Fiducials are dense markers used by certain stereotactic radiosurgery systems (Cyberknife and others) for real-time tracking of tumors. Initially fiducials were placed under CT guidance using a transthoracic approach, with a significant risk of pneumothorax. Fiducials can also be placed using navigation bronchoscopy. The working channel is guided to the lesion, and biopsies are performed. Gold or platinum markers are typically used as they are of sufficient density not to be confused with steel or titanium clips. Rigid gold rods (Civco; 1 × 3 mm) may be placed into the end of a cytology brush and deployed in and around the tumor. The markers are placed under fluoroscopy to assure good seating. After placement of the initial marker, the working channel is repositioned under either fluoroscopic or navigation guidance several centimeters away for placement of additional markers. Ideally, at least three to four markers should be placed: one in the tumor and the remainder 2 cm apart. The use of platinum coils (VortX18; Boston Scientific, Natick, MA USA) has decreased the rate of expectoration of the markers (Fig. 5).
The success of ENB biopsies is determined largely by lesion size and location. Lesions typically need to be greater or equal to 8 mm in size. Above this size, the diagnostic yield depends most upon accessibility from the bronchial tree. Lesions in direct line with a bronchus that is visible on fine cut CCT are more likely to be successfully biopsied. Lesions in the apical segments of the upper lobe and the superior segments of the lower lobes tend to be more challenging. ENB can also be used to biopsy peribronchial lymph nodes (Fig. 6).
Clinicians who are skilled bronchoscopists can be proctored for about five cases when learning ENB. The bronchoscopy suite assistant must also be trained in the setup and use of the electromagnetic navigation (EMN) system. The system must be calibrated with the room—the addition of other large equipment into the room, or even the presence of metallic objects such as beepers or cell phones, can alter the magnetic field and affect navigation. With the recent development of software that automatically plans a bronchoscopic path to the lesion and allows for “autoregistration” of the patients real-time anatomy with the stored 3D CT scan reconstruction, the learning curve has been accelerated. After approximately 15 to 20 cases, most of the nuances of steering the working channel, use of different biopsy instruments (brush, needle, and forceps), and benefit of fluoroscopic confirmation can be learned.
Two large studies have been reported, both using the SuperDimension system. Gildea et al4 studied 54 patients with peripheral lesions. The mean procedure time was 51 ± 13 minutes. The mean lesion size was 23 mm (range, 8–78 mm) and 57% were less than 2 cm in diameter. Pneumothorax occurred in 3.5% of patients. Seventy four percent of peripheral lesions (40/54) yielded a “definitive” diagnosis. It should be noted, however, that for all malignant lesions (total 43) only 32 (74.4%) were successfully diagnosed by ENB. In another study, Eberhardt et al5 biopsied 92 peripheral lesions in 89 subjects. No fluoroscopy was used. Mean procedure time was 27 ± 6.5 minutes. Mean lesion size was 24 mm (range, 10–58 mm). The incidence of pneumothorax was 2.3%. The overall diagnostic yield was 67% and appeared to be independent of size. The sensitivity for malignant disease was only 60%, and the negative predictive value for malignant disease was just 44%.
Eberhardt et al6 performed a randomized trial using ENB, radial probe EBUS, and EBUS combined with ENB. The use of a radial probe EBUS allows for real-time visualization of peripheral nodules, but there can still be difficulty navigating to the lesion. It was hypothesized that use of electromagnetic navigation along with real-time EBUS visualization of the lesion would increase diagnostic yield. One hundred eighteen patients with peripheral nodules were randomized to EBUS, ENB, or EBUs combined with ENB. The results are shown in Table 1. The diagnostic yield of 88% obtained by combined ENB and EBUS was superior to the diagnostic yield of either technique alone (59%–69%). More importantly, the negative predictive value for malignant lesions increased from 44% to 75% with the combined use of ENB and a radial EBUS probe.
It must be emphasized that the false-negative rate (closely related to the negative predictive value) is significant. The false-negative rate of transthoracic needle aspiration is in the range of 0.20 to 0.30 and is not too dissimilar to that seen with EMN done without radial EBUS.7 Thus, in a patient with a suspicious nodule, EMN, similar to transthoracic needle biopsy, cannot be used to rule out malignancy. The single study mentioned above combining radial EBUS with EMN is encouraging but is yet to be confirmed by other institutions.
Complications with EMN are rare. The pneumothorax rate is in the range of 3% to 8%.6 The pneumothorax rate appears to be much lower than the 30% rate seen with transthoracic needle biopsy.2 Scant hemoptysis has been noted, with no cases of severe hemoptysis. Other less serious complications such as sore throat, chest discomfort, and fever have also infrequently been noted.4 No deaths have been described in the literature.
ENB has also been used to place fiducial markers for stereotactic radiosurgery. These markers are used by certain stereotactic radiosurgery systems to obtain real-time, breath to breath localization of the tumor. Fiducials, made of dense material such as gold or platinum and placed in and around the tumor, are visualized by a real-time fluoroscopic system and guide the 3D treatments. The accuracy of such systems is claimed to be superior to nonfiducial-based systems, although no head to head trials have been performed. In a feasibility study, Anantham et al8 placed 39 fiducials via navigation bronchoscopy into nine patients. There was a 10% migration rate after placement, likely due to coughing. One patient suffered a chronic obstructive pulmonary disease exacerbation, and there were no instances of pneumothorax. In another study, a combination of EMN and radial EBUS was used to place fiducials in 43 patients.9 Although 13 of the patients suffered displacement of fiducials (30%), all were able to undergo stereotactic radiosurgery. Only one pneumothorax was seen.
Recently, our group published the largest series to date on the use of ENB for fiducial placement.10 Fifty-two consecutive medically inoperable patients with isolated lung tumors underwent fiducial placement with or without biopsy using ENB. Following an initial 47% migration rate with the rigid cylinder gold fiducials, the remainder of the patients had platinum coil fiducials placed with a 1% loss rate. Two of the patients with migration of gold markers required replacement of their markers; none of the platinum coil patients required a repeat procedure. In this high-risk group of patients, three suffered a pneumothorax (5.8%), two of whom required pigtail tube placement with admission. (Most of the patients undergoing fiducial placement are medically inoperable and suffer from advanced chronic obstructive pulmonary disease.)
In summary, ENB is a new technology that allows for the safe biopsy of peripheral lung tumors. The risk of pneumothorax seems lower than that for CT fine needle aspiration (FNA). The sensitivity and negative predictive value for malignant lesions, however, may not be better than CT-guided FNA. ENB does allow for the safe bronchoscopic placement of fiducial markers in almost any patient.
1. Baaklini WA, Reinoso MA, Gorin AB, et al. Diagnostic yield of fiberoptic bronchoscopy in evaluating solitary pulmonary nodules. Chest.
2. Geraghty PR, Kee ST, McFarlane G, et al. CT-guided transthoracic needle aspiration biopsy of pulmonary nodules: needle size and pneumothorax rate. Radiology.
3. Becker H, Herth F, Ernst A. Bronchoscopic biopsy of peripheral lung lesions under electromagnetic guidance: a pilot study. J Bronchol.
4. Gildea TR, Mazzone PJ, Karnak D, et al. Electromagnetic navigation diagnostic bronchoscopy: a prospective study. Am J Respir Crit Care Med.
5. Eberhardt R, Anantham D, Herth F, et al. Electromagnetic navigation diagnostic bronchoscopy in peripheral lung lesions. Chest.
6. Eberhardt R, Anantham D, Ernst A, et al. Mutimodality bronchoscopic diagnosis of peripheral lung lesions: a randomized controlled trial. Am J Respir Crit Care Med.
7. Tremblay A. Real-time electromagnetic navigation bronchoscopy for peripheral lesions: what about the negative predictive value? Chest.
8. Anantham D, Feller-Kopman D, Shanmugham LN, et al. Electromagnetic navigation bronchoscopy-guided fiducial placement for robotic stereotactic radiosurgery of lung tumors: a feasibility study. Chest.
9. Harley DP, Krimsky WS, Sarkar S, et al. Fiducial marker placement using endobronchial ultrasound and navigational bronchoscopy for stereotactic radiosurgery: an alternative strategy. Ann Thorac Surg.
10. Schroeder C, Hejal R, Linden PA. Coil spring fiducial markers placed safely using navigation bronchoscopy in inoperable patients allows accurate delivery of CyberKnife stereotactic radiosurgery. J Thorac Cardiovasc Surg
Keywords:© 2011 Lippincott Williams & Wilkins, Inc.
Navigation bronchoscopy; Stereotactic radiotherapy; Lung cancer