Project: AI for new signatures and models for tailored organ preservation approaches in laryngeal and hypopharyngeal cancer.

Acronym	Preserve (Reference Number: ERAPERMED2020-283)
Project Topic	Locally advanced laryngeal (LAR) and hypopharyngeal (HYPO) squamous cell carcinoma may be treated with induction chemotherapy (IC) followed (in case of response > 50%) by radiotherapy (RT) for larynx preservation (LP) as an alternative to total laryngectomy (TL). However, not all patients (pts) benefit from LP strategy and up to 30-40% have a TL; we miss biomarkers for pts selection and treatment optimization, as well as for the exploitation of new therapeutic options. The current proposal will personalize pts management to increase the rate of LP in LAR/HYPO cancer, by maximizing the probability of response to induction treatment. Main objectives are to assess a multimodal signature predictive of response to IC and to define alternative pathways to be tackled in pts non-responding to IC. Preserve will collect and integrate a large series of clinically annotated data from LAR/HYPO cancer pts treated with IC followed by RT, to assess a multi-omic signature of response to IC and to define alternative pathways. Transcriptomic analysis, molecular data on cell lines and radiomic evaluation will be main components of this signature. Our predictive models integrated into an intuitive clinical decision support system will be validated in a phase II feasibility trial with 49 pts treated with tailored systemic induction treatments, according to the discovered signature, providing evidence for clinical translation. Main endpoints of the trial are: overall response rate to tailored induction treatment in at least 80% of the pts, with overall grade > 3 toxicities in less than 20% of the pts. We will implement ethical and legal frameworks for FAIR data management and transnational data exchange. A cost-utility analysis of our personalized treatment in LAR/HYPO cancer integrating QoL measures will assess sustainability of PM in clinical setting. We have involved patients’ associations for QoL measurement, evaluation of our approach and wide dissemination of study results.
Network	ERA PerMed
Call	3rd Joint Transnational Call for Proposals (2020)

Project partner

Number	Name	Role	Country
1	ASST Spedali Civili Brescia	Coordinator	Italy
2	Istituto Europeo di Oncologia - IEO	Partner	Italy
3	Bellvitge Biomedical Research	Partner	Spain
4	University of Leipzig	Partner	Germany
5	University of Oslo	Partner	Norway
6	Athens Technology Center Anonymi Biomichaniki Emporiki kai Techniki Etaireia Efarmgon Ypsilis Technologias -	Partner	Greece