Bronchoscopic treatment of thoracic malignancy

Introduction

Background

Thoracic oncology is a rapidly evolving field that focuses on studying and treating cancers in the chest region. Within this field, interventional pulmonologists face significant challenges in managing malignant central airway obstruction (MCAO) and peripheral lung malignancies.

Rationale and knowledge gap

The bronchoscopic management of MCAO and peripheral lung malignancies presents specific areas that require special attention and exploration. Numerous therapeutic bronchoscopic modalities, encompassing ablative procedures and the use of airway stents, are available. Nevertheless, the strategic application of these modalities, either singly or in combination, has been sparingly addressed in prior literature. While the utilization of these modalities has been individually examined in distinct scenarios, such as early-stage lung cancer and peripheral lung malignancies, there is a notable scarcity of comparative analyses between them.

Objective

Our objective in this review is to explore and discuss the bronchoscopic management of MCAO and peripheral lung malignancies, aiming to contribute to improved patient care strategies in thoracic oncology.

MCAO

MCAO is characterized by a luminal obstruction of over 50% of the trachea, mainstem bronchi, bronchus intermedius or a lobar bronchus (1). Patients with MCAO may experience symptoms such as cough, hemoptysis, and shortness of breath, which can range from mild to severe respiratory distress (2). The diagnosis of MCAO is often made through CT imaging of the chest, which is both sensitive and non-invasive (3). MCAO is known to be associated with a decrease in quality of life and an increase in mortality (4).

MCAO can have various causes, with lung cancer being the most common. Up to 30% of patients with lung cancer develop clinically evident MCAO during the course of their disease (2). Other malignancies that more commonly cause MCAO include tumors of airway origin such as adenoid cystic carcinoma (ACC), carcinoid tumor, and mucoepidermoid carcinoma. Intrathoracic extrapulmonary malignancies, such as esophageal, thyroid cancer, and lymphoma, as well as extrathoracic metastases, such as head and neck cancer, renal cell carcinoma, and colon cancer, are all known to spread directly to the airways (2,5,6).

Regardless of the underlying cause, MCAO can be classified into three major subtypes: intrinsic, extrinsic, and mixed obstruction. Intrinsic or endoluminal obstruction refers to a tumor that is confined inside the airway lumen. Extrinsic or extraluminal obstruction occurs when mass outside the airway within the adjacent parenchyma compresses and narrows the airway. Mixed obstruction describes a process that involves both intrinsic and extrinsic compression. The Cotton-Myer system can be used to grade MCAO, with Grade I indicating an obstruction of 0–50%, Grade II indicating 51–70%, grade III indicating 71–99%, and grade IV indicating complete obstruction at 100% (7).

Bronchoscopic treatment is typically considered a palliative measure for relieving MCAO (8). However, the immediate success rate of the procedure, defined as more than 50% of luminal patency, is generally high (1). Small retrospective studies have also shown a survival benefit and improvement in quality of life, though this effect is likely more significant in patients with more favorable pre-procedural functional status (9,10).

Anesthesia and airway management

Patients undergoing therapeutic bronchoscopy for MCAO can pose challenges in terms of anesthesia and airway management. In certain patients, concerns arise regarding the anesthetic agents and muscle relaxants that may reduce the muscle tone in the rib cage and diaphragm, leading to loss of airway distending pressure (11). Therefore, adequate ventilation under general anesthesia can be problematic with standard ventilation. In severe cases, the proceduralist needs to consider the risk of catastrophic complete airway obstruction that can occur with full induction of general anesthesia. This may be most relevant in patients with pedunculated mass, or high body mass index (12). In such cases, initial awake flexible bronchoscopy can be advantageous as it permits an airway exam while the patient is spontaneous breathing. It is particularly useful when the clinician is uncertain about the patient’s ability to tolerate increased levels of sedation or the degree of airway obstruction. However, it is important to note that the scope partially occludes about 10–15% of the normal trachea, potentially resulting in a decrease in partial pressure of oxygen (PaO₂) by 10–20 mmHg (13).

Clinical practice regarding the initial airway approach for patients with MCAO varies across different centers. Some physicians prefer using a laryngeal mask airway (LMA) or an endotracheal (ET) tube for initial evaluation, transitioning to a rigid bronchoscope if necessary. On the other hand, others opt for direct use of a rigid bronchoscope. No studies have directly compared these two approaches to determine which is superior. Therefore, the choice of approach remains at the discretion of the physician. Compared with LMA and ET tube, rigid bronchoscopy and jet ventilation allow an unobstructed view of the lesion while providing high-pressure air flow that passes the obstruction more easily (14,15). It also offers advantages such as the capability to remove large pieces of tumor, and control bleeding through tamponade, while allowing for the use of multiple instruments (16,17). Barotrauma and hypercapnia can occur with prolonged use (14,15). During airway stenting, employing controlled ventilation with muscle relaxants was found to lower the occurrence of desaturation events and maintain a favorable respiratory status (18). In severe cases, the procedure may require extracorporeal membrane oxygenation (ECMO) support depending on the severity of the obstruction and patient’s comorbidities (19).

Under special circumstances, case reports have suggested the use of non-invasive ventilation (NIV) during therapeutic bronchoscopy in patient with MCAO (20-22). However, the precise role of NIV in this context remains unclear, as it is not considered a stable airway management technique.

Ablative modalities

Ablative therapies are commonly employed to reduce tumor size in the airway. These therapies can be categorized into those that have an immediate effect and those with a delayed effect. Among the ablative modalities with immediate effect, two main types can be distinguished: thermal and non-thermal methods (Figure 1). Thermal ablative modalities can be further divided into contact and non-contact techniques. Contact thermal ablative modalities typically include electrocautery and microwave ablation (MWA), while non-contact thermal modalities encompass argon plasma coagulation (APC) and laser treatments. On the other hand, non-thermal ablative modalities that result in immediate tumor debulking include rigid coring, cryo-debulking and microdebrider techniques. Furthermore, there are several ablative modalities with a delayed effect, such as cryotherapy, cryospray, photodynamic therapy (PDT) and brachytherapy (Table 1).

Figure 1 Bronchoscopic tumor debulking. PDT, photodynamic therapy; APC, argon plasma coagulation.

Airway stents

Airway stents are indicated for patients with pure extrinsic compression, mixed obstruction where significant obstruction remains after tumor debulking, or tracheoesophageal fistula (49,50). They are considered palliative treatment for symptomatic patients with MCAO who experience shortness of breath or post-obstructive pneumonia (51). Stent placement can maintain the benefit of therapeutic bronchoscopy for dyspnea, obstruction recurrence and the need for repeat bronchoscopy (52). The approach to airway stent placement demonstrates global variability, encompassing differences in airway selection, anesthesia methods, and the application of rigid bronchoscopy and fluoroscopy (53,54).

There are two major types of stents available: (I) metallic stents and (II) silicone stents. Metallic stents can be further divided into fixed-diameter stents and self-expanding metallic stents (SEMSs). Metallic stents come in three forms—uncovered, partially covered and covered. Most fixed-diameter stents and SEMSs can be easily placed using prepackaged deployment catheters through existing airways, such as LMA or ET (55,56). It does not always require rigid bronchoscopy for placement. The deployment catheter is placed along the side of the flexible bronchoscopy, and the scope is placed at the proximal end of the stent. Smaller stent deployment catheters can fit through the 2.8 mm working channel of a therapeutic bronchoscope. Both flexible bronchoscope and fluoroscopy can both be used as real-time guidance during SEMS placement. Metallic stents can also be placed under fluoroscopy without bronchoscope visualization (57). Based on the findings of a survey study, 23% of providers from around the world consistently utilized fluoroscopic guidance during tracheobronchial stent placement; while 26.5% employing it selectively for specific cases (54).

Silicone stents come in different shapes, forms and sizes (49). There are straight, hourglass, or Y-shape silicone stents available. Pre-made silicone stents can be customized by cutting them short or creating additional openings. Custom-designed silicone Y stents are also available (58). The selection of a stent hinges upon factors such as the nature of the stenosis, the expertise of the operator, and the range of available equipment (59). The placement of silicone stents always requires rigid bronchoscopy and a stent deployer.

Complications arising from the use of stents in airway management encompass a range of issues, including stent migration/malposition, granulation tissue formation, tumor ingrowth, mucoid impaction, infection, stent fracture, and halitosis (49). It is important to note that the specific complication profiles may vary slightly between metallic stents and silicone stents. For instance, certain studies have indicated a higher risk of granulation tissue with metallic stents (60,61), whereas silicone stents are more prone to migration (62,63). Additionally, the use of silicone stents has been associated with an increased risk of mucus plugging (62). Due to epithelialization, bare metal stents tend to have infrequent migration, however, their removal can be problematic (64). In contrast, covered SEMSs and silicone stents are typically easier to remove. For optimal respiratory outcomes and to mitigate airway complications (65), it is recommended to promptly remove all airway stents.

Combined modalities

All of the aforementioned modalities have demonstrated effectiveness and are frequently utilized in together in clinical practice (1,23). However, previous studies have not identified any modality as superior to the others. Each modality possesses distinct characteristics and indications for application. Decisions on which modalities to use must be decided based on user experience, local resources, as well as specific patient characteristics.

For example, a patient’s fraction of inspired oxygen (FiO₂) requirement during bronchoscopy can often limit which ablative modalities can be utilized. Therapies like electrocautery, APC and laser carry a risk of airway fire. Consequently, it is crucial to maintain FiO₂ below 40% during application of these techniques (24). For patients who are unable to tolerate a lower FiO₂, alternative modalities such as cryodebulking, must be utilized.

Additional, tumor characteristics also dictate which tools may be effect. APC has limited tissue penetration and may not be the most effective method for tumor debulking (31). Nonetheless, it proves effective in achieving hemostasis (24). To achieve immediate tumor debulking, effective modalities include rigid coring, cryodebulking, microdebrider, MVA and certain electrocautery tools, such as snares (refer to Table 1 for details). Both electrocautery and APC are particularly useful for achieving hemostasis (24). In a study by Lee et al., rigid coring was employed for tumor tissue removal, followed by APC application for hemostasis (66). Laser therapy is effective in both debulking and hemostasis, but requires specialized training and is associated with higher equipment cost (35). Cryospray, cryotherapy, PDT and brachytherapy exhibit delayed effects and are not optimal for managing symptomatic high-grade obstruction which immediate stenosis relief is required.

Airway stents play a crucial role in maintaining airway patency and are typically indicated when there is >50% stenosis due to extrinsic or mixed obstruction or when addressing defects like fistulas. According to a randomized control trial, patients who underwent stent placement experienced longer-lasting improvement in dyspnea and fewer unattended bronchoscopies compared to those without stenting, although no significant change in the survival curve was observed (52). It is worth noting that airway stents carry their own complication profiles (49).

In summary, it is a common practice to employ a combination of modalities based on tumor characteristics and the availability of equipment.

Bronchoscopic management in early-stage, airway-limited thoracic malignancy

There are several types of malignancies arising predominantly from the central airways, including squamous cell carcinomas (SCCs), and ACCs, which are the most common malignant tracheal tumors (67-69). Other less common types include carcinoid tumors, mucoepidermoid carcinoma, non-squamous cell bronchogenic carcinomas, sarcomas, and pleomorphic adenomas (70). The adjunctive use of narrow-band imaging, autofluorescence and confocal laser endomicroscopy alongside traditional bronchoscopy has in the identification of malignant lesions within the airway has been reported in the literature though their actual utility is unclear (71-74). Radial probe endobronchial ultrasonography (RP-EBUS) can be used to evaluate the depth of tumor invasion, which is essential in determining the durable efficacy of bronchoscopic management of these lesions. If tumor invasion is seen on RP-EBUS beyond or within the cartilaginous layer, the goal of bronchoscopic ablation of these tumors should be palliative rather than curative (75,76).

There are several bronchoscopic options available, including PDT, cryotherapy, electrocautery, APC and laser. Compared with surgery, endobronchial treatment is less invasive and has a lower morbidity and mortality, with the major risk of potential underestimation of the tumor’s extensiveness (77). The best candidates for bronchoscopic treatments are patients with lesions that are smaller than 10 mm without cartilaginous invasion (78).

PDT is a treatment option for early, airway limited, lung cancer and typically achieves a complete response rate exceeding 70% of cases (43,44,79-84). The success of the treatment is impacted by the size of the lesion, with lesions of SCC smaller than 10 mm having a complete response rate of more than 90%; while those larger than 20 mm have a complete response rate of only 30–40% (44,83). PDT can also be used as the initial treatment to enable less extensive surgical resection (85).

Cryotherapy is another treatment option that has demonstrated a high remission rate of 91% at 1 year in a multicenter study involving 35 patients with bronchogenic carcinoma (86). Cryotherapy was also found to be effective in treating both typical and atypical endoluminal-restricted carcinoid cases (87-90). However, the narrowness of the treatment area and the 3 mm depth of its cytotoxic action are the major pitfalls associated with cryotherapy (91).

Electrocautery is a less commonly used treatment option, but it has shown to have an 80% response rate and no recurrence after 22 months in a small retrospective study (92).

Nd-YAG laser treatment for airway-limited lung cancer has not been extensively investigated. However, a retrospective study demonstrated a complete response rate of 100% among 19 patients with carcinoma in situ (93). The median interval for repeat bronchoscopy was reported to be 100 days, but long-term outcomes were not reported.

Brachytherapy has been studied in a large cohort of 226 patients, which showed a 93.6% compete response rate in 3 months and a 5-year survival of 29% (94). However, fatal hemoptysis occurred in 5% of cases.

Overall, there are several bronchoscopic treatment options available for central airway malignancies. PDT has the largest evidence base for curative intent in early-stage airway malignancies.

Emerging options for MCAO

The field of bronchoscopic management of MCAO is seeing several developments. A robotic system for rigid bronchoscopy was designed to treat CAO, as described in Gafford et al.’s 2020 study (95). The system has two robot arms that pass through a 10 mm rigid bronchoscope. Each arm consists of two pre-curved Nitinol tubes with two degrees of freedom each, allowing for telescopic extension and axial rotation. A monopolar electrosurgical probe was inserted through one of the arms, while a second robotic manipulator was used for retraction and tissue manipulation. However, this system has only been tested on cadavers so far.

In addition, intratumoral injection of chemotherapy has been studied as a treatment for CAO. Mehta et al.’s study found that cisplatin has sustained effects on airway patency when given one to four times, weekly apart (96). Guan et al.’s study showed that para-toluenesulfonamide had a rapid debulking effect when given for 2–3 sessions weekly within 2 weeks to patients with ACC (97). Moreover, a retrospective study of 206 patients found that cisplatin plus rh-endostatin intratumoral injection is effective and safe for the therapy of MCAO caused by primary squamous cell lung cancer (98).

Drug-eluding silicone stents were also studied for the use in lung cancer. The study found that paclitaxel incorporated into a silicone matrix in airway stents can reduce cancer relapse, though this has not yet been tested on human subjects (99).

Therapeutic bronchoscopy for peripheral lung cancer

There are two primary reasons for treating peripheral lung cancer bronchoscopically. The first is to address early-stage cancer with curative intent in patients who are not suitable candidates for surgery or who choose not to undergo surgery. The second reason is to stimulate immune responses by administering local treatments to either the primary tumor or lymph nodes, which can potentially assist with subsequent treatments.

Ablative therapy

A significant body of research has been dedicated to the local treatment of peripheral lung cancer, primarily through percutaneous computed tomography (CT)-guided therapy. However, there are two major concerns regarding complications associated with percutaneous CT-guided procedures in thoracic malignancies—pneumothorax and pleural seeding. A review article published in 2014 reported an average pneumothorax rate of 20% (ranging from 9–54%) from transthoracic needle biopsy (100,101). Additionally, a meta-analysis demonstrated an increased risk of ipsilateral pleural recurrence, with a hazard ratio of 2.58 [confidence interval (CI): 1.15–5.78], when comparing transthoracic biopsy with other diagnostic procedures (100,102). Although the data from transthoracic percutaneous biopsy cannot be directly extrapolated to therapy, there are shared concerns. Advancements in bronchoscopic navigation, such as augmented fluoroscopy and advanced intraprocedural cross-sectional imaging, have made bronchoscopic treatment of peripheral lung cancer a feasible option. This approach potentially mitigates the aforementioned concerns as the procedure theoretically involves fewer violations of the pleura. Currently, research in this area is still in the early stage of development.

Several ablative modalities mentioned above, such as MWA, PDT, cryotherapy, and brachytherapy, have been investigated for the ablation of peripheral lung cancer.

Initially, MWA for lung tumors was primarily studied in the percutaneous setting. A meta-analysis demonstrated promising results with percutaneous MWA treatment for lung cancer, showing an overall survival of 79.3% and a progression-free survival of 64.7% at 1 year (103). The review reported complications, such as pneumothorax (33.9% rate, CI: 23.8–44.8%) and pleural effusion (9.6% rate, CI: 1.5–22.4%). More recently MWA via bronchoscopy has been investigated to improve safety. Chan et al. investigated transbronchial MWA with electromagnetic navigation bronchoscopy, reporting a 100% technical success rate with no progression during a median follow-up of 12 months (104). Complications included pain, pneumothorax requiring drainage (6.67%), post-ablation syndrome, pleural effusion, and hemoptysis. Lau et al. reported their 3.5-year experience of bronchoscopic MVA, including primary lung cancer and oligometastatic nodules with no 30-day mortality or pneumothorax (105). After a median follow-up of 404 days, 20% patients developed local recurrence of the ablated nodule. A more recent study focused on the safety and feasibility of the NEUWAVE^TM FLEX MWA system (Ethicon Inc., Raritan, NJ, USA). It demonstrated 100% technical success and technique efficacy in all 10 patients with 11 tumors (10 NSCLC, 1 carcinoid), using navigational bronchoscopy guided by cone-beam CT with augmented fluoroscopy (106). Two serious adverse events occurred within 30 days, including a COPD exacerbation and a death of unknown cause. The NEUWAVE FLEX MWA system has been reported to be safely used in animal models for single or multiple MWAs, in conjunction with robotic-assisted bronchoscopy (RAB) (107). A prospective multicenter single-arm study using this MWA system and RAB is currently underway (POWER study).

CT-guided transthoracic PDT was examined in a study involving nine patients (108). Seven out of nine patients achieved partial remission, and two cases of pneumothorax was reported. Chen et al. treated three patients with peripheral lung cancer using PDT bronchoscopically via electromagnetic navigation bronchoscopy (109). All nodules were successfully ablated, and follow-up CT scans demonstrated significant tumor shrinkage. No major procedure-related complications occurred. Additionally, a recently published case report described navigational bronchoscopy-guided PDT for a patient with early-stage peripheral lung cancer, who underwent lobectomy on day 30 and subsequent pathology revealed no viable remaining tumor (110).

Lung parenchymal cryotherapy has also been widely adopted using the percutaneous approach. In one prospective study, 217 CT-guided percutaneous cryotherapy sessions were conducted in 187 patients (111). CT scans identified ice formation, with a mean coverage of 99% for peripheral masses ≤4 cm and 80% for central masses >4 cm. After 6 months, 86% of masses showed reduced or stable size. The incidence of pneumothorax was reported at 12%. In contrast, the application of bronchoscopic cryotherapy for the treatment of lung cancer is currently limited to animal studies. One such study concluded that a flexible cryoprobe using a bronchoscope in ex viva pig lung demonstrated a sufficiently safe treatment method (112).

Brachytherapy can be performed either under CT guidance or bronchoscopically using a catheter. One advantage of bronchoscopic therapy over CT-guided therapy is that the catheter with radioactive seeds can be fixed and left in place for several days, allowing for the implementation of highly fractioned irradiation schedules (113). In a prospective feasibility trial, a patient with right upper lobe lung cancer received combined external-beam radiotherapy and brachytherapy via electromagnetic navigational bronchoscopy (113). The brachytherapy catheter was well tolerated for 5 days. During the 12-month follow-up, CT scans showed partial remission while repeated biopsies confirmed complete remission. Another study reported two cases of bronchoscopic high dose rate (HDR) brachytherapy (114). In this study, barium was injected as a marker and 7 days later, ¹⁹²Ir was inserted using the HDR after-loading system. CT scans demonstrated focal radiation fibrosis at the treatment site and no change in tumor size in 18 months in the one patient, while the other patient experienced a 75% decrease in tumor size in 10 months.

In addition to the ablative therapies mentioned above, three other modalities, radiofrequency ablation (RFA), bronchoscopic thermal vapor ablation (BTVA), and pulsed electric field (PEF), have also been utilized for the treatment of peripheral lung cancer.

RFA employs an electromagnetic wave to generate a high frequency current for heating and coagulating tissues. Percutaneous CT-guided thermal ablation of stage I–II NSCLC has been shown to be effective (115-117). A systematic review indicated a median complete necrosis rate of 90% with a 1-year survival rate of 63–85% (118). A meta-analysis reported an overall survival of 89.2% and a progression-free survival of 62.4% in 1 year (103). Pneumothorax was the most common complication associated with CT-guided RFA, reported up to 57% of previous studies (115-117). To address this, bronchoscopic RFA catheters have been developed. Koizumi et al. performed bronchoscopy-guided RFA in 20 patients with stage IA–IB diseases, reporting a median progression-free survival of 35 months (95% CI: 22–45) with no reported incidents of pneumothorax (119). Xie et al. utilized a novel RFA probe with a ‘flower-like’ appearance to increase the treatment volume of the probe, achieving either partial or complete response in all three patients with no significant complications (120). However, the interest in researching RFA has diminished due to the reported advantages of MWA over RFA. These advantages include shorter procedural time, reduced heat-sink effect, large ablation zones, decreased susceptibility to tissue impedance and the ability to use multiple antennae simultaneously (121).

Another modality, BTVA is being explored in the local treatment of peripheral lung cancer after its initial inception to treat emphysema (122). This technique delivers steam that travels along air-filled spaces, confining to the anatomical boundaries of the subsegment of the treated lung parenchyma (123). In a study of six subjects with peripheral lung cancers who received BTVA, 5 out of 6 patients received surgical resection and pathological examination showed complete necrosis in two of the patients (124). Two subjects reported post-procedural pleuritic chest pain.

PEF is a nonthermal ablative modality that induces electroporation by utilizing strong pulsed electrical fields to create microscopic pores in cell membranes. The Aliya system (Galvanize Therapeutics, GTI-00018 investigational device, San Carlos, CA, USA) is a commercially available biphasic monopolar PEF system that uses a single percutaneous probe to target a lesion of interest. This process ultimately leads to a change in membrane permeability and necrosis (125). Additionally, local PEF has demonstrated the ability to induce immunogenic cell death and increase T cell infiltration in tumors, and the combination of PEF with immune checkpoint inhibitor therapy has shown a synergistic immunostimulatory cytokine profile (126). A porcine model has confirmed the safety and histological efficacy of bronchoscopic delivery of PEF in lung tissue (127). There is a forthcoming ablate and resect clinical trial designed to further delineate the treatment effects of PEF in-vivo when used either percutaneously or via bronchoscopy. ClinicalTrials.gov identifier: NCT04732520. Updated January 9, 2023. Accessed July 1, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04732520.

Peripheral tumor injection of chemotherapy or gene therapies

Intratumoral injection of chemotherapy theoretically increases local drug level while minimizing systemic toxicity (128). Cisplatin is the most frequently used agent in the previous studies focused on the central airway and lymph nodes (129-131). Due to the uncertainties surrounding patient selection, optimal dosage and long-term outcomes, the adoption of these approaches in clinical practice has been limited.

Bronchoscopic delivery of therapeutic genes for lung cancer patients has also been investigated. These studies aim to investigate the role of local therapy in cancer immune response. A phase I trial reported intratumoral injection of CCL21 gene-modified dendritic cells for patients with stage IIIB/IV NSCLC, results in induction of systemic tumor antigen-specific immune response and increased tumor PD-L1 expression (132). Additionally, bronchoscopic delivery of a recombinant adenovirus carrying the wild-type p53 gene was given to patients with NSCLC in combination with radiotherapy (133). In 63% of patients, biopsy-proven nonviable tumor was observed. Another phase I trial investigated the use of an adenovirus vector containing the HSV-tk gene (AdV-tk) in patients with resectable NSCLC (134). The use of bronchoscopic AdV-tK injection resulted in minimal vector-related adverse events and a significantly increase in infiltration of CD8⁺ T cells in surgically resected tumors.

Conclusions

In summary, there are various bronchoscopic management modalities available for the treatment of MCAO, each with its own unique characteristics that need to be considered in clinical applications. Interventional pulmonologists often combine different modalities to achieve the most satisfactory results. Anesthesia and airway management can pose challenges, and the choice typically depends on the patient’s clinical stability and the selected bronchoscopic modality. For early-stage, airway limited malignancies, curative bronchoscopic treatments are available. Furthermore, emerging treatment options are being explored. Interventional pulmonology has also expanded its scope to include local treatment of peripheral lung cancer. However, additional research is needed to establish its efficacy and potential benefits of these interventions.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Jonathan Kurman and Bryan S. Benn) for the series “Diagnostic & Therapeutic Bronchoscopy” published in AME Medical Journal. The article has undergone external peer review.

Peer Review File: Available at https://amj.amegroups.com/article/view/10.21037/amj-23-102/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://amj.amegroups.com/article/view/10.21037/amj-23-102/coif). The series “Diagnostic & Therapeutic Bronchoscopy” was commissioned by the editorial office without any funding or sponsorship. DD received research grants to institution from Gala Therapeutics and Auris Medical, Inc.; and received personal consulting fees from Olympus, Johnson & Johnson, Intuitive Surgical and Auris Medical, Inc. KM received research grants to institution from Right Air, Inc. and Pulmonx; received personal consulting fees from Pulmonx; and served as an advisory board member of Polarean, Inc. and Verona Pharmaceutical (paid). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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