Objectives

1. To describe clinical manifestations of patients with obstructing airway lesions associated with lung cancer.
2. To describe three main types of malignant airway obstruction.
3. To discuss the management of endobronchial, extrinsic, and mixed obstructing airway lesions.
4. To review different endoscopic treatment modalities.
5. To discuss multimodality treatment of patients with advanced lung cancer.

Abbreviations

FB = flexible bronchoscope; HDR = high-dose-rate; LPR = laser photoresection; NSCLC = non-small cell lung cancer; PDT = photodynamic therapy; RB = rigid bronchoscope; XRT = external beam radiation therapy

In the 21st century, lung cancer is the second most common cancer and the leading cause of cancer death in the United States.¹ Only 20 to 25% of lung cancer cases can be cured at the time of diagnosis. For the large majority, treatment remains palliative, ^2-4 which includes external beam radiation therapy (XRT), chemotherapy or a combination of both. For small cell lung cancer, cure is possible in 10 to 15% of cases; for non-small cell lung cancer (NSCLC), cure is possible only in early stages I to II and in select cases of stage IIIA NSCLC.

Approximately 30% of patients with lung cancer will present with airway obstruction, and 35% of this group will die as a result of local intrathoracic complications such as hemoptysis, postobstuctive pneumonia, and asphyxia. Local tumor control with bronchoscopic techniques followed by XRT or chemotherapy results in rapid relief of symptoms, improved quality of life, and prolonged survival.⁵

Clinical Presentation

The grave prognosis of lung cancer is largely due to the late onset of symptoms that bring the patient to the physician. A majority of symptomatic patients who seek medical attention often have stage III to IV disease at presentation. In fact, tracheobronchial obstructions are silent until ≥ 50% of the airway diameter is reduced.

Clinical manifestations of malignant airway obstruction include cough, hemoptysis, dyspnea, stridor, hypoxemia, respiratory failure requiring mechanical ventilation, and postobstructive pneumonia. Pathognomonic late inspiratory localized wheezing, chest radiographic features of atelectasis or postobstructive pneumonia, anddecreased flow rates such as FEV₁ or FVC, as well as truncated flow-volume loops may be observed.

Bronchoscopic Treatment of Lung Cancer

The goal of bronchoscopic techniques is to relieve large airway obstruction attributed to the tumor. Although XRT has been considered a standard therapy for locally advanced NSCLC, XRT may be effective in only 25% of patients, and some patients gain no relief of airway obstruction.^6,7 For these patients, who may previously have undergone surgery, XRT, or chemotherapy, local bronchoscopic techniques might be more useful and could represent the only alternative treatment modality. An exception to the general approach would be in the management of the patient with untreated small cell lung cancer or lymphoma. Even if such a patient has a severe obstruction of > 50% of the airway diameter, chemotherapy should be instituted first unless he or she is in extremis , as dramatic response to chemotherapy may be observed within 1 to 2 days. The following discussion will center largely on the management of obstructing airway lesions associated with NSCLC.

Selection of a therapeutic strategy for malignant central airway obstruction depends on the type of lesion (Fig 1), acuity of presentation, stage of disease, the patient's general, cardiac, and pulmonary status, and the physician's expertise (Fig 2). At present, ethical issues have precluded randomized trials comparing each treatment modality.

Management of Malignant Airway Obstruction

Laser Therapy

The most widely used technique for the treatment of endobronchial obstruction involves the Nd-YAG laser,^8,9 which can be used emergently or electively to restore airway patency. At low power, the Nd-YAG laser causes tissue coagulation, and at high power, tissue vaporization.

Nd-YAG laser photoresection (LPR) is very effective in palliating such symptoms as cough, dyspnea, and hemoptysis, as well as in achieving endoscopic, radiographic, spirometric, and quality-of-life improvement.^10-15 Importantly, it helps patients presenting with respiratory distress to avoid mechanical ventilation, and facilitates weaning and successful extubation in those who are receiving mechanical ventilation.^16,17 LPR can be performed with the rigid bronchoscope (RB) or the flexible bronchoscope (FB); the choice of instrument depends on the operator's expertise and patient factors. Factors that influence the outcome of LPR are listed in Table 1. Figure 3 shows an endobronchial tumor that is an ideal candidate for laser LPR.

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Figure 3. An ideal endobronchial tumor for laser photoresection. Note the 90% luminal obstruction of the trachea with visible distal lumen.

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Endobronchial Electrosurgery

Good airway patency is also observed after endobronchial electrosurgery (EBES) is performed on an endobronchial tumor.¹⁸ Like LPR, EBES can be used for both elective and emergent procedures with either the RB or FB, depending on the operator's expertise.

Two main EBES techniques are used: (1) tumor debulking by cutting the stalk of a polypoid lesion with a cutting loop, and (2) electrodestruction of tumor by direct contact with the probe. The electric current can be set to “coagulate” at high amperage and low voltage, “cut” at low amperage and high voltage, or “blend” at a setting midway between the cut and coagulate settings. The current passes through the probe, the tissues, and finally to a grounded neutral plate attached to the patient.

Recent advances in equipment design allow the application of electrical current via a noncontact method. The argon plasma coagulator¹⁹ uses ionized argon gas, which acts as an electrical conductor between the electrode and tissue. This instrument is ideal for superficial hemorrhagic tumors, inaccessible upper lobe segmental bronchial tumors, and superior basal lobar bronchial tumors.

Brachytherapy, Cryotherapy, and Photodynamic Therapy  

Airway lesions that do not necessitate immediate restoration of airway patency can be treated with brachytherapy, cryotherapy, or photodynamic therapy (PDT). These techniques are used singly or in combination.

Brachytherapy: Endobronchial brachytherapy is a form of local radiation treatment involving temporary placement of encapsulated radioactive sources within or near the tumor. The advantages of brachytherapy over XRT include (1) delivery of a higher dose of radiation directly to the tumor; (2) rapid decrease in radiation outside the treatment region; (3) precise dose localization; and (4) adaptability to the tumor shape. Brachytherapy is indicated for the palliation of malignant tracheobronchial obstructive lesions (endobronchial, submucosal, or peribronchial) and contraindicated in patients with tumor invasion of major arteries and mediastinum.

Recent improvements in the afterloading technique with 192 Ir enable the administration of high-dose-rate (HDR) brachytherapy on an outpatient basis, with minimal hazard to health-care personnel. The tip of a polyethylene catheter is usually placed 2 to 4 cm distal to the endobronchial tumor via an FB. Once the position of the catheter is confirmed radiologically, the bronchoscope is withdrawn and the catheter is mechanically loaded with 192 Ir.

Symptomatic relief is achieved in 85% of patients treated with HDR brachytherapy²⁰ ; response can be correlated with tumor size, with good results observed in small endobronchial and peripherally located tumors.^21,22 Tubiana et al²³ demonstrated a 96% complete response rate for small endobronchial tumors and a median survival time of 17 months after HDR brachytherapy. HDR brachytherapy is usually administered 3 to 20 Gy per fraction, 1 cm from the source axis, for 1 to 6 fractions at an interval of 1 to 3 weeks. In patients who have undergone prior XRT for palliation, a regimen comprising 2 to 3 fractions at 7 to 10 Gy per fraction is recommended. Complications include radiation bronchitis in 10% and hemoptysis in 7% of patients after HDR brachytherapy.²⁴

Cryotherapy:Cryotherapy is effective in the treatment of benign and malignant obstructing airway lesions.²⁵ The ideal lesion for cryotherapy is a small, polypoidal tumor that is accessible to the probe, with distal visibility of bronchial segments and functional lung. A major contraindication is in the treatment of patients with impending respiratory failure due to acute airway obstruction.²⁶ Cryotherapy can be performed with the RB or FB, and has been shown to potentiate the effects of chemotherapy and XRT.^27,28

Photodynamic Therapy:PDT involves the administration of a tumor-localizing photosensitizing agent, dihematoporphyrin ether/ester (Photofrin Axcan Scandipharm, Inc; Birmingham, AL), followed by activation with argon pump-dye laser at a wavelength of 630 nm via FB.

After the IV administration of dihematoporphyrin ether/ester (which is retained preferentially by tumor, reticuloendothelial tissues, and skin), the tumor is exposed to laser light 40 to 50 h later. This results in tumor necrosis from cellular destruction by superoxide and hydroxyl radicals as well as vascular occlusions from thromboxane A 2 release.²⁹ Clean-up bronchoscopy is often necessary 2 to 4 days after the procedure.

PDT is indicated for the palliation of advanced obstructing cancers of the tracheobronchial tree. It appears to be effective against polypoid tumors and hazardous in patients with submucosal and peribronchial disease.³⁰ Moghissi et al³¹ found that the mean endoluminal obstruction of 100 patients treated with PDT improved by 68%, with corresponding increases in FVC and FEV₁ . The median survival of patients with advanced lung cancer treated with PDT was also shown to be better than that observed with other treatment modalities.³²

Other indications for PDT include treatment of synchronous³³ and early lung cancers, which are considered inoperable due to high surgical risks, or treatment of patients who refuse surgery. For these patients, PDT may represent an alternative treatment modality if the following criteria are met: roentgenographically occult lung cancer; squamous cell carcinoma; superficial mucosal tumors by bronchoscopic inspection; and < 3 cm 2 in surface area and ≤ 1 mm in depth.³⁴

The advantage of PDT over LPR lies in its technical ease and safety. Distal lobar obstructions not amenable to LPR can be treated with PDT under local anesthesia. Complications of PDT are minimal and include dyspnea from airway obstruction due to tissue swelling and edema, photosensitivity, and hemoptysis.

One disadvantage of PDT is its slow onset of action; therefore, PDT is not useful for patients with acute respiratory distress. Other drawbacks include the need to avoid exposure to sunlight for 4 to 6 weeks and the frequency with which clean-up bronchoscopies are needed.

Stents

If an airway is obstructed as a result of extrinsic compression by tumor, simple dilatation with tubes of increasing size, an RB, or an angioplasty balloon can be performed. However, the beneficial effect of mechanical dilatation in malignant disease is short-lived and stent placement is often required. Stenting can be used as an adjunct to other treatment modalities and is useful for both mixed and extrinsic airway obstructions. Stent types, indications for placement, and the choice of stents are shown in Figure 4 and Tables 2 and 3.  

Figure 4. Top, models of silicone and hybrid stents available on the market. a = Rüsch Y stent; b = Dumon tracheal stent; c = Dumon bronchial stent; d = Montgomery T-tube; e = Hood bronchial stent; f = Orlowski stent; g = modified Dumon tracheobronchial stent; h = covered Schneider Wallstent. Reprinted with permission from Colt HG. Silicone airway stents. In: Beamis JF Jr, Mathur PN, eds. Interventional pulmonology. New York, NY: McGraw-Hill, 1999; 97–112. Bottom , covered and uncovered Ultraflex stent.

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Stent-Related Complications and Management: Tube stents are advantageous as they can be repositioned and removed without difficulty. The major disadvantages include stent migration, granuloma formation, and mucus obstruction. In the largest study on silicone stents (1,574 stents placed in 1,058 patients, 698 of whom had malignant airway obstruction), stent migration occurred in 9.5%, granuloma formation in 8%, and stent obstruction by mucus in 4%.³⁵ To minimize these complications, selection of stent type, size, and position is important, and prompt treatment of infection and inflammation with antibiotics and topical steroids is recommended.

Metallic Stents: are gaining popularity worldwide, as they can be placed with an FB under local anesthesia in an outpatient setting.³⁶ Other advantages include greater airway cross-sectional diameter, better conformity to tortuous airways, and maintenance of mucociliary clearance and ventilation across a lobar bronchial orifice. Major disadvantages include stent-related granuloma and the technical difficulty of removing or repositioning a stent after epithelialization has occurred.³⁷ Other complications, such as strut fracture and bronchial and vascular perforations observed with the Gianturco stent, are rarely observed now with newer alloys and designs.

Because tumors can grow through the gaps of uncovered metal stents, polymer or covered metallic stents of appropriate size and length should be used. If the airway becomes occluded by tumor or granulation tissue, the use of LPR should be avoided, as covered stents are generally flammable. Other techniques, such as cryotherapy or argon plasma coagulation,³⁸ can be used together with brachytherapy to good result.

Conclusion

Management of patients with obstructing lesions due to lung cancer involves multimodality treatment. In those who have < 50% obstruction and are asymptomatic, XRT or chemotherapy would suffice. However, in patients who present with life-threatening or symptomatic airway obstruction due to endobronchial or mixed lesions, LPR and EBES are preferred over PDT, cryotherapy, or brachytherapy, as they result in immediate restoration of airway patency and relief of symptoms. On the other hand, extrinsic or mixed lesions may require dilatation and stent placement. Radiation or chemotherapy is often considered and initiated within 2 weeks of the procedure in order to consolidate the local effect.

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