Grant Number:	1U01CA308978-01 Interpret this number
Primary Investigator:	Cerhan, James
Organization:	Mayo Clinic Rochester
Project Title:	The Lymphoma Epidemiology of Outcomes (LEO) Cohort Study
Fiscal Year:	2026

In 2025, an estimated 80,350 people in the US will be diagnosed with non-Hodgkin lymphoma (NHL), and 19,390 will die from this cancer. NHL survival rates began improving in the 1990s with the advent of improved treatment strategies, leading to the current 5-year survival rate of 74%. These trends led to a growth in the number of NHL survivors, estimated at 808,413 as of January 1, 2024. To address the unmet health needs of this patient population, in 2002 we established the Molecular Epidemiology Resource, which was expanded nationally in 2015 as Lymphoma Epidemiology of Outcomes (LEO) cohort study. LEO enrollment is currently over 17,000 NHL participants (and >19,000 at the start of this grant), with <1% loss to follow-up and 73% alive and in follow-up. LEO abstracts pathology, demographic, address (to derive neighborhood variables), clinical, treatment and outcome data, and collects patient reported epidemiologic risk factors and quality of life (QoL) outcomes. Importantly, LEO enrollment (2015-2020) had similar distributions of participants by demographic and NHL subtype as the national Surveillance, Epidemiology, and End Results (SEER) registry, making LEO the largest and most representative prospective cohort of lymphoma outcomes reflecting NHL patients in the US. Cumulatively, LEO has supported numerous publications, prior and ongoing grants (NIH, foundation, industry), NCI Supplements, and career development awards. Under this funding mechanism, we propose to use the LEO cohort to drive the next generation of NHL prognosis and survivorship studies, define patient subgroups with poor outcomes in need of clinical trials, and identify unmet needs for long-term survivors. We will develop and validate novel clinical risk prediction models across NHL subtypes utilizing both the extensive existing LEO data and proposed ongoing follow-up. Our aims are: 1) To develop, validate, and disseminate new clinical models for early treatment failure (ETF) across the major NHL subtypes; 2) To define the intermediate and long-term outcomes and longitudinal QoL in NHL patients who achieve a functional cure with standard of care (SOC) management; and 3) To evaluate the impact of rurality and social determinants of health (SDOH) using individual and area-level measures on NHL outcomes in the context of clinical and lifestyle factors, comorbidities, frailty and QoL. To achieve these aims, we will leverage existing data from the LEO cohort and further annotate the cohort with new data on outcomes, longitudinal and pulse surveys, and external data sources. Maintenance of the cohort also will provide outcomes for ongoing and new studies utilizing the LEO biorepository, and completion of our proposed aims will provide validated clinical models to integrate with biologic studies. This proposal addresses key research questions in outcomes and survivorship for patients with NHL (an understudied cancer) and in understudied populations, including rural and adolescent and young adults. Our results will directly inform clinical guidelines and risk assessment, and support development of novel studies and interventions to improve the outcomes of NHL patients.