Faculty Bibliography

The field of Interventional Pulmonology suffers from a paucity of methodologically robust studies to inform patient care, often relying on retrospective, single-center, non-comparative cohorts of commercialized products. The Interventional Pulmonary Outcomes Group (IPOG) was established to address the critical need for increased scientific rigor within the Interventional Pulmonology community. IPOG convened a meeting to assess the current state and future needs for minimally invasive lung cancer diagnostics and treatment. The goals of this meeting were to review the current landscape, and identify gaps and barriers in lung cancer diagnostics and therapeutics research. From this discussion short- and long-term research goals and priorities were identified. Nineteen international experts from various institutions and disciplines participated. The top short-term priorities identified were: 1) harmonization of core outcome measures in interventional pulmonology trials, 2) validation of a pathway/structure for the introduction of new technology, 3) establishment of a patient advisory board with focus on patient centered outcomes, 4) early engagement with industry partnerships during clinical trial design. The top long-term priorities identified were: 1) characterize the development, implementation, and role of bronchoscopic ablation, 2) validation and clinical utility of biomarker use and artificial intelligence, 3) implement research training skills for junior investigators in interventional pulmonology, 4) deliver 5 prospective, large clinical trials, with at least one adaptive trial, 5) develop a biorepository accessible to investigators. This perspective reviews the colloquium discussions, the identified priorities and the plans to help address those priorities as well as progress made in the year since its inception. Keywords: Interventional Pulmonology Outcomes Group; Interventional Pulmonology; Lung Cancer; Research; Outcomes.

INTRODUCTION/UNASSIGNED:Outcomes for NSCLC remain suboptimal. Recent data suggest that cryoablation can generate antitumor immune effects. In this first-in-human phase I clinical trial, we investigated the safety and feasibility of bronchoscopic cryoimmunotherapy (BCI) delivered during standard-of-care bronchoscopy and explored associated systemic immune responses. METHODS/UNASSIGNED:Subjects with known or suspected advanced-stage NSCLC were recruited. BCI was delivered in dose-escalated freeze-thaw cycles to determine maximum dose tolerance. Feasibility assessment was determined with a pre-set goal of achieving successful BCI in more than or equal to 80% of subjects. Safety was assessed by review of BCI-related complications, including grades 2 to 3 bleeding, pneumothorax requiring intervention, and National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 to 5 adverse events. Pre- and post-BCI blood samples were collected to explore changes in the systemic immune profile. RESULTS/UNASSIGNED:Subjects with predominantly clinical TNM stage 3 or 4 adenocarcinoma or squamous cell carcinoma were enrolled. We reached the maximum dose of 30 seconds with 100% feasibility and no BCI-related adverse events. In peripheral blood analysis, we observed a significant decrease in derived neutrophil-to-lymphocyte ratio in the high-dose BCI group in comparison to the low-dose BCI cohort. We also observed increases in inflammatory cytokines-GM-CSF, IFN-γ, IL-1β, IL-17A, and IL-2-and effector memory T cells post-BCI. CONCLUSION/UNASSIGNED:BCI is safe and feasible. In addition, we provide preliminary evidence that at higher dose levels there is a systemic immune response consistent with a cytotoxic profile. Further immune analyses will determine the potential of BCI as an adjunctive therapy in combination with immune checkpoint inhibition in NSCLC treatment.

Pleural effusions are commonly encountered in the practice of pulmonary medicine, and their clinical evaluation is usually straightforward. However, up to 20% of pleural effusions are not diagnosed despite clinical evaluation and pleural fluid analysis. Further investigation of the undiagnosed pleural effusion requires a systematic evaluation using clues from a patient's history, physical examination, imaging, and pleural fluid analysis help narrow down the differential diagnosis. Occasionally, pleural biopsy may be necessary via several minimally invasive techniques, especially if malignancy is considered.

Therapeutic bronchoscopy is well established for palliative treatment of advanced malignancies, including for recanalization of malignant central airway obstruction. Although less common in clinical practice, bronchoscopic treatments (including thermal ablation) may also be considered for curative endobronchial treatment in several clinical scenarios including benign or occasionally low-grade purely endoluminal neoplasms. In this article, we highlight evidence for where endobronchial therapies for curative intent may be considered based on clinical experience over several decades. Although treatment of peripheral lung malignancies remains investigational at this time, advantages and disadvantages of several ablative techniques and potential immunostimulatory therapies are also discussed.

PURPOSE OF REVIEW:Percutaneous tracheostomy and gastrostomy are minimally invasive procedures among the most common performed in intensive care units. Practices across centres vary considerably, and questions remain about the optimal timing, performance and postoperative care related to these procedures. RECENT FINDINGS:The COVID-19 pandemic has triggered a reevaluation of the practice of percutaneous tracheostomy and gastrostomy in the ICU. Combined percutaneous tracheostomy and gastrostomy at the bedside has potential benefits, including improved nutrition, decreased exposure to anaesthetics, decreased patient transport and decreased hospital costs. Percutaneous ultrasound gastrostomy is a novel technique that eliminates the need for an endoscope that may allow intensivists to perform gastrostomy at the bedside. SUMMARY:Multidisciplinary care is essential to the follow up of critically ill patients receiving tracheostomy and gastrostomy. Combined tracheostomy and gastrostomy has numerous potential benefits to patients and hospital systems. Interventional pulmonologists are uniquely qualified to perform both procedures and serve on a tracheostomy and gastrostomy team.

Despite remarkable advances in tumor response and patient survival in the past decade, systemic immunotherapies for lung cancer result in an objective response in only around half of patients treated. On the basis of this limitation, combination strategies are being investigated to improve response rates. Cryoablation has been proposed as one such technique to induce immunogenic cell death and synergize with systemic immunotherapies, including immune checkpoint inhibitors. Cryoablation has been traditionally delivered percutaneously with imaging guidance although recent technological advances allow for bronchoscopic delivery. Herein, we review the pre-clinical and clinical evidence for the use of cryoablation in non-small cell lung cancer and potential induction of anti-tumor immunity. We highlight ongoing studies involving this approach and propose areas of future investigation.

BACKGROUND:Despite recent advances in guided bronchoscopy, the yield of bronchoscopic biopsy of a peripheral pulmonary nodule (PPN) remains highly variable. OBJECTIVE:The aim of the study was to evaluate which features of robotic assisted bronchoscopy (RAB) contribute to a successful biopsy in a cadaver model. METHODS:A preclinical, prospective, single-blinded trial using a ventilated human cadaveric model assessed the successful puncture of implanted pulmonary nodules using various localization techniques with RAB. The different approaches included positioning the robotic catheter at predefined distances from the target nodule (<10 mm, 10-20 mm, 20-30 mm), bronchoscopist correction of divergence between the software virtual map and bronchoscopic view if observed, and impact of fluoroscopy and radial endobronchial ultrasound (rEBUS). The primary endpoint was a central target hit (defined as an inner 2/3 target puncture) verified by cone-beam computed tomography. RESULTS:Thirty-eight RAB procedures were performed to target 16 PPNs. Median nodule size was 16.2 mm. All targets were located in the outer 1/3 of the lung with a bronchus sign in 31.3%. Central target hit rates were improved when the robotic catheter tip was closer to the nodule (<10 mm 68%, 10-20 mm 66%, 20-30 mm 11%, p < 0.001). Multivariable analysis confirmed the strongest predictor of a central target hit was robotic catheter distance to nodule (OR 0.89 per increase in 1 mm, p < 0.001), independent of the presence of a bronchus sign, divergence or concentric rEBUS view. CONCLUSIONS:Utilizing a RAB platform, closer proximity of the robotic catheter to the target nodule results in an increase in peripheral nodule biopsy success.

Pneumothorax is a common medical condition encountered in a wide variety of clinical presentations, ranging from asymptomatic to life threatening. When symptomatic, it is important to remove air from the pleural space and provide re-expansion of the lung. Additionally, patients who experience a spontaneous pneumothorax are at high risk for recurrence, so treatment goals also include recurrence prevention. Several recent studies have evaluated less invasive management strategies for pneumothorax, including conservative or outpatient management. Future studies may help to identify who is greatest at risk for recurrence and direct earlier definitive management strategies, including thoracoscopic surgery, to those patients.

The past decade has brought remarkable improvements in the treatment of non-small cell lung cancer (NSCLC) with novel therapies, such as immune checkpoint inhibitors, although response rates remain suboptimal. Direct intratumoural injection of therapeutic agents via bronchoscopic approaches poses the unique ability to directly target the tumour microenvironment and offers several theoretical advantages over systemic delivery including decreased toxicity. Increases in understanding of the tumour microenvironment and cancer immunology have identified many potential options for intratumoural therapy, especially combination immunotherapies. Herein, we review advances in the development of novel bronchoscopic treatments for NSCLC over the past decade with a focus on the potential of intratumoural immunotherapy alone or in combination with systemic treatments.