Stability of endoscopic ultrasound-guided fiducial marker placement for esophageal cancer target delineation and image-guided radiation therapy

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1 Practical Radiation Oncology (2013) 3, Original Report Stability of endoscopic ultrasound-guided fiducial marker placement for esophageal cancer target delineation and image-guided radiation therapy Daniel C. Fernandez MD, PhD a,, Sarah E. Hoffe MD a, James S. Barthel MD b, Shivakumar Vignesh MD b, Jason B. Klapman MD b, Cynthia Harris MD b, Khaldoun Almhanna MD, MPH b, Matthew C. Biagioli MD, MS a, Kenneth L. Meredith MD b, Vladimir Feygelman PhD a, Nikhil G. Rao MD a, Ravi Shridhar MD, PhD a a Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida b Gastrointestinal Tumor Program, H. Lee Moffitt Cancer Center, Tampa, Florida Received 29 November 2011; revised 2 February 2012; accepted 27 February 2012 Abstract Purpose: Fiducial markers have been integrated into the management of multiple malignancies to guide more precise delivery of radiation therapy (RT). Fiducials placed at the margins of esophageal tumors are potentially useful to facilitate both RT target delineation and image-guided RT (IGRT). In this study, we report on the stability of endoscopic ultrasound (EUS)-guided fiducial placement for esophageal cancers and utilization for radiation treatment planning and IGRT. Methods: An institutional review board-approved database was queried for patients treated for esophageal cancer with chemoradiotherapy (CRT). Patients included in the analysis had a diagnosis of esophageal cancer, were referred for treatment with CRT, and had fiducials placed under EUS guidance. Images acquired at time of radiation treatment planning, daily IGRT imaging, post-treatment restaging, and surveillance scans were analyzed to determine the stability of implanted markers. Results: We identified 60 patients who underwent EUS-guided fiducial marker placement near the margins of their esophageal tumors in preparation for RT treatment planning. A total of 105 fiducial markers were placed. At time of CT simulation, 99 markers were visualized. Fifty-seven patients had post-treatment imaging available for review. Of the 100 implanted fiducials in these 57 patients, 94 (94%) were visible at time of RT simulation. Eighty-eight (88%) fiducials were still present posttreatment imaging at a median of 107 days (range, days) after implantation. Conclusions: EUS-guided fiducial marker placement for esophageal cancer aids in target delineation for radiation planning and daily IGRT. Fiducial stability is reproducible and facilitates conformal treatment with image-guided RT techniques American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. Conflicts of interest: None. Corresponding author. Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Magnolia Blvd, Tampa, FL address: daniel.fernandez@moffitt.org (D.C. Fernandez) /$ see front matter 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

2 Practical Radiation Oncology: January-March 2013 Introduction Radiation therapy (RT) plays an important role in the multimodality treatment of esophageal cancer. Esophageal cancers present several challenges for accurate RT planning and delivery. Target delineation of the primary tumor and involved regional adenopathy at the time of treatment planning present significant challenges and can have substantial impact on RT treatment volumes. RT target volumes directly impact the amount of dose received by adjacent radiosensitive normal tissues and subsequent acute and late RT toxicities, and accurate identification of a mobile target is crucial to prevent marginal misses during treatment and to limit dose to surrounding normal tissues. Modern RT planning relies heavily on computed tomography (CT) scanning performed in the treatment position after appropriate patient immobilization. Primary esophageal tumor extent can often be difficult to visualize with confidence on standard RT planning computed tomographic images even with the use of intravenous contrast, especially since there can be concomitant edema at some levels rather than tumor which can cause increased CT wall thickening. Modern diagnostic techniques used routinely in the diagnosis and staging of esophageal tumors include barium esophagram, endoscopy, endoscopic ultrasound (EUS) scanning, 18 fluorodeoxyglucose ( 18 FDG)-positron emission tomography (PET), and hybrid PET-CT scanning. Diagnostic EUS has evolved into the preferred modality for locoregional staging of esophageal tumors and numerous studies and meta-analyses have established its role. 1 The major strength of EUS for esophageal cancer staging is the ability to spatially resolve the depth of tumor penetration through the various anatomic layers of the esophageal wall, as well as the ability to identify dimensions and sonographic characteristics of periesophageal lymph nodes that can be sampled via EUS-guided fine needle aspiration (FNA) to confirm involvement by disease. Radio-opaque surgical clips have long been used to aid target delineation for postoperative RT at many disease sites. Minimally invasive techniques to implant fiducial markers have been adopted widely to both improve identification of targets at RT planning, and more recently to significantly reduce interfraction RT setup uncertainty through the use of image-guided RT (IGRT). Fiducial marker-based IGRT has become routine at many centers for prostate cancer treatment and also has an increasing role in stereotactic RT at many extracranial sites. EUS-guided fiducial placement has been described more extensively for pancreatic tumors, but a few reports include esophageal tumors. 2-4 These scant reports include limited data regarding the short-term stability of EUSguided fiducial markers in the esophagus and no information with respect to the long-term stability of these markers during treatment, which is essential if they are to be used for IGRT during fractionated courses of RT. Since 2008, we have routinely employed EUS-guided fiducial marker placement to assist with RT planning target delineation and IGRT. Herein we report the results of the stability of fiducial markers placed under EUS guidance for esophageal cancers prior to RT planning for esophageal cancers. Materials and methods Patients An institutional review board-approved database of radiation oncology patients treated for gastrointestinal malignancies was queried to identify patients who had fiducials placed under EUS-guidance for esophageal cancer. Patient characteristics, including age, gender, date of fiducial implantation, number of fiducials placed and location (distance from incisors) of fiducial placement, Table 1 Fiducial markers and esophageal cancer 33 Patient characteristics Characteristic No. (value) No. of patients 60 Age (y) Median 66 Range Sex Male 51 (85%) Female 9 (15%) Histology Adenocarcinoma 54 (90%) Squamous cell carcinoma 6 (10%) Histologic grade X 17 (28%) 1 2 (3%) 2 27 (45%) 3 14 (23%) Stage a IA 2 (3%) IB 4 (7%) IIA 0 (0%) IIB 12 (20%) IIIA 18 (30%) IIIB 14 (23%) IIIC 4 (7%) IV 5 (8%) Primary tumor location Upper 2 (3%) Middle 4 (7%) Distal 27 (45%) GEJ 27 (45%) X, grade not reported or available; GEJ, gastroesophageal junction. a American Joint Committee on Cancer 7th edition stage grouping.

3 34 D.C. Fernandez et al Practical Radiation Oncology: January-March 2013 and subsequent radiation and surgical treatments were extracted from review of the electronic medical record and are listed in Table 1. All patients completed clinical staging with EUS, CT of the thorax and abdomen, and PET-CT scanning. Patients who required treatment with chemoradiotherapy were referred for EUS-guided fiducial placement. EUS-guided fiducial placement All patients underwent EUS with a linear-array echoendoscope (GF-UC140P-AL5; Olympus America, Center Valley, PA) under propofol-based sedation with monitored anesthesia care. For the majority of patients, a 19-gauge EUS-FNA needle (Cook Endoscopy, Winston Salem, NC) was used for fiducial placement. After withdrawing the stylet 7 to 8 mm from the needle, a gold cylindrical fiducial marker measuring 0.75 mm 10 mm (Visicoil, RadioMed, Inc, Tingsboro, MA) was backloaded into the needle tip by using sterile forceps and sealed into place with sterile bone wax. The needle could then be advanced down the operating channel of the echoendoscope without losing the fiducial. Once a safe insertion window away from critical structures was identified, the EUS needle was then inserted into the target area under EUS guidance. Most fiducials were placed into the submucosa just proximal or distal to the tumor and not into the lesion itself in an attempt to mitigate fiducial loss during the course of RT due to tumor response. Upon needle insertion into or adjacent to the target lesion, the fiducial was deployed by simultaneously retracting the needle while advancing the stylet. The EUS needle was then withdrawn from the echoendoscope and reloaded with a new fiducial, and the technique repeated until the desired number of markers had been placed (Fig 1). In a few patients, smaller diameter Visicoil fiducials were used (0.35 mm 10 mm) and in such cases a 22-gauge EUS-FNA needle was used with the same Figure 1 Appearance of a T3N1M0 (stage IIIA) adenocarcinoma of the distal esophagus at time of endoscopic ultrasound (EUS)- guided placement of two 0.75 mm 10 mm fiducial markers at the proximal and distal margins of the primary tumor. (A) Exophytic primary lesion at esophagogastroduodenoscopy. (B) Diagnostic radial EUS revealing a suspicious periesophageal lymph node. Postimplantation radial EUS scanning images confirming placement of fiducial markers at the distal (C) and proximal margins (D) of the primary tumor.

4 Practical Radiation Oncology: January-March 2013 technique described above. All fiducials were placed under EUS guidance alone; fluoroscopy was not used. Preprocedural intravenous antibiotics (ciprofloxacin 400 mg) Fiducial markers and esophageal cancer 35 were administered prophylactically in all patients. All endoscopy procedure reports, post-procedure orders, 24-hour post-procedure telephone notes and all electronic Figure 2 Appearance of implanted fiducial markers on pretreatment computed tomographic (CT), positron emission tomography (PET)-CT, daily kilovoltage cone-beam computed tomography (KV-CBCT), and post-treatment (TX) CT scan performed 54 days after completion of radiation therapy (RT) and 107 days after implantation. Red circles indicate fiducial locations. ITV, internal target volume; PTV, planning target volumes.

5 36 D.C. Fernandez et al Practical Radiation Oncology: January-March 2013 medical record entries occurring in the 4 weeks after fiducial placement were reviewed to determine if any acute or subacute complications related to fiducial placement occurred. RT planning, IGRT, stability After fiducial placement, patients generally underwent CT simulation the same day or next day for radiation treatment planning in a customized immobilization device. Four-dimensional computed tomography (4D-CT) scans were obtained to assess tumor motion from respiration and used to generate internal target volumes of gross disease. A clinical target volume encompassing a 3-4 cm superior margin, a 3-4 cm distal margin, and a 3-5 mm radial margin was contoured. Regional abdominal lymphatics were covered in distal or gastroesophageal junction tumor sites. Planning target volumes were created with margins individualized based on whether daily image guidance was used. All but one patient was treated with intensity modulated radiation therapy (IMRT). IMRT motion management strategies included using abdominal compression or a compensator approach. IMRT plan constraints consisted of the following: lung (mean b16 Gy, V20 b30%, V5 b60%), heart (mean b30 Gy), spinal cord (max b50 Gy), kidneys (mean b12 Gy), and liver (V30 b30%). Total radiation dose ranged from 45 Gy to 60 Gy in 1.8 Gy or 2 Gy fractions. Concurrent chemotherapy was delivered in all patients with the regimen chosen at the discretion of the medical oncologist. CT-simulation images were reviewed to determine the presence of fiducial markers in the expected location at the time of treatment planning. For patients who underwent IGRT, daily pretreatment kilovoltage (KV) planar imaging or cone-beam CT (CBCT) imaging were reviewed to determine the routine visibility of the fiducial markers in the RT treatment room. Subsequent post-rt CT scans were reviewed to evaluate the stability of fiducials after RT. For patients who did not undergo esophagectomy, the most recent surveillance CT or PET-CT images were reviewed to determine the presence and stability of the implanted fiducial markers. Results We identified 60 patients with esophageal cancer who underwent EUS-guided implantation of one or more fiducial markers between February 2008 and May 2011 just proximal or distal to the margins of the tumor. The pretreatment characteristics of this group of patients are shown in Table 1. The median age was 66 years (range, years), 85% were male, 90% had adenocarcinoma, 90% had distal and gastroesophageal tumors, 98% were treated with IMRT. Fiducial marker placement was performed prior to CT simulation in all cases. Figure 1 depicts the appearance of a primary T3N1M0 adenocarcinoma of the distal esophagus at endoscopy and diagnostic EUS, as well as the EUS appearance of fiducial markers after submucosal implantation at the proximal and distal tumor margins. A total of 105 markers were placed in 60 patients. Twenty patients (33%) had placement of a single fiducial marker, generally at the proximal margin of a distal tumor where distal fiducial placement was felt to be technically challenging or a tumor was too obstructing to permit passage of the echoendoscope to the distal margin of the tumor. Thirty-five patients (58%) had placement of 2 fiducials, generally at the proximal and distal margins of their primary tumors. The remaining 5 patients (8%) had 3 fiducials placed. All 60 patients underwent fiducial placement on an outpatient basis and all were discharged to home. One patient complained of moderate abdominal pain following the procedure. Acute abdominal series radiography and electrocardiography were obtained and showed no abnormalities. This patient's pain resolved spontaneously prior to discharge. One patient was noted to have transient asymptomatic hypotension during recovery from anesthesia that responded to a small fluid bolus. One patient with significant preexisting cardiopulmonary comorbidities was discharged home and subsequently was admitted to an outside hospital b24 hours later with diagnoses of congestive heart failure exacerbation and pneumonia. No other documented complications (such as bleeding, infection, etc) were noted. The median time to CT simulation following marker placement was 1 day (range, 0-87 days). Figure 2 depicts axial, sagittal, and coronal views of implanted fiducials at the proximal and distal tumor margins at time of planning CT, PET-CT, daily CBCT prior to treatment, and posttreatment restaging CT scan performed 54 days after completion of chemoradiotherapy. Both fiducials are clearly identifiable in the expected location on all 4 sets of imaging scans. Radiotherapy treatment details are listed in Table 2. Fifty-eight patients (97%) received RT to their esophageal tumors to a median tumor dose of 5040 cgy (range, cgy). One patient after further staging was felt to have a primary gastric tumor and was treated with neoadjuvant chemotherapy followed by surgery. A second patient was found to have liver metastasis prior to starting RT and was treated with chemotherapy. IMRT was used in all but one patient who received 3-D conformal treatment. Forty-two patients (72%) were treated using daily image guidance (IGRT). The type of image guidance used was daily kilovoltage (KV)-CBCT in 31 patients, daily megavoltage helical CT (MVCT) in 2 patients, daily orthogonal KV planar radiographs with weekly KV-CBCT in 8 patients, and daily KV planar radiographs alone in one patient. In 16 patients treated with compensator-based solid IMRT, traditional weekly megavoltage port films were used for setup verification.

6 Practical Radiation Oncology: January-March 2013 Table 2 Treatment details Characteristic No. Value No. of patients 60 Fiducials markers Placed at EUS 105 Visible at CT simulation 99 94% No. of fiducials placed per patient % % 3 5 8% Visicoil fiducial size used 0.35 mm 10 mm 10 10% 0.50 mm 10 mm 1 1% 0.75 mm 10 mm 94 89% Time from fiducial placement to CT simulation Median 1 Day Range 0-87 Days No. of patients who received RT 58 97% Total RT dose to GTV Median 5040 cgy Range cgy RT treatment technique IMRT 57 98% 3D-conformal 1 2% Patients treated with IGRT 42 72% Daily KV-CBCT 31 74% Daily KV-XR + weekly KV-CBCT 8 19% Daily helical MV-CT 2 4% Daily KV-XR alone 1 2% CT, computed tomography; EUS, endoscopic ultrasound; GTV, gross tumor volume; IMRT, intensity modulated radiation therapy; 3D, 3-dimensional; IGRT, image-guided radiation therapy; KV-CBCT, kilovoltage cone-beam computed tomography; KV-XR, kilovoltage planar radiography; MV-CT, megavoltage computed tomography; RT, radiation therapy. Fiducial markers and esophageal cancer 37 Table 3 contains the results of our analysis of short- and long-term fiducial marker stability as assessed by their visibility in the initial implanted location on subsequent CT scans. At the time of CT simulation, 99 (94%) fiducial markers were clearly visible on the planning CT scans. In 2 patients whose CT simulation was performed on the same day as fiducial placement, 2 dislodged fiducial markers were visualized more distally within the lumen of the gastrointestinal tract. Of the 60 initial patients, 57 patients (95%) had subsequent CT scans available for review to assess post-treatment fiducial stability. The most recent available CT scan expected to contain fiducials (ie, last preoperative scan in those patients who went for esophagectomy) was used to assess post-treatment stability. Of the 100 fiducials implanted in these 57 patients, 94 (94%) fiducials were still present at CTsimulation. Eighty-eight (88%) fiducials were still present in their initial implanted positions at a median time of 107 days (range, days) after implantation. Thirty-two patients who had a total of 60 fiducials implanted eventually underwent esophagectomy. Of the 56 (93%) fiducials present in these 32 patients at time of CT simulation, 52 (87%) were still present on the last CT scan prior to surgery, at a median 104 days (range, days) after implantation. Twenty-five of the 28 patients who did not have surgery had post-treatment CT imaging available for review. Of the 40 fiducials implanted in these 25 patients, 38 (95%) were present at the time of CT simulation. Thirty-six (90%) fiducials were visible on the most recent CT scan at a median time of 165 days (range, days) following implantation. Three of these patients underwent high-dose-rate (HDR) brachytherapy boost treatment to their tumors and the implanted fiducials were well visualized on brachytherapy treatment planning Table 3 Characteristic Fiducial stability Group All patients (n = 60) Esophagectomy (n = 32) No surgery (n = 28) Patients with post-treatment CT scans 57 (95%) 32 (100%) 25 (89%) Time from fiducial placement to last post-treatment CT expected to contain fiducials Median 107 days 104 days 165 days Range days days days Fiducial markers in patients with post-treatment CT Placed at EUS n = 100 n = 60 n = 40 Visible at CT simulation 94 (94%) 56 (93%) 38 (95%) Visible on last post-treatment CT 88 (88%) 52 (87%) 36 (90%) Patients who received HDR brachytherapy boost 3 (5%) Fiducials placed n = 6 Visible at CT simulation 4 (66%) Visible on last post-treatment CT 4 (66%) Visible on brachytherapy CT simulation 4 (66%) CT, computed tomography; EUS, endoscopic ultrasound; HDR, high dose rate.

7 38 D.C. Fernandez et al Practical Radiation Oncology: January-March 2013 CT scans and used to help identify target volumes for brachytherapy treatment. There was no difference noted in visibility of 0.35 versus 0.75 mm diameter markers with respect to any volumetric imaging technique used. All markers were well visualized on every diagnostic CT, simulation CT, PET- CT, daily KV-CBCT, and MVCT. While not quantitatively analyzed, on review of those patients treated with daily IGRT using planar KV imaging, we note that 0.75-mm diameter fiducials were easier in general to visualize than the smaller diameter fiducials, particularly in patients with larger body habitus. Discussion Several groups have reported on techniques and success rates for EUS-guided fiducial marker implantation for a variety of malignancies including pancreatic cancers, 4-10 lung cancers, 4 prostate cancer, 11,12 cholangiocarcinoma, 10 esophageal cancers, 2-4 as well as metastases from a variety of primary cancers. 4,10 Many of these reports have focused on the technical aspects of EUS-guided fiducial implantation and several of the more recent papers focus on the improved technical success with using 0.35 mm 10 mm Visicoil fiducials in conjunction with a 22-gauge needle over past techniques employing larger caliber fiducials with 19-gauge needles. 3,8,10,13 Few published reports have included detailed analyses of fiducial visibility on subsequent RT planning and treatment imaging scans from daily IGRT. To our knowledge, this is the largest published series of EUSguided fiducial marker placement to aid in target localization and IGRT in patients with esophageal tumors and the only study reporting on fiducial stability both at time of CT simulation and after treatment. DiMaio et al 2 reported a series of EUS-guided fiducial placement in 30 patients with GI malignancies, of which 18 patients were esophageal tumors. Technical success (defined as the ability to place fiducials in the desired location) was achieved in all but one patient in whom a small esophageal tumor was unable to be identified with the echoendoscope. In this series, fiducial markers could be identified on simulation scans in only 10 of 12 patients who had follow-up information available. In 2 of these patients only 1 of the 2 implanted markers could be identified, which the authors concluded was likely due to fiducial migration. A smaller series of 4 esophageal cancers for which EUS-guided fiducial placement was performed was reported in abstract form by Ghassemi and Faigel. 3 A total of 7 fiducials were placed in 4 patients with a 100% success rate. Two of the 4 patients had pretreatment CT scans available for review and all implanted fiducials were visible. A third series of 13 patients with mostly pancreatic tumors who underwent EUS-guided fiducial placement prior to Cyberknife RT included one patient with recurrent esophageal cancer at the gastroesophageal junction after prior chemoradiotherapy; however, no evaluation of the ability to visualize the implanted fiducials at the time of RT simulation or treatment was performed. Pfau et al 14 reported on the placement of mucosal clips at the superior and inferior margins of 7 esophageal tumors as visualized at standard endoscopy. Patients on this study underwent RT simulation within 7 days of clip placement and 100% of clips were visible on radiographic simulation films. While this technique was shown to be useful and impacted RT portal size, it does have several limitations compared with the EUS-guided submucosal implantation of fiducial markers described in this study. First, traditional endoscopy is limited in its ability to define the true extent of submucosal disease and has no ability to identify adjacent lymphadenopathy. Second, mucosal clips are temporary markers and typically dislodge over the course of days to weeks when placed for hemostasis. There are no reports on the stability of hemoclips during RT treatment but one would expect that tumor regression would significantly impact stability, limiting the ability to use such markers during a typical 5-6 week course of fractionated RT. Our report clearly shows that routine implantation of fiducial markers for esophageal cancer is feasible and that the retention rate is high at time of CT simulation. The presence of fiducials allowed for more confident target volume delineation and improved assessment of respiratory tumor motion on 4-dimensional CT simulation for internal target volume delineation. This was particularly helpful in patients with smaller lesions and for those who received induction chemotherapy with substantial response. In many patients this led to smaller treatment margins though a quantitative analysis of such impact was not possible due to the retrospective nature of the current work. We also demonstrated that only a small fraction of markers are lost after RT, which allowed for their use to aid in IGRT during a fractionated course of RT and subsequently smaller planning target volume margins. Several patients in our series who were determined not to be surgical candidates underwent tumor boost doses with several different techniques, most commonly a simultaneous integrated boost delivered via IMRT with daily IGRT. Additionally, 3 nonsurgical patients had local boosts delivered by HDR brachytherapy and fiducials were still present and easily visible on CT simulation allowing for confident targeting even after significant tumor regression with preceding external beam chemoradiotherapy. All IGRT images were reviewed and 100% of markers present at time of CT simulation were visible on every KV-CBCT and helical MVCT that was performed. We also note that the larger diameter markers (0.75 mm 10 mm) were easier to routinely identify on KV planar

8 Practical Radiation Oncology: January-March 2013 radiography and that visibility of fiducial markers on planar imaging also appeared to depend on other patient variables including body habitus, choice of planar imaging beam orientation, and presence or absence of palliative esophageal stents. Conclusions EUS-guided submucosal fiducial marker placement represents a reliable technique to assist the radiation oncologist with several aspects of treatment planning including target delineation of primary esophageal tumor, daily IGRT, simultaneous integrated boost IMRT, and brachytherapy. Fiducial stability and visualization on treatment planning CT scans, in-room daily IGRT images, and post-treatment diagnostic imaging after RT is excellent. It is now routine practice at our institution for esophageal cancer patients to undergo EUS-guided fiducial marker placement in conjunction with PET-CT scanning in the treatment planning position prior to neoadjuvant or definitive RT. References 1. Lightdale CJ, Kulkarni KG. Role of endoscopic ultrasonography in the staging and follow-up of esophageal cancer. J Clin Oncol. 2005;23: 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: Ghassemi S, Faigel DO. EUS-guided placement of fiducial markers using a 22-gauge needle. [Abstract] Gastrointest Endosc. 2009;69: AB337-AB338. Fiducial markers and esophageal cancer Pishvaian AC, Collins B, Gagnon G, Ahlawat S, Haddad NG. EUSguided fiducial placement for CyberKnife radiotherapy of mediastinal and abdominal malignancies. Gastrointest Endosc. 2006;64: Owens DJ, Savides TJ. EUS placement of metal fiducials by using a backloaded technique with bone wax seal. Gastrointest Endosc. 2009;69: Park WG, Yan BM, Schellenberg D, et al. EUS-guided gold fiducial insertion for image-guided radiation therapy of pancreatic cancer: 50 successful cases without fluoroscopy. Gastrointest Endosc. 2010;71: Varadarajulu S, Trevino JM, Shen S, Jacob R. The use of endoscopic ultrasound-guided gold markers in image-guided radiation therapy of pancreatic cancers: a case series. Endoscopy. 2010;42: Vignesh S, Hoffe SE, Shridhar R, Klapman J, Barthel JS. The feasibility, safety, and technique of endoscopic ultrasound (EUS)- guided fiducial marker placement for stereotactic body radiation therapy (SBRT) in borderline resectable pancreatic cancer. [Abstract]. J Clin Oncol. 2011;29(Suppl 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: Ammar T, Coté GA, Creach KM, Kohlmeier C, Parikh PJ, Azar RR. Fiducial placement for stereotactic radiation by using EUS: feasibility when using a marker compatible with a standard 22- gauge needle. Gastrointest Endosc. 2010;71: Yang J, Abdel-Wahab M, Ribeiro A. EUS-guided fiducial placement before targeted radiation therapy for prostate cancer. Gastrointest Endosc. 2009;70: Yang J, Abdel-Wahab M, Ribeiro A. EUS-guided fiducial placement after radical prostatectomy before targeted radiation therapy for prostate cancer recurrence. Gastrointest Endosc. 2011; 73: Vignesh S, Hoffe SE, Saif MW. EUS-guided pancreatic diagnosis and beyond. Highlights from the 2011 ASCO gastrointestinal cancers symposium. San Francisco, CA, USA. January 20-22, JOP. 2011;12: Pfau PR, Pham H, Ellis R, Das A, Isenberg G, Chak A. A novel use of endoscopic clips in the treatment planning for radiation therapy (XRT) of esophageal cancer. J Clin Gastroenterol. 2005;39: