TY - JOUR
T1 - Multifocality and recurrence risk
T2 - A quantitative model of field cancerization
AU - Foo, Jasmine
AU - Leder, Kevin
AU - Ryser, Marc D.
PY - 2014/8/21
Y1 - 2014/8/21
N2 - Primary tumors often emerge within genetically altered fields of premalignant cells that appear histologically normal but have a high chance of progression to malignancy. Clinical observations have suggested that these premalignant fields pose high risks for emergence of recurrent tumors if left behind after surgical removal of the primary tumor. In this work, we develop a spatio-temporal stochastic model of epithelial carcinogenesis, combining cellular dynamics with a general framework for multi-stage genetic progression to cancer. Using the model, we investigate how various properties of the premalignant fields depend on microscopic cellular properties of the tissue. In particular, we provide analytic results for the size-distribution of the histologically undetectable premalignant fields at the time of diagnosis, and investigate how the extent and the geometry of these fields depend upon key groups of parameters associated with the tissue and genetic pathways. We also derive analytical results for the relative risks of local vs. distant secondary tumors for different parameter regimes, a critical aspect for the optimal choice of post-operative therapy in carcinoma patients. This study contributes to a growing literature seeking to obtain a quantitative understanding of the spatial dynamics in cancer initiation.
AB - Primary tumors often emerge within genetically altered fields of premalignant cells that appear histologically normal but have a high chance of progression to malignancy. Clinical observations have suggested that these premalignant fields pose high risks for emergence of recurrent tumors if left behind after surgical removal of the primary tumor. In this work, we develop a spatio-temporal stochastic model of epithelial carcinogenesis, combining cellular dynamics with a general framework for multi-stage genetic progression to cancer. Using the model, we investigate how various properties of the premalignant fields depend on microscopic cellular properties of the tissue. In particular, we provide analytic results for the size-distribution of the histologically undetectable premalignant fields at the time of diagnosis, and investigate how the extent and the geometry of these fields depend upon key groups of parameters associated with the tissue and genetic pathways. We also derive analytical results for the relative risks of local vs. distant secondary tumors for different parameter regimes, a critical aspect for the optimal choice of post-operative therapy in carcinoma patients. This study contributes to a growing literature seeking to obtain a quantitative understanding of the spatial dynamics in cancer initiation.
KW - Cancer initiation
KW - Evolution
KW - Stochastic spatial models
UR - http://www.scopus.com/inward/record.url?scp=84899887965&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899887965&partnerID=8YFLogxK
U2 - 10.1016/j.jtbi.2014.02.042
DO - 10.1016/j.jtbi.2014.02.042
M3 - Article
C2 - 24735903
AN - SCOPUS:84899887965
SN - 0022-5193
VL - 355
SP - 170
EP - 184
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
ER -