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

M C Van Maaren; T A Hueting; D J P van Uden; M van Hezewijk; L de Munck; M A M Mureau; P A Seegers; Q J M Voorham; M K Schmidt; G S Sonke; C G M Groothuis-Oudshoorn; S Siesling; NABOR project group

doi:10.1016/j.breast.2024.103829

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

Breast. 2024 Oct 28:79:103829. doi: 10.1016/j.breast.2024.103829. Online ahead of print.

Authors

Affiliations

¹ Department of Health Technology and Services Research, Technical Medical Centre, University of Twente, Enschede, the Netherlands; Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, the Netherlands. Electronic address: m.c.vanmaaren@utwente.nl.
² Evidencio Medical Decision Support, Haaksbergen, the Netherlands.
³ Department of Surgical Oncology, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands.
⁴ Radiotherapiegroep, Institution for Radiation Oncology, Arnhem, the Netherlands.
⁵ Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, the Netherlands.
⁶ Department of Plastic and Reconstructive Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁷ Palga Foundation, Houten, the Netherlands.
⁸ Division of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, the Netherlands.
⁹ Department of Medical Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, the Netherlands.
¹⁰ Department of Health Technology and Services Research, Technical Medical Centre, University of Twente, Enschede, the Netherlands.
¹¹ Department of Health Technology and Services Research, Technical Medical Centre, University of Twente, Enschede, the Netherlands; Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, the Netherlands.

Abstract

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.

Keywords: Breast cancer; Contralateral breast cancer; Follow-up; Locoregional recurrence; Prediction; Surveillance.