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Abstract & Commentary
Synopsis: Endobronchial obstruction and/or hemoptysis from intrinsic bronchial lesions may develop at some point in the disease process in those patients with inoperable or recurrent lung cancer. For many patients, particularly those who have been previously treated with external beam radiotherapy, endobronchial high-dose rate brachytherapy is an attractive palliative modality. Kelly and colleagues from the M.D. Anderson Cancer Center reviewed their experience with one of the largest series in the literature and concluded that most patients treated in this fashion exhibit an objective response that confers a statistically significant survival benefit.
Source: Kelly JF, et al. Int J Radiat Oncol Biol Phys. 2000;48:697-702.
During the years 1988 through 1997, 175 patients with primary or recurrent lung cancer presented for palliative evaluation to the M.D. Anderson Cancer Center with debilitating dyspnea (85%), cough (76%), hemoptysis (34%), and wheezing (27%) due to intraluminal tumor. Most patients presented with non-small cell lung cancer, with the predominant histologic subtype being squamous carcinoma (90 cases, 51%). Only 2 patients (5%) had small cell carcinoma. One hundred sixty-three patients (92%) had a history of prior thoracic radiotherapy (RT) which precluded further external-beam RT. Median age for the group was 60 years (28-79), and the median Karnofsky Performance Score (KPS) was 70 (50-100). Lesions involved the trachea in 9% of cases, carina in 2%, mainstem bronchus in 40%, and lobar bronchi in 66%.
Following the administration of intravenous sedation, all lesions were visualized bronchoscopically. Thereafter, a 6-French-nylon-brachytherapy catheter was inserted through the bronchoscope to a point at least 4 cm beyond the tumor. If necessary, a Nd:YAG laser was used for tumor ablation to permit passage of the catheter through any area of complete airway obstruction (20 patients, 11%). In some instances, 2 catheters were inserted in order to treat more than 1 disease site. The procedure was repeated at 2-week intervals from 1 to 4 times per patient, with 2 being the most commonly prescribed number of treatments (115 patients, 66%). The radiation dose was prescribed as 15 Gy to a radial distance of 6-7.5 mm from the line of the iridium-192 radioactive source, which was fed down the nylon brachytherapy catheter along a stainless steel cable. A Nucletron Microselectron HDR remote afterloading unit was used. The iridium-192 source had the capacity to move along a potential treatment length of 24 cm at 5 mm incremental dwell settings. Doses ranged from 5-45 Gy, with 23% receiving 15 Gy in one fraction, 30 Gy to 58% in 2 fractions, and 45 Gy to 7% in 3 fractions.
Tumor response was evaluated subjectively via a patient questionnaire, and objectively with repeat bronchoscopy and chest x-ray within 2 weeks of completion. One hundred fifteen patients (66%) noted subjective symptomatic improvement, equally divided between considerable and slight. There was a 78% overall objective response rate among patients undergoing repeat endoscopy (116, 66%), including 14 complete responses (8%) and 76 (43%) greater than 50% partial responses. Twenty-three patients (13%) had no response, and 2 patients (1%) showed progression of disease. There was a significant association between subjective assessment and objective response (P = .02). The mean response duration was 3.8 months. Overall mean actuarial survival was 6 months (0-54). Actuarial survival was significantly longer in the responders (7 vs 4 months, P = .003). No pretreatment factors predicted for response to endobronchial HDR therapy.
The actuarial-hazard rate for all complications was 13% at one year. The most common fatal complication resulting from endobronchial HDR was pulmonary hemorrhage (3 patients, 2%). Five other patients bled to death, but their hemoptysis was not attributed to the HDR therapy. There was 1 fatal complication each secondary to necrosis with fistula formation, and necrosis with stenosis. The most common nonfatal complication was pneumothorax (4 patients, 2%), followed by nonfatal hemoptysis (2 patients, 1%), necrosis (2 patients, 1%) and esophageal stricture (1 patient, 0.6%). There was no correlation between the number of HDR applications and toxicity.
COMMENT BY EDWARD J. KAPLAN, MD
The purpose of the Kelly paper was to evaluate the toxicity and efficacy of endobronchial HDR brachytherapy in the palliative setting. Kelly et al illustrated that toxicity from reirradiation using the HDR approach was acceptable, and palliation was immediate. Disparities in types of symptoms relieved, if any, were not described. Those patients whose lesions regressed with therapy enjoyed a 75% increase in survival, which was a statistically significant benefit. Although the mean duration of symptom relief was 3.8 months, it is unclear whether actuarial symptom relief correlated with actuarial survival.
In some instances, laser ablation was used in conjunction with HDR by the M.D. Anderson group in order to traverse areas of complete airway occlusion. This sort of dual modality technique was recently reported by Chella, who conducted a small, randomized comparison of length of symptom relief following laser alone vs. laser with endobronchial brachytherapy. The symptom-free period grew from 2.8 months without HDR to 8.5 months with HDR (P < .05). The fractionation scheme and prescription parameters selected by Kelly et al were similar to those used in other series cited in their paper. The most common number of applications was 2, where patients who only received 1 treatment tended to have deteriorated, and patients who received 3 treatments tended to exhibit a slower response. Where most series report 5-10 Gy per fraction prescribed to a radial distance of 10 mm from the source, the present study used 15 Gy prescribed to 6 mm. In fact, that prescription is dosimetrically equivalent to 8.4 Gy prescribed to 10 mm, ie, an average dose. Since there are no rigid prescription guidelines, the prescription parameters are flexible, and are left up to the discretion of the treating physician.
As mentioned, there are many advantages to HDR therapy. Radiation exposure to the clinical staff is minimized by virtue of the afterloading technique used with HDR therapy. That is, the radioactive source is housed in a shielded repository until it is deployed into the nylon catheter and reeled down to the area of lesion where it dwells at a string of sequential stations along a designated length for the time required to impart the prescription dose. The patient is kept in a shielded room during the actual deployment of the source. The dosimetry plan is customized for each patient’s tumor. The procedure is fairly short, so displacement of the catheter is less likely than might be expected using low dose rate brachytherapy, which is typically done on an inpatient basis over several days. HDR can be used for either tracheal or bronchial lesions, and is done on an outpatient basis using intravenous sedation. HDR administration can be repeated as needed depending upon the tumor’s response and the patient’s overall status.
The integration of chemotherapy, possibly as a radiosensitizer, along with HDR remains under investigation. Likewise, for those patients who are candidates for external beam RT, its relative advantages and disadvantages in comparison to HDR for relief of endobronchial obstruction are not clear. A randomized trial was attempted by the MRC in an effort to answer that question, but was abandoned in 1996 because of poor accrual. Finally, photodynamic therapy has also been investigated and may have a role along with RT and chemotherapy for relief of intraluminal obstruction.
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2. Moghissi K, et al. Clin Oncol (R Coll Radiol). 1999;11:179-183.
3. Ost D. Oncology (Huntingt). 2000;14:379-386.