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.

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Lung screenings are an important diagnostic tool for early detection of cancer, but low-dose CT scans cannot determine whether the pulmonary nodules identified in the imaging are cancerous or benign.

Specially trained radiologists, pulmonologists and thoracic surgeons analyze the imaging and then decide whether invasive biopsies are warranted to make that determination — a process called risk stratification of indeterminate pulmonary nodules.

An estimated 10% to 15% of the resections of these nodules turn out to be surgeries for benign tissue. Risk prediction software using artificial intelligence, such as the Lung Cancer Prediction Score, which was developed by Optellum, a lung health technology company, and approved by the Food and Drug Administration in 2021, aids clinicians in determining whether surgical resections are necessary. In a recent study, Vanderbilt Health researchers determined that AI-assisted decision-making with this software is cost-effective compared to clinician assessment alone.

The study, published March 5 in PLOS ONE, showed that AI-assisted decision-making resulted in an incremental cost-effective ratio of $4,485 per life year gained.

“Artificial intelligence-based tools offer promising assistance to busy clinicians who evaluate suspicious lung nodules and seem to be cost-effective,” said the study’s corresponding author, Eric Grogan, MD, MPH, Ingram Professor of Cancer Research and professor of Thoracic Surgery at Vanderbilt Health.

To determine cost-effectiveness, the researchers constructed a decision model assuming guideline-based care from a payer perspective with a lifetime horizon. The base case is a 1.1 centimeter indeterminate pulmonary nodule in a 60-year-old patient who benefits from surgery. This nodule’s risk for lung cancer is about 65%. The model classified patients as low, medium or high risk using either clinician reasoning or clinician-plus-AI reasoning.

“When we think of these AI clinical decision aids, they may not really help the true clinical expert, the thoracic radiologist or pulmonologist who sees 20 of these a day. Where the larger health care system impact occurs is when generalist physicians can rely on these tools to remove the easy, cancer and not cancer cases, so they can focus or get a consult on the most difficult,” said the study’s senior author, Stephen Deppen, PhD, associate professor of Thoracic Surgery and co-director of the Early Detection Research Network Lung Group’s National Clinical Validation Center.

Other Vanderbilt Health authors are Caroline Godfrey, MD, MPH, Ashley Leech, PhD, MS, Kevin McGann, MD, Jinyi Zhu, PhD, MPH, Hannah Marmor, MD, MPH, Sophia Pena, Fabien Maldonado, MD, MSc, Evan Osmundson, MD, PhD, and Stacie Dusetzina, PhD. The researchers received support from National Institutes of Health grants T32CA106183, K01DA050740, R01CA253923, P30CA068485, U01CA152662, R01CA252964 and U01CA152662.

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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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