Fabien Maldonado1,2, Rory Lee3
1Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA; 2Department of Thoracic Surgery, Vanderbilt University School of Medicine, Nashville, TN, USA; 3JTD Editorial Office, AME Publishing Company
Correspondence to: Rory Lee. JTD Editorial Office, AME Publishing Company. Email: jtd@amepc.org.
Editor’s note
Journal of Thoracic Disease (JTD) has published a number of special series in recent years, receiving overwhelming responses from academic readers around the world. Our success cannot be achieved without the contribution of our distinguished guest editors. This year JTD launched a new column, “Interviews with Guest Editors”, to better present our guest editors and to further promote the special series. We also hope to express our heartfelt gratitude for their tremendous effort and to further uncover the stories behind the special series.
The special series “Novel Diagnostic Techniques for Lung Cancer” (1) led by Dr. Fabien Maldonado (Figure 1) and Dr. Robert J. Lentz from Vanderbilt University School of Medicine has attracted many readers since its publication. It was our sincere hope that the state-of-the-art reviews on relevant and debated topics in lung nodule management in the special series will stimulate discussions, encourage research and inform clinical decisions to hopefully ultimately improve patient care. At this moment, we are honored to have an interview with Dr. Maldonado to share his scientific career experience and insights on this special series.
Figure 1 Dr. Fabien Maldonado.
Expert introduction
Dr. Fabien Maldonado’s main research interests primarily revolve around the development and evaluation of advanced bronchoscopic approaches to diagnosis and treatment of lung cancer and the development and assessment of novel imaging biomarkers for thoracic malignancies. His areas of research expertise include radiomics and machine learning as well as pragmatic clinical trials. His laboratory developed a number of imaging biomarkers such as CANARY (Computer Aided Nodule Assessment and Risk Yield) using quantitative imaging based on chest CT imaging to risk-stratify lung adenocarcinomas, and BRODERS (Benign versus aggressive nodule evaluation using radiomic stratification), which facilitates the non-invasive characterization of peripheral lung nodules. As part of an NCI-funded project, the team is leveraging data from the electronic health record to model the probability of malignant lung nodules in combination with novel deep learning-based radiomic approaches (delta radiomics) and temporal trends in a blood-based biomarker (CYFRA21-1 measured by compensated interferometer). His lab has also developed expertise in pragmatic clinical trials in the field of lung biopsy and is currently conducting the first investigator-initiated multicenter clinical trial comparing navigational bronchoscopy to CT-guided biopsy (VERITAS, NCT05705544) as well as the first clustered randomized control trial comparing robotic to electromagnetic navigational bronchoscopy (RELIANT, NCT05705544).
Interview
JTD: What drove you into the field of lung cancer research?
Dr. Maldonado: Lung cancer remains the most common cause of cancer mortality in the US and in the world. While it is primarily driven by smoking exposure, the rate of lung cancer in never smokers has been consistently rising in the past two decades. The landscape of lung cancer has changed as well, previously dominated by large central tumors such as small cell lung cancer and squamous cell carcinoma but now primarily characterized by peripheral lung adenocarcinoma. Despite these changes, the prognosis of lung cancer remains dismal compared to other cancers for which effective screening strategies exist. While lung cancer screening has been clearly established as a very effective way to decrease lung cancer mortality, it remains largely underutilized. Furthermore, a majority of lung cancers remain diagnosed in patients who are not eligible for lung cancer screening. There is a critical need for early detection to improve patient outcomes, which highlights the need for improved noninvasive and invasive strategies to identify these patients early.
JTD: A variety of novel bronchoscopic tools have emerged over recent years, such as radial probe endobronchial ultrasound (REBUS), thin/ultrathin bronchoscopes, virtual bronchoscopic navigation (VBN) and so on. How do these new bronchoscopies differ from traditional bronchoscopies of diagnosing lung cancer?
Dr. Maldonado: There has been a true revolution in the past 10 to 15 years in the field of interventional pulmonology. When I started my general pulmonary fellowship at Mayo Clinic in 2006, peripheral bronchoscopy essentially consisted of conventional flexible bronchoscopy with the use of C-arm fluoroscopy. We now have a variety of advanced tools at our disposal including digital tomosynthesis, cone-beam CT, robotic bronchoscopy, radial ultrasound among others. Biopsy tools are evolving as well with the advent of cryobiopsy. Yet, it is unclear as to whether these unprecedented technological advances have resulted in significantly improved diagnostic yields. Most studies consist primarily of single arm retrospective and often single center studies. There is a clear signal that we have markedly improved from a diagnostic standpoint, yet comparative effectiveness studies remain rare. There is a critical need for methodologically robust data in this space to identify which technologies should be adopted and which should be abandoned. This is an exciting time for interventional pulmonary research.
JTD: What are the benefits of using these new diagnostic techniques for patients with lung nodules?
Dr. Maldonado: Our approach to diagnosing pulmonary nodules has shifted dramatically, in spite of the aforementioned lack of robust evidence. A very appealing aspect of peripheral bronchoscopy compared to other strategies such as surgical lung biopsy or CT guided biopsy, is the relatively low rate of complications, but more importantly the ability to stage the mediastinum in the same setting and occasionally biopsy more than one nodule. Yet, a critical evaluation of the pros and cons of all these technologies will require robust comparative effectiveness data. They are many efforts in this space with the recent establishment of the interventional pulmonary outcomes group (IPOG), which has led to a number of ongoing randomized controlled trials which will inform optimal patient care.
JTD: Could you briefly introduce the latest advancements in lung cancer diagnostic techniques? Are these new techniques widely available, or are they still at the experimental stage?
Dr. Maldonado: This is a great question. One of the main issues for clinicians like myself is that most of these new technologies are cleared for commercialization on the basis of perceived equivalence with already commercialized technologies. In the US, this is accomplished through the Food and Drug administration 510(k) pathway which allows commercialization of new devices provided the device manufacturer is able to demonstrate substantial equivalence to a preexisting, so-called predicate device. The issue with this pathway is that clinical data demonstrating improved patient outcomes are almost never requested and when requested, not made available to clinicians. The process is similar in Europe which has led to a real data vacuum. This represents a fantastic opportunity for clinical researchers and a number of research networks have emerged over the past few years to respond to this need.
JTD: Is the topic of this special series associated with any of your recent research projects? Would you please share some significant researches you are working on?
Dr. Maldonado: I share my research time between two research laboratories: the Vanderbilt MASLAB (multidisciplinary assessment of lung cancer using biomarkers), which is primarily funded by the National Cancer Institute in the US to develop, validate and implement novel noninvasive biomarkers for early detection of lung cancer. These include not only blood-based biomarkers, but also quantitative imaging (radiomics), and advanced machine learning strategies to leverage big data available both in imaging datasets and electronic health records. The other research laboratory I lead is the Vanderbilt Interventional Pulmonary Research laboratory which is primarily focused on running investigator-initiated pragmatic comparative effectiveness randomized clinical trials.
JTD: If given an opportunity to update this special series, what would you like to moderate, add or emphasize to provide a more comprehensive series?
Dr. Maldonado: I would focus on the major efforts pursued recently to establish benchmarks for relevant clinical outcomes for clinical trials, the emergence of a solid infrastructure for randomized clinical trials in the field of interventional pulmonology, and the shift from discovery and validation in the preclinical setting for biomarkers to implementation and evaluation of clinical utility clearly establishing improved patient outcomes. The past five years have been transformative in terms of translational and clinical research in this space and it is my deep desire that these efforts soon translate into quantifiable improved patient outcomes for this terrible disease.
Reference
- Novel Diagnostic Techniques for Lung Cancer Available online: https://jtd.amegroups.com/post/view/novel-diagnostic-techniques-for-lung-cancer