Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer : a report of the international immuno-oncology biomarker working group on breast cancer

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Authors

Thagaard, Jeppe
Broeckx, Glenn
Page, David B.
Jahangir, Chowdhury Arif
Verbandt, Sara
Kos, Zuzana
Gupta, Rajarsi R.
Khiroya, Reena
Abduljabbar, Khalid
Haab, Gabriela Acosta

Journal Title

Journal ISSN

Volume Title

Publisher

Wiley

Abstract

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer.

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Keywords

Deep learning, Machine learning, Digital pathology, Guidelines, Image analysis, Pitfalls, Prognostic biomarker, Triple-negative breast cancer, Tumor-infiltrating lymphocytes, SDG-03: Good health and well-being, SDG-09: Industry, innovation and infrastructure, Tumor-infiltrating lymphocytes (TILs)

Sustainable Development Goals

SDG-03:Good heatlh and well-being
SDG-09: Industry, innovation and infrastructure

Citation

Thagaard, J., Broeckx, G., Page, C.B. et al. 2023, 'Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer : a report of the international immuno-oncology biomarker working group on breast cancer', Journal of Pathology, vol. 260, pp. 498-513. DOI: 10.1002/path.6155