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 .

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.

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.

Long-term fear of cancer recurrence in patients treated endoscopically for early Barrett's neoplasia.

Previous studies on fear of cancer recurrence after endoscopic treatment for early Barrett's neoplasia focused on fear during a relatively short period after the intervention. The aim of this study was to explore whether fear of cancer (recurrence) persists during long-term follow-up in patients treated endoscopically for Barrett's neoplasia compared to patients treated surgically for a more advanced stage of esophageal adenocarcinoma. Participants previously participated in a prospective longitudinal study investigating quality of life and fear of cancer recurrence and were treated endoscopically for early Barrett's neoplasia (high-grade dysplasia-T1sm1N0M0) or surgically for a more advanced esophageal adenocarcinoma (T1N0M0-T3N1M0). For the present study, participants were again invited to complete a set of questionnaires including the fear of cancer recurrence scale (FORS), worry for cancer scale (WOCS), and the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS Anxiety). Thirty-nine patients were eligible in the endoscopy group and 28 in the surgical group. The median time between the baseline measurement (original study) and the long-term follow-up assessment was 4 years (interquartile range 3-5 years). Fear and worry for cancer recurrence and general anxiety diminished over time in both treatment groups. However, at long-term follow-up, endoscopically treated patients had significantly higher levels of worry for cancer and general anxiety than surgically treated patients. Fear of cancer recurrence did not significantly differ between endoscopically and surgically treated patients. We found that worry and fear of cancer recurrence and general anxiety in endoscopically treated patients declined over time, but not as much as in surgically treated patients.

Tumor immune microenvironment in therapy-naive esophageal adenocarcinoma could predict the nodal status.

Currently, preoperative staging of esophageal adenocarcinoma (EAC) has modest reliability and accuracy for pT and pN stages prediction, which heavily affects overall survival. The interplay among immune checkpoints, oncogenes, and intratumoral and peritumoral immune infiltrating cells could be used to predict loco-regional metastatic disease in early EAC. We prospectively evaluated immune markers expression and oncogenes status as well as intratumoral and peritumoral immune infiltrating cells populations in esophageal mucosa samples obtained from neoadjuvant therapy-naïve patients who had esophagectomy for EAC. Vascular invasion and high infiltration of lamina propria mononuclear cells resulted associated with nodal metastasis. Low infiltration of activated CD8+ CD28+ T cells was observed in both intratumoral and peritumoral mucosa of patients with nodal metastasis. Low levels of CD69, MYD88, and TLR4 transcripts were detected in the intratumoral specimen of patients with lymph node involvement. Receiver operating characteristic curve analysis showed good accuracy for detecting nodal metastasis for all the markers tested. Significant lower infiltration of CD8 T cells and M1 macrophages and a lower expression of CD8A, CD8B, and TBX21 were found also in Esophageal Adenocarcinoma TCGA panCancer Atlas in the normal tissue of patients with nodal metastasis. Our data suggest that immune surveillance failure is the main driver of nodal metastasis onset. Moreover, nodal metastasis containment also involves the immune microenvironment of the peritumoral healthy tissue.

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.

Effect of adding immunotherapy to standard of care on survival in patients with esophageal cancer: Analysis of NCDB database.

325 Background: Combined immuno-chemotherapy has been shown to be more effective than chemotherapy alone in advanced esophageal cancer. However, the association of immunotherapy and overall survival (OS) of patients with esophageal cancer, regardless of stage and combined therapy, is unknown. The objective is to explore the association of immunotherapy with OS in patients with all stage esophageal adenocarcinoma or squamous cell carcinoma who received any treatment. Subset analysis was conducted on OS for patients who received chemoradiation with and without immunotherapy. Methods: This study included 85,900 adult patients in the National Cancer Database diagnosed between 2004 and 2017 with stage I-IV esophageal adenocarcinoma or squamous cell carcinoma. The association of immunotherapy with OS was assessed with Cox proportional hazards regression, adjusted for age at diagnosis, race, sex, stage, histology, Charlson score, education, income, insurance, hospital type, place of living, region, distance to facility, year of diagnosis and treatment modality. Results: Of 85,900 patients, 69,264 (81%) were men, 85,159 (88%) were White and 7,875 (9%) were Black. The median (range) age at diagnosis was 64 (18-90) years. Overall, 1990 (2.3%) received immunotherapy. Immunotherapy did not improve median OS in stage I-II (31 vs 27M, p &gt;.05) but improved median OS in stage III (from 18 to 30 M, p &lt;.0001) and IV (from 8 to 14 M p &lt;.0001). In the multivariable COX analysis, patients who received immunotherapy had significantly improved OS compared with no immunotherapy (HR 0.756; 95% CI 0.713-0.801; P =.001). Treatment with CRT without surgery plus immunotherapy was associated with significantly improved OS compared with CRT alone (HR 0.817; 95% CI 0.745-0.896; P =.001). Interestingly, addition of immunotherapy to CRT with surgery did not improve OS compared with CRT and surgery. After stratified by stage, immunotherapy was found to be associated with improved OS only in stage IV patients either in all patients (HR 0.685; 95% CI 0.641-0.731, p &lt; 0.001) or in patients who received CRT without surgery (HR 0.758; 95% CI 0.682-0.841). Conclusions: In this study, the addition of immunotherapy to standard of care, especially chemoradiation without surgery was associated with improved OS compared with standard of care (or chemoradiation) alone in patients with advanced stage esophageal cancer.

Favorable effect of endoscopic reassessment of clinically staged T2 esophageal adenocarcinoma: a multicenter prospective cohort study

BACKGROUND : Clinical tumor stage of esophageal adenocarcinoma (EAC) is determined by endoscopic ultrasound and/or computed tomography scan, which have low accuracy for stages T1 and T2, potentially leading to overtreatment. We aimed to assess the proportion of cT2 EACs downstaged to cT1 after endoscopic reassessment (ERA) by an experienced interventional endoscopist. METHODS : We performed a prospective multicenter cohort study. Patients with cT2N0M0 EAC were included and underwent ERA. The primary outcome was proportion of cT2 EACs downstaged to cT1 after ERA. RESULTS : 15/25 included patients (60 %) were downstaged from cT2 to cT1 EAC after ERA and underwent attempted endoscopic resection. Endoscopic resection was aborted in 3/15 patients because of tumor invasion into the muscle layer; all three underwent successful surgical resection. Endoscopic resection was successful in 12/15 patients (80 %), all of whom had pT1 tumors. Overall, 10/25 (40 %) were treated with endoscopic resection alone. CONCLUSIONS : ERA downstaged about half of the cT2 tumors to cT1, rendering them suitable for endoscopic resection. ERA had substantial clinical impact on therapeutic management, preventing overtreatment in 40 % of patients.

Endoscopic ultrasound for staging of esophageal and gastric cancers

Background: Gastric adenocarcinoma (GAC) and esophageal adenocarcinoma (EAC) are one of the leading causes of mortality from gastrointestinal cancer worldwide. Endoscopic ultrasound (EUS) has proved to be a valuable tool for preoperative staging of GAC and EAC in selected cases. Objective: The aim of this study was to evaluate the usefulness of EUS for staging of EAC and GAC and selecting patients who are candidates for neoadjuvant therapy, as compared with the previous stage before the implementation of EUS, in a surgical center in Argentina. Material and methods: Consecutive patients with EAC and GAC between 2013-2019 were included. Patients with criteria of unresectable cancer or who underwent emergency surgery were excluded. The sample was divided into four groups G1 and G2 (EAC with and without EUS, respectively) and G3 and G4 (GAC with and without EUS, respectively). The clinical and anatomopathological variables and survival were evaluated in all the groups. Results: A total of 89 patients were included, 40 with EAC (30 in G1 and 10 in G2, and 49 with GAC, 20 in G3 and 29 in G4. Of the patients undergoing EUS staging in G1, 23 (75%) received neoadjuvant therapy vs. 2 patients in G2 (20%) (P ≤ 0.005). Eight patients (40%) in G3 and 2 (7%) in G4 received perioperative chemotherapy (P ≤ 0.005). Lymph node metastases were observed in 9 (30%) of surgical specimens of EAC in G1 and in 60% in G2 (P ≤ 0.005), and in 45% in G3 and G4. After a mean follow-up of 36 months (6-72), we observed a non-significant trend toward higher overall survival and disease-free survival in patients undergoing EUS staging. Conclusion: EUS for preoperative staging pf EAC and GAC is a useful tool. Although the use of EUS use may be a challenging task in many centers in Argentina, future efforts are needed to include this test in selected cases for staging patients with these types of cancers

Current research progress in the role of reactive oxygen species in esophageal adenocarcinoma.

In the past few decades, the incidence of esophageal adenocarcinoma has increased by six-fold in western countries, as the proton pump inhibitor targeting the gastric acid reflux has failed to control the disease. It is currently suggested that deoxycholic acid reflux leads to esophageal adenocarcinoma. As an inflammation-related cancer, the formation and progression of esophageal adenocarcinoma are closely related to the concentration of reactive oxygen species (ROS). Meanwhile, the critical developmental stage of esophageal adenocarcinoma involves characteristic pathological changes in which the distal esophageal squamous epithelial cells are replaced by intestinal columnar epithelial cells, suggesting the involvement of cancer stem cells. Thus, esophageal adenocarcinoma is a good model to study the interplay between ROS and stem cells in cancer. Until now, some important questions related to ROS in esophageal adenocarcinoma remain unanswered. For example, the molecular mechanism by which deoxycholic acid induces malignant transformation in esophageal adenocarcinoma remains unclear. In addition, whether ROS are involved in the induction of cancer stem cell formation by chemotherapeutic drugs and deoxycholic acid stimulation in esophageal adenocarcinoma remains to be further explored. This review summarizes current research progress on ROS and stemness activity, regulation of ROS by stanniocalcin-1 (STC1)/uncoupling protein 2 (UCP2), and inspiration for ROS in esophageal adenocarcinoma to guide further research and provide insight into the clinical treatment of esophageal adenocarcinoma.

Clinical Risk Prediction Model for Neoadjuvant Therapy in Resectable Esophageal Adenocarcinoma.

Clinical staging with endoscopic ultrasound (EUS) and positron emission tomography (PET) is used to identify esophageal adenocarcinoma (EAC) patients with locally advanced disease and therefore, benefit from neoadjuvant therapy. However, EUS is operator dependent and subject to interobserver variability. Therefore, we aimed to identify clinical predictors of locally advanced EAC and build a predictive model that can be used as an adjunct to current staging methods. This was a cross-sectional study of patients with EAC who underwent preoperative staging with EUS and PET scan followed by definitive therapy at our institution from January 2011 to December 2017. Demographic data, symptoms, endoscopic findings, EUS, and PET scan findings were obtained. Four hundred and twenty-six patients met the study criteria, of which 86 (20.2%) patients had limited stage EAC and 340 (79.8%) had locally advanced disease. The mean age was 65.4±10.3 years of which 356 (83.6%) were men and 393 (92.3%) were White. On multivariable analysis, age (above 75 or below 65 y), dysphagia [odds ratio (OR): 2.84], weight loss (OR: 2.06), protruding tumor (OR: 2.99), and tumor size >2 cm (OR: 3.3) were predictive of locally advanced disease, while gastrointestinal bleeding (OR: 0.36) and presence of visible Barrett's esophagus (OR: 0.4) were more likely to be associated with limited stage. A nomogram for predicting the risk of locally advanced EAC was constructed and internally validated. We constructed a nomogram to facilitate an individualized prediction of the risk of locally advanced EAC. This model can aid in decision making for neoadjuvant therapy in EAC.

Incidence trends of esophageal cancer in the Czech Republic by histological subtype and stage and prescription rate of acid suppressing drugs

BackgroundIncidence of esophageal adenocarcinoma (EAC) associated with gastroesophageal reflux disease has increased substantially in developed countries during the past decades. We aimed to analyze trends in incidence of esophageal cancer (EC) by histological subtypes and trends in acid suppressing drugs prescription in the Czech Republic. MethodsThe incidence of EC by histological subtypes, sex, and stage from 1984–2017 was examined using data from the Czech National Cancer Registry. Defined daily doses of acid inhibiting drugs were analyzed from annual reports by the State Institute for Drug Control. ResultsAge standardized incidence of EAC in men increased annually by 4.88 % with 95 % confidence interval (CI) (4.32, 5.45) from 1984 to 2017, and by 5.11 % (95 % CI, 4.02, 6.20) in women. Squamous cell carcinoma increased annually by 5.52 % (95 % CI, 2.49, 8.64) from 1984 to 1994 with subsequent slower increase by 0.87 % (95 % CI, 0.25, 1.50) from 1994 to 2017. It still represents 50 % of all EC in 2017. The comparable early stages of EAC showed similar annual percentage change of 5.77 %. From 2001 to 2018 the use of proton pump inhibitors increased dramatically from 6.8 to 72.9 defined daily doses per 1000 inhabitants. ConclusionThe incidence of EAC is still increasing in the Czech Republic, however it represents less than half of ECs. The incidence of squamous cell carcinoma is relatively stable. Broad use of acid suppressing drugs did not seem to impact the incidence of EAC even in early stages.

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

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.

Ensemble of Deep Convolutional Neural Networks for Classification of Early Barrett’s Neoplasia Using Volumetric Laser Endomicroscopy

Barrett’s esopaghagus (BE) is a known precursor of esophageal adenocarcinoma (EAC). Patients with BE undergo regular surveillance to early detect stages of EAC. Volumetric laser endomicroscopy (VLE) is a novel technology incorporating a second-generation form of optical coherence tomography and is capable of imaging the inner tissue layers of the esophagus over a 6 cm length scan. However, interpretation of full VLE scans is still a challenge for human observers. In this work, we train an ensemble of deep convolutional neural networks to detect neoplasia in 45 BE patients, using a dataset of images acquired with VLE in a multi-center study. We achieve an area under the receiver operating characteristic curve (AUC) of 0.96 on the unseen test dataset and we compare our results with previous work done with VLE analysis, where only AUC of 0.90 was achieved via cross-validation on 18 BE patients. Our method for detecting neoplasia in BE patients facilitates future advances on patient treatment and provides clinicians with new assisting solutions to process and better understand VLE data.