TY - JOUR
T1 - Metastases Growth Patterns in vivo—A Unique Test Case of a Metastatic Colorectal Cancer Patient
AU - Hochman, Gili
AU - Shacham-Shmueli, Einat
AU - Heymann, Tchia
AU - Raskin, Stephen
AU - Bunimovich-Mendrazitsky, Svetlana
N1 - Publisher Copyright:
© Copyright © 2019 Hochman, Shacham-Shmueli, Heymann, Raskin and Bunimovich-Mendrazitsky.
PY - 2019/11/12
Y1 - 2019/11/12
N2 - Colorectal cancer (CRC) is one of the most common causes of cancer-related mortality worldwide. Most cases of deaths result from metastases, assumed to be shed, in many cases, before disease detection. Providing reliable predictions of the metastases' growth pattern may help planning treatment. Available mathematical tumor growth models rely mainly on primary tumor data, and rarely relate to metastases growth. The aim of this work was to explore CRC lung metastases growth patterns. We used data of a metastatic CRC patient, for whom 10 lung metastases were measured while untreated by seven serial computed tomography (CT) scans, during almost 3 years. Three mathematical growth models—Exponential, logistic, and Gompertzian—were fitted to the actual measurements. Goodness of fit of each of the models to actual growth was estimated using different scores. Factors affecting growth pattern were explored: size, location, and primary tumor resection. Exponential growth model demonstrated good fit to data of all metastases. Logistic and Gompertzian growth models, in most cases, were overfitted and hence unreliable. Metastases inception time, calculated by backwards extrapolation of the fitted growth models, was 8–19 years before primary tumor diagnosis date. Three out of ten metastases demonstrated enhanced growth rate shortly after primary tumor resection. Our unique data provide evidence that exponential growth of CRC lung metastases is a legitimate approximation, and encourage focusing research on short-term effects of surgery on metastases growth rate. Significance: Providing reliable predictions of the metastases' growth pattern using mathematical models may help determining the optimal treatment plan that fits a given patient best and maximizes the probability of cure.
AB - Colorectal cancer (CRC) is one of the most common causes of cancer-related mortality worldwide. Most cases of deaths result from metastases, assumed to be shed, in many cases, before disease detection. Providing reliable predictions of the metastases' growth pattern may help planning treatment. Available mathematical tumor growth models rely mainly on primary tumor data, and rarely relate to metastases growth. The aim of this work was to explore CRC lung metastases growth patterns. We used data of a metastatic CRC patient, for whom 10 lung metastases were measured while untreated by seven serial computed tomography (CT) scans, during almost 3 years. Three mathematical growth models—Exponential, logistic, and Gompertzian—were fitted to the actual measurements. Goodness of fit of each of the models to actual growth was estimated using different scores. Factors affecting growth pattern were explored: size, location, and primary tumor resection. Exponential growth model demonstrated good fit to data of all metastases. Logistic and Gompertzian growth models, in most cases, were overfitted and hence unreliable. Metastases inception time, calculated by backwards extrapolation of the fitted growth models, was 8–19 years before primary tumor diagnosis date. Three out of ten metastases demonstrated enhanced growth rate shortly after primary tumor resection. Our unique data provide evidence that exponential growth of CRC lung metastases is a legitimate approximation, and encourage focusing research on short-term effects of surgery on metastases growth rate. Significance: Providing reliable predictions of the metastases' growth pattern using mathematical models may help determining the optimal treatment plan that fits a given patient best and maximizes the probability of cure.
KW - exponential growth
KW - gompertzian growth
KW - logistic growth
KW - lung metastases
KW - mathematical growth models
KW - primary tumor resection
UR - http://www.scopus.com/inward/record.url?scp=85077625097&partnerID=8YFLogxK
U2 - 10.3389/fams.2019.00056
DO - 10.3389/fams.2019.00056
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AN - SCOPUS:85077625097
SN - 2297-4687
VL - 5
JO - Frontiers in Applied Mathematics and Statistics
JF - Frontiers in Applied Mathematics and Statistics
M1 - 56
ER -