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Amsterdam-Zuidoost, Netherlands

Simkens L.H.J.,University of Amsterdam | Van Tinteren H.,Netherlands Cancer Institute | May A.,University Utrecht | Ten Tije A.J.,Amphia Hospital | And 19 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 ClinicalTrials.gov, 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. Source

Cherny N.I.,Shaare Zedek Medical Center | Sullivan R.,Kings 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. Source

Van Hulsteijn L.T.,Leiden University | Corssmit E.P.M.,Leiden University | Van Der Hiel B.,Leiden University | Smit J.W.A.,Leiden University | Stokkel M.P.,Antoni van Leeuwenhoek Hospital
Clinical Nuclear Medicine | Year: 2012

PURPOSE: The aim of this study was to systematically review literature, exploring the role of radioguided surgery with iodine-labeled metaiodobenzylguanidine (MIBG) in resection of neuroendocrine tumors. METHODS: PubMed, EMBASE, Web of Science, COCHRANE, CINAHL, Academic Search Premier, ScienceDirect, Wiley, and references of key articles were searched to identify potentially relevant studies. RESULTS: Twenty studies were included. A total of 130 procedures in 120 patients were performed. Ninety percent of included studies concerned case reports or case series. It is described that radioguided surgery with iodine-labeled MIBG can improve the quality of macroscopic resection of neuroendocrine tumors in selected cases, ie, in cases where the tumor is small, nonpalpable, difficult to visualize on conventional imaging studies, or located in an area with adhesional scar tissue from previous surgery. However, in a substantial number of cases the gamma probe failed due to technical problems. CONCLUSIONS: Since there is limited evidence that radioguided surgery contributes substantially in resection of neuroendocrine tumors, we cannot advocate its use in general. However, we can conclude that it can seemingly improve the quality of resection in selected cases. When radioguided surgery is performed in neuroendocrine tumors, we advocate the use of I to label MIBG. Copyright © 2012 by Lippincott Williams & Wilkins. Source

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. Source

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. Source

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