To the Editors:
As a result of the increased sensitivity of videobronchoscopy (including narrow-band and video autofluorescence imaging) and a specific interest in surveillance of pre-invasive lesions, an increase in diagnosis of radiographically occult lung carcinoma (ROLC) can be anticipated. Described for the first time in the late 1970s by Martini and Melamed 1 and in the early 1980s by Cortese et al. 2, surgery still remains the treatment of choice for ROLC 3. However, patients can be functionally inoperable due to comorbidity, advanced age, multiple primary lesions or irresectable, centrally localised tumours, or because they refuse surgery 2. Therefore, varieties of endoscopic techniques, such as photodynamic therapy, cryotherapy, laser therapy, electrocautery and brachytherapy, were developed as alternatives to surgery 3–5. The combination of high-dose external-beam radiotherapy (EBRT) with intraluminal radiotherapy (IR) using low 6–8, middle 9 and high dose-rate 10 iridium-192, has been investigated in ROLC with promising results. EBRT has obvious advantages to surgery, as it is less invasive and better tolerated by the patient. A major issue is, however, the localisation of the tumour for the guidance of EBRT, since these tumours are radiologically occult. Previously, in those studies combining EBRT with IR 6–10, localisation of tumour was determined under fluoroscopy using the tip of the bronchoscope. Radiation was given using small anterior–posterior opposed portals. Obviously, this is less reliable, precise and comfortable, as might be anticipated. To overcome this problem, we hypothesised that metallic clips, the same as used in gastroenterology to obtain haemostasis, could be used as beacons to locate the tumour during EBRT. In a postoperative setting, the same principle is often used to orient EBRT in incomplete resections. Radiation fields are collimated using metallic clips placed by the surgeon.
In a prospective pilot series (June–October 2008) we assessed the feasibility and safety of EZ-Clips HX 610-090 (Olympus, Aartselaar, Belgium) in inoperable patients with ROLC to guide high-dose EBRT. The standard length of these clips is 6 mm when deployed, and when opened the angle of the jaws is 90° (fig. 1). Patient characteristics and tumour locations are summarised in table 1. All four patients were male, smokers with a median age of 68 yrs and fitted the criteria for ROLC as described by the Japan Society of Lung Cancer 8. They underwent white light and autofluorescence video bronchoscopy (fig. 1) because of haemoptysis (case 1), persistent infiltrate (case 2), screening for second primary (case 3) and persistant cough (case 4). Pathology of the endobronchial biopsies was invasive squamous cell carcinoma for all patients. One was staged cT2N0M0 and three were cT1N0M0. Staging was performed according to the 6th edition of the TNM (tumour, nodes, metastasis) Classification of Malignant Tumours 11. Patients 1, 2 and 4 received brachytherapy with one fraction of 10 Gy at 1 cm from the catheter. Patient 3 did not receive endobronchial brachytherapy because of a concurrent supraglottic tumour. Before EBRT, the patients underwent a second bronchoscopy to place two endobronchial metallic clips: one on the proximal carina and one on the distal carina, relative to the ROLC (fig. 1). This was performed under local anaesthesia and was well tolerated by all patients. The time needed to place the clips was estimated to be no longer than an ordinary flexible bronchoscopy with biopsies. Although one clip loosened immediately after placement, it could be removed using biopsy forceps. No other complications occurred. As can be seen in figure 1, the clips are radiographically identifiable. The clips were used for delineation of the clinical target volume on the treatment planning system (fig. 1). In addition, the clips served as beacons facilitating the correct positioning of the patient with cone-beam computed tomography (CT) during hypofractionated radiation therapy (8×7.5 Gy EBRT).
3–4 weeks after EBRT, the patients underwent another bronchoscopy to remove the endobronchial clips by means of biopsy forceps. In cases 1 and 4, both clips were easily retrieved. In case 2, one of the clips was missing, and in case 3 both clips had disappeared. Thorough examination of all cone-beam computed tomography imaging revealed that one clip was already lost at the time of treatment planning, while two were lost during radiation therapy.
During the removal procedure, we also reassessed the mucosa and, interestingly, the macroscopic aspect of the tumour was unchanged in two cases, while in the other two, the tumour was no longer endoscopically identifiable (fig. 1). More importantly, endobronchial biopsies taken showed only inflammatory changes in all patients without signs of malignancy.
At follow-up, the patient treated with EBRT alone did very well, while the others treated with brachytherapy and EBRT developed either airway stenosis, infection or haemoptysis. The patient with haemoptysis succumbed 10 months after therapy. These complications fit with the data from Furuta et al. 10. Therefore, we think the adverse events experienced were due to the effects of brachytherapy and not to the use of metallic clips or EBRT.
In conclusion, although surgery remains the first choice to treat ROLC, a considerable number of patients are inoperable. EBRT is an alternative, but is hampered since the ROLC is effectively invisible. We report that the use of metallic clips placed during bronchoscopy can make ROLC visible for the radiation oncologist. The clips appear to be safe, well tolerated and removable in inoperable patients with ROLC who are candidates for EBRT. In the future, this technique could facilitate EBRT or even stereotactical beam radiotherapy in patients with ROLC. Prospective studies further investigating this technique are warranted.
- ©2010 ERS