Prediction of Overall Disease Burden in (y)pN1 Breast Cancer Using Knowledge-Based Machine Learning Model.

Background: We aimed to construct an expert knowledge-based Bayesian network (BN) model for assessing the overall disease burden (ODB) in (y)pN1 breast cancer patients and compare ODB across arms of ongoing trials.

Methods: Utilizing institutional data and expert surveys, we developed a BN model for (y)pN1 breast cancer. Expert-derived probabilities and disability weights for radiotherapy-related benefit (e.g., 7-year disease-free survival [DFS]) and toxicities were integrated into the model. ODB was defined as the sum of disability weights multiplied by probabilities. In silico predictions were conducted for Alliance A011202, PORT-N1, RAPCHEM, and RT-CHARM trials, comparing ODB, 7-year DFS, and side effects.

Results: In the Alliance A011202 trial, 7-year DFS was 80.1% in both arms. Axillary lymph node dissection led to higher clinical lymphedema and ODB compared to sentinel lymph node biopsy with full regional nodal irradiation (RNI). In the PORT-N1 trial, the control arm (whole-breast irradiation [WBI] with RNI or post-mastectomy radiotherapy [PMRT]) had an ODB of 0.254, while the experimental arm (WBI alone or no PMRT) had an ODB of 0.255. In the RAPCHEM trial, the radiotherapy field did not impact the 7-year DFS in ypN1 patients. However, there was a mild ODB increase with a larger irradiation field. In the RT-CHARM trial, we identified factors associated with the major complication rate, which ranged from 18.3% to 22.1%.

Conclusions: The expert knowledge-based BN model predicted ongoing trial outcomes, validating reported results and assumptions. In addition, the model demonstrated the ODB in different arms, with an emphasis on quality of life.