Canadian Neighbor Pharmacy: Discussion of Palliation of Bronchogenic Carcinoma with 198Au Implantation Using the Fiberoptic Bronchoscope

malignant diseaseMost patients with malignant disease of the lungs will, at some time in their course, require palliative therapy. Previously, this has centered on radiotherapy for non-small cell and chemotherapy and/or radiotherapy for small cell tumors. The prospects for those who remain symptomatic or whose symptoms recur after maximum tolerated radiotherapy are bleak. Symptomatic therapy with increasing doses of narcotics or cough suppressants are all that can usually be offered.

Bronchoscopic placement of radiation sources was first reported by Ormerod in 1937. He implanted radon seeds into 67 patients via the rigid bronchoscope. Without quoting specific response rate, he noted a number of successful implantations. Pool reported on 44 patients who underwent similar implantations. Two of his patients died during the procedure, but he was impressed with the techniques utility for treating tracheal lesions or bronchial stump recurrence. More recently, Hilaris et al, also using a rigid bronchoscope, implanted Radon or 1 into 62 patients. Local control was achieved in 52 to 54 percent of his patients. All patients with hemoptysis responded. In a small series of six patients, Mendiondo et al successfully palliated local recurrence of tumor using endobronchial radiation delivered by a variety of techniques. We believe that ours is the first report of the use of the fiberoptic bronchoscope for implantation of radiation sources specifically to palliate endobronchial neoplasm.

The recent interest in endobronchial laser therapy sometimes combined with hematoporphyrin has stimulated us to review the use of gold seed implantation at this institution since 1979. As demonstrated, this technique is no more invasive than routine fiberoptic bronchoscopy. It does not require general anesthesia, rigid bronchoscopy, or even for the patient to be hospitalized. It is also easily mastered by any physician trained in fiberoptic bronchoscopy.

The “seeds” themselves are 198Au which is prepared in a nuclear reactor by accepting a neutron. It decays with a half life of 2.7 days to mercury. For that reason, they are coated with platinum. Although studies for mercury toxicity were not performed, no patient exhibited a compatible syndrome. The emission is gamma radiation with an energy of 412 kev (for comparison, cobalt commonly used for external beam radiation, has emission of1250 kev). At this institution, those patients with total implants of less than 35 mCi may be discharged home immediately after the procedure. The majority of implants are less than this figure.Canadian Neighbor Pharmace has the official website full of all-absorbing facts concerning medicine and pharmacy which are so popular to tals about nowadays especially.

Following the last ten procedures, emissions were measured at a distance of 1 meter from the patient, yielding a figure of 4.1 meter REMS/hour (range 2.0 to 9.0). This would decrease at the inverse square of the distance (example: at 2 meters would be 0.25 X 4.1 = 1.025) and would also decrease with a half life of 2.7 days. Thus, we do not believe that the use of 198Au poses a significant risk of radiation exposure to family or attendants.

The procedure is remarkably effective in selected patients; those with prominent hemoptysis had a particularly gratifying response, which is not surprising considering the sensitivity of the endothelial mainstem bronchicell to radiation. Bulky central lesions obstructing the mainstem bronchi or impinging upon the tracheal lumen also responded very well. It was difficult to assess benefit in this retrospective review in the group with nonobstructing lesions as routine follow-up bronchoscopy or spirometry was not performed. Although we cannot draw conclusions from a single patient, it appears that surgery was avoided and a cure obtained in the patient implanted for carcinoma in situ. The use of gold seeds in this patient allowed an increase in the dose of radiation delivered from 5,500 rads by XRT to over 10,000 rads with combined radiotherapy and 198Au seeds. This dose may be tumoricidal.

A subgroup that manifested significant pleural effusion together with endobronchial disease could not be shown to benefit, probably related to the advanced stage of the disease with extensive infiltration of either the pleura or the mediastinum. This subgroup had a short mean survival of 1.7 months.

The two patients who have had peripheral lesions implanted have both had a very good response, one with a Pancoast tumor causing severe pain which relapsed following XRT had complete relief of pain for more than a month after first implanted; the other with no symptoms had a peripheral adenocarcinoma (unre-sectable by virtue of poor pulmonary function) treated with combined XRT and gold seeds. Combined therapy allowed delivery of in excess of10,000 rads which is potentially curative. The lesion has shown marked shrinkage on chest x-ray film.

The trend toward better response of more proximal tumors is probably related to more extensive infiltration of the parenchyma by tumors located in more peripheral parts of the bronchial tree. The procedure was, by and large, well tolerated, certainly not less so than any routine fiberoptic bronchoscopy. There were no deaths during insertion, and one death from massive hemoptysis occurred four days postimplantation. The other major events occurred long after the seeds became inactive, and all were thought to be part of the natural history of the malignant disease, eg, tracheoesophageal fistula or hemoptysis.

Relative to endobronchial laser therapy, this procedure appears to have several advantages. No general anesthesia or rigid bronchoscopy is necessary as currently recommended for laser. 198Au seed implantation does not require that the lumen of the bronchus be visualized or that the axis of the bronchus be known, as is the case with laser, where inadvertent perforation of the bronchus may occur if the fiber is not aligned parallel to the airway wall prior to firing. The implantation technique is easily learned and has the theoretical advantage of deliverying therapy to that part of the tumor lying outside of the bronchial or tracheal wall. The requirement for a nuclear reactor to charge the seeds is not a factor that should limit the availability of this technique. The half life of 2.7 days would allow delivery by overnight service to most locations in the United States with more than adequate energy remaining for effective usage. The mean MCI/seed of 6.7 (vs 10 for a fully charged seed) indicates that most implantations in this study were done one to two days after charging of seeds.

Accurately defining which subgroups would benefit most from this technique as opposed to laser will require further prospective study. However, we would speculate that this technique would be most appropriate for central obstructing endobronchial lesions where the precise bronchial anatomy is obscured by tumor, and thus, laser would be relatively contraindicated. It may also be more appropriate at smaller institutions where laser expertise may be unavailable or purchase of an Nd-YAG laser may not be cost effective. We believe that fiberoptic bronchoscopy is widely available in the United States and that this technique is easily learned by any endoscopist. Laser photoresection may be more appropriate where critical airway narrowing requires immediate relief.

In summary, we believe endobronchial implantation can offer palliation of airway symptoms to certain subgroups of patients with unresectable disease of the lung, is no more invasive than routine fiberoptic bronchoscopy, has low morbidity and is potentially widely available.