Endobronchial involvement can be seen in primary or recurrent lung cancer and lung metastases from other primary tumors. Curative and palliative approaches include external beam radiotherapy (EBRT), high dose rate endobronchial brachytherapy (HDR-EBBT), cryotherapy, laser therapy, photodynamic therapy, and endobronchial stent insertion [
HDR-EBBT successfully palliated symptoms in the majority of patients in several studies [
After institutional research ethics board approval, a retrospective review of all patients with endobronchial (lung or metastatic) tumor (≥18 years old) with or without extrabronchial tumor, who had been treated in our institution between 2007 and 2013 with HDR-EBBT with either curative or palliative intent, alone or in combination with other treatment modalities, was conducted.
HDR-EBBT was carried out on an outpatient basis. The depth of the prescribed dose was modified based on the diameter of the airways in curative cases: 10, 7, and 5 mm for tumors of the trachea, main bronchi, and lobar bronchi, respectively [
In curative setting, HDR-EBBT was considered alone for in situ non-small cell lung cancer (NSCLC) or positive microscopic endobronchial margin, while invasive endobronchial NSCLC was treated with a combination of EBRT (40–45 Gy at 1.8–2 Gy/fraction) and HDR-EBBT (16 Gy in 2 sessions or 15 Gy in 3 sessions). For tumors with extension beyond the bronchus, with nodal disease or synchronous parenchymal tumor, EBRT delivered 60 Gy in 30 fractions for 6 weeks with HDR-EBBT of 10 Gy in 2 sessions, sequential or during the course of EBRT.
In palliative setting, patients were treated with HDR-EBBT of 10 Gy in 1 session or 14 Gy in 2 sessions with a week in between, either alone or in combination with EBRT of 20 Gy in 5 fractions or equivalent dose in a sequential approach.
Subjective response in terms of resolution of the pretreatment symptoms was extracted from patients’ medical charts within 8 weeks from the first HDR-EBBT session and categorized as complete, partial, or no resolution. Clinical response was evaluated by bronchoscopy and/or chest CT at 2 to 3 months following the treatment. Follow-up evaluations were performed every 6 months and included chest CT and surveillance bronchoscopy; biopsies were taken in case of suspicious lesions.
For curatively treated patients, the estimated rate of LC was calculated using the competing risk method, and overall survival (OS) was analyzed by Kaplan-Meier method.
Overall, 23 patients with endobronchial tumor were treated, 20 of them with primary or recurrent NSCLC and 3 patients with lung metastases (from colon cancer and thymoma). The patients’ and tumor characteristics are summarized in Table
Patients’ and tumor characteristics.
Characteristic | Value |
---|---|
Median age (range), year | 70 (37–92) |
|
|
Median follow-up (range), months | 17 (1.5–86) |
|
|
Gender | |
Male | 14 (61%) |
Female | 9 (39%) |
|
|
Smoking history | |
Yes | 13 (65%) |
No | 7 (35%) |
Unknown | 3 |
|
|
ECOG performance status | |
0 | 1 (4%) |
1 | 17 (74%) |
2 | 5 (22%) |
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|
Histology | |
Primary lung tumor | 20 (87%) |
SCC | 9 (39%) |
Adenocarcinoma | 9 (39%) |
Others | 2 (9%) |
Lung metastases | 3 (13%) |
Colon adenocarcinoma | 2 (9%) |
Thymoma | 1 (4%) |
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|
Site | |
Central (trachea, main bronchi) | 11 (48%) |
Peripheral (lobar bronchi) | 12 (52%) |
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Previous lung tumor | |
Yes | 16 (70%) |
No | 7 (30%) |
|
|
Treatment to previous lung tumor | |
Surgery | 7 (30%) |
Lobectomy | 4 (17%) |
Pneumonectomy | 1 (4%) |
Metastasectomy | 2 (9%) |
Radiotherapy | 10 (43%) |
Chemotherapy | 9 (39%) |
Photodynamic therapy | 1 (4%) |
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|
Tumor visible on CT | 18 (78%) |
EBRT: external beam radiotherapy.
Treatments administered to the treated endobronchial tumors.
Treatment | Curative |
Palliative |
---|---|---|
HDR-EBBT alone | 2 | 6 |
HDR-EBBT + EBRT | 5 | 1 |
HDR-EBBT + chemotherapy | 0 | 2 |
HDR-EBBT + EBRT + chemotherapy | 2 | 2 |
HDR-EBBT + surgery + EBRT | 1 | 2 |
HDR-EBBT: high dose rate endobronchial brachytherapy; EBRT: external beam radiotherapy.
Ten patients were treated with curative intent, only 2 of them received brachytherapy (BT) alone (1 at the site of postoperative positive microscopic endobronchial margin and the other one had in situ NSCLC), while 8 patients received HDR-EBBT in combination with EBRT for endobronchial tumor without extrabronchial extension (
Palliative HDR-EBBT was given for patients with endobronchial lung metastases (
Twenty out of 23 patients had documentation in the chart regarding subjective symptom response. Initial symptoms were dyspnea (65%), cough (61%), hemoptysis (13%), and chest pain and wheeze (each, 9%). Most patients had either complete or partial palliation within 8 weeks from initial BT session (Table
Short term palliation rate.
Before BT |
CR |
PR |
|
---|---|---|---|
Dyspnea | 15 (65) | 7 (47) | 6 (40) |
Cough | 14 (61) | 8 (57) | 4 (29) |
Hemoptysis | 3 (13) | 2 (67) | 1 (33) |
Chest pain | 2 (9) | 1 (50) | 1 (50) |
Wheeze | 2 (9) | 1 (50) | 1 (50) |
BT: brachytherapy, CR: complete resolution, and PR: partial resolution.
Clinical response was assessed in 17 patients by CT, with (
Among patients treated with curative intent, the median follow-up was 17 months and the 2-year LC was 89% (95% CI: 79–99%); only 1 patient had local failure (LF) at 7 months and was treated with chemotherapy and subsequently developed multiple-site distant metastases, while, in patients treated with palliative intent, 3 had LF at 7, 12, and 36 months and were further palliated with another palliative HDR-EBBT of 5 Gy in 1 session (
The 2-year OS for curatively treated patients was 67% (95% CI: 51–83%) (Figure
Overall survival in patients treated with high dose rate endobronchial brachytherapy with curative intent.
No serious complications were recorded during HDR-EBBT procedure. Eighteen patients were alive 6 months after therapy, of whom only 1 patient had bronchial stenosis. Fatal hemoptysis was reported in one patient (that patient was previously treated with lung stereotactic radiotherapy with 54 Gy in 3 fractions and postmortem examination indicated recurrent disease in the lung).
Therapeutic modalities for endobronchial tumors include EBRT, HDR-EBBT, laser therapy, phototherapy, endobronchial stent insertion, and combinations of these techniques [
A 2012 Cochrane review of palliative HDR-EBBT for NSCLC analyzed 14 randomized controlled trials (RCTs) involving 953 participants but a meta-analysis was not done due to heterogeneity in the patient characteristics, radiotherapy doses used, and outcomes measured [
A variety of fractionation schemes have been used in palliative HDR-EBBT, which precludes meaningful comparison between studies [
The value of HDR-EBBT as a curative treatment is not widely accepted, in either definitive or postoperative setting. The use of HDR-EBBT as a sole treatment of endobronchial NSCLC without nodal or visceral metastases was reported by Hennequin et al. [
Muto et al. [
In most of studies, the dose of HDR-EBBT is prescribed at fixed depth regardless of the site of the tumor. As the intention is to prescribe the dose at bronchial mucosa, it is important to modify the prescription depth based on the diameter of the airways in order to avoid excessive dose to mucosa and underdosage to endobronchial tumor. Kawamura et al. [
Our experience, albeit with relatively small number of patients, is consistent with other literature that HDR-EBBT can provide effective palliation and can even be used in curative setting in properly selected patients with endobronchial tumors. In our curative protocol, the 2-year LC and OS were 89% and 67%, respectively. We believe that the therapeutic ratio of HDR-EBBT could be maximized by proper fractionation schedule and modifying the depth of the prescribed dose according to the diameter of the airway. Another important factor is to use the protective applicator whenever airways allow protecting the bronchial mucosa from high doses and immobilizing the catheter containing the radioactive source. Avoiding very high dose per fraction and combining EBRT also help in maintaining dose homogeneity; however further research is required to determine incremental benefit of addition of HDR-EBBT to EBRT especially in curative setting.
HDR-EBBT is a promising palliative and curative treatment with tolerable complication if used in properly selected patients with proper fractionation schedule; however its combination with other treatment modalities needs further studies.
Research was conducted at the Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada. Elantholiparameswaran Saibishkumar is currently working at the British Columbia Cancer Agency, Victoria, BC, Canada.
The authors declared no competing interests.