Highlights • One fifth of operated colorectal cancer patients will develop metachronous metastases. • Colon and rectal cancer patients have different patterns of metastatic spread. • Median time to ...diagnosis depends on site of metastasis. • The risk for metastases is associated with patient and tumour characteristics.
IMPORTANCE Use of aspirin (which inhibits platelet function) after a colon cancer diagnosis is associated with improved overall survival. Identifying predictive biomarkers of this effect could ...individualize therapy and decrease toxic effects. OBJECTIVE To demonstrate that survival benefit associated with low-dose aspirin use after a diagnosis of colorectal cancer might depend on HLA class I antigen expression. DESIGN, SETTING, AND PARTICIPANTS A cohort study with tumor blocks from 999 patients with colon cancer (surgically resected between 2002 and 2008), analyzed for HLA class I antigen and prostaglandin endoperoxide synthase 2 (PTGS2) expression using a tissue microarray. Mutation analysis of PIK3CA was also performed. Data on aspirin use after diagnosis were obtained from a prescription database. Parametric survival models with exponential (Poisson) distribution were used to model the survival. MAIN OUTCOMES AND MEASURES Overall survival. RESULTS The overall survival benefit associated with aspirin use after a diagnosis of colon cancer had an adjusted rate ratio (RR) of 0.53 (95% CI, 0.38-0.74; P < .001) when tumors expressed HLA class I antigen compared with an RR of 1.03 (0.66-1.61; P = .91) when HLA antigen expression was lost. The benefit of aspirin was similar for tumors with strong PTGS2 expression (0.68; 0.48-0.97; P = .03), weak PTGS2 expression (0.59; 0.38-0.97; P = .02), and wild-type PIK3CA tumors (0.55; 0.40-0.75; P < .001). No association was observed with mutated PIK3CA tumors (0.73; 0.33-1.63; P = .44). CONCLUSIONS AND RELEVANCE Contrary to the original hypothesis, aspirin use after colon cancer diagnosis was associated with improved survival if tumors expressed HLA class I antigen. Increased PTGS2 expression or the presence of mutated PIK3CA did not predict benefit from aspirin. HLA class I antigen might serve as a predictive biomarker for adjuvant aspirin therapy in colon cancer.
Gastric cancer often presents in a metastasized stage. We conducted a population-based study to evaluate trends in systemic treatment and survival of metastatic noncardia gastric cancer.
All patients ...with noncardia adenocarcinoma of the stomach, diagnosed between 1990 and 2011 in the Eindhoven Cancer Registry area in the Netherlands were included (N = 4797). We conducted multivariable logistic regression analysis to evaluate trends in administration of palliative chemotherapy and multivariable proportional hazards regression analyses to evaluate trends in crude overall survival.
The proportion of patients presenting with metastatic gastric cancer increased from 24% in 1990 to 44% in 2011 (P < 0.0001). The use of palliative chemotherapy increased, from 5% in 1990 to 36% in 2011, with a strong increase in particular after 2006 (P < 0.0001). Younger patients <50 years: adjusted odds ratio (ORadj) 3.9, P < 0.001; 50–59 years: ORadj 1.7, P = 0.01 and patients with a high socioeconomic status (ORadj 1.7, P = 0.01) more often received chemotherapy. In contrast, older patients (70–79 years: ORadj 0.3, P < 0.001; 80+ years: ORadj 0.02, P < 0.001), patients with comorbidity (ORadj 0.6, P = 0.03), linitis plastica (ORadj 0.5, P = 0.03) and multiple distant metastases (ORadj 0.5, P = 0.01) were less often treated with chemotherapy. A large hospital variation was observed in the administration of palliative chemotherapy (9%–27%). Median overall survival remained constant between 15 95% confidence interval (CI) 11.9–17.7 and 17 (95% CI 15.0–20.0) weeks (P = 0.10).
The increased administration of chemotherapy in patients with metastatic gastric cancer did not lead to an increase in population-based overall survival. Identification of the subgroup of patients which benefits from palliative chemotherapy is of utmost importance to avoid unnecessary treatment.
Treatment for oesophageal cancer has evolved due to developments including the centralisation of surgery and introduction of neoadjuvant treatment. Therefore, this study evaluated trends in stage ...distribution, treatment and survival of oesophageal cancer patients in the last 26 years in the Netherlands.
Patients with oesophageal cancer diagnosed in the period 1989–2014 were selected from the Netherlands Cancer Registry. Patients were divided into two groups: non-metastatic (M0) and metastatic (M1). Trends in stage distribution, treatment and relative survival rates were evaluated according to histology.
Among all 35,760 patients, the percentage of an unknown tumour stage decreased from 34% to 10% during the study period, whereas the percentage of patients with metastatic disease increased from 21% to 34%. Among surgically treated patients 32% underwent a resection in a high-volume hospital in 2005 which increased to 92% in 2014. Use of neoadjuvant chemoradiotherapy increased in non-metastatic oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC) patients from respectively 4% and 2% in 2000–2004 to 43% and 26% in 2010–2014. Five-year relative survival increased from 8% to 22% for all patients; from 12% to 36% for non-metastatic OAC and from 9% to 27% for non-metastatic OSCC over 26 years. Median overall survival of metastatic patients improved from 18 to 22 weeks.
In the Netherlands, survival for oesophageal cancer patients improved significantly, especially in the period 2005–2014 which might be the result of better treatment related to the centralisation of surgery and introduction of neoadjuvant chemoradiotherapy.
•Five-year relative survival more than doubled in last 26 years for oesophageal cancer.•The use of neoadjuvant chemoradiotherapy increased significantly.•The percentage of patients who underwent surgery in a high-volume hospital increased.•Improved survival might be the result of the two abovementioned developments.
Highlights • 14% of 6620 colon cancer patients started adjuvant chemotherapy >8 weeks. • Elderly patients were more likely to start chemotherapy >8 weeks post-surgery. • Various treatment factors ...were associated with starting chemotherapy >8 weeks. • Starting adjuvant chemotherapy >8 weeks was associated with decreased survival. • Starting adjuvant chemotherapy 5–8 versus <4 weeks showed no difference in survival.
Abstract Introduction Population-based data on metachronous peritoneal carcinomatosis (PC) after curative resection of colorectal origin are scarce. The aim of this study was to investigate the ...incidence of and risk factors for developing metachronous PC from colorectal cancer as well as survival since diagnosis of PC. Methods Data on metachronous metastases were collected between 2010 and 2011 for all patients diagnosed with M0 colorectal cancer between 2003 and 2008 in the Dutch Eindhoven Cancer Registry. Median follow-up was 5.0 years. Survival was defined as time from metastases diagnosis to death. Results Of the 5671 colorectal cancer patients, 1042 (18%) were diagnosed with metachronous metastases of whom 197 (19%) developed metachronous PC. The peritoneal surface was the only site of metastasis in 81 (41%) patients while 116 (59%) patients were diagnosed with both PC and metastases elsewhere. Median survival after diagnosis of PC was 6 months compared to 15 months for patients with distant metastases in other organs. Patients with an advanced primary tumour stage, positive lymph nodes at initial diagnosis, primary mucinous adenocarcinoma, positive resection margin and a primary tumour located in the colon were at increased risk of developing metachronous PC. Conclusion Of the colorectal cancer patients who developed metachronous metastases, approximately one fifth is diagnosed with PC. Prognosis of these patients is poor with a median survival of 6 months after diagnosis. Identifying patients at high risk for developing metachronous PC is important as it may contribute to more accurate patient information, tailor-made follow-up schemes, and more adequate treatment.
Abstract Background Survival of gastric cancer in the Western world remains poor. We conducted a retrospective population-based study to evaluate trends in incidence, treatment and outcome of gastric ...adenocarcinoma. Methods All patients diagnosed with gastric adenocarcinoma during 1990–2007 in the Dutch Eindhoven Cancer Registry area were included ( n = 4797). Trend analyses were conducted for incidence, mortality, tumour and patient characteristics, treatment and crude overall survival, according to tumour location (cardia versus non-cardia). Temporal changes in the odds of undergoing surgery and the risk of death were analysed by means of multivariable regression methods. Results Age-standardised incidence decreased among males (24–12 per 100,000 inhabitants) and females (10–6); mortality rates decreased at a similar pace. The proportion of cardia tumours remained stable. Stage distribution worsened over time among patients with cardia (stages I and II: 32% in 1990–1993 and 22% in 2006–2007, p = 0.005) and non-cardia (stage IV: 33% in 1990–1993 and 40% in 2006–2007, p = 0.0003) cancer. Chemotherapy rates increased in all settings. Five-year survival worsened over time for patients with non-cardia tumours. Age and stage had significant influence on survival after stratification for tumour localisation. After adjustments for relevant factors (i.e. stage), the risk of death decreased since the late 90s for patients with a cardia tumour (hazard ratio 0.8, p = 0.01). Conclusion The absence of improvement in survival rates indicates the need for earlier detection and prospective studies to evaluate new therapy regimens with standardised surgery and pathology.
Background
Centralization of surgery has been shown to improve outcomes for oesophageal and pancreatic cancer, and has been implemented for gastric cancer since 2012 in the Netherlands. This study ...evaluated the impact of centralizing gastric cancer surgery on outcomes for all patients with gastric cancer.
Methods
Patients diagnosed with non‐cardia gastric adenocarcinoma in the intervals 2009–2011 and 2013–2015 were selected from the Netherlands Cancer Registry. Clinicopathological data, treatment characteristics and mortality were assessed for the periods before (2009–2011) and after (2013–2015) centralization. Cox regression analyses were used to assess differences in overall survival between these intervals.
Results
A total of 7204 patients were included. Resection rates increased slightly from 37·6 per cent before to 39·6 per cent after centralization (P = 0·023). Before centralization, 50·1 per cent of surgically treated patients underwent gastrectomy in hospitals that performed fewer than ten procedures annually, compared with 9·2 per cent after centralization. Patients who had gastrectomy in the second interval were younger and more often underwent total gastrectomy (29·3 per cent before versus 41·2 per cent after centralization). Thirty‐day postoperative mortality rates dropped from 6·5 to 4·1 per cent (P = 0·004), and 90‐day mortality rates decreased from 10·6 to 7·2 per cent (P = 0·002). Two‐year overall survival rates increased from 55·4 to 58·5 per cent among patients who had gastrectomy (P = 0·031) and from 27·1 to 29·6 per cent for all patients (P = 0·003). Improvements remained after adjustment for case mix; however, adjustment for hospital volume attenuated this association for surgically treated patients.
Conclusion
Centralization of gastric cancer surgery was associated with reduced postoperative mortality and improved survival.
Practice makes perfect?
Background
Centralization of pancreatic surgery has been shown to reduce postoperative mortality. It is unknown whether resection rates and survival have also improved. The aim of this study was to ...analyse the impact of nationwide centralization of pancreatic surgery on resection rates and long‐term survival.
Methods
All patients diagnosed in the Netherlands between 2000 and 2009 with cancer of the pancreatic head were identified in the Netherlands Cancer Registry. Changes in referral pattern, resection rates and survival after pancreatoduodenectomy were analysed. Multivariable regression analysis was used to assess the impact of hospital volume (20 or more procedures per year) on survival after resection.
Results
Between 2000 and 2009, 11 160 patients were diagnosed with cancer of the pancreatic head. The resection rate increased from 10·7 per cent in 2000–2004 to 15·3 per cent in 2005–2009 (P < 0·001). No significant difference in survival after resection was observed between the two intervals (P = 0·135), although survival was significantly better in high‐volume hospitals (median survival 18 months versus 16 months in low/medium‐volume hospitals; P = 0·017). After adjustment for patient and tumour characteristics, high hospital volume remained associated with better overall survival after resection (hazard ratio 0·70, 95 per cent confidence interval 0·58 to 0·84; P < 0·001).
Conclusion
Centralization of pancreatic cancer surgery led to increased resection rates. High‐volume centres had significantly better survival rates. Centralization improves patient outcomes and should be encouraged.
More evidence to support the volume outcome relationship
Molecular markers in colon cancer are needed for a more accurate classification and personalized treatment. We determined the effects on clinical outcome of the BRAF mutation, microsatellite ...instability (MSI) and KRAS mutations in stage II and stage III colon carcinoma.
Stage II colon carcinoma patients (n = 106) treated with surgery only and 258 stage III patients all adjuvantly treated with 5-fluorouracil chemotherapy were included. KRAS mutations in codons 12 and 13, V600E BRAF mutation and MSI status were determined.
Older patients (P < 0.001), right-sided (P = 0.018), better differentiated (P = 0.003) and MSI tumors (P < 0.001) were significantly more frequent in stage II than stage III. In both groups, there was a positive association between mutated BRAF and MSI (P = 0.001) and BRAF mutation and right-sided tumors (P = 0.001). Mutations in BRAF and KRAS were mutually exclusive. In a multivariate survival analysis with pooled stage II and stage III data, BRAF mutation was an independent prognostic factor for overall survival (OS) and cancer-specific survival hazards ratio (HR) = 0.45, 95% confidence interval (CI) 0.25–0.8 for OS and HR = 0.47, 95% CI 0.22–0.99. KRAS mutation conferred a poorer disease-free survival (HR = 0.6, 95% CI 0.38–0.97).
The V600E BRAF mutation confers a worse prognosis to stage II and stage III colon cancer patients independently of disease stage and therapy.
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