TY - JOUR
T1 - Metastasis Initiation Precedes Detection of Primary Cancer—Analysis of Metastasis Growth in vivo in a Colorectal Cancer Test Case
AU - Hochman, Gili
AU - Shacham-Shmueli, Einat
AU - Raskin, Stephen P.
AU - Rosenbaum, Sara
AU - Bunimovich-Mendrazitsky, Svetlana
N1 - Publisher Copyright: © Copyright © 2020 Hochman, Shacham-Shmueli, Raskin, Rosenbaum and Bunimovich-Mendrazitsky.
PY - 2020/12/17
Y1 - 2020/12/17
N2 - Most cases of deaths from colorectal cancer (CRC) result from metastases, which are often still undetectable at disease detection time. Even so, in many cases, shedding is assumed to have taken place before that time. The dynamics of metastasis formation and growth are not well-established. This work aims to explore CRC lung metastasis growth rate and dynamics. We analyzed a test case of a metastatic CRC patient with four lung metastases, with data of four serial computed tomography (CT) scans measuring metastasis sizes while untreated. We fitted three mathematical growth models—exponential, logistic, and Gompertzian—to the CT measurements. For each metastasis, a best-fitted model was determined, tumor doubling time (TDT) was assessed, and metastasis inception time was extrapolated. Three of the metastases showed exponential growth, while the fourth showed logistic restraint of the growth. TDT was around 93 days. Predicted metastasis inception time was at least 4–5 years before the primary tumor diagnosis date, though they did not reach detectable sizes until at least 1 year after primary tumor resection. Our results support the exponential growth approximation for most of the metastases, at least for the clinically observed time period. Our analysis shows that metastases can be initiated before the primary tumor is detectable and implies that surgeries accelerate metastasis growth.
AB - Most cases of deaths from colorectal cancer (CRC) result from metastases, which are often still undetectable at disease detection time. Even so, in many cases, shedding is assumed to have taken place before that time. The dynamics of metastasis formation and growth are not well-established. This work aims to explore CRC lung metastasis growth rate and dynamics. We analyzed a test case of a metastatic CRC patient with four lung metastases, with data of four serial computed tomography (CT) scans measuring metastasis sizes while untreated. We fitted three mathematical growth models—exponential, logistic, and Gompertzian—to the CT measurements. For each metastasis, a best-fitted model was determined, tumor doubling time (TDT) was assessed, and metastasis inception time was extrapolated. Three of the metastases showed exponential growth, while the fourth showed logistic restraint of the growth. TDT was around 93 days. Predicted metastasis inception time was at least 4–5 years before the primary tumor diagnosis date, though they did not reach detectable sizes until at least 1 year after primary tumor resection. Our results support the exponential growth approximation for most of the metastases, at least for the clinically observed time period. Our analysis shows that metastases can be initiated before the primary tumor is detectable and implies that surgeries accelerate metastasis growth.
KW - clinical metastasis growth data
KW - colorectal cancer
KW - exponential growth
KW - liver metastasectomy
KW - logistic growth
KW - lung metastases
KW - mathematical growth models
KW - primary tumor resection
UR - http://www.scopus.com/inward/record.url?scp=85098622208&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fphys.2020.533101
DO - https://doi.org/10.3389/fphys.2020.533101
M3 - مقالة
SN - 1664-042X
VL - 11
JO - Frontiers in Physiology
JF - Frontiers in Physiology
M1 - 533101
ER -