When Dan Hannon, 72, received guidance to have part of a lung taken out whether nodules were cancerous or not, he wanted a second opinion to see if he would indeed live the rest of his life without a full set of lungs.

After incidentally learning of a suspicious spot in his lungs while getting imaging to diagnose a kidney stone in 2025, he was advised to get his lungs checked. Several months later, he had a diagnostic PET scan under the care of a Georgia pulmonologist near his home in Buford, Georgia.

Some spots “lit up,” indicating metabolic activity, which often means cancer but may be due to infection or inflammation. He went on to get a bronchoscopy, a minimally invasive procedure using a camera on a thin tube to examine his lungs and obtain biopsy tissue.

He and his wife, Janice, learned the areas that were successfully biopsied were benign, but there were two additional areas the physician couldn’t reach.

Thus came the recommendation for an open surgery to remove the undefined tissue for biopsy. It was also advised that Hannon have a sizeable portion of his affected lung removed while still under anesthesia, regardless of the biopsy results.

That didn’t sit well with the couple, so they drove four hours to Vanderbilt Health in Nashville. Their son had been successfully treated for cancer there in the past.

“The prior lack of knowledge of whether I had cancer or not, and being told I should have surgery and get part of my lung cut out — whether it was cancer or not — was very bothersome,” Hannon said. “I decided to get a second opinion. I wanted all the information I could get to make a good decision, and that’s exactly what’s happened.”

At Vanderbilt Health, a new approach to a difficult diagnosis

The Hannons met with Fabien Maldonado, MD, MSc, professor of Medicine and Thoracic Surgery and director of Interventional Pulmonology at the Vanderbilt Lung Institute. Maldonado told them he was pretty confident he could reach those areas for biopsy using robotic bronchoscopy, the standard of care at Vanderbilt University Hospital.

“Robotic bronchoscopy, combined with cone-beam CT, has transformed the way we do things,” said Maldonado, who holds the Pierre Massion Directorship in Lung Cancer Research. “Ninety-five percent of people with lung nodules don’t have cancer, but for the 5% that do, they need to receive a diagnosis and get treatment as soon as possible.

Inside the robotic bronchoscopy advancing lung care

During a robotic bronchoscopy, physicians use a controller to precisely guide a bronchoscopy tube, which is typically smaller and more flexible than traditional tubes. The additional agility allows access into the lung’s harder-to-reach peripheral structures so biopsy tissue can be obtained. A 3D, high-resolution image of the lung obtained through cone-beam computed tomography (CBCT) is displayed on a monitor to guide the interventional pulmonologist’s progress.

At Vanderbilt Health, the four board-certified interventional pulmonologists who do the robotic bronchoscopies have all completed a fellowship and an additional year of interventional pulmonology training before receiving board certification from the American Association for Bronchology and Interventional Pulmonology.

Oncologist Mohamed Shanshal, MBChB, assistant professor of Medicine, said robotic bronchoscopy significantly improves getting patients the appropriate treatment as soon as possible, reducing their anxiety and improving care.

To expand access to the diagnostic procedure, the Vanderbilt Health Interventional Pulmonology program recently bought two additional robot and CBCT systems, making it one of the largest interventional pulmonology programs in the South. Four state-of-the-art bronchoscopy suites are slated to open later this year.

“This reduces diagnostic uncertainty and helps us move more quickly from suspicion to confirmed diagnosis,” Shanshal said. “Earlier and more accurate tissue diagnosis allows us to initiate treatment sooner, including surgery, targeted therapy, immunotherapy or clinical trials. In lung cancer, timing and adequate tissue for molecular testing are critical to optimizing outcomes.”

Maldonado explained that the Interventional Pulmonology program is a national leader in testing new technologies for safety and results.

“Many new technologies related to lung nodule biopsies have come on the market without any data to prove their benefit,” Maldonado said. “We are doing the randomized controlled trials here to prove whether something new is better than what we’re already doing. We study these technologies carefully and quickly, and within six months to a year, we know if the new is more beneficial and needs to be adopted.”

From uncertainty to action: What Hannon’s biopsy uncovered

For the Hannons, having the assurance that the robotic bronchoscopy would reach the spots in his lung and offer clearer details about their makeup was important.

“With the help of the robot, Dr. Maldonado was able to get what he needed, and it came back as adenocarcinoma,” Hannon said. “He was awesome when he explained his findings and everything we needed to do.”

Hannon has mucinous adenocarcinoma, a rare, non-small cell lung cancer that accounts for 2-10% of all lung adenocarcinomas and is most often found in the outer regions of the lung.

During a return visit to Nashville in late February, Hannon had a pulmonary function test, and met with Konrad Hoetzenecker, MD, PhD, professor of Thoracic Surgery, who will soon surgically remove the cancerous spots, and with Shanshal, his new oncologist.

“We’ve had a fantastic experience at Vanderbilt, and we’ve got a fantastic team of medical professionals we’re working with,” Hannon said. “We’re prepared for surgery and any future treatment because of the consultations we’ve had with Dr. Maldonado, Dr. Hoetzenecker and Dr. Shanshal. This has given me confidence in what has to happen.”

And as the Hannons move with hope toward healing, they’re looking forward to future cruises and travels to visit family.

The post How robotic bronchoscopy helped a Georgia man avoid unnecessary lung surgery appeared first on Vanderbilt Health News.

Excessive consumption of dietary sodium (salt) is a significant, independent risk factor for new-onset heart failure, according to a report from Vanderbilt Health.

In a group of predominantly Black and low-income people from the southeastern United States, consuming a population average of about 4,200 milligrams of dietary sodium a day (the recommended maximum is 2,300 milligrams) was associated with a 15% increase in the risk of incident (new) cases of heart failure.

“Even modest reductions in sodium consumption may significantly reduce the burden of heart failure in this high-risk population,” the researchers reported March 17 in the Journal of the American College of Cardiology: Advances.

Reducing dietary salt consumption is not a simple matter, however, cautioned the paper’s corresponding author, Deepak Gupta, MD, MSCI, associate professor of Medicine and director of the Vanderbilt Translational and Clinical Cardiovascular Research Center (VTRACC).

Multilevel, public health strategies may be required to address grocery store availability and limited transportation options that make it difficult for residents of many low-income, high-risk communities to access healthier food options, Gupta said.

Leonie Dupuis, MD, a third-year resident physician in internal medicine at Vanderbilt Health, is first author of the paper, which analyzed dietary and health records of more than 25,300 participants in the federally funded Southern Community Cohort Study.

The SCCS has tracked the health of predominantly Black and low-income residents of 12 southeastern states since 2001. Most of them were enrolled in this and other studies through community health centers.

Average daily sodium consumption in this group was 4,269 milligrams per day, well above the daily, 2,300-milligram limit recommended by federal dietary guidelines.

The increased risk of heart failure linked to sodium was independent of sociodemographic factors, including diet quality and caloric intake, as well as health conditions such as high blood pressure and high lipid blood levels.

Heart failure contributes to 425,000 deaths in the United States each year. The cost of caring for the estimated 1 million new cases of heart failure diagnosed annually runs into the tens of billions of dollars.

Even a modest reduction in dietary salt, to 4,000 milligrams a day or less, could reduce heart failure cases by 6.6% over 10 years, the researchers predicted. That would translate into fewer deaths from heart failure and a nearly $2-billion-a-year reduction in national health expenditures.

Co-authors of the paper are Meng Xu, MS, Audrey White, MD, Debra Dixon, MD, MS, Jane Ferguson, PhD, Xiao-Ou Shu, PhD, Danxia Yu, PhD, and Loren Lipworth, ScD. The SCCS is supported by National Cancer Institute grants R01CA092447, U01CA202979 and 3R01CA029447, with additional research support from National Institutes of Health grants R01HL133860, R01HL153607, K23HL168331, P30HS029767 and R38HL167237.

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The clonal growth of precancerous blood cells known as CHIP (clonal hematopoiesis of indeterminate potential) occurs in 1 in 10 people over age 70. It is known to increase the risk of blood cancer and death from cardiovascular, lung and liver disease.

Last year, researchers at Harvard’s Massachusetts General Hospital reported that CHIP also dramatically increased the risk of inflammatory heart disease. Their study analyzed genomic and health records data from more than 335,000 participants in the England-based UK Biobank.

To validate these findings, Vanderbilt Health researchers analyzed data from more than 361,000 participants in two large U.S. biobanks — one of them, BioVU, based at Vanderbilt Health, and the other, part of the National Institutes of Health’s All of Us Research Program.

Their report, published March 18 in the journal JAMA Cardiology, identified a specific link between CHIP and pericarditis, a potentially life-threatening inflammation of the thin sac surrounding the heart. It suggests that treating patients for the blood condition could reduce their risk of heart inflammation.

“Both CHIP and pericarditis are thought to be a result of the same types of inflammation,” said the paper’s first author, Yash Pershad, an MD/PhD student in the lab of Alexander Bick, MD, PhD. “Targeting CHIP-associated inflammation may represent a therapeutic strategy for preventing or treating pericardial inflammation in some at-risk individuals.”

Each year in the United States, an estimated 160,000 people develop pericarditis, which can cause sharp chest pain and often requires hospitalization. The condition, which also is associated with autoimmune disease, cardiac procedures, and infections, can lead to a dangerous buildup of fluid around the heart that impairs heart function.

CHIP is thought to fuel inflammation through specific molecular pathways — including a cellular alarm system called the NLRP3 inflammasome and a signaling protein called interleukin-1beta — that are also central to pericarditis.

Drugs that block these pathways are already approved to treat recurrent pericarditis and potentially could be used as preventive therapy, Pershad noted.

Bick, the paper’s corresponding author, directs the Division of Genomic Medicine and Clinical Pharmacology at Vanderbilt Health. Other co-authors are Kun Zhao, PhD, a postdoctoral researcher in the Bick lab, and Brett Heimlich, MD, PhD, assistant professor of Medicine. The research was supported by National Institutes of Health grants DP5OD029586, R01AG088657 and K08HL171833, a Burroughs Wellcome Fund Career Award for Medical Scientists, a Pew-Stewart Scholar for Cancer Research award, and a Hevolution/AFAR New Investigator Award in Aging Biology and Geroscience Research.

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When colorectal adenomas — polyps that can develop into colon cancer — are removed during a colonoscopy, patients look for guidance about when to have another colonoscopy to look for new growths.

Current surveillance guidelines emphasize polyp characteristics, but a new study led by Vanderbilt Health researchers demonstrates that demographic factors also influence colorectal adenoma recurrence. Their findings, reported in the journal JAMA Network Open, underscore the need for surveillance strategies that factor in polyp characteristics and population-specific risk profiles, as well as variation over time.

Colorectal cancer is the second most common cause of cancer-related death in the United States, according to the National Cancer Institute. Removing precancerous polyps during colonoscopy procedures significantly reduces the burden of colorectal cancer. But about 30% of patients who have a colorectal adenoma removed will develop recurrent adenomas, putting them at increased risk for developing cancer.

“The current guidelines for surveillance after polyp removal stratify recurrence risk primarily based on polyp characteristics including size, histology and number,” said Xingyi Guo, PhD, associate professor of Medicine in the Division of Epidemiology and co-corresponding author of the new study. “The guidelines universally neglect demographic variables such as race, sex, family history, age and obesity, and may therefore be inadequately addressing population heterogeneity in recurrence risk and timing.”

The researchers, led by Guo and co-corresponding author Zhijun Yin, PhD, associate professor of Biomedical Informatics, conducted a retrospective cohort study using Vanderbilt Health electronic health records for about 3.5 million patients.

They identified a study group of 59,667 adult patients who had an initial colonoscopy with polyp removal between January 1990 and July 2024, and up to 25 years of follow-up. About 29.5% of the patients experienced adenoma recurrence within five years.

The researchers evaluated associations between recurrence and demographic variables: race and ethnicity, sex, obesity (body mass index greater than 30), family history of colorectal cancer or polyps, and age at time of initial adenoma (younger than 50 versus 50 and older). They examined associations with adenoma features including histology, size, number and dysplasia (abnormal cell structure).

Among their notable findings:

• High-grade dysplasia had the largest association with early (less than five years) adenoma recurrence, but not with mid- (five to 10 years) or late-term (10 or more years) recurrence.
• Villous histology exhibited a biphasic pattern: an early elevation and late-term resurgence in recurrence risk.
• Obesity conferred persistent risk across all surveillance intervals.
• Female patients with high-risk adenomas had marked late-term risk, exceeding male patients.
• Colorectal adenoma recurrence demonstrated distinct heterogeneity over time, rather than constant risk.

The researchers noted that the study cohort’s predominantly non-Hispanic white population (87.2%) may limit generalizability of the findings, and other factors that could affect risk like socioeconomic status and lifestyle exposures (e.g., tobacco and alcohol use, physical activity and diet) were not consistently available in health records and could not be included in the analysis.

“Our findings suggest that both histopathologic and demographic factors show time-dependent associations with adenoma recurrence, supporting a shift toward dynamic and individualized surveillance strategies,” Yin said.

Usman Ayub Awan, PhD, epidemiology postdoctoral fellow, and Qingyuan Song, PhD, computer science and biomedical informatics graduate student, are co-first authors of the JAMA Network Open study. Guo, Yin and Wanqing Wen, MD, MPH, research professor of Medicine in the Division of Epidemiology, are co-senior authors of the study. The research was supported by the National Cancer Institute (grants R01CA297582 and R01CA269589).

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When Sallie Bailey’s husband, John Bailey, was diagnosed with cholangiocarcinoma (bile duct cancer) in July 2018, the news came as a shock. Just months earlier, his physical appearance showed no difference.

The first sign was subtle: jaundice in one eye. The jaundice quickly spread throughout John’s entire body, the point at which he and Sallie met with Benjamin Womack, MD, associate professor of Clinical Medicine. Despite the care of Womack, Patrick Yachimski, MD, MPH, professor of Medicine, and Kristen Ciombor, MD, MSCI, associate professor of Medicine, John passed away in November 2018, only four months after his diagnosis.

“Until the jaundice appeared, there were no symptoms,” Sallie recalls. “It’s a silent disease, and by the time it’s detected, it’s often too late.”

John was more than a patient at Vanderbilt-Ingram Cancer Center. He was a man with a passion for good food and wine. A talented chef, he worked in San Francisco, Chicago, France, and Washington, D.C., before retiring from professional kitchens. Even then, he continued creating memorable meals for family and friends and sought out locally owned restaurants and new wines to enjoy. His welcoming smile made everyone feel special, and he loved traveling, especially to California wine country.

After moving to Nashville in 2011, Sallie and John chose Vanderbilt Health for their care because they valued being part of a teaching hospital. That decision connected them to a team of experts who provided compassionate care during an incredibly difficult time. Sallie’s experience inspired her to take action. Today, she supports research led by Ciombor and Yachimski, hoping to help scientists detect cholangiocarcinoma earlier and slow its progression.

“Ultimately, I hope researchers will find a way to treat the cancer so that it isn’t a death sentence,” Sallie says. “Dr. Yachimski and Dr. Ciombor have both told me their goal is to work themselves out of a job. I admire and support that goal.”

Through her gifts, Sallie honors John’s legacy in a deeply meaningful way. Her support helps researchers pursue earlier detection methods, develop treatments that slow disease progression, and improve quality of life for patients. It also fuels innovation in clinical trials and provides hope for families facing rare cancers like cholangiocarcinoma. Every contribution moves science closer to a future where this diagnosis is no longer a death sentence.

“Particularly for a rare tumor type such as cholangiocarcinoma, contributions like Sallie’s propel our understanding of the molecular underpinnings of these tumors forward and set the stage for future therapeutic advances,” Ciombor said. “Philanthropic support such as Sallie’s provides critical resources at a time when patients with cancer need better treatment options more than ever.”

Learn more about supporting cancer research and making a gift by clicking here. When making a gift, please write in the comment field that you’d like your donation to support cholangiocarcinoma initiatives.

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Vanderbilt Health investigators have received a grant from AstraZeneca to lead a multisite, randomized controlled trial aimed at refining the standard of care when using robotic bronchoscopy combined with three-dimensional imaging to obtain lung samples for malignancy assessment and gene sequencing.

“Recent advances in minimally invasive bronchoscopic techniques have improved the diagnostic yield, particularly for peripheral pulmonary lesions, and in the recent VERITAS trial, we demonstrated that navigational bronchoscopy can achieve a diagnostic accuracy of around 79%,” said Fabien Maldonado, MD, MSc, professor of Medicine and Thoracic Surgery and director of Interventional Pulmonology at Vanderbilt Health. “That is statistically comparable to transthoracic needle biopsy, which is around 74% accurate.”

“Because of the proven success of navigational bronchoscopy, we now want to determine whether or not the rapid, on-site evaluation (ROSE) of biopsy material remains a necessary step. We’ll test the hypothesis that this advanced bronchoscopy procedure done without ROSE guidance is non-inferior to bronchoscopy with ROSE. This could have immediate patient care implications, potentially shortening procedure time, improving specimen quality and avoiding complications from additional, unnecessary biopsies.”

ROSE has been the standard of care for decades in navigational bronchoscopy, but it adds time, cost and may paradoxically result in lower quality specimens. It can also lead to complications from unnecessary biopsies motivated by unclear intraprocedural results. With modern techniques such as robotic bronchoscopy with cone-beam CT technology, which is rapidly becoming the standard of care, the need for ROSE needs to be studied, said Maldonado, who holds the Pierre Massion Directorship in Lung Cancer Research.

The development of better biopsy approaches is driven by the fact that lung cancer kills more than 130,000 Americans annually, and survival depends on early diagnosis, which requires biopsy to be definitive. Current approaches make accurate biopsy challenging or even impossible for many hard-to-reach lesions.

These modern bronchoscopy techniques extend the range of bronchoscopes and the ability to access lesions reliably and safely throughout the lung, including in the peripheral zone, said study co-investigator Rafael Paez, MD, MSCI, assistant professor of Medicine in the Division of Allergy, Pulmonary and Critical Care Medicine.

The Advanced Robotic Techniques and Rapid Onsite Evaluation for Minimally Invasive Diagnosis and Next-Generation Sequencing (ARTEMIS) trial will be conducted at Vanderbilt Health and nine other United States medical centers. Expected enrollment will be 440 adults who are scheduled for a navigational bronchoscopy for the evaluation of a pulmonary lesion. Participants will be randomized to have the procedure with the addition of ROSE or to have the procedure without ROSE.

The primary objective is to assess the diagnostic yield of robotic bronchoscopy with and without ROSE for peripheral lung lesions. A secondary objective is to compare the adequacy of malignant tissue samples for next-generation sequencing (NGS) between the two intervention strategies.

ROSE involves the immediate microscopic assessment of biopsy specimens, typically performed by a cytotechnologist or cytopathologist, to confirm the adequacy of biopsy samples obtained during a bronchoscopy for the diagnosis of malignancy. This has also been an important step in the past to ensure sufficient tissue is obtained for NGS to identify genetic mutations to guide treatment decisions, said Maldonado.

A 2023 Rapid On-site Evaluation Practice Variability Appraisal survey of interventional pulmonologists revealed significant variation in ROSE utilization. Of the 137 respondents, 88% reported ROSE availability, while time constraints (28%), availability of cytology (22%) and scheduling conflicts (20%) were the most reported barriers to ROSE utilization.

“Additional motivation for determining if ROSE use and non-ROSE use yield similar outcomes during diagnostic procedures is that ROSE is historically poorly reimbursed and uses considerable hospital resources,” Maldonado said. “Our findings will guide interventional pulmonologists in optimizing workflow and technology during robotic bronchoscopy, aiming to maintain the nearly 80% diagnostic yield seen in trials like VERITAS, thus improving patient care as we evaluate pulmonary lesions.”

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Hematologists with Vanderbilt-Ingram Cancer Center have published strategies for implementing outpatient treatment programs for bispecific antibodies, an immunotherapy that can cause adverse reactions.

The recommendations, published recently in JCO Oncology Practice, detail a comprehensive overview of the potential risks, treatment options for dealing with reactions, prophylactic protocols to prevent them from occurring, and the roles of an interdisciplinary care team within an outpatient program. The team at Vanderbilt-Ingram has expertise in outpatient care models for immunotherapy treatment because Vanderbilt-Ingram was among the first in the nation to establish outpatient protocols for another personalized immunotherapy, CAR-T.

Bispecific antibodies (BsAb) utilize engineered antibodies, molecular spikes, which bind to both cancer cells and immune cells, activating a patient’s T cells to attack hematologic malignancies. With CAR-T (chimeric antigen receptor T-cell therapy), T cells are harvested from a patient, then reengineered to recognize and destroy cancer cells before being infused back into the patient’s body. Both therapies can elicit strong immune responses with complications that pose risks, including cytokine release syndrome, a potentially life-threatening reaction that can damage healthy tissues and organs.

For this reason, the BsAb and CAR-T therapies typically require inpatient monitoring, which can be an economic and logistical burden for both patients and hospitals.

“Bispecific antibodies are a major advance in the field of cancer immunotherapy,” said the article’s corresponding author, Bhagirathbhai Dholaria, MBBS, associate professor of Medicine. “This class of drugs is available off the shelf, which makes them ideal for utilization in the community settings. In this article, we have provided a comprehensive framework to establish an outpatient bispecific antibodies program, especially for community practices, which do not have an already established CAR-T program. Our strategy has the potential to greatly reduce the logistical and financial burden during step-up dosing of bispecific antibodies while maintaining safety of the patients.”

The protocols suggested are for seven BsAb therapies that have been approved by the Food and Drug Administration for non-Hodgkin lymphoma and multiple myeloma. They address potential complications, including cytokine release syndrome, infections, cytopenia, tumor flare reactions, and immune effector cell-mediated neurotoxicity syndrome.

The authors noted that while outpatient programs for CAR-T were established before bispecific antibodies, CAR-T poses higher risks for adverse reactions. Their recommendations prioritize early recognition and intervention for these complications, particularly in the first cycle of treatment with BsAb when most cytokine release syndrome events are likely to occur.

The paper provides an infrastructure and workflow guide for how clinicians can work with patients to implement monitoring and address care needs. They also stress the importance of educating both patients and family/friend caregivers about proper protocols for remote monitoring.

The article’s additional authors are Kian Rahbari, MD, and Raul del Toro Mijares, MD, Kathryn Kennedy, RN, Leslie Mader, RN, Salyka Sengsayadeth, MD, Reena Jayani-Kosarzycki, MD, James Jerkins, MD, Andrew Jallouk, MD, Tae Kon Kim, MD, Shakthi Bhaskar, MD, Vivek Patel, MD, Brittney Baer, RN, Sarah Moseley, RN, David Morgan, MD, Bipin Savani, MD, Adetola Kassim, MD, Muhamed Baljevic, MD, and Olalekan Oluwole, MD.

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About 1 in 5 patients with cancer who undergo genetic testing are incidentally found to have mutations in their blood called clonal hematopoiesis of indeterminate potential (CHIP). A study from Vanderbilt Health researchers reveals that it puts them at increased risk for heart disease following cancer treatment.

The findings, published Jan. 8 in JAMA Oncology, support the potential benefits of screening patients for CHIP before they undergo cancer treatment so they can be more closely monitored for heart complications. CHIP is a condition, not a disease, characterized by age-related variants in blood stem cells, and it is typically asymptomatic.

The researchers were able to determine which patients had CHIP by using Vanderbilt Health’s biorepository, BioVU, to link electronic health records with whole-genome sequencing data. They compared the cardiovascular health outcomes of the patients with CHIP to outcomes of patients without the condition. All the patients had been diagnosed with solid tumors, and none had heart failure, ischemic heart disease or arrhythmia before undergoing cancer treatment.

Over a 10-year period following treatment, patients with CHIP had a significantly higher incidence of heart failure (20.3% versus 14.5%) and ischemic cardiovascular disease (25.3% versus 18.5%). The effect was amplified in patients who received more intensive chemotherapy.

“We frequently find CHIP in patients with cancer, but previously we did not consider this to be an important result for their care. We now know that these patients are at higher risk of heart disease and would likely benefit from including cardiologists in their care team,” said the study’s corresponding author, Alexander Bick, MD, PhD, associate professor of Medicine, holder of the Edward Claiborne Stahlman Chair, and director of the Division of Genetic Medicine and Clinical Pharmacology.

The patients received chemotherapy, radiotherapy, immunotherapy, or a combination of the treatments. Cardiovascular disease is the leading cause of noncancer deaths among cancer survivors.

The researchers analyzed data from 8,004 patients, and 549 of them were identified with CHIP. To their knowledge, the study is the largest to date evaluating the association between CHIP and cardiovascular disease in patients with solid tumors who underwent cancer treatment. Most patients with CHIP were male (54% versus 45%) and had hypertension (78% versus 69%) compared to patients without the condition.

The clinical implications of the study are that there may be value in testing patients for CHIP prior to cancer treatment to stratify risk and tailor monitoring for cardiovascular diseases and offering early cardio-oncology consultations as well as consideration of cardioprotective strategies.  

The researchers received support from the National Institutes of Health (grants DP5OD029586 and T32GM007347). The sequencing of 250,000 individuals who have donated samples to BioVU has been funded by the Alliance for Genomic Discovery.

The study’s first authors are Derek Shyr, PhD, and Yash Pershad. The study was jointly supervised by Bick and Leo Luo, MD, assistant professor of Radiation Oncology at Vanderbilt Health.

Other Vanderbilt Health authors on the study are Ashwin Kishtagari, MD, Robert Corty, MD, PhD, Eric Shinohara, MD, MSCI, Ben Ho Park, MD, PhD, and Brett Heimlich, MD, PhD.

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A multi-institutional research team that included genomic scientists from Vanderbilt Health has identified a potential target for blood cancer prevention and treatment.

Their report, published Jan. 1 in the journal Science, could lead to new treatments for blood cancers, which kill an estimated 23,540 people in the United States every year.

The research team, led by scientists from Boston Children’s Hospital, Dana-Farber Cancer Institute, the Broad Institute of MIT and Harvard, and Memorial Sloan Kettering Cancer Center, found that the protein Musashi-2 (MSI2) is essential for the function of blood-forming stem cells.

High levels of MSI2 can support the unchecked growth of abnormal stem cells, a precancerous condition known as clonal hematopoiesis of indeterminate potential, or CHIP.

The researchers used a genome-wide association study (GWAS) meta-analysis to identify a haplotype, or inherited grouping of genomic variants, which reduces MSI2 expression, thereby protecting against CHIP.

To validate these findings in humans, Alexander Bick, MD, PhD, Yash Pershad, and colleagues leveraged Vanderbilt Health’s DNA biobank, BioVU, the world’s largest repository of genetic material linked to de-identified electronic health records based at a single academic center.

By analyzing a unique longitudinal cohort of 3,000 patients with genetic sequencing performed approximately six years apart, the Vanderbilt Health team tested whether a variant which reduced the expression of MSI2 protected against the expansion of precancerous mutations.

Patients who carried the protective variant had precancerous clones that grew significantly more slowly than those without the variant. In many of these patients, the abnormal cells were transient; that is, they disappeared entirely over the study period rather than expanding into cancer.

“Most genetic studies only provide information from a snapshot in time, but the longitudinal samples in BioVU allowed us to study the mutations over six years,” noted Pershad, an MD/PhD student in the Bick lab, who with Bick is among the paper’s co-authors.

“We could clearly see that in people with the protective variant, precancerous clones behaved fundamentally differently than we expected — they shrunk or disappeared rather than expanding and becoming cancer,” Pershad said.

While CHIP results from somatic (acquired) blood stem cell mutations, this protection against it is inherited. This human genetic evidence suggests a potential way to prevent blood cancer by targeting MSI2 through small molecule inhibition or genome editing.

“More broadly,” the researchers concluded, “we provide an example of how resilience to cancer can arise through inherited genetic variation, motivating the search for other natural pathways that could be leveraged to prevent or treat malignancy.”

Bick, the Edward Claiborne Stahlman Professor, associate professor of Medicine, and director of the Division of Genetic Medicine and Clinical Pharmacology at Vanderbilt Health, is internationally known for his research on the genetics of blood disorders.

His research is supported in part by National Institutes of Health grants DP5OD029586, R01AG088657 and R01AG083736, a Burroughs Wellcome Fund Career Award, a Pew-Stewart Scholar for Cancer Research award, and a Hevolution/AFAR New Investigator Award in Aging Biology and Geroscience Research.

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Vanderbilt Health’s Lucy Spalluto, MD, MPH, professor of Radiology and Radiological Sciences, and Jennifer Lewis, MD, assistant professor of Medicine in the Division of Hematology and Oncology, have received a grant from AstraZeneca to understand and improve veteran access to mobile lung cancer screening.

The study, “REACHing veterans at high risk for lung cancer outside the guidelines and through mobile screening,” will receive approximately $1 million in total grant funding over a four-year period. As explained by Spalluto and Lewis, lung cancer is the leading cause of cancer death in the United States, with incidence higher in veterans compared to the civilian population.

“Improving access to lung cancer screening for a broader population, including those who live in rural areas, through mobile services can increase the early detection of lung cancer and improve lung cancer outcomes,” Spalluto says. “The REACH study explores the impact of mobile lung cancer screening in the Veterans Health Administration. An important component of the REACH study is understanding veterans’ perspectives of mobile screening.”

Screening for lung cancer with low-dose CT scans is an effective strategy to detect lung cancer early and improve mortality. However, this screening is widely underutilized, including in the Veterans Health Administration. Veterans living in rural areas are less likely to be screened for lung cancer, and individuals living in rural areas have higher mortality from lung cancer compared to those who live in nonrural areas.

In response to the low screening and high mortality rates, the VA’s Midsouth Veterans Integrated Service Network has partnered with the VA Lung Precision Oncology Program to offer mobile lung cancer screening to better reach veterans who reside in rural areas. Spalluto and Lewis have been awarded the REACH grant through AstraZeneca to understand the reach of mobile lung cancer screening among veterans within and outside current screening eligibility criteria, as well as veterans’ experiences with mobile lung cancer screening.

This work is particularly pertinent to veterans who may have been exposed to war-related chemical, waste and other similar smoke inhalation.

“Exposures that veterans have had because of their military service, such as Agent Orange and burn pits, may place them at high risk for lung cancer,” Lewis explains. “This study will help us understand how many veterans are eligible for lung cancer screening not only based on age and smoking history, but also other important risk factors, such as family history, personal history of cancer, diagnosis of COPD and military environmental exposures. These data will be critical for VA leadership.”

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