Multi-omics integrative modelling for stereotactic body radiotherapy in early-stage non-small cell lung cancer: clinical trial protocol of the MONDRIAN study.

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).

Infectious diseases and social distancing under state-dependent probabilities.

We analyze the implications of infectious diseases and social distancing in an extended SIS framework to allow for the presence of stochastic shocks with state dependent probabilities. Random shocks give rise to the diffusion of a new strain of the disease which affects both the number of infectives and the average biological characteristics of the pathogen causing the disease. The probability of such shock realizations changes with the level of disease prevalence and we analyze how the properties of the state-dependent probability function affect the long run epidemiological outcome which is characterized by an invariant probability distribution supported on a range of positive prevalence levels. We show that social distancing reduces the size of the support of the steady state distribution decreasing thus the variability of disease prevalence, but in so doing it also shifts the support rightward allowing eventually for more infectives than in an uncontrolled framework. Nevertheless, social distancing is an effective control measure since it concentrates most of the mass of the distribution toward the lower extreme of its support.