Antoni van Leeuwenhoek Hospital

Amsterdam, Netherlands

Antoni van Leeuwenhoek Hospital

Amsterdam, Netherlands
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The founding members of the Elekta MR-linac Consortium are: University Medical Center Utrecht, the Netherlands (UMCU); The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; The University of Texas MD Anderson Cancer Center, Houston, Texas; the Institute of Cancer Research, working with its clinical partner The Royal Marsden NHS Foundation Trust, London, England; Froedtert & the Medical College of Wisconsin Clinical Cancer Center at Froedtert Hospital, Milwaukee, Wisconsin; The Christie NHS Foundation Trust, Manchester, UK and the Odette Cancer Centre, Sunnybrook Health Sciences Centre in Toronto. Clinicians and scientists from the Princess Margaret Cancer Centre, University Health Network, Toronto, Canada; Odense University Hospital, Denmark; Tübingen University Hospital, Germany; Uppsala University Hospital, Sweden; and William Beaumont Hospital, United States also participated in this year's consortium meeting. Elekta's MR-linac is the only MR/RT system that integrates a high-field (1.5 Tesla) MR scanner, from MR technology partner Philips, with an advanced linear accelerator and intelligently-designed software. The system is expected to deliver precisely targeted radiation doses while simultaneously capturing highest-quality MR images, which will allow clinicians to visualize tumors and surrounding normal tissue at any time and adapt the treatment accordingly. Elekta introduced the MR-linac technology under the name of Elekta Unity during the ESTRO congress in Vienna, Austria in April 2017. "The 10th Consortium meeting demonstrated the high collaborative capacity of our consortium across different disciplines and geographies," said Kevin Brown, Elekta's Global Vice President of Scientific Research. "We are gratified that the consortium continues to generate data that demonstrates the technical functionality and clinical utility of our MR-linac system and expect that the input from the additional sites will further expand the robust body of evidence supporting MR/RT as a transformative approach to radiation therapy." "The development of MR-linac has truly been a global effort, and the participation of clinicians and scientists from five additional cancer centers in this year's meeting has underscored the value of including insights from a broad array of experts," said Christopher Schultz, MD, FACR, Medical College of Wisconsin Professor and Chairman of the Department of Radiation Oncology, at the Froedtert & MCW Cancer Network and Chair of the Elekta MR-linac Consortium. "As MR-linac advances toward the clinic, we will continue to seek input from radiation oncologists, medical physicists and imaging experts around the world. We believe that this broad and inclusive approach is the most effective way to ensure that our vision for MR/RT meets the needs of patients, physicians, and cancer care centers." Key discussion points of the Consortium meeting were: "MR-guided radiotherapy has the potential to transform the treatment of cancer by enabling more precise, adaptive tumor targeting, and we are excited about helping to bring this important advancement to patients," said Michael Milosevic, MD, Director of Research, Radiation Medicine Program, Princess Margaret Cancer Centre and Vice-Chair (Research) Department of Radiation Oncology, University of Toronto. "The Consortium has been very effective at promoting collaborative innovation in MR-guided radiotherapy and we look forward to continuing to move this evolving area of radiation oncology and precision cancer medicine forward." "The MR-linac consortium together with the five new centers is an impressive novel network within the radiation oncology community," said Daniel Zips, MD, Chair, Professor Radiation Oncology at Tübingen University Hospital. "Mastering the new technology towards innovation in radiation therapy requires joint efforts and combined expertise. The Tübingen group is happy to contribute to this endeavor which will bring radiation oncology to the next level." The growing body of evidence supporting Elekta's MR-linac system as the first to truly enable MR/RT will be showcased at the 59thAmerican Association of Physicists in Medicine (AAPM) Annual Meeting & Exhibition (July 30 - August 3, Denver) and the upcoming 2017 ASTRO Annual Meeting (September 24-27, San Diego). Elekta Unity is a work in progress and not available for sale or distribution. For further information, please contact: This information was brought to you by Cision The following files are available for download:

Cherny N.I.,Shaare Zedek Medical Center | Sullivan R.,King's College London | Dafni U.,National and Kapodistrian University of Athens | Kerst J.M.,Antoni van Leeuwenhoek Hospital | And 5 more authors.
Annals of Oncology | Year: 2015

The value of any new therapeutic strategy or treatment is determined by the magnitude of its clinical benefit balanced against its cost. Evidence for clinical benefit from new treatment options is derived from clinical research, in particular phase III randomised trials, which generate unbiased data regarding the efficacy, benefit and safety of new therapeutic approaches. To date, there is no standard tool for grading the magnitude of clinical benefit of cancer therapies, which may range from trivial (median progression-free survival advantage of only a few weeks) to substantial (improved longterm survival). Indeed, in the absence of a standardised approach for grading the magnitude of clinical benefit, conclusions and recommendations derived from studies are often hotly disputed and very modest incremental advances have often been presented, discussed and promoted as major advances or 'breakthroughs'. Recognising the importance of presenting clear and unbiased statements regarding the magnitude of the clinical benefit from new therapeutic approaches derived from high-quality clinical trials, the European Society for Medical Oncology (ESMO) has developed a validated and reproducible tool to assess the magnitude of clinical benefit for cancer medicines, the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS). This tool uses a rational, structured and consistent approach to derive a relative ranking of the magnitude of clinically meaningful benefit that can be expected from a new anti-cancer treatment. The ESMO-MCBS is an important first step to the critical public policy issue of value in cancer care, helping to frame the appropriate use of limited public and personal resources to deliver cost-effective and affordable cancer care. The ESMO-MCBS will be a dynamic tool and its criteria will be revised on a regular basis. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Krabbe P.F.M.,University of Groningen | Tromp N.,Radboud University Nijmegen | Ruers T.J.M.,Antoni van Leeuwenhoek Hospital | van Riel P.L.C.M.,Radboud University Nijmegen
Health and Quality of Life Outcomes | Year: 2011

Background: Many studies have found discrepancies in valuations for health states between the general population (healthy people) and people who actually experience illness (patients). Such differences may be explained by referring to various cognitive mechanisms. However, more likely most of these observed differences may be attributable to the methods used to measure these health states. We explored in an experimental setting whether such discrepancies in values for health states exist. It was hypothesized that the more the measurement strategy was incorporated in measurement theory, the more similar the responses of patients and healthy people would be.Methods: A sample of the general population and two patient groups (cancer, rheumatoid arthritis) were included. All three study groups judged the same 17 hypothetical EQ-5D health states, each state comprising the same five health domains. The patients did not know that apart from these 17 states their own health status was also included in the set of states they were assessing. Three different measurement strategies were applied: 1) ranking of the health states; 2) placing all the health states simultaneously on a visual analogue scale (VAS); 3) separately assessing the health states with the time trade-off (TTO) technique. Regression analyses were performed to determine whether differences in the VAS and TTO can be ascribed to specific health domains. In addition, effect of being member of one of the two patient groups and the effect of the assessment of the patients' own health status was analyzed.Results: Except for some moderate divergence, no differences were found between patients and healthy people for the ranking task or for the VAS. For the time trade-off technique, however, large differences were observed between patients and healthy people. The regression analyses for the effect of belonging to one of the patient groups and the effect of the value assigned to the patients' own health state showed that only for the TTO these patient-specific parameters did offer some additional information in explaining the 17 hypothetical EQ-5D states.Conclusions: Patients' assessment of health states is similar to that of the general population when the judgments are made under conditions that are defended by modern measurement theory. © 2011 Krabbe et al; licensee BioMed Central Ltd.

Simkens L.H.J.,University of Amsterdam | Van Tinteren H.,Netherlands Cancer Institute | May A.,University Utrecht | Ten Tije A.J.,Amphia Hospital | And 20 more authors.
The Lancet | Year: 2015

Background The optimum duration of first-line treatment with chemotherapy in combination with bevacizumab in patients with metastatic colorectal cancer is unknown. The CAIRO3 study was designed to determine the efficacy of maintenance treatment with capecitabine plus bevacizumab versus observation. Methods In this open-label, phase 3, randomised controlled trial, we recruited patients in 64 hospitals in the Netherlands. We included patients older than 18 years with previously untreated metastatic colorectal cancer, with stable disease or better after induction treatment with six 3-weekly cycles of capecitabine, oxaliplatin, and bevacizumab (CAPOX-B), WHO performance status of 0 or 1, and adequate bone marrow, liver, and renal function. Patients were randomly assigned (1:1) to either maintenance treatment with capecitabine and bevacizumab (maintenance group) or observation (observation group). Randomisation was done centrally by minimisation, with stratification according to previous adjuvant chemotherapy, response to induction treatment, WHO performance status, serum lactate dehydrogenase concentration, and treatment centre. Both patients and investigators were aware of treatment assignment. We assessed disease status every 9 weeks. On first progression (defined as PFS1), patients in both groups were to receive the induction regimen of CAPOX-B until second progression (PFS2), which was the study's primary endpoint. All endpoints were calculated from the time of randomisation. Analyses were done by intention to treat. This trial is registered with, number NCT00442637. Findings Between May 30, 2007, and Oct 15, 2012, we randomly assigned 558 patients to either the maintenance group (n=279) or the observation group (n=279). Median follow-up was 48 months (IQR 36-57). The primary endpoint of median PFS2 was significantly improved in patients on maintenance treatment, and was 8·5 months in the observation group and 11·7 months in the maintenance group (HR 0·67, 95% CI 0·56-0·81, p<0·0001). This difference remained significant when any treatment after PFS1 was considered. Maintenance treatment was well tolerated, although the incidence of hand-foot syndrome was increased (64 [23%] patients with hand-foot skin reaction during maintenance). The global quality of life did not deteriorate during maintenance treatment and was clinically not different between treatment groups. Interpretation Maintenance treatment with capecitabine plus bevacizumab after six cycles of CAPOX-B in patients with metastatic colorectal cancer is effective and does not compromise quality of life. Funding Dutch Colorectal Cancer Group (DCCG). The DCCG received financial support for the study from the Commissie Klinische Studies (CKS) of the Dutch Cancer Foundation (KWF), Roche, and Sanofi-Aventis. © 2015 Elsevier Ltd.

Gerards M.C.,Slotervaart Hospital | Terlou R.J.,Academical Medical Center | Yu H.,Antoni van Leeuwenhoek Hospital | Koks C.H.W.,Antoni van Leeuwenhoek Hospital | Gerdes V.E.A.,Slotervaart Hospital
Atherosclerosis | Year: 2015

Objective: To verify the safety and effectiveness of traditional Chinese red yeast rice-extract (RYR) for reduction of LDL cholesterol. Methods: Systematic literature review and meta-analysis. Medline and EMBASE were searched until November 2014. We selected randomized studies in which RYR with a known content of the active substance monacolin K was tested against placebo or an active control group. Outcome measures were the effect of RYR on LDL cholesterol and incidence of adverse reactions with emphasis on liver and kidney injury and muscle symptoms. Results: Twenty studies were analyzed. Quality of safety assessment was low in the majority of studies. RYR lowered LDL cholesterol with 1.02mmol/L [-1.20;-0.83] compared to placebo. Effect of RYR on LDL was not different from statin therapy (0.03mmol/L [-0.36; 0.41]). The incidence of liver and kidney injury was 0-5% and the risk was not different between treatment and control groups (risk difference-0.01 [-0.01; 0.0] and 0.0 [-0.01; 0.02]). Conclusions: RYR exerts a clinically and statistically significant reduction of 1.02mmol/L LDL cholesterol. Only when the mild profile of adverse reactions can be affirmed in studies with adequate methodology for safety assessment, RYR might be a safe and effective treatment option for dyslipidemia and cardiovascular risk reduction in statin intolerant patients. © 2015 Elsevier Ireland Ltd.

Geubbels N.,Metabolic | de Brauw L.M.,Metabolic | Acherman Y.I.Z.,Metabolic | van de Laar A.W.J.M.,Metabolic | And 2 more authors.
Obesity Surgery | Year: 2015

Background: The learning curve of laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery has been well investigated. The learning curve is defined by complications and/or by duration of surgery (DOS). Previous studies report an inverse relationship between patient outcome and patient volume. In this study, we investigate whether the learning curve of preceding bariatric surgeons is of additional influence for surgeons who start to perform LRYGB in the same centre. Materials and Methods: We retrospectively analysed the records of all 713 consecutive primary LRYGB patients operated in our centre from December 2007 until July 2012. Surgeon 1 and 3 had previous laparoscopic bariatric experience whilst Surgeon 2 and 4 had not. We stratified the data between the four surgeons with different levels of experience and in a chronology of 50 cases. Results: Sixty-seven (9.4 %) complications occurred in the study period. Surgeon 1 had more complications occurring within the first 50 cases than Surgeon 4 (10 versus 1, p < 0.05). There was no difference in complication rate between groups of 50 consecutive cases. None of the patients died. DOS decreased for every consecutive surgeon, irrespective of their experience. The learning curve defined by DOS was steepest for Surgeon 1, followed by Surgeon 2, 3 and 4. Conclusion: In this study, we show that the learning curve of the preceding surgeon positively influences the learning curve of latter surgeons, irrespective of their experience. Therefore, the ‘preceding surgeon factor’ should be taken in account in addition to volume requirements when starting new bariatric facilities. © 2014, Springer Science+Business Media New York.

Geubbels N.,Metabolic | Lijftogt N.,Leiden University | Fiocco M.,Leiden University | Van Leersum N.J.,Leiden University | And 2 more authors.
British Journal of Surgery | Year: 2015

Background The aim of this study was to provide a systematic and quantitative summary of the association between laparoscopic Roux-en-Y gastric bypass (LRYGB) and the reported incidence of internal herniation (IH). The route of the Roux limb and closure of mesenteric and/or mesocolonic defects are described as factors of influence. Methods MEDLINE, Embase, the Cochrane Library and Web of Science were searched for relevant literature, references and citations according to the PRISMA statement. Two independent reviewers selected studies that evaluated incidence of IH after LRYGB and possible techniques for prevention. Data were pooled by route of the Roux limb and closure/non-closure of the mesenteric and/or mesocolonic defects. Results Forty-five articles included data on 31 320 patients. Lowest IH incidence was in the antecolic group, with closure of all defects (1 per cent; P < 0·001), followed by the antecolic group, with all defects left open and the retrocolic group with closure of the mesenteric and mesocolonic defect (both 2 per cent; P < 0·001). The incidence of IH was highest in the antecolic group, with closure of the jejunal defect, and in the retrocolic group, with closure of all defects (both 3 per cent). Conclusion The present systematic review includes a random-effects meta-analysis. The antecolic procedure, with closure of both the mesenteric and Petersen defects, has the lowest internal herniation incidence following laparoscopic Roux-en-Y gastric bypass. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

Obdeijn I.-M.,Erasmus University Rotterdam | Winter-Warnars G.A.O.,Antoni Van Leeuwenhoek Hospital | Mann R.M.,University Medical Center Nijmegen | Hooning M.J.,Erasmus Medical Center | And 4 more authors.
Breast Cancer Research and Treatment | Year: 2014

BRCA1 mutation carriers are offered screening with MRI and mammography. Aim of the study was to investigate the additional value of digital mammography over MRI screening. BRCA1 mutation carriers, who developed breast cancer since the introduction of digital mammography between January 2003 and March 2013, were included. The images and reports were reviewed in order to assess whether the breast cancers were screen-detected or interval cancers and whether they were visible on mammography and MRI, using the breast imaging and data system classification allocated at the time of diagnosis. In 93 BRCA1 mutation carriers who underwent screening with MRI and mammography, 82 invasive breast cancers and 12 ductal carcinomas in situ (DCIS) were found. Screening sensitivity was 95.7%(90/94). MRI detected 88 of 94 breast cancers (sensitivity 93.6%), and mammography detected 48 breast cancers (sensitivity 51.1%) (two-sided p < 0.001). Forty-two malignancies were detected only by MRI (42/94 = 44.7%). Two DCIS were detected only with mammography (2/94 = 2.1%) concerning a grade 3 in a 50-year-old patient and a grade 2 in a 67-year-old patient. Four interval cancers occurred (4/94 = 4.3%), all grade 3 triple negative invasive ductal carcinomas. In conclusion, digital mammography added only 2% to the breast cancer detection in BRCA1 patients. There was no benefit of additional mammography in women below age 40. Given the potential risk of radiation-induced breast cancer in young mutation carriers, we propose to screen BRCA1 mutation carriers yearly with MRI from age 25 onwards and to start with mammographic screening not earlier than age 40. © Springer Science+Business Media 2014.

Van Leeuwen A.C.,Antoni Van Leeuwenhoek Hospital | Buckle T.,Antoni Van Leeuwenhoek Hospital | Bendle G.,Antoni Van Leeuwenhoek Hospital | Vermeeren L.,Antoni Van Leeuwenhoek Hospital | And 4 more authors.
Journal of Biomedical Optics | Year: 2011

To improve surgical guidance toward prostate draining lymph nodes, we investigate the potential of intraoperative fluorescence imaging and combined pre- and intraoperative multimodality imaging approaches. Transgenic adenocarcinoma mouse prostate mice with spontaneous prostate tumors are injected intratumorally with: 1. a cocktail of patent blue (Pb) and indocyanine green (ICG); 2. a cocktail of albumin radiocolloids (99mTc-NanoColl), Pb, and ICG; or 3. a cocktail of radiolabeled albumin (99mTc-Vasculosis), Pb, and ICG. The distribution of these imaging agents over the lymph nodes (LNs) are studied at different time points after injection. We find that at 60-min postinjection, ICG significantly improves the detection of the LNs compared to Pb, 53 versus 7, respectively. Moreover, a cocktail of ICG and 99mTc-NanoColl improves the fluorescent detection rate to 86, equalling that of the clinically applied 99mTc-NanoColl. A similar overlap is observed in our initial clinical pilot data. Fluorescent detection of the LNs using a ICG with 99mTc-Vasculosis gives similar results as free ICG (58; 60 min). A 99mTc-NanoColl, Pb, and cocktail ICG enriches the standard 99mTc-NanoColl approach by adding optical detection of the sentinel lymph nodes. Furthermore, this approach improves fluorescent-based guidance and enables both accurate surgical planning and intraoperative detection, based on a single injection. © 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

Stiekema A.,Netherlands Cancer Institute | Boldingh Q.J.A.J.,Netherlands Cancer Institute | Korse C.M.,Netherlands Cancer Institute | Van Der Noort V.,Netherlands Cancer Institute | And 4 more authors.
Gynecologic Oncology | Year: 2015

Objective: About 5-15% of all malignant ovarian tumors are metastases from other malignancies such as gastrointestinal tumors, breast cancer or melanoma. Also other gynecological tumors can metastasize to the ovaries. It is crucial to differentiate between primary epithelial ovarian cancer (EOC) and ovarian metastases because different treatment is required. The clinical value of human epididymal secretory protein 4 (HE4) as a serum biomarker in primary ovarian cancer has been established. The use of HE4 in the differentiation between primary ovarian cancer and ovarian metastases from other malignancies has never been investigated. Methods: HE4, CA125 and CEA were measured in 192 patients with EOC (n = 147) or ovarian metastases (n = 40). Univariate and multivariate logistic regression analyses were done. Sensitivity, specificity and area under the curve (AUC) were calculated for all markers and ratios hereof using receiver operating characteristics methodology. Results: Median serum HE4 concentration was significantly higher in patients with EOC compared to patients with ovarian metastases (431 pmol/L vs 68 pmol/L, p < 0.001). HE4 and CEA were independent factors in differentiating between EOC and ovarian metastases (both p < 0.001) while CA125 was not (p = 0.33). The HE42.5/CEA ratio demonstrated the highest discriminative value (ROC-AUC 0.94) compared to HE4, CEA, CA125 or CA125/CEA ratio (0.88, 0.78, 0.80 and 0.89 respectively) and showed a specificity of 82.5% at set sensitivity of 90% in discriminating EOC from ovarian metastases. Conclusion: HE4 can be used in combination with CEA to make the distinction between EOC and ovarian metastases from gastrointestinal origin. © 2014 Elsevier Inc. All rights reserved.

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