Risk of Lymph Node Metastasis in T1b Gastric Cancer: An International Comprehensive Analysis from the Global Gastric Group (G3) Alliance.

OBJECTIVE: We sought to define criteria associated with low lymph node metastasis risk in patients with submucosal (pT1b) gastric cancer from 3 Western and 3 Eastern countries. SUMMARY BACKGROUND DATA: Accurate prediction of lymph node metastasis risk is essential when determining the need for gastrectomy with lymph node dissection following endoscopic resection. Under present guidelines, endoscopic resection is considered definitive treatment if submucosal invasion is only superficial, but this is not routinely assessed. METHODS: Lymph node metastasis rates were determined for patient groups defined according to tumor pathological characteristics. Clinicopathological predictors of lymph node metastasis were determined by multivariable logistic regression and used to develop a nomogram in a randomly selected subset that was validated in the remainder. Overall survival was compared between Eastern and Western countries. RESULTS: Lymph node metastasis was found in 701 of 3166 (22.1%) Eastern and 153 of 560 (27.3%) Western patients. Independent predictors of lymph node metastasis were female sex, tumor size, distal stomach location, lymphovascular invasion, and moderate or poor differentiation. Patients fulfilling the National Comprehensive Cancer Network guideline criteria, excluding the requirement that invasion not extend beyond the superficial submucosa, had a lymph node metastasis rate of 8.9% (53/594). Excluding moderately differentiated tumors lowered the rate to 3.4% (10/296). The nomogram's area under the curve was 0.690. Regardless of lymph node status, overall survival was better in Eastern patients. CONCLUSIONS: The lymph node metastasis rate was lowest in patients with well differentiated tumors that were ≤3 cm and lacked lymphovascular invasion. These criteria may be useful in decisions regarding endoscopic resection as definitive treatment for pT1b gastric cancer.

Conventional regression analysis and machine learning in prediction of anastomotic leakage and pulmonary complications after esophagogastric cancer surgery.

BACKGROUND AND OBJECTIVES: With the current advanced data-driven approach to health care, machine learning is gaining more interest. The current study investigates the added value of machine learning to linear regression in predicting anastomotic leakage and pulmonary complications after upper gastrointestinal cancer surgery. METHODS: All patients in the Dutch Upper Gastrointestinal Cancer Audit undergoing curatively intended esophageal or gastric cancer surgeries from 2011 to 2017 were included. Anastomotic leakage was defined as any clinically or radiologically proven anastomotic leakage. Pulmonary complications entailed: pneumonia, pleural effusion, respiratory failure, pneumothorax, and/or acute respiratory distress syndrome. Different machine learning models were tested. Nomograms were constructed using Least Absolute Shrinkage and Selection Operator. RESULTS: Between 2011 and 2017, 4228 patients underwent surgical resection for esophageal cancer, of which 18% developed anastomotic leakage and 30% a pulmonary complication. Of the 2199 patients with surgical resection for gastric cancer, 7% developed anastomotic leakage and 15% a pulmonary complication. In all cases, linear regression had the highest predictive value with the area under the curves varying between 61.9 and 68.0, but the difference with machine learning models did not reach statistical significance. CONCLUSION: Machine learning models can predict postoperative complications in upper gastrointestinal cancer surgery, but they do not outperform the current gold standard, linear regression.

Effect of Hospital Volume With Respect to Performing Gastric Cancer Resection on Recurrence and Survival: Results From the CRITICS Trial.

OBJECTIVE: We examined the association between surgical hospital volume and both overall survival (OS) and disease-free survival (DFS) using data obtained from the international CRITICS (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) trial. SUMMARY BACKGROUND DATA: In the CRITICS trial, patients with resectable gastric cancer were randomized to receive preoperative chemotherapy followed by adequate gastrectomy and either chemotherapy or chemoradiotherapy. METHODS: Patients in the CRITICS trial who underwent a gastrectomy with curative intent in a Dutch hospital were included in the analysis. The annual number of gastric cancer surgeries performed at the participating hospitals was obtained from the Netherlands Cancer Registry; the hospitals were then classified as low-volume (1-20 surgeries/year) or high-volume (≥21 surgeries/year) and matched with the CRITICS trial data. Univariate and multivariate analyses were then performed to evaluate the hazard ratio (HR) between hospital volume and both OS and DFS. RESULTS: From 2007 through 2015, 788 patients were included in the CRITICS trial. Among these 788 patients, 494 were eligible for our study; the median follow-up was 5.0 years. Five-year OS was 59.2% and 46.1% in the high-volume and low-volume hospitals, respectively. Multivariate analysis revealed that undergoing surgery in a high-volume hospital was associated with higher OS [HR = 0.69, 95% confidence interval (CI) = 0.50-0.94, P = 0.020] and DFS (HR = 0.73, 95% CI: 0.54-0.99, P = 0.040). CONCLUSIONS: In the CRITICS trial, hospitals with a high annual volume of gastric cancer surgery were associated with higher overall and DFS. These findings emphasize the value of centralizing gastric cancer surgeries in the Western world.

Surgicopathological Quality Control and Protocol Adherence to Lymphadenectomy in the CRITICS Gastric Cancer Trial.

OBJECTIVE: The purpose of this study was to evaluate surgicopathological quality and protocol adherence for lymphadenectomy in the CRITICS trial. SUMMARY OF BACKGROUND DATA: Surgical quality assurance is a key element in multimodal studies for gastric cancer. In the multicenter CRITICS trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach), patients with resectable gastric cancer were randomized for preoperative chemotherapy, followed by gastrectomy with a D1+ lymphadenectomy (removal of stations 1 to 9 and 11), followed by either chemotherapy or chemoradiotherapy. METHODS: Surgicopathological compliance was defined as removal of ≥15 lymph nodes. Surgical compliance was defined as removal of the indicated lymph node stations. Surgical contamination was defined as removal of lymph node stations that should be left in situ. The Maruyama Index (MI, lower is better), which has proven to be an indicator of surgical quality and is strongly associated with survival, was analyzed. RESULTS: Between 2007 and 2015, 788 patients were randomized, of whom 636 patients underwent a gastrectomy with curative intent. Surgicopathological compliance occurred in 72.8% (n = 460) of the patients and improved from 55.0% (2007) to 90.0% (2015). Surgical compliance occurred in 41.1% (n = 256). Surgical contamination occurred in 59.6% (n = 371). Median MI was 1 (range 0 to 136). CONCLUSION: Surgical quality in the CRITICS trial was excellent, with a MI of 1. Surgicopathological compliance improved over the years. This might be explained by the quality assurance program within the study and centralization of gastric cancer surgery in the Netherlands.

The influence of a composite hospital volume on outcomes for gastric cancer surgery: A Dutch population-based study.

BACKGROUND: Volume-outcome associations for complex surgical procedures have motivated centralization of care worldwide. The aim of this study was to investigate the association between overall hospital experience with complex upper gastrointestinal (GI) cancer resections and outcomes after gastric cancer surgery. METHODS: Data on all patients (n = 4837) who underwent a resection for non metastatic invasive gastric cancer between 2005 and 2014 were obtained from the Netherlands Cancer Registry (NCR). Annual hospital volume categories were based on the combined volume of gastrectomies, esophagectomies, and pancreatectomies (composite hospital volume). Volume-outcome analyses were performed for lymph node yield, 30-day mortality, and overall survival. RESULTS: The proportion of gastric cancer resections performed in hospitals with an annual composite hospital volume of ≥40 upper GI cancer resections increased from 6% in 2005 to 80% in 2014. A higher composite hospital volume was univariably associated with a higher lymph node yield, lower 30-day mortality, and increased overall survival. Statistical significance was lost after adjusting for case mix. But, sub group analysis including only elderly patients (≥75 years) showed a significant association between composite hospital volume and 30-day mortality. CONCLUSION: In the Netherlands, an increasing proportion of gastric cancer resections is performed in hospitals with a high composite hospital volume of gastric, esophageal, and pancreatic cancer resections. Special attention is warranted to referral of elderly patients, as these patients might specifically benefit from this centralization.

Recent trends and predictors of multimodality treatment for oesophageal, oesophagogastric junction, and gastric cancer: A Dutch cohort-study.

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.

Centralization of esophagectomy: how far should we go?

BACKGROUND: This study was designed to define a statistically sound and clinically meaningful cutoff point for annual hospital volume for esophagectomy. Higher hospital volumes are associated with improved outcomes after esophagectomy. However, reported optimal volumes in literature vary, and minimal volume standards in different countries show considerable variation. So far, there has been no research on the noncategorical, nonlinear, volume-outcome relationship in esophagectomy. METHODS: Data were derived from the Netherlands Cancer Registry. Restricted cubic splines were used to investigate the nonlinear effects of annual hospital volume on 6 month and 2 year mortality rates. Outcomes were adjusted for year of diagnosis, case-mix, and (neo)adjuvant treatment. RESULTS: Between 1989 and 2009, 10,025 patients underwent esophagectomy for cancer in the Netherlands. Annual hospital volumes varied between 1 and 83 year, increasing over time. Increasing annual hospital volume showed a continuous, nonlinear decrease in hazard ratio (HR) for mortality along the curve. Increasing hospital volume from 20 year (baseline, HR = 1.00) to 40 and 60 year was associated with decreasing 6 month mortality, with a HR of 0.73 (95 % confidence interval (0.65-0.83) and 0.67 (0.58-0.77) respectively. Beyond 60 year, no further decrease was detected. Higher hospital volume also was associated with decreasing 2 year mortality until 50 esophagectomies year with a HR of 0.86 (0.79-0.93). CONCLUSIONS: Centralization of esophagectomy to a minimum of 20 resections/year has been effectively introduced in the Netherlands. Increasing annual hospital volume was associated with a nonlinear decrease in mortality up to 40-60 esophagectomies/year, after which a plateau was reached. This finding may guide quality improvement efforts worldwide.

Gastric cancer: decreasing incidence but stable survival in the Netherlands.

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.

Quality of care indicators for the surgical treatment of gastric cancer: a systematic review.

BACKGROUND: Quality assurance is increasingly acknowledged as a crucial factor for the (surgical) treatment of gastric cancer. The purpose of the current study was to define a minimum set of evidence-based quality of care indicators for the surgical treatment of locally advanced gastric cancer. METHODS: A systematic review of the literature published between January 1990 and May 2011 was performed, using search terms on gastric cancer, treatment, and quality of care. Studies were selected based on predefined selection criteria. Potential quality of care indicators were assessed based on their level of evidence and were grouped into structure, process, and outcome indicators. RESULTS: A total of 173 articles were included in the current study. For structural measures, evidence was found for the inverse relationship between hospital volume and postoperative mortality as well as overall survival. Regarding process measures, the most common indicators concerned surgical technique, perioperative care, and multimodality treatment. The only outcome indicator with supporting evidence was a microscopically radical resection. CONCLUSIONS: Although specific literature on quality of care indicators for the surgical treatment of locally advanced gastric cancer is limited, several quality of care indicators could be identified. These indicators can be used in clinical audits and other quality assurance programs.

Conditional probability of survival nomogram for 1-, 2-, and 3-year survivors after an R0 resection for gastric cancer.

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.

Randomized trials and quality assurance in gastric cancer surgery.

A D2 lymphadenectomy can be considered standard of surgical care for advanced resectable gastric cancer. Currently, several multimodality strategies are used, including postoperative monochemotherapy in Asia, postoperative chemoradiotherapy in the United States, and perioperative chemotherapy in Europe. As the majority of gastric cancer patients are treated outside the framework of clinical trials, quality assurance programs, including referral to high-volume centers and clinical auditing are needed to improve gastric cancer care on a nationwide level.

Lymph node dissection in resectable advanced gastric cancer.

The extent of surgery for gastric cancer has been debated since Billroth performed his first gastrectomy in 1881. This review gives an overview of the available literature on the extent of gastrectomy and lymphadenectomy for advanced resectable gastric cancer. Subtotal gastrectomy is associated with lower morbidity and mortality compared with total gastrectomy, without compromising long-term survival. However, a positive resection margin decreases the chance of curation. Frozen section examination may prevent this. For poorly differentiated singlet ring cell tumors, there may be an argument to perform a total gastrectomy in all cases. In 1981, the Japanese Research Society for the Study of Gastric Cancer provided guidelines for the standardization of surgical treatment and pathological evaluation of gastric cancer. Since then, D2 lymph node dissections have become the standard of care in Japan. Because of the superior stage-specific survival rates in Japan, a D2 dissection was evaluated in several Western randomized controlled trials, but no survival benefit was found for a D2 over a D1 dissection. This might be explained by the increased mortality in the D2 dissection groups which might be the result of a standard pancreaticosplenectomy and low experience with D2 dissections. Adding the removal of the para-aortic nodes to a D2 dissection does not further improve survival. The removal of lymph node stations 10 and 11 by splenectomy showed an increased morbidity, no survival benefit, and a very poor prognosis if lymph nodes were affected. Therefore, pancreaticosplenectomy should only be performed in cases of tumor invasion into these organs. A D2 dissection without routine splenectomy and pancreatic tail resection in experienced hands should be considered standard of care for advanced resectable gastric cancer, both in Asian and in Western patients. Centralization and auditing may further improve outcomes after gastrectomy.

Prospective impact of tumor grade assessment in biopsies on tumor stage and prognostic grouping in gastroesophageal adenocarcinoma: relevance of the seventh edition American Joint Committee on Cancer Staging Manual revision.

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.

The New American Joint Committee on Cancer/International Union Against Cancer staging system for adenocarcinoma of the stomach: increased complexity without clear improvement in predictive accuracy.

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.

Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS).

BACKGROUND: Radical surgery is the cornerstone in the treatment of resectable gastric cancer. The Intergroup 0116 and MAGIC trials have shown benefit of postoperative chemoradiation and perioperative chemotherapy, respectively. Since these trials cannot be compared directly, both regimens are evaluated prospectively in the CRITICS trial. This study aims to obtain an improved overall survival for patients treated with preoperative chemotherapy and surgery by incorporating radiotherapy concurrently with chemotherapy postoperatively. METHODS/DESIGN: In this phase III multicentre study, patients with resectable gastric cancer are treated with three cycles of preoperative ECC (epirubicin, cisplatin and capecitabine), followed by surgery with adequate lymph node dissection, and then either another three cycles of ECC or concurrent chemoradiation (45 Gy, cisplatin and capecitabine). Surgical, pathological, and radiotherapeutic quality control is performed. The primary endpoint is overall survival, secondary endpoints are disease-free survival (DFS), toxicity, health-related quality of life (HRQL), prediction of response, and recurrence risk assessed by genomic and expression profiling. Accrual for the CRITICS trial is from the Netherlands, Sweden, and Denmark, and more countries are invited to participate. CONCLUSION: Results of this study will demonstrate whether the combination of preoperative chemotherapy and postoperative chemoradiotherapy will improve the clinical outcome of the current European standard of perioperative chemotherapy, and will therefore play a key role in the future management of patients with resectable gastric cancer. TRIAL REGISTRATION: clinicaltrials.gov NCT00407186.

Performance of a nomogram predicting disease-specific survival after an R0 resection for gastric cancer in patients receiving postoperative chemoradiation therapy.

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.

Treatment of resectable gastric cancer.

Stomach cancer is one of the most common cancers worldwide, despite its declining overall incidence. Although there are differences in incidence, etiology and pathological factors, most studies do not separately analyze cardia and noncardia gastric cancer. Surgery is the only potentially curative treatment for advanced, resectable gastric cancer, but locoregional relapse rate is high with a consequently poor prognosis. To improve survival, several preoperative and postoperative treatment strategies have been investigated. Whereas perioperative chemotherapy and postoperative chemoradiation (CRT) are considered standard therapy in the Western world, in Asia postoperative monochemotherapy with S-1 is often used. Several other therapeutic options, although generally not accepted as standard treatment, are postoperative combination chemotherapy, hyperthermic intraperitoneal chemotherapy and preoperative radiotherapy and CRT. Postoperative combination chemotherapy does show a statistically significant but clinically equivocal survival advantage in several meta-analyses. Hyperthermic intraperitoneal chemotherapy is mainly performed in Asia and is associated with a higher postoperative complication rate. Based on the currently available data, the use of postoperative radiotherapy alone and the use of intraoperative radiotherapy should not be advised in the treatment of resectable gastric cancer. Western randomized trials on gastric cancer are often hampered by slow or incomplete accrual. Reduction of toxicity for preoperative and especially postoperative treatment is essential for the ongoing improvement of gastric cancer care.

Increased incidence and survival for oesophageal cancer but not for gastric cardia cancer in the Netherlands.

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.