NEW YORK – Researchers across three cancer centers in North Carolina, South Carolina, and Virginia have established a consortium to address race-based disparities in lung cancer screening, biobanking, and genomic testing.
The effort, dubbed Southeastern Consortium for Lung Cancer Health Equity, or SC3, is supported by a $3 million grant, sponsored by Bristol Myers Squibb and part of the charitable organization Stand Up To Cancer's larger Health Equity Initiative. Researchers from the Virginia Commonwealth University (VCU) Massey Cancer Center, Medical University of South Carolina (MUSC) Hollings Cancer Center, and University of North Carolina (UNC) Lineberger Comprehensive Cancer Center are involved in the consortium.
"We've come up with a very innovative model," VCU Massey Director Robert Winn said, explaining how the consortium is focused on breaking down silos that too often set apart genetic and biological research from social and population-based research. Winn has long been a proponent of connecting these research fields to move the needle on cancer disparities.
Through what the researchers are calling a "cell-to-society" approach, SC3 will focus initially on two areas: improving lung cancer screening rates among the Black population in the region and collecting biospecimens and clinical data to create what they hope will be the largest databank to date of Black Americans with lung cancer and those at risk for the disease.
SC3 sought to build lung cancer screening and research resources in North Carolina, South Carolina, and Virginia because these tobacco-producing states are simultaneously home to one of the largest Black communities and one of the largest smoking populations in the nation. The region is also straddled with deep race-based cancer incidence and mortality disparities including unequal access to screening and biomarker testing and disproportionately low Black patient representation in drug trials and biorepositories.
Biobanking, inclusive risk scores
The researchers hope the data and biospecimens they collect in their repository will advance genetic and genomic research in the Black population for years to come, but their first goal is to generate a lung cancer risk score that includes data from more Black individuals, thereby more accurately assessing risk for the population.
"There's been a 10-SNP genetic risk score that has been used almost exclusively on predominantly white populations," Winn said, explaining how the pervasive lack of diversity in genetic and genomic databases for years has resulted in cancer risk scores that don't necessarily hold up in Black populations. "This will be the first time we've ever used that as a genetic risk score in this population. … We're not only looking to validate, but to tweak it."
Using the data collected through SC3, the researchers plan to generate a composite lung cancer risk score that reflects the Black population. With the saliva and blood samples collected in the biobank, they'll run a 10 single-nucleotide polymorphism (SNP) panel, then combine it with clinical risk scores to create a composite score.
"By this very exercise, we may find out that there are other things that we can tweak that we didn't know about … and we have a powerhouse of scientists who are putting all of their brainpower into figuring out how we can not only validate this model but improve upon it," said Winn.
These scientists, in the hopes of addressing the multifaceted nature of race-based cancer disparities, will collect from research participants a host of data points beyond genetics.
"There are social determinants of health as contributors, and there are biologic contributors and environmental contributors," said Marvella Ford, MUSC Hollings Cancer Center's associate director of cancer disparities and a research team co-leader of one of SC3's projects. "We know that unless we build these translational science teams, we're each only going to be able to address a snippet of the contributors."
The researchers involved in SC3 bring expertise from population health and biology spheres alike and will be collecting information on the barriers hindering equitable screening, testing, and care in addition to the biospecimens for genetic and genomic analyses.
Patient navigators, FQHC partnerships
To build the SC3 biorepository, researchers will first need to reach Black patients and convince them to participate. To accomplish this, each cancer center has partnered with regional federally qualified health centers (FQHCs). VCU Massey will partner with the Capital Area Health Network, Vernon Harris FQHC in Virginia; MUSC Hollings will partner with the Fetter Health Care Network in South Carolina; and UNC Lineberger will partner with the Kintegra FQHC system in North Carolina. Community navigators at the FQHCs will team up with nurse and financial navigators within each cancer center to guide lung cancer patients interested in participating through screening and any subsequent care.
Navigators will help manage financial and transportation issues, facilitate clear communication between patients and care teams, and address fear and mistrust, among other barriers. A database system, called REDCap, will be used to track patients' progress as well as the specific barriers they faced, how the issues were resolved, and how the solutions impacted their outcomes. Other health systems can use the data gathered through the project to replicate the model locally, Ford said.
So far, according to Ford, researchers have found that fear and mistrust of the science and medical establishment are the top barrier to screening and treatment access for the Black population in the region. Ford was surprised by the finding. "I thought it was going to be transportation, but that was second," she said, underscoring that helping patients navigate screening and research participation in this project and truthful communication are crucial to mitigating their fear and mistrust.
The concept of using patient navigators to help address disparities in access to screenings and care is not new, but Ford noted that similar programs have had a tough time taking off in FQHCs, in part because of strapped resources. Navigation interventions like the ones built into SC3's plan require significant financial investment and manpower.
"If we had gone to [the FQHCs] and asked them to take on the role of navigating patients to the cancer centers for screening without giving them the resources to do so, that would not have been a good faith partnership," Ford said, noting that after two years of dealing with the disproportionate impact of the COVID-19 pandemic in these communities, local providers and FQHCs are already stretched thin.
The SC3 consortium has also brought in patient advocates to help craft culturally sensitive communication and educational materials, which are critical for bringing patients on to participate in the biobanking part of the initiative.
"There is this myth that when you're dealing with African American communities, they won't participate in studies, nor will they give up samples," said Winn, who was involved in the early days of the National Institutes of Health's All of Us Research Program, an initiative to sequence 1 million individuals and improve understanding of human health and disease. Participants can also decide to learn through the project their own genetic risk for certain diseases and likelihood of responding to certain drugs.
"What I found out [through All of Us] is that African American men and women … will give you their blood and sputum if you frame why it's important and talk to them about what's going to happen," said Winn, who is himself the first Black director of an NCI-designated comprehensive cancer center.
"What happens is, we typically go and talk our 'doctor-talk' or 'science-talk' to people and then scratch our heads about why they aren't participating," he said. "We should always talk in the language of the community and explain with grace and humility why this [sample collection] will not only help people in the future, but potentially help them if they were to get cancer."
BMS involvement, biomarker testing
Although the initial goals of the SC3 consortium are to improve screening rates in the Black population and build a research biorepository, the program's leaders also hope to improve biomarker test access for lung cancer patients. Biomarker testing has shown to have multiple uses in lung cancer, from early diagnoses to personalized treatment.
"We're hoping to identify markers of early lung cancer, and that ties directly into treatment," Ford said. "The earlier the lung cancer is detected, the sooner we can get patients in and start treating them."
"Biomarker testing now is equivalent to giving people a second chance on life," Winn added. "Having biomarker testing done is no longer an experimental portion; it is standard of care."
Smoking-related lung cancers, of note, have been shown across numerous studies to harbor heavier mutational burdens than non-smoking related lung cancers, and the lung cancer driver mutations with the most established and effective targeted drugs — including EGFR and ALK — are less common in smokers with lung cancer than non-smokers. Accordingly, there is a significant need to identify better biomarkers and treatments for this population.
BMS, the drugmaker sponsoring the SU2C grant supporting SC3, markets the checkpoint inhibitor Opdivo (nivolumab) as a first-line treatment for advanced, PD-L1 positive non-small cell lung cancers that do not harbor EGFR or ALK gene alterations. The company is also evaluating Opdivo across multiple lung cancer trials in earlier treatment lines and in combinations with other agents, such as its investigational LSD1 inhibitor CC-90011 for patients with certain small cell lung cancers.
While SC3 wasn't advanced with a specific goal of adding diversity to BMS' lung cancer trials, the studies and patients could certainly benefit if navigators are successful in encouraging participation in the community. Drugmakers have come under scrutiny for their failure to enroll diverse populations in their drug trials, and ineffective community outreach is often cited as a challenge. Lawmakers are currently considering addressing the issue with the Diverse and Equitable Participation in Clinical Trials, or DEPICT, Act.
Even though the grant funds SC3 for four years, Winn is optimistic that the partnerships already solidified within the SC3 consortium will give the initiative staying power.
"Our ultimate goal between our three institutions is to treat more people with cancer … and not just to give them chemotherapy, but to use the tools we have of molecular-targeted therapy and biomarkers," Winn said. "To deliver that you need to build community trust, not by just going into the community, but by involving the community. That building block of trust allows us to do much better research and have much more of an impact on these communities with our findings."