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Background: Preoperative randomization for postoperative treatment might affect quality of surgery. In the CRITICS trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach), patients were randomized before treatment to receive chemotherapy prior to a D1 + gastrectomy (removal of lymph node station (LNS) 1-9 + 11), followed by either chemotherapy (CT) or chemoradiotherapy (CRT). In this analysis, the influence of upfront randomization on the quality of surgery was evaluated., Methods: Quality of surgery was analyzed in both study arms using surgicopathological compliance (removal of ≥ 15 lymph nodes), surgical compliance (removal of the indicated LNS), and surgical contamination (removal of LNS that should be left in situ). Furthermore, the 'Maruyama Index of Unresected disease' (MI) was evaluated in both study arms, and validated with overall survival., Results: Between 2007 and 2015, 788 patients with gastric cancer were included in the CRITICS study of which 636 patients were operated with curative intent. No difference was observed between the CT and CRT group regarding surgicopathological compliance (74.8% vs 70.9%, P = 0.324), surgical compliance (43.2% vs 39.2%, P = 0.381), and surgical contamination (59.4% vs 59.9%, P = 0.567). Median MI was 1 in both groups (range CT 0-88 and CRT 0-136, P = 0.700). A MI below 5 was associated with better overall survival (CT: P = 0.009 and CRT: P = 0.013)., Conclusion: Surgical quality parameters were similar in both study arms in the CRITICS gastric cancer trial, indicating that upfront randomization for postoperative treatment had no impact on the quality of surgery. A Maruyama Index below five was associated with better overall survival.

Introduction: The optimal time between end of neoadjuvant chemoradiotherapy (nCRT) and oesophagectomy is unknown. The aim of this study was to assess the association between this interval and pathologic complete response rate (pCR), morbidity and 30-day/in-hospital mortality., Methods: Patients with oesophageal cancer treated with nCRT and surgery between 2011 and 2016 were selected from a national database: the Dutch Upper Gastrointestinal Cancer Audit (DUCA). The interval between end of nCRT and surgery was divided into six periods: 0-5 weeks (n = 157;A), 6-7 weeks (n = 878;B), 8-9 weeks (n = 972;C), 10-12 weeks (n = 720;D), 13-14 weeks (n = 195;E) and 15 or more weeks (n = 180;F). The association between these interval groups and outcomes was investigated using univariable and multivariable analysis with group C (8-9 weeks) as reference., Results: In total, 3102 patients were included. The pCR rate for the groups A to F was 31%, 28%, 26%, 31%, 40% and 37%, respectively. A longer interval was associated with a higher probability of pCR (≥10 weeks for adenocarcinoma: odds ratio [95% confidence interval]: 1.35 [1.00-1.83], 1.95 [1.24-3.07], 1.64 [0.99-2.71] and ≥13 weeks for squamous cell carcinoma: 2.86 [1.23-6.65], 2.67 [1.29-5.55]. Patients operated ≥10 weeks after nCRT had the same probability for intraoperative/postoperative complications. Patients from groups D and F had a higher 30-day/in-hospital mortality (1.80 [1.08-3.00], 3.19 [1.66-6.14])., Conclusion: An interval of ≥10 weeks for adenocarcinoma and ≥13 weeks for squamous cell carcinoma between nCRT and oesophagectomy was associated with a higher probability of having a pCR. Longer intervals were not associated with intraoperative/postoperative complications. The 30-day/in-hospital mortality was higher in patients with extended intervals (10-12 and ≥15 weeks); however, this might have been due to residual confounding., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: In recent years, evidence supporting multimodality treatment for oesophageal, oesophagogastric junction (OGJ), and gastric cancer has accumulated. This population-based cohort-study investigates trends and predictors of utilisation of multimodality treatment for oesophagogastric cancer in the Netherlands., Patients and Methods: Data were obtained from the Netherlands Cancer Registry regarding patients with oesophageal (n = 5450), OGJ (n = 2168) and gastric cancer (n = 6683) without distant metastases who had undergone R0 or R1 surgery diagnosed between 2000 and 2012. Follow-up was completed until February 2014. Preoperative/postoperative chemotherapy and/or radiotherapy combined with surgery were considered multimodality treatment. Logistic regression analysis was performed to analyse the association of age, gender, socioeconomic status, clinical T and N classification, hospital type, comprehensive cancer centre network region, and year of diagnosis, with multimodality treatment receipt. Additional analyses were performed to explore differences in trends of utilisation of multimodality treatment between academic and non-academic hospitals., Results: Multimodality treatment utilisation for oesophageal, OGJ and gastric cancer increased significantly to 90%, 85% and 56% in 2012, respectively. In oesophageal and OGJ cancer patients, preoperative chemoradiotherapy was most frequently administered (85% and 47% in 2012, respectively), and in gastric cancer patients preoperative chemotherapy (47% in 2012). Lower age, higher clinical T and N classification, and diagnosis in more recent years were significantly associated with more frequent multimodality treatment receipt. The adoption of most types of multimodality treatment in academic hospitals preceded non-academic hospitals by a year., Conclusion: In the Netherlands, the utilisation of multimodality treatment for oesophagogastric cancer has significantly increased during the past decade, especially in oesophageal and OGJ cancer. Multimodality treatment utilisation was especially dependent on patient and tumour characteristics and year of diagnosis, but multimodality treatment trends seem to be related to the publication of landmark studies, participation in nationally running clinical trials, and hospital type, preceding national guidelines.

Purpose: The internationally validated Memorial Sloan-Kettering Cancer Center (MSKCC) gastric carcinoma nomogram was based on patients who underwent curative (R0) gastrectomy, without any other therapy. The purpose of the current study was to assess the performance of this gastric cancer nomogram in patients who received chemoradiation therapy after an R0 resection for gastric cancer., Methods and Materials: In a combined dataset of 76 patients from the Netherlands Cancer Institute (NKI), and 63 patients from MSKCC, who received postoperative chemoradiation therapy (CRT) after an R0 gastrectomy, the nomogram was validated by means of the concordance index (CI) and a calibration plot., Results: The concordance index for the nomogram was 0.64, which was lower than the CI of the nomogram for patients who received no adjuvant therapy (0.80). In the calibration plot, observed survival was approximately 20% higher than the nomogram-predicted survival for patients receiving postoperative CRT., Conclusions: The MSKCC gastric carcinoma nomogram significantly underpredicted survival for patients in the current study, suggesting an impact of postoperative CRT on survival in patients who underwent an R0 resection for gastric cancer, which has been demonstrated by randomized controlled trials. This analysis stresses the need for updating nomograms with the incorporation of multimodal strategies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Gastric cardia and non-cardia cancer exhibit differences in biological and epidemiological features across the world. The aims of this study were to analyze trends in incidence, stage distribution, and survival over a 20-year period in the Netherlands, separately for both types of gastric cancer., Methods: Data on all patients with a diagnosis of gastric cancer in the period 1989-2008 were obtained from the nationwide Netherlands Cancer Registry. Time trends in incidence [analyzed as European Standard Rate per 100 000 (ESR)] and relative survival were separately analyzed for cardia and non-cardia gastric cancer., Results: A total of 47 295 patients were included. Incidence rates per 100 000 for cardia cancer declined from 5.7 to 4.3 for males and remained stable for females (1.2). For non-cardia cancer, the incidence in males declined from 25 to 14 and in females from 10 to 7. Proportional incidence in stage IV cardia and non-cardia cancer increased in 2004-2008 (cardia 32-42%, non-cardia 33-45%). Five-year survival rates for stage I-III and X (unknown) remained stable (cardia cancer: 20%, non-cardia gastric cancer: 31%). Five-year survival for stage IV disease was 1.9% and 1.0% for cardia and non-cardia gastric cancer., Conclusion: The incidence of gastric cancer in the Netherlands markedly decreased over the past decades, in particular of non-cardia cancer. Survival remained dismal. Improvement of survival remains a challenge for the multidisciplinary team involved in gastric cancer treatment.

Background: Survival estimates after curative surgery for gastric cancer are based on AJCC staging, or on more accurate multivariable nomograms. However, the risk of dying of gastric cancer is not constant over time, with most deaths occurring in the first 2 years after resection. Therefore, the prognosis for a patient who survives this critical period improves. This improvement over time is termed conditional probability of survival (CPS). Objectives of this study were to develop a CPS nomogram predicting 5-year disease-specific survival (DSS) from the day of surgery for patients surviving a specified period of time after a curative gastrectomy and to explore whether variables available with follow-up improve the nomogram in the follow-up setting., Methods: A CPS nomogram was developed from a combined US-Dutch dataset, containing 1,642 patients who underwent an R0 resection with or without chemotherapy/radiotherapy for gastric cancer. Weight loss, performance status, hemoglobin, and albumin 1 year after resection were added to the baseline variables of this nomogram., Results: The CPS nomogram was highly discriminating (concordance index: 0.772). Surviving 1, 2, or 3 years gives a median improvement of 5-year DSS from surgery of 7.2, 19.1, and 31.6 %, compared with the baseline prediction directly after surgery. Introduction of variables available at 1-year follow-up did not improve the nomogram., Conclusions: A robust gastric cancer nomogram was developed to predict survival for patients alive at time points after surgery. Introduction of additional variables available after 1 year of follow-up did not further improve this nomogram.

Purpose: To evaluate the changes in the 7th edition American Joint Committee on Cancer (AJCC) staging system for stomach cancer compared to the 6th edition; to compare the predictive accuracy of the two staging systems., Methods: In a combined database containing 2,196 patients who underwent an R0 resection for gastric adenocarcinoma, differences between the two staging systems were evaluated and stage-specific survival estimates compared. Concordance probability and Brier scores were estimated for both systems to examine the predictive accuracy., Results: Nodal status cutoff values were changed, leading to a more even distribution for the redefined N1, N2, and N3 group. AJCC 6th edition stage II reflected a highly heterogeneous population, which is now adequately subdivided in the AJCC 7th edition into stages IIA, IIB, and IIIA. The predictive accuracy of N classification improved significantly as measured by concordance. Despite increased complexity, the predictive accuracy of AJCC 7th stage grouping was significantly worse than that of the AJCC 6th edition., Discussion: The increased complexity of the 7th edition staging system is accompanied by improvements in the predictive value of nodal staging as compared to the 6th edition, but it was no better in overall stage-specific predictive accuracy. Future refinements of the tumor, node, metastasis staging system should consider whether increased complexity is balanced by improved prognostic accuracy.

Introduction: A worldwide increasing incidence is seen for oesophageal adenocarcinoma, but not for oesophageal squamous cell carcinoma (SCC) and gastric cardia adenocarcinoma. Purposes of the current study were to evaluate the changing incidence rates of oesophageal and gastric cardia cancer, and to assess survival trends., Patients and Methods: Patients diagnosed with oesophageal adenocarcinoma (N=12,195) or SCC (N=9046), or gastric cardia adenocarcinoma (N=9900) between 1989 and 2008 in the Netherlands were included. Changes in European Standard Population (ESP) and relative survival over time were evaluated., Results: Incidence rates for oesophageal adenocarcinoma increased in males (+7.5%, P<0.001) and females (+5.2%, P<0.001), while the incidence for oesophageal SCC remained stable in males (-0.2%, P=0.6) and slightly increased in females (+1.7%, P=0.001). The incidence for gastric cardia cancer decreased in males (-1.2%, P<0.006), and remained stable in females (-0.2%, P=0.7). Five-year survival for both M0 and M1 oesophageal carcinoma doubled over the last 20 years. No significant changes in survival were found for M0 and M1 gastric cardia carcinoma., Discussion: In the Netherlands, a rising incidence is seen for oesophageal adenocarcinoma, but not for gastric cardia adenocarcinoma. This finding most likely reflects true changes in disease burden, rather than being the result of changes in diagnosis or classification. The increased survival for oesophageal carcinoma can be attributed to centralisation of surgery, and an increased use of multimodality therapy, factors hardly acknowledged for gastric cancer., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: While it is suggested that more than 15 lymph nodes (LNs) should be evaluated for accurate staging of gastric cancer, LN yield in western countries is generally low. The effect of preoperative chemotherapy on LN yield in gastric cancer is unknown. The aim of the present study is to determine whether preoperative chemotherapy is associated with any difference in the number of LNs obtained from specimens of patients who underwent curative surgery for gastric adenocarcinoma., Patients and Methods: In 1205 patients from Memorial Sloan-Kettering Cancer Center (MSKCC) and 1220 patients from the Netherlands Cancer Registry (NCR) who underwent a gastrectomy with curative intent for gastric adenocarcinoma without receiving preoperative radiotherapy, LN yield was analyzed, comparing patients who received preoperative chemotherapy and patients who received no preoperative therapy., Results: Of the 2425 patients who underwent a gastrectomy, 14% received preoperative chemotherapy. Median LN yields were 23 at MSKCC and 10 in the NCR. Despite this twofold difference in LN yield between the two populations, with multivariate Poisson regression, chemotherapy was not associated with LN yield of either population. Variables associated with increased LN yield were institution, female sex, lower age, total (versus distal) gastrectomy and increasing T-stage., Conclusions: In this patient series, treatment at MSKCC, female sex, lower age, total gastrectomy and increasing primary tumor stage were associated with a higher number of evaluated LNs. Preoperative chemotherapy was not associated with a decrease in LN yield. Evaluating more than 15 LNs after gastrectomy is feasible, with or without preoperative chemotherapy., (© 2012 Elsevier Ltd. All rights reserved.)

Background: In the seventh edition of the American Joint Committee on Cancer (AJCC) staging system for esophageal cancer, tumor grade was introduced as an independent determinant of stage grouping in early stage tumors. With the significantly lower prognosis for poorly differentiated early stage adenocarcinomas, patients with these tumors may become candidates for neoadjuvant therapy given an accurate identification of these tumors with preoperative staging. The objective of the current study was to investigate the accuracy of preoperative histopathologic grading and the effect of preoperative grade on tumor stage/prognostic grouping., Methods: Preoperative tumor grade was compared with postoperative tumor grade in 427 patients who underwent surgery without receiving neoadjuvant therapy for adenocarcinoma of the esophagus. The impact of preoperative tumor grade on stage/prognostic grouping was investigated., Results: The overall accuracy of preoperative tumor grade assessment was 76% when unknown differentiation was regarded as well/moderately differentiated as recommended by the AJCC, whereas accuracy was 73% after the exclusion of tumors with unknown grade. In patients who have tumors classified as T1 or T2 and lymph node-negative (N0) (T1-T2N0) disease, 16% were assigned to a lower stage group based on preoperative pathology, whereas 5% were assigned to a higher stage group. In the T1-T2N0 group, sensitivity for detecting a poorly differentiated tumor was 0.43 (95% confidence interval [CI], 0.30-0.56), whereas specificity was 0.94 (95% CI, 0.90-0.98)., Conclusions: With increasing use of neoadjuvant therapy, the accuracy of preoperative biopsy assessment has become increasingly important. In the current study, the accuracy of preoperative tumor grade assessment was 73%, leading to changes in AJCC stage/prognostic group in 21% of patients with T1-T2N0 esophageal adenocarcinomas. The authors concluded that caution should be exhibited in staging patients with esophageal adenocarcinoma based on preoperative biopsy data., (Copyright © 2011 American Cancer Society.)

Purpose: The Intergroup 0116 trial has demonstrated that postoperative chemoradiotherapy (CRT) improves survival in gastric cancer. We retrospectively compared survival and recurrence patterns in two phase I/II studies evaluating more intensified postoperative CRT with those from the Dutch Gastric Cancer Group Trial (DGCT) that randomly assigned patients between D1 and D2 lymphadenectomy., Patients and Methods: Survival and recurrence patterns of 91 patients with adenocarcinoma of the stomach who had received surgery followed by radiotherapy combined with fluorouracil and leucovorin (n = 5), capecitabine (n = 39), or capecitabine and cisplatin (n = 47) were analyzed and compared with survival and recurrence patterns of 694 patients from the DGCT (D1, n = 369; D2, n = 325). For both groups, the Maruyama Index of Unresected Disease (MI) was calculated and correlated with survival and recurrence patterns., Results: With a median follow-up of 19 months in the CRT group, local recurrence rate after 2 years was significantly higher in the surgery only (DGCT) group (17% v 5%; P = .0015). Separate analysis of CRT patients who underwent a D1 dissection (n = 39) versus DGCT-D1 (n = 369) showed fewer local recurrences after chemoradiotherapy (2% v 8%; P = .001), whereas comparison of CRT-D2 (n = 25) versus DGCT-D2 (n = 325) demonstrated no significant difference. CRT significantly improved survival after a microscopically irradical (R1) resection. The MI was found to be a strong independent predictor of survival., Conclusion: After D1 surgery, the addition of postoperative CRT had a major impact on local recurrence in resectable gastric cancer.