Robotic Bronchoscopy for Peripheral Pulmonary Lesions

Abstract

BackgroundThe diagnosis of peripheral pulmonary lesions (PPL) continues to present clinical challenges. Despite extensive experience with guided bronchoscopy, the diagnostic yield has not improved significantly. Robotic-assisted bronchoscopic platforms have been developed potentially to improve the diagnostic yield for PPL. Presently, limited data exist that evaluate the performance of robotic systems in live human subjects.Research QuestionWhat is the safety and feasibility of robotic-assisted bronchoscopy in patients with PPLs?Study Design and MethodsThis was a prospective, multicenter pilot and feasibility study that used a robotic bronchoscopic system with a mother-daughter configuration in patients with PPL 1 to 5 cm in size. The primary end points were successful lesion localization with the use of radial probe endobronchial ultrasound (R-EBUS) imaging and incidence of procedure related adverse events. Robotic bronchoscopy was performed in patients with the use of direct visualization, electromagnetic navigation, and fluoroscopy. After the use of R-EBUS imaging, transbronchial needle aspiration was performed. Rapid on-site evaluation (ROSE) was used on all cases. Transbronchial needle aspiration alone was sufficient when ROSE was diagnostic; when ROSE was not diagnostic, transbronchial biopsy was performed with the use of the robotic platform, followed by conventional guided bronchoscopic approaches at the discretion of the investigator.ResultsFifty-five patients were enrolled at five centers. One patient withdrew consent, which left 54 patients for data analysis. Median lesion size was 23 mm (interquartile range, 15 to 29 mm). R-EBUS images were available in 53 of 54 cases. Lesion localization was successful in 51 of 53 patients (96.2%). Pneumothorax was reported in two of 54 of the cases (3.7%); tube thoracostomy was required in one of the cases (1.9 %). No additional adverse events occurred.InterpretationThis is the first, prospective, multicenter study of robotic bronchoscopy in patients with PPLs. Successful lesion localization was achieved in 96.2% of cases, with an adverse event rate comparable with conventional bronchoscopic procedures. Additional large prospective studies are warranted to evaluate procedure characteristics, such as diagnostic yield.Clinical Trial RegistrationClinicalTrials.gov; No.: NCT03727425; URL: www.clinicaltrials.gov. The diagnosis of peripheral pulmonary lesions (PPL) continues to present clinical challenges. Despite extensive experience with guided bronchoscopy, the diagnostic yield has not improved significantly. Robotic-assisted bronchoscopic platforms have been developed potentially to improve the diagnostic yield for PPL. Presently, limited data exist that evaluate the performance of robotic systems in live human subjects. What is the safety and feasibility of robotic-assisted bronchoscopy in patients with PPLs? This was a prospective, multicenter pilot and feasibility study that used a robotic bronchoscopic system with a mother-daughter configuration in patients with PPL 1 to 5 cm in size. The primary end points were successful lesion localization with the use of radial probe endobronchial ultrasound (R-EBUS) imaging and incidence of procedure related adverse events. Robotic bronchoscopy was performed in patients with the use of direct visualization, electromagnetic navigation, and fluoroscopy. After the use of R-EBUS imaging, transbronchial needle aspiration was performed. Rapid on-site evaluation (ROSE) was used on all cases. Transbronchial needle aspiration alone was sufficient when ROSE was diagnostic; when ROSE was not diagnostic, transbronchial biopsy was performed with the use of the robotic platform, followed by conventional guided bronchoscopic approaches at the discretion of the investigator. Fifty-five patients were enrolled at five centers. One patient withdrew consent, which left 54 patients for data analysis. Median lesion size was 23 mm (interquartile range, 15 to 29 mm). R-EBUS images were available in 53 of 54 cases. Lesion localization was successful in 51 of 53 patients (96.2%). Pneumothorax was reported in two of 54 of the cases (3.7%); tube thoracostomy was required in one of the cases (1.9 %). No additional adverse events occurred. This is the first, prospective, multicenter study of robotic bronchoscopy in patients with PPLs. Successful lesion localization was achieved in 96.2% of cases, with an adverse event rate comparable with conventional bronchoscopic procedures. Additional large prospective studies are warranted to evaluate procedure characteristics, such as diagnostic yield. ClinicalTrials.gov; No.: NCT03727425; URL: www.clinicaltrials.gov. An estimated 1.5 million new pulmonary nodules are expected to be detected in the United States annually.1Gould M.K. Tang T. Liu I.L. et al.Recent trends in the identification of incidental pulmonary nodules.Am J Respir Crit Care Med. 2015; 192: 1208-1214Crossref PubMed Scopus (327) Google Scholar Widespread adoption of lung cancer screening programs is expected to further increase these numbers in the coming years. Although the majority of these nodules may simply require surveillance imaging, many will require biopsy. Despite technologic advancements in guided bronchoscopy such as electromagnetic navigation bronchoscopy, ultrathin bronchoscopy, and radial probe endobronchial ultrasound (R-EBUS) imaging, the diagnostic yield of bronchoscopic approaches for peripheral nodules has been inconsistent in randomized controlled studies, ranging from 40% to 60%.2Tanner N.T. Yarmus L. Chen A. et al.Standard bronchoscopy with fluoroscopy vs thin bronchoscopy and radial endobronchial ultrasound for biopsy of pulmonary lesions: a multicenter, prospective, randomized trial.Chest. 2018; 154: 1035-1043Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar, 3Oki M. Saka H. Ando M. et al.Ultrathin bronchoscopy with multimodal devices for peripheral pulmonary lesions: a randomized trial.Am J Respir Crit Care Med. 2015; 192: 468-476Crossref PubMed Scopus (142) Google Scholar, 4Eberhardt R. Anantham D. Ernst A. et al.Multimodality bronchoscopic diagnosis of peripheral lung lesions: a randomized controlled trial.Am J Respir Crit Care Med. 2007; 176: 36-41Crossref PubMed Scopus (442) Google Scholar Potential limitations to current approaches include challenges that advance the bronchoscope into peripheral airways due to size limitations of the scope as subsegmental bronchi become progressively smaller as they extend peripherally. In addition, subsegmental bronchi often branch at varying angles, which may be difficult to negotiate with the use of conventional bronchoscopes. These factors may limit operators’ ability to advance the bronchoscope into close proximity to peripheral pulmonary lesions when attempting biopsy and may negatively affect the diagnostic yield of the procedure. Robotic surgery has been performed across many platforms that include urologic, gynecologic, and thoracic surgery and offers potential advantages of improved dexterity and visualization while maintaining minimally invasive approaches.5Veronesi G. Robotic lobectomy and segmentectomy for lung cancer: results and operating technique.J Thorac Dis. 2015; 7: S122-S130PubMed Google Scholar Early preclinical experience with a robotic endoscopic system within human cadaveric lungs demonstrated increased reach into the lung periphery with the robotic platform compared with a similarly sized bronchoscope in both tortuous and relatively straightforward segmental bronchi.6Chen A.C. Gillespie C.T. Robotic endoscopic airway challenge: REACH assessment.Ann Thorac Surg. 2018; 106: 293-297Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar Additional preclinical studies demonstrated high accuracy with the use of the robotic system to perform transbronchial needle aspiration (TBNA) of simulated tumor targets sized 1 to 3 cm in cadaveric lungs and the ability to place biopsy instruments within targeted lesions in cadaver models with a greater degree of accuracy compared with conventional guided approaches.7Chen A.C. Pastis N.J. Machuzak M.S. et al.Accuracy of a robotic endoscopic system in cadaver models with simulated tumor targets: ACCESS study.Respiration. 2020; 99: 56-61Crossref PubMed Scopus (31) Google Scholar,8Yarmus L. Akulian J. Wahidi M. et al.A prospective randomized comparative study of three guided bronchoscopic approaches investigating pulmonary nodules: the PRECISION-1 study.Chest. 2020; 157: 694-701Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar Presently, very few data exist regarding the use of a robotic endoscopic system in live human subjects with peripheral lesions in need of biopsy.9Rojas-Solano J.R. Ugalde-Gamboa L. Machuzak M. Robotic bronchoscopy for diagnosis of suspected lung cancer: a feasibility study.J Bronchol Interv Pulmonol. 2018; 25: 168-175Crossref PubMed Scopus (69) Google Scholar,10Chaddha U. Kovac S.P. Manley C. et al.Robot-assisted bronchoscopy for pulmonary lesion diagnosis: results from the initial multicenter experience.BMC Pulm Med. 2019; 19: 243Crossref PubMed Scopus (72) Google Scholar This study was performed to assess the feasibility of performing robotic bronchoscopy to locate peripheral lesions in patients and to evaluate the safety and performance characteristics of procedures in a multicenter, prospective trial. This was a multicenter, prospective pilot study of robotic bronchoscopy in patients with peripheral pulmonary lesions 1 to 5 cm in size and no evidence of disease in mediastinal or hilar lymph nodes by CT or PET imaging. CT scans were performed with the use of a standardized protocol with slice thickness of 1 to 1.25 mm, with variations dependent on the manufacturer of the CT scanner. Five study sites participated; each site enrolled 11 study patients. Consecutive patients who met inclusion and exclusion criteria were considered for this study. All study procedures were performed with general anesthesia in a dedicated operating room or endoscopy suite. The study was approved by each center’s institutional review board. Flexible bronchoscopy with airway inspection was performed initially to exclude the presence of endobronchial disease and to provide topical anesthesia, as per the discretion of the bronchoscopist. Following this, the robotic bronchoscopic system (Monarch; Auris Health) was connected to the existing endotracheal tube. The robotic bronchoscopic system is composed of a tower with monitor and a unit that houses arms that control insertion, retraction, and articulation of an outer sheath (6.0 mm outer diameter) and inner scope (4.4 mm outer diameter) that has a 2.1-mm working channel. With the use of a hand-held controller, the sheath and scope may be driven independently or simultaneously as a unit (Fig 1). Electromagnetic navigation bronchoscopy is incorporated into the system to provide navigational support with a CT scan that was obtained within 2 weeks of the procedure (Fig 2).Figure 2Robotic system user interface shows live bronchoscopic, electromagnetic navigation bronchoscopy with targeting, and multiplanar CT views.View Large Image Figure ViewerDownload Hi-res image Download (PPT) With the robotic system in place, the sheath and scope were driven simultaneously to the targeted lobe where the outer sheath was left in position. Subsequently, the inner scope was advanced distally into the lobar and segmental bronchi with a combination of direct visualization, electromagnetic navigation, and fluoroscopic guidance towards the targeted lesion. Once the robotic scope was positioned at the targeted location, a R-EBUS imaging probe (UM S20-17S; Olympus Tokyo) was introduced through the working channel of the system and was used to survey the lung parenchyma and confirm lesion localization. Radial ultrasound images were recorded as “concentric” when the ultrasound representation of the targeted lesion surrounded the R-EBUS imaging probe and “eccentric” when the ultrasound image was biased to one side of the probe with no component of the lesion surrounding the probe. If no lesion could be identified with the use of R-EBUS imaging, this was also recorded. After evaluation with R-EBUS imaging, biopsy of the targeted lesion was performed with TBNA (Fig 3). Three TBNA specimens were obtained from each lesion, which was followed by rapid on-site evaluation (ROSE) of plated specimens. In cases in which ROSE was diagnostic, no further biopsy specimens were required. In cases in which ROSE was not diagnostic, three transbronchial biopsies were performed. For cases in which TBNA with ROSE were not diagnostic, conventional bronchoscopic approaches such as electromagnetic navigation or thin bronchoscopy with radial ultrasound imaging were performed at the discretion of the bronchoscopist after transbronchial biopsy as described earlier. Pathologic specimens that were collected through crossover procedures were separated from those that were collected during robotic bronchoscopy; characteristics (such as procedure time, biopsy instruments, and diagnostic yield) were likewise noted. All patients received postprocedure chest radiography within 2 hours after bronchoscopy to evaluate for the presence of pneumothorax. Patients were recovered and discharged as per each institution’s standard practice. The primary efficacy end point of this study was confirmation of lesion localization with R-EBUS imaging; the primary safety end point was the incidence of procedure- or device-related adverse events. The secondary end points included procedure time, insertion depth by bronchus generation count, and the distance from the tip of the robotic scope to the center of the targeted lesion. An exploratory end point was diagnostic yield at 12-month follow up. Peripheral pulmonary lesions were defined as lesions surrounded by pulmonary parenchyma that were deemed inaccessible with convex probe endobronchial ultrasound imaging by the bronchoscopist and without any evidence of endobronchial disease during airway inspection. Procedure or device adverse events were defined as (1) pneumothorax of any kind, regardless of the need for tube thoracostomy, (2) bleeding during bronchoscopy that required intervention, and (3) change in patient status after bronchoscopy, such as hospital admission (if outpatient) or transfer to the ICU. A “diagnostic” specimen was based on cytopathologic results and was defined as a biopsy that resulted in a specific malignant process or a specific diagnosis of a nonmalignant process that explained the presence of a peripheral pulmonary lesion (ie, granuloma, fungal A biopsy that was considered diagnostic the targeted lesion demonstrated or on imaging or biopsy specimens the of If imaging was a of was considered reported as were considered specimens that pulmonary on cytopathologic were also considered regardless of on imaging, these biopsy specimens were not to be of the targeted peripheral lesion. All patients received follow for at 1 and all biopsy results were independently by two G. A. for was performed with The was used for data were as the with were reported as the (interquartile was used to The was for of to the of an A of was considered Fifty-five patients were enrolled across five study One patient withdrew that results in 54 patients available for data analysis. Median lesion size as on imaging was 23 mm 15 to 29 with 23 of 54 nodules to mm, with of 54 nodules to mm, and of 54 lesions to of lesions were mm, which pulmonary of 54 patients a bronchus defined as a bronchus that was on or CT that in with any of the lesion. Lesion is reported in patients one patient withdrew as on CT imaging. location, Fifty-five patients one patient withdrew as on CT imaging. in a new R-EBUS imaging was available in 53 of 54 cases. Lesion localization was with radial probe endobronchial ultrasound imaging in 51 of 53 patients R-EBUS imaging were obtained in of 51 cases and R-EBUS imaging in of 51 cases Median to lesion confirmation was to Pneumothorax in two of 54 cases which required tube thoracostomy in one No evidence of airway was on insertion or of the robotic No adverse events were noted. Median procedure time, defined as robotic scope insertion to was 51 Median insertion depth by bronchus generation was Median distance from the tip of the robotic scope to the center of the targeted lesion was 23 mm Procedure time, to radial endobronchial ultrasound depth by bronchus generation from scope tip to center of lesion, (interquartile in a new (interquartile A diagnosis was obtained in of 54 patients for of patients in a diagnosis was nonmalignant for of cases follow was not available in one results were as not The diagnostic yield for peripheral lesions with a was compared with for lesions 3 and endobronchial ultrasound probe for one yield radial endobronchial ultrasound Lesion Radial endobronchial ultrasound probe for one in a new by based on 54 one on and on based on 54 one on and on imaging. in a new procedures after ROSE cases were performed in five of one was diagnostic with the use of thin bronchoscopy and R-EBUS with In an additional crossover the from the robotic procedure was ROSE was not the crossover procedure was not In the three cases, both robotic bronchoscopy and crossover procedures were not The of clinical guided bronchoscopy for the diagnosis of peripheral pulmonary lesions when lung cancer is A.C. Wahidi the diagnosis of lung cancer: and of lung of clinical Full Text Full Text PDF PubMed Scopus Google Scholar Despite experience with a of bronchoscopic approaches the the diagnosis of peripheral nodules continues to present a to Although data reported diagnostic of for guided bronchoscopic results from randomized controlled with defined end points have been which that the diagnostic yield may be to 40% to and is when peripheral nodules are to the N.T. Yarmus L. Chen A. et al.Standard bronchoscopy with fluoroscopy vs thin bronchoscopy and radial endobronchial ultrasound for biopsy of pulmonary lesions: a multicenter, prospective, randomized trial.Chest. 2018; 154: 1035-1043Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar, 3Oki M. Saka H. Ando M. et al.Ultrathin bronchoscopy with multimodal devices for peripheral pulmonary lesions: a randomized trial.Am J Respir Crit Care Med. 2015; 192: 468-476Crossref PubMed Scopus (142) Google Scholar, 4Eberhardt R. Anantham D. Ernst A. et al.Multimodality bronchoscopic diagnosis of peripheral lung lesions: a randomized controlled trial.Am J Respir Crit Care Med. 2007; 176: 36-41Crossref PubMed Scopus (442) Google of guided bronchoscopy for the evaluation of the pulmonary Full Text Full Text PDF PubMed Scopus Google A.C. A. J. M. D. Radial probe endobronchial ultrasound for peripheral pulmonary lesions: a 5 institutional Thorac PubMed Scopus Google Scholar This the prospective, multicenter of robotic bronchoscopy in patients with peripheral pulmonary Robotic bronchoscopic approaches in of and this study to the in the the primary end point was to assess the ability to to peripheral in with the use of R-EBUS imaging. The ability to use the robotic system to locate and confirm lesion localization in 96.2% of patients that the current system within close proximity to targeted which is a to performing the adverse event rate of procedures was who not used the new of cadaver A.C. Gillespie C.T. Robotic endoscopic airway challenge: REACH assessment.Ann Thorac Surg. 2018; 106: 293-297Abstract Full Text Full Text PDF PubMed Scopus (56) Google A.C. Pastis N.J. Machuzak M.S. et al.Accuracy of a robotic endoscopic system in cadaver models with simulated tumor targets: ACCESS study.Respiration. 2020; 99: 56-61Crossref PubMed Scopus (31) Google Scholar This may be of in conventional bronchoscopy, robotic systems not provide the with Although cadaver studies the ability to peripheral safety data could not be In this was no evidence of airway during robotic bronchoscopy, and the pneumothorax rate was to has been reported when current guided bronchoscopic were R. Anantham D. Ernst A. D. bronchoscopic diagnosis of peripheral lung lesions: a randomized controlled trial.Am J Respir Crit Care Med. 2007; 176: 36-41Crossref PubMed Scopus Google Scholar additional required to the robotic procedure were comparable with with the use of navigational D. et navigation diagnostic a prospective J Respir Crit Care Med. PubMed Scopus Google Scholar the limitations of efficacy in a pilot that the diagnostic yield of achieved in this study with new with of that have diagnostic when similarly were in randomized controlled Although et M. Saka H. et of an ultrathin vs thin bronchoscope for peripheral pulmonary lesions: a randomized trial.Chest. 2019; Full Text Full Text PDF PubMed Scopus Google Scholar reported a diagnostic yield of ultrathin bronchoscopy, bronchoscopic navigation, and radial ultrasound imaging for pulmonary a prospective, randomized controlled that compared thin bronchoscopy with R-EBUS to conventional transbronchial biopsy with fluoroscopy demonstrated a diagnostic yield of for guided bronchoscopy, which was not from the yield of conventional N.T. Yarmus L. Chen A. et al.Standard bronchoscopy with fluoroscopy vs thin bronchoscopy and radial endobronchial ultrasound for biopsy of pulmonary lesions: a multicenter, prospective, randomized trial.Chest. 2018; 154: 1035-1043Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar An additional large prospective study that used reported a diagnostic yield of patients who were guided bronchoscopic J. et evaluation of diagnostic yield from the of procedure and degree of for 2020; 157: Full Text Full Text PDF PubMed Scopus Google Scholar Although are limitations in this study with randomized controlled the reported yield in this study is for new and will require further through An additional was that the performance characteristics of robotic bronchoscopy not to be by lesion to the The diagnostic yield of for lesions is this to the of to 40% reported in the in this patient et related to diagnostic yield of transbronchial biopsy endobronchial with a sheath in peripheral pulmonary 2007; Full Text Full Text PDF PubMed Scopus Google Scholar in diagnostic yield for lesions has clinical lesions were in 40% of patients in this study and in as many as of patients in A.C. A. L. J. D. of peripheral pulmonary lesions a of and radial probe endobronchial ultrasound Thorac PubMed Scopus Google Scholar The limitations of this study be related to the relatively size. a pilot and feasibility the specific were to the feasibility of the use of the robotic system in and the ability to the robotic to the targeted lesion. This study was with the use of the that a diagnostic biopsy is a of successful navigation to the targeted lesion followed by successful biopsy of the targeted lesion. successful navigation and lesion that diagnostic biopsy specimens be An additional of this study be the clinical of successful lesion localization as to on diagnostic yield. In this lesion localization was and the diagnostic yield was additional studies will factors such as increased user biopsy or factors may the lesion localization and diagnostic yield. data that R-EBUS images may be by during bronchoscopy procedures and that the of may increase with procedure M. et bronchoscopy for diagnosis of peripheral lung nodules: a prospective study.J Thorac Dis. 2018; PubMed Scopus (69) Google Scholar Although this is an of that R-EBUS imaging characteristics such as surrounding the targeted lesion and a R-EBUS imaging lesion that with by chest CT the of image robotic bronchoscopy was performed to convex of the to further the of the of of this study that may improve of results include the of the study and protocol towards performing procedures that to evaluate specific of robotic at sites a standardized diagnostic yield was not a primary end that the used to diagnostic specimens are an additional of the study and may be with that are and to assess diagnostic yield and of robotic criteria were to any potential or and required cytopathologic evidence that the targeted lesion been In cases of this was reported as a specific diagnosis of were considered not cases required a specific diagnosis such as or cytopathologic evidence of a process such as that demonstrated within the follow up. that demonstrated pulmonary on with on imaging were considered not diagnostic was no evidence that the targeted lesion been In the results of this study the feasibility and safety of performing robotic bronchoscopy in patients with peripheral pulmonary lesions with the use of a multicenter with of diagnostic and biopsy specimens. of lesion localization in of with an adverse event rate comparable with conventional that safety and the ability to locate peripheral lesions is an in the of this of in the reported diagnostic yield of current guided bronchoscopic to perform an of robotic additional studies that will diagnostic yield and factors that this be performed in prospective comparative with defined end A. 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