A two-drug combination for treating advanced kidney cancer had sustained and durable clinical benefit in more than five years of follow-up, according to a study published Aug. 1 in Nature Medicine. 

The study reports final clinical data and biomarker analyses from the Phase 3 KEYNOTE-426 trial, which compared the drug combination pembrolizumab plus axitinib versus the single drug sunitinib for patients with previously untreated advanced clear cell renal cell carcinoma, the most common type of kidney cancer.

“KEYNOTE-426 was the first trial to combine a PD-1 inhibitor immunotherapy (pembrolizumab) with a VEGF receptor inhibitor antiangiogenic drug (axitinib) in the first-line setting for advanced renal cell carcinoma. It therefore has the longest follow-up duration among the various trials comparing these types of drug combinations,” said Brian Rini, MD, a medical oncologist at Vanderbilt-Ingram Cancer Center and the study’s lead and corresponding author. 

Immunotherapy drugs like pembrolizumab stimulate the immune system to kill tumor cells. VEGF receptor inhibitors like axitinib and sunitinib block angiogenesis — the development of blood vessels that tumors need to grow and spread. Pembrolizumab plus axitinib and other immunotherapy-antiangiogenic drug combinations are now standard first-line treatments for advanced kidney cancer. 

“Before the development of antiangiogenic drugs and immunotherapies, advanced renal cell carcinoma had a very poor prognosis. These drug combinations have dramatically improved treatment options and outcomes for patients,” said Rini, Thomas F. Frist Sr. Professor of Medicine. 

The first interim analysis of outcomes from KEYNOTE-426, published Feb. 16, 2019, in the New England Journal of Medicine, demonstrated that trial participants treated with pembrolizumab plus axitinib had longer overall and progression-free survival, and higher objective response rates compared to those taking sunitinib. The median follow-up was 12.8 months. 

Now, with a median follow-up of 67.2 months, the current analysis confirms and extends the interim analysis and provides valuable information about biomarkers that could help guide treatment decisions. 

The study in Nature Medicine reports that pembrolizumab plus axitinib had longer overall survival (47.2 months versus 40.8 months for sunitinib) and longer progression-free survival (15.7 months versus 11.1 months for sunitinib). The objective response rate was 60.6% for pembrolizumab plus axitinib and 39.6% for sunitinib. 

The researchers reported a variety of associations between the expression of biomarkers and outcomes (overall survival, progression-free survival, objective response rate). The biomarkers they evaluated included an 18-gene T-cell-inflamed expression profile, angiogenesis signature, and PD-1 ligand expression. 

“There is an unmet need for biomarkers that are predictive of patient outcomes following treatment with available first-line therapies for advanced renal cell carcinoma,” Rini said. “Although our analysis showed potential clinical utility of some RNA signatures in identifying patients who are likely to benefit the most from each treatment, further prospective clinical studies are needed.” 

Pembrolizumab plus axitinib is a first-line treatment option for patients with advanced renal cell carcinoma regardless of biomarker subtypes, he noted. 

The research was supported by the pharmaceutical company Merck Sharp & Dohme LLC, which played a role in the study design and conduct.

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Walking fast for just 15 minutes per day reduced the risk of death in a large study group of mostly low-income participants. 

The research findings, published July 29 in the American Journal of Preventive Medicine, support promoting brisk walking as a strategy for improving health outcomes in all communities. 

Although the health benefits of walking are widely recognized, there has been limited research on the effect of factors such as walking pace on mortality, particularly in low-income and Black populations, said the study’s senior author, Wei Zheng, MD, PhD, MPH, the Anne Potter Wilson Professor of Medicine and director of the Vanderbilt Epidemiology Center. 

“This is one of the few studies to quantify the effect of daily walking on mortality in a low-income and predominantly Black U.S. population,” said Zheng, who also directs the Division of Epidemiology at Vanderbilt University Medical Center. “By demonstrating the benefits of fast walking — which is a low-cost and largely accessible activity — we provide direct evidence to inform targeted public health interventions and policies to improve health outcomes.” 

The study analyzed data from the Southern Community Cohort Study (SCCS), which enrolled about 85,000 participants ages 40-79 between 2002 and 2009. Most participants (86%) were recruited in collaboration with community health centers serving low-income populations across 12 southeastern states. Participants provided baseline information, including daily walking pace and time, demographic and lifestyle factors, and medical history, using structured questionnaires. 

The current study, led by first author Lili Liu, PhD, MPH, included data from 79,856 of the SCCS participants (racial groups: 66% Black, 30% white, 4% other). In the baseline survey, participants reported the average amount of time per day (in minutes) they typically spend “walking slowly (such as moving around, walking at work, walking the dog or engaging in light exercise)” and “walking fast (such as climbing stairs, brisk walking or exercising).”

The cohort was linked to the National Death Index to obtain vital status and cause of death information through Dec. 31, 2022. Over a median follow-up of 16.7 years, 26,862 deaths occurred. 

The researchers found that fast walking as little as 15 minutes per day was associated with a nearly 20% reduction in total mortality. Slow walking more than three hours per day was associated with a smaller reduction in mortality. The benefit of fast walking remained strong even after accounting for other lifestyle factors, such as leisure-time physical activity levels. 

In addition to reducing premature death from all causes, fast walking reduced death specifically from cardiovascular diseases — the No. 1 cause of death in the United States. The researchers suggested that fast walking might reduce cardiovascular mortality by improving the heart’s efficiency and output, and by reducing the prevalence of obesity and its associated cardiovascular risks such as hypertension and high cholesterol. 

“Brisk walking offers a convenient, accessible and low-impact activity that individuals of all ages and fitness levels can use to improve general health and cardiovascular health specifically,” Zheng said. 

The authors acknowledge that self-reported data on daily walking may have included other types of physical activity, which could introduce misclassification errors. Also, the physical activity data was only collected at baseline, so changes over time could not be considered. The study’s long follow-up and large sample size contribute to “robust and reliable estimates,” they noted. 

Other VUMC co-authors are Guochang Jia, PhD, Martha Shrubsole, PhD, Wanqing Wen, MD, MPH, and Staci Sudenga, PhD. The research was supported in part by the National Institutes of Health (grant U01CA202979).

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The first class has completed the VERTICAL Program at Vanderbilt-Ingram Cancer Center, which provides medical and graduate school preparation for aspiring oncologists and cancer researchers.

The program was established in 2023 with financial support from the American Cancer Society, and Vanderbilt-Ingram had an inaugural class of four fellows. This was followed by the enrollment of another fellow in 2024.

“This is a two-year program that gives trainees a robust mentored research experience,” said Kimberly Dahlman, PhD, associate professor of Medicine, who is the assistant director of Research Education at Vanderbilt-Ingram. “In addition to being embedded in a cancer research laboratory, fellows also participate in professional development and cancer education activities, including career-path, lunch-and-learn sessions and cancer biology coursework.

“They are also involved in community service projects related to cancer. This program gives them dedicated time to prepare for their medical school or graduate school applications, in addition to their research experiences.”

In August, another class of four fellows will start the VERTICAL Program, which is kept small so it can be tailored to individual development plans. The participants do not receive credits toward graduate degrees, but they do become more competitive for acceptance into medical and graduate school programs.

“The VERTICAL Program gave me the final push I needed to pursue a PhD,” said Asia Miller, a member of the inaugural class from Indiana, who has a bachelor’s degree from Vanderbilt University in Biological Sciences “I was not confident in my identity as a researcher before the program, despite having done research in all four years of college. This was the best professional and personal development experience I have ever had.”

Bryan Hernandez, another inaugural class member who has a bachelor’s degree in Neuroscience from The University of Texas at El Paso, said he is looking forward to a career as a physician-scientist.

“The VERTICAL Program provided me with the perfect combination of structured mentoring and independent guidance throughout my two years in the program,” Hernandez said. “This dynamic exposed me to more robust career-building opportunities in areas of cancer research and medicine I was not previously familiar with. Thanks to my time in the VERTICAL Program, I was able to progress into the next formative step in my intended career path as a physician-scientist with a newfound outlook on the field of science and medicine I had been interested in.”

VERTICAL is an acronym for Vanderbilt Education Research and Training in Cancer and Leadership Program. It is open to individuals with bachelor’s degrees from nationally accredited colleges or universities who desire to pursue doctoral degrees and careers in science or medicine with a focus on cancer. Participants are paid a living wage.

“We also pay for MCAT preparation for fellows who want to take the MCAT for medical school applications,” said Dahlman, who is also co-director of the third- and fourth-year undergraduate medical education curriculum at Vanderbilt University School of Medicine.

VERTICAL fellows at Vanderbilt-Ingram are also offered the opportunity to do clinical shadowing and are provided financial support to attend one conference a year to present their research.

Vanderbilt-Ingram was selected as one of the five initial pilot locations for the postbaccalaureate fellows program, which was started by the American Cancer Society. Each of the pilot institutions has its own name for the program. Debra Friedman, MD, MS, holder of the E. Bronson Ingram Chair in Pediatric Oncology and deputy director of Vanderbilt-Ingram, serves as assistant director of the VERTICAL Program. Caroline Hartford is the senior program manager of VERTICAL.

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A new prospective clinical trial with updated data on COVID-19 hospitalizations and deaths among patients with cancer confirms the importance of vaccination and sheds light on which conditions put patients most at risk. 

Patients who had been vaccinated had a 50% reduction in risk of hospitalization, according to data from the National Cancer Institute COVID-19 in Cancer Patients Study (NCCAPS) published July 17 in JAMA Oncology.

Death incidence was highest in patients with lymphoma, intermediate in patients with acute leukemia and lung cancer, and lowest in patients with other solid tumors or with blood cancers other than lymphoma. Patients who had undergone chemotherapy or who had a history of stroke, atrial fibrillation and pulmonary embolism were at higher risk for hospitalization. 

The finding that patients with lymphoma had the highest risk of death suggests a potential detrimental effect of B-cell-depleting therapy on COVID-19 outcomes, the study stated, but the authors noted that this hypothesis was confounded by the inherent immunosuppression in patients with lymphoma. 

“These results are important because they represent the only prospective clinical trial in patients with a recent diagnosis of COVID and an active cancer undergoing therapy,” said the study’s lead author Brian Rini, MD, Ingram Professor of Cancer Research and Thomas F. Frist Sr. Professor of Medicine. 

Rini is one of two principal investigators of NCCAPS. The other is Lorissa Korde, MD, with NCI’s Cancer Therapy Evaluation Program, who is the study’s senior author. Patients were accrued for the study between 2020 and 2022, and the statistical analysis took place between September 2024 and April 2025. 

The study involved 1,572 adult patients who had a COVID-19 diagnosis within 14 days while receiving active treatment for cancer or had a prior stem cell transplant or CAR-T cellular treatment therapy. In addition to outcomes, investigators analyzed COVID-19 therapies patients received and disruptions in cancer treatment. The most common type of disruption was a delayed cancer treatment. 

The majority of patients had already been accrued for analysis before the Food and Drug Administration gave emergency use authorization for the antiviral treatment nirmatrelvir with ritonavir, which is most commonly known by its brand name, Paxlovid. Of the patients who enrolled in the study after the first COVID-19 vaccine received FDA emergency use authorization, 41.5% were fully vaccinated. 

“These data provide a road map to protect the most vulnerable cancer populations not only from COVID, but from potential future pandemics,” Rini said. 

Patients hospitalized for COVID-19 within 90 days of enrollment accounted for 18.4% of the study group. Among the hospitalized patients, 23.4% were admitted to an intensive care unit.  

The study was funded in part by the Coronavirus Aid, Relief, and Economic Security (CARES) Act, and also by the National Cancer Institute National Clinical Trials Network, Experimental Therapeutics Clinical Trials Network, and Community Oncology Research Program grants via the U10 funding mechanism.  

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Susan G. Komen has awarded $10.8 million in new research grants that will help propel innovative science and deliver hope to those facing breast cancer. The grant recipients include three researchers from Vanderbilt University Medical Center.

The grants support 25 cutting-edge projects at 17 institutions — marking a powerful commitment to improving outcomes for people living with breast cancer today and in the future.

“We are proud to support these exceptional researchers who are pushing the boundaries of what’s possible in breast cancer science,” said Paula Schneider, president and CEO of Susan G. Komen. “Research saves lives, and now more than ever, we must invest in science that brings hope to patients — especially those facing the most aggressive forms of breast cancer.”

The three VUMC researchers were each awarded Komen Leadership Grants of $400,000. The Komen Leadership Grant Program supports innovative, hypothesis-driven breast cancer research that aligns with Komen’s mission to save lives and improve personalized care and outcomes for all. Open to Komen’s Scientific Advisors and to Komen Scholars, the program funds bold, high-risk/high-reward projects with the potential to significantly advance the field of breast cancer research.

The VUMC recipients are Tuya Pal, MD, Ingram Professor of Cancer Research and professor of Medicine; Ben Ho Park, MD, PhD, Benjamin F. Byrd Jr. Professor of Oncology and professor of Medicine; and Jennifer Pietenpol, PhD, Ingram Professor of Cancer Research and professor of Biochemistry.

Through this research investment, Komen is prioritizing the most pressing challenges facing patients, including metastatic breast cancer, optimal health for all and the need for more precise, personalized treatment strategies to improve care and outcomes for everyone impacted by breast cancer.

“Komen’s commitment to breast cancer research comes at a pivotal time and will drive meaningful advances in our understanding of the disease and care of patients,” said Ann Partridge, MD, MPH, Chief Scientific Advisor for Komen. “By fueling science that is both innovative and inclusive, we’re accelerating progress where patients need it most — while building a foundation for individualized care for all.”

Komen is the largest nonprofit funder of breast cancer research outside the U.S. government, investing nearly $1.1 billion since its inception. Unlike many research institutions, Komen’s work is powered entirely by the generosity of individual donors, corporate partners and community supporters.

“Investing in top scientific talent is one of the most powerful ways we can drive progress,” said Pietenpol, PhD, Chief Scientific Advisor for Komen. “Komen’s commitment, especially to early-career researchers, cultivates a vibrant ecosystem where bold ideas and pioneering research can thrive, accelerating our path toward the cures we urgently seek.”

Pietenpol holds the Brock Family Directorship in Career Development at VUMC. Park is director of the Vanderbilt-Ingram Cancer Center and a member of the Komen Scientific Advisory Board. Pal is a Komen Scholar.

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One person in 10 over the age of 70 will experience an explosive, clonal growth of abnormal blood cells, called clonal hematopoiesis of indeterminant potential or CHIP, that increases the risk of blood cancer and death from cardiovascular, lung and liver disease. 

The risk of blood cancer differs significantly, however, depending upon whether patients with CHIP also develop cytopenia (low blood cell count). 

An analysis of genetic sequencing data from more than 34,000 people over a 17-year period by researchers at Vanderbilt University Medical Center has found that persistent cytopenia appears to be a critical step in the progression of CHIP to blood cancer. 

For patients with CHIP who developed cytopenia, the risk of progression to blood cancer was 10 times higher than it was for patients without cytopenia — a 1-in-200 chance per year versus 1 in 2,000, the researchers report in the June 2025 issue of the Lancet journal, eClinicalMedicine.  

These findings suggest that checking blood counts regularly may be an effective way to monitor patients with CHIP for their risk of developing blood cancer, and cytopenia-free survival may be a valuable endpoint for clinical trials aimed at preventing blood cancer in these patients.

“This work is the largest longitudinal analysis of its kind and provides a roadmap for identifying high-risk CHIP patients who may benefit from closer monitoring or early intervention,” said the paper’s corresponding author, Alexander Bick, MD, PhD, associate professor of Medicine and director of the Division of Genetic Medicine at VUMC. 

“It also lays the groundwork for more feasible and targeted clinical trials in blood cancer prevention,” he said. 

Bick is internationally known for his research on the genetics of blood disorders. He and his colleagues have advanced the understanding of somatic (non-inherited) mutations in blood stem cells that can trigger a potentially life-threatening clonal growth of abnormal cells known as CHIP.  

Blood cancer (myeloid neoplasm) results from the abnormal growth of myeloid (blood) cells in the bone marrow. The current study compared blood cancer rates in patients with CHIP who did not develop cytopenia, to those with both CHIP and concurrent, clonal cytopenia of undetermined significance. 

Led by the paper’s first authors, James Brogan, MD, MS, a resident physician in the Department of Medicine, and Ashwin Kishtagari, MD, assistant professor of Medicine in the Division of Hematology and Oncology, the study required large numbers. 

The researchers pulled genetic sequencing data from three major population-level cohorts: the National Institutes of Health (NIH) All of Us Research Program, the UK (United Kingdom) Biobank and VUMC’s biobank, BioVU. 

With roughly 350,000 DNA samples collected to date, BioVU is the world’s largest repository of genetic material linked to de-identified electronic health records (EHRs) based at a single academic center.  

Access to whole genome sequences linked to EHRs for more than 107,000 adults enrolled in BioVU between 2006 and 2023 was provided through the Alliance for Genomic Discovery (AGD), a unique endeavor to accelerate the application of large-scale genomics to biomedical science and therapeutic development. 

Launched in 2022 by Nashville Biosciences LLC, a wholly owned VUMC subsidiary, and the global DNA sequencing giant Illumina Inc., AGD now includes eight major pharmaceutical companies that support the development and availability of whole genome sequences for research aimed at identifying disease associations and targets for intervention. 

The report in eClinicalMedicine “is one of the first papers to leverage data from the BioVU/Alliance for Genomic Discovery whole genome sequencing effort,” Bick said. “It also highlights how at VUMC medical trainees are doing cutting-edge research while developing as physicians.” 

Between the three biobanks, the researchers had access to 805,000 whole genome sequences. From this pool, they identified 8,114 individuals with CHIP who did not develop cytopenia and 1,260 who did. These 9,374 cases were matched with 24,749 controls who did not have CHIP. 

The annual blood cancer progression rate for participants with CHIP who did not develop cytopenia was nearly the same as the rate observed in the control population without CHIP (0.06% versus 0.04%), whereas the rate was 10 times higher for those with both CHIP and cytopenia (0.5% per year). 

Approximately 13% of participants with CHIP developed a cytopenia within five years. Men, smokers and older individuals (over 64) were at a higher risk of developing cytopenia, as were those who had two or more mutations or any high-risk mutations associated with CHIP. 

“Given the substantial risk of cytopenia, patients with multiple high-risk features may benefit from regular monitoring for cytopenia progression,” the researchers concluded. The good news is that this five-year window before the development of cytopenia and blood cancer “provides an opportunity for early intervention with potential disease-modifying therapies,” they wrote.  

Treatments for cytopenia range from drugs that stimulate the production of certain blood cell types to bone marrow or stem cell transplants. 

Co-authors from the Bick lab included rheumatology fellow Robert Corty, MD, PhD, Yash Pershad, an MD-PhD student, and Brian Sharber, MS. Other VUMC co-authors included faculty members Brett Heimlich, MD, PhD, Leo Luo, MD, Brent Ferrell Jr., MD, Michael Savona, MD, and Yaomin Xu, PhD. 

This research was supported by NIH grants DP5OD029586, R01AG088657, R01AG083736, and P30CA068485, the Burroughs Wellcome Fund Career Award for Medical Scientists, the Edward P. Evans Foundation, and the Pew Charitable Trusts and the Alexander and Margaret Stewart Trust. 

Savona holds the Beverly and George Rawlings Directorship. Bick is supported in part by a Hevolution/AFAR New Investigator Award in Aging Biology and Geroscience Research, and Brogan is supported in part by an American Society of Hematology HONORS Award.

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Cases of appendiceal cancer tripled for Americans born between 1976 to 1984 and quadrupled for those born between 1981 to 1989, according to a study published June 9 in the Annals of Internal Medicine. 

The study compared chronological data in five-year intervals from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Program, using 1941 to 1949 as the baseline. The lead author, Andreana Holowatyj, PhD, MSCI, assistant professor of Medicine at Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, said the findings reveal the need for increased awareness about appendiceal cancer from both clinicians and the public as well as more research to determine the reasons for the sharp spike in incidence.  

“When you take these alarming rates that we are seeing for appendiceal cancer across generations, together with the fact that 1 in every 3 patients diagnosed with appendiceal cancer is diagnosed under the age of 50, these point to a timely need for everyone to be aware of the signs and symptoms of appendix cancer.

“Albeit cancer of the appendix is rare, it is important for individuals who have these symptoms to see a health care professional. Ruling out the possibility of an appendix cancer diagnosis, or diagnosing it early, is important for this cancer as we continue to learn what factors may be contributing to this worrisome trend,” Holowatyj said.

Symptoms may include abdominal pain, bloating, changes in bowel habits, and loss of appetite. 

Appendiceal cancer is a rare cancer with about 3,000 new cases diagnosed every year in the United States, according to prior studies, but Holowatyj and colleagues took a closer look at statistics by combing through the SEER database. 

“As incidence rates in younger generations are often indicative of future disease burden, these results support the need for histology-specific investigations of appendiceal adenocarcinoma, as well as increased education and awareness of appendiceal adenocarcinomas among health care providers and the public,” the study stated. 

Appendiceal cancer has had no standardized screening guidelines, risk factors or tumor classifications — a lack of clinical evidence that has resulted in late diagnosis and poor prognosis. Up to 1 of every 2 patients is diagnosed with distant metastatic disease, and five-year survival rates vary between 10% and 63%.  

Earlier this year, Holowatyj and a team of experts identified six key research priority areas to deliver a fundamental understanding of appendiceal tumors and to improve treatments and outcomes for patients.  

The recommendations published Feb. 20 in Nature Reviews Cancer are the result of a concerted focus by the Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation to better understand the disease that afflicts an estimated 3,000 new patients across all age groups each year. 

The recommendations arose from the inaugural ACPMP Research Foundation Scientific Think Tank, sponsored by ACPMP and chaired by Holowatyj at Vanderbilt-Ingram Cancer Center in December 2023. 

The current study in the Annals of Internal Medicine received support from ACPMP and the National Institutes of Health (grants K12HD043483 and P50CA236733). 

Other authors on the study are Mary Kay Washington, MD, PhD, professor of Pathology, Microbiology and Immunology at VUMC, Richard Goldberg, MD, of the West Virginia University School of Medicine, and Caitlin Murphy, PhD, MPH, of the UT Health Houston School of Public Health. 

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Andreana Holowatyj, PhD, MSCI, assistant professor of Medicine, has been named to the 40 Under 40 In Cancer Class of 2025 by the Association for Value-Based Cancer Care.

This year’s class was selected from more than 3,000 nominations. The awards initiative identifies and recognizes contributions across the field of cancer by rising stars and emerging leaders under the age of 40. 

Holowatyj’s research is focused on early-onset cancers, including colorectal and appendiceal cancers. She has received the National Cancer Institute’s Method to Extend Research in Time (MERIT) Award to support her ongoing investigation into how early-onset colorectal cancer and its treatments impact reproductive health. MERIT Awards provide longer-term funding than is typical for most grants to early-stage investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner. As part of this Award, Holowatyj established and leads the Preserving Fertility After Colorectal Cancer (PREFACE) clinical study, which is currently recruiting patients.  

She is focused on providing evidence-based guidance that will ultimately improve clinical care and outcomes for individuals ages 18 to 49 when diagnosed with cancer. Holowatyj and her team discovered that 1 in 2 young cancer patients report that a health care provider involved in their cancer care did not discuss options to preserve fertility prior to starting cancer treatment. 

Her research has been published in high-impact medical research journals and has led to clinical practice changes and revisions to consensus guidelines. She has also been invited to serve on several international committees, including the American Joint Committee on Cancer Lower Gastrointestinal Tract Expert Panel that updates clinical cancer staging systems, the Fight Colorectal Cancer Global Early-Onset Colorectal Cancer Think Tank, and as the inaugural chair of the Scientific Advisory Board for the Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation. This year, with the support of the ACPMP Research Foundation, she led an expert recommendation report in the journal Nature Reviews Cancer that identified six key research priority areas to deliver a fundamental understanding of appendiceal tumors and to improve treatments and outcomes for patients with this rare cancer.

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Navigational bronchoscopy is as effective as the traditionally used transthoracic needle biopsy for diagnosing lung nodules, but with significantly fewer complications, per a new study published May 18 in the New England Journal of Medicine. This development may shift medical practice and reduce hospitalizations for patients undergoing lung nodule biopsies, said researchers.  

Each year, millions of lung nodules are detected during routine X-rays or CT scans. While most nodules are benign, some are cancerous and when found at this stage they are the earliest and most curable stage of lung cancer.   

Accurate biopsy of lung nodules is often required to tell benign nodules from malignant ones. To date, the most commonly used method, CT-guided transthoracic needle biopsy, carries a high complication rate — including pneumothorax, or partial lung collapse, affecting about 25% of patients. Treatment of the partially collapsed lung often requires a chest tube during a multiple day inpatient stay.  

This study is the first to directly compare these biopsy techniques and the results are compelling, said first author Robert Lentz, MD, associate professor of Medicine and Thoracic Surgery in the Division of Allergy, Pulmonary and Critical Care Medicine at Vanderbilt University Medical Center. The study, conducted across seven centers in the United States, compared the two techniques in a multicenter, randomized trial involving 234 patients with lung nodules between 10-30 mm.  

Navigational bronchoscopy uses a sophisticated targeting system and 3D imaging to guide biopsy tools through small peripheral airways directly to a lung nodule.   

The comparison revealed a diagnostic accuracy of 79% using navigational technology, closely matching the 74% accuracy of transthoracic biopsy. More importantly, the risk of pneumothorax was significantly lower, occurring in only 3% of bronchoscopy patients compared to 35% in those undergoing transthoracic biopsy. Severe cases requiring hospital admission or chest tube insertion were less than 1% with bronchoscopy, as opposed to 14% with the traditional method.  

“With approximately 300,000 lung nodule biopsies performed annually in the U.S., shifting to navigational bronchoscopy could greatly reduce complications and hospital stays. This study confirms its diagnostic efficacy and superior safety profile, making it the preferred choice for lung nodule diagnosis,” said senior author Fabien Maldonado, MD, MSc, professor of Medicine and Thoracic Surgery and director of Interventional Pulmonology.  

The research team plans to continue exploring optimal biopsy techniques, comparing different navigational and robotic bronchoscopy systems, and studying novel biopsy tools, said Maldonado, Pierre Massion Director in Lung Cancer Research.  

They are also involved in research on bronchoscopic ablation of lung cancer, advancing the field of interventional pulmonology.  

“As a relatively new medical subspecialty, we are quite proud and excited to have matured our research infrastructure to the point of being able to produce high quality multicenter trials like this, and hope that publication of this trial will serve as an introduction of sorts for interventional pulmonology to the larger general medical audience,” said Lentz.   

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A grant from VoLo Foundation will augment federal funding for the Southern Environmental Health Study, an initiative to determine whether environmental exposures are contributing to cancer cases in the region.

The study received its initial funding from the National Cancer Institute and the Vanderbilt-Ingram Cancer Center. A grant from VoLo Foundation — a private nonprofit organization dedicated to accelerating global impact through science-based solutions, education enhancement, and health improvement initiatives — will allow investigators to recruit additional participants and conduct methylation- and proteomics-based biological aging assays to check for biomarkers of early disease risk.

On cancer incidence and mortality maps, some of the highest rates in the country appear in the southern U.S., but whether environmental exposures are a contributing factor has not been scientifically determined. The study is a long-term cohort investigation that will follow participants for at least 10 to 20 years. The participants are between the ages of 40 and 70 and live in Alabama, Arkansas, Delaware, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, Missouri, North Carolina, Oklahoma, South Carolina, Texas, Tennessee, Virginia, West Virginia or the District of Columbia.

“Humans are exposed to large numbers of chemicals and their mixtures with more than 80,000 chemicals having been registered by the Environmental Protection Agency,” said Wei Zheng, MD, PhD, MPH, the Anne Potter Wilson Professor of Medicine and the director of the Vanderbilt Epidemiology Center. “However, very few of them have been adequately investigated in relation to human cancers and other diseases in epidemiologic studies. There are considerable challenges in studying environmental exposures in epidemiologic studies.”

Participants will wear silicone wristbands designed to collect chemicals, which researchers will use to measure exposure to approximately 500 compounds. They will also analyze blood samples to assess the internal exposome using both liquid chromatography and gas chromatography with high-resolution mass spectrometry, allowing them to detect approximately 1,500 confirmed chemicals and endogenous metabolites. To identify potential environmental carcinogens, the researchers will use an innovative exposome-wide association study to link chemical exposures with disease biomarkers, including indicators of biological aging and inflammation.

“Supporting the Southern Environmental Health Study aligns with our mission to advance data-driven solutions that can lead to healthier, more resilient communities. This research has the potential to uncover possible links between environmental exposures and chronic diseases,” said David Vogel, co-founder and chief scientist of VoLo Foundation.

Vogel and his wife, Thais Lopez Vogel, formed the VoLo Foundation in 2014.

“We are very grateful for the support of the VoLo Foundation and believe that this study will generate significant amounts of novel data regarding potential impacts of environmental exposures on human health and pave the way for future studies in this important area,” Zheng said.

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