European Colorectal Cancer Research Articles

Patterns of care for European colorectal cancer patients diagnosed 1996–1998: A EUROCARE High Resolution Study

Objective. To identify disparities in the management of colon and rectal cancer across Europe by assessing population-based information from 12 European cancer registries (CR) participating in EUROCARE, together with additional information obtained from individual clinical records. Methods and patients. We considered five indicators: (a) resection with curative intent; (b) post-operative mortality; (c) proportion of stage II/III colon cancer cases given adjuvant chemotherapy; (d) proportion of rectal cancer cases receiving radiotherapy; and (e) proportion of curative intent resections with 12 or more lymph nodes examined. Results. A total of 6 871 colorectal cancer patients, diagnosed between 1996–1998, were examined. Overall 71% of patients received resection with curative intent, range 44–86% by CR; 46% of stage III colon cancer cases (range 24–73% by CR) and 22% of stage II cases (not then recommended) received adjuvant chemotherapy; 12% of rectal cancer cases received adjuvant radiotherapy, range ≤2% in five CRs to >51% in two CRs. For only 29% of curative intent resections were 12 or more lymph nodes examined. Conclusions. This study reveals that, although most patients received surgery with curative intent, disparities in treatment for colorectal cancer across Europe in the late 1990s were unexpectedly large, with many patients not receiving treatments indicated by published clinical trials. Consensus guidelines for CRC management are now becoming available and should be adopted across Europe. It is hoped that dissemination of guidelines will improve the use of scientifically proven treatments for the disease, but this should be monitored by further population-based studies.

Recommendations to improve identification of hereditary and familial colorectal cancer in Europe

Familial colorectal cancer (CRC) accounts for 10-15% of all CRCs. In about 5% of all cases, CRC is associated with a highly penetrant dominant inherited syndrome. The most common inherited form of non-polyposis CRC is the Lynch syndrome which is responsible for about 2-4% of all cases. Surveillance of individuals at high risk for CRC prevents the development of advanced CRC. About 1 million individuals in Western Europe are at risk for Lynch syndrome. We performed a survey to evaluate the strategies currently used to identify individuals at high risk for CRC in 14 Western European countries. Questionnaires were distributed amongst members of a European collaborative group of experts that aims to improve the prognosis of families with hereditary CRC. The survey showed that in all countries obtaining a family history followed by referral to clinical genetics centres of suspected cases was the main strategy to identify familial and hereditary CRC. In five out of seven countries with a (regional or national) CRC population screening program, attention was paid in the program to the detection of familial CRC. In only one country were special campaigns organized to increase the awareness of familial CRC among the general population. In almost all countries, the family history is assessed when a patient visits a general practitioner or hospital. However, the quality of family history taking was felt to be rather poor. Microsatellite instability testing (MSI) or immunohistochemical analysis (IHC) of CRC are usually recommended as tools to select high-risk patients for genetic testing and are performed in most countries in patients suspected of Lynch syndrome. In one country, IHC was recommended in all new cases of CRC. In most countries there are no specific programs on cancer genetics in the teaching curriculum for medical doctors. In conclusion, the outcome of this survey and the discussions within an European expert group may be used to improve the strategies to identify individuals at high risk of CRC. More attention should be given to increasing the awareness of the general population of hereditary CRC. Immunohistochemical analysis or MSI-analysis of all CRCs may be an effective tool for identifying all Lynch syndrome families. The cost-effectiveness of this approach should be further evaluated. All countries with a CRC population screening program should obtain a full family history as part of patient assessment.

Primary colon cancer: ESMO Clinical Recommendations for diagnosis, adjuvant treatment and follow-up

Staging provides essential prognostic information relevant for choosing adequate therapy and should also identify patients with resectable distant metastases. Preoperative staging consists of clinical examination, blood counts, liver and renal function tests, carcino-embryonic antigen (CEA), chest X-ray or preferably chest CT-scan, CT scan of the abdomen including the pelvis and a colonoscopy of the entire large bowel, i.e. with postoperative repeat colonoscopy if proximal parts of the colon were not accessible preoperatively. Pathologic staging should be done according to the 2002TNM system with optional listing of the modified Dukes stage, as described in Table 1. Risk factors for colorectal cancer are: family history, familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) syndromes, hereditary non-polyposis colorectal cancer (HNPCC) syndrome, past history of colorectal cancer or adenoma, chronic ulcerative colitis and Crohn’s disease. prognosis

EUROCARE-4 studies bring new data on cancer survival

The EUROCARE studies represent an excellent example of a largely informal collaboration, which now involves over 80 cancer registries across 23 countries. Previous studies have studied differences in survival for individual cancers between countries for patients diagnosed in 1985–89 (EUROCARE-2) 1 Berrino F Capocaccia R Estève J et al. Survival of cancer patients in Europe: the EUROCARE-2 study. IARC Scientific Publications, number 151. IARC Press, Lyon1999 Google Scholar and 1990–94 (EUROCARE-3). 2 Berrino F Capocaccia R Coleman MP et al. Survival of cancer patients in Europe: the EUROCARE-3 study. Ann Oncol. 2003; 14: 1-155 PubMed Google Scholar Possible explanations for differences in survival have been explored for some cancers through so-called high-resolution studies. 3 Sant M Allemani C Capocaccia R et al. Stage at diagnosis is a key explanation of differences in breast cancer survival across Europe. Int J Cancer. 2003; 106: 416-422 Crossref PubMed Scopus (230) Google Scholar , 4 Gatta G Capocaccia R Sant M et al. Understanding variations in survival for colorectal cancer in Europe: a EUROCARE high resolution study. Gut. 2000; 47: 533-538 Crossref PubMed Scopus (222) Google Scholar , 5 Sant M Aareleid T Artioli ME et al. Ten-year survival and risk of relapse for testicular cancer: a EUROCARE high resolution study. Eur J Cancer. 2007; 43: 585-592 Summary Full Text Full Text PDF PubMed Scopus (49) Google Scholar These studies involved much smaller numbers of patients, but attempted to study the effect of disease stage at diagnosis and of treatment through analysis of individual patient records. Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995–99: results of the EUROCARE-4 studyIncreases in survival and decreases in geographic differences over time, which are mainly due to improvements in health-care services in countries with poor survival, might indicate better cancer care. Wealthy countries with high TNEH generally had good cancer outcomes, but those with conspicuously worse outcomes than those with similar TNEH might not be allocating health resources efficiently. Full-Text PDF Recent cancer survival in Europe: a 2000–02 period analysis of EUROCARE-4 dataCancer-service infrastructure, prevention and screening programmes, access to diagnostic and treatment facilities, tumour-site-specific protocols, multidisciplinary management, application of evidence-based clinical guidelines, and recruitment to clinical trials probably account for most of the differences that we noted in outcomes. Full-Text PDF Does the UK really have an effective cancer plan?In this issue of The Lancet Oncology, we publish findings from EUROCARE-4: the largest international population-based analysis of cancer survival based on data from 83 registries in 23 countries. In keeping with earlier EUROCARE analyses (in 1995, 1999, and 2003), the latest findings show 5-year cancer survival in Europe continues to improve and rates in eastern Europe are catching up with western Europe. Cancer care is, therefore, getting better, and patients in Europe are achieving outcomes closer to those seen for patients treated in the USA. Full-Text PDF

Colorectal cancer screening awareness in European primary care

Background: Adjustment for stage at diagnosis markedly reduces USA versus European colorectal cancer survival differences and a screening bias was therefore suspected. Moreover, little is known about colorectal cancer screening habits in European primary care and the history of guidelines implementation. The purpose of the study was to index the overall colorectal cancer screening attitudes of European physicians involved in primary care activities. Methods: A systematic literature-search was performed in three major medical libraries: PubMed/MEDLINE, ISI web of science, and COCHRANE. Results: We found only five eligible studies, but valuable data were presented only in four. Colorectal cancer screening was recommended by 65–95% of physicians, but the major part of them implemented it only among high-risk individuals; stool occult blood testing was advised by 42–83% and prescription of screening endoscopic modalities was inconsistent. Most European reports found were not eligible and were mainly focused on diagnostic delay in symptomatic subjects rather than on screening procedures among asymptomatic individuals. Conclusion: In comparison with European practice, colorectal cancer screening habits of American physicians are to a greater extent rational, evidence-based and well monitored and have a longer tradition in medical care thus allowing better prevention services for asymptomatic individuals.

Circadian Rhythm in Dihydropyrimidine Dehydrogenase Activity and Reduced Glutathione Content in Peripheral Blood of Nasopharyngeal Carcinoma Patients

Dihydropyrimidine dehydrogenase (DPD) is a rate‐limiting enzyme of 5‐fluorouracil (5‐FU) catabolism. Glutathione (GSH) is a tripeptide involved in platinum complex detoxification. This study explored the circadian rhythms of DPD activity and GSH concentration in the peripheral blood of 16 patients with histologically proven nasopharyngeal carcinoma (NPC) in order to guide the establishment of chronotherapeutic schedules for this cancer. DPD activity and GSH concentration were determined by high performance liquid chromatography (HPLC). Both variables displayed significant circadian rhythms (Cosinor analysis: p=0.009 and 0.012, respectively). Peak DPD activity occurred at about 02:30 h; whereas, peak GSH concentration occurred around 12:40 h. The differences between the peak and nadir mean values were 25.5% and 38.7%, respectively. The study showed that the circadian rhythms in DPD activity and GSH concentration in Chinese NPC are similar to those reported for western patients with colorectal cancer, despite the differences in race and kinds of cancer. These findings imply that the chronotherapeutic schedule of 5‐FU and platinum used to treat European colorectal cancer patients probably is applicable to Chinese NPC patients.

Public awareness of risk factors and screening for colorectal cancer in Europe

Colorectal cancer (CRC) is the commonest site for malignancy in Europe. The Commissioner for Health wishes to promote screening for colorectal, breast and cervical cancer in Europe. The aim of this study was to assess public knowledge of CRC in Europe and likely take up of free screening. To this end 20710 members of the public from 21 European countries were interviewed by means of a regular survey amongst consumers (Omnibus survey) using 13 stem questions. Forty-eight per cent thought the population were at equal risk of CRC, only 57% were aware of age and 54% of family history as risk factors. Although 70% were aware of dietary factors, only 30% knew that lack of exercise might be a risk factor. Only 51% had knowledge of CRC screening but 75% were 'very', or 'quite interested, in taking up faecal occult blood (FOB) screening if offered free. Barriers to screening were lack of awareness of risk (31%), youth (22%) and an un-anaesthetic test (19%). There was a big cultural difference in willingness of the public to discuss bowel symptoms: there was a major barrier in Finland (91%), Britain (84%), Luxembourg (82%), Poland (81%) and Portugal (80%); less of a barrier in Spain (49%), Italy (44%) and Iceland (39%). In conclusion, the challenge of achieving high compliance for CRC screening must be a major objective amongst EU member states and non-aligned countries of Europe in the next decade, because it is known that the non-compliant group are those at greatest risk of death from CRC. This study has shown that awareness of CRC is low in Europe and that an educational programme will be essential to achieve high compliance for CRC screening as a means of reducing deaths from bowel cancer.

Introduction

The burden of colorectal cancer in Europe is severe and increasing, and there is political as well as some medical impetus in the direction of nationwide screening programs. The specific strategies for screening vary, however, indicating the lack of hard evidence on the best choice. Even more variation is seen in the choice of tactics for implementing the strategy chosen. The challenge of motivating the public to adhere to screening programs is daunting, and different countries choose widely different strategies to accomplish this.

Screening for colorectal cancer in Europe

Screening for colorectal cancer in Europe

Differences in colorectal cancer survival between European and US populations: the importance of sub-site and morphology

A previous study has shown a lower survival for colorectal cancer in Europe than in the United States of America (USA). It is of interest to examine the extent to which anatomical location and morphological type influence this difference in colorectal cancer survival. We analysed survival for 151 244 European and 53 884 US patients diagnosed with colorectal cancer aged 15–99 years during the period of 1985–1989, obtained from 40 cancer registries that contribute to the EUROCARE study from 17 countries, and nine Surveillance, Epidemiology and End-Results (SEER) registries in the USA. Cases included in the analysis were first primary malignant tumours (ICD-O behaviour code 3 or higher). Relative survival was estimated to correct for competing causes of mortality. The Hakulinen–Tenkanen multiple regression approach was used to examine the prognostic impact of sub-site and ICD-O histology codes. Relative excess risks (RERs) derived from this approach estimate the extent to which the hazard of death differs from that in a reference region after adjustment for mortality in the general population. In order to explore geographical variation, we defined three groups of European registries within which survival rates were known to be broadly similar. The proportion of cases with unspecified sub-site was higher in Europe than the USA (10% versus 2%), but sub-site distributions were broadly similar in the two populations. With the exception of appendix, 5-year survival was 13–22% higher in the USA than in Europe for each anatomical sub-site. The proportion of non-microscopically-verified cases was higher in Europe than the USA (16 versus 3%). Adenocarcinomas arising in a polyp (ICD-O-2 8210, 8261, 8263) were more frequent in the USA than Europe (13 versus 2%). Five-year survival was higher in the USA than Europe for each morphological group, with the exception of non-microscopically-verified cases. When age, gender and sub-site were considered, RERs ranged from 1.52 to 2.40 for the European populations (with the USA as a reference). After inclusion of morphology codes, the range of RERs fell to between 1.28 and 1.86, mainly because of the high frequency of adenocarcinoma in polyps in the USA. This analysis suggests that the large survival advantage for colorectal cancer patients in the USA can only marginally be explained by differences in the distribution of sub-site and morphology. The main explanatory difference is the proportion of adenocarcinoma in polyps.

Therapeutic strategies for colorectal cancer in Europe and the United States: focus on chemotherapy for advanced colorectal cancer.

Therapeutic strategies for colorectal cancer in Europe and the United States: focus on chemotherapy for advanced colorectal cancer.

New therapeutic options in colon cancer: focus on oxaliplatin.

Colon cancer is the third leading cause of cancer death in the United States and the second leading cause in the Northern, Central, and Southern Americas. Appropriate treatment depends on the stage of malignancy, which is determined using the tumor-lymph node-metastases system. In stage III disease, adjuvant chemotherapy increases disease-free and long-term survival following surgery, and chemotherapy is the mainstay of treatment for advanced disease. New therapies are being evaluated, including oxaliplatin, a third-generation platinum analogue approved as first- and second-line therapy for metastatic colorectal cancer in Europe; the drug shows great promise combined with 5-fluorouracil/leucovorin or with irinotecan. The dose-limiting toxicity of oxaliplatin is neurologic, which can be acute or chronic; this can be prevented or reduced in some cases through patient education. Nurses play a critical role in education concerning prevention and management of oxaliplatin-related side effects.

Dukes C結腸癌におけるリンパ節転移個数と予後との関連に関する検討

Background:The number of metastatic lymph nodes is considered an important prognostic factor in colorectal cancer in Europe and North America. Methods:We studied prognostic factors in 144 patients with Dukes C colon cancer undergoing curative surgery. Results:No significant differences was seen in survival due to the histological depth of tumor invasion and lymphatic or venous invasion. No significant differences was seen in 5-year survival between patients with n1 metastasis (n=94, 72.2%) and n2+n3 metastasis (n=45+5, 66.2%) based on the Japanese Classification of Colorectal Carcinoma (JCCC). Five-year survival in patients with 2 or fewer metastatic lymph nodes (n=86, 80.7%) was statistically higher than that in those with 3 or more metastatic lymph nodes (n=58, 52.8%) (p=0.011). Five-year survival in those with 3 or fewer metastatic nodes (n=104, 78.3%) was also statistically higher than that in those with 4 or more metastatic nodes (n=40, 46.7%) (p=0.022), as is the TNM Classification. Discussion:The number of metastatic lymph nodes, i.e., -2 vs 3-or-3 vs 4-, is a prognostic factor in patients with Dukes C colon cancer. The metastatic lymph node number is thus to be included in the JCCC.

Understanding variations in survival for colorectal cancer in Europe: a EUROCARE high resolution study

BACKGROUNDMarked differences in population based survival across Europe were found for colorectal cancers diagnosed in 1985–1989.AIMSTo understand the reasons for these differences in survival in a new analysis of colorectal...

123 P - Breast and colo-rectal cancer in Europe: problems related to collection and analysis of dietary data

Assessment of dietary intake is important in epidemiological studies of diet and cancer at many sites, but is crucial when considering cancer of the colon, rectum and breast. In the framework of the Collaborative, Multicentre, Case-Control Study of Breast Cancer and Colo-Rectal Cancer food frequency questionnaires (FFQs) and food composition databases (FDBs) were tailored specifically for the participating centres. Here problems and approaches in developing and validating FFQs and FDBs for the centres in Italy, Slovenia and Ireland will be described and comparison made of the resulting instruments. All FFQs are interviewer administered. The Italian FFQ includes 78 questions on the frequency of consumption of specific foods, or groups of foods, as well as additional questions on fat consumption. An ad hoc FDB including almost 2000 foods and dishes was developed for this study, mainly from data provided by the National Nutrition Institute of Rome. In Slovenia, the food frequency questionnaire was developed with a structure that is very similar to that of the Italian instrument. A total of 136 items, plus alcoholic beverages and coffee, are included in the questionnaire. In Ireland the final list of questions includes 176 foods, plus alcoholic beverages and coffee. The complete FDB includes approximately 3000 items and is mainly derived from the British food composition tables. The final versions will be a major resource for cancer research in these countries for many years.

DNA-damaging activity in ethanol-soluble fractions of feces from New Zealand groups at varying risks of colorectal cancer.

Using repair-proficient and repair-deficient strains of E. coli, we investigated the application of a liquid incubation assay to measure the DNA-damaging activity of ethanol-soluble fecal extracts. This method appears to be suitable for the study of a wide range of sample types. It was used to measure the DNA-modifying activity of ethanol-soluble fecal extracts from a group of European colorectal cancer patients. Data were compared with those from Europeans of similar age and sex distribution who did not have bowel cancer. We also studied groups of Maoris, Samoans, and European Seventh-Day Adventists who followed an ovo-lacto vegetarian diet. There are significant levels of DNA-modifying materials in the feces of many Europeans on a mixed diet, regardless of whether or not they have cancer. The number of positive samples was less in the Polynesian groups, and there were no samples that could be unequivocally scored as positive in the Seventh-Day Adventist groups. We conclude that diet can significantly reduce the level of ethanol-soluble mutagens, at least in New Zealand Europeans. The data may provide an explanation for the reduced incidence of bowel cancer in Seventh-Day Adventist groups.