Early-stage Esophageal Adenocarcinoma Research Articles

Organ preservation with durvalumab-based immunotherapy in combination with chemoradiation as definitive therapy for early stage, cT1, and cT2N0 esophageal adenocarcinoma with indication for radical surgery: A prospective, multicenter study of the FLOT-AIO Gastric Cancer Group (IKF-t057/PRESTO trial).

TPS431 Background: The outcome of patients (pts) with adenocarcinomas of stomach and esophagogastric junction (GEJ) remains unsatisfactory (5-year survival rates of 24-84%), whereby surgical resection is considered as cornerstone of the curative treatment for pts with early stage esophageal adenocarcinoma (EGA), however, it is associated with mortality, morbidity and an impact on the patient’s quality of life. Recent investigations showed that in locally advanced stage EGA surgery with neoadjuvant chemoradiotherapy (CROSS trial) is beneficial over surgery alone. Further benefit was achieved for locally advanced EGA by perioperative treatment with FLOT acc. to FLOT4- trial data. Immuno-oncology (IO) therapy by using checkpoint inhibitors is approved in the palliative and adjuvant EGA situation. In this trial we aim for the organ preservation treatment of EGA pts with a combination of the anti PD-L1 antibody durvalumab- FLOT - and chemoradio-therapy. Methods: This is a multicenter, single arm, open-label, phase II trial including a total of 32 pts with T1-T2N0 EGA (including GEJ) with indication for radical surgery. Enrolled pts will receive immunotherapy with durvalumab (1500 mg Q4W) in parallel to 2 cycles FLOT (50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 calcium folinate and 2600 mg/m2 5FU, Q2W) induction followed by 3 cycles of mFOLFOX (85 mg/m2 oxaliplatin, 200 mg/m2 calcium folinate, 400 mg/m2 5FU bolus and 1600 mg/m2 5FU over 48h, Q2W) plus concomitant radiation (25 daily fractions with 2.0 Gy = Σ50Gy). 8 weeks after last treatment, pts will undergo tumor assessment by esophagogastroduodenoscopy with biopsies, endoscopic ultrasonography, and CT- or MRI-scans. Surgical resection would be offered only to pts in whom a locoregional persistence is confirmed. Pts with complete remission will enter the maintenance phase and will receive durvalumab monotherapy (1500 mg, Q4W) for a maximum of 12 cycles accompanied by regular tumor re-evaluation. Primary endpoint is the rate of cCR/pCR at time of re-evaluation. Secondary endpoints include rate of cCR/pCR at 1, 2 and 3 years, rate of salvage surgery, 90 day and 1 year mortality after start of treatment, safety and quality of life. In this exploratory trial a cCR/pCR rate of ≥75% would indicate that the study treatment should be further investigated, whereas a rate < 55% indicates no further investigation. First patient was enrolled on 2023-08-28. Currently one patient is recruited. Clinical trial information: NCT05713838 .

Optimizing management for early-stage esophageal adenocarcinoma: longitudinal results from a multidisciplinary program.

The management of early-stage esophageal cancer is nuanced. A multidisciplinary approach may optimize management through selection of candidates for surgical or endoscopic therapies. The objective of this research was to examine long-term outcomes of patients with early-stage esophageal cancer who undergo treatment with endoscopic resection or surgery. Data on patient demographics, co-morbidities, pathology results, OS and RFS were obtained for both the endoscopic resection group and esophagectomy group. Univariate analysis of OS and RFS were conducted using the Kaplan-Meier method with calculation of the log-rank test. Multivariate cox-proportional hazards models were created for OS and RFS using a hypothesis-driven approach. A multivariate logistic regression model was created to identify predictors of esophagectomy among patients undergoing initial endoscopic resection. A total of 111 patients were included. The median OS for the surgery group was 67.0months compared to 74.0months in the endoscopic resection group (log-rank p = 0.93). The median RFS for the surgery group was 109.4months compared to 63.3months in the endoscopic resection group (log-rank p = 0.0127). On multivariable analysis, patients undergoing endoscopic resection had significantly worse RFS (HR 2.55, 95% CI 1.09-6.00; p = 0.032), but equivalent OS (HR 1.03, 95% CI 0.46-2.32; p = 0.941), compared to patients undergoing esophagectomy. High-grade disease (OR 5.43, 95% CI 1.13-26.10; p = 0.035) and submucosal involvement (OR 7.75, 95% CI 1.90-31.40; p = 0.004) were identified as significant predictors of proceeding to esophagectomy. Through a multidisciplinary approach, patients with early-stage esophageal cancer achieve excellent RFS and OS. Submucosal involvement and high-grade disease place patients at increased risk for local disease recurrence; these patients may undergo endoscopic resection safely if treated with a multidisciplinary approach incorporating endoscopic surveillance and surgical consultation. Further risk-stratification models may enable better patient selection and optimization of long-term outcomes.

Long-term outcomes following successful endoscopic treatment of T1 esophageal adenocarcinoma: a multicenter cohort study

Endoscopic eradication therapy (EET) is guideline endorsed for management of early-stage (T1) esophageal adenocarcinoma (EAC). Patients with baseline high grade dysplasia (HGD) and EAC are at highest risk of recurrence following successful EET, but limited data exist on long-term (> 5 year) recurrence outcomes. We aimed to assess the incidence and predictors of long-term recurrence in a multicenter cohort of T1EAC patients treated with EET. Patients with T1 EAC achieving successful endoscopic cancer eradication with a minimum of 5-years clinical follow-up were included. The primary outcome was neoplastic recurrence, defined as dysplasia or EAC, and was characterized as early (<2 years), intermediate (2-5 years), or late (>5 years). Predictors of recurrence were assessed by time to event analysis. 84 T1 EAC patients (75 T1a, 9 T1b) with a median 9.1 years (range 5.1-18.3 years) of follow-up were included. The overall incidence of neoplastic recurrence was 2.0/100 patient years of follow up. 7 recurrences (3 dysplasia, 4 EAC) occurred after 5 years of EAC remission. 88% of recurrences were treated successfully endoscopically. EAC recurrence-related mortality occurred in 3 patients at a median of 5.2 years from EAC remission. Complete eradication of intestinal metaplasia (CE-IM) was independently associated with reduced recurrence (HR 0.13). Following successful EET of T1 EAC, neoplastic recurrence occurred after 5 years in 8.3% of cases. Careful long-term surveillance should be continued in this patient population. CE-IM should be the therapeutic endpoint for EET.

Abstract 3130: Extrachromosomal DNA in the cancerous transformation of Barrett’s esophagus

Abstract Oncogene amplification on extrachromosomal DNA (ecDNA) drives rapid tumor evolution, treatment resistance, and poor outcomes for patients. Computational tools can detect ecDNA in whole-genome sequencing (WGS) data from biopsies. However, the lack of longitudinal studies tracking patients from pre-cancer to cancer have made it difficult to determine how ecDNAs contribute to the malignant transformation. Two independent surveillance studies of Barrett’s esophagus (BE) patients enabled us to study this transition, as BE is the precursor lesion of esophageal adenocarcinoma (EAC). The studies included a longitudinal case-control study and an independent, cross-sectional surveillance cohort, both with histological correlatives, providing an unprecedented opportunity to study the role of ecDNA in the transition of BE to EAC. We analyzed WGS data from 206 patients in a cross-sectional surveillance cohort from Cambridge University UK, with biopsy-validated BE, including 42 patients who never developed high-grade dysplasia (HGD) or EAC during multi-year follow-ups, 25 patients with HGD, 51 patients with early-stage EAC, and 88 patients with late-stage EAC. ecDNA frequency increased between early-stage EAC (24%) and late-stage EAC (43%), suggesting continual ecDNA formation during cancer progression. We additionally analyzed WGS and histology data collected from multi-regional sampling of BE and EAC tissue at two time points from 80 BE patients in an observational case-control study at the Fred Hutchinson Cancer Center (FHCC), where 40 of the patients developed BE-associated EAC during the study and 40 did not. Among FHCC patients, 33% who developed EAC had at least one esophageal biopsy with ecDNA prior to, or at EAC diagnosis. In biopsies collected before cancer diagnosis, ecDNA presence in the biopsy was enriched among patients who later developed EAC compared to patients who did not. When linked to histology data, ecDNA-positive biopsies associated with worsened histological states before cancer diagnosis (p=0.015), and also at cancer diagnosis (p=0.037), with the pre-cancer timepoint being on average 2.1 years prior to cancer diagnosis. The ecDNAs had diverse collections of oncogenes and immunomodulatory genes, and showed higher copy number states than other focal amplification types. Furthermore, ecDNAs showed increasing copy number and structural complexity in more advanced disease stages highlighting their positive selection and ongoing structural evolution. In both FHCC and Cambridge cohorts, we found an association of TP53 loss with ecDNA formation demonstrating the role of prior genomic instability to form ecDNA. In total, our findings illustrate that oncogenic ecDNA can develop early in the malignant transformation, and that they are tied to worsening patient disease status. Citation Format: Jens Luebeck, Alvin W. Ng, Patricia C. Galipeau, Xiaohong Li, Annalise Katz-Summercorn, Hoon Kim, Sriganesh Jammula, Yudou He, Roel Verhaak, Carlo C. Maley, Ludmil B. Alexandrov, Rebecca C. Fitzgerald, Thomas G. Paulson, Howard Y. Chang, Sihan Wu, Vineet Bafna, Paul S. Mischel. Extrachromosomal DNA in the cancerous transformation of Barrett’s esophagus [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3130.

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

Socioeconomic Disparities Affect Outcomes in Early-Stage Esophageal Adenocarcinoma: A SEER Analysis

Socioeconomic determinants of health are understudied in early stage esophageal adenocarcinoma. We aimed to assess how socioeconomic status influences initial treatment decisions and survival outcomes in patients with T1a esophageal adenocarcinoma. We performed an observational study using the 2018 submission of the Surveillance, Epidemiology, and End Results-18 database. A total of 1526 patients from 2004 to 2015 with a primary T1aN0M0 esophageal adenocarcinoma were subdivided into 3 socioeconomic tertiles based on their median household income. Endoscopic trends over time, rates of endoscopic and surgical treatment, 2- and 5-year overall survival, cancer-specific mortality, and non-cancer-specific mortality were calculated. Statistical analysis was performed using R-studio. Patients within the lowest median household income tertile ($20,000-$54,390) were associated with higher cancer-specific mortality at 2 years (P < .01) and 5 years (P < .02), and lower overall survival at 2 and 5 years (P < .01) compared with patients in higher income tertiles. Patients with a higher income had a decreased hazard ratio for cancer-specific mortality (hazard ratio, 0.66; 95% CI, 0.45-0.99) in a multivariate Cox proportional hazards regression model. Patients within the higher income tertile were more likely to receive endoscopic intervention (P < .001), which was associated with improved cancer-specific mortality compared with patients who received primary surgical intervention (P= .001). The South had lower rates of endoscopy compared with other regions. Lower median household income was associated with higher rates of cancer-specific mortality and lower rates of endoscopic resection in T1aN0M0 esophageal adenocarcinoma. Population-based strategies aimed at identifying and rectifying possible etiologies for these socioeconomic and geographic disparities are paramount to improving patient outcomes in early esophageal cancer.

Impact of neoadjuvant chemoradiation in early stage esophageal and gastro-esophageal junction adenocarcinoma

Background: Esophageal adenocarcinoma (EAC) poses a therapeutic challenge due to late-stage presentation, requiring multimodal management, with ensuing high-mortality, despite our best efforts. Current guidelines recommend use of neoadjuvant chemoradiation on patients with T1a EAC patients due to reported increased rates of R0 resection attained. However, recent literature has challenged the morbidity and survival benefits of the use of neoadjuvant radiation.

Detection of Early Esophageal Neoplastic Barrett Lesions with Quantified Fluorescence Molecular Endoscopy Using Cetuximab-800CW.

Esophageal adenocarcinoma causes 6% of cancer-related deaths worldwide. Near-infrared fluorescence molecular endoscopy (NIR-FME) uses a tracer that targets overexpressed proteins. In this study, we aimed to investigate the feasibility of an epidermal growth factor receptor (EGFR)-targeted tracer, cetuximab-800CW, to improve detection of early-stage esophageal adenocarcinoma. Methods: We validated EGFR expression in 73 esophageal tissue sections. Subsequently, we topically administered cetuximab-800CW and performed high-definition white-light endoscopy (HD-WLE), narrow-band imaging, and NIR-FME in 15 patients with Barrett esophagus (BE). Intrinsic fluorescence values were quantified using multidiameter single-fiber reflectance and single-fiber fluorescence spectroscopy. Back-table imaging, histopathologic examination, and EGFR immunohistochemistry on biopsy samples collected during NIR-FME procedures were performed and compared with invivo imaging results. Results: Immunohistochemical preanalysis showed high EGFR expression in 67% of dysplastic tissue sections. NIR-FME visualized all 12 HD-WLE-visible lesions and 5 HD-WLE-invisible dysplastic lesions, with increased fluorescence signal in visible dysplastic BE lesions compared with nondysplastic BE as shown by multidiameter single-fiber reflectance/single-fiber fluorescence, reflecting a target-to-background ratio of 1.5. Invisible dysplastic lesions also showed increased fluorescence, with a target-to-background ratio of 1.67. Immunohistochemistry analysis showed EGFR overexpression in 16 of 17 (94%) dysplastic BE lesions, which all showed fluorescence signal. Conclusion: This study has shown that NIR-FME using cetuximab-800CW can improve detection of dysplastic lesions missed by HD-WLE and narrow-band imaging.

Abstract P058: Rapid, noninvasive, office-based, esophageal cell collection for early detection of esophageal precancer and cancer

Abstract Purpose: Esophageal Adenocarcinoma (EAC) is the second most lethal (&amp;lt;20% five-year survival) and fastest growing (&amp;gt;500% increase in incidence over 40 years) cancer in the U.S. All EAC is believed to arise from a metaplastic esophageal precancer, Barrett’s Esophagus (BE), in at-risk patients with gastroesophageal reflux disease (GERD). Non-dysplastic BE can be monitored for progression to dysplastic BE, which can be ablated endoscopically, reliably halting progression to EAC. Since mortality is high even in early stage EAC (&amp;lt;50% five-year survival), clinical practice guidelines recommend BE screening in GERD patients with multiple risk factors. Since, endoscopic BE screening has failed (&amp;lt;10% compliance with guidelines), recently updated guidelines from both the American College of Gastroenterology and American Gastroenterological Association now support non-endoscopic biomarker screening as an acceptable alternative to endoscopy. EsoCheck®, a noninvasive swallowable balloon capsule catheter device, is the only FDA 510(k)-cleared esophageal cell collection device which permits anatomically targeted and protected sampling of distal esophageal mucosal cells. The sample is collected in a less than five-minute office procedure, without sedation or anesthesia, and sent to a central laboratory for molecular biomarker testing. We report our initial clinical experience using EsoCheck® for collection of esophageal cells in outpatient test centers. Experimental Design: 687 patients underwent EsoCheck® distal esophageal cell sampling by a trained nurse practitioner (average sampled length 5 cm). Patient tolerance was rated on a five-point scale for gag reflex (GR) severity: 1 = no GR; 2 = minimal GR; 3 = mild GR; 4 = severe GR; and 5 = worst GR therefore collection could not be completed. DNA was extracted using the QIAamp DNA Mini kit and quantitated using Qubit™ dsDNA Assay kit. Cytologic assessment using H&amp;E staining was performed on 15 samples. Results: 98% of patients successfully completed the procedure. 88% tolerated it well (rating ≤ 3); 10% experienced severe gagging (rating 4); and only 2% were unable to complete the procedure (rating 5). Average procedure time was 3.5 min (range: 1 min to 15 min). Average DNA yield was 868 ng (range: 0 ng to 19 µg) and 92% yielded at least 100 ng. The samples undergoing cytologic assessment averaged 500,000 cells (range: 100,000 to 2.5 million). Conclusion: Rapid, noninvasive, office-based, anatomically-targeted, and protected sampling of distal esophageal mucosal cells using EsoCheck® can be successfully performed in nearly all patients and is broadly well-tolerated. Cellular and DNA yields were very good and are expected to improve with clinical experience and assay optimization. When combined with a highly sensitive molecular biomarker test, the EsoCheck® device has the potential to significantly improve BE screening compliance and prevent EAC deaths. Citation Format: Suman M. Verma, Ivy T. Le, Abhisek B. Ghosal, Marci L. Hageman, Victoria T. Lee, Brian J. deGuzman, Lishan Aklog. Rapid, noninvasive, office-based, esophageal cell collection for early detection of esophageal precancer and cancer. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P058.

The role of endoscopic resection in early-stage esophageal adenocarcinoma: Esophagectomy is associated with improved survival in patients presenting with clinical stage T1bN0 disease

BackgroundStudies evaluating endoscopic resection for early-stage (cT1N0M0) esophageal adenocarcinoma include small numbers of patients with T1b tumors. The role of endoscopic resection in esophageal adenocarcinoma remains incompletely defined. MethodsWe queried the National Cancer Database to identify patients presenting with esophageal adenocarcinoma between 2010 and 2017. Those treated with neoadjuvant chemoradiotherapy and endoscopic ablation were excluded. Patients undergoing endoscopic resection for cT1a and cT1b tumors were separately 1:1 propensity matched for relevant demographic and tumor factors to those undergoing esophagectomy for disease of like clinical stage. The Kaplan-Meier method was used to compare 5-year overall survival for matched cohorts. ResultsA total of 3,157 patients met the inclusion criteria. Of these patients, 2,024 (64.1%) had cT1a and 1133 (35.9%) had cT1b disease. Among those with cT1a tumors, 461 (22.8%) underwent esophagectomy, 1,357 (67.0%) endoscopic resection, and 206 (10.2%) treatment with chemoradiotherapy alone. Among those with cT1b tumors, 649 (57.3%) underwent esophagectomy, 293 (25.9%) endoscopic resection, and 191 (16.8%) chemoradiotherapy. On unadjusted comparison, patients treated for esophageal adenocarcinoma with chemoradiotherapy had a lower rate of overall survival than those treated with endoscopic resection or esophagectomy (26.1% vs 73.1% vs 75.5%, P < .001). On comparison of matched cohorts, patients undergoing endoscopic resection for cT1b tumors demonstrated lower rates of overall survival than those undergoing esophagectomy (60.6% vs 74.1%, P = .0013), whereas those undergoing endoscopic resection for cT1a tumors demonstrated rates of overall survival statistically similar to those undergoing esophagectomy (77.8% vs 80.2%, P = .75). ConclusionEsophagectomy is associated with improved overall survival relative to endoscopic resection in patients presenting with cT1bN0M0 but not in those with cT1a esophageal adenocarcinoma.

Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer

BackgroundThe surveillance and therapy of early-stage cancer would be better for patients’ prognosis. However, the extreme trace amount of tissue samples in different stages have limited in portraying the characterization of early-stage cancer. Therefore, we focused on and presented comprehensive proteomic and phosphoproproteomic profiling of the trace FFPE samples from early-stage gastrointestinal cancer, and then explored the potential biomarkers of early-stage gastrointestinal cancer.MethodsIn this study, a quantitative proteomic method with chromatography with mass spectrometry (LC-MS/MS) was used to analyse the proteomic difference between the trace early-stage esophageal squamous cell carcinoma (EESCC) and early-stage duodenum adenocarcinoma cancer (EDAC).ResultsWe identified ~ 6000 proteins and > 10,000 phosphosites in single trace FFPE samples. Comparative analysis disclosed the diverse proteomic features of tumor tissues compared with paired normal tissue of EESCC and EDAC, and revealed the difference of EESCC and EDAC was derived from their origin normal tissue. The distinct separation of EESCC and EDAC illustrated the functions of cell cycle (RB1 T373, EGFR T693) in EESCC, and the positive impacts of apoptosis, metabolic processes (MTOR and MTOR S1261) in EDAC. Furthermore, we deconvoluted the immune infiltration of early-stage gastrointestinal cancer, in which higher immune cell signatures were detected in EDAC, and showed the specific cytokines in EESCC and EDAC. We performed kinases-substates relationship analysis and elucidated the specific proteomic kinase characterization of EESCC and EDAC, and proposed the medicative effects and corresponding drugs for EESCC and EDAC at the clinic.ConclusionWe disclosed the specific immune characterization of the early-stage gastrointestinal cancer, and presented potential makers of EESCC (EGFR, PDGFRB, CDK4, WEE1) and EDAC (MTOR, MAP2K1, MAPK3). This study represents a major stepping stone towards investigating the carcinogenesis mechanism of gastrointestinal cancer, and providing a rich resource for medicative strategy in the clinic.Graphical

Expression of Neighbor of Punc E11 (NOPE) in early stage esophageal adenocarcinoma is associated with reduced survival

Current recommendations suggest neoadjuvant treatment in node-positive esophageal cancer or tumors staged T3 and upwards but some T2 N0 patients might benefit from neoadjuvant therapy. It is of clinical relevance to identify this subgroup. Loss of epithelial apicobasal polarity is a key factor in the development of invasive capabilities of carcinoma. The oncofetal stem/progenitor cell marker NOPE is expressed in adult depolarized murine hepatocytes and in murine/human hepatocellular carcinoma. We analyzed NOPE expression in 363 patients with esophageal adenocarcinoma using an RNA Scope Assay on a tissue microarray and correlated results with clinical data. Median follow-up was 57.7 months with a 5-year survival rate of 26.6%. NOPE was detectable in 32 patients (8.8%). In pT1/2 stages, NOPE expression was associated with a significantly reduced median OS of 6.3 months (95% CI 1.2–19.4 months), the median OS is not reached in the NOPE-negative group (calculated mean OS 117.1 months) (P = 0.012). In advanced tumor stages, a NOPE dependent survival difference was not detected. This is the first report of NOPE expression demonstrating a prognostic value in esophageal cancer. Early stage, NOPE positive patients are at a high risk of tumor progression and may benefit from neoadjuvant treatment analogous to advanced stage cancer.

Long-term outcomes of endoscopic mucosal resection for early-stage esophageal adenocarcinoma.

With growing application of endoscopic therapy for early-stage esophageal cancer, we sought to review our experience of endoscopic mucosal resections (EMRs). The aim of our study was to understand the natural course of these patients, especially with positive margins. A prospectively maintained database of all patients undergoing endoscopic therapies at Georgetown University Hospital for esophageal cancer was used for the analysis between 2010 and 2020. Of 80 patients in the EMR database, 35 were performed as index cases for esophageal adenocarcinoma. Majority (74.3%) had a pre-treatment ultrasound confirming absence of regional adenopathy. There were no post-EMR bleeding or perforation events requiring re-intervention. Complete R0 resection was achieved in 22/35 (62.9%) after initial EMR. Thirteen patients had positive margins. Of these 13 patients, only 7 patients underwent repeat endoscopic resection, 2 underwent subsequent esophagectomy, 2 received definitive radiation given poor surgical candidacy, and 2 were lost to follow-up. Overall and 5-year survival of all patients undergoing EMR was 67.9months and 85%, respectively. Subset analysis of the 13 patients with R1 resection demonstrated an overall survival of 49.2months and 60% 5-year survival vs overall survival of 78.9months and 93% 5-year survival for R0 resection. At a median follow-up of 60.5months, cancer recurrence occurred in 3 patients. All of them were successfully managed with repeat EMR. Endoscopic resections represent a safe and effective treatment for early-stage esophageal cancer. Patients with high-risk features should be counseled to undergo an esophagectomy if they are operable candidates.

Defining low-risk lesions in early-stage esophageal adenocarcinoma

ObjectiveAs endoscopic approaches become more widely used to treat early-stage esophageal cancer, reliably identifying patients with less-aggressive tumors is paramount. We sought to identify risk factors for recurrence in patients with completely resected T1 esophageal adenocarcinoma. MethodsWe retrospectively analyzed a single-institutional database for all patients with completely resected pathologic T1 esophageal adenocarcinoma (1996-2016). Risk factors for recurrence were identified using competing-risk regression methods. Risk stratification was performed on the basis of known preoperative clinicopathologic factors; this model's discriminative power for overall survival was evaluated using a Cox proportional hazards model. ResultsOf 243 patients, 32 experienced recurrence. At a median follow-up among survivors of 4 years (range, 0.05-19 years), the 5-year cumulative incidence of recurrence was 15%, and median time to recurrence was 2 years (range, 0.26-6.13 years). On univariable analysis, submucosal invasion, N1 disease, poor differentiation, tumor length, lymphovascular invasion, and multicentricity were significantly associated with recurrence. On multivariable analysis, N1 disease (hazard ratio, 2.93; 95% confidence interval, 1.17-7.34; P = .022) and tumor length (hazard ratio, 1.44; 95% confidence interval, 1.12-1.86; P = .004) were independently associated with recurrence. Risk stratification showed that patients without lymphovascular invasion and a with median tumor length of 0.8 cm (range, 0.10-1.70 cm) had a <10% risk of recurrence and improved survival. ConclusionsPathologic T1 tumors have a 5-year cumulative incidence of recurrence of 15%. Nodal involvement and tumor length were independent risk factors for recurrence, whereas tumors <2 cm in length without lymphovascular invasion were associated with a low risk of recurrence.

Artificial Intelligence and Its Role in Identifying Esophageal Neoplasia.

Randomized trials have demonstrated that ablation of dysplastic Barrett's esophagus can reduce the risk of progression to cancer. Endoscopic resection for early stage esophageal adenocarcinoma and squamous cell carcinoma can significantly reduce postoperative morbidity compared to esophagectomy. Unfortunately, current endoscopic surveillance technologies (e.g., high-definition white light, electronic, and dye-based chromoendoscopy) lack sensitivity at identifying subtle areas of dysplasia and cancer. Random biopsies sample only approximately 5% of the esophageal mucosa at risk, and there is poor agreement among pathologists in identifying low-grade dysplasia. Machine-based deep learning medical image and video assessment technologies have progressed significantly in recent years, enabled in large part by advances in computer processing capabilities. In deep learning, sequential layers allow models to transform input data (e.g., pixels for imaging data) into a composite representation that allows for classification and feature identification. Several publications have attempted to use this technology to help identify dysplasia and early esophageal cancer. The aims of this reviews are as follows: (a) discussing limitations in our current strategies to identify esophageal dysplasia and cancer, (b) explaining the concepts behind deep learning and convolutional neural networks using language appropriate for clinicians without an engineering background, (c) systematically reviewing the literature for studies that have used deep learning to identify esophageal neoplasia, and (d) based on the systemic review, outlining strategies on further work necessary before these technologies are ready for "prime-time," i.e., use in routine clinical care.

Inaccurate pretreatment staging can impact survival in early stage esophageal adenocarcinoma.

Given the survival advantage of neoadjuvant treatment for locally advanced esophageal cancer, accurate clinical staging is necessary. The aim of this study was to assess the clinical (c) and pathologic (p) staging concordance rates for presumably early stage esophageal adenocarcinoma patients that had upfront esophagectomy (UFE) and evaluate if survival (OS) was negatively affected by inaccurate preoperative staging and subsequent treatment selection. An NCDB retrospective review of nonmetastatic esophageal adenocarcinoma patients that had UFE. The rates of concordance between c and p staging system and OS were calculated. Of 2775 patients, most patients presented with cN0 (82.8%) and cT1 tumors (53.6%). The overall concordance between c and p staging was 78.8% for T-classification (moderate agreement; weighted κ = 0.729; P < .001) and 78.8% for N-classification (weak agreement; weighted κ = 0.448; P < .001). Patients that were upstaged due to a lack of concordance between T-classification had decreased 5- and 10-year OS (30% and 16%, P < .001) and those upstaged due to discordant N-classification had decreased 5- and 10-year OS (28% and 23%, P < .001)." Preoperative staging of esophageal adenocarcinoma has moderate reliability and accuracy for predicting pT and pN classification. Up to 25% of patients have discordant clinical and pathological staging, which impacts OS.

Radiofrequency Ablation of Barrett's Esophagus: Have We Gone Too Far, or Not Far Enough?

Barrett's esophagus (BE) is a premalignant condition of the esophagus associated with an increased risk for esophageal adenocarcinoma (EAC). Radiofrequency ablation (RFA) is a safe and effective first-line treatment for dysplastic BE and early stage EAC. This report reviews clinically relevant evidence published over the last 3years regarding RFA for BE. Our use of this technology has simultaneously gone too far, in that many patients who may not derive a benefit from these treatments are receiving them, and not far enough, in that many patients who would be eligible for ablative therapy never undergo screening exams to assess them for dysplastic BE, or do not have endoscopic therapy considered part of the treatment of superficial invasive cancer. Research to better identify patients with BE, risk stratify those patients, improve the quality of RFA treatment, and inform surveillance practices has the potential to optimize the benefit of RFA, and minimize the harms, costs, and risks.

Treatment of early stage (T1) esophageal adenocarcinoma: Personalizing the best therapy choice

Treatment of early stage (T1) esophageal adenocarcinoma: Personalizing the best therapy choice

AGA Clinical Practice Update on the Utility of Endoscopic Submucosal Dissection in T1b Esophageal Cancer: Expert Review

AGA Clinical Practice Update on the Utility of Endoscopic Submucosal Dissection in T1b Esophageal Cancer: Expert Review

Detection of Circulating Tumor DNA in Plasma: A Potential Biomarker for Esophageal Adenocarcinoma

Recent literature has demonstrated the potential of "liquid biopsy" and detection of circulating tumor (ct)DNA as a cancer biomarker. However, to date there is a lack of data specific to esophageal adenocarcinoma (EAC). This study was conducted to determine how detection and quantification of ctDNA changes with disease burden in patients with EAC and evaluate its potential as a biomarker in this population. Blood samples were obtained from patients with stage I to IV EAC. Longitudinal blood samples were collected from a subset of patients. Imaging studies and pathology reports were reviewed to determine disease course. Tumor samples were sequenced to identify mutations. Mutations in plasma DNA were detected using custom, barcoded, patient-specific sequencing libraries. Mutations in plasma were quantified, and associations with disease stage and response to therapy were explored. Plasma samples from a final cohort of 38 patients were evaluated. Baseline plasma samples were ctDNA positive for 18 patients (47%) overall, with tumor allele frequencies ranging from 0.05% to 5.30%. Detection frequency of ctDNA and quantity of ctDNA increased with stage. Data from longitudinal samples indicate that ctDNA levels correlate with and precede evidence of response to therapy or recurrence. ctDNA can be detected in plasma of EAC patients and correlates with disease burden. Detection of ctDNA in early-stage EAC is challenging and may limit diagnostic applications. However, our data demonstrate the potential of ctDNA as a dynamic biomarker to monitor treatment response and disease recurrence in patients with EAC.