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Purpose: There is limited evidence regarding the prognostic effects of pathologic lymph node (LN) regression after neoadjuvant chemotherapy for esophageal adenocarcinoma, and a definition of LN response is lacking. This study aimed to evaluate how LN regression influences survival after surgery for esophageal adenocarcinoma., Methods: Multicenter cohort study of patients with esophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection at five high-volume centers in the United Kingdom. LNs retrieved at esophagectomy were examined for chemotherapy response and given a LN regression score (LNRS)-LNRS 1, complete response; 2, <10% residual tumor; 3, 10%-50% residual tumor; 4, >50% residual tumor; and 5, no response. Survival analysis was performed using Cox regression adjusting for confounders including primary tumor regression. The discriminatory ability of different LN response classifications to predict survival was evaluated using Akaike information criterion and Harrell C-index., Results: In total, 17,930 LNs from 763 patients were examined. LN response classified as complete LN response (LNRS 1 ≥1 LN, no residual tumor in any LN; n = 62, 8.1%), partial LN response (LNRS 1-3 ≥1 LN, residual tumor ≥1 LN; n = 155, 20.3%), poor/no LN response (LNRS 4-5; n = 303, 39.7%), or LN negative (no tumor/regression; n = 243, 31.8%) demonstrated superior discriminatory ability. Mortality was reduced in patients with complete LN response (hazard ratio [HR], 0.35; 95% CI, 0.22 to 0.56), partial LN response (HR, 0.72; 95% CI, 0.57 to 0.93) or negative LNs (HR, 0.32; 95% CI, 0.25 to 0.42) compared with those with poor/no LN response. Primary tumor regression and LN regression were discordant in 165 patients (21.9%)., Conclusion: Pathologic LN regression after neoadjuvant chemotherapy was a strong prognostic factor and provides important information beyond pathologic TNM staging and primary tumor regression grading. LN regression should be included as standard in the pathologic reporting of esophagectomy specimens.

Objectives: 2-deoxy-2[ 18 F]Fluoro-D-glucose (FDG) PET-CT has an emerging role in assessing response to neoadjuvant therapy in oesophageal cancer. This study evaluated FDG PET-CT in predicting pathological tumour response (pTR), pathological nodal response (pNR) and survival., Methods: Cohort study of 75 patients with oesophageal or oesophago-gastric junction (GOJ) adenocarcinoma treated with neoadjuvant chemotherapy then surgery at Guy's and St Thomas' NHS Foundation Trust, London (2017-2020). Standardised uptake value (SUV) metrics on pre- and post-treatment FDG PET-CT in the primary tumour (mTR) and loco-regional lymph nodes (mNR) were derived. Optimum SUV max thresholds for predicting pathological response were identified using receiver operating characteristic analysis. Predictive accuracy was compared to PERCIST (30% SUV max reduction) and MUNICON (35%) criteria. Survival was assessed using Cox regression., Results: Optimum tumour SUV max decrease for predicting pTR was 51.2%. A 50% cut-off predicted pTR with 73.5% sensitivity, 69.2% specificity and greater accuracy than PERCIST or MUNICON (area under the curve [AUC] 0.714, PERCIST 0.631, MUNICON 0.659). Using a 30% SUV max threshold, mNR predicted pNR with high sensitivity but low specificity (AUC 0.749, sensitivity 92.6%, specificity 57.1%, p = 0.010). pTR, mTR, pNR and mNR were independent predictive factors for survival (pTR hazard ratio [HR] 0.10 95% confidence interval [CI] 0.03-0.34; mTR HR 0.17 95% CI 0.06-0.48; pNR HR 0.17 95% CI 0.06-0.54; mNR HR 0.13 95% CI 0.02-0.66)., Conclusions: Metabolic tumour and nodal response predicted pTR and pNR, respectively, in patients with oesophageal or GOJ adenocarcinoma. However, currently utilised response criteria may not be optimal. pTR, mTR, pNR and mNR were independent predictors of survival., Key Points: • FDG PET-CT has an emerging role in evaluating response to neoadjuvant therapy in patients with oesophageal cancer. • Prospective cohort study demonstrated that metabolic response in the primary tumour and lymph nodes was predictive of pathological response in a cohort of patients with adenocarcinoma of the oesophagus or oesophago-gastric junction treated with neoadjuvant chemotherapy followed by surgical resection. • Patients who demonstrated a response to neoadjuvant chemotherapy in the primary tumour or lymph nodes on FDG PET-CT demonstrated better survival and reduced rates of tumour recurrence., (© 2023. The Author(s).)

Purpose: Type I gastric neuroendocrine neoplasms (g-NENs) have a low risk of metastasis and a generally favourable prognosis. Patients with small type I g-NENs (≤10 mm) frequently require no treatment, whereas those with larger polyps usually undergo resection. We evaluated the safety and outcomes of endoscopic surveillance after no initial treatment in selected patients with type I g-NENs., Methods: Retrospective analysis of type I g-NEN patients across two European Neuroendocrine Tumour Society Centers of Excellence 2003-2019., Results: Following initial assessment, 87 of 115 patients with type I g-NEN (75 with polyps ≤10 mm) received no initial treatment and underwent endoscopic surveillance. 79/87 (91%) demonstrated no clinically meaningful change in tumour size or grade over a median 62 month follow up. Only two patients developed NEN progression that required a change in management and two other patients developed gastric adenocarcinoma/high grade dysplasia; all four initially had ≥11 mm g-NENs., Conclusions: Patients with ≤10 mm type I g-NENs were unlikely to develop clinically significant tumour progression and in most cases, resection was not needed. The endoscopic surveillance interval could therefore potentially be safely increased to every 2-3 years in such patients. However, lifelong surveillance is still advocated due to the additional risk of developing gastric adenocarcinoma., (© 2022. The Author(s).)

Background: Peri-operative chemotherapy improves survival in patients with locally advanced oesophago-gastric adenocarcinoma. Two regimens with proven survival benefits are epirubicin, cisplatin plus capecitabine or fluorouracil (Medical Research Council Adjuvant Gastric Infusional Chemotherapy, MAGIC) and fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT). This study aimed to compare the effect of these regimens on survival (primary aim) and pathological response, surgical complications, adverse events and chemotherapy completion rates., Methods: Cohort study including 946 patients treated with FLOT (n = 257) or MAGIC (n = 689) who underwent surgical resection for oesophageal (n = 743) or gastric (n = 203) adenocarcinoma between 2002 and 2021 at St Thomas' Hospital or The Royal Marsden Hospital, London, UK. Survival analysis was performed using multivariable Cox regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, clinical T-stage, clinical N-stage, tumour grade and presence of signet ring cells., Results: Patients treated with FLOT had better overall survival (HR = 0.69, 95% CI 0.50-0.94) and disease-free survival (HR = 0.75, 95% CI 0.58-0.98) than MAGIC. Patients treated with FLOT were more likely to have a complete pathological response (9.5% FLOT versus 5.5% MAGIC, p = 0.027) and were less likely to have a positive resection margin (19.1% FLOT versus 32.2% MAGIC, p < 0.001). The stratified analysis revealed similar results for oesophageal and gastric tumours. Rates of surgical complications, chemotherapy-associated adverse events and completion were similarly distributed between treatment groups., Conclusions: Patients with oesophageal or gastric adenocarcinoma treated with peri-operative FLOT had better survival and pathological response than those treated with peri-operative MAGIC. Rates of surgical complications, adverse events and chemotherapy completion were comparable., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Neoadjuvant chemotherapy is often used prior to surgical resection for oesophageal adenocarcinoma but remains ineffective in a high proportion of patients. The histological Mandard tumour regression grade is used to determine chemoresponse but is not available at the time of treatment decision-making. The aim of this cohort study was to identify factors that predict chemotherapy response prior to surgery., Methods: A prospectively collected database of patients undergoing surgical resection for oesophageal adenocarcinoma from a high-volume UK institution was used. Patients were subcategorised using pathological tumour response into 'responders' (Mandard grade 1-3) and 'non-responders' (Mandard grade 4 and 5). Multivariable logistic regression analysis was performed to calculate crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) for responder status adjusting for a variety of parameters. Receiver operating characteristic (ROC) curves were calculated., Results: Among 315 patients included, 102 (32%) were responders and 213 (68%) non-responders. A decrease in radiological tumour volume (OR 1.92 95%CI 1.02-3.62; p  = 0.05), a 'partial response' RECIST score (OR 7.16 95%CI 1.49-34.36; p  = 0.01), a clinically improved dysphagia score (OR 2.79 95%CI 1.05-7.04; p  = 0.04) and lymphovascular invasion (OR 0.06 95%CI 0.02-0.13; p  = 0.000) influenced responder status. ROC curve analysis for responder status utilising all available parameters had an area under the curve (AUC) of 0.86., Conclusion: This study has highlighted the potential for using pre-defined factors to identify those patients who have responded to neoadjuvant chemotherapy, prior to surgical resection, potentially facilitating a more individualised therapeutic approach.

Background: Most patients presenting with oesophageal cancer do so with advanced disease not suitable for surgery. However, there are examples of encouraging survival following surgery in highly selected patients who respond well to chemotherapy., Methods: This was a retrospective cohort study of patients who presented with advanced but nonvisceral metastatic oesophageal cancer. Consecutive patients on a prolonged primary chemotherapy pathway who underwent surgical resection following a favourable response to chemotherapy were included. Survival and recurrence rates were analysed using Cox regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs)., Results: A total of 57 patients included in the cohort operated between 2007 and 2015, the overall median survival was 44 months and the 5-year survival was 42%. Prechemotherapy cN0/cN1 (HR: 0.27, 95% CI: 0.12-0.62) conferred an independent survival advantage compared to cN2 and cN3 disease. Poor differentiation (HR: 2.46, 95% CI: 1.11-5.42), R1 resection (HR: 2.43, 95% CI: 1.14-5.19) and advanced nodal status (HR: 3.28, 95% CI: 1.44-7.47) predicted worse survival on univariable analysis. Poor differentiation (HR: 3.93, 95% CI: 1.62-9.56) was independently associated with poor survival when adjusted for other variables., Conclusion: Patients who present with advanced inoperable oesophageal cancer who have a favourable response to chemotherapy represent a limited group of patients who may benefit from surgery., (© 2021 Wiley Periodicals LLC.)

Background: The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy (NAC) and surgery is contentious. In UK practice, surgical resection margin status is often used to classify patients into receiving adjuvant treatment. This study aimed to assess any survival benefit of adjuvant therapy in patients with clear resection margins., Methods: This was a retrospective collaborative cohort study combining two prospectively collected UK institutional databases of patients with oesophageal adenocarcinoma. Multivariable Cox regression and propensity matched analyses were used to compare overall and recurrence-free survival according to the adjuvant treatment., Results: Of 374 patients with clear resection margins, 221 patients (59%) had no adjuvant treatment, 137 patients (37%) had adjuvant chemotherapy and 16 patients (4%) had adjuvant chemoradiotherapy. For patients who had received NAC (290, 76%), when adjuvant chemotherapy was compared to no adjuvant treatment, hazard ratios (HRs) favoured adjuvant chemotherapy but did not reach independent significance (overall survival [OS] HR 0.65 95% confidence interval [CI] 0.40-1.06; p  .0.087). Responders to NAC (Mandard 1-3) were seemingly more likely to demonstrate a survival benefit from adjuvant chemotherapy (HR 0.42 95% CI 0.15-1.11; p  .1.081)., Conclusions: Although no independent survival benefit was observed, the point estimates favoured adjuvant treatment, predominantly in patients with chemo-responsive tumours.

Background: A high Mandard score implies a non-response to chemotherapy in oesophageal adenocarcinoma. However, some patients exhibit tumour volume reduction and a nodal response despite a high score. This study examines survival and recurrence patterns in these patients., Methods: Clinicopathological factors were analysed using multivariable Cox regression assessing time to death and recurrence. Computed tomography-estimated tumour volume change was examined in a subgroup of consecutive patients., Results: Five hundred and fifty-five patients were included. Median survival was 55 months (Mandard 1-3) and 21 months (Mandard 4 and 5). In the Mandard 4 and 5 group (332 patients), comparison between complete nodal responders and persistent nodal disease showed improved survival (90 vs 18 months), recurrence rates (locoregional 14.75 vs 28.74%, systemic 24.59 vs 48.42%) and circumferential resection margin positivity (22.95 vs 68.11%). Complete nodal response independently predicted improved survival (hazard ratio 0.34 (0.16-0.74). Post-chemotherapy tumour volume reduction was greater in patients with a complete nodal response (-16.3 vs -7.7 cm 3 , p = 0.033) with no significant difference between Mandard groups., Conclusion: Patients with a complete nodal response to chemotherapy have significantly improved outcomes despite a poor Mandard score. High Mandard score does not correspond with a non-response to chemotherapy in all cases and patients with nodal downstaging may still benefit from adjuvant chemotherapy.

Aim: 18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) is valuable in the management of patients with oesophageal cancer, but a role in gastric cancer staging is debated. Our aim was to review the role of FDG PET-CT in a large gastric cancer cohort in a tertiary UK centre., Methods: We retrospectively reviewed data from 330 patients presenting with gastric adenocarcinoma between March 2014 and December 2016 of whom 105 underwent pre-treatment staging FDG PET-CT scans. FDG PET-CT scans were graded qualitatively and quantitatively (SUV max ) and compared with staging diagnostic CT and operative pathology results (n = 30) in those undergoing resection., Results: Of the 105 patients (74 M, median age 73 years) 86% of primary tumours were metabolically active (uptake greater than normal stomach) on FDG PET-CT [41/44 (93%) of the intestinal histological subtype (SUV max 14.1 ± 1.3) compared to 36/46 (78%) of non-intestinal types (SUV max 9.0 ± 0.9), p = 0.005]. FDG PET-CT upstaged nodal or metastastic staging of 20 patients (19%; 13 intestinal, 6 non-intestinal, 1 not reported), with 17 showing distant metastases not evident on other imaging. On histological analysis, available in 30 patients, FDG PET-CT showed low sensitivity (40%) but higher specificity (73%) for nodal involvement., Conclusion: FDG PET-CT provides new information in a clinically useful proportion of patients, which leads to changes in treatment strategy, most frequently by detecting previously unidentified metastases, particularly in those with intestinal-type tumours.

Background: To evaluate the prognostic role of Positron Emission Tomography/Computed Tomography (PET/CT) and Endoscopic Ultrasound (EUS) performed before neoadjuvant chemotherapy (NAC) and surgery for oesophageal adenocarcinoma (OAC) patients, focusing on lymph node (LN) assessment. Methods: OAC patients treated in a single tertiary center during January 2008 until December 2014 were retrospectively studied. All patients had PET/CT and EUS before NAC and oesophagectomy. PET-FDG-avid local LNs and maximum standardized uptake value (SUVmax) of the primary tumour, EUS positive LNs and EUS tumour length were recorded. Univariate, multivariate and survival analyses were performed. Results: Following exclusions 151consecutive patients met the inclusion criteria, (median age 62 years). PET/CT and EUS sensitivity for local LNs metastasis was 39.2% and 88.6%, with specificities of 83.33% and 19.15% respectively. No overall survival (OS) difference was found between patients with PET/CT FDG-avid LNs and those with negative LNs (p=0.347). SUVmax uptake was divided into high and low (median cut-off value: 10) with no significant difference in OS between groups (p=0.141). EUS tumour length was not prognostic (OS, p=0.455). Conclusions: Initial LN staging in OA is inaccurate. Although PET/CT and EUS assessments may be complimentary, none independently predicted survival., (Celsius.)