The impact of random microenvironmental fluctuations on tumor control probability.
Gillespie algorithm
Random fluctuations
Stochastic model
Tumor control probability
Journal
Journal of theoretical biology
ISSN: 1095-8541
Titre abrégé: J Theor Biol
Pays: England
ID NLM: 0376342
Informations de publication
Date de publication:
21 01 2021
21 01 2021
Historique:
received:
14
01
2020
revised:
27
08
2020
accepted:
12
09
2020
pubmed:
27
9
2020
medline:
22
6
2021
entrez:
26
9
2020
Statut:
ppublish
Résumé
The tumor control probability (TCP) is a metric used to calculate the probability of controlling or eradicating tumors through radiotherapy. Cancer cells vary in their response to radiation, and although many factors are involved, the tumor microenvironment is a crucial one that determines radiation efficacy. The tumor microenvironment plays a significant role in cancer initiation and propagation, as well as in treatment outcome. We have developed stochastic formulations to study the impact of arbitrary microenvironmental fluctuations on TCP and extinction probability (EP), which is defined as the probability of cancer cells removal in the absence of treatment. Since the derivation of analytical solutions are not possible for complicated cases, we employ a modified Gillespie algorithm to analyze TCP and EP, considering the random variations in cellular proliferation and death rates. Our results show that increasing the standard deviation in kinetic rates initially enhances the probability of tumor eradication. However, if the EP does not reach a probability of 1, the increase in the standard deviation subsequently has a negative impact on probability of cancer cells removal, decreasing the EP over time. The greatest effect on EP has been observed when both birth and death rates are being randomly modified and are anticorrelated. In addition, similar results are observed for TCP, where radiotherapy is included, indicating that increasing the standard deviation in kinetic rates at first enhances the probability of tumor eradication. But, it has a negative impact on treatment effectiveness if the TCP does not reach a probability of 1.
Identifiants
pubmed: 32979339
pii: S0022-5193(20)30349-0
doi: 10.1016/j.jtbi.2020.110494
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110494Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.