| 1. |
- Birgisson, Helgi, et al.
(author)
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Preoperative plasma TIMP-1 is an independent prognostic indicator in patients with primary colorectal cancer : a prospective validation study
- 2010
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 46:18, s. 3323-3331
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Journal article (peer-reviewed)abstract
- Background: Previous studies have suggested plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) as a stage independent prognostic marker in colorectal cancer (CRC) patients. The aim was to validate plasma TIMP-1 and serum carcino-embryonic antigen (CEA) levels as prognostic indicators in an independent population-based cohort of patients with CRC. Patients and methods: During 2000-2003, plasma and serum were collected preoperatively from 322 patients treated for primary CRC. TIMP-1 and CEA levels were determined by validated ELISA platforms. Results: High TIMP-1 and CEA levels each associated with poor overall survival (OS); TIMP-1 (hazard ratio (HR) 2.1; 95% confidence interval (CI) 1.6-2.7) and CEA (HR 1.2; 95% CI 1.1-1.3), and disease-free survival (DFS); TIMP-1 (HR 2.0; 95% CI: 1.5-2.6) and CEA (HR 1.2; 95% CI: 1.1-1.4) in univariate analyses. In stratified analyses of stages II and III, TIMP-1 levels associated significantly with OS and DFS in stages II and III, associations were not found for CEA. Multivariate analysis for OS, including TIMP-1 and CEA levels and clinico-pathological baseline variables, revealed significant association of TIMP-1 (HR 1.8; 95% CI 1.3-2.4) but not CEA levels. Conclusions: This independent prospective validation study confirms the significant association between preoperative plasma TIMP-1 levels and survival of CRC patients: TIMP-1 provided stronger prognostic information than CEA. Thus, this study brings plasma TIMP-1 to the next level of evidence for its clinical use as a prognostic marker in CRC patients.
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| 2. |
- Bonnetain, Franck, et al.
(author)
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Guidelines for time-to-event end-point definitions in trials for pancreatic cancer : Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials)
- 2014
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 50:17, s. 2983-2993
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Research review (peer-reviewed)abstract
- Background: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. Methods: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). Results: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. Conclusion: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.
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| 3. |
- Brændengen, Morten, et al.
(author)
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Health-related quality of life (HRQoL) after multimodal treatment for primarily non-resectable rectal cancer : Long-term results from a phase III study
- 2012
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 48:6, s. 813-819
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Journal article (peer-reviewed)abstract
- BACKGROUND: A randomised study in non-resectable rectal cancer showed that preoperative chemoradiotherapy (CRT) resulted in better local control and disease-specific survival, but not overall survival than radiotherapy alone. The present paper presents long-term (>4years) health-related quality of life (HRQoL) and a comparison between the results and reference values from the Norwegian general population. MATERIAL AND METHODS: A total of 207 patients with primarily non-resectable rectal cancer were randomised to preoperative CRT (2Gyx25+5FU/leucovorin) or RT (2Gyx25) before surgery. HRQoL was assessed using EORTC QLQ-C30, completed at baseline and sent to all patients alive in Norway and Sweden (n=105) after a minimum of 4years post treatment. A difference of ⩾5 points on the 0-100 scales was considered clinically significant. RESULTS: Seventy-six (72%) patients answered at follow-up. No statistically significant differences between the CRT and RT groups appeared at follow-up, although clinically significant differences in social functioning, dyspnoea and diarrhoea were found. Over time, a clinically significant reduction in physical functioning was found in both groups. Moreover, reduced social functioning and less diarrhoea in the CRT group and better role functioning and more diarrhoea in the RT group were found. Comparisons between the study group and age and gender matched reference values indicate impaired social functioning and more diarrhoea among the patients. CONCLUSION: There were no statistically significant differences in HRQoL between the randomisation groups. In general, despite having impaired social functioning and more diarrhoea, patients reported HRQoL comparable with the reference population several years after treatment.
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| 4. |
- Cavalli-Björkman, Nina, 1970-, et al.
(author)
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Differences according to educational level in the management and survival of colorectal cancer in Sweden
- 2011
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 47:9, s. 1398-1406
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Journal article (peer-reviewed)abstract
- Socioeconomic status (SES) affects survival after a cancer diagnosis. The extent to which differences in management can explain this is not known. Record-linkage between two Swedish Regional Clinical Quality Registers of colorectal cancer and a socio-economic database generated a dataset with information on diagnostic procedures, treatment and survival in patients of different educational background. Three thousand eight hundred and ninety-nine rectal cancer patients from the years 1995 to 2006 and 5715 colon cancer patients from 1997 to 2006 were evaluated. Compared to patients with high education, those with shorter education had poorer relative and overall survival (57.9% 5-year relative survival versus 63.8% in colon cancer, 58.7% versus 69.1% in rectal cancer). There were also differences in diagnostic activity with preoperative computer tomography (40% versus 47.3%) and colonoscopy (56.3% versus 62.8%) being more frequent in highly educated groups (p = 0.001 and 0.037, respectively). Surgery resulting in colostomy was performed in 26.9% of rectal cancer patients of high education compared to 35.5% of those with low education (p = 0.005). Although rectal cancer has poorer prognosis than colon cancer, it was noted that among the highly educated, rectal cancer patients had better survival than colon cancer patients (69.1% versus 63.8% 5-year relative survival). It thus appears that improved rectal cancer management has benefited mainly patients of middle and higher educational levels. We conclude that socioeconomic differences exist in diagnostic activity and management of colorectal cancer, which may affect survival.
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| 5. |
- Eloranta, S., et al.
(author)
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Does socioeconomic status influence the prospect of cure from colon cancer - A population-based study in Sweden 1965-2000
- 2010
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 46:16, s. 2965-2972
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Journal article (peer-reviewed)abstract
- Aim of study Differences in the survival of colon cancer patients by socioeconomic status have been demonstrated in several populations but the underlying reasons for the differences are not well understood By simultaneously estimating the proportion of patients cured from colon cancer and the survival times of the uncured we hope to increase under standing of how socioeconomic status affects survival following a diagnosis of colon cancer Methods We conducted a population based cohort study of 58 873 patients diagnosed with colon cancer in Sweden 1965-2000 Socioeconomic status was classified based on occupation We fitted mixture cure models and Poisson regression models adjusted for age sex and calendar period Results We observed higher excess mortality lower proportion cured and shorter survival times among the uncured in patients from lower socioeconomic groups compared to the highest socioeconomic group There was no evidence that the gap between the socioeconomic groups reduced over time Farmers had the lowest odds of cure (odds ratio (OR) 0 85 95% confidence interval (Cl) 0 75-0 95) compared to higher non manual workers followed by self employed (0 91, 0 81-1 03) manual workers (0 93, 0 85-1 03) and lower non manual workers (0 91 0 89-1 08) Conclusion Patients from lower socioeconomic groups in Sweden experience worse survival following a diagnosis of colon cancer Differences exist in both the cure proportion and the survival time of the uncured suggesting that socioeconomic differences cannot be attributed solely to lead time bias Although this study has furthered our under standing of socioeconomic differences in survival more detailed studies are required in order to identify and subsequently remove the underlying reasons for the differences.
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| 6. |
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| 7. |
- Olsson, L. I., et al.
(author)
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Socioeconomic inequalities in the use of radiotherapy for rectal cancer : A nationwide study
- 2011
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 47:3, s. 347-353
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Journal article (peer-reviewed)abstract
- Preoperative radiotherapy (PRT) in rectal cancer reduces the risk of local recurrence by at least half but the influence of the socioeconomic status of patients on the use of PRT is little investigated in Europe. METHODS: Individually attained data on civil status, education and income were linked to the Swedish Rectal Cancer Registry 1995-2005 (n=16,713) and analysed by logistic regression. RESULTS: Forty-six percentage of the patients received PRT and the crude rate varied with age, gender, civil status, education and income as well as with sublocalisation, stage, type of hospital and health care region. In a multivariate analysis, all civil status groups had PRT to a lesser extent compared with married patients; odds ratio (OR) for unmarried patients was 0.67 (95% confidence interval (CI) 0.59-0.76). Patients with secondary and university education had PRT to the same extent as those with compulsory school (OR 1.04 (0.94-1.15) and 0.92 (0.81-1.06)). The use of PRT was associated with income; OR for patients with income Q1 versus Q4 was 0.76 (0.67-0.86). The inequalities by civil status and income remained unchanged also in groups with a relatively stronger indication for adjuvant radiotherapy, i.e. younger patients and in low rectal cancer. CONCLUSION: Unmarried and low-income patients are at increased risk for not receiving PRT in rectal cancer. Comorbidity may explain some differences but increased awareness of the role of non-medical variables for the use of PRT is warranted.
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| 8. |
- Sclafani, F., et al.
(author)
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RAS mutations and cetuximab in locally advanced rectal cancer : Results of the EXPERT-C trial
- 2014
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 50:8, s. 1430-1436
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Journal article (peer-reviewed)abstract
- Background: RAS mutations predict resistance to anti-epidermal growthfactor receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer. We analysed RAS mutations in 30 non-metastatic rectal cancer patients treated with or without cetuximab within the 31 EXPERT-C trial. Methods: Ninety of 149 patients with tumours available for analysis were KRAS/BRAF wild-type, and randomly assigned to capecitabine plus oxaliplatin (CAPOX) followed by chemoradiotherapy, surgery and adjuvant CAPOX or the same regimen plus cetuximab (CAPOX-C). Of these, four had a mutation of NRAS exon 3, and 84 were retrospectively analysed for additional KRAS (exon 4) and NRAS (exons 2/4) mutations by using bi-directional Sanger sequencing. The effect of cetuximab on study end-points in the RAS wild-type population was analysed. Results: Eleven (13%) of 84 patients initially classified as KRAS/BRAF wild-type were found to have a mutation in KRAS exon 4 (11%) or NRAS exons 2/4 (2%). Overall, 78/149 (52%) assessable patients were RAS wild-type (CAPOX, n = 40; CAPOX-C, n = 38). In this population, after a median follow-up of 63.8 months, in line with the initial analysis, the addition of cetuximab was associated with numerically higher, but not statistically significant, rates of complete response (15.8% versus 7.5%, p = 0.31), 5-year progression-free survival (75.5% versus 67.5%, hazard ratio (HR) 0.61, p = 0.25) and 5-year overall survival (83.8% versus 70%, HR 0.54, p = 0.20). Conclusions: RAS mutations beyond KRAS exon 2 and 3 were identified in 17% of locally advanced rectal cancer patients. Given the small sample size, no definitive conclusions on the effect of additional RAS mutations on cetuximab treatment in this setting can be drawn and further investigation of RAS in larger studies is warranted. (C) 2014 Elsevier Ltd. All rights reserved.
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| 9. |
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| 10. |
- van de Velde, Cornelis J. H., et al.
(author)
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EURECCA colorectal : Multidisciplinary Mission statement on better care for patients with colon and rectal cancer in Europe
- 2013
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 49:13, s. 2784-2790
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Journal article (peer-reviewed)abstract
- Background: Care for patients with colon and rectal cancer has improved in the last twenty years however still considerable variation exists in cancer management and outcome between European countries. Therefore, EURECCA, which is the acronym of European Registration of cancer care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012 the first multidisciplinary consensus conference about colon and rectum was held looking for multidisciplinary consensus. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries.Methods: The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Experts commented and voted on the two web-based online voting rounds before the meeting (between 4th and 25th October and between the 20th November and 3rd December 2012) as well as one online round after the meeting (4th-20th March 2013) and were invited to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. All sentences that were voted on are available on the EURECCA website www.canceraudit.eu. The consensus document was divided in sections describing evidence based algorithms of diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and stage IV separately. Consensus was achieved using the Delphi method.Results: The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members.Conclusions: It is feasible to achieve European Consensus on key diagnostic and treatment issues using the Delphi method. This consensus embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe.
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