Advances in Diagnostics and Therapeutics Propel Interventional Pulmonology Forward

Nathaniel Ivanick, MD, FCCP

Significant developments with advanced diagnostics and therapeutics have pushed the field of interventional pulmonology into a period of rapid change, said Nathaniel Ivanick, MD, FCCP, who added that cutting-edge technologies such as robotic navigational bronchoscopy have enabled the identification and treatment of lung nodules to become more accurate, stable, and effective than conventional approaches.

“This is an exciting time to be an interventional pulmonologist,” said Ivanick. “We are making a lot of advancements in advanced diagnostics of peripheral lesions, as well as treatment of central tumors. We are forging ahead in both areas. One day soon, I hope to be able to wake a patient up [after a bronchoscopy] and tell them that the bad news is I found cancer, but the good news is that they have had their first treatment while they were asleep during the procedure.”

In an interview with OncLive^®, Ivanick, an interventional pulmonologist in the Department of Thoracic Surgery and an assistant professor of oncology and thoracic surgery at Roswell Park Comprehensive Cancer Center, discussed the evolution of interventional pulmonology, the benefits of robotic navigational bronchoscopy and other novel technologies in the field, and ongoing research that could further push the paradigm forward.

OncLive^®:How has the field of interventional pulmonology evolved?

Ivanick: Interventional pulmonology] has evolved quite a bit in that it has come into being. It wasn’t really a thing 20 years ago, but because of the lung cancer epidemic and increased diagnostic abilities, the specialties have recognized this need for someone who provides the careful thought of a pulmonologist with the advanced procedural skill of a surgeon without being a true surgeon.

[The field] has grown with the ability to perform robotic bronchoscopy in the past few years, peripheral navigation extending back about 15 years, and finally, endobronchial ultrasound [EBUS] to stage the mediastinum. These have probably been the greatest growths in our field over the past 20 years.

[Additionally, we’ve seen] the management of malignant airway obstruction and other [procedures] that we do on a fairly routine basis to palliate symptoms of airway disease.

There have been a lot of exciting developments in our field. The first is with advanced diagnostic capabilities. This started with conventional bronchoscopy and being able to get out further into lesions. That was followed by radial EBUS, which allowed us to identify whether we were able to get into the center of these more peripheral lesions and greatly increase our diagnostic accuracy. After that came navigational bronchoscopy and, finally, robotic navigational bronchoscopy, which has allowed us to get into the center of a lot of these targets that were previously too small or too near the periphery to adequately biopsy.

On the horizon is also the possibility of not just diagnostics, but therapeutics to the periphery with microwave ablation or photodynamic therapy. In the next 5 years, quite a few additional therapies will edge into the mainstream.

What can community practices do to improve upon their diagnostic strategies?

We have known about lung cancer screening for 10 years. In 2011, the [National Lung Screening Trial] showed us that we can enact a stage shift that lets us identify lung cancer at earlier stages and have more therapeutic options. Despite that, only about 5% of eligible patients in the United States are screened. Recently, the United States Preventive Services Task Force has broadened the scope of who can be screened. It was previously patients aged 55 to 75 years with a previous 30-pack-year history of smoking and under 15 years since cessation. It’s now broadened to 50 to 80 years of age with a 20-pack-year history of smoking. [The guideline] still [states that patients should be] under 15 years since smoking cessation.

Therefore, 5% nationwide is what we are doing for our ability to identify patients who would be eligible and screening them appropriately. In Western New York, we are right at that 5% mark, but New York overall is about 8.5%. If we make improvements in this area, we will see a lot more patients come to light that are able to be treated at an earlier stage. The COVID-19 pandemic has unfortunately knocked all this back a lot because people were delayed in seeking care. We have not seen a positive stage shift; we are seeing sicker patients now. Hopefully, as the pandemic ends, [screening] will improve.

How do you define the role of interventional pulmonologists in the management of lung cancer?

I break interventional pulmonology into 2 major roles within the field of lung cancer care and thoracic care in general: advanced diagnostics and therapeutics.

The advanced diagnostics are done for early-stage and late-stage disease. It includes going after small peripheral lung nodules. Wherein we had previously not had the ability, we can now go after those [nodules] with the robotic navigational scope technology that we have to achieve diagnoses earlier where surgery is a definite possibility.

Then we have cancers that spread into the hilar and mediastinal lymph nodes. In those instances, we use something that has been around for about 20 years: linear EBUS. [With that,] we can identify lymph nodes that sit close to the surface of the airway and biopsy them with a needle. Previously, this was accomplished through a mediastinoscopy or a CT-guided biopsy of the lymph nodes for interventional radiologists who were extremely brave. Luckily, going through the airway now allows us to identify malignancies in small lymph nodes down to about 5 mm. We have really advanced the diagnostic spectrum with that.

Finally, [advanced diagnostics includes] identifying malignancies within the pleura and identifying treatments that can be accomplished in [pleural disease].

Then there is the therapeutics side. In the field of lung cancer care, therapeutics and interventional pulmonology primarily center on palliation of locally advanced or metastatic disease. When there is an airway obstruction, which causes substantial narrowing of the airways, we can go in with rigid therapeutic bronchoscopy, ablate tumors that are in the airways, and place stents to keep the airways open longer. That way patients have fewer negative adverse effects afterward. In the pleura, we can place tunnel pleural catheters or perform pleuroscopy and pleurodesis to allow the edge of the lung, called the pleura, to stick against the chest wall and palliate symptoms of metastatic disease in those areas.

How do you determine whether robotic navigational bronchoscopy is the right approach for a patient?

Navigational bronchoscopy evolved from a recognition that we needed to be able to get to the periphery of the lung to take biopsies. It uses an updated, very high-resolution CT scan of the chest that can create a virtual bronchoscopic image such that we are able to identify where a nodule is within the space of the chest. We then combine that with an electromagnetic [EM] field, which is placed on or around the patient. The combination of those with an updated software that is continuously talking to the EM field with the virtual bronchoscope tells us where we are within the airways, at least as compared with the CT scan that was obtained.

Robotic bronchoscopy takes that a step further and allows us to do all those things with a scope that maintains stability, extends our reach, and allows us to get out to the periphery to make micro-adjustments to sample a multitude of areas within a given nodule depending on its size.

For me, the choice is easy. I don’t use conventional navigational bronchoscopy any longer because I’ve found that my diagnostic yield and safety profile are significantly enhanced when using robotic bronchoscopy.

How do you choose between conventional bronchoscopy and any sort of navigational bronchoscopy?

There are several factors that play [into the decision]. First, I want to go after peripheral targets with navigational bronchoscopy. That’s a basic statement, but what I mean is that if we can see a tumor within the airways, there is no need to use the more expensive and advanced navigational software. Second, if a PET scan has already been obtained, and a patient has identified mediastinal or hiler lymph nodes that are markedly PET avid, there is no reason why we would need to resort to robotic bronchoscopy. Identification of the tumor within the lymph nodes is viewed as sufficient [in these cases]. Finally, if a lesion is not completely central but is large enough that we could navigate a scope and extend, for instance, radial EBUS out to the periphery, we likely don’t need robotic bronchoscopy.

Those [instances that call for conventional bronchoscopy] account for perhaps 30% to 40% of the scopes that I do, so we still have a large proportion of patients where robotic scope technology is necessary.

What makes robotic navigational bronchoscopy a cutting-edge technology?

Several things make robotic bronchoscopy a cutting-edge addition [to interventional pulmonology]. The first is reach. [Alexander C. Chen, MD, of Washington University Physicians] and colleagues at the University of Washington demonstrated that robotic navigational bronchoscopy can extend the distance that we are able to travel to the periphery by about 4 divides of the airway. That means that the airways branch somewhere between 17 and 24 times in between the main windpipe and the smallest of the air cells. [Robotic bronchoscopy] gets us 4 to 5 branch points further and often, that is enough to get to the edge of a nodule that we can successfully biopsy.

[Robotic bronchoscopy] was compared with an ultra-thin bronchoscope, which has the same diameter. The difference is that the ultra-thin bronchoscope doesn’t have the stiffness and stability to extend itself as far out as necessary. Therefore, it can’t advance any further. [Robotic bronchoscopy] was groundbreaking in its ability to get several branch points further [than ultra-thin bronchoscope].

The second [cutting-edge factor of robotic bronchoscopy] is vision. With certain types of robotic scope—I use the MONARCH platform—we can visualize ourselves at the edge of the lesion far further than we would be able to otherwise. We can often see the tumor within the airway. Also, [with robotic bronchoscopy], we are sending a biopsy instrument up an airway. When we use more conventional techniques and get back information from pathologists, this is just bronchial cells, even though it looks like you are directly in the center [of the lesion]. With robotic bronchoscopy, we can make micro-adjustments to target the nodules much better.

The third [cutting-edge factor of robotic bronchoscopy] is stability. With older navigational platforms, the bronchoscopist extends an extended working channel by standing at the head of the bed for an hour and a half straight. They do not move. Although they might make tiny adjustments, anything that they did would require reassessment of where they were in relation to the lesion.

Fast forward to today when we can drive the scope out with a controller that looks like a PlayStation controller. Once we are present, we can park the controller and take biopsies. I can walk over and look at the slides I’m making. I can review those slides in another room with a pathologist. That stability is an incredible advantage.

Finally, we can make micro-adjustments such that when I am targeting a lesion that is 2 cm to 3 cm, I am able to start on one side of the lesion and work my way slowly across to the other side. If the diagnostic information that I am getting at the first sight is not sufficient, I can move it over slightly and take additional biopsies. This will be hugely important when we are looking at semi-solid nodules that have ground glass and solid components. We can see if there is a difference in tumor biology in these different areas by starting at one side and moving to another.

Is there ongoing research you are involved in that you would like to call attention to?

I’m very fortunate at Roswell to be able to work in a busy clinical practice, as well as a research practice. I have several studies in mind that are exciting and will offer therapeutic benefits [to patients].

The first study is evaluating interstitial photodynamic therapy [PDT]. We are [evaluating PDT] in a pilot trial [NCT03735095] that was recently completed. We are identifying areas of tumor within the central airway, planning out exactly where the tumor is, giving patients a photosensitizer that goes into the tumor as part of PDT. Then, we act directly on those sites using a laser that is directed in through an EBUS needle. [With this technology], we can treat tumors within the airway, as well as those just outside of the airway, to hopefully palliate symptoms of locally advanced or metastatic disease. We have recently completed that study and we have a phase 2a study that is sponsored by the NIH [National Institutes of Health] to expand the scope of where we are going with [PDT].

Secondly, despite all the advances that we are making in peripheral targets, we know astonishingly little about central targets in terms of how often they happen, the natural history and epidemiology of these malignant central airway obstructions, how they affect patients, when we see it in the greatest frequency, what we can do about it, and how those treatments affect patients long term.

With the Roswell robust database, I’m conducting a massive retrospective review of all patients diagnosed with an airway obstruction in the past 20 years at Roswell. Stay tuned for that because I’m excited for the data.

I’m also doing several other studies looking directly with the MONARCH robot at the first real-world evaluation. What is our diagnostic yield? What are the complications? What is the procedure time? We are looking at all sorts of important and intuitive questions that will enlighten us to choose the best treatment moving forward.

I’m also involved in some therapeutic trials that may allow us to assess what we can do for patients who have just been diagnosed with lung cancer.

Finally, I’m involved with several trials evaluating the field of effective cancer. So, we see cancer in a lung nodule, but the airways might not be normal either. Is there a field of effective cancer? Does it extend beyond that central nodule to more central airway divides or even the main airway divide?