Science Philanthropy / Gustave Roussy
PREVALUNG: Personalized lung cancer risk assessment leading to stratified Interception
Cancer continues to exert a heavy toll after cardiovascular diseases (CVD), accounting for nearly 10 million deaths worldwide in 2020, and nearly one in six deaths. Europe accounts for 22.8% of the total cancer cases and 19.6% of the cancer deaths, although it represents 9.7% of the global population. Lung cancer (LC) is the leading cause of cancer mortality in the world. Over the last 2 decades, sex-based LC incidence disparities have increased, with higher incidence in females, despite lower tobacco use among them. Three years relative survival rates after the diagnosis of LC have improved from 9% in the 1990s up to 18% (peaking to 30% in PDL-1high LC) in 2021 with the advent of targeted and immunotherapies, but remain poor. Hence, prevention and early detection of LC became a worldwide priority. Two major randomized clinical trials conducted by investigators of this consortium showed that low dose computed tomography (LDCT) based- LC screening can significantly reduce LC mortality by 8-26% for men and 26-61% in women. Results from the National Lung Screening trial (NLST) indicated that the risk for LC incidence and mortality was 3-4 times higher for those with a positive versus negative baseline screen. Similarly, the NELSON trial concluded that the 5.5-year risk for screen-detected LC was 1.0% and 48.3% for those with a negative and positive baseline screening, respectively. While 70% of all clinical cases are detected at an advanced stage, about 55% of all cases in the LDCT arm of NLST and NELSON were detected in stages I or II. Risk assessment to advise LDCT LC screening program represents an unmet medical need.
- Validate in both retrospective biobanks and large prospective cohorts, classifiers representing four functional drivers of chronic inflammation detecting CVD individuals pre-symptomatic and at early stages of lung carcinogenesis: this will allow to implement patient stratification for preventive interventions based on dysmetabolism, innate immunosuppression, clonal hematopoiesis or gut microbiota dysbiosis (4 main drivers).
- Demonstrate the actionability of such biomarkers: develop and test specific interceptive measures for each of the 4 main drivers of inflammation using food supplements or pharmacological agents (on the top of diet and lifestyle modifications) to return to homeostasis
Carolina Alves Costa Silva