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Using transfer learning on whole slide images to predict tumor mutational burden in bladder cancer patients

Hongming Xu, Sunho Park, Sung Hak Lee, Tae Hyun Hwang
doi: https://doi.org/10.1101/554527
Hongming Xu
1Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44195, USA
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Sunho Park
1Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44195, USA
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Sung Hak Lee
2Department of Hospital Pathology, Seoul St.Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
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Tae Hyun Hwang
1Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44195, USA
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  • For correspondence: hwangt@ccf.org
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Abstract.

The tumor mutational burden (TMB) is a genomic biomarker, which can help in identifying patients most likely to benefit from immunotherapy across a wide range of tumor types including bladder cancer. DNA sequencing, such as whole exome sequencing (WES) is typically used to determine the number of acquired mutations in the tumor. However, WES is expensive, time consuming and not applicable to all patients, and hence it is difficult to be incorporated into clinical practice. This study investigates the feasibility to predict bladder cancer patients TMB by using histological image features.

We design an automated whole slide image analysis pipeline that predicts bladder cancer patient TMB via histological features extracted by using transfer learning on deep convolutional networks. The designed pipeline is evaluated to publicly available large histopathology image dataset for a cohort of 253 patients with bladder cancer obtained from The Cancer Genome Atlas (TCGA) project. Experimental results show that our technique provides over 73% classification accuracy, and an area under the receiver operating characteristic curve of 0.75 in distinguishing low and high TMB patients. In addition, it is found that the predicted low and high TMB patients have statistically different survivals, with the p value of 0.047. Our results suggest that bladder cancer patient TMB is predictable by using histological image features derived from digitized H&E slides. Our method is extensible to histopathology images of other organs for predicting patient clinical outcomes.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 19, 2019.
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Using transfer learning on whole slide images to predict tumor mutational burden in bladder cancer patients
Hongming Xu, Sunho Park, Sung Hak Lee, Tae Hyun Hwang
bioRxiv 554527; doi: https://doi.org/10.1101/554527
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Using transfer learning on whole slide images to predict tumor mutational burden in bladder cancer patients
Hongming Xu, Sunho Park, Sung Hak Lee, Tae Hyun Hwang
bioRxiv 554527; doi: https://doi.org/10.1101/554527

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