Preserve

Principal investigator: Carla Rognoni (CeRGAS) 

Team UB/Cergas: Rosanna Tarricone 

Partners: ASST Spedali Civili Brescia (ASSTBS), Istituto Europeo di Oncologia (IEO), Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), University of Leipzig (Uleipzig), University of Oslo (UiO), Athens Technology Center Anonymi Biomichaniki Emporiki kai Techniki Etaireia Efarmgon Ypsilis Technologias (ATC); Bocconi University (subcontractor of the University of Leipzig) 

Sponsor: ERAPerMed Joint Transnational Call for proposals “Multidisciplinary research projects on personalized medicine – PRE-/CLINICAL RESEARCH, BIG DATA AND ICT, IMPLEMENTATION AND USER’S PERSPECTIVE” (ERA Net Grant 779282) 

Duration: 36 months (2021-ongoing) 

Abstract: 

Locally advanced laryngeal (LAR) and hypopharyngeal (HYPO) squamous cell carcinoma may be treated with induction chemotherapy followed (in case of response > 50%) by radiotherapy for larynx preservation as an alternative to total laryngectomy. However, not all patients benefit from larynx preservation strategy and up to 30-40% have a total laryngectomy. We miss biomarkers for patient selection and treatment optimization, as well as for the exploitation of new therapeutic options. 

The current proposal will personalize patients’ management to increase the rate of larynx preservation 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 induction chemotherapy and to define alternative pathways to be tackled in patients non-responding to induction chemotherapy. 

Preserve will collect and integrate a large series of clinically annotated data from LAR/HYPO cancer patients treated with induction chemotherapy followed by radiotherapy, to assess a multi-omic signature of response to induction chemotherapy and to define alternative pathways. Transcriptomic analysis, molecular data on cell lines and radiomic evaluation will be main components of this signature. 

The predictive models, integrated into an intuitive clinical decision support system, will be validated in a phase II feasibility trial with 49 patients treated with tailored systemic induction treatments, according to the discovered signature, providing evidence for clinical translation. Main endpoints of the trial will be: overall response rate to tailored induction treatment in at least 80% of the patients, with overall grade > 3 toxicities in less than 20% of the patients. A cost-utility analysis of the personalized treatment in LAR/HYPO cancer integrating QoL measures will assess sustainability of personalized medicine in clinical setting.  Patient associations will be involved for QoL measurement, evaluation of research approach and wide dissemination of study results. 

Material produced and publications: Is precision medicine the solution to increase organ preservation in laryngeal/hypopharyngeal cancer? A position paper by Preserve Research Group (in preparation) 

Dissemination:

Consensus Conference on Larynx Preservation for Laryngeal/Hypopharyngeal Squamous Cell Carcinoma,