Abstract
OBJECTIVE: To implement artificial neural network (ANN) algorithms for noninvasive lymph node staging (NILS) to a decision support tool and facilitate the option to omit surgical axillary staging in breast cancer patients with low-risk of nodal metastasis. METHODS: The NILS tool is a further development of an ANN prototype for the prediction of nodal status. Training and internal validation of the original algorithm included 15 clinical and tumor-related variables from a consecutive cohort of 800 breast cancer cases. The updated NILS tool included 10 top-ranked input variables from the original prototype. A workflow with four ANN pathways was additionally developed to allow different combinations of missing preoperative input values. Predictive performances were assessed by area under the receiver operating characteristics curves (AUC) and sensitivity/specificity values at defined cut-points. Clinical utility was presented by estimating possible sentinel lymph node biopsy (SLNB) reduction rates. The principles of user-centered design were applied to develop an interactive web-interface to predict the patient's probability of healthy lymph nodes. A technical validation of the interface was performed using data from 100 test patients selected to cover all combinations of missing histopathological input values. RESULTS: ANN algorithms for the prediction of nodal status have been implemented into the web-based NILS tool for personalized, noninvasive nodal staging in breast cancer. The estimated probability of healthy lymph nodes using the interface showed a complete concordance with estimations from the reference algorithm except in two cases that had been wrongly included (ineligible for the technical validation). NILS predictive performance to distinguish node-negative from node-positive disease, also with missing values, displayed AUC ranged from 0.718 (95% CI, 0.687-0.748) to 0.735 (95% CI, 0.704-0.764), with good calibration. Sensitivity 90% and specificity 34% were demonstrated. The potential to abstain from axillary surgery was observed in 26% of patients using the NILS tool, acknowledging a false negative rate of 10%, which is clinically accepted for the standard SLNB technique. CONCLUSIONS: The implementation of NILS into a web-interface are expected to provide the health care with decision support and facilitate preoperative identification of patients who could be good candidates to avoid unnecessary surgical axillary staging.