T1b Esophageal Adenocarcinoma Research Articles

Predictors for Lymph Node Metastasis and Survival of Patients with T1b Esophageal Adenocarcinoma Treated with Surgery and Endoscopic Therapy: An Analysis of Surveillance, Epidemiology, and End Results Database

Limited data exists regarding the long-term outcomes of endoscopic therapy (ET) with or without chemoradiation therapy (CRT) for T1b esophageal adenocarcinoma (EAC). Our aim was to identify the risk factors for lymph node metastasis (LNM) in T1b EAC and assess how the chosen treatment modality affects overall survival (OS) and cancer-specific survival (CSS). We analyzed histologically confirmed T1b EAC patients diagnosed between 2004 and 2018 using Surveillance Epidemiology and End Results database. Focusing on T1bN0M0 staging, we divided the patients into two groups: ET (n=174) and surgery (n=769), and calculated OS and CSS rates. Out of 1418 patients with T1b EAC, 228 cases (16.1%) exhibited LNM at diagnosis. Notable risk factors for LNM included poorly differentiated tumor and lesion size ≥20 mm. For T1bN0M0 cases, ET was commonly performed from 2009 to 2018 (OR 4.3), especially for patients aged ≥ 65 years (OR 3.1) with tumor size <20mm (OR 2.3). During 50 months median follow-up, age ≥ 65 years (HR 1.9), ET (HR 1.5), and CRT (HR 1.4) were associated with poorer OS. Factors linked to decreased CSS were age ≥ 65 years (sub hazard ratio (SHR) 1.6), poorly differentiated tumors (SHR 1.5), and CRT (SHR 1.5). In T1b EAC, tumor size ≥20mm and poor differentiation are notable risk factors for LNM. ET showed comparable CSS outcomes to surgery for carefully selected T1bN0M0 lesions. CRT did not provide additional survival benefit for these lesions; however, large scale studies are required to validate this finding.

Diagnosis and management of Barrett esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

MR1 : ESGE recommends the following standards for Barrett esophagus (BE) surveillance:- a minimum of 1-minute inspection time per cm of BE length during a surveillance endoscopy- photodocumentation of landmarks, the BE segment including one picture per cm of BE length, and the esophagogastric junction in retroflexed position, and any visible lesions- use of the Prague and (for visible lesions) Paris classification- collection of biopsies from all visible abnormalities (if present), followed by random four-quadrant biopsies for every 2-cm BE length.Strong recommendation, weak quality of evidence. MR2: ESGE suggests varying surveillance intervals for different BE lengths. For BE with a maximum extent of ≥ 1 cm and < 3 cm, BE surveillance should be repeated every 5 years. For BE with a maximum extent of ≥ 3 cm and < 10 cm, the interval for endoscopic surveillance should be 3 years. Patients with BE with a maximum extent of ≥ 10 cm should be referred to a BE expert center for surveillance endoscopies. For patients with an irregular Z-line/columnar-lined esophagus of < 1 cm, no routine biopsies or endoscopic surveillance are advised.Weak recommendation, low quality of evidence. MR3: ESGE suggests that, if a patient has reached 75 years of age at the time of the last surveillance endoscopy and/or the patient's life expectancy is less than 5 years, the discontinuation of further surveillance endoscopies can be considered. Weak recommendation, very low quality of evidence. MR4: ESGE recommends offering endoscopic eradication therapy using ablation to patients with BE and low grade dysplasia (LGD) on at least two separate endoscopies, both confirmed by a second experienced pathologist.Strong recommendation, high level of evidence. MR5: ESGE recommends endoscopic ablation treatment for BE with confirmed high grade dysplasia (HGD) without visible lesions, to prevent progression to invasive cancer.Strong recommendation, high level of evidence. MR6: ESGE recommends offering complete eradication of all remaining Barrett epithelium by ablation after endoscopic resection of visible abnormalities containing any degree of dysplasia or esophageal adenocarcinoma (EAC).Strong recommendation, moderate quality of evidence. MR7: ESGE recommends endoscopic resection as curative treatment for T1a Barrett's cancer with well/moderate differentiation and no signs of lymphovascular invasion.Strong recommendation, high level of evidence. MR8: ESGE suggests that low risk submucosal (T1b) EAC (i. e. submucosal invasion depth ≤ 500 µm AND no [lympho]vascular invasion AND no poor tumor differentiation) can be treated by endoscopic resection, provided that adequate follow-up with gastroscopy, endoscopic ultrasound (EUS), and computed tomography (CT)/positrion emission tomography-computed tomography (PET-CT) is performed in expert centers.Weak recommendation, low quality of evidence. MR9: ESGE suggests that submucosal (T1b) esophageal adenocarcinoma with deep submucosal invasion (tumor invasion > 500 µm into the submucosa), and/or (lympho)vascular invasion, and/or a poor tumor differentiation should be considered high risk. Complete staging and consideration of additional treatments (chemotherapy and/or radiotherapy and/or surgery) or strict endoscopic follow-up should be undertaken on an individual basis in a multidisciplinary discussion.Strong recommendation, low quality of evidence. MR10 A: ESGE recommends that the first endoscopic follow-up after successful endoscopic eradication therapy (EET) of BE is performed in an expert center.Strong recommendation, very low quality of evidence. B: ESGE recommends careful inspection of the neo-squamocolumnar junction and neo-squamous epithelium with high definition white-light endoscopy and virtual chromoendoscopy during post-EET surveillance, to detect recurrent dysplasia.Strong recommendation, very low level of evidence. C: ESGE recommends against routine four-quadrant biopsies of neo-squamous epithelium after successful EET of BE.Strong recommendation, low level of evidence. D: ESGE suggests, after successful EET, obtaining four-quadrant random biopsies just distal to a normal-appearing neo-squamocolumnar junction to detect dysplasia in the absence of visible lesions.Weak recommendation, low level of evidence. E: ESGE recommends targeted biopsies are obtained where there is a suspicion of recurrent BE in the tubular esophagus, or where there are visible lesions suspicious for dysplasia.Strong recommendation, very low level of evidence. MR11: After successful EET, ESGE recommends the following surveillance intervals:- For patients with a baseline diagnosis of HGD or EAC:at 1, 2, 3, 4, 5, 7, and 10 years after last treatment, after which surveillance may be stopped.- For patients with a baseline diagnosis of LGD:at 1, 3, and 5 years after last treatment, after which surveillance may be stopped.Strong recommendation, low quality of evidence.

A158 FINDINGS FROM A MULTIDISCIPLINARY DATABASE FOR PATIENTS WITH BARRETT'S ESOPHAGUS AND EARLY ESOPHAGEAL ADENOCARCINOMA

Abstract Background Previously, Barrett’s esophagus (BE) with high grade dysplasia (HGD) or neoplasia was treated with esophagectomy; however, recent guidelines support the use of endoscopic mucosal resection (EMR) for T1a esophageal adenocarcinoma (EAC) and potentially T1b EAC. Long term data for outcomes from EMR are lacking and these treatments are often provided with minimal collaboration between gastroenterologists and thoracic surgeons. Purpose Our primary aim was to describe the findings from our multidisciplinary database of patients with Barrett’s esophagus and EAC undergoing endoscopic treatment. Secondary aims were to compare the overall survival and recurrence-free survival of patients undergoing endoscopic resection to those undergoing esophagectomy. Method For the endoscopic resection cohort, a combined retrospective and prospective database was created containing demographic, clinical, and oncologic variables for patients undergoing endoscopic resection for early stage EAC from 2009 to 2021. For the esophagectomy cohort, a pre-existing retrospective database including patients undergoing esophagectomy for esophageal cancer from 2012 to 2018 at a single institution was used. A multivariate cox proportional hazards model was developed for recurrence-free survival and overall survival using a hypothesis driven approach. A kaplan-meier (KM) curve with associated log-rank test was created to evaluate recurrence-free survival and overall survival stratified by treatment modality. Result(s) A total of 108 patients were included in the analysis (73 EMR, 35 esophagectomy). Baseline characteristics including age, sex, and co-morbidities were similar among the two groups. KM curves stratified by treatment modality are provided in Figure 1. Esophagectomy was associated with greater DFS on univariate log-rank test (p = 0.0127), but no difference in OS (p = 0.9306). There was no significant difference between esophagectomy and endoscopic resection in the cox-model for OS (HR 1.03, 95% CI 0.45-2.32, p = 0.914). Endoscopic resection was associated with increased hazards of disease recurrence in the cox model for DFS (HR 2.56, 95% CI 1.1-6.0, p = 0.032). In the logistic regression model, high grade disease (OR 5.43, 95% CI 1.1 – 26.1, p = 0.035) and submucosal involvement (OR 7.8, 1.9-31.4, p = 0.004) were identified as significant predictors of positive margin necessitating esophagectomy after initial endoscopic resection. All patients who experienced a positive margin after endoscopic therapy were evaluated by a thoracic surgeon and proceeded to esophagectomy. Conclusion(s) In this largely retrospective analysis, our multidisciplinary approach was shown to be highly efficacious in the treatment of BE with EAC. Through optimizing collaboration between thoracic surgeons and gastroenterologists, patients receive the best therapeutic approach for their unique condition, taking into account oncologic factors and clinical comorbidities. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

A127 ENDOSCOPIC MUCOSAL RESECTION FOR DYSPLASTIC AND NEOPLASTIC BARRETT’S ESOPHAGUS: FINDINGS FROM A FOREGUT NEOPLASIA MULTIDISCIPLINARY DATABASE

Abstract Background Previously, Barrett’s esophagus with high grade dysplasia (HGD) or neoplasia was treated with esophagectomy, which is associated with a high postoperative morbidity and mortality rate. Recent guidelines support the use of endoscopic mucosal resection (EMR) for T1a esophageal adenocarcinoma (EAC) and potentially T1b EAC; however, data on long term outcomes of endoscopic treatment is lacking. We created a combined prospective and retrospective multidisciplinary database to monitor outcomes of patients with Barrett’s esophagus undergoing endoscopic treatment. Aims Our primary aim was to compare outcomes of EMR and esophagectomy in patients presenting with BE and HGD, and/or early EAC. Methods A collaboration of gastroenterologists, general surgeons and thoracic surgeons from the University of Alberta, Edmonton, Alberta, provided input on the development of the database. All patients referred to the Northern Alberta Endoscopic Ablation Program from 2009–2021 who received at least one endoscopic treatment were included. A sub-analysis of all patients with pathologic confirmation of HGD, and/or early EAC was conducted to compare outcomes of EMR and esophagectomy. Results A total of 212 patients have been entered into the database. The most common findings were HGD, low grade dysplasia (LGD), and adenocarcinoma, respectively. All patients (n=48) who had at least LGD reached complete eradication of dysplasia (CE-D) and 95.8% reached complete eradication of intestinal metaplasia (CE-IM). Of those patients that reached CE-D, 8.3% developed recurrence of dysplasia (n=4). In the sub-analysis, 74 patients (76.3%) received endoscopic therapy while 23 patients (23.7%) received endoscopic therapy then ultimately an esophagectomy. There were significantly more T1b lesions in the esophagectomy group compared to the EMR group ( p&amp;lt;0.0001). Of all the patients in the EMR group, only 5.4% (n=4) had treatment related complications. Of patients receiving an esophagectomy, 60.9% (n=14) experienced treatment related complications. The mean length of stay for patients in the EMR group was 1.03 +/- 0.2 days, compared to 16.5 +/- 11.8 days for esophagectomy ( p&amp;lt;0.0001). Conclusions EMR provides definitive and durable treatment for BE lesions classified as T1b or less severe, with fewer complications and a shorter length of hospital stay than esophagectomy. Funding Agencies Alberta Innovates Health Solutions

Lymphovascular invasion quantification could improve risk prediction of lymph node metastases in patients with submucosal (T1b) esophageal adenocarcinoma

AimTo quantify lymphovascular invasion (LVI) and to assess the prognostic value in patients with pT1b esophageal adenocarcinoma.MethodsIn this nationwide, retrospective cohort study, patients were included if they were treated with surgery or endoscopic resection for pT1b esophageal adenocarcinoma. Primary endpoint was the presence of metastases, lymph node metastases, or distant metastases, in surgical resection specimens or during follow‐up. A prediction model to identify risk factors for metastases was developed and internally validated.Results248 patients were included. LVI was distributed as follows: no LVI (n = 196; 79.0%), 1 LVI focus (n = 16; 6.5%), 2–3 LVI foci (n = 21; 8.5%) and ≥4 LVI foci (n = 15; 6.0%). Seventy‐eight patients had metastases. The risk of metastases was increased for tumors with 2–3 LVI foci [subdistribution hazard ratio (SHR) 3.39, 95% confidence interval (CI) 2.10–5.47] and ≥4 LVI foci (SHR 3.81, 95% CI 2.37–6.10). The prediction model demonstrated a good discriminative ability (c‐statistic 0.81).ConclusionThe risk of metastases is higher when more LVI foci are present. Quantification of LVI could be useful for a more precise risk estimation of metastases. This model needs to be externally validated before implementation into clinical practice.

S427 Predictors for Lymph Node Metastasis and Survival of Patients With T1b Esophageal Adenocarcinoma Treated With Surgery and Endoscopic Therapy: An Analysis of Surveillance, Epidemiology, and End Results Database

Introduction: There have been a few population-based studies to compare the long-term outcomes of patients those received surgery versus with endotherapy (ET) for T1b esophageal adenocarcinoma (EAC). In this study, we aimed to determine the risk factors of lymph node metastasis (LNM) and evaluate the long-term survival of patients with T1b EAC who underwent ET or surgery. Methods: We used the Surveillance Epidemiology and End Result database to identify patients with T1b histologically confirmed EAC diagnosed between 2004-2018. Patients were grouped based on whether they received ET (n=185) or surgery (n=935). Prevalence of LNM at initial diagnosis was analyzed. Multivariate logistic regression was performed to identify factors associated with LNM and endoscopic therapy. A Cox proportional hazards model was performed to examine the association of treatment options and survival after controlling for potential confounders. Results: Overall, 16% of cases had LNM at the time of diagnosis. The risk factors for LNM included lesion size ≥20 mm (OR 1.7, 95%CI 1.2-2.4) and poor tumor differentiation (OR 1.6, 95%CI 1.2-2.3). The use of ET increased progressively, from 0.8% in 2008 to 1.6% in 2018. ET was more commonly performed in patients with age >65 yr (OR 2.7, 95%CI 1.5-4.6), tumor size ≤20mm (OR 2.1, 95%CI 1.3-3.7), recent year of diagnosis (2008-2018 vs 2004-2007; OR 3.1, 95%CI 1.7-5.7) and those without LNM. Three-year overall survival was higher in surgery group than in the ET group (65.4% vs 54.4%, p = 0.04). Of 946 patients with T1bN0M0 EAC, 177 underwent ET and 769 had radical surgery. After adjusting for patient and tumor specific factors, patients with T1bN0M0 EAC treated by ET had a worse overall survival outcome (HR 1.4, 95% CI 1.06-1.97, P=0.01) compared to those received surgery. ET and surgery resulted in statistically equivalent in esophageal cancer mortality [HR 0.98, 95%CI 0.62-1.56, P=0.96]. Conclusion: In T1b EAC, tumor size ≥20mm and poor differentiation are the significant risk factors for LNM. Cancer specific survival in patients with T1bN0M0 EAC treated with ET appears to be similar to those treated with surgery. We found that patients who have significant coexisting conditions such as older age, are less likely to undergo surgery, as reflected in our study that older patients were more likely to have ET, which could partly explain higher overall mortality in ET group.Figure 1.: A: In a multivariate Cox proportional hazards model, adjusted for clinical and tumor-related factors, ET was associated with increased cumulative hazard (HR 1.4, 95% CI 1.06-1.97) compared to surgery. B: No difference was noted in cancer specific survival between the treatment groups when adjusted for age, sex, race, tumor size, tumor differentiation, and year of diagnosis.

Feasibility of sentinel node navigated surgery in high-risk T1b esophageal adenocarcinoma patients using a hybrid tracer of technetium-99\xa0m and indocyanine green

BackgroundMinimally invasive esophagectomy with two-field lymphadenectomy is standard of care for T1b esophageal adenocarcinoma (EAC) with a high risk of lymph node metastasis. Sentinel node navigation surgery (SNNS) is a well-known concept to tailor the extent of lymphadenectomy. The aim of this study was to evaluate the feasibility and safety of SNNS with a hybrid tracer (technetium-99 m/indocyanine green/nanocolloid) for patients with high-risk T1b EAC.MethodsIn this prospective, multicenter pilot study, 5 patients with high-risk T1b EAC were included. The tracer was injected endoscopically around the endoscopic resection scar the day before surgery, followed by preoperative imaging (lymphoscintigraphy/SPECT-CT). During surgery, first the SNs were localized and resected based on preoperative imaging and intraoperative gammaprobe- and fluorescence-based detection, followed by esophagectomy. Primary endpoints were the percentage of patients with detectable SNs, concordance between preoperative and intraoperative SN detection, and the additive value of indocyanine green.ResultsSNs could be identified and resected in all patients (median 3 SNs per patient, range 2–7). There was a high concordance between preoperative and intraoperative SN detection. In 2 patients additional peritumoral SNs were identified with fluorescence-based detection. None of the resected lymph nodes showed signs of (micro)metastases and no nodal metastases were detected in the surgical resection specimen.ConclusionsSNNS using technetium-99 m/indocyanine green/nanocolloid seems feasible and safe in patients with high-risk T1b EAC. Indocyanine green fluorescence seems to be of additive value for detection of peritumoral SNs. Whether this approach can optimize selection for esophagectomy needs to be studied in future research.

Individual risk calculator to predict lymph node metastases in patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study.

Lymph node metastasis (LNM) is possible after endoscopic resection of early esophageal adenocarcinoma (EAC). This study aimed to develop and internally validate a prediction model that estimates the individual risk of metastases in patients with pT1b EAC. A nationwide, retrospective, multicenter cohort study was conducted in patients with pT1b EAC treated with endoscopic resection and/or surgery between 1989 and 2016. The primary end point was presence of LNM in surgical resection specimens or detection of metastases during follow-up. All resection specimens were histologically reassessed by specialist gastrointestinal pathologists. Subdistribution hazard regression analysis was used to develop the prediction model. The discriminative ability of this model was assessed using the c-statistic. 248 patients with pT1b EAC were included. Metastases were seen in 78 patients, and the 5-year cumulative incidence was 30.9 % (95 % confidence interval [CI] 25.1 %-36.8 %). The risk of metastases increased with submucosal invasion depth (subdistribution hazard ratio [SHR] 1.08, 95 %CI 1.02-1.14, for every increase of 500 μm), lymphovascular invasion (SHR 2.95, 95 %CI 1.95-4.45), and for larger tumors (SHR 1.23, 95 %CI 1.10-1.37, for every increase of 10 mm). The model demonstrated good discriminative ability (c-statistic 0.81, 95 %CI 0.75-0.86). A third of patients with pT1b EAC experienced metastases within 5 years. The probability of developing post-resection metastases was estimated with a personalized predicted risk score incorporating tumor invasion depth, tumor size, and lymphovascular invasion. This model requires external validation before implementation into clinical practice.

S0344 Endoscopic Resection of T1b Esophageal Adenocarcinoma Is Comparable to Esophagectomy: A Surveillance, Epidemiology, and End Results Database Study

INTRODUCTION: Current guidelines recommend consideration of endoscopic therapy when treating T1a esophageal adenocarcinoma. However, it remains unclear if endoscopy is appropriate for treating T1b lesions with and without lymph node metastasis. Our study aims to compare survival outcomes following surgical resection and endoscopy in treating T1b esophageal adenocarcinoma. METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results database from 2000 to 2016 of patients with T1b esophageal adenocarcinoma treated with endoscopic resection or esophagectomy. Kaplan Meier estimations and cox proportional hazards models were used to assess survival outcomes. RESULTS: A total of 603 patients with T1b esophageal carcinoma were identified, of whom 87.7% were male. Median age at diagnosis was 67 ± 10.6 years. Overall, males had a higher prevalence of T1b esophageal carcinoma compared to females (87.7% vs. 12.1 per 100,000 per year). Tumors were most common among White patients (95.2%). Most tumors were moderately differentiated (45%), followed by poorly differentiated (33%), well differentiated (10.4%), and undifferentiated (1.0%). Most tumors occurred in the distal third of the esophagus (83.4%) followed by the mid esophagus (8.6%) and the proximal third (1.8%). About 84 (13.9%) underwent endoscopic resection and 367 (60.9%) underwent esophagectomy. One, 3- and 5-year survival for cancer-specific death was associated with survival rates of 91%, 78%, and 74%, respectively, for endoscopic resection. Esophagectomy was associated with 1-, 3 and 5-year survival rates of 91%, 85%, and 73%, respectively. Subgroup analysis showed that in patients with lymph node metastasis (LMN), no significant difference in mortality was observed following surgical and endoscopic resection (Log Rank test = 0.903). Adjusted hazard models indicated that LMN was associated with 2 times higher mortality [HR 2.16, 95% CI 1.250-23.742, P = 0.0.006], and surgical intervention was associated with a non-significant reduction in mortality [HR 0.78, 95% CI 0.414-1.480, P = 0.451]. CONCLUSION: Endoscopic resection was associated with similar cancer-specific survival outcomes compared with esophagectomy in stage T1b esophageal adenocarcinoma, regardless of lymph node metastasis. Endoscopic removal of T1b esophageal adenocarcinoma is an effective strategy for patients including those either refusing esophagectomy or not a candidate for surgical intervention.Figure 1.: Survival following endoscopic resection (ER) and surgical resection (SR).

Is Local Endoscopic Resection a Viable Therapeutic Option for Early Clinical Stage T1a and T1b Esophageal Adenocarcinoma?: A Propensity-matched Analysis.

The aim of this study was to evaluate the outcome of endoscopic resection (ER) versus esophagectomy in node-negative cT1a and cT1b esophageal adenocarcinoma. The role of ER in the management of subsets of clinical T1N0 esophageal adenocarcinoma is controversial. Data from the National Cancer Database (2010-2015) were used to identify patients with clinical T1aN0 (n = 2545) and T1bN0 (n = 1281) esophageal adenocarcinoma that received either ER (cT1a, n = 1581; cT1b, n = 335) or esophagectomy (cT1a, n = 964; cT1b, n = 946). Propensity score matching and Cox analyses were used to account for treatment selection bias. ER for cT1a and cT1b disease was performed more commonly over time. The rates of node-positive disease in patients with cT1a and cT1b esophageal adenocarcinoma were 4% and 15%, respectively. In the matched cohort for cT1a cancers, ER had similar survival to esophagectomy [hazard ratio (HR): 0.85, 95% confidence interval (CI): 0.70-1.04, P = 0.1]. The corresponding 5-year survival for ER and esophagectomy were 70% and 74% (P = 0.1), respectively. For cT1b cancers, there was no statistically significant difference in overall survival between the treatment groups (HR: 0.87, 95% CI: 0.66-1.14, P = 0.3). The corresponding 5-year survival for ER and esophagectomy were 53% versus 61% (P = 0.3), respectively. This study demonstrates ER has comparable long-term outcomes for clinical T1aN0 and T1bN0 esophageal adenocarcinoma. However, 15% of patients with cT1b esophageal cancer were found to have positive nodal disease. Future research should seek to identify the subset of T1b cancers at high risk of nodal metastasis and thus would benefit from esophagectomy with lymphadenectomy.

Mo1292 EFFICACY AND OUTCOMES OF ENDOSCOPIC MUCOSAL RESECTION IN T1B ESOPHAGEAL ADENOCARCINOMA: CAN ESOPHAGECTOMY BE AVOIDED IN SELECT PATIENTS?

The incidence of esophageal adenocarcinoma (EAC) has continued to increase over the past several decades. While endoscopic mucosal resection (EMR) is highly effective for intramucosal EAC (T1a lesions), there is limited data on outcomes of patients following EMR with T1b EAC in the era of modern chemoradiation and cryotherapy modalities. While the current standard of care for T1b EAC relies on esophagectomy, with its high risk of morbidity and mortality, it remains uncertain whether select patients with T1b EAC can be definitively treated with EMR along with chemoradiation or additional endoscopic therapies. The aim of this study is to evaluate the outcomes of patients with T1b EAC after initial EMR. A retrospective cross-sectional study was performed using a prospective electronic endoscopy database at a tertiary care academic medical center. All patients who underwent esophageal EMR for T1b EAC between February 2015 and September 2019 were included. Data on patient and disease characteristics were collected. The primary outcome was presence of residual disease (local or metastatic) during follow-up. A total of 13 patients with T1b EAC who underwent EMR were identified. The mean age was 71 years and 85% were male. Seven of these patients (54%) underwent esophagectomy while 6 patients had endoscopic and clinical surveillance. Patients who underwent esophagectomy and endoscopic surveillance had similar characteristics except that patients who underwent esophagectomy had a lower Charlson comorbidity index (5.7 vs. 7.8, P = 0.04). In patients who underwent endoscopic surveillance, 67% were deemed too high-risk for surgery, while 33% refused surgery. Among the 6 patients who underwent endoscopic surveillance after EMR, 3 were additionally treated with cryotherapy, 1 was treated with radiofrequency ablation (RFA) and 1 underwent chemoradiation. One of these 6 patients was found to have residual disease at a mean follow-up of 478 days. Among the 7 patients who underwent esophagectomy after EMR, 3 (43%) had residual tumor on surgical pathology, however none of these 7 patients underwent chemoradiation prior to surgery. Of all 13 T1b EAC patients who underwent EMR, 69.2% (N = 9) had no evidence of subsequent residual disease with a follow-up of 739 days. None of the patients with residual disease underwent prior chemoradiation. These results suggest that select patients with T1b EAC who are at high-risk for esophagectomy may be successfully managed with local therapy of EMR followed by the addition of chemoradiation and alternative endoscopic treatment modalities. Further prospective studies are needed to validate these findings and guide optimal patient selection.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Endoscopic eradication therapy for Barrett's oesophagus: state of the art.

Barrett's oesophagus is the only identifiable precursor lesion to oesophageal adenocarcinoma. The stepwise progression of Barrett's oesophagus to dysplasia and invasive carcinoma provides the opportunity to intervene and reduce the morbidity and mortality associated with this lethal cancer. Several studies have demonstrated the efficacy and safety of endoscopic eradication therapy (EET) for the management of Barrett's oesophagus related neoplasia. The primary goal of EET is to achieve complete eradication of intestinal metaplasia (CE-IM) followed by enrolment of patients in surveillance protocols to detect recurrence of Barrett's oesophagus and Barrett's oesophagus related neoplasia. EET depends on early and accurate detection and diagnosis of Barrett's oesophagus related neoplasia. All visible lesions should be resected followed by ablation of the remaining Barrett's epithelium. After treatment, patients should be enrolled in endoscopic surveillance programmes. For nondysplastic Barrett's oesophagus, surveillance alone is recommended. For low-grade dysplasia, both surveillance and ablation are reasonable options and should be decided on an individual basis according to patient risk factors and preferences. EET is preferred for high-grade dysplasia and intramucosal carcinoma. For T1b oesophageal adenocarcinoma, esophagectomy remains the standard of care, but endoscopic therapy can be considered in select cases. EET is now standard of care and endorsed by societal guidelines for the treatment of Barrett's oesophagus related neoplasia. Future studies should focus on risk stratification models using a combination of clinical data and biomarkers to identify ideal candidates for EET, and to predict recurrence. Optimal therapy for T1b cancer and surveillance strategy after CE-IM are topics that require further study.

The real risk of nodal disease in T1 oesophageal adenocarcinoma

Lymph node status is regarded as an important factor in the prognosis of oesophageal cancer. T1 oesophageal adenocarcinoma management has to include endoscopic management as part of the algorithm. We reviewed the literature to assess the true risk of lymph node metastasis in patients with T1 oesophageal adenocarcinoma. Medline, Embase, PubMed and Cochrane where searched for manuscripts in English reviewing lymph node metastasis in superficial (T1) oesophageal adenocarcinoma. The main outcome was probability of lymph node metastasis in T1a and T1b oesophageal adenocarcinoma. Secondary outcome was the rate of lymph node metastasis of submucosal involvement of T1b (SM1, SM2 and SM3). There were 38 studies identified. 22 studies were excluded due to low lymph node yield (<15) or insufficient statistical analysis. For the 16 remaining studies, a total of 1382 cases were included: T1a adenocarcinoma (533 patients) with 11 (2%) node positive and T1b adenocarcinoma (849 patients) with 189 (22%) node positive. Subgroup analysis of T1b lesions was available in 8 reports (365 patients). Node positivity for SM1, SM2 and SM3 was 19.9%, 20.2% and 32.9%, respectively. T1a disease on endoscopic mucosal resection (EMR) demonstrates a 2% nodal metastasis rate, T1b disease a rate of 22%. T1a disease may be safely treated by EMR. T1a disease appears suitable for endoscopic therapy; however, T1b disease presents a high rate of nodal metastasis.

Outcomes of patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study

The treatment of submucosal (T1b) esophageal adenocarcinoma (EAC) remains in evolution, with some evidence supporting endoscopic management of low-risk lesions. Using a multicenter cohort, we evaluated outcomes of patients with T1b EAC and predictors of survival. Patients diagnosed between 2001 and 2016 with T1b EAC were identified from 3 academic medical centers in the United States. Demographic, clinical, and outcome data were collected. Outcomes studied were overall and cancer-free survival. Cox proportional hazards models were constructed to assess independent predictors of survival. One hundred forty-one patients were included, of whom 68 (48%) underwent esophagectomy and 73 (52%) were treated endoscopically. Most patients (85.8%) had high-risk histologic features. Thirty-day operative mortality was 2.9%. Median follow-up in the esophagectomy and endoscopic cohorts was 49.4 and 43.4 months, respectively. Patients treated endoscopically were older with higher comorbidity scores, with 46 (63%) achieving histologic remission. Nineteen patients (26.0%) also received chemoradiation. Five-year overall survival rates in the surgical and endoscopic cohorts were 89% and 59%, respectively, whereas 5-year cancer-free survival rates were 92% and 69%. Presence of high-risk histologic features was associated with reduced overall survival. In this large multicenter study of patients with T1b EAC, esophagectomy was associated with improved overall but not cancer-free survival. High-risk histologic features were associated with poorer survival.

Tumor size increases the risk for lymph node metastases in T1b esophageal adenocarcinoma

Background: The decision to give adjuvant therapy after endoscopic resection (ER) of T1b esophageal adenocarcinoma (EAC) in those who are not surgical candidates is largely based on a lesion’s risk of lymph node metastasis (LNM). However, risk factors for LNM in esophageal T1b EAC are not clearly defined. The aim is to evaluate risk factors for LNM in T1b EAC patients who underwent esophagectomy or ER with ≥5 years of follow-up post-procedurally. Methods: This is a retrospective analysis completed at a large tertiary referral center. Patients who underwent esophagectomy or ER with ≥5 years follow-up, with histologically proven T1b EAC between 2010 and 2017 were included. LNM was considered positive with histologically or radiologically confirmed metastasis in esophagectomy specimens or within 5 years of follow-up post-ER. Results: Forty patients (median age 69 years; 85% males) formed the study cohort of which 36 patients (90.0%) underwent esophagectomy and 4 patients who were not surgical candidates underwent ER. Seven (17.5%) patients developed LNM per study criteria. Tumor size was significantly (P=0.019) associated with the risk of LNM, and the optimal threshold at which tumor size as associated with metastasis was 3 cm. No other risk factors including lymphovascular invasion, differentiation on pathology, or infiltration growth pattern were associated with LNM. Conclusions: In T1b EAC, tumor size greater than 3 cm is the variable with the most potential as a risk factor for metastasis following surgical or ER. Adjuvant therapy should be considered in patients with tumor size greater than 3 cm.

396 Endoscopic Submucosal Dissection for Resection of T1b N0 Esophageal Cancer: Retrospective Multicenter Study

INTRODUCTION: While esophagectomy is the standard treatment for submucosal (T1b) esophageal adenocarcinoma (EAC) and squamous cell cancer (SCC), many elderly patients -the age group that esophageal cancer tends to affect- are not candidates for surgery. Endoscopic submucosal dissection (ESD) is a minimally invasive procedure that allows for en-bloc resection of early esophageal cancer and allows for precise histopathologic staging of the tumor. ESD could be curative in submucosal cancer without lymph node metastasis, and it allows for precise histopathologic staging. To evaluate the long-term outcomes of ESD in patients with EUS-staged T1b esophageal cancer. METHODS: A retrospective multicenter study was performed at three academic hospitals in the U.S. Patients who underwent ESD with a pre-procedural or post-procedural histopathologic diagnosis of T1b N0 M0 EAC or SCC were included in the study. Data was collected on demographics, tumor and procedure characteristics, procedure pathology, and follow-up. Local recurrence was confirmed by endoscopic findings and pathological analysis. Metastasis was confirmed by cross-sectional imaging. The main outcome was a composite of rate of metastasis and local recurrence. Follow-up time was defined as months from initial procedure to recurrence or last follow-up visit if recurrence-free. A time-to-event analysis was performed to evaluate recurrence. RESULTS: Fifty-two patients underwent ESD (mean age 69.6 years +/-9; 35 males) (Table 1). Based on available comorbidity data, 42% patients were not fit for surgery, as determined by an age-adjusted Charlson Comorbidity Index &gt; 6. Twenty tumors (62%) were found to be HGD or T1a on post-ESD specimen analysis, while one was staged as T2. Nineteen patients were staged as T1b after ESD. Immediately after ESD, 6 patients were referred for surgery, 3 underwent chemoradiation therapy, and 6 radiation alone (Table 2). Patients were followed for a median of 18 months, and the calculated 24-month recurrence rate was 13% (Figure 1). CONCLUSION: This multicenter trial showed that ESD for T1b esophageal cancer can be acceptable for patients who deemed not surgical candidates. However, close follow up is necessary. ESD can also serve as a staging procedure, as our data confirms inaccurate EUS-staging of T1b cancer, with 62% of tumors being down-staged to T1a, as has been previously reported.

1766 Can We Avoid Esophagectomy in T1b Esophageal Adenocarcinoma?

INTRODUCTION: Current guidelines recommend esophagectomy for Esophageal Adenocarcinoma stage T1b. There are limited data regarding multimodality therapy for Esophageal Adenocarcinoma T1b using endoscopic therapy instead of a surgical option. We present a case of EAC stage T1b patient who was successfully treated by multimodality treatments. CASE DESCRIPTION/METHODS: An 84 years old female with a history of Barrett’s esophagus underwent an endoscopy and was found to have esophageal adenocarcinoma with deep submucosal invasion (T1b) with no surrounding lymphadenopathy on EUS. She was recommended to have an esophagectomy but refused and requested a less invasive approach. She was offered endoscopic mucosal resection (EMR) and cryoablative treatments. Over the course of one year, the patient underwent several sessions of endoscopic EMR followed by cryoablative therapy. The fourth EMR specimen revealed positive deep margins involving the submucosa with lymphovascular invasion (LVI). Further sessions of cryoablation and EMR were done and she was also referred to oncology for adjuvant therapy. Oncology recommended both chemotherapy (with paclitaxel and carboplatin) as well as radiotherapy. However, the patient couldn’t tolerate more than two sessions of chemotherapy so it was discontinued while radiotherapy was continued. Few months after the patient finished radiotherapy she underwent a follow-up EGD with multiple biopsies which showed no evidence of dysplasia or malignancy. DISCUSSION: Endoscopic eradication therapy is the treatment of choice for early esophageal cancer. Surgical management for T1b is recommended given higher rates of LVI. Our case represents a successful case of eradicated adenocarcinoma using a multidisciplinary approach involving gastroenterology, thoracic surgery, medical oncology, and radiation oncology. More data will be helpful in assessing the effectiveness of a multimodality approach in treating T1b esophageal adenocarcinoma with LVI without invasive surgery.

Alternative Strategies to Esophagectomy in the Management of T1b Esophageal Adenocarcinoma

The standard of care for nonsuperficial T1b esophageal adenocarcinoma (EAC) is esophagectomy. However, esophagectomy is associated with increased morbidity and mortality. The role of endoscopic resection (ER) and adjuvant therapy for T1b EAC has not been adequately investigated. We compared survival outcomes in patients with T1b esophageal adenocarcinoma undergoing various treatment modalities. The National Cancer Database was queried for patients with T1b EAC diagnosed from 2010 to 2015 undergoing esophagectomy, ER with or without ablation, ER with radiation therapy with or without chemotherapy, and definitive chemoradiation. Patients with nodal or metastatic disease were excluded. Multivariable Cox regression and propensity score matching were used to adjust survival analyses for clinical and demographic covariates. Patients were stratified by age, sex, race, grade, Charlson-Deyo comorbidity index, and tumor size. Overall, 615 patients with T1b EAC met inclusion criteria. Patients were divided into four treatments groups: esophagectomy (n=477; 78%), ER with or without ablation (n=96; 16%), ER with radiation therapy with or without chemotherapy (n=24; 3.9%), and definitive chemoradiation (n=13; 2.1%). On multivariate analysis esophagectomy did not result in improved OS compared to ER with or without ablation (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 0.79-1.90, P = 0.36), ER with radiation with or without chemotherapy (HR=0.97, 95% CI 0.45-2.09, P=0.94), or definitive chemoradiation (HR=1.52, 95% CI 0.60-3.82, P=0.38). Covariates including age, sex, race, grade, Charlson-Deyo comorbidity index, and tumor size were not significantly associated with survival. There was no significant difference in survival between T1b esophageal adenocarcinoma patients undergoing various treatment options compared to esophagectomy alone. Thus, ER may be a reasonable alternative treatment to esophagectomy in these patients. Factors that have been known to be associated with improved survival in esophageal cancer, such as lower grade, smaller size, and younger age, may not have as much of an impact on T1b esophageal cancer patients given its early stage. Further studies are needed specifically in this population to investigate optimal therapeutic strategies that improve outcomes while minimizing toxicity.

Staging of T1 esophageal adenocarcinoma with volumetric laser endomicroscopy: a feasibility study.

Background and study aims Precise staging in T1 esophageal adenocarcinoma (EAC) is critical in determining candidacy for curative endoscopic resection. High-frequency endoscopic ultrasound (EUS) has demonstrated suboptimal accuracy in T1 EAC staging due to insufficient spatial resolution. Volumetric laser endomicroscopy (VLE) allows for high-resolution wide-field visualization of the esophageal microstructure. We aimed to investigate the role of VLE in staging T1 EAC. Patients and methods Patients undergoing endoscopic mucosal resection (EMR) were prospectively enrolled and only T1 EAC cases were included. EMR specimens were imaged using second-generation VLE immediately after resection. VLE images were analyzed for signal intensity by depth and signal attenuation (dB/mm) in both cross-sectional and en-face orientation. A decision tree model was constructed to combine measured VLE parameters and delineate diagnostic thresholds. Results Thirty EMR scans were obtained – 15 T1a specimens from 9 patients and 15 T1b specimens from 11 patients. T1b specimen VLE scans exhibited higher signal intensity ( P < 0.0001) and higher signal attenuation compared to T1a specimens ( P = 0.03). A combination of signal attenuation and signal intensity at 150 µm depth yielded optimal diagnostic thresholds and an area under the curve (AUC) of 0.77. VLE signal attenuation was significantly associated with grade of differentiation, irrespective of EAC stage. Conclusions VLE signal intensity and signal attenuation are quantitatively distinct in T1a and T1b EAC and associated with grade of differentiation. This is the first study examining the role of VLE for staging of T1 EAC and demonstrates promising diagnostic performance. With further in vivo validation, VLE may serve a role in staging superficial EAC.

Survival outcomes comparable between endoscopic resection and surgical resection for T1b esophageal adenocarcinoma.

100 Background: Current guidelines recommend esophagectomy for submucosal T1b esophageal cancer. Data regarding efficacy of endoscopic resection (ER) of T1b esophageal cancer are limited. Our goal was to compare survival outcomes of ER as opposed to conventional surgical resection (SR) in a large cohort of patients with T1b cancers from a large national database. Methods: Data were obtained from the large national database maintained by the Commission on Cancer. Patients with T1b esophageal cancers with clinical stage 1A and 1B who underwent ER and SR between 2010 and 2014 were identified using the American Joint Committee on Cancer (AJCC Version 7). Patients undergoing ER and SR were identified. Patients who underwent neoadjuvant therapy or had incomplete survival data were excluded. The primary outcome was survival for age and Deyo-Charlson comorbidity index. We also evaluated 30-Day and 90-Day Mortality outcomes. Results: There were 1071 patients with T1b esophageal cancer with complete mortality data. After selecting and excluding patients above, 141 patients were identified who underwent EET and 286 who underwent esophagectomy. Average age was 71.5 years in the ER group and 64.5 years in the SR group (p &lt; 0.001). In the group, 30-Day mortality after surgery was 1/134 (0.8%, 7 missing) compared to surgery with 30-Day mortality of 6/283 (2.1%, 3 missing) (P = 0.308). 90-Day mortality after surgery for the ER group was 3/134 (2.2%, 7 missing) compared with the surgery with 90-Day mortality of 11/281 (3.9%, 5 missing) (P = 0.377). Adjusted for age and Deyo-Charlson comorbidity index, there was a HR of 1.051 (95% CI 0.695-1.589, p = 0.815) for mortality associated with surgery compared with ER. Mean follow-up of 42.6 months for the ER group and 55.7 months for surgery group. Conclusions: Based on the data from a large national cancer data base ER seems to be comparable to SR in terms of short term (30 day and 90 day) mortality. Overall survival seems to be similar in both groups Prospectively done randomized studies comparing ER versus SR are desirable.