Chemotherapy response prediction with diffuser elapser network
Batuhan Koyuncu1,2, Ahmet Melek3,2, Defne Yilmaz4,2
1Department of Computer Engineering, Bogazici University, Istanbul, 34342, Turkey.
Abstract:
In solid tumors, elevated fluid pressure and inadequate blood perfusion resulting from unbalanced angiogenesis are the prominent reasons for the ineffective drug delivery inside tumors. To normalize the heterogeneous and tortuous tumor vessel structure, antiangiogenic treatment is an effective approach. Additionally, the combined therapy of antiangiogenic agents and chemotherapy drugs has shown promising effects on enhanced drug delivery. However, the need to find the appropriate scheduling and dosages of the combination therapy is one of the main problems in anticancer therapy. Our study aims to generate a realistic response to the treatment schedule, making it possible for future works to use these patient-specific responses to decide on the optimal starting time and dosages of cytotoxic drug treatment. Our dataset is based on our previous in-silico model with a framework for the tumor microenvironment, consisting of a tumor layer, vasculature network, interstitial fluid pressure, and drug diffusion maps. In this regard, the chemotherapy response prediction problem is discussed in the study, putting forth a proof of concept for deep learning models to capture the tumor growth and drug response behaviors simultaneously. The proposed model utilizes multiple convolutional neural network submodels to predict future tumor microenvironment maps considering the effects of ongoing treatment. Since the model has the task of predicting future tumor microenvironment maps, we use two image quality evaluation metrics, which are structural similarity and peak signal-to-noise ratio, to evaluate model performance. We track tumor cell density values of ground truth and predicted tumor microenvironments. The model predicts tumor microenvironment maps seven days ahead with the average structural similarity score of 0.973 and the average peak signal ratio of 35.41 in the test set. It also predicts tumor cell density at the end day of 7 with the mean absolute percentage error of [Formula: see text].
Insights
This study introduces a deep learning model to predict chemotherapy response in solid tumors. The model forecasts tumor microenvironment changes, aiding in personalized treatment scheduling for improved drug delivery.
Area of Science:
- Oncology
- Computational Biology
- Medical Imaging
Background:
- Solid tumors exhibit high fluid pressure and poor perfusion, hindering drug delivery.
- Antiangiogenic therapy can normalize tumor vasculature, improving drug penetration.
- Optimizing combination therapy scheduling (antiangiogenics + chemotherapy) is crucial for effective cancer treatment.
Purpose of the Study:
- To develop a deep learning model for predicting patient-specific responses to chemotherapy treatment schedules.
- To provide a framework for optimizing the timing and dosage of cytotoxic drugs in combination cancer therapy.
- To simulate tumor microenvironment dynamics under various treatment scenarios.
Main Methods:
- Utilized an in-silico tumor microenvironment model including tumor layer, vasculature, interstitial fluid pressure, and drug diffusion.
- Developed a deep learning framework employing multiple convolutional neural network submodels.
- Predicted future tumor microenvironment maps and tumor cell density.
Main Results:
- The model achieved high accuracy in predicting tumor microenvironment maps seven days ahead, with an average structural similarity score of 0.973 and peak signal-to-noise ratio of 35.41.
- Predicted tumor cell density at day 7 showed a mean absolute percentage error of [Formula: see text].
- Demonstrated the capability of deep learning to simultaneously capture tumor growth and drug response.
Conclusions:
- The developed deep learning model shows promise for predicting chemotherapy response and optimizing treatment strategies.
- This approach can facilitate personalized medicine by enabling patient-specific treatment schedule decisions.
- Further research can build upon this proof-of-concept for enhanced anticancer drug delivery and efficacy.
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