cist) is ready and approved by the radiation oncologist, a physicist performs a second check before the treatment commences. The purpose for this is to fnd and eliminate potential errors. The treatment plan is then transferred to the HDR remote afterloader computer, in order to deliver the prescribed dose.

The computer used for the treatment will receive from the TPS the information regarding the HDR source, dwell positions, and corresponding dwell times along the catheter(s). The patient is identifed by two means, then a patient-­ specifc quality assurance checklist is flled out by the radiation oncologist and physicist before the treatment starts. Both the radiation oncologist and physicist must be present at the HDR console area during treatment and should be available if any emergency occurs. It is a good practice to acquire the images and treat the patient in the same position. If the patient cannot lie down during treatment, he/she can be treated while sitting in a chair. The catheter is checked again using a

gauge wire to ensure there is no obstruction, the catheter exit marking is verifed, and then the catheter is connected to the HDR remote afterloader. There is no need for respiratory motion management during treatment, since the bronchial catheter moves with the anatomy. For the multi-insertion approach, the catheter is removed by the radiation oncologist after each HDR-­ EBBT treatment. After treatment completion and catheter removal, the patient and room should be surveyed to ensure that the radioactive source was returned to its storage location. The patient should be observed after the procedure and discharged when stable.

Evidence-Based Review

The 2001 ABS guidelines recommended the use of EBBT for palliation, particularly for endobronchial lesions not amenable to laser therapy or stenting.

Patient selection is based on the typical symptoms of malignant airway obstruction including dyspnea, cough, lobar collapse, or post-­obstructive pneumonia. These patients often have not responded or are not candidates for standard chemotherapy or EBRT. The lesion must be amenable to bronchoscopy including placement of a small-bore catheter in the airway. Tumors in the airway that show signifcant vascular involvement or ulceration should be considered for other options due to higher risk of complications such as hemoptysis and further airway damage. It is important to note that the patients with acute or severe symptoms of airway obstruction should have an alternative ablative technique as frst-line treatment due to the delayed effects of EBBT on restoring airway patency. As a general rule, EBBT is typically not selected or recommended as a frst-line therapy for obstructing endobronchial malignancy [3, 14]. EBBT can be performed in the vicinity of metal airway stents, but data from esophageal metal stents show that mucosal doses can be increased substantially in the immediate adjacent tissue [15].

EBBT remains a viable option to provide localized radiation in order to reestablish airway patency, reduce symptoms, and enhance performance status with minimal side effects. The radiation oncology database of patients treated with EBBT at Lahey Clinic from 1996 to 2009 was used to perform a retrospective chart review of 88 patients. Each patient record was reviewed for symptoms of cough, dyspnea, chest pain, hemoptysis, pneumothorax, respiratory failure necessitating hospital admission before and after EBBT. A small percentage of procedure-related sided effects were noted in our cohort (4.5%). One patient (1.1%) developed a cough immediately after the procedure. Three patients (3.4%) developed respiratory failure after the procedure, necessitating transfer to a higher level of care for either increased oxygen therapy or closer monitoring (without endotracheal intubation). There were no deaths during treatment. There were no documented symptoms of shortness of breath, chest pain, hemoptysis, or pneumothorax documented related to EBBT. EBBT seemed to result

in improvement in the following symptoms: hemoptysis (90.9%), respiratory failure (85.7%), cough (79.5%), chest pain (76.9%), and shortness of breath (73.2%). Upper lobe position of the brachytherapy catheter can pose technical challenges. The likelihood of catheter malposition was 25% in the right upper lobe (RUL). The survival beneft was documented as days alive after EBBT. Survival was broken down by diagnostic category into small cell carcinoma, non-­ small cell carcinoma, and metastatic or other (that included carcinoid tumors). The survival beneft was highest in the metastatic/other category (272 days), followed by non-small cell carcinoma (122 days), and small cell carcinoma (112 days) [16].

A Cochran meta-analysis in 2012 reviewed 14 randomized clinical trials involving EBBT either as isolated therapy or in combination with other modalities. There was no clear survival advantage with fewer vs. multiple fractions of EBBT or when added to EBRT or compared to Nd:YAG laser [17]. A large retrospective study of 648 patients showed no difference in effcacy or survival in groups treated with 1 fraction versus multiple fractions [18]. Another larger randomized trial of 142 patients showed improved local tumor response in 2 fractions versus 4 fractions with similar overall survival but a trend toward reduced fatal hemoptysis with fewer fractions [19].

Adjuvant Treatment

The combination of brachytherapy and EBRT is not commonly used for palliative purposes. However, combined therapy can be used in cases where it is felt that prolonged palliation is achievable [7].

The ABS suggests 2 fractions of 7.5 Gy each, 3 fractions of 5 Gy each, or 4 fractions of 4 Gy each (prescribed at 1.0 cm) should be given when HDR therapy is used as a planned boost to supplement palliative EBRT of 30 Gy in 10–12 fractions, when patients have no previous history of radiation treatment to the chest. The interval between fractions is generally weekly [7].

Palliative Treatment

Patients with endobronchial malignant lesions can present with airway obstruction, dyspnea, hemoptysis, and pain. Intraluminal brachytherapy can provide symptomatic relief if they are not amenable to other treatment modality. This is more common in non-small cell carcinoma since it is quite unusual for small cell carcinoma to have luminal mucosal involvement [2]. Chella et al. reported a small randomized study of 29 patients with NSCLC who were treated with Nd-YAG laser combined with HDR-EBBT or laser only. It was found that the combination of Nd-YAG laser and HDR-EBBT for central airway malignant lesions is superior to laser alone in terms of symptoms free survival (8.5 vs. 2.8 months p < 0.05) and progression free survival (7.5 vs. 2.2 months p < 0.05). There were no treatment-associated morbidities or mortalities reported [20]. Also, HDR-EBBT can be safely combined with photodynamic therapy achieving complete endoscopic response in 87.5% of the patients at 24 months [21]. In a retrospective analysis consisting of 226 patients treated with EBBT with or without EBRT, the complete endoscopic response rate was 93.6% at 3 months [22].

Defnitive Treatment

Standard defnitive therapy for unresectable lung cancer is a combination of chemotherapy and EBRT. Selected patients (those with predominantly endobronchial tumor) may beneft from EBBT, either alone or as a boost to EBRT. The ideal patients for curative EBBT alone are those with occult carcinomas of the lung confned to a bronchus or trachea. Moreover, EBBT can be used as a boost treatment for selected patients with inoperable non-small cell carcinoma, in combination with EBRT. Brachytherapy boost is especially advantageous in cases of post-­obstructive pneumonia or lung collapse to overcome bronchial obstruction, so that the lung is aerated and

the tumor volume is better defned. This allows sparing of the normal lung from external beam radiation. Brachytherapy with curative intent can be an option in early-stage patients who are medically inoperable. Additionally, EBBT can be used as adjuvant treatment after surgical resection with minimal residual disease [7].

Complications

EBBT is generally considered to be a safe procedure with minimal side effects. Nevertheless, complications occur in around 3–30% of patients, including fstula formation, radiation bronchitis, tracheal perforation, ulcers, hemorrhage, bronchial stenosis or necrosis with some complications being fatal [23]. Catheter dislodgement when attempting to treat upper lobe bronchi is a common procedure-related complication which was noted in our Lahey cohort [16].

Post-treatment bronchoscopy may be needed to diagnose and treat urgent complications (i.e., to address hemoptysis, or to clear airway from radiation induced mucosal debris).

Summary and Recommendations

EBBT is a safe procedure with relatively low complication rate. Careful patient selection and modifcation of the number of intended treatments in cases where there is evidence of radiation-­induced damage to the airway epithelium seems to avert signifcant procedural complications. Patients with endobronchial ulceration, fstula formation, or severe airway tumor obstruction are typically not recommended for EBBT [14]. Patients may require monitoring for transient worsening airway obstruction from sloughing tissue or edema, and may require repeat bronchoscopy in the frst few days following treatment [14].

EBBT in conjunction with other invasive interventional procedures can be used for palliating respiratory symptoms caused by endoluminal tumor burden in carefully selected patients.

Acknowledgment  The authors are indebted to Professor Gene Wong, MD, for his major contributions to this chapter and for his patient guidance throughout the project. We are grateful to Joan Gabriel, RN, and Nicole Walker for the photographs in this chapter.

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