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- Moayyeri, Alireza, et al.
(author)
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Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:11, s. 3054-3068
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Journal article (peer-reviewed)abstract
- Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
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- 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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| 5. |
- van de Velde, Cornelis J H, et al.
(author)
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EURECCA colorectal: Multidisciplinary management: European consensus conference colon & rectum.
- 2014
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In: European journal of cancer (Oxford, England : 1990). - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 50:1
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Journal article (peer-reviewed)abstract
- Care for patients with colon and rectal cancer has improved in the last 20years; however considerable variation still exists in cancer management and outcome between European countries. Large variation is also apparent between national guidelines and patterns of cancer care in Europe. 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 cancer of the colon and rectum was held. 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.
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| 6. |
- Lawler, Mark, et al.
(author)
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A Catalyst for Change: The European Cancer Patient's Bill of Rights.
- 2014
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In: The Oncologist. - : Oxford University Press (OUP). - 1549-490X .- 1083-7159.
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Journal article (peer-reviewed)abstract
- The European Cancer Concord is a unique patient-centered partnership that will act as a catalyst to achieve improved access to an optimal standard of cancer care and research for European citizens. In order to provide tangible benefits for European cancer patients, the partnership proposes the creation of a “European Cancer Patient's Bill of Rights,” a patient charter that will underpin equitable access to an optimal standard of care for Europe's citizens.
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| 7. |
- van Gijn, W., et al.
(author)
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The EURECCA project : Data items scored by European colorectal cancer audit registries
- 2012
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In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 38:6, s. 467-471
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Journal article (peer-reviewed)abstract
- Aims: The EURECCA (European Registration of Cancer Care) consortium is currently formed by nine independently founded national colorectal audit registrations, of which most already run for many years. The cumulative experience of EURECCA's participants could be used to identify a 'core dataset' that covers all important aspects needed for high quality auditing and at the same time lacking needless data items that only consumes administrative effort. The aim of this study is to compare the data items used by the nine registries participating in EURECCA to identify a core dataset and explore options for future research. Methods: All colorectal outcome registrations participating in the EURECCA project were asked to supply a list with all the data items they score. Items were scored 'present' if they appeared literally in a registration or in case they could he calculated using other items in the same registration. The definition of a 'shared data item' was that at least eight of the nine participating registries scored the item. Results: The number of registered data items varied between 254 (Belgium) and 83 (Norway). Among the 45 variables were patient data, data about preoperative staging, surgical treatment, pre- or postoperative radio- and/or chemotherapy, and follow-up. Items about tumour recurrence or quality of life were scored too little to become shared data items. Conclusions: A total of 45 items were collected by 8 or more of the participating registries and subsequently met the criteria for a shared data item.
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| 8. |
- de Kruijf, E M, et al.
(author)
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The prognostic role of TGF-β signaling pathway in breast cancer patients
- 2013
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 24:2, s. 384-390
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Journal article (peer-reviewed)abstract
- BackgroundThe transforming growth factor-β (TGF-β) pathway has dual effects on tumor growth. Seemingly, discordant results have been published on the relation between TGF-β signaling markers and prognosis in breast cancer. Improved prognostic information for breast cancer patients might be obtained by assessing interactions among TGF-β signaling biomarkers.Patients and methodsThe expression of nuclear Smad4, nuclear phosphorylated-Smad2 (p-Smad2), and the membranous expression of TGF-β receptors I and II (TβRI and TβRII) was determined on a tissue microarray of 574 breast carcinomas. Tumors were stratified according to the Smad4 expression in combination with p-Smad2 expression or Smad4 in combination with the expression of both TGF-β receptors.ResultsTumors with high expression of TβRII, TβRI and TβRII, and p-Smad2 (P = 0.018, 0.005, and 0.022, respectively), and low expression of Smad4 (P = 0.005) had an unfavorable prognosis concerning progression-free survival. Low Smad4 expression combined with high p-Smad2 expression or low expression of Smad4 combined with high expression of both TGF-β receptors displayed an increased hazard ratio of 3.04 [95% confidence interval (CI) 1.390-6.658] and 2.20 (95% CI 1.464-3.307), respectively, for disease relapse.ConclusionsCombining TGF-β biomarkers provides prognostic information for patients with stage I-III breast cancer. This can identify patients at increased risk for disease recurrence that might therefore be candidates for additional treatment.
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| 10. |
- Van den Broek, C. B. M., et al.
(author)
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Differences in pre-operative treatment for rectal cancer between Norway, Sweden, Denmark, Belgium and the Netherlands
- 2014
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In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 40:12, s. 1789-1796
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Journal article (peer-reviewed)abstract
- Several studies have shown remarkable differences in colorectal cancer survival across Europe. Most of these studies lacked information about stage and treatment. In this study we compared short-term survival as well as differences in tumour stage and treatment strategies between five European countries: Norway, Sweden, Denmark, Belgium, and the Netherlands. For this retrospective cohort study all patients aged 18 years or older and operated on adenocarcinoma of the rectum without distant metastases and diagnosed in 2008 and 2009 were selected in national audit registries from Norway, Sweden, Denmark, Belgium, and the Netherlands. Differences in pre-operative treatment between the countries were compared using univariable and multivariable logistic regression. One year relative survival and one year relative excess risk of death (RER) were compared between the five countries. Large variation in the use of preoperative radiotherapy and chemoradiation was found between the countries. Even though, there was little variation in relative survival between the countries, except Sweden, which had a significant better one year RER of death among the elderly patients after adjustment. The differences in survival are expected to be caused by differences in pen-operative care, selection of patients, and especially management of elderly patients. The effects of preoperative treatment are expected to be seen on long term follow-up.
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| 11. |
- Dikken, J. L., et al.
(author)
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Differences in outcomes of oesophageal and gastric cancer surgery across Europe
- 2013
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In: British Journal of Surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 100:1, s. 83-94
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Journal article (peer-reviewed)abstract
- Background: In several European countries, centralization of oesophagogastric cancer surgery has been realized and clinical audits initiated. The present study was designed to evaluate differences in resection rates, outcomes and annual hospital volumes between these countries, and to analyse the relationship between hospital volume and outcomes. Methods: National data were obtained from cancer registries or clinical audits in the Netherlands, Sweden, Denmark and England. Differences in outcomes were analysed between countries and between hospital volume categories, adjusting for available case-mix factors. Results: Between 2004 and 2009, 10 854 oesophagectomies and 9010 gastrectomies were registered. Resection rates in England were 18.2 and 21.6 per cent for oesophageal and gastric cancer respectively, compared with 28.529.9 and 41.441.9 per cent in the Netherlands and Denmark (P < 0.001). The adjusted 30-day mortality rate after oesophagectomy was lowest in Sweden (1.9 per cent). After gastrectomy, the adjusted 30-day mortality rate was significantly higher in the Netherlands (6.9 per cent) than in Sweden (3.5 per cent; P = 0.017) and Denmark (4.3 per cent; P = 0.029). Increasing hospital volume was associated with a lower 30-day mortality rate after oesophagectomy (odds ratio 0.55 (95 per cent confidence interval 0.42 to 0.72) for at least 41 versus 110 procedures per year) and gastrectomy (odds ratio 0.64 (0.41 to 0.99) for at least 21 versus 110 procedures per year). Conclusion: Hospitals performing larger numbers of oesophagogastric cancer resections had a lower 30-day mortality rate. Differences in outcomes between several European countries could not be explained by differences in hospital volumes. To understand these differences in outcomes and resection rates, with reliable case-mix adjustments, a uniform European upper gastrointestinal cancer audit with recording of standardized data is warranted. Copyright (c) 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
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- de Louw, P. G. B., et al.
(author)
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Quantifying water and salt fluxes in a lowland polder catchment dominated by boil seepage : a probabilistic end-member mixing approach
- 2011
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In: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 15, s. 2101-2117
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Journal article (peer-reviewed)abstract
- Upward saline groundwater seepage is leading to surface water salinization of deep lying polders in the Netherlands. Identifying measures to reduce the salt content requires a thorough understanding and quantification of the dominant sources of water and salt on a daily basis. However, as in most balance studies, there are large uncertainties in the contribution from groundwater seepage. Taking these into account, we applied a probabilistic (GLUE) end-member mixing approach to simulate two years of daily to weekly observations of discharge, salt loads and salt concentration of water pumped out of an artificially drained polder catchment area. We were then able to assess the contribution from the different sources to the water and salt balance of the polder and uncertainties in their quantification. Our modelling approach demonstrates the need to distinguish preferential from diffuse seepage. Preferential seepage via boils contributes, on average, 66% to the total salt load and only about 15% to the total water flux into the polder and therefore forms the main salinization pathway. With the model we were able to calculate the effect of future changes on surface water salinity and to assess the uncertainty in our predictions. Furthermore, we analyzed the parameter sensitivity and uncertainty to determine for which parameter the quality of field measurements should be improved to reduce model input and output uncertainty. High frequency measurements of polder water discharge and weighted concentration at the outlet of the catchment area appear to be essential for obtaining reliable simulations of water and salt fluxes and for allotting these to the different sources.
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- Nilsson, Per J., et al.
(author)
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Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer - the RAPIDO trial
- 2013
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 13, s. 279-
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Journal article (peer-reviewed)abstract
- Background: Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer. Methods and design: Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life. Discussion: Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative chemotherapy. In a multi-centre setting this regimen is compared to current standard with the aim of improving survival for patients with locally advanced rectal cancer.
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| 17. |
- van Gijn, Willem, et al.
(author)
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Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer : 12-year follow-up of the multicentre, randomised controlled TME trial
- 2011
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In: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 12:6, s. 575-582
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Journal article (peer-reviewed)abstract
- Background The TME trial investigated the value of preoperative short-term radiotherapy in combination with total mesorectal excision (TME). Long-term results are reported after a median follow-up of 12 years. Methods Between Jan 12, 1996, and Dec 31, 1999, 1861 patients with resectable rectal cancer without evidence of distant disease were randomly assigned to TME preceded by 5 x 5 Gy radiotherapy or TME alone (ratio 1:1). Randomisation was based on permuted blocks of six with stratification according to centre and expected type of surgery. The primary endpoint was local recurrence, analysed for all eligible patients who underwent a macroscopically complete local resection. Findings 10-year cumulative incidence of local recurrence was 5% in the group assigned to radiotherapy and surgery and 11% in the surgery-alone group (p<0.0001). The effect of radiotherapy became stronger as the distance from the anal verge increased. However, when patients with a positive circumferential resection margin were excluded, the relation between distance from the anal verge and the effect of radiotherapy disappeared. Patients assigned to radiotherapy had a lower overall recurrence and when operated with a negative circumferential resection margin, cancer-specific survival was higher. Overall survival did not differ between groups. For patients with TNM stage III cancer with a negative circumferential resection margin, 10-year survival was 50% in the preoperative radiotherapy group versus 40% in the surgery-alone group (p=0.032). Interpretation For all eligible patients, preoperative short-term radiotherapy reduced 10-year local recurrence by more than 50% relative to surgery alone without an overall survival benefit. For patients with a negative resection margin, the effect of radiotherapy was irrespective of the distance from the anal verge and led to an improved cancer-specific survival, which was nullified by an increase in other causes of death, resulting in an equal overall survival. Nevertheless, preoperative short-term radiotherapy significantly improved 10-year survival in patients with a negative circumferential margin and Trim stage III. Future staging techniques should offer possibilities to select patient groups for which the balance between benefits and side-effects will result in sufficiently large gains.
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