The INFLUENCE 3.0 model: updated predictions of locoregional recurrence and contralateral breast cancer, now also suitable for patients treated with neoadjuvant systemic therapy

Background: Individual risk prediction of 5-year locoregional recurrence (LRR) and contralateral breast cancer (CBC) supports decisions regarding personalised surveillance. The previously developed INFLUENCE tool was rebuild, including a recent population and patients who received neoadjuvant systemic therapy (NST). Methods: Women, surgically treated for nonmetastatic breast cancer, diagnosed between 2012 and 2016, were selected from the Netherlands Cancer Registry. Cox regression with restricted cubic splines was compared to Random Survival Forest (RSF) to predict five-year LRR and CBC risks. Separate models were developed for NST patients. Discrimination and calibration were assessed by 100x bootstrap resampling. Results: In the non-NST and NST group, 49,631 and 10,154 patients were included, respectively. Age, mode of detection, histology, sublocalisation, grade, pT, pN, hormonal receptor status ± endocrine treatment, HER2 status ± targeted treatment, surgery ± immediate reconstruction ± radiation therapy, and chemotherapy were significant predictors for LRR and/or CBC in non-NST patients. For NST patients this was similar, but excluding (y)pT and (y)pN status, and including presence of ductal carcinoma in situ, axillary lymph node dissection and pathologic complete response. For non-NST patients, the Cox and RSF models were integrated in the online tool with 5-year AUCs of 0.77 (95%CI:0.77–0.77) and 0.68 (95%CI:0.67–0.68)] for LRR and CBC prediction, respectively. For NST patients, the RSF model performed best (AUCs 0.77 (95%CI:0.76–0.78) and 0.73 (95%CI:0.69–0.76) for LRR and CBC, respectively). Regarding calibration, observed-predicted differences were all <1 %. Conclusion: This INFLUENCE 3.0 models showed moderate performance in LRR and CBC prediction. The models have been made available as online tool to enable clinical decision support regarding personalised follow-up.