METASTRA represents a formidable undertaking funded by the European Union through the Horizon Europe program, specifically the "Tools and Technologies for a Healthy Society" call. This visionary project is orchestrated under the auspices of the University of Bologna, and it brings together a consortium of 15 prominent institutions spanning diverse European Member States, with a substantial financial allocation amounting to 6.7 million EUR over a span of five years. Our meticulously crafted research agenda, underpinned by a multidisciplinary approach, is poised to make significant strides in the realm of medical research.

Within the context of European healthcare, advances in early cancer detection and therapeutic interventions have led to notable improvements in the life expectancy of cancer patients. Nevertheless, approximately 1 million individuals confront the formidable challenge of secondary tumour progression, with bone metastases afflicting a substantial proportion—ranging from 30% to 70%—of this demographic. These metastases precipitate a significant reduction in spinal load-bearing capacity and, alarmingly, give rise to fractures in approximately 30% of cases. The current clinical landscape offers limited, often uncertain, choices for practitioners, chiefly involving surgical interventions for spinal stabilisation or the acceptance of an elevated risk of fractures. These decisions, fraught with ambiguity, bear profound implications for patient well-being and the trajectory of cancer treatment.

The existing clinical protocols for fracture risk assessment predominantly rely on scoring systems entrenched in radiographic imaging, with scant regard for the intricacies of local biomechanical dynamics. This approach, regrettably, yields precise surgical indications in merely 40% of cases, underscoring the exigency for a paradigm shift towards more precise risk quantification and patient stratification methodologies.

METASTRA aspires to bridge this critical gap by pioneering innovative computational models that harness the power of Artificial Intelligence (AI) and Physiology-based (VPH) mechanical principles. These computational models are meticulously trained using an expansive dataset that encompasses clinical data.

To facilitate clinical decision-making within the research and academic context, METASTRA envisages integrating these computational models into an accessible Decision Support System (DSS) tailored to meet regulatory standards and future commercialization prospects. Our innovative guidelines for patient stratification and management hold the promise of reducing the rate of uncertain diagnoses from the prevailing 60% to a mere 20% of cases. This transformative leap forward is poised to alleviate patient suffering and potentially yield annual healthcare cost savings of up to 2.4 billion euros.