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

In this project FRRB finances the Coordinator: ASST Spedali Civili Brescia - ASSTBS. The Principal Investigator responsible of the project is Dr. Paolo Bossi.

FRRB also finances partner number 1: Istituto Europeo di Oncologia - IEO. The Principal Investigator is Dr. Susanna Chiocca

Pathology of interest: Laryngeal and hypopharyngeal cancer
Area of research: Oncology
Start date:  15th June 2021
End date:  14th June 2024
Funding:  € 481.700,00
Project partners:   - ASST Spedali Civili Brescia - ASSTBS 
  - Istituto Europeo di Oncologia - IEO 
  - Bellvitge Biomedical Research Institute (IDIBELL), ICO (Catalan Institute of Oncology)
  - University of Leipzig - ULeipzig
  - University of Oslo - UiO 
  - Athens Technology Center Anonymi Biomichaniki Emporiki kai Techniki Etaireia Efarmgon Ypsilis Technologias - ATC


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; they 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.  The 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.

The project will implement ethical and legal frameworks for FAIR data management and transnational data exchange.

A cost-utility analysis of personalized treatment in LAR/HYPO cancer integrating QoL measures will assess sustainability of PM in clinical setting. Project entities have involved patients’ associations for QoL measurement, evaluation of the approach and wide dissemination of study results.