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Ann Thorac Surg 2002;74:1928-1933
© 2002 The Society of Thoracic Surgeons
a Joseph Brown Whitehead Department of Surgery, Section of General Thoracic Surgery,, Emory University School of Medicine, Atlanta, Georgia, USA
b Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia, USA
* Address reprint requests to Dr Miller, Section of General Thoracic Surgery, The Emory Clinic, Inc, 1365 Clifton Rd, Atlanta GA 30322, USA.
e-mail: jmille6331{at}aol.com
Presented at the Forty-eighth Annual Meeting of the Southern Thoracic Surgical Association, San Antonio, TX, Nov 8–10, 2001.
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Abstract |
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METHODS: A 12-year retrospective review (1988 to 1999) of 121 consecutive patients with inoperable malignant airway obstruction (MAO) was performed. Sixty-five patients received high-dose-rate brachytherapy (HDR) alone, 32 received HDR plus neodymium:yttrium-aluminum garnet laser (YAG) therapy, 16 received YAG only, 4 patients were stented, and 4 received photodynamic therapy (PDT). Follow-up was obtained by chart review and contact.
RESULTS: Seventy-seven men and 44 women, median age 62 years (range 30 to 86 years), underwent 378 endobronchial procedures for relief of MAO. Good to excellent results were achieved in 77% (93/121) of patients. Seventy-two percent (23/32) of patients undergoing HDR plus YAG received a good to excellent result. All 8 patients receiving either stents or PDT had good to excellent palliation. There were no intraoperative deaths, but there were two in-hospital deaths. Complications occurred in 4% (5/121) of patients. Forty-four percent (53/121) of our patients were lost to follow-up. Mean survival was 6.7 months after the last treatment.
CONCLUSIONS: Temporary relief of inoperable MAO can be accomplished with a number of endobronchial treatments used either singularly or in combination. The majority of patients managed with HDR, YAG, or HDR plus YAG received good to excellent short-term palliation.
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Introduction |
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There are a number of types of endobronchial therapy that are clinically applicable for primary or recurrent inoperable cancer of the trachea and bronchi. These modalities include rigid bronchoscopy "core out," neodymium:yttrium-aluminum-garnet (YAG) laser, high-dose-rate endobronchial brachytherapy (HDR), endobronchial stents, photodynamic therapy (PDT), and various combinations of these. Our purpose is to review our experience with palliative management of malignant airway disease.
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Material and methods |
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The age of the patients ranged from 30 to 86 years, with a median age of 62 years. There were 77 men and 44 women. All procedures were carried out on the cardiothoracic surgical service of Emory University Affiliated Hospitals. All palliative types of therapy were performed by the same surgeon with the aid of two radiation colleagues in delivering the afterloading endobronchial brachytherapy.
All patients underwent clinical examination, chest roentgenography, chest computed tomograpy (CT) scan, and an endobronchial exam with either a flexible or rigid bronchoscope. Helical CT scans became available at our institution in 1995; previous to that year, all patients had received standard CT scans with 7-mm cuts. All patients exhibited evidence of high-grade endobronchial or extrinsic compression at the time of therapy. The type of modality utilized in this series of patients consisted of HDR (65 patients, 54%), HDR + YAG (32, 26%), YAG only (16, 13%), stents (4, 3.5%), and PDT (4, 3.5%). The etiology and types of tumors are listed in Table 1. Eighty-four percent of patients with malignant airway obstruction in our series had non–small cell lung cancer. Most of the miscellaneous tumors were either metastatic colon or metastatic renal cell carcinomas. Table 2 lists the most common location of obstructing tumors.
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In both classification systems, an excellent result is associated with reopening of more that 80% of the normal lumen, with corresponding improvement and objective variables and clinical status. A good result is associated with reopening of more than 50% of the normal lumen, with some improvement in clinical symptomatology. A fair result is associated with the reopening of less that 50% of the bronchial lumen and the presence of major clinical symptoms. A poor result in both categories is associated with no response to therapy.
Laser therapy
YAG laser therapy was performed utilizing a standard technique as previously described [4]. All patients were treated in the operating room. Operative management included an initial fiberoptic bronchoscopy performed under local anesthesia to be sure the patient was a candidate for the planned procedure, followed by induction of general anesthesia. A rigid number 9 ventilating Jackson bronchosope or Wolfe-Dumon Laserscope was inserted, depending on the location of the lesion. An Olympus (New York, NY) fiberpotic bronchoscope was passed through the rigid scope and laser therapy was performed at a power density of 50 W with a pulse width of 0.5 seconds on all patients. The coagulation mode of the laser was predominately used. After coagulation of the tumor blood supply, the majority of the tumor was quickly removed with a large biopsy forceps from the rigid endoscopic system. During laser therapy, concentration of oxygen was kept at less than 50%. Total laser time was less than 20 minutes in all patients, and operative time was 
1 hour.
HDR endobronchial brachytherapy
All endobronchial brachytherapy was performed with a Nucletron Selectron high-dose radiation remote afterloading unit using an iridium-192 source. The Selectron system is a three-channel high-dose-rate remote afterloading system. It houses a treatment unit that stores the sources within a lead-shielded safe in a desktop-controlled unit. The unit has a memory for 100 standard sources loading with the treatment times. These are anatomically corrected for source decay. The treatment time and number and positions of source can be programmed independently for each channel to give the required dose distribution for a particular patient or tumor geometry. The accuracy of source positioning is within ± 1 mm. The iridium-192 source is placed through a number 2 afterloading catheter. Definitive or palliative radiation therapy in doses ranging from 30 to 60 Gy had been given previously or concurrently in all patients.
Catheter placement for HDR was performed in the outpatient bronchoscopy suite with the patient under conscious sedation with topical anesthetic. A number 2 afterloading catheter was advanced through the working channel of the bronchoscope and into the desired location, and the bronchoscope was withdrawn over the catheter. The catheter was secured at the nasal orifice, and the patient was transferred to the radiation suite. A dummy source was placed in the length of the catheter, with the target area to be determined based on chest roentgenography and bronchoscopic findings. An iridium-192 line source was placed in the catheter at the targeted position. Planned dosimetry was 30 Gy for the total dose, delivered as 7.5 Gy in one fraction with a total of four sessions given 2 weeks apart. Total time of delivery of each dose ranged from 10 to 14 minutes depending on the source, strength, and the length of the oscillation. After completion of the brachytherapy, the afterloading catheter was removed, and the patient was observed for 30 minutes and then discharged if stable. No subsegmental orifices were considered suitable for endobronchial brachytherapy.
Stents and PDT
All stents were placed under general anesthesia through an endotracheal tube with fiberoptic visualization and fluoroscopy. First-generation self-expanding metallic stents were used in the trachea and mainstem bronchus in 2 patients, and third-generation covered metallic Ultraflex stents were used in the trachea of 2 patients.
PDT was initiated at our institution in June 2000, and it was used in selected patients. An intravenous injection of a hematoporphyrin derivative, a photosentizing agent (Photofrin, porfimer sodium), was administered at a dose of 2 mg/kg. The injection was followed 48 hours later by laser therapy with an excimer dye laser at a wavelength of 630 nm. The technique of laser insertion was similar to that utilized with YAG laser therapy. Initial fiberoptic bronchoscopy was performed under local anesthesia followed by the induction of general anesthesia and insertion of a number 9 rigid ventilating Jackson bronchoscope. An Olympus fiberoptic bronchoscope was passed through the rigid scope, and laser therapy was performed with a total dose of 100 to 200 J, depending on location of the tumor. A cleanup bronchoscopy was performed on all patients undergoing PDT 48 hours after laser therapy.
Survival could be estimated from the time of last contact with the patient, and a Kaplan-Meier curve (Fig 1) was constructed from these data.
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Results |
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Morbidity and mortality
There were two in-hospital deaths in our series of 121 patients. Both patients with early deaths received HDR only for mucosal disease in the right mainstem bronchus. One patient died from hemorrhage and exanguination several days after placement of the afterloading catheter, and a second patient suffered a cardiac arrest during the hospital stay. There were no intraoperative deaths. There were three other complications in this series; 2 patients developed pneumonia and 1 patient developed atrial fibrillation.
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Comment |
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As pointed out by De La Torre and colleagues, management of patients with malignant airway obstruction "depends on the urgency of the presentation, the etiology, localization, extent of obstruction, and the prognosis of disease" [7]. Complications from the obstruction, the therapeutic measures available, and the experience of the physician influence the management of these patients. Expedient palliation with relief of symptoms and minimal risk to the patient is the goal of all palliative therapy for malignant airway obstruction. Predominate methods of palliation of malignant airway disease are as previously described, and these techniques may be used in alone or in combinational sequence.
Mathisen and colleagues have favored the rigid bronchoscopy core-out technique as the most immediate method of alleviation of high-grade malignant airway obstruction in the trachea and mainstem bronchus [8]. Significant relief of symptoms was achieved in 91% (51/56) of patients. We have tended not to use this method in exophytic lesions because of bleeding and instead have favored the YAG laser.
At out institution, we consider YAG laser therapy as our predominant modality in the relief of malignant exophytic high-grade airway obstruction, whether at the time of initial presentation or at a later time in the patient’s course. If a patient is considered to have an inoperable bronchogenic carcinoma on the basis of physiologic, anatomic, or medical reasons, and has major exophytic airway obstruction, we have used a combination of YAG laser therapy, followed by endobronchial brachytherapy as part of our initial management. Once the high-grade malignant airway obstruction is relieved, conventional chemotherapy and radiation can then be utilized.
YAG laser therapy provides a means to immediately reopen large occluded bronchi. The results, when the trachea or main stem bronchi are occluded with a high-grade obstruction, are quite dramatic. The technique for laser therapy has resulted in a short operating time of 15 to 30 minutes with coagulation of the tumor’s blood supply, followed by bulk removal with a large forceps. All laser therapy is completed at a single sitting; rarely is a second procedure required. We had previously reported on 130 patients who underwent YAG laser therapy, and 21 who underwent a combination of YAG laser therapy plus HDR, with significant improvement achieved in 80% [4]. Schrady in 1989 reported on 61 patients who underwent a combination of HDR and YAG laser, with improvement in 64% [9].
The term "brachytherapy" refers to that form of radiotherapy intervention with a short distance between the radiation source and the target area [10]. The principle use of HDR has been to deliver a very high-dose beam to a small target volume. HDR is useful in residual mucosal disease after laser therapy, and it has advantages in treating disease at the lobar level. When there is obstructive disease at a major lobar bronchus with significant symptoms (infection), particularly in a patient who has received conventional chemotherapy, HDR can provide benefit.
HDR has the ability to deliver high-intensity radiation to a control position without damage to external tissues. The patient’s comfort and safety are easy to maintain, because the accuracy of dosimetry is precise. Complication rates are low, and the response rates are high. When the dosimetry is kept to 750 rad at each treatment session, with the total dosimetry not exceeding 3000 rad, the stricture rate is minimal. HDR can be used concurrently with or after maximal external radiotherapy without causing major radiation consequences.
Montgomery, an otolaryngologist at the Massachusetts General Hospital, initially pioneered the use of stents in the tracheo-bronchial tree [11]. However, it was not until 1990, when Fraçois Dumon published his preliminary results using a reconfigured silicon stent in 66 patients, that stenting of tracheobronchial disease progressed [12, 13].
Presently, metal expandable stents and coated expandable stents are most frequently placed for malignant disease causing extrinsic compression on the airways. The preliminary experience at the Cleveland Clinic, reported by Dasgupta and associates, demonstrated immediate symptomatic improvement in 95% of the patients with granulation buildup in only 16% [14]. The placement of stents after relief of high-grade airway obstruction, particularly the coated expandable type, can frequently prevent the reformation of obstructing airway disease.
PDT has recently been introduced in this country and approved by the FDA for the relief of malignant airway obstruction. It has been useful in patients with exophytic disease at the lobar, mainstem, and tracheal levels. The procedure entails the intravenous injection of a hemotoporphyrin derivative (Photofrin) that acts as a tumor photosensitizer, and excimer laser therapy 48 hours later. The patient then undergoes a "toilet" bronchoscopy 48 hours after laser therapy. This mode of therapy has been used at several institutions in a significant number of patients, and it has a growing popularity within the United States. The advantages of PDT reside in its abilities to treat lobar exophytic disease and "clean up" residual disease after core-out bronchoscopy or YAG therapy. PDT may be repeated in the same patient; however, PDT does render the patient photosensitive to light for 4 to 6 weeks after therapy.
Due to limited grading standards, difficulty exists in efforts to analyze results in the endobronchial treatment of malignant airway disease. For our study, we used two classification systems to quantitate improvement and survival in our methods of therapy. In our 65 patients who were treated with HDR, 28 patients survived greater than or equal to 6 months, with 23 surviving greater than 1 year, and several surviving greater than 2 years (Fig 1). In this group of 65, 33 were lost to follow-up. In the group of 32 patients receiving HDR and YAG therapy, 17 survived greater than 6 months, 7 survived greater than 1 year, and 14 were lost to follow-up. In the group of patients undergoing YAG laser therapy alone, 10 patients survived greater than 6 months, 4 were alive for greater than 1 year, and 6 were lost to follow-up. Statistical comparisons for survival could not be made between groups because of inadequate sample sizes and limited follow-up in many patients. Our experience with stent therapy and PDT has been too limited to make valid claims on these techniques for malignant airway obstruction. We believe that stents and PDT provide useful adjuncts to other types of therapy.
Based on our results in this study, we believe the following is a reasonable consideration in the management of inoperable initial or recurrent non–small cell bronchogenic carcinoma (Fig 2). For endoluminal exophytic high-grade obstructive disease in the trachea, mainstem bronchi, or bronchus intermedius, we would begin with initial YAG laser therapy, followed in 48 hours by HDR. If there were subsequent residual disease, we would treat with PDT. In general, using these modalities early would apply only with initial or recurrent high-grade obstruction disease in the trachea, mainstem, or bronchus intermedius.
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In the patient with malignant airway obstruction due to extrinsic compression, the location of the obstruction determines the type of treatment. When the obstruction is at a lobar level, we do not believe that there is any significant modality that helps extrinsic compression here. However, when extrinsic compression exists in the trachea or mainstem without mucosal disease, we recommend placing a stent of the walled-lined type. If mucosal disease were present, the mucosal disease would be treated with PDT or HDR and followed with stent placement.
The combination of various types of endobronchial techniques for relief of a malignant airway obstruction improves the quality of life in more than 80% of patients, and it appears to enhance a longer period of survival.
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Discussion |
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Second, we are seeing a lot of patients where the problem is really external compression of the trachea or main stem either by tumor or nodal disease. I noticed you only placed four stents, and we really favor stents for those types of patients. Would you comment on whether you think the use of stents is low in your series because of seeing predominantly endoluminal disease or because stents are relatively new?
And third, how many of the patients in your series had acute respiratory failure, and if they did and required emergency intubation, et cetera, how do you handle those patients? Do you have anything special to add for those patients? For example, do you favor perhaps rigid bronchoscopy coreout for those patients?
Thank you. I really enjoyed your paper.
DR MORRIS: Thank you very much, Dr Reed, for your questions. I will take the question regarding the length of stay. We did not look at that specifically. It varied, as you could imagine, and as we got better with our treatment plans, it actually shortened, but we did not look at that specifically. That is an excellent question.
With regards to placement of stents, as you saw, we stopped our study in December 1999, so we have actually done quite a bit more since that time. So I do not think it necessarily reflects the disease pattern but more what we are used to doing. So we have done quite a bit more with that.
And as far as the use of rigid bronchoscopy and a core-out technique that has been well described by Dr Mathisen and others, we feel like that, in our hands, for those patients who would be treated with that, we prefer the YAG laser, because we have run into some problems with bleeding with the core-out technique. You also asked about the number of patients that had respiratory distress. I do not have a percentage on that, but there were quite a few of our patients, and I would say maybe close to 10%. That may be underestimating it a little bit.
I hope that answers your questions. Thank you.
DR ROBERT J. CERFOLIO (Birmingham, AL): Drs Morris and Miller are to be congratulated on a nice series of very difficult patients. I appreciate you letting me look at the manuscript. Just a couple of quick questions: the stenting is a critical issue and Dr Reed has already addressed that. How about photodynamic therapy? I know your PDT experience has mostly come after you have completed the paper, but now, even in your algorithm, you do not have PDT for patients with main stem bronchus or lobar bronchial disease. My question would be, one, do you now recommend that PDT over YAG in that situation, as we do? Two, what about the edema with PDT and brachytherapy? Do you recommend the delay in treatment of a few weeks, as we do in Birmingham? And number three, what dose of PDT do you use in the obese patient (now, maybe patients in Birmingham are just a little heavier than they are in Atlanta, but it is $2000.00 per vial); we found that if you use less than 2 mg/kg for mean body weight it seems to work just as well. Have you had any experience in using a lower dose of PDT, as we have, with the same efficacy?
DR MORRIS: Thank you very much, Dr Cerfolio. Just addressing the dose question first, we still stick with the 2-mg/kg dose and of course tell our patients that they are to avoid sunlight for a period of time after that. So I do not have any experience with a lower dose.
As far as treating edema after these procedures, we certainly do see it, and we do not end up waiting, certainly if our follow-up is at 6 weeks after the last treatment. We do wait 48 hours after the initial treatment, for instance, if you remember back to the algorithm that I showed, and that leads me into your other question. We still like to use YAG laser therapy for main stem and bronchus intermedius, and in order to allow some decrease in the edema, we only wait 48 hours, and we have not seen too many problems associated with that.
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This article has been cited by other articles:
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  A. Ernst, D. Feller-Kopman, H. D. Becker, and A. C. Mehta Central Airway Obstruction Am. J. Respir. Crit. Care Med., June 15, 2004; 169(12): 1278 - 1297. [Abstract] [Full Text] [PDF]
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 C. E. Reed General thoracic surgery and the Southern Thoracic Surgical Association: the second 25 years Ann. Thorac. Surg., November 1, 2003; 76(90050): S14 - 16. [Full Text] [PDF]
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