Causal multi-modal AI for personalized chemosensitivity prediction

arXiv:2609.13567v1 Announce Type: new Abstract: Chemotherapy improves survival for some patients with breast cancer, but doctors cannot reliably predict who. Current guidelines rely on recurrence scores as a proxy for treatment benefit, which may contribute to the overprescription of chemotherapy. Here we present a causal multi-modal AI model that predicts personalized chemosensitivity using routinely collected pathology and clinical information. We developed our model on a multi-national dataset of 9,141 patients (twelve cohorts, nine countries) and evaluated it on another 1,994 patients (five cohorts, three countries). The model generated treatment-specific recurrence probabilities for each patient, with near-perfect calibration and strong prognostic discrimination across both 5- and 10-year follow-up horizons. Moreover, its chemotherapy benefit predictions demonstrated robust predictive performance, and out-performed existing recurrence-score-based tests. Compared to the standard of care, using the model to support personally tailored therapeutic decisions could reduce the number of patients receiving chemotherapy by 30% while achieving the same recurrence-free rate. Tumors predicted to be highly chemosensitive displayed concordant molecular and morphological programs of proliferation, cell cycle progression, and replication stress. The model's predictive capabilities transferred zero-shot to non-breast cancers, indicating our causal multi-modal AI approach may provide a universal strategy to predict treatment outcomes across cancer types.

Authors:Dhruva Biswas, Jeroen Berrevoets, Alec McClean, Linus Bao, Jungkyu Park, Ken G. Zeng, Joseph Cappadona, Cerise Tang, Chuwen Liu, Bartosz Machura, Yin Wu, Valerie Speirs, Hatem Soliman, Rohit Bhargava, Sheheryar Kabraji, Thaer Khoury, David Page, Brian Piening, Carlo Bifulco, Claudia Meurs, Pieter Westenend, Sylvie Chabaud, Jerome Lemonnier, Paul H. Cottu, Florence Dalenc, Fabrice Andre, Frederique Madeleine Penault-Llorca, Thomas Bachelot, Frederick Howard, Francisco J. Esteva, Kevin Kalinsky, Lajos Pusztai, Jan Witowski, Krzysztof J. Geras

Abstract:Chemotherapy improves survival for some patients with breast cancer, but doctors cannot reliably predict who. Current guidelines rely on recurrence scores as a proxy for treatment benefit, which may contribute to the overprescription of chemotherapy. Here we present a causal multi-modal AI model that predicts personalized chemosensitivity using routinely collected pathology and clinical information. We developed our model on a multi-national dataset of 9,141 patients (twelve cohorts, nine countries) and evaluated it on another 1,994 patients (five cohorts, three countries). The model generated treatment-specific recurrence probabilities for each patient, with near-perfect calibration and strong prognostic discrimination across both 5- and 10-year follow-up horizons. Moreover, its chemotherapy benefit predictions demonstrated robust predictive performance, and out-performed existing recurrence-score-based tests. Compared to the standard of care, using the model to support personally tailored therapeutic decisions could reduce the number of patients receiving chemotherapy by 30% while achieving the same recurrence-free rate. Tumors predicted to be highly chemosensitive displayed concordant molecular and morphological programs of proliferation, cell cycle progression, and replication stress. The model's predictive capabilities transferred zero-shot to non-breast cancers, indicating our causal multi-modal AI approach may provide a universal strategy to predict treatment outcomes across cancer types.

Artificial Intelligence (cs.AI)

arXiv:2609.13567 [cs.AI]

(or arXiv:2609.13567v1 [cs.AI] for this version)

https://doi.org/10.48550/arXiv.2609.13567 arXiv-issued DOI via DataCite (pending registration)

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Causal multi-modal AI for personalized chemosensitivity prediction

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