Sjoerd G Elias

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (130)

  • [Show abstract] [Hide abstract] ABSTRACT: Background: Nutritional deprivation during growth and development may contribute to colorectal cancer (CRC) risk in later life. Methods: We studied 7906 women who were aged 0-21 years during the 1944-45 Dutch famine, who enrolled in the Prospect-EPIC study between 1993 and 1997. We used Cox proportional hazard analyses to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for colorectal (proximal, distal and rectal) cancer risk across self-reported famine exposure and exposure-age categories, while adjusting for potential confounders. Results: During a median of 17.3 years of follow-up, 245 CRC cases occurred. Moderately and severely famine-exposed women showed a respective 24% and 44% higher CRC risk compared with women who reported no exposure [HRmoderate 1.24 (95% CI: 0.93-1.64); HRsevere 1.44 (1.03-2.03); Ptrend 0.027]. This relation attenuated when adjusted for potential confounders [adjusted HRmoderate 1.15 (0.87-1.53); HRsevere 1.35 (0.96-1.90); Ptrend 0.091]. Stratified results suggested that severe famine exposure between 10 and 17 years of age was particularly related to CRC risk[adjusted HRmoderate 1.39 (0.91-2.11); HRsevere 1.76 (1.10-2.83); Ptrend 0.019; Pinteraction(famine*10-17yrs) 0.096]. Overall, we found no differences in famine effects across CRC subsites, but age-at-exposure stratified results suggested an increased risk for proximal CRC in those aged 10-17 years during exposure to the famine [adjusted HRmoderate 2.14 (1.06-4.32), HRsevere 2.96 (1.35-6.46); Ptrend 0.005]. Overall and within age-at-exposure categories, tests for subsite specific heterogeneity in famine effects were not significant. Conclusions: Our findings suggest that severe exposure to a short period of caloric restriction in pre-adult women may relate to CRC risk decades later.
    Article · Aug 2016 · International Journal of Epidemiology
  • A. M. F. Verschoor · A. Kuijer · J. Verloop · [...] · S. G. Elias
    [Show abstract] [Hide abstract] ABSTRACT: Over recent years, adjuvant systemic treatment guidelines (AST) for early-stage breast cancer have changed considerably. We aimed to assess the impact of these guideline changes on the administration of AST in early-stage breast cancer patients and to what extent these guidelines are adhered to at a nation-wide level. We used Netherlands Cancer Registry data to describe trends in AST prescription, adherence to AST guidelines, and to identify clinicopathological determinants of nonadherence. Between 1990 and 2012, 231,648 Dutch patients were diagnosed with early breast cancer, of whom 124,472 received AST. Adjuvant endocrine treatment (ET) use increased from 23 % of patients (1990) to 56 % (2012), and chemotherapy from 11 to 44 %. In 2009–2012, 8 % of patients received ET and 3 % received chemotherapy without guideline indication. Conversely, 10–29 % of patients did not receive ET and chemotherapy, respectively, despite a guideline indication. Unfavorable clinicopathological characteristics generally decreased the chance of undertreatment and increased the chance for overtreatment. Remarkable was the increased chance of ET undertreatment in younger women (RR < 35 vs 60–69 years 1.79; 95 % CI 1.30–2.47) and in women with HER2+ disease (RR 1.64; 95 % CI 1.46–1.85). Over the years, AST guidelines expanded resulting in much more Dutch early breast cancer patients receiving AST. In the majority of cases, AST administration was guideline concordant, but the high frequency of chemotherapy undertreatment in some subgroups suggests limited AST guideline support in these patients.
    Article · Aug 2016 · Breast Cancer Research and Treatment
  • Anne Kuijer · Kay Schreuder · Sjoerd G. Elias · [...] · Thijs van Dalen
    [Show abstract] [Hide abstract] ABSTRACT: Background: Breast cancer guidelines suggest the use of gene expression profiles (GEPs) in estrogen receptor-positive (ER+) breast cancer patients in whom controversy exists regarding adjuvant chemotherapy benefit based on traditional prognostic factors alone. We evaluated the current use of GEPs in these patients in the Netherlands. Patients and methods: Primary breast cancer patients treated between January 1, 2011 and December 31, 2014 and eligible for GEP use according to the Dutch national breast cancer guideline were identified in the Netherlands Cancer Registry: ER+ patients <70 years with grade 1 tumors >2 cm or grade 2 tumors 1-2 cm without overt lymph node metastases (pN0-Nmi). Mixed-effect logistic regression analysis was performed to associate characteristics of patients, tumors and hospitals with GEP use. Results: GEPs were increasingly deployed: 12% of eligible patients received a GEP in 2011 versus 46% in 2014. Lobular versus ductal morphology (OR 0.58, 95% CI 0.47-0.72), pN1mi status (versus pN0, OR 0.52, 95% CI 0.40-0.68), and tumor size (>3 cm vs. >2 cm, OR 0.33, 95% CI 0.14-0.88) were inversely associated with GEP use. High socioeconomic status (SES) (OR 1.32, 95% CI 1.06-1.64) and younger age (OR 0.96/year increasing age, 95% CI 0.95-0.96) were positively associated with GEP use. GEP use per hospital did vary, but no predefined institutional factors remained independently associated with GEP use. Conclusion: GEP use increased over time and was influenced by patient- and tumor-associated factors as well as by SES.
    Article · Aug 2016 · Public Health Genomics
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    Full-text Article · Jul 2016 · Epidemiology
  • Kaitlyn Goey · Sjoerd Elias · Harm van Tinteren · [...] · Miriam Koopman
    Conference Paper · Jun 2016
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    Dataset: S1 Table
    [Show abstract] [Hide abstract] ABSTRACT: Prevalence ratios and 95% CI for smoking status, according to level of famine exposure, stratified by age category. (DOCX)
    Full-text Dataset · May 2016
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    Dataset: S2 Table
    [Show abstract] [Hide abstract] ABSTRACT: Association between famine exposure and pack years of smoking, stratified by age category, regression coefficients and 95% CI, n = 3,894. (DOCX)
    Full-text Dataset · May 2016
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    Dataset: S6 Table
    [Show abstract] [Hide abstract] ABSTRACT: Association between famine exposure and modified Mediterranean Diet Score (excluding alcohol), stratified by age category, regression coefficients and 95% CI, n = 7,525. (DOCX)
    Full-text Dataset · May 2016
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    [Show abstract] [Hide abstract] ABSTRACT: Background: A healthy diet is important for normal growth and development. Exposure to undernutrition during important developmental periods such as childhood and adolescence can have effects later in life. Inhabitants of the west of the Netherlands were exposed to severe undernutrition during the famine in the last winter of the second World War (1944-1945). Objective: We investigated if exposure of women to the Dutch famine during childhood and adolescence was associated with an unhealthy lifestyle later in life. Design: We studied 7,525 women from the Prospect-EPIC cohort, recruited in 1993-97 and aged 0-18 years during the Dutch famine. An individual famine score was calculated based on self-reported information about experience of hunger and weight loss. We investigated the association between famine exposure in early life and four lifestyle factors in adulthood: smoking, alcohol consumption, physical activity level and a Mediterranean-style diet. Results: Of the 7,525 included women, 46% were unexposed, 38% moderately exposed and 16% severely exposed to the Dutch famine. Moderately and severely exposed women were more often former or current smokers compared to women that did not suffer from the famine: adjusted prevalence ratio 1.10 (95% CI: 1.05; 1.14) and 1.18 (1.12; 1.25), respectively. They also smoked more pack years than unexposed women. Severely exposed women were more often physically inactive than unexposed women, adjusted prevalence ratio 1.32 (1.06; 1.64). Results did not differ between exposure age categories (0-9 and 10-17 years). We found no associations of famine exposure with alcohol consumption and no dose-dependent relations with diet. Conclusions: Exposure to famine early in female life may be associated with higher prevalence of smoking and physical inactivity later in life, but not with unhealthy diet and alcohol consumption.
    Full-text Article · May 2016 · PLoS ONE
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    Dataset: S5 Table
    [Show abstract] [Hide abstract] ABSTRACT: Prevalence ratios and 95% CI for having an unhealthy diet, according to level of famine exposure, stratified by age category. (DOCX)
    Full-text Dataset · May 2016
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    Dataset: S7 Table
    [Show abstract] [Hide abstract] ABSTRACT: Prevalence ratios and 95% CI for being physically inactive, according to level of famine exposure, stratified by age category. (DOCX)
    Full-text Dataset · May 2016
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    Dataset: S3 Table
    [Show abstract] [Hide abstract] ABSTRACT: Prevalence ratios and 95% CI for being a heavy drinker, according to level of famine exposure, stratified by age category. (DOCX)
    Full-text Dataset · May 2016
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    Dataset: S4 Table
    [Show abstract] [Hide abstract] ABSTRACT: Association between famine exposure and alcohol intake in grams ethanol per day, stratified by age category, regression coefficients and 95% CI, n = 5,092. (DOCX)
    Full-text Dataset · May 2016
  • A Kuijer · C.A. Drukker · S.G. Elias · [...] · Th. van Dalen
    [Show abstract] [Hide abstract] ABSTRACT: Ten years ago gene-expression profiles were introduced to aid adjuvant chemotherapy decision-making in breast cancer. Since then subsequent national guidelines gradually expanded the indication area for adjuvant chemotherapy. In this nation-wide study the evolution of the proportion of patients with estrogen-receptor positive (ER+) tumors receiving adjuvant chemotherapy in relation to gene-expression profile use in patient groups that became newly eligible for chemotherapy according to national guideline changes over time is assessed. Data on all surgically treated early breast cancer patients diagnosed between 2004-2006 and 2012-2014 were obtained from the Netherlands Cancer Registry. ER+/Her2- patients with tumor-characteristics making them eligible for gene-expression testing in both cohorts and a discordant chemotherapy recommendation over time (2004 guideline not recommending and 2012 guideline recommending chemotherapy) were identified. We identified 3864 patients eligible for gene-expression profile use during both periods. Gene-expression profiles were deployed in 5% and 35% of the patients in the respective periods. In both periods the majority of patients was assigned to a low genomic risk-profile (67% and 69% respectively) and high adherence rates to the test result were observed (86% and 91% respectively). Without deploying a gene-expression profile 8% and 52% (p <0.001) of the respective cohorts received chemotherapy while 21% and 28% of these patients received chemotherapy when a gene-expression profile was used (p 0.177). In conclusion, in ER+/Her2- early stage breast cancer patients gene-expression profile use was associated with a consistent proportion of patients receiving chemotherapy despite an adjusted guideline-based recommendation to administer chemotherapy. This article is protected by copyright. All rights reserved.
    Article · Apr 2016 · International Journal of Cancer
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    Andor van den Hoven · Charlotte Rosenbaum · Sjoerd Elias · [...] · Marnix Lam
    [Show abstract] [Hide abstract] ABSTRACT: Methods: 30 patients with unresectable chemorefractory CRLM were treated with resin (90)Y-microspheres in a prospective phase II clinical trial. Tumor absorbed dose was quantified on (90)Y-PET. Metabolic tumor activity, defined as tumor lesion glycolysis (TLG*) on (18)F-FDG-PET, was measured at baseline and 1 month posttreatment. The relationship between tumor absorbed dose and posttreatment metabolic activity was assessed per metastasis, with a linear mixed effects regression model. Results: 133 treated metastases were identified. Mean tumor absorbed dose was 51 ± 28 Gy (range 7 - 174 Gy). A 50% reduction in TLG* was achieved in 46% of metastases, and in 11/30 (37%) patients for the sum of metastases. The latter was associated with prolonged median overall survival (11.6 vs. 6.6 months, P = 0.02). A strong, and statistically significant dose-response relationship was found (P < 0.001). The dose-effect depended on baseline TLG* (P < 0.01). Effective tumor absorbed dose was conservatively estimated at a minimum of 40 - 60 Gy. Conclusion: A strong dose-response relationship exists for the treatment of CRLM with resin microspheres (90)Y-radioembolization. Treatment efficacy is however still limited, because the currently used pretreatment activity calculation methods curb potentially achievable tumor absorbed dose values. A more personalized approach to radioembolization is required before concluding on its clinical potential.
    Full-text Article · Feb 2016 · Journal of Nuclear Medicine
  • [Show abstract] [Hide abstract] ABSTRACT: Objectives: Ductal carcinoma in situ (DCIS) is a risk factor for incomplete resection of breast cancer. Especially, extensive DCIS (E-DCIS) or extensive intraductal component often results in positive resection margins. Detecting DCIS around breast cancer before treatment may therefore alter surgery. The purpose of this study was to develop a prediction model for E-DCIS around early-stage invasive breast cancer, using clinicohistopathological and dynamic contrast-enhanced magnetic resonance imaging (MRI) features. Materials and methods: Dynamic contrast-enhanced MRI and local excision were performed in 322 patients with 326 ductal carcinomas. Tumors were segmented from dynamic contrast-enhanced MRI, followed by 3-dimensional extension of the margins with 10 mm. Amount of fibroglandular tissue (FGT) and enhancement features in these extended margins were automatically extracted from the MRI scans. Clinicohistopathological features were also obtained. Principal component analysis and multivariable logistic regression were used to develop a prediction model for E-DCIS. Discrimination and calibration were assessed, and bootstrapping was applied for internal validation. Results: Extensive DCIS occurred in 48 (14.7%) of 326 tumors. Incomplete resection occurred in 56.3% of these E-DCIS-positive versus 9.0% of E-DCIS-negative tumors (P < 0.001). Five components with eigenvalue exceeding 1 were identified; 2 were significantly associated with E-DCIS. The first, positively associated, component expressed early and overall enhancement in the 10-mm tissue margin surrounding the MRI-visible tumor. The second, positively associated, component expressed human epidermal growth factor receptor 2 and amount of FGT around the MRI-visible tumor. The area under the curve value was 0.79 (0.76 after bootstrapping). Conclusions: Human epidermal growth factor receptor 2 status, early and overall enhancement in the 10-mm margin around the MRI-visible tumor, and amount of FGT in the 10 mm around the MRI-visible tumor were associated with E-DCIS.
    Article · Feb 2016 · Investigative Radiology
  • [Show abstract] [Hide abstract] ABSTRACT: The 'cohort multiple randomized controlled trial', a new design for pragmatic trials, embeds multiple trials within a cohort. The cohort multiple RCT is an attractive alternative to conventional RCTs in fields where recruitment is slow, multiple new (competing) interventions for the same condition have to be tested, new interventions are highly preferred by patients and doctors, and the risk of disappointment bias, cross-over, and contamination is considerable. In order to prevent these unwanted effects, the cohort multiple RCT provides information on randomization to the intervention group/arm only, and only after randomization (i.e. pre-randomization). To some, especially in a clinical setting, this is not ethically acceptable.In this paper, we argue that pre-randomization in the cohort multiple RCT can be avoided by adopting a staged-informed consent procedure. In the first stage, at entry into the cohort, all potential participants are asked for their informed consent to participate in a cohort study and broad consent to be either randomly selected to be approached for experimental interventions or to serve as control without further notice during participation in the cohort. In a second stage, at the initiation of an RCT within the cohort, informed consent to receive the intervention is then only sought in those randomly selected for the intervention arm. At the third stage, after completion of each RCT, all cohort participants receive aggregate disclosure of trial results.This staged-informed consent procedure avoids pre-randomization in cmRCT and aims to keep participants actively engaged in the research process.
    Article · Jan 2016 · Epidemiology
  • [Show abstract] [Hide abstract] ABSTRACT: Purpose: The Dutch national guideline advises use of gene-expression signatures, such as the 70-gene signature (70-GS), in case of ambivalence regarding the benefit of adjuvant chemotherapy (CT). In this nationwide study, the impact of 70-GS use on the administration of CT in early breast cancer patients with a dubious indication for CT is assessed. Methods: Patients within a national guideline directed indication area for 70-GS use who were surgically treated between November 2011 and April 2013 were selected from the Netherlands Cancer Registry database. The effect of 70-GS use on the administration of CT was evaluated in guideline- and age-delineated subgroups addressing potential effect of bias by linear mixed-effect modeling and instrumental variable (IV) analyses. Results: A total of 2,043 patients within the indicated area for 70-GS use were included, of whom 298 received a 70-GS. Without use of the 70-GS, 45% of patients received CT. The 70-GS use was associated with a 9.5% decrease in CT administration (95% confidence interval (CI): -15.7 to -3.3%) in linear mixed-effect model analyses and IV analyses showed similar results (-9.9%; 95% CI: -19.3 to -0.4). Conclusion: In patients in whom the Dutch national guidelines suggest the use of a gene-expression profile, 70-GS use is associated with a 10% decrease in the administration of adjuvant CT.Genet Med advance online publication 19 November 2015Genetics in Medicine (2015); doi:10.1038/gim.2015.152.
    Article · Nov 2015 · Genetics in medicine: official journal of the American College of Medical Genetics
  • [Show abstract] [Hide abstract] ABSTRACT: Recurrence rates after inguinal hernia repair have been reduced to a few per cent, since mesh repair has become standard of care. Lightweight meshes reduce post-operative pain and stiffness in open anterior repair, but for endoscopic repair, the discussion about this benefit is ongoing. This study was done to analyse the effects of lightweight mesh versus heavyweight mesh following endoscopic totally extraperitoneal (TEP) hernia repair. In a single-centre double-blindly randomized clinical trial, 950 patients with unilateral primary inguinal hernia were randomized to undergo endoscopic TEP using either an Ultrapro(®) or a Prolene(®) mesh. Data were collected by validated questionnaires at day 1, day 7, after 6 weeks and after 3 months, and clinical assessment was performed after 3 months. The presence of groin pain after 3 months, defined as an NRS score >3, was evaluated as the primary outcome measure. Secondary outcomes were foreign body feeling and the impact of pain and foreign body feeling on daily activities. At 3-month follow-up, the incidence of pain (NRS 4-10) was 2 versus 0.9 % in the lightweight and heavyweight mesh group, respectively (p = 0.17). Pain interfered with daily activities in 1.7 % of the lightweight and 1.5 % of heavyweight group. In the lightweight group, 20 % of patients reported a foreign body feeling versus 18 % in the heavyweight group (p = 0.62). No differences between the groups were observed regarding time to return to work, interference with sports and sexual activities, testicular pain and ejaculatory pain. Severe preoperative pain (OR 2.01, 95 % CI 1.21-3.35, p = 0.01) was the only independent predictor of any post-operative pain after 3 months. Three months after TEP inguinal repair, there were no significant differences between lightweight and heavyweight mesh use regarding the incidence of pain, foreign body feeling or any other endpoint.
    Article · Nov 2015 · Surgical Endoscopy
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    W A van Gemert · C I Lanting · R A Goldbohm · [...] · S G Elias
    [Show abstract] [Hide abstract] ABSTRACT: We aimed to estimate the proportion of Dutch postmenopausal breast cancer cases in 2010 that is attributable to lifestyle-related risk factors. We calculated population attributable fractions (PAFs) of potentially modifiable risk factors for postmenopausal breast cancer in Dutch women aged >50 in 2010. First, age-specific PAFs were calculated for each risk factor, based on their relative risks for postmenopausal breast cancer (from meta-analyses) and age-specific prevalence in the population (from national surveys) around the year 2000, assuming a latency period of 10 years. To obtain the overall PAF, age-specific PAFs were summed in a weighted manner, using the age-specific breast cancer incidence rates (2010) as weights. 95 % confidence intervals for PAF estimates were derived by Monte Carlo simulations. Of Dutch women >40 years, in 2000, 51 % were overweight/obese, 55 % physically inactive (<5 days/week 30 min activity), 75 % regularly consumed alcohol, 42 % ever smoked cigarettes and 79 % had a low-fibre intake (<3.4 g/1000 kJ/day). These factors combined had a PAF of 25.7 % (95 % CI 24.2–27.2), corresponding to 2,665 Dutch postmenopausal breast cancer cases in 2010. PAFs were 8.8 % (95 % CI 6.3–11.3) for overweight/obesity, 6.6 % (95 % CI 5.2–8.0) for alcohol consumption, 5.5 % (95 % CI 4.0–7.0) for physical inactivity, 4.6 % (95 % CI 3.3–6.0) for smoking and 3.2 % (95 % CI 1.6–4.8) for low-fibre intake. Our findings imply that modifiable risk factors are jointly responsible for approximately one out of four Dutch postmenopausal breast cancer cases. This suggests that incidence rates can be lowered substantially by living a more healthy lifestyle. Electronic supplementary material The online version of this article (doi:10.1007/s10549-015-3447-7) contains supplementary material, which is available to authorized users.
    Full-text Article · Jun 2015 · Breast Cancer Research and Treatment

Publication Stats

2k Citations


  • 2003-2014
    • University Medical Center Utrecht
      • Julius Center for Health Sciences and Primary Care
      Utrecht, Utrecht, Netherlands
  • 2009
    • Jeroen Bosch Ziekenhuis
      Hertogenbosch, North Brabant, Netherlands
  • 2003-2005
    • Utrecht University
      Utrecht, Utrecht, Netherlands