The Lung Cancer Prediction Model "Stress Test": Assessment of Models' Performance in a High-Risk Prospective Pulmonary Nodule Cohort.

BACKGROUND: Pulmonary nodules represent a growing health care burden because of delayed diagnosis of malignant lesions and overtesting for benign processes. Clinical prediction models were developed to inform physician assessment of pretest probability of nodule malignancy but have not been validated in a high-risk cohort of nodules for which biopsy was ultimately performed. RESEARCH QUESTION: Do guideline-recommended prediction models sufficiently discriminate between benign and malignant nodules when applied to cases referred for biopsy by navigational bronchoscopy? STUDY DESIGN AND METHODS: We assembled a prospective cohort of 322 indeterminate pulmonary nodules in 282 patients referred to a tertiary medical center for diagnostic navigational bronchoscopy between 2017 and 2019. We calculated the probability of malignancy for each nodule using the Brock model, Mayo Clinic model, and Veterans Affairs (VA) model. On a subset of 168 patients who also had PET-CT scans before biopsy, we also calculated the probability of malignancy using the Herder model. The performance of the models was evaluated by calculating the area under the receiver operating characteristic curves (AUCs) for each model. RESULTS: The study cohort contained 185 malignant and 137 benign nodules (57% prevalence of malignancy). The malignant and benign cohorts were similar in terms of size, with a median longest diameter for benign and malignant nodules of 15 and 16 mm, respectively. The Brock model, Mayo Clinic model, and VA model showed similar performance in the entire cohort (Brock AUC, 0.70; 95% CI, 0.64-0.76; Mayo Clinic AUC, 0.70; 95% CI, 0.64-0.76; VA AUC, 0.67; 95% CI, 0.62-0.74). For 168 nodules with available PET-CT scans, the Herder model had an AUC of 0.77 (95% CI, 0.68-0.85). INTERPRETATION: Currently available clinical models provide insufficient discrimination between benign and malignant nodules in the common clinical scenario in which a patient is being referred for biopsy, especially when PET-CT scan information is not available.

Robotic versus Electromagnetic bronchoscopy for pulmonary LesIon AssessmeNT: the RELIANT pragmatic randomized trial.

BACKGROUND: Robotic-assisted bronchoscopy has recently emerged as an alternative to electromagnetic navigational bronchoscopy for the evaluation of peripheral pulmonary lesions. While robotic-assisted bronchoscopy is proposed to have several advantages, such as an easier learning curve, it is unclear if it has comparable diagnostic utility as electromagnetic navigational bronchoscopy. METHODS: Robotic versus Electromagnetic bronchoscopy for pulmonary LesIon AssessmeNT (RELIANT) is an investigator-initiated, single-center, open label, noninferiority, cluster randomized controlled trial conducted in two operating rooms at Vanderbilt University Medical Center. Each operating room (OR) is assigned to either robotic-assisted or electromagnetic navigational bronchoscopy each morning, with each OR day considered one cluster. All patients undergoing diagnostic bronchoscopy for evaluation of a peripheral pulmonary lesion in one of the two operating rooms are eligible. Schedulers, patients, and proceduralists are blinded to daily group allocations until randomization is revealed for each operating room each morning. The primary endpoint is the diagnostic yield defined as the proportion of cases yielding lesional tissue. Secondary and safety endpoints include procedure duration and procedural complications. Enrolment began on March 6, 2023, and will continue until 202 clusters have been accrued, with expected enrolment of approximately 400 patients by the time of completion in March of 2024. DISCUSSION: RELIANT is a pragmatic randomized controlled trial that will compare the diagnostic yield of the two most commonly used bronchoscopic approaches for sampling peripheral pulmonary lesions. This will be the first known cluster randomized pragmatic trial in the interventional pulmonology field and the first randomized controlled trial of robotic-assisted bronchoscopy. TRIAL REGISTRATION: ClinicalTrials.gov registration (NCT05705544) on January 30, 2023.

Navigational Bronchoscopy versus Computed Tomography-guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules: protocol and rationale for the VERITAS multicenter randomized trial.

Background: Lung nodule incidence is increasing. Many nodules require biopsy to discriminate between benign and malignant etiologies. The gold-standard for minimally invasive biopsy, computed tomography-guided transthoracic needle biopsy (CT-TTNB), has never been directly compared to navigational bronchoscopy, a modality which has recently seen rapid technological innovation and is associated with improving diagnostic yield and lower complication rate. Current estimates of the diagnostic utility of both modalities are based largely on non-comparative data with significant risk for selection, referral, and publication biases. Methods: The VERITAS trial (na V igation E ndoscopy to R each Indeterminate lung nodules versus T ransthoracic needle A spiration, a randomized controlled S tudy) is a multicenter, 1:1 randomized, parallel-group trial designed to ascertain whether electromagnetic navigational bronchoscopy with integrated digital tomosynthesis is noninferior to CT-TTNB for the diagnosis of peripheral lung nodules 10-30 mm in diameter with pre-test probability of malignancy of at least 10%. The primary endpoint is diagnostic accuracy through 12 months follow-up. Secondary endpoints include diagnostic yield, complication rate, procedure duration, need for additional invasive diagnostic procedures, and radiation exposure. Discussion: The results of this rigorously designed trial will provide high-quality data regarding the management of lung nodules, a common clinical entity which often represents the earliest and most treatable stage of lung cancer. Several design challenges are described. Notably, all nodules are centrally reviewed by an independent interventional pulmonology and radiology adjudication panel relying on pre-specified exclusions to ensure enrolled nodules are amenable to sampling by both modalities while simultaneously protecting against selection bias favoring either modality. Conservative diagnostic yield and accuracy definitions with pre-specified criteria for what non-malignant findings may be considered diagnostic were chosen to avoid inflation of estimates of diagnostic utility. Trial registration: ClinicalTrials.gov NCT04250194.

Diagnostic Yield vs Diagnostic Accuracy for Peripheral Lung Biopsy Evaluation: Evidence Supporting a Future Pragmatic End Point.

BACKGROUND: Diagnostic yield and accuracy endpoints have been used inconsistently in the evaluation of advanced diagnostic bronchoscopy devices and techniques, limiting between-study comparisons. In addition, diagnostic accuracy can be adjudicated only after prolonged clinical follow-up, which delays reporting on the performance of novel devices. RESEARCH QUESTION: Will a conservative diagnostic yield definition result in few false-negative initial results to closely approximate diagnostic accuracy and represent a useful outcome for future studies of diagnostic utility? METHODS: Commonly used definitions of diagnostic yield were applied to a prospective data set of consecutive peripheral pulmonary lesions sampled by navigational bronchoscopy from 2017 to 2019. All consider malignancy to be diagnostic but differ in their classification of nonmalignant biopsy findings, which were subcategorized as specific benign, nonspecific benign, or normal lung. Diagnostic yield calculations were also compared with diagnostic accuracy, defined as the proportion of biopsy specimens deemed diagnostic by each definition that were confirmed accurate through 2 years of follow-up. RESULTS: A total of 450 biopsy specimens of lesions were analyzed. The prevalence of malignancy was 60.9% (274 of 450). On initial bronchoscopy pathology, there were 227 malignant diagnoses (50.4%), with a single false positive (0.4%). Among 104 biopsy specimens with specific benign findings, only two were false negative for malignancy (1.9%). There were 119 nonspecific benign biopsy specimens, with 46 false negatives for malignancy (38.7%). The discrepancy between diagnostic yield and accuracy was 0.7% for the conservative definition, which only considered malignant or specific benign findings as diagnostic. INTERPRETATION: A conservative diagnostic yield definition excluding nonspecific benign diagnoses closely approximated diagnostic accuracy through 2 years' follow-up, with a less than 1% discrepancy. Using this conservative yield definition may allow for dissemination of reliable diagnostic utility data without protracted delays needed for follow-up data in this era of rapid technological change in advanced diagnostic bronchoscopy.

Social vulnerability and lung malignancy mortality.

INTRODUCTION: Lung cancer is a major cause of death in the United States. Social determinants of health (SDOH) are important factors that impact the treatment and prognosis of lung cancer. The social vulnerability index (SVI) is a validated measure of SDOH. This cross-sectional study aimed to investigate the impact of the SVI on lung cancer mortality using descriptive epidemiology. METHODS: Mortality data for lung malignancies from 2014 to 2018 was obtained from the CDC database and was age-adjusted and standardized to the population in the year 2000. The SVI for the same years was obtained from the CDC Agency for Toxic Substances and Disease Registry database. Age-adjusted mortality rates (AAMR) were estimated for each SVI quartile (SVI-Q) and demographic subgroup. RESULTS: We found that counties in SVI-Q4 (most vulnerable) had a higher cumulative AAMR compared to counties in SVI-Q1 (least vulnerable), accounting for a 4.48 excess death rate per 100,000 person-years. AAMR among males in SVI-Q4 was higher compared to SVI-Q1, accounting for a 9.96 excess death rate per 100,000 person-years, whereas no mortality differences were observed for female populations between SVI-Q4 and SVI-Q1. AAMR in SVI-Q4 was higher for both Hispanic and non-Hispanic populations, except for American Indian/Alaska Native populations. Similar trends were observed in both metropolitan and non-metropolitan counties. CONCLUSION: Our study suggests that the SVI may play a significant role in lung cancer mortality and highlights the need for interventions targeting vulnerable populations to improve outcomes.

Robotic versus Electromagnetic Bronchoscopy for Pulmonary LesIon AssessmeNT: the RELIANT pragmatic randomized trial.

Background: Robotic assisted bronchoscopy has recently emerged as an alternative to electromagnetic navigational bronchoscopy for the evaluation of peripheral pulmonary lesions. While robotic assisted bronchoscopy is proposed to have several advantages, such as an easier learning curve, it is unclear if it has comparable diagnostic utility as electromagnetic navigational bronchoscopy. Methods: Robotic versus Electromagnetic Bronchoscopy for Pulmonary LesIon AssessmeNT (RELIANT) is an investigator-initiated, single-center, open label, noninferiority, cluster randomized controlled trial conducted in two operating rooms at Vanderbilt University Medical Center. Each operating room is assigned to either robotic assisted or electromagnetic navigational bronchoscopy each morning, with each OR day considered one cluster. All patients undergoing diagnostic bronchoscopy for evaluation of a peripheral pulmonary lesion in one of the two operating rooms are eligible. Schedulers, patients and proceduralists are blinded to daily group allocations until randomization is revealed for each operating room each morning. The primary endpoint is the diagnostic yield defined as the proportion of cases yielding lesional tissue. Secondary and safety endpoints include procedure duration and procedural complications. Enrolment began on March 6, 2023, and will continue until 202 clusters have been accrued, with expected enrolment of approximately 400 patients by the time of completion in March of 2024. Discussion: RELIANT is a pragmatic randomized controlled trial that will compare the diagnostic yield of the two most commonly used bronchoscopic approaches for sampling peripheral pulmonary lesions. This will be the first known cluster randomized pragmatic trial in the interventional pulmonology field and the first randomized controlled trial of robotic assisted bronchoscopy. Trial registration: ClinicalTrials.gov registration (NCT05705544) on January 30, 2023.

Feasibility and Efficacy of a Non-Opioid Based Pain Management After Medical Thoracoscopy.

BACKGROUND: Prescription opioids are a major cause of the opioid epidemic. Despite the minimally invasive nature of medical thoracoscopy (MT), data on the efficacy of non-opioid-based pain control after MT is lacking. The purpose of this study is to assess the feasibility and efficacy of a non-opioid-based pain management strategy in patients who underwent MT. METHODS: We performed a retrospective analysis of all patients who underwent MT in the Mayo Clinic (Minnesota and Arizona) outpatient setting. We assessed their pain level and the need for analgesia post-MT from August 1, 2019, to May 24, 2021. RESULTS: Forty patients were included. In the first 24 hours, 5/40 (12.5%) reported no pain. Twenty-eight patients out of 40 (70%) reported minor pain (pain scale 1-3), and 7/40 (17.5%) reported moderate pain (pain scale 4-6). No patients reported severe pain. Twenty-two out of 35 patients who experienced discomfort (63%) required acetaminophen, 6/35 patients (17%) required nonsteroidal anti-inflammatory drug, and 7/35 patients (20%) did not require analgesia. Of the 7 patients who had moderate pain, 5 (71%) reported that the moderate pain improved to mild at 72 hours post-MT. Zero patients required opioids, and none reported contacting any provider to manage the pain post-MT. Fourteen patients (78%) who had both parietal pleural biopsies and tunneled pleural catheter placed reported minor pain, 3 patients (17%) reported moderate pain, and 1 patient (6%) experienced no discomfort. CONCLUSION: MT is well-tolerated by patients with non-opioid-based pain management strategy as needed if there is no absolute contraindication.

Shape-Sensing Robotic-Assisted Bronchoscopy vs Digital Tomosynthesis-Corrected Electromagnetic Navigation Bronchoscopy: A Comparative Cohort Study of Diagnostic Performance.

BACKGROUND: Electromagnetic navigational bronchoscopy has been the dominant bronchoscopic technology for targeting small peripheral lesions and now includes digital tomosynthesis-electromagnetic navigational bronchoscopy (DT-ENB), allowing near-real-time intraprocedural nodule visualization. Shape-sensing robotic-assisted bronchoscopy (ssRAB), with improved catheter stability and articulation recently became available. Although the diagnostic performance of these two methods seems higher than that of legacy systems, data remain limited. We sought to compare the diagnostic yield of these two novel platforms after their introduction at our institution. RESEARCH QUESTION: Does the diagnostic yield of ssRAB differ significantly from that of DT-ENB in patients undergoing biopsy of peripheral pulmonary lesions (PPLs)? STUDY DESIGN AND METHODS: This retrospective comparative cohort study analyzed prospectively collected data on consecutive procedures performed with DT-ENB and ssRAB in their first 6 months of use at our institution. Biopsies were considered diagnostic if histopathologic analysis revealed malignancy or specific benign features that readily explained the presence of a PPL. Nonspecific inflammation, normal lung or airway, and atypia not diagnostic of malignancy were considered nondiagnostic. RESULTS: SSRAB was used to biopsy 143 PPLs in 133 patients and DT-ENB was used to biopsy 197 PPLs in 170 patients. Diagnostic yield was 77% for ssRAB (110 of 143 PPLs) and 80% (158 of 197 PPLs) for DT-ENB (OR, 0.8; 95% CI, 0.5-1.4; P = .4). Median lesion diameters were 17 and 19 mm, respectively. No difference in diagnostic yield was found after adjustment for lesion size, bronchus sign, peripheral vs middle third location, and sex. Pneumothorax complicated 1.5% of ssRAB and 1.8% of DT-ENB procedures (P = .86). INTERPRETATION: SSRAB and DT-ENB showed comparable diagnostic yields and safety profiles in this comparative cohort study.

Complications of Endobronchial Valve Placement for Bronchoscopic Lung Volume Reduction: Insights From the Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE).

BACKGROUND: Patients with advanced emphysema experience breathlessness due to impaired respiratory mechanics and diaphragm dysfunction. Bronchoscopic lung volume reduction (BLVR) is a minimally invasive bronchoscopic procedure done to reduce hyperinflation and air trapping, promoting atelectasis in the targeted lobe and allowing improved respiratory mechanics. Real-world data on safety and complications outside of clinical trials of BLVR are limited. METHODS: We queried the US Food and Drug Administrations (FDA) Manufacturers and User Device Experience database from May 2019 to June 2020 for reports involving BLVR with endobronchial valve (EBV) placement. Events were reviewed for data analysis. RESULTS: We identified 124 cases of complications during BLVR with EBV implantation. The most-reported complication was pneumothorax (110/124, 89%), all of which required chest tube placement. A total of 54 of these cases (54/110, 49%) were complicated by persistent air leak requiring additional interventions. Repeat bronchoscopy was needed to remove the valves in 28 patients, 12 were discharged with a Heimlich valve, and 10 had an additional pleural catheter placed. The other complications of BLVR with EBV placement included respiratory failure (6/124, 5%), pneumonia (4/124, 3%), hemoptysis (2/124, 1.6%), valve migration (1/124, 1%), and pleural effusion (1/124, 1%). A total of 14 deaths were reported during that year. CONCLUSION: Pneumothorax is the most-reported complication for BLVR with EBV placement, and in 65% of cases, pneumothorax is managed without removing valves. Importantly, 14 deaths were reported during that timeframe. Further studies are needed to estimate the true magnitude of the complications associated with BLVR.

A multidisciplinary approach to the work up and management of pulmonary carcinoid tumors and DIPNECH: a narrative review.

Background and Objective: Low and intermediate grade neuroendocrine tumors of the lung are uncommon malignancies representing 2% of all lung cancers. These are termed typical and atypical pulmonary carcinoid tumors. These can arise in the setting of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). The presentation, workup, management and outcomes of patients with these tumors can overlap with more common lung cancers but differ in that many of these patients have a prolonged clinical course. The objective of this narrative review is to summarize the literature and provide evidence and expert-based algorithms for work up and treatment of pulmonary carcinoids and DIPNECH. Methods: A search of PubMed and Web of Science databases ending April 15, 2022, with the following keywords "lung carcinoid", "DIPNECH", "lung neuroendocrine," and "bronchopulmonary carcinoid". Key Content and Findings: Pulmonary carcinoid tumors benefit from a multidisciplinary approach. Pre-treatment imaging with contrast-enhanced computed tomography, and DOTATATE positron emission tomography is required. Surgical resection is the gold standard for curative intent, and possibly including sublobar resections. Patients can recur or develop new primaries thus emphasizing the importance of surveillance; national guidelines recommend at least a 10-year follow up. A growing body of literature support the use of endobronchial therapy, with long responses documented. Systemic therapy consists of everolimus, somatostatin analogs, peptide receptor radionuclide therapy, and chemotherapy. Diffuse idiopathic pulmonary neuroendocrine tumor cell hyperplasia is rare, but series suggest somatostatin analogs may confer clinical benefit. Conclusions: Pulmonary carcinoid tumors and DIPNECH are rare. Despite lack of regulatory approvals for advanced disease, multiple options are available but should be sequenced according to the clinical status and disease biology. Each patient should be discussed in a multidisciplinary setting and clinical trials should be considered if available.

Indwelling pleural catheter tract metastasis from renal cell carcinoma.

This case highlights the importance of recognizing any new soft tissue abnormalities in cancer patients with an indwelling pleural catheter (IPC) or who has had an IPC. This report also describes the first case of catheter tract metastasis (CTM) due to renal cell carcinoma (RCC) and the second case of CTM post-IPC removal.

Endobronchial Valves Therapy for Advanced Emphysema: A Meta-Analysis of Randomized Trials.

BACKGROUND: Trials suggest that bronchoscopic lung volume reduction (BLVR) with endobronchial valve (EBV) implantation may produce similar effects as lung volume reduction surgery, by inducing atelectasis and reducing hyperinflation through a minimally invasive procedure. This study sought to investigate the efficacy and safety of BLVR with EBV for advanced emphysema. METHODS: We searched PubMed, EMBASE, Web of Science, CINAHL, ClinicalTrials.gov, and Cochrane Library databases for randomized controlled trials comparing EBV implantation versus standard medical treatment or sham bronchoscopy. The main outcome of interest was the percentage change of forced expiratory volume in 1 second. RESULTS: Data analyzed from 5 randomized controlled trials with 703 patients revealed improvement in percentage change of forced expiratory volume in 1 second in EBV group compared with control group [weighted mean difference (WMD)=11.43; 95% confidence interval (CI), 6.05-16.80; P<0.0001] and improvement in the St. George's Respiratory Questionnaire score (WMD=-5.69; 95% CI, -8.67 to -2.70; P=0.0002). There is no difference shown in the 6-minute walking test (WMD=14.12; 95% CI, -4.71 to 32.95; P=0.14). The overall complication rate of EBV was not significantly different except for an increased rate of pneumothorax [relative risk (RR)=8.16; 95% CI, 2.21-30.11; P=0.002), any hemoptysis (RR=5.01; 95% CI, 1.12-22.49; P=0.04)] and valve migration (RR=8.64; 95% CI, 2.01-37.13; P=0.004). CONCLUSION: BLVR using EBV shows short-term improvement in lung function and quality of life, but with increased risk of minor hemoptysis, pneumothorax, and valve migration. Follow-up data on the studies are needed to determine its long-term efficacy.