Cynthia L. Harris

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

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 post-treatment imaging at a median of 107 days (range, 33-471 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.

Radiosensitivity index predicts for survival with adjuvant radiation in resectable pancreatic cancer.

BACKGROUND AND PURPOSE Adjuvant radiation therapy for resectable pancreatic cancer remains controversial. Sub-populations of radiosensitive tumors might exist given the genetic heterogeneity of pancreatic cancers. We evaluated whether RSI is predictive of survival in pancreatic cancer treated with radiation. MATERIALS AND METHODS We identified 73 genomically-profiled pancreas cancer patients treated with upfront surgery between 2000 and 2011 (48 radiation, 25 no radiation). Briefly, RSI score is derived from the expression of 10 specific genes and a linear regression algorithm modeled on SF2 of 48 cancer cells. The primary endpoint was to assess the association of RSI with overall survival. RESULTS Median follow-up was 67months for surviving patients. On multivariate analysis, patients with radioresistant tumors had a trend toward worse survival (Hazard ratio [HR] 2.1 [95% CI 1.0-4.3], p=0.054). Among high-risk, irradiated patients (positive margins, positive lymph nodes, or a post-operative CA19-9 >90; n=31), radiosensitive patients had significantly improved survival compared with radioresistant patients (median 31.2 vs. 13.2months; HR 0.42 [0.19, 0.94], p=0.04). Among irradiated patients (n=48), low-risk patients lived longer than both high-risk patients with radiosensitive tumors and radioresistant tumors (HR 2.7 [1.0, 7.2], p=0.04 and HR 6.3 [2.3, 17.0], p<0.001, respectively). CONCLUSIONS Integrating RSI with standard high-risk variables has the potential to refine the classification of high-risk resected pancreatic cancer patients treated with radiation therapy.

Cryoablation of persistent Barrett's epithelium after definitive chemoradiation therapy for esophageal adenocarcinoma

BACKGROUND Dysplastic Barretts epithelium (BE) persists after chemoradiation therapy for esophageal adenocarcinoma (EAC) arising in Barretts esophagus. This phenomenon may present a significant risk for development of metachronous adenocarcinoma. OBJECTIVE To analyze the safety and efficacy of endoscopic cryoablation therapy for persistent dysplastic BE in patients with complete clinical response after definitive chemoradiation therapy for EAC. DESIGN Retrospective cohort study. SETTING Single National Cancer Institute Comprehensive Cancer Center experience. PATIENTS Radiation and endoscopic oncology treatment records were reviewed between January 2004 and September 2009. Fourteen patients with EAC who had been treated with definitive chemoradiation therapy followed by cryoablation were identified. INTERVENTION Cryoablation therapy. MAIN OUTCOME MEASUREMENTS Reduction in Prague Classification and dysplasia status following cryoablation therapy. Complications reported at 24 hour after the procedure telephone survey and at subsequent endoscopy. RESULTS After complete clinical response of EAC to chemoradiation therapy, the median length of persistent BE was Prague classification C1M4 (C = circumferential extent, M = maximal extent). Cryoablation reduced the median length of persistent BE to Prague classification C0M1 (P = .009 with respect to circumferential extent and P = .004 with respect to maximal extent of BE). All 14 patients had dysplastic BE. Cryoablation resulted in histological downgrading in all 14 patients. Among patients with high-grade dysplasia, 20% (2/10) were reduced to low-grade dysplasia, 60% (6/10) to BE with no dysplasia, and 20% (2/10) to no BE. Among patients with low-grade dysplasia, 75% (3/4) were reduced to BE with no dysplasia, and 25% (1/4) to no BE. The median number of cryoablation treatments administered to the 14 patients evaluated was 1 (mean 1.5, range 1-5). Eighty-six percent (12/14) of patients reported no complaints during the 24 hours after cryoablation. No occurrences of perforation and no esophageal strictures were reported at surveillance endoscopy. LIMITATIONS Single-center, retrospective design involving a small number of patients. CONCLUSION Our observations suggest that cryoablation therapy is safe and effective for the treatment of persistent BE after definitive chemoradiation.

A Prospective Multicenter Study Evaluating Learning Curves and Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography Among Advanced Endoscopy Trainees: The Rapid Assessment of Trainee Endoscopy Skills Study

BACKGROUND & AIMS: On the basis of the Next Accreditation System, trainee assessment should occur on a continuous basis with individualized feedback. We aimed to validate endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) learning curves among advanced endoscopy trainees (AETs) by using a large national sample of training programs and to develop a centralized database that allows assessment of performance in relation to peers. METHODS: ASGE recognized training programs were invited to participate, and AETs were graded on ERCP and EUS exams by using a validated competency assessment tool that assesses technical and cognitive competence in a continuous fashion. Grading for each skill was done by using a 4‐point scoring system, and a comprehensive data collection and reporting system was built to create learning curves by using cumulative sum analysis. Individual results and benchmarking to peers were shared with AETs and trainers quarterly. RESULTS: Of the 62 programs invited, 20 programs and 22 AETs participated in this study. At the end of training, median number of EUS and ERCP performed/AET was 300 (range, 155–650) and 350 (125–500), respectively. Overall, 3786 exams were graded (EUS, 1137; ERCP‐biliary, 2280; ERCP‐pancreatic, 369). Learning curves for individual end points and overall technical/cognitive aspects in EUS and ERCP demonstrated substantial variability and were successfully shared with all programs. The majority of trainees achieved overall technical (EUS, 82%; ERCP, 60%) and cognitive (EUS, 76%; ERCP, 100%) competence at conclusion of training. CONCLUSIONS: These results demonstrate the feasibility of establishing a centralized database to report individualized learning curves and confirm the substantial variability in time to achieve competence among AETs in EUS and ERCP. ClinicalTrials.gov: NCT02509416.

Endoscopic ultrasound-guided fiducial marker placement for image-guided radiation therapy without fluoroscopy: safety and technical feasibility

Background and study aims: Endoscopic ultrasound (EUS)-guided fiducial marker placement for image-guided radiation treatment (IGRT) is becoming more widespread. Most case series report the procedure performed using fluoroscopy for spatial geometry although the benefits of this are unclear. The aim of our study is to report the technical feasibility, safety, and migration rate of fiducial marker placement in a large cohort of patients with gastrointestinal malignancies who underwent EUS-guided fiducial marker placement for IGRT without fluoroscopy. Patients and methods: A retrospective chart review was performed on all patients referred for EUS-guided fiducial marker placement from 08/1/07 to 7/31/14 at Moffitt Cancer Center. Results: During the study period, 514 patients underwent placement of 1093 gold fiducial markers under EUS-guidance. Two hundred and forty patients with esophageal/gastro-esophageal junction cancer had 405 fiducials placed. In 188 patients with pancreatic ancer, 510 fiducials were placed. In 54 patients with rectal cancer, 103 fiducials were placed and 32 patients had 75 fiducials placed into other gastrointestinal tract lesions. Minor bleeding, which resolved spontaneously, occurred in two patients. Technical difficulty in placing fiducials was noted in 18 patients. Intraprocedural fiducial migration was noted in two patients and only 2/1093 fiducials (.002%) in two esophageal patients migrated as noted on simulation computed tomography scan. Conclusions: EUS-guided fiducial marker placement without fluoroscopy is technically feasible and safe. There were minimal intraprocedure/post-procedure complications. Imaging at the time of simulation also revealed the migration rate to be extremely low. These results may allow for more widespread adoption of EUS-guided fiducial marker placement.

Endoscopic ultrasound staging for early esophageal cancer: Are we denying patients neoadjuvant chemo-radiation?

AIM To evaluate the accuracy of endoscopic ultrasound (EUS) in early esophageal cancer (EC) performed in a high-volume tertiary cancer center. METHODS A retrospective review of patients undergoing esophagectomy was performed and patients with cT1N0 and cT2N0 esophageal cancer by EUS were evaluated. Patient demographics, tumor characteristics, and treatment were reviewed. EUS staging was compared to surgical pathology to determine accuracy of EUS. Descriptive statistics was used to describe the cohort. Student’s t test and Fisher’s exact test or χ2 test was used to compare variables. Logistic regression analysis was used to determine if clinical variables such as tumor location and tumor histology were associated with EUS accuracy. RESULTS Between 2000 and 2015, 139 patients with clinical stageIorIIA esophageal cancer undergoing esophagectomy were identified. There were 25 (18%) female and 114 (82%) male patients. The tumor location included the middle third of the esophagus in 11 (8%) and lower third and gastroesophageal junction in 128 (92%) patients. Ninety-three percent of patients had adenocarcinoma. Preoperative EUS matched the final surgical pathology in 73/139 patients for a concordance rate of 53%. Twenty-nine patients (21%) were under-staged by EUS; of those, 19 (14%) had unrecognized nodal disease. Positron emission tomography (PET) was used in addition to EUS for clinical staging in 62/139 patients. Occult nodal disease was only found in 4 of 62 patients (6%) in whom both EUS and PET were negative for nodal involvement. CONCLUSION EUS is less accurate in early EC and endoscopic mucosal resection might be useful in certain settings. The addition of PET to EUS improves staging accuracy.

Fiducial markers coupled with 3D PET/CT offer more accurate radiation treatment delivery for locally advanced esophageal cancer

Background and aims  The role of three-dimensional positron emission tomography/computed tomography (3 D PET/CT) in esophageal tumors that move with respiration and have potential for significant mucosal inflammation is unclear. The aim of this study was to determine the correlation between gross tumor volumes derived from 3 D PET/CT and endoscopically placed fiducial markers. Methods  This was a retrospective, IRB approved analysis of 40 patients with esophageal cancer with fiducials implanted and PET/CT. The centroid of each fiducial was identified on PET/CT images. Distance between tumor volume and fiducials was measured using axial slices. Image features were extracted and tested for pathologic response predictability. Results  The median adaptively calculated threshold value of the standardized uptake value (SUV) to define the metabolic tumor volume (MTV) border was 2.50, which corresponded to a median 23 % of the maximum SUV. The median distance between the inferior fiducial centroid and MTV was – 0.60 cm (– 3.9 to 2.7 cm). The median distance between the superior fiducial centroid and MTV was 1.25 cm (– 4.2 to 6.9 cm). There was no correlation between MTV-to-fiducial distances greater than 2 cm and the gastroenterologist who performed the fiducial implantation. Eccentricity demonstrated statistically significant correlations with pathologic response. Conclusions  There was a stronger correlation between inferior fiducial location and MTV border compared to the superior extent. The etiology of the discordance superiorly is unclear, potentially representing benign secondary esophagitis, presence of malignant nodes, inflammation caused by technical aspects of the fiducial placement itself, or potential submucosal disease. Given the concordance inferiorly and the ability to more precisely set up the patient with daily image guidance matching to fiducials, it may be possible to minimize the planning tumor volume (PTV) margin in select patients, thereby, limiting dose to normal structures.

Small caliber covered self-expanding metal stents in the management of malignant dysphagia.

BACKGROUND Use of large caliber [≥18 mm body diameter (BD)] self-expanding metal stents (SEMS) for management of malignant dysphasia is associated with substantial adverse event (AE) and mortality rates (MRs). We sought to determine dysphagia response, stent migration rates, and AE and MRs, for small caliber covered SEMS (sccSEMS) with BDs between 10-16 mm in malignant dysphagia. METHODS Thirty-one patients underwent direct endoscopic placement of 50 sccSEMS between January 2008 and March 2011. Patients were monitored for change in dysphagia score (DS), stent migration, AEs, and death through May 2011. RESULTS DS improved in 30 of 31 patients (97%). The median DS decreased from 3 to 2 (P<0.0001). The median effective duration of first sccSEMS placement was 116 (95% CI: 75-196) days. Major and minor AE rates were 6.5% and 19.4% respectively. No stent related deaths were encountered. The overall migration rate was 36% (18/50). The anticipated migration rate was 45.7% (16/35) and the unanticipated migration rate was 13.3% (2/15) (P=0.052). Positive effective clinical outcome occurred in 93.5% (29/31) of cases. CONCLUSIONS In malignant dysphagia, direct endoscopic sccSEMS placement provided acceptable dysphagia control and migration rates with substantial reductions in stent related AEs and MRs compared to those reported for large caliber SEMS.

Accuracy of clinical staging with EUS for early stage esophageal cancer: Are we denying patients beneficial neoadjuvant chemo-radiation?

163 Background: Esophagectomy alone has been considered the standard of care for early stage esophageal cancer (EC) while neoadjuvant therapy is now standard for locally advanced disease. The choice of treatment therefore hinges on accurate locoregional staging by endoscopic ultrasound (EUS). Our objective is to evaluate the accuracy of EUS performed in a high-volume tertiary cancer center in clinical stage T1N0 (cT1N0) and T2N0 (cT2N0) esophageal cancer patients undergoing esophagectomy without neoadjuvant therapy. Methods: A retrospective review of the esophageal cancer database at a single institution was performed. Patients with cT1N0 and cT2N0 esophageal cancer based on EUS undergoing esophagectomy without neoadjuvant treatment were evaluated. Patient demographics, tumor characteristics, and treatment were reviewed. Surgical pathology was compared to EUS staging. Results: Between 2000 and 2015, 139 patients were identified. There were 25 (18%) female and 114 (82%) male patients. The tumor location in...

Small caliber covered self expanding metal stents in the management of malignant dysphagia.

151 Background: Use of large caliber ( ≥ 18 mm body diameter) self expanding metal stents (SEMS) for management of malignant dysphasia is associated with substantial adverse event (AE) and mortality rates (MRs). We sought to determine dysphagia response, stent migration rates, and AE and MRs, for small caliber covered SEMS (sccSEMS) with body diameters (BDs) between 10 - 16 mm in malignant dysphagia. Methods: We identified 31 patients underwent direct endoscopic placement of 50 sccSEMS. Patients were monitored for change in dysphagia score (DS), stent migration, AEs, and death. Results: The cohort consisted of 23 (74%) men and 8 (26%) women with a median age of 64 years (35 - 87 years). Esophageal adenocarcinoma (AC) was present in 19 (61%) patients and squamous cell carcinoma (SCCA) in 12 (39%) patients. Of the patients with SCCA, 2 tumors were located in the proximal esophagus, 7 in the mid-esophagus and 3 in the distal esophagus. All 19 ACs were located in the distal esophagus. The AJCC clinical stages...