Who can benefit from postmastectomy radiotherapy among HR+/HER2- T1-2 N1M0 breast cancer patients? An explainable machine learning mortality prediction based approach.

Objective: The necessity of postmastectomy radiotherapy(PMRT) for patients with HR+/HER2 T1-2 N1M0 breast cancer remains controversial. We want to use explainable machine learning to learn the feature importance of the patients and identify the subgroup of the patients who may benefit from the PMRT. Additionally, develop tools to provide guidance to the doctors.

Methods: In this study, we trained and validated 2 machine learning survival models: deep learning neural network and Cox proportional hazard model. The training dataset consisted of 35,347 patients with HR+/HER2- T1-2 N1M0 breast cancer who received mastectomies from the SEER database from 2013 to 2018. The performance of survival models were assessed using a concordance index (c-index).Then we did subgroup analysis to identify the subgroup who could benefit from PMRT. We also analyzed the global feature importance for the model and individual feature importance for individual survival prediction. Finally, we developed a Cloud-based recommendation system for PMRT to visualize the survival curve of each treatment plan and deployed it on the Internet.

Results: A total of 35,347 patients were included in this study. We identified that radiotherapy improved the OS in patients with tumor size >14mm and age older than 54: 5-year OS rates of 91.9 versus 87.2% (radio vs. nonradio, P <0.001) and cohort with tumor size >14mm and grade worse than well-differentiated, 5-year OS rates of 90.8 versus 82.3% (radio vs. nonradio, P <0.001).The deep learning network performed more stably and accurately in predicting patients survival than the random survival forest and Cox proportional hazard model on the internal test dataset (C-index=0.776 vs 0.641) and in the external validation(C-index=0.769 vs 0.650).Besides, the deep learning model identified several key factors that significantly influence patient survival, including tumor size, examined regional nodes, age at 45-49 years old and positive regional nodes (PRN).

Conclusion: Patients with tumor size >14mm and age older than 54 and cohort with tumor size >14mm and grade worse than well-differentiated could benefit from the PMRT. The deep learning network performed more stably and accurately in predicting patients survival than Cox proportional hazard model on the internal test. Besides, tumor size, examined regional nodes, age at 45-49 years old and PRN are the most significant factors to the overall survival (OS).