Multi-omics integrative modelling for stereotactic body radiotherapy in early-stage non-small cell lung cancer: clinical trial protocol of the MONDRIAN study
Stefania Volpe,
Mattia Zaffaroni,
Gaia Piperno,
Maria Giulia Vincini,
Maria Alessia Zerella,
Federico Mastroleo,
Federica Cattani,
Cristiana Iuliana Fodor,
Federica Bellerba,
Tiziana Bonaldi,
Giuseppina Bonizzi,
Francesco Ceci,
Marta Cremonesi,
Nicola Fusco,
Sara Gandini,
Cristina Garibaldi,
Davide La Torre,
Roberta Noberini,
Giuseppe Petralia,
Lorenzo Spaggiari,
Konstantinos Venetis,
Roberto Orecchia,
Monica Casiraghi,
Barbara Alicja Jereczek-Fossa
Affiliations
Stefania Volpe
Division of Radiation Oncology, IEO European Institute of Oncology IRCCS
Mattia Zaffaroni
Division of Radiation Oncology, IEO European Institute of Oncology IRCCS
Gaia Piperno
Division of Radiation Oncology, IEO European Institute of Oncology IRCCS
Maria Giulia Vincini
Division of Radiation Oncology, IEO European Institute of Oncology IRCCS
Maria Alessia Zerella
Division of Radiation Oncology, IEO European Institute of Oncology IRCCS
Federico Mastroleo
Division of Radiation Oncology, IEO European Institute of Oncology IRCCS
Federica Cattani
Unit of Medical Physics, European Institute of Oncology (IEO) IRCCS
Cristiana Iuliana Fodor
Division of Radiation Oncology, IEO European Institute of Oncology IRCCS
Federica Bellerba
Department of Experimental Oncology, IEO European Institute of Oncology IRCCS
Tiziana Bonaldi
Department of Oncology and Hemato-Oncology, University of Milan
Giuseppina Bonizzi
Biobank for Translational and Digital Medicine, IEO, European Institute of Oncology IRCCS
Francesco Ceci
Department of Oncology and Hemato-Oncology, University of Milan
Marta Cremonesi
Unit of Radiation Research, IEO European Institute of Oncology, IRCCS
Nicola Fusco
Department of Oncology and Hemato-Oncology, University of Milan
Sara Gandini
Department of Experimental Oncology, IEO European Institute of Oncology IRCCS
Cristina Garibaldi
Unit of Radiation Research, IEO European Institute of Oncology, IRCCS
Davide La Torre
Department of Oncology and Hemato-Oncology, University of Milan
Roberta Noberini
Department of Experimental Oncology, IEO European Institute of Oncology IRCCS
Giuseppe Petralia
Department of Oncology and Hemato-Oncology, University of Milan
Lorenzo Spaggiari
Department of Oncology and Hemato-Oncology, University of Milan
Konstantinos Venetis
Unit of Radiation Research, IEO European Institute of Oncology, IRCCS
Roberto Orecchia
Scientific Directorate, IEO European Institute of Oncology IRCCS
Monica Casiraghi
Department of Oncology and Hemato-Oncology, University of Milan
Barbara Alicja Jereczek-Fossa
Division of Radiation Oncology, IEO European Institute of Oncology IRCCS
Abstract Background Currently, main treatment strategies for early-stage non-small cell lung cancer (ES-NSCLC) disease are surgery or stereotactic body radiation therapy (SBRT), with successful local control rates for both approaches. However, regional and distant failure remain critical in SBRT, and it is paramount to identify predictive factors of response to identify high-risk patients who may benefit from more aggressive approaches. The main endpoint of the MONDRIAN trial is to identify multi-omic biomarkers of SBRT response integrating information from the individual fields of radiomics, genomics and proteomics. Methods MONDRIAN is a prospective observational explorative cohort clinical study, with a data-driven, bottom-up approach. It is expected to enroll 100 ES-NSCLC SBRT candidates treated at an Italian tertiary cancer center with well-recognized expertise in SBRT and thoracic surgery. To identify predictors specific to SBRT, MONDRIAN will include data from 200 patients treated with surgery, in a 1:2 ratio, with comparable clinical characteristics. The project will have an overall expected duration of 60 months, and will be structured into five main tasks: (i) Clinical Study; (ii) Imaging/ Radiomic Study, (iii) Gene Expression Study, (iv) Proteomic Study, (v) Integrative Model Building. Discussion Thanks to its multi-disciplinary nature, MONDRIAN is expected to provide the opportunity to characterize ES-NSCLC from a multi-omic perspective, with a Radiation Oncology-oriented focus. Other than contributing to a mechanistic understanding of the disease, the study will assist the identification of high-risk patients in a largely unexplored clinical setting. Ultimately, this would orient further clinical research efforts on the combination of SBRT and systemic treatments, such as immunotherapy, with the perspective of improving oncological outcomes in this subset of patients. Trial registration The study was prospectively registered at clinicaltrials.gov (NCT05974475).
