necrotic cellular debris
Red dots in centre of duct: clinically-detectable microcalcifications

Method: Agent-based, lattice-free model. Cell velocities determined by balance of adhesive and repulsive forces. Each cell has a phenotypic state governed by stochastic processes derived from nonhomogeneous Poisson processes. Results: First-of-its-kind calibration to patient pathology. Model quantitative predictions that we validate against the clinical literature, such as: Linear growth in ducts due to necrotic core biomechanics -- agreement with mammography literature Growth rates 7.5 mm/year to 10.2 mm/year -- quantitative agreeement with clinical literature Linear correlation between mammography size and pathology size -- quantitative agreement with 87 patient measurements spanning two orders of magnitude in clinical literature Age-structured, layered necrotic core microstructure -- agreement with patient pathology Tear at perinecrotic boundary due to necrotic cell biomechanics (first explanation for the "artifacts" in DCIS pathology) -- agreement with patient pathology New predictions of long-time necrotic core and microcalcification evolution -- agreement with mammography and biochemistry literature Source: Macklin et al. 2011 in review.
See: http://www.MathCancer.org/Publications.php#macklin11_jtb

Science > Applied Mathematics and Statistics > Numerical Analysis and Simulation

Science > Microbiology > Clinical Microbiology

Science > Microbiology > Disease Dynamics

Health > Oncology > Breast Cancer

Health > Oncology > Women's Cancer

Engineering > ICT > Algorithms

Engineering > ICT > Bioinformatics

Engineering > ICT > Computer Vision

Engineering > ICT > Numerical Analysis and Simulation

Engineering > Robotics and AI > Biomedical Robotics

Keywords: patient-calibrated model, DCIS, ductal carcinoma in situ, breast cancer, Immunohistochemistry, histopathology, comedonecrosis, Necrosis, agent-based model

Posted by: Paul Macklin

Posted on: 14 Oct 2011

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