Performance of a new preloaded fiducial needle to guide radiation therapy of upper gastrointestinal cancers

• Abstract
• Introduction
• Methods
• Statistical analysis
• Results
• Discussion
• References

Abstract

Background Insertion of fiducials to outline the targeted lesion allows image-guided radiotherapy, and is best achieved by endoscopic ultrasound (EUS). This study is a performance comparison of the new EUS-guided preloaded fiducial needle against Visicoil fiducials.

Methods Technical success, visibility score, procedural time, costs, and complications for patients who underwent EUS-guided fiducial placement in upper gastrointestinal malignancies were prospectively collected.

Results 60 patients with upper gastrointestinal cancers had fiducials (14 Visicoil; 46 preloaded fiducials) inserted for image-guided radiotherapy. Technical success was 100 %, with a shorter mean (standard deviation) insertion time of 0.94 minutes (0.28 minutes) vs. 5.5 minutes (1.9 minutes; P < 0.001) and higher visibility score on fluoroscopy of 2 vs. 1.18 (P < 0.001) in the preloaded group. Neither group had major complications related to fiducial insertion. The cost of consumables per patient was lower in the preloaded group at US$480 (US$124) vs. US$643 (US$123; P < 0.001).

Conclusion Fiducial insertion for image-guided radiotherapy using the new preloaded needle is associated with 100 % technical success, shorter insertion time, and higher visibility, and is more cost-effective than the Visicoil system.

Introduction

Image-guided radiotherapy, either in the form of brachytherapy or stereotactic body radiotherapy, has emerged as a technique for delivering high doses of radiation accurately over a short timespan for the treatment of esophageal, gastric, and pancreatic cancers [1] [2]. The best method to outline the target for image-guided radiotherapy is the implantation of inert gold markers, known as fiducials, at or around the lesion using endoscopic ultrasound (EUS) guidance [3] [4].

Visicoil (Dosimetry, Schwarzenbruck, Germany) is the most commonly used fiducial system, which requires the loading of a single flexible gold coil individually onto the tip of a 19G or 22G fine needle aspiration (FNA) needle, which is then sealed with sterile bone wax prior to each deployment. Once the needle tip is inserted into the lesion, the gold coil is expelled by pushing the stylet out of the needle tip [5]. This process needs to be repeated for each fiducial placed.

More recently, a dedicated 22 G EUS-guided fiducial needle with four 5-mm gold bars preloaded at the tip of the needle (Cook Medical, Indiana, USA) was designed to overcome the weakness of the Visicoil system ([Fig. 1]). The use of this preloaded needle was found to be safe in porcine models, with high technical success and good visibility on fluoroscopy [6]. Data on the use of this needle are lacking in humans. This study aimed to examine the performance of the preloaded fiducial needle compared with the Visicoil fiducial system for image-guided radiotherapy of upper gastrointestinal (GI) cancers.

Methods

In this single center, open label, feasibility study, data on patients who underwent EUS-guided fiducial placement for image-guided radiotherapy of GI malignancies, including esophagogastric, pancreatic, and hepatic cancers, was collected between January 2015 and March 2017. The study was approved by the Research Ethics Committee at the Royal Adelaide Hospital. Relevant data included patient demographics, tumor characteristics, and procedural details.

The two fiducial systems used in the current study were: (i) Visicoil Fiducial Markers and (ii) fiducial bars from a preloaded EchoTip Fiducial Needle (Cook Medical, Bloomington, Indiana, USA). In all cases, the procedure was performed with the patient under deep sedation using the GF-UCT180 linear echoendoscope (Olympus, Center Valley, Pennsylvania, USA) by a highly experienced endosonographer (N.N.). All patients received prophylactic intravenous antibiotics (Ceftriaxone 1 g) prior to the procedure.

The method for loading and deploying the Visicoil Fiducials was as previously described using 22G or 19G EchoTip needles [7]. For the preloaded system, four 5-mm gold bars are part of a 22 G needle and are preloaded at the tip of the needle. There are small spaces between the preloaded fiducials, assisting the endoscopist to know when the fiducial is deployed.

For esophagogastric lesions, the fiducials were placed to mark the proximal and distal margin, and, if feasible, the middle portion of the lesion. For the solid mass lesion in the hepatopancreatic region, fiducials were placed with an aim to outline the medial, lateral, anterior, and posterior edges of the lesion.

We monitored all patients for 2 hours after the procedure for any early complications. Late complications were assessed at day 30 after insertion in clinic. Computed tomography (CT) imaging was done at 5 to 7 days and again at 4 weeks after insertion.

The clinical outcomes assessed in the current study were:

• technical success, defined as the ability to outline the target lesion via fiducial insertion (minimum two fiducials at two opposite borders)

• number of fiducials placed

• procedural complications, including GI perforation, bleeding, post-procedure pancreatitis, infections, or seed migration

• fiducial insertion time, defined as the total time taken to load the fiducials, insert the needle into the lesion, and to deploy the fiducials

• procedural cost, determined by the cost of insertion equipment (cost of the preloaded needles used or EUS-FNA needles with fiducial kits and bone wax)

• Fiducial visibility, assessed by a subjective visual analogue scale (VAS) from 0 to 2, where a score of 0 is not visible, 1 is barely visible, and 2 is clearly visible. The score was assessed from images of CT scans as well as fluoroscopic images (Figs. 2 and 3). This was performed by two independent reviewers (R.D. and H.L.), who were blinded to the insertion devices used.

Statistical analysis

Continuous variables were expressed as mean and standard deviation (SD). Variables were compared using unpaired t test and significance was accepted at a P value of < 0.05.

Results

A total of 60 patients with various GI cancers had fiducials (14 Visicoil; 46 preloaded) inserted for image-guided radiotherapy ([Table 1]). Fiducial-guided brachytherapy was delivered to 27 patients with esophageal (n = 26) and gastric (n = 1) cancers. There were no differences in the patient’s characteristics or the location and size of the tumor between the Visicoil and the preloaded groups ([Table 2]). The rest of the cohort (n = 33) received stereotactic ablative radiotherapy for solid cancers from the pancreas (n = 28) and liver (n = 5) ([Table 1]).

Technical success was achieved in all patients of both groups, allowing all patients to successfully complete image-guided radiotherapy. All patients had at least two fiducials inserted (mean [SD] fiducials per lesion: hepatopancreatic cancers 3.9 [1.0]; esophagogastric cancers 2.8 [0.7]). Compared to the Visicoil group, the preloaded group had more fiducials inserted per lesion (3.9 [1.0] vs. 2.1 [0.7]; P < 0.001) and had a shorter insertion time (0.9 [0.3] vs. 5.5 [1.9] minutes overall, and 0.73 [0.27] vs. 4.96 [0.76] minutes for esophageal lesions; both P < 0.001) ([Table 3]). Although the visibility score was similar for both fiducial systems on CT scanning, the preloaded group had higher visibility scores on fluoroscopy during brachytherapy (median VAS 2 vs. 1.18; P < 0.001). The cost of consumables for the insertion per patient was lower with the preloaded fiducial system, as compared to the Visicoil group (US$481 [US$124] vs. US$643 [US$123]; P < 0.001).

There were no intraprocedural or immediate post-procedural complications in either group. Only one patient developed fever 24 hours after fiducial insertion for a liver lesion, which responded quickly to antibiotics and the patient was discharged 1 day later; follow-up imaging did not reveal any evidence of abscess formation. None of the fiducials migrated on re-imaging with CT on either week 1 or week 4 after insertion.

Discussion

This is the first clinical report on the performance of the new preloaded EUS-guided fiducial needle in assisting image-guided radiotherapy of upper GI cancers, and it showed a 100 % technical success rate, with a shorter insertion time, and higher visibility score, and was more cost-effective than the Visicoil system. These findings suggest that the preloaded fiducial needle is the preferred system for EUS-guided marking for image-guided radiotherapy of upper GI cancers.

A number of advantages are associated with the use of the preloaded fiducial system over the Visicoil system in the current study. Given the avoidance of the need to individually “load” each Visicoil fiducial, use of the preloaded device will shorten the insertion time. Furthermore, even with a minimum use of two Visicoil fiducials, the cost of the consumables is less with the preloaded system. In comparison to use of the Visicoil system, use of the preloaded fiducial needle was as safe, with 100 % technical success, which is consistent with the animal data from Draganov et al. [6]. The high technical success is most likely related to the excellent flexibility of the 22 G fiducial needles, which enabled insertion of fiducials in the most difficult-to-reach locations, such as segment 6/7/8 of the liver (n = 1) and the hilum (n = 1).

In order to perform brachytherapy, the fiducial marking must be clearly visualized on fluoroscopy, thereby allowing accurate placement of the radiotherapy applicator [8]. Although both types of fiducials are clearly visualized on planning CT scans, the thick gold bars of the preloaded system were better visualized than the Visicoils on fluoroscopy ([Fig. 2] and [Fig. 3]). The ultrathin diameter of the Visicoils, as well as the deformity that can occur during deployment creating a “coiled ball,” reduced the visibility of the fiducial on fluoroscopy. Therefore, the preloaded needle would seem to be a better fiducial system for brachytherapy of GI luminal cancers.

Given that fiducials are foreign bodies, there is always a potential risk of infection. As observed in our study, one patient experienced transient fever that settled rapidly with antibiotic treatment. It is important to note that this complication occurred despite the use of intravenous antibiotics pre-insertion. The current literature suggests that the risk of infection related to fiducial insertion varies from 1 % to 2 % [9] [10]. Together, these findings support the routine use of prophylactic perioperative antibiotics for all patients.

In contrast to previous reports, fiducial migration was not observed in our study. The rate of migration of fiducials ranges from 0 to 8 % [4] [7] [10] [11] [12] [13] [14], and this appears to be more common in the marking of luminal cancers [12]. This may in part be due to the limited thickness of the cancer wall or to superficial insertion of the fiducials. In the current study, these issues were overcome by creating a submucosal bleb to ensure placement of the fiducials in the submucosal space, which is particularly useful for ulcerative esophageal cancers of less than 10 mm in thickness. Migration is significantly less for pancreatic masses, where the fiducials are inserted deeply into the pancreatic tissue, in a “target-sign” fashion, as previously reported by Khashab et al. [5].

A few weaknesses should be acknowledged in the current study, including a relatively small sample size; a heterogeneous patient group, with fewer Visicoil fiducials used; and the non-randomized design. The heterogeneous patient group impacted the mean number of fiducials inserted, with pancreatic cancers having a higher number placed compared with esophageal cancers (and also being the predominant lesions in the preloaded group). The higher number of pancreatic cancer patients in the preloaded group reflects the development of stereotactic ablative radiotherapy treatment for pancreatic cancer patients at our center, which closely coincided with the availability of the preloaded device.

Whilst it would be ideal to perform this trial in a randomized fashion, this study has clearly demonstrated several advantages of the preloaded system over the Visicoils. Furthermore, use of the preloaded system would prevent the potential needle-stick injury caused by the “loading procedure” with the Visicoil system, which clearly has major advantages in terms of occupational health and safety.

In conclusion, fiducial marking with gold bars from the new preloaded fiducial needle is as safe and technically successful as the Visicoil system. The preloaded system is however better in that it has a much shorter insertion time, offers better visibility, and is more cost-effective than the Visicoil system, indicating that it should be the preferred system for image-guided radiotherapy.

Competing interests

None.

• References

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Corresponding author

• References

• 1 Chuong MD, Springett GM, Freilich JM. et al. Stereotactic body radiation therapy for locally advanced and borderline resectable pancreatic cancer is effective and well tolerated. Int J Radiat Oncol Biol Phys 2013; 86: 516-522
  CrossrefPubMedSearch in Google Scholar
• 2 Fernandez DC, Hoffe SE, Barthel JS. et al. Stability of endoscopic ultrasound-guided fiducial marker placement for esophageal cancer target delineation and image-guided radiation therapy. Pract Radiat Oncol 2013; 3: 32-39
  CrossrefPubMedSearch in Google Scholar
• 3 Javed S, Bhutani MS. Endoscopic ultrasound-guided radiation therapy in pancreatic cancer. Minerva Gastroenterol Dietol 2013; 59: 377-386
  PubMedSearch in Google Scholar
• 4 Sanders MK, Moser AJ, Khalid A. et al. EUS-guided fiducial placement for stereotactic body radiotherapy in locally advanced and recurrent pancreatic cancer. Gastrointest Endosc 2010; 71: 1178-1184
  CrossrefPubMedSearch in Google Scholar
• 5 Khashab MA, Kim KJ, Tryggestad EJ. et al. Comparative analysis of traditional and coiled fiducials implanted during EUS for pancreatic cancer patients receiving stereotactic body radiation therapy. Gastrointest Endosc 2012; 76: 962-971
  CrossrefPubMedSearch in Google Scholar
• 6 Draganov PV, Chavalitdhamrong D, Wagh MS. Evaluation of a new endoscopic ultrasound-guided multi-fiducial delivery system: a prospective non-survival study in a live porcine model. Dig Endosc 2013; 25: 615-621
  CrossrefPubMedSearch in Google Scholar
• 7 Valentine K, Cabrera T, Roberge D. Implanting metal fiducials to guide stereotactic liver radiation: McGill experience and review of current devices, techniques and complications. Technol Cancer Res Treat 2014; 13: 253-258
  CrossrefPubMedSearch in Google Scholar
• 8 Lettmaier S, Strnad V. Intraluminal brachytherapy in oesophageal cancer: defining its role and introducing the technique. J Contemp Brachytherapy 2014; 6: 236-241
  PubMedSearch in Google Scholar
• 9 Pishvaian AC, Collins B, Gagnon G. et al. EUS-guided fiducial placement for CyberKnife radiotherapy of mediastinal and abdominal malignancies. Gastrointest Endosc 2006; 64: 412-417
  CrossrefPubMedSearch in Google Scholar
• 10 DiMaio CJ, Nagula S, Goodman KA. et al. EUS-guided fiducial placement for image-guided radiation therapy in GI malignancies by using a 22-gauge needle (with videos). Gastrointest Endosc 2010; 71: 1204-1210
  CrossrefPubMedSearch in Google Scholar
• 11 Choi JH, Seo DW, Park DH. et al. Fiducial placement for stereotactic body radiation therapy under only endoscopic ultrasonography guidance in pancreatic and hepatic malignancy: practical feasibility and safety. Gut Liver 2014; 8: 88-93
  CrossrefPubMedSearch in Google Scholar
• 12 Dhadham GC, Hoffe S, Harris CL. et al. Endoscopic ultrasound-guided fiducial marker placement for image-guided radiation therapy without fluoroscopy: safety and technical feasibility. Endosc Int Open 2016; 4: E378-E382
  Thieme ConnectPubMedSearch in Google Scholar
• 13 Law JK, Singh VK, Khashab MA. et al. Endoscopic ultrasound (EUS)-guided fiducial placement allows localization of small neuroendocrine tumors during parenchymal-sparing pancreatic surgery. Surg Endosc 2013; 27: 3921-3926
  CrossrefPubMedSearch in Google Scholar
• 14 van der Horst A, Wognum S, Davila Fajardo R. et al. Interfractional position variation of pancreatic tumors quantified using intratumoral fiducial markers and daily cone beam computed tomography. Int J Radiat Oncol Biol Phys 2013; 87: 202-208
  CrossrefPubMedSearch in Google Scholar