C J van de Velde

Leiden University Medical Centre, Leyden, South Holland, Netherlands

Are you C J van de Velde?

Claim your profile

Publications (326)1821.22 Total impact

  • Cancer Research 05/2015; 75(9 Supplement):S2-01-S2-01. DOI:10.1158/1538-7445.SABCS14-S2-01 · 9.28 Impact Factor
  • Gastroenterology 04/2015; 148(4):S-951. DOI:10.1016/S0016-5085(15)33243-1 · 13.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The optimal duration and regimen of adjuvant hormonal therapy for premenopausal and postmenopausal patients with hormone receptor positive early breast cancer has not yet been established. This review will give an overview of published and ongoing studies concerning extended endocrine treatment. Most of the currently published studies are based on the adjuvant treatment regime of 5years tamoxifen, which has been proven to be inferior compared to aromatase inhibitor (AI)-containing regimes. Therefore, until today, there is no clear evidence for the extension of endocrine therapy after upfront AI-based adjuvant treatment regimes. Multiple clinical trials, which will be discussed in this review, are ongoing to elucidate on this matter. We emphasize the need for tailoring of extended adjuvant endocrine treatment. The quest for predictive biomarkers, which are currently being investigated in the context of decision-making whether or not to start adjuvant chemotherapy, should be expanded to include the feasibility of extended endocrine treatment based on these markers. By tailoring the extension of endocrine treatment, overtreatment, side effects and unnecessary costs will be prevented. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Cancer Treatment Reviews 02/2015; 41:271-276. DOI:10.1016/j.ctrv.2015.02.004 · 6.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Several studies have suggested that AR expression, particularly in luminal cancers following endocrine therapy, may be associated with improved outcome in early breast cancer. We performed an analysis of AR expression in the TEAM pathology cohort to test the hypothesis that AR would represent an independent predictor of residual risk following adjuvant endocrine therapy. Methods: Triplicate 0.6mm2 TMA cores from the TEAM pathology cohort (N=4,598) were stained using AR clone ER179(2) on a Ventana automated staining platform and analysed by image analysis using the Ariol Image analysis platform. Continuous histoscores were generated as previously described (Bartlett et al, JCO 2011). Results: AR histoscores were generated from 3866/4598 (84%) of available cases. Median AR histoscores were 227 (interquartile range 195-262). In a univariate Cox proportional hazard model with AR histoscore as a continuous variable, increased AR histoscores were significantly associated with a reduced hazard of distant disease relapse or death from breast cancer. The hazard ratio (HR) associated with a 50 unit increase in the histoscore was 0.88, 95% confidence interval (95%CI) 0.83-0.93, P<0.0001. There was evidence that a log transformation of the histoscore resulted in a better fitting model (P<0.0001) resulting in the following model estimates HR= 0.93, 95% CI 0.89-0.98, P=0.006. However, a multivariate model of AR histoscore including other known prognostic factors such as age, grade, tumour size, number of positive nodes, HER2 status, ER and PgR histoscores found AR histoscore was not independently prognostic for distant relapse or death (HR=1.00, 95% CI 0.94-1.06, P=0.96). There was no significant interaction between AR expression and type of endocrine treatment (Tamoxifen →exemestane versus exemestane alone) in either univariate (HR 1.003 95%CI 0.91-1.11, p=0.96) or multivariate (HR 0.92, 95%CI 0.81-1.04, p=0.18) analysis. Logistic regression analysis was performed to investigate the association between AR histoscore (2 groups above and below the median) and the known prognostic factors mentioned above. Increased AR histoscore is associated with good risk factors; young age, low grade, small tumours, decreasing ki67 and increasing ER and PgR histoscores. Conclusion: AR expression is common in luminal breast cancers. However, in this study AR histoscore does not add residual risk information beyond what can already be assessed using conventional prognostic factors. High AR expression is associated with good prognostic factors, including young age, low tumour grade, small tumour size, lower Ki67 and higher ER/PgR expression.
    Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR;; 01/2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Mucinous carcinoma (MC) is a distinct form of rectal cancer (RC) comprising 10 % of all cases and has been associated with an impaired prognosis compared with non-mucinous adenocarcinoma (AC). The benefit of today’s modern treatment for MC patients is unknown but a prospective randomized trial to answer this does not seem feasible. This study provides an analysis of the modern treatment of rectal MC and efficacy of preoperative therapies for MC patients. Methods Data from three large (trial) cohorts were used. Data from the Netherlands Cancer Registry (NCR) were used to analyze the prognosis of RC patients over time (N = 38,035). To study the benefit of preoperative short-term radiotherapy, patients from the total mesorectal excision (TME) trial (N = 1,530) were selected, and the benefit from preoperative chemoradiotherapy was analyzed with data on 540 locally advanced RC (LARC) patients from two hospitals. Results Data from the NCR confirmed that 5-year overall survival for MC was significantly worse from 1989 to 1998, but no longer different from AC from 1999 onwards. MC patients had a higher rate of positive circumferential resection margin than AC patients (TME trial 27.2 vs. 16.5 %, p = 0.006; LARC cohort 34.5 vs. 9.8 %, p Conclusions Modern treatment of RC has benefited MC patients, leading to equal survival for MC and AC patients. Enhancements in the fields of imaging and quality of surgery have improved outcome and preoperative therapies should be recommended for both histological subtypes.
    Annals of Surgical Oncology 01/2015; 25(suppl 2). DOI:10.1245/s10434-014-4339-5 · 3.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It is widely recognised that colorectal cancer has become a complex disease and involves many medical disciplines. The mission of the European Multidisciplinary Colorectal Cancer Congress (EMCCC), which is an initiative of the Dutch Colorectal Cancer Group (DCCG), is to facilitate the interaction between relevant disciplines on current issues of research. The three-day meeting in Amsterdam in November 2014 assembled approximately 450 participants with nine different disciplines from 38 countries worldwide. On day one, workshops on imaging, surgery, medical oncology/pathology, radiotherapy, and genetics were followed by the keynote lecture of the congress. On day two and three, a total of 35 established international opinion leaders presented lectures in plenary sessions on prevention and screening of early colorectal cancer, genetics, translational research, biomarkers, organ-saving treatment in rectal cancer, current controversies, and multidisciplinary management. Posters from submitted abstracts were displayed, with selected abstracts being orally presented.
    ecancermedicalscience 01/2015; 9:497. DOI:10.3332/ecancer.2015.497 · 1.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Several studies have suggested that AR expression, particularly in luminal cancers following endocrine therapy, may be associated with improved outcome in early breast cancer. We performed an analysis of AR expression in the TEAM pathology cohort to test the hypothesis that AR would represent an independent predictor of residual risk following adjuvant endocrine therapy. Methods: Triplicate 0.6mm2 TMA cores from the TEAM pathology cohort (N=4,598) were stained using AR clone ER179(2) on a Ventana automated staining platform and analysed by image analysis using the Ariol Image analysis platform. Continuous histoscores were generated as previously described (Bartlett et al, JCO 2011). Results: AR histoscores were generated from 3866/4598 (84%) of available cases. Median AR histoscores were 227 (interquartile range 195-262). In a univariate Cox proportional hazard model with AR histoscore as a continuous variable, increased AR histoscores were significantly associated with a reduced hazard of distant disease relapse or death from breast cancer. The hazard ratio (HR) associated with a 50 unit increase in the histoscore was 0.88, 95% confidence interval (95%CI) 0.83-0.93, P<0.0001. There was evidence that a log transformation of the histoscore resulted in a better fitting model (P<0.0001) resulting in the following model estimates HR= 0.93, 95% CI 0.89-0.98, P=0.006. However, a multivariate model of AR histoscore including other known prognostic factors such as age, grade, tumour size, number of positive nodes, HER2 status, ER and PgR histoscores found AR histoscore was not independently prognostic for distant relapse or death (HR=1.00, 95% CI 0.94-1.06, P=0.96). There was no significant interaction between AR expression and type of endocrine treatment (Tamoxifen →exemestane versus exemestane alone) in either univariate (HR 1.003 95%CI 0.91-1.11, p=0.96) or multivariate (HR 0.92, 95%CI 0.81-1.04, p=0.18) analysis. Logistic regression analysis was performed to investigate the association between AR histoscore (2 groups above and below the median) and the known prognostic factors mentioned above. Increased AR histoscore is associated with good risk factors; young age, low grade, small tumours, decreasing ki67 and increasing ER and PgR histoscores. Conclusion: AR expression is common in luminal breast cancers. However, in this study AR histoscore does not add residual risk information beyond what can already be assessed using conventional prognostic factors. High AR expression is associated with good prognostic factors, including young age, low tumour grade, small tumour size, lower Ki67 and higher ER/PgR expression.
    Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13;; 12/2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background The 1-year mortality after colorectal cancer surgery is high and explains age related differences in colorectal cancer survival. To gain better insight in its etiology, cause of death for these patients was studied. Methods All 1924 patients who had a resection for stage I-III colorectal cancer from 2006 to 2008 in the Western region of the Netherlands were identified. Data were merged with cause of death data from the Central Bureau of Statistics Netherlands. To calculate excess mortality as compared to the general population, national data were used. Results Overall 13.2% of patients died within the first postoperative year. One-year mortality increased with age. It was as high as 43% in elderly patients that underwent emergency surgery. In 75% of patients, death was attributed to the colorectal cancer. In 25% of all patients, registered deaths were attributed to postoperative complications. Elderly patients with comorbidity more frequently died due to complications (p<0.01). Death of other causes was similar to background mortality according to age group. Conclusion In the presently studied cohort of patients that died within one year of surgery, cause of death was predominantly attributed to colorectal cancer. However, because it is not to be expected that in this cohort the number of deaths from recurrences is very high, the excess 1-year mortality indicates a prolonged impact of the surgery,especially in elderly patients. Therefore, in these patients we should focus on limiting the physiological impact of the surgery and be more involved in the post-hospital period.
    European Journal of Surgical Oncology 11/2014; DOI:10.1016/j.ejso.2014.05.010 · 2.89 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Numerous changes in epigenetic mechanisms have been described in various types of tumors. In search for new biomarkers, we investigated the expression of Polycomb-group (PcG) proteins EZH2, BMI1 and SUZ12 and associated histone modification H3K27me3 in colorectal cancer. Nuclear expression of PcG proteins and histone modification H3K27me3 were immunohistochemically (IHC) stained on a tissue microarray (TMA), including 247 tumor tissues and 47 normal tissues, and scored using the semi-automated Ariol system. Tumor tissues showed higher expression of EZH2 (p = 0.05) and H3K27me3 (p<0.001) as compared to their normal counterparts. Combined marker trend analyses indicated that an increase in the number of markers showing high expression was associated with better prognosis. High expression of all four markers in the combined marker analyses was correlated with the best patient survival and the longest recurrence-free survival, with overall survival (p = 0.01, HR 0.42(0.21-0.84)), disease-free survival (p = 0.007, HR 0.23(0.08-0.67) and local recurrence-free survival (p = 0.02, HR 0.30(0.11-0.84)). In conclusion, we found that expression of PcG proteins and H3K27me3 showed prognostic value in our study cohort. Better stratification of patients was obtained by combining the expression data of the investigated biomarkers as compared to the individual markers, underlining the importance of investigating multiple markers simultaneously
    PLoS ONE 09/2014; 9(9-9):e108265-. DOI:10.1371/journal.pone.0108265 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Breast cancer is a heterogeneous disease with a highly variable clinical outcome in which both genetic and epigenetic changes have critical roles. We investigated tumor expression levels of histone-modifying enzymes LSD1, HDAC2 and SIRT1 in relation with patient survival and tumor relapse in a retrospective cohort of 460 breast cancer patients. Additionally, we correlated expression levels with tumor differentiation and tumor cell proliferation.
    BMC Cancer 08/2014; 14(1):604. DOI:10.1186/1471-2407-14-604 · 3.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Post-translational modification of histone tails by methylation plays an important role in tumorigenesis. In this study, we investigated the nuclear expression of H3K4me3, H3K9me3 and H4K20me3 in early-stage colon cancer in relation to clinical outcome.
    BMC Cancer 07/2014; 14(1):531. DOI:10.1186/1471-2407-14-531 · 3.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Evasion of immune surveillance and suppression of the immune system are important hallmarks of tumorigenesis. The goal of this study was to establish distinct patterns that reflect a rectal tumors’ immune-phenotype and to determine their relation to patient outcome. Methods The study population consisted of 495 Stage I-IV non-preoperatively treated rectal cancer patients of which a tissue micro array (TMA) was available. Sections of this TMA were immunohistochemically stained and quantified for presence of Foxp3+ cells (Tregs) and tumor expression of HLA Class I and non-classical HLA-E and HLA-G. All markers were, separate and combined, analyzed for clinical prognostic value. Results Expression of HLA class I (DFS HR 0.637 (0.458-0.886), p = 0.013), Foxp3+ infiltration above median (OS HR 0.637 (0.500-0.813), p < 0.001 and DFS HR 0.624 (0.491-0.793), p < 0.001) and expression of HLA-G (DFS HR 0.753 (0.574-0.989), p = 0.042) were related to a better clinical prognosis. When these markers were combined, patients with 2 or 3 markers associated with poor prognosis (loss of HLA Class I, Foxp3+ below median, and weak HLA-G expression), showed a significantly worse survival (OS and DFS p < 0.001). This immune-phenotype was an independent predictor for DFS (HR 1.56 (1.14-2.14), p = 0.019). Conclusions In conclusion, rectal tumors showing loss of HLA class I expression, Foxp3+ infiltration below median and weak HLA-G expression were related to a worse OS and DFS. Combining these immune markers lead to the creation of tumor immune-phenotypes , which related to patient outcome and were significant independent clinical prognostic markers in rectal cancer.
    BMC Cancer 07/2014; 14(1):486. DOI:10.1186/1471-2407-14-486 · 3.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although the incidence of gastric cancer has fallen steadily in developed countries over the past 50 years, outcomes in Western countries remain poor, primarily due to the advanced stage of the disease at presentation. While earlier diagnosis would help to improve outcomes for patients with gastric cancer, better understanding of the biology of the disease is also needed, along with advances in therapy. Indeed, progress in the treatment of gastric cancer has been limited, mainly because of its genetic complexity and heterogeneity. As a result, there is an urgent need to apply precision medicine to the management of the disease in order to ensure that individuals receive the most appropriate treatment. This article suggests a number of strategies that may help to accelerate progress in treating patients with gastric cancer. Incorporation of some of these approaches could help to improve the quality of life and survival for patients diagnosed with the disease. Standardisation of care across Europe through expansion of the European Registration of Cancer Care (EURECCA) registry – a European cancer audit that aims to improve quality and decrease variation in care across the region – may also be expected to lead to improved outcomes for those suffering from this common malignancy.
    Cancer Treatment Reviews 07/2014; 40(6). DOI:10.1016/j.ctrv.2014.03.002 · 6.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The receptor for urokinase-type plasminogen activator (uPAR) is associated with cancer development and progression. Within the tumor microenvironment uPAR is expressed by malignant cells as well as tumor-associated stromal cells. However, the contribution of uPAR expression in these stromal cells to malignancy and patient survival in colorectal cancer is still unclear. This study compares the association of uPAR expression in both colorectal tumor-associated stromal cells and neoplastic cells with clinico-pathological characteristics and patient survival using tissue micro arrays (TMA). Immunohistochemical staining of uPAR expression was performed on tumor tissue from 262 colorectal cancer patients. Kaplan-Meier, log rank, and uni- and multivariate Cox's regression analyses were used to calculate associations between uPAR expression and patient survival. In the colorectal tumor-associated stromal microenvironment, uPAR is expressed in macrophages, (neoangiogenic) endothelial cells and myofibroblasts. uPAR expression in tumor-associated stromal cells and neoplastic cells (and both combined) were negatively associated with overall survival (OS) and Disease Free Survival (DFS). Uni- and multivariate Cox's regression analysis for combined uPAR expression in tumor-associated stromal and neoplastic cells showed significant and independent negative associations with OS and DFS. Only uPAR expression in tumor-associated stromal cells showed independent significance in the uni- and multivariate analysis for DFS. This study demonstrates a significant independent negative association between colorectal cancer patient survival and uPAR expression in especially tumor-associated stromal cells.
    BMC Cancer 04/2014; 14(1):269. DOI:10.1186/1471-2407-14-269 · 3.32 Impact Factor
  • Cancer Research 03/2014; 73(24 Supplement):P1-08-19-P1-08-19. DOI:10.1158/0008-5472.SABCS13-P1-08-19 · 9.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: This study was designed to define a statistically sound and clinically meaningful cutoff point for annual hospital volume for esophagectomy. Higher hospital volumes are associated with improved outcomes after esophagectomy. However, reported optimal volumes in literature vary, and minimal volume standards in different countries show considerable variation. So far, there has been no research on the noncategorical, nonlinear, volume-outcome relationship in esophagectomy. METHODS: Data were derived from the Netherlands Cancer Registry. Restricted cubic splines were used to investigate the nonlinear effects of annual hospital volume on 6 month and 2 year mortality rates. Outcomes were adjusted for year of diagnosis, case-mix, and (neo)adjuvant treatment. RESULTS: Between 1989 and 2009, 10,025 patients underwent esophagectomy for cancer in the Netherlands. Annual hospital volumes varied between 1 and 83 year, increasing over time. Increasing annual hospital volume showed a continuous, nonlinear decrease in hazard ratio (HR) for mortality along the curve. Increasing hospital volume from 20 year (baseline, HR = 1.00) to 40 and 60 year was associated with decreasing 6 month mortality, with a HR of 0.73 (95 % confidence interval (0.65-0.83) and 0.67 (0.58-0.77) respectively. Beyond 60 year, no further decrease was detected. Higher hospital volume also was associated with decreasing 2 year mortality until 50 esophagectomies year with a HR of 0.86 (0.79-0.93). CONCLUSIONS: Centralization of esophagectomy to a minimum of 20 resections/year has been effectively introduced in the Netherlands. Increasing annual hospital volume was associated with a nonlinear decrease in mortality up to 40-60 esophagectomies/year, after which a plateau was reached. This finding may guide quality improvement efforts worldwide.
  • 12/2013; 2(4):188-200. DOI:10.3390/jcm2040188
  • [Show abstract] [Hide abstract]
    ABSTRACT: IMPORTANCE There is growing interest in reducing the variations and deficiencies in the multidisciplinary management of gastric cancer. OBJECTIVE To define optimal treatment strategies for gastric adenocarcinoma (GC). DESIGN, SETTING, AND PARTICIPANTS RAND/UCLA Appropriateness Method involving a multidisciplinary expert panel of 16 physicians from 6 countries. INTERVENTIONS Gastrectomy, perioperative chemotherapy, adjuvant chemoradiation, surveillance endoscopy, and best supportive care. MAIN OUTCOMES AND MEASURES Panelists scored 416 scenarios regarding treatment scenarios for appropriateness from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores from 1 to 3 were considered inappropriate; 4 to 6, uncertain; and 7 to 9, appropriate. Agreement was reached when 12 of 16 panelists scored the scenario similarly. Appropriate scenarios agreed on were subsequently scored for necessity. RESULTS For patients with T1N0 disease, surgery alone was considered appropriate, while there was no agreement over surgery alone for patients T2N0 disease. Perioperative chemotherapy was appropriate for patients who had T1-2N2-3 or T3-4 GC without major symptoms. Adjuvant chemoradiotherapy was classified as appropriate for T1-2N1-3 or T3-4 proximal GC and necessary for T1-2N2-3 or T3-4 distal GC. There was no agreement regarding surveillance imaging and endoscopy following gastrectomy. Surveillance endoscopy was deemed to be appropriate after endoscopic resection. For patients with metastatic GC, surgical resection was considered inappropriate for those with no major symptoms, unless the disease was limited to positive cytology alone, in which case there was disagreement. CONCLUSIONS AND RELEVANCE Patients with GC being treated with curative intent should be considered for multimodal treatment. For patients with incurable disease, surgical interventions should be considered only for the management of major bleeding or obstruction.
    JAMA SURGERY 11/2013; 149(1). DOI:10.1001/jamasurg.2013.3959 · 4.30 Impact Factor
  • Journal of Geriatric Oncology 10/2013; 4:S42. DOI:10.1016/j.jgo.2013.09.045 · 1.15 Impact Factor
  • Journal of Geriatric Oncology 10/2013; 4:S26. DOI:10.1016/j.jgo.2013.09.009 · 1.15 Impact Factor

Publication Stats

12k Citations
1,821.22 Total Impact Points

Institutions

  • 1977–2015
    • Leiden University Medical Centre
      • • Department of Surgery
      • • Department of Clinical Oncology
      Leyden, South Holland, Netherlands
  • 1987–2013
    • Leiden University
      • Molecular Cell Biology Group
      Leyden, South Holland, Netherlands
  • 2009
    • Universidad de Salamanca
      Helmantica, Castille and León, Spain
  • 2001
    • Uppsala University
      Uppsala, Uppsala, Sweden
  • 1998
    • Institut Jules Bordet
      Bruxelles, Brussels Capital Region, Belgium
    • Erasmus MC
      • Department of Oncological Surgery
      Rotterdam, South Holland, Netherlands
    • European Organisation for Research and Treatment of Cancer
      Bruxelles, Brussels Capital Region, Belgium
  • 1994
    • Erasmus Universiteit Rotterdam
      • Center for Clinical Decision Sciences
      Rotterdam, South Holland, Netherlands
    • National Cancer Center, Japan
      Edo, Tōkyō, Japan