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Background: This study aims to assess the impact of nationwide centralization of surgery on travel distance and travel burden among patients with oesophageal, gastric, and pancreatic cancer according to age in the Netherlands. As centralization of care increases to improve postoperative outcomes, travel distance and experienced burden might increase., Materials and Methods: All patients who underwent surgery between 2006 and 2017 for oesophageal, gastric and pancreatic cancer in the Netherlands were included. Travel distance between patient's home address and hospital of surgery in kilometres was calculated. Questionnaires were used to assess experienced travel burden in a subpopulation (n = 239). Multivariable ordinal logistic regression models were constructed to identify predictors for longer travel distance., Results: Over 23,838 patients were included, in whom median travel distance for surgical care increased for oesophageal cancer (n = 9217) from 18 to 28 km, for gastric cancer (n = 6743) from 9 to 26 km, and for pancreatic cancer (n = 7878) from 18 to 25 km (all p < 0.0001). Multivariable analyses showed an increase in travel distance for all cancer types over time. In general, patients experienced a physical and social burden, and higher financial costs, due to traveling extra kilometres. Patients aged >70 years travelled less often independently (56% versus 68%), as compared to patients aged ≤70 years., Conclusion: With nationwide centralization, travel distance increased for patients undergoing oesophageal, gastric, and pancreatic cancer surgery. Younger patients travelled longer distances and experienced a lower travel burden, as compared to elderly patients. Nevertheless, on a global scale, travel distances in the Netherlands remain limited., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The Intergroup 0116 and the MAGIC trials changed clinical practice for resectable gastric cancer in the Western world. In these trials, overall survival improved with post-operative chemoradiotherapy (CRT) and perioperative chemotherapy (CT). Intention-to-treat analysis in the CRITICS trial of post-operative CT or post-operative CRT did not show a survival difference. The current study reports on the per-protocol (PP) analysis of the CRITICS trial., Patients and Methods: The CRITICS trial was a randomized, controlled trial in which 788 patients with stage Ib-Iva resectable gastric or esophagogastric adenocarcinoma were included. Before start of preoperative CT, patients from the Netherlands, Sweden and Denmark were randomly assigned to receive post-operative CT or CRT. For the current analysis, only patients who started their allocated post-operative treatment were included. Since it is uncertain that the two treatment arms are balanced in such PP analysis, adjusted proportional hazards regression analysis and inverse probability weighted analysis were used to minimize the risk of selection bias and to estimate and compare overall and event-free survival., Results: Of the 788 patients, 478 started post-operative treatment according to protocol, 233 (59%) patients in the CT group and 245 (62%) patients in the CRT group. Patient and tumor characteristics between the groups before start of the post-operative treatment were not different. After a median follow-up of 6.7 years since the start of post-operative treatment, the 5-year overall survival was 57.9% (95% confidence interval: 51.4% to 64.3%) in the CT group versus 45.5% (95% confidence interval: 39.2% to 51.8%) in the CRT group (adjusted hazard ratio CRT versus CT: 1.62 (1.24-2.12), P = 0.0004). Inverse probability weighted analysis resulted in similar hazard ratios., Conclusion: After adjustment for all known confounding factors, the PP analysis of patients who started the allocated post-operative treatment in the CRITICS trial showed that the CT group had a significantly better 5-year overall survival than the CRT group (NCT00407186)., Competing Interests: Disclosure MIVBH reports grants from Olympus and Stryker; personal fees from Johnson and Johnson, Medtronic, Mylan and Alesi Surgical. All fees paid to institution outside the submitted work. All remaining authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: With currently available techniques, the prediction of pathologic complete response after neoadjuvant chemoradiotherapy is insufficient. The tumor-stroma ratio (TSR) has proven to be a predictor of survival for several types of cancer, including esophageal. The aim of this study was to investigate the value of TSR in predicting pathologic response after neoadjuvant chemoradiotherapy in esophageal cancer patients., Materials and Methods: Patients with esophageal adenocarcinoma or squamous cell carcinoma who received neoadjuvant chemoradiotherapy followed by a resection were selected. Haematoxylin and eosin (H&E) stained sections of diagnostic biopsies were collected and TSR was independently assessed by two investigators. Patients were categorized in stroma-low (≤50% stroma) and stroma-high (>50% stroma) groups for further analyses. The tumor regression grade (TRG) was assessed on H&E stained sections of the resected primary tumor to determine pathologic response., Results: A total of 94 patients were included in this study, of which 76 patients were categorized as stroma-low and 18 as stroma-high. Forty-two (45%) patients had a major pathologic response (TRG 1-2), whereas 52 (55%) were considered non-responders. After adjustment for gender, tumor type, cT-status and differentiation grade, patients with a stroma-high tumor showed a higher chance of no response compared to patients with a stroma-low tumor (OR 3.57, 95%CI 1.03-12.31, P  = 0.04)., Conclusion: TSR showed to have the potential to aid in the prediction of pathologic response in esophageal cancer patients receiving neoadjuvant chemoradiotherapy. Larger validation studies are necessary before implementing this method in daily practice., Competing Interests: 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 paper., (© 2019 The Author(s).)

Background: As older gastric cancer patients are often excluded from randomized clinical trials, the most appropriate treatment strategy for these patients remains unclear. The current study aimed to gain more insight in treatment strategies and relative survival of older patients with resectable gastric cancer across Europe., Methods: Population-based cohorts from Belgium, Denmark, The Netherlands, Norway, and Sweden were combined. Patients ≥70 years with resectable gastric cancer (cT1-4a, cN0-2, cM0), diagnosed between 2004 and 2014 were included. Resection rates, administration of chemotherapy (irrespective of surgery), and relative survival within a country according to stage were determined., Results: Overall, 6698 patients were included. The percentage of operated patients was highest in Belgium and lowest in Sweden for both stage II (74% versus 56%) and stage III disease (57% versus 25%). For stage III, chemotherapy administration was highest in Belgium (44%) and lowest in Sweden (2%). Three year relative survival for stage I, II, and III disease in Belgium was 67.8% (95% CI:62.8-72.6), 41.2% (95% CI:37.3-45.2), 17.8% (95% CI:12.5-24.0), compared with 56.7% (95% CI:51.5-61.7), 31.3% (95% CI:27.6-35.2), 8.2% (95% CI:4.4-13.4) in Sweden. There were no significant differences in treatment strategies of patients with stage I disease., Conclusion: Substantial treatment differences are observed across North European countries for patients with stages II and III resectable gastric cancer aged 70 years or older. In the present comparison, treatment strategies with a higher proportion of patients undergoing surgery seemed to be associated with higher survival rates for patients with stages II or III disease., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction: The aim of this study is to provide insight in accuracy of diagnosing, current treatment and survival in patients with resectable esophageal and gastric neuroendocrine- and mixed adenoneuroendocrine carcinomas (NEC, MANEC)., Methods: All patients with esophageal or gastric (MA)NEC, who underwent surgical resection between 2006 and 2016, were identified from the Dutch national registry for histo- and cytopathology (PALGA). Patients with a neuroendocrine tumor lower than grade 3 were excluded. Data on patients, treatment and outcomes were retrieved from the patient records. Diagnosis by endoscopic biopsy was compared with diagnosis by resection specimen. Kaplan Meier survival analysis was performed., Results: A total of 49 patients were identified in 25 hospitals, including 21 patients with esophageal (MA)NEC and 26 patients with gastric (MA)NEC on resection specimen. Biopsy diagnosis of (MA)NEC was correct in 23/27 patients. However, 20/47 patients with definitive diagnosis of (MA)NEC, were misdiagnosed on biopsy. Neoadjuvant therapy was administered in 13 (62%) esophageal (MA)NECs and 12 (46%) gastric (MA)NECs. Survival curves were similar with and without neoadjuvant therapy. One (4.8%) esophageal (MA)NEC and 4 (15%) gastric (MA)NECs died within 90 days postoperatively. For esophageal (MA)NEC the median overall survival (OS) after surgery was 37 months and 1-, 3- and 5-year OS were 71%, 50% and 35%, respectively. For gastric (MA)NEC, the median OS was 23 months and 1-, 3- and 5-year OS were 62%, 50% and 39%, respectively., Conclusion: Localized esophageal and gastric (MA)NEC are often misdiagnosed on endoscopic biopsies. After resection, long-term survival was achieved in respectively 35% and 39% of patients., (Copyright © 2018. Published by Elsevier Ltd.)

Background: In order to determine the optimal combination of perioperative chemotherapy and chemoradiotherapy for Western patients with advanced resectable gastric cancer, the international multicentre CRITICS trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) was initiated. In this trial, patients with resectable gastric cancer were randomised before start of treatment between adjuvant chemotherapy or adjuvant chemoradiotherapy following neoadjuvant chemotherapy plus gastric cancer resection. The purpose of this study was to report on surgical morbidity and mortality in this trial, and to identify factors associated with surgical morbidity., Methods: Patients who underwent a gastrectomy with curative intent were selected. Logistic regression analyses were used to assess risk factors for developing postoperative complications., Results: Between 2007 and 2015, 788 patients were included in the CRITICS trial, of whom 636 patients were eligible for current analyses. Complications occurred in 296 patients (47%). Postoperative mortality was 2.2% (n = 14). Complications due to anastomotic leakage was cause of death in 5 patients. Failure to complete preoperative chemotherapy (OR = 2.09, P = 0.004), splenectomy (OR = 2.82, P = 0.012), and male sex (OR = 1.55, P = 0.020) were associated with a greater risk for postoperative complications. Total gastrectomy and oesophago-cardia resection were associated with greater risk for morbidity compared with subtotal gastrectomy (OR = 1.88, P = 0.001 and OR = 1.89, P = 0.038)., Conclusion: Compared to other Western studies, surgical morbidity in the CRITICS trial was slightly higher whereas mortality was low. Complications following anastomotic leakage was the most important factor for postoperative mortality. Important proxies for developing postoperative complications were failure to complete preoperative chemotherapy, splenectomy, male sex, total gastrectomy, and oesophago-cardia resection., (Copyright © 2018. Published by Elsevier Ltd.)

Aims: Outcomes for patients with oesophago-gastric cancer are variable across Europe. The reasons for this variability are not clear. The aim of this study was to describe and analyse clinical pathways to understand differences in service provision for oesophageal and gastric cancer in the countries participating in the EURECCA Upper GI group., Methods: A questionnaire was devised to assess clinical presentation, diagnosis, staging, treatment, pathology, follow-up and service frameworks across Europe for patients with oesophageal and gastric cancer. The questionnaire was issued to experts from 14 countries. The responses were analysed quantitatively and qualitatively and compared., Results: The response rate was (10/14) 71.4%. The approach to diagnosis was similar. Most countries established a diagnosis within 3 weeks of presentation. However, there were different approaches to staging with variable use of endoscopic ultrasound reflecting availability. There has been centralisation of treatments in most countries for oesophageal surgery. The most consistent area was the approach to pathology. There were variations in access to specialist nurse and dietitian support. Although most countries have multidisciplinary teams, their composition and frequency of meetings varied. The two main areas of significant difference were research and audit and overall service provision. Observations on service framework indicated that limited resources restricted many of the services., Conclusion: The principle approaches to diagnosis, treatment and pathology were similar. Factors affecting the quality of patient experience were variable. This may reflect availability of resources. Standard pathways of care may enhance both the quality of treatment and patient experience., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Esophageal and gastric cancer is associated with a poor prognosis since many patients develop recurrent disease. Treatment requires specific expertise and a structured multidisciplinary approach. In the Netherlands, this type of expertise is mainly found at the University Medical Centers (UMCs) and a few specialized nonacademic centers. Aim of this study is to implement a national infrastructure for research to gain more insight in the etiology and prognosis of esophageal and gastric cancer and to evaluate and improve the response on (neoadjuvant) treatment. Clinical data are collected in a prospective database, which is linked to the patients' biomaterial. The collection and storage of biomaterial is performed according to standard operating procedures in all participating UMCs as established within the Parelsnoer Institute. The collected biomaterial consists of tumor biopsies, blood samples, samples of malignant and healthy tissue of the resected specimen and biopsies of recurrence. The collected material is stored in the local biobanks and is encoded to respect the privacy of the donors. After approval of the study was obtained from the Institutional Review Board, the first patient was included in October 2014. The target aim is to include 300 patients annually. In conclusion, the eight UMCs of the Netherlands collaborated to establish a nationwide database of clinical information and biomaterial of patients with esophageal and gastric cancer. Due to the national coverage, a high number of patients are expected to be included. This will provide opportunity for future studies to gain more insight in the etiology, treatment and prognosis of esophageal and gastric cancer., (© 2015 International Society for Diseases of the Esophagus.)

Introduction: EURECCA (EUropean REgistration of Cancer CAre) is a network aiming to improve cancer care by auditing outcome. EURECCA initiated an international survey to share and compare patient outcome for oesophagogastric cancer. The present study assessed how a uniform dataset could be introduced for oesophagogastric cancer in Europe., Methods: Participating countries presented data using common data items describing patients', disease, strategies, and outcome characteristics. Patients treated with curative surgery for squamous cell carcinoma (SCC) or adenocarcinoma (ACA) were included., Results: United Kingdom, the Netherlands, France, Spain and Ireland participated. There were differences in data source ranging from national registries to large collaborative groups. 4668 oesophagogastric cancer cases over a 12 months period were included. The predominant histological type was ACA. Disease stage tended to be earlier in France and Ireland. In oesophageal and junctional cancers neoadjuvant chemoradiotherapy was preferred in the Netherlands and Ireland contrasting with chemotherapy in the UK and France. All countries used perioperative chemotherapy in gastric cancer but 1/3 of patients received this treatment. The mean R0 resection rate was 86% for oesophageal and junctional resections and 88% for gastric resections. Postoperative mortality varied from 1% to 7%., Conclusion: This European survey shown that implementing a uniform treatment and outcome data format of oesophagogastric cancer is feasible. It identified differences in disease presentation, treatment approaches and outcome, which need to be investigated, especially by increasing the number of participating countries. Future comparisons will facilitate developments in treatment for the benefit of patient outcomes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aims: Seven countries (Denmark, France, Ireland, the Netherlands, Poland, Sweden, United Kingdom) collaborated to initiate a EURECCA (European Registration of Cancer Care) Upper GI project. The aim of this study was to identify a core dataset of shared items in the different data registries which can be used for future collaboration between countries., Methods: Item lists from all participating Upper GI cancer registries were collected. Items were scored 'present' when included in the registry, or when the items could be deducted from other items in the registry. The definition of a common item was that it was present in at least six of the seven participating countries., Results: The number of registered items varied between 40 (Poland) and 650 (Ireland). Among the 46 shared items were data on patient characteristics, staging and diagnostics, neoadjuvant treatment, surgery, postoperative course, pathology, and adjuvant treatment. Information on non-surgical treatment was available in only 4 registries., Conclusions: A list of 46 shared items from seven participating Upper GI cancer registries was created, providing a basis for future quality assurance and research in Upper GI cancer treatment on a European level., (Copyright © 2013 Elsevier Ltd. All rights reserved.)