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Metastasis Initiation Precedes Detection of Primary Cancer—Analysis of Metastasis Growth in vivo in a Colorectal Cancer Test Case

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 wor...

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Autores principales: Hochman, Gili, Shacham-Shmueli, Einat, Raskin, Stephen P., Rosenbaum, Sara, Bunimovich-Mendrazitsky, Svetlana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773782/
https://www.ncbi.nlm.nih.gov/pubmed/33391005
http://dx.doi.org/10.3389/fphys.2020.533101
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author Hochman, Gili
Shacham-Shmueli, Einat
Raskin, Stephen P.
Rosenbaum, Sara
Bunimovich-Mendrazitsky, Svetlana
author_facet Hochman, Gili
Shacham-Shmueli, Einat
Raskin, Stephen P.
Rosenbaum, Sara
Bunimovich-Mendrazitsky, Svetlana
author_sort Hochman, Gili
collection PubMed
description 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.
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spelling pubmed-77737822021-01-01 Metastasis Initiation Precedes Detection of Primary Cancer—Analysis of Metastasis Growth in vivo in a Colorectal Cancer Test Case Hochman, Gili Shacham-Shmueli, Einat Raskin, Stephen P. Rosenbaum, Sara Bunimovich-Mendrazitsky, Svetlana Front Physiol Physiology 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. Frontiers Media S.A. 2020-12-17 /pmc/articles/PMC7773782/ /pubmed/33391005 http://dx.doi.org/10.3389/fphys.2020.533101 Text en Copyright © 2020 Hochman, Shacham-Shmueli, Raskin, Rosenbaum and Bunimovich-Mendrazitsky. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Hochman, Gili
Shacham-Shmueli, Einat
Raskin, Stephen P.
Rosenbaum, Sara
Bunimovich-Mendrazitsky, Svetlana
Metastasis Initiation Precedes Detection of Primary Cancer—Analysis of Metastasis Growth in vivo in a Colorectal Cancer Test Case
title Metastasis Initiation Precedes Detection of Primary Cancer—Analysis of Metastasis Growth in vivo in a Colorectal Cancer Test Case
title_full Metastasis Initiation Precedes Detection of Primary Cancer—Analysis of Metastasis Growth in vivo in a Colorectal Cancer Test Case
title_fullStr Metastasis Initiation Precedes Detection of Primary Cancer—Analysis of Metastasis Growth in vivo in a Colorectal Cancer Test Case
title_full_unstemmed Metastasis Initiation Precedes Detection of Primary Cancer—Analysis of Metastasis Growth in vivo in a Colorectal Cancer Test Case
title_short Metastasis Initiation Precedes Detection of Primary Cancer—Analysis of Metastasis Growth in vivo in a Colorectal Cancer Test Case
title_sort metastasis initiation precedes detection of primary cancer—analysis of metastasis growth in vivo in a colorectal cancer test case
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773782/
https://www.ncbi.nlm.nih.gov/pubmed/33391005
http://dx.doi.org/10.3389/fphys.2020.533101
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