INTRODUCTION Brachytherapy refers to the placement of a radioactive source within or in close proximity to a malignancy in order to provide local radiation therapy. This approach delivers the highest doses of radiation in close proximity to the tumor and thus offers a theoretical advantage over external beam radiation therapy . The technique is most commonly used for palliation, although is has also been employed as definitive therapy on rare occasions. The use of endobronchial brachytherapy for the treatment of bronchogenic carcinoma will be reviewed here. HISTORY The initial use of endobronchial brachytherapy for bronchogenic carcinoma was reported in the early 1920s by Yankauer, who implanted radium capsules into an endobronchial tumor using a rigid bronchoscope, and removed them several days later through the mouth via an attached string . Over the next decade, Kernan, Cracovaner, and Pancoast also described the use of endobronchial radium to treat malignancy . Most of these cases required general anesthesia and either rigid bronchoscopy or thoracotomy for direct introduction into the tumor . The next major advance occurred in 1964, when Henschke developed the remote afterloading device, thus reducing radiation exposure to the healthcare staff . Almost 20 years after this, the current practice of enclosing the brachytherapy source within a polyethylene catheter and implanting it via a flexible fiberoptic bronchoscope was described. In addition, Iridium-192 became the isotope of choice for brachytherapy around this time . In the mid 1980s, publications distinguishing "low dose rate" (LDR) from "high dose rate" (HDR) brachytherapy appeared. Low dose rate brachytherapy implies delivery of less than 2 Gray (Gy)/hour and a total dose of 1500 to 5000 Gy, given over up to three days . HDR involves greater than 10 to 12 Gy/hour, with the total dose ranging from 500 to 4000 Gy, and the dose per session (fraction) varying from approximately 300 to 1000 Gy. The American Brachytherapy Society issued guidelines for the treatment of lung cancer in 2001 . TECHNIQUE Endobronchial brachytherapy requires implantation or insertion of a radioactive source into a patient's airway. In the past, rigid bronchoscopy was used for permanent interstitial implantation of a low energy radioactive source . This method has been replaced by the use of a flexible fiberoptic bronchoscope to place an afterloading polyethylene catheter within an airway adjacent to the tumor under direct visualization. Catheter position is verified radiographically (fluoroscopically and with a plain chest radiograph), after which the catheter is loaded with a radioactive source, either manually or with a remote afterloading device. Centering devices, such as balloons, cages, or sheaths, can be employed to maintain the radioactive source within the center of the bronchial lumen and avoid dose inhomogeneity . The dose rate of brachytherapy depends upon the energy and rate of decay of the radionuclide used. LDR brachytherapy requires manual manipulation of the radionuclide, 30 to 70 hours of treatment, and cumbersome radiation protection measures. HDR brachytherapy usually using iridium-192 is more commonly employed because it permits a dramatic reduction of treatment time, thus converting brachytherapy from an inpatient to an outpatient procedure. The shorter time that the catheter needs to dwell endobronchially decreases the likelihood that it will become displaced, improves patient convenience, and reduces treatment cost. Heavily shielded treatment rooms and the use of afterloading techniques (ie, inserting the radionuclide into the bronchoscopically-placed catheter by means of a remotely controlled device) have simplified radiation protection practices. HDR brachytherapy treatment is usually delivered in a series of dose fractions in order to optimize its effectiveness and minimize side effects. A wide variety of treatment schedules have been utilized; generally patients are treated no more than every one to two weeks because of the discomfort and logistical difficulties associated with more frequent bronchoscopies. PATIENT SELECTION The usual goal of brachytherapy is palliation of symptoms caused by large airway obstruction. However, the technique has also been employed postoperatively in patients found to have tumor at resection margins in an attempt to improve cure rates, or in patients with early stage lung cancer who can only tolerate sublobar resections . While the use of endobronchial brachytherapy to treat nonmalignant lesions has been reported , the technique has been used almost exclusively in patients with endobronchial tumors. Although the specific indications for this treatment modality vary among institutions, general criteria for treatment include:
Patients with unresectable and/or recurrent lung carcinomas or malignancies metastatic to the airways are potential candidates for endobronchial brachytherapy. The lesion to be treated should be visible by bronchoscopy and generally located in the trachea, main stem, or lower lobe bronchi. Tumor can be either extrinsic or intrinsic to the airway and may involve submucosal infiltration, as long as a catheter for deliver of the radiation source can be passed distally . Contraindications to endobronchial brachytherapy include the presence of fistulas between bronchi and other structures. Patients with endotracheal lesions causing high grade obstruction should be treated with Nd:YAG laser and possible placement of a stent before brachytherapy, because immediate use of brachytherapy may result in postradiation tissue edema and complete airway obstruction. Brachytherapy is not practical in patients who cannot safely undergo bronchoscopy, and is not indicated in patients who are moribund. COMPLICATIONS Both early and late complications of brachytherapy can occur. Early complications are due primarily to bronchoscopy and catheter insertion. These complications are infrequent in experienced hands. Radiation bronchitis and stenosis may occur days or weeks after therapy and can manifest with cough or wheezing. Risk factors include large cell carcinoma histology, use of brachytherapy for curative intent, prior laser resection, and concurrent external beam radiation . Serious late complications of endobronchial brachytherapy include massive hemoptysis and fistula formation; different series report that such adverse outcomes occur in between 0 and 42 percent of patients . Some authors suggest that involvement of the major arteries, significant destruction in the bronchial wall, and mediastinal invasion should be excluded by means of computed tomography, magnetic resonance imaging, or digital subtraction angiography prior to the institution of endobronchial brachytherapy, particularly when treating lesions in close proximity to large vessels . EFFICACY The major use of endobronchial brachytherapy is for the palliation of symptoms related to central airway obstruction; data pertaining to its use with curative intent are limited. Objective responses in tumor size have been evaluated by chest radiography and bronchoscopy. An obstruction score has been used by some authors but has not been widely utilized . A greater than 50 percent improvement in patency has been reported in approximately 70 percent of patients, and the positive response generally persists for at least six months . However, different series have enrolled patients with different characteristics, resulting in selection bias and making the results difficult to generalize. A significant number of patients in some reports refused subsequent bronchoscopy, potentially resulting in an overestimation of effectiveness. Palliation Subjective improvement following brachytherapy has been reported in 20 to 100 percent of patients, depending upon the series and the symptom complex prior to the procedure . One study of 50 patients who were treated with HDR endobronchial brachytherapy found that hemoptysis was relieved in 24 of 28 patients, breathlessness in 21 of 33, and cough in 9 of 18 patients; these responses were maintained for four months . Hemoptysis tends to improve most readily, with a greater than 90 percent response rate in many series. Cough and dyspnea improve less reliably, probably because they frequently are due in part to underlying conditions such as chronic obstructive pulmonary disease or radiation fibrosis . One report documented the treatment outcomes of 175 patients with lung cancer who received HDR brachytherapy for metastatic or locally recurrent lung cancer at a single institution over a ten year period . Symptomatic improvement was reported by 115 (66 percent); and repeat bronchoscopy demonstrated a 78 percent objective response rate (defined as 50 percent or more of the normal lumen reopened following therapy). Treatment-related complications were only evident in 19 patients (11 percent). Curative therapy Brachytherapy might be curative in selected patients . This is illustrated by the following observational studies:
Comparison with other modalities There are no high quality studies directly comparing other local modalities or external beam radiation with endobronchial brachytherapy. Conventional external beam radiation therapy palliates symptoms of hemoptysis, dyspnea, or chest pain in 50 to 80 percent of patients for approximately 3 months . Brachytherapy appears comparable or superior for the relief of these symptoms, but involves greater resources and patient discomfort. Brachytherapy has been combined with external beam radiation, and offers theoretical advantages which may translate into improved safety and efficacy . As an example, one study of 98 patients found that patients who received two treatments of endobronchial brachytherapy in addition to external beam radiation experienced superior local control of tumor compared with patients treated with external beam radiation alone. However, no significant differences in survival were observed. Limited data also suggest that the addition of endobronchial brachytherapy may provide results that are superior to endobronchial laser therapy alone . CONCLUSIONS Intraluminal brachytherapy is effective in palliating complications caused by malignant endobronchial tumors such as dyspnea, hemoptysis, intractable cough, atelectasis, and postobstructive pneumonia. Brachytherapy can be combined with external beam radiation, Nd:YAG laser therapy, or chemotherapy and may improve the degree and duration of palliation experienced by some patients. Further investigations are necessary to determine optimal dose fractionation and the ideal adjunctive use of the technique.
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