Yazdjer2019 - reinforcement learning-based control of tumor growth under anti-angiogenic therapy

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Model Identifier
BIOMD0000000821
Short description
This model is based on: Reinforcement learning-based control of tumor growth under anti-angiogenic therapy Authors: Parisa Yazdjerdi, Nader Meskin, Mohammad Al-Naemi, Ala-Eddin Al Moustafa, Levente Kovacs Abstract: Background and objectives: In recent decades, cancer has become one of the most fatal and destructive diseases which is threatening humans life. Accordingly, different types of cancer treatment are studied with the main aim to have the best treatment with minimum side effects. Anti-angiogenic is a molecular targeted therapy which can be coupled with chemotherapy and radiotherapy. Although this method does not eliminate the whole tumor, but it can keep the tumor size in a given state by preventing the formation of new blood vessels. In this paper, a novel model-free method based on reinforcement learning (RL) framework is used to design a closed-loop control of anti-angiogenic drug dosing administration. Methods: A Q-learning algorithm is developed for the drug dosing closed-loop control. This controller is designed using two different values of the maximum drug dosage to reduce the tumor volume up to a desired value. The mathematical model of tumor growth under anti-angiogenic inhibitor is used to simulate a real patient. Results: The effectiveness of the proposed method is shown through in silico simulation and its robustness to patient parameters variation is demonstrated. It is demonstrated that the tumor reaches its minimal volume in 84 days with maximum drug inlet of 30 mg/kg/day. Also, it is shown that the designed controller is robust with respect to  ± 20% of tumor growth parameters changes. Conclusion: The proposed closed-loop reinforcement learning-based controller for cancer treatment using anti-angiogenic inhibitor provides an effective and novel result such that with a clinically valid and safe dosage of drug, the volume reduces up to 1mm3 in a reasonable short period compared to the literature.
Format
SBML (L2V4)
Related Publication
  • Reinforcement learning-based control of tumor growth under anti-angiogenic therapy.
  • Yazdjerdi P, Meskin N, Al-Naemi M, Al Moustafa AE, Kovács L
  • Computer methods and programs in biomedicine , 5/ 2019 , Volume 173 , pages: 15-26 , PubMed ID: 31046990
  • Department of Electrical Engineering, Qatar University, Qatar. Electronic address: py1005599@qu.edu.qa.
  • BACKGROUND AND OBJECTIVES:In recent decades, cancer has become one of the most fatal and destructive diseases which is threatening humans life. Accordingly, different types of cancer treatment are studied with the main aim to have the best treatment with minimum side effects. Anti-angiogenic is a molecular targeted therapy which can be coupled with chemotherapy and radiotherapy. Although this method does not eliminate the whole tumor, but it can keep the tumor size in a given state by preventing the formation of new blood vessels. In this paper, a novel model-free method based on reinforcement learning (RL) framework is used to design a closed-loop control of anti-angiogenic drug dosing administration. METHODS:A Q-learning algorithm is developed for the drug dosing closed-loop control. This controller is designed using two different values of the maximum drug dosage to reduce the tumor volume up to a desired value. The mathematical model of tumor growth under anti-angiogenic inhibitor is used to simulate a real patient. RESULTS:The effectiveness of the proposed method is shown through in silico simulation and its robustness to patient parameters variation is demonstrated. It is demonstrated that the tumor reaches its minimal volume in 84 days with maximum drug inlet of 30 mg/kg/day. Also, it is shown that the designed controller is robust with respect to  ± 20% of tumor growth parameters changes. CONCLUSION:The proposed closed-loop reinforcement learning-based controller for cancer treatment using anti-angiogenic inhibitor provides an effective and novel result such that with a clinically valid and safe dosage of drug, the volume reduces up to 1mm3 in a reasonable short period compared to the literature.
Contributors
Submitter of the first revision: Szeyi Ng
Submitter of this revision: Szeyi Ng
Modellers: Szeyi Ng

Metadata information

is (2 statements)
BioModels Database BIOMD0000000821
BioModels Database MODEL1909240003

isDescribedBy (1 statement)
PubMed 31046990

hasProperty (5 statements)
Experimental Factor Ontology cancer
Mathematical Modelling Ontology Ordinary differential equation model
Gene Ontology angiogenesis
NCIt Administration
NCIt Tumor Angiogenesis


Curation status
Curated


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Model files

Yazdjer2019 - reinforcement learning-based control of tumor growth under anti-angiogenic therapy.xml SBML L2V4 file for the model 43.61 KB Preview | Download

Additional files

Fig 1.png PNG plot of the model simulation Figure 1 26.58 KB Preview | Download
Yazdjer2019 - reinforcement learning-based control of tumor growth under anti-angiogenic therapy.cps COPASI 4.24 (Build 197) file for the model 60.80 KB Preview | Download

  • Model originally submitted by : Szeyi Ng
  • Submitted: Sep 24, 2019 2:16:01 PM
  • Last Modified: Sep 24, 2019 2:16:01 PM
Revisions
  • Version: 3 public model Download this version
    • Submitted on: Sep 24, 2019 2:16:01 PM
    • Submitted by: Szeyi Ng
    • With comment: Automatically added model identifier BIOMD0000000821
Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
endothelial volume x 2

dTDP-5-dimethyl-L-lyxose
1.0 mmol
concentration of administrated inhibitor x 3

Concentration ; Inhibitor
0.0 mmol
tumor volume x 1

Tumor Volume
1.0 mmol
Reactions
Reactions Rate Parameters
endothelial_volume_x_2 => ; tumor_volume_x_1 compartment*d*endothelial_volume_x_2*tumor_volume_x_1^(2/3)*a a = 1.0; d = 0.00873 1/(mm^2*day)
=> concentration_of_administrated_inhibitor_x_3 compartment*u u = 0.0 mg/kg/d
concentration_of_administrated_inhibitor_x_3 => compartment*lambda_3*concentration_of_administrated_inhibitor_x_3*a lambda_3 = 1.3 1/d; a = 1.0
tumor_volume_x_1 => ; endothelial_volume_x_2 compartment*lambda_1*tumor_volume_x_1*ln(tumor_volume_x_1/endothelial_volume_x_2)*a lambda_1 = 0.192 1/d; a = 1.0
endothelial_volume_x_2 => compartment*lambda_2*endothelial_volume_x_2*a a = 1.0; lambda_2 = 0.0 1/d
=> endothelial_volume_x_2; tumor_volume_x_1 compartment*b*tumor_volume_x_1*a a = 1.0; b = 5.85 1/d
endothelial_volume_x_2 => ; concentration_of_administrated_inhibitor_x_3 compartment*e*endothelial_volume_x_2*concentration_of_administrated_inhibitor_x_3*a a = 1.0; e = 0.66 kg/mg*d
Curator's comment:
(added: 24 Sep 2019, 14:15:35, updated: 24 Sep 2019, 14:15:35)
The figure is reproduced using the uploaded file and COPASI, by setting the time =120 s. To reproduce other figures of the publication, please change the values of a and u accordingly.