Abstract

First-line treatments of cancer do not always work, and even when they do, they cure the disease at unequal rates mostly owing to biological and clinical heterogeneity across patients. Accurate prediction of clinical outcome and survival following the treatment can support and expedite the process of comparing alternative treatments. We describe the methodology to dynamically determine remission probabilities for individual patients, as well as their prospects of progression-free survival (PFS). The proposed methodology utilizes the ex vivo drug sensitivity of cancer cells, their immunophenotyping results, and patient information, such as age and breed, in training machine learning (ML) models, as well as the Cox hazards model to predict the probability of clinical remission (CR) or relapse across time for a given patient. We applied the methodology using the three types of data obtained from 242 canine lymphoma patients treated by (L)-CHOP chemotherapy. The results demonstrate substantial enhancement in the predictive accuracy of the ML models by utilizing features from all the three types of data. They also highlight superior performance and utility in predicting survival compared to the conventional stratification method. We believe that the proposed methodology can contribute to improving and personalizing the care of cancer patients.

Highlights

  • Cancer heterogeneity has been extensively reported and studied over the past five decades

  • Three types of data—drug sensitivity (DS), flow cytometry (FC), and patient information (PI)—were obtained for each lymphoma patient included in this study (Figure 1)

  • We developed the machine learning (ML) models for predicting clinical outcomes of canine lymphoma patients treated by (L-)CHOP chemotherapy, which is the standard treatment of choice based on previous clinical trials [23]

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Summary

Introduction

Cancer heterogeneity has been extensively reported and studied over the past five decades. The findings have enabled classification and categorization of tumors into subtypes sharing, for example, the same molecular features such as the overexpression of antigens. Inspired by the latest advances in artificial intelligence (AI) that are effective in dealing with complex systems, researchers began to apply AI, especially machine learning (ML) techniques, to subtyping cancer. Recent advances in computing power have enabled the processing of more complex data such as radiographic images. The latest work in the field began to employ combinations of different data such as MRI and genomics for subtyping tumors as well as predicting survival, with the end goal of assisting and improving treatment choices [7,8,9]

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