Time filter

Source Type

Rotterdam, Netherlands

Gravendeel L.A.M.,Erasmus Medical Center | De Rooi J.J.,Erasmus Medical Center | Eilers P.H.C.,Erasmus Medical Center | Van Den Bent M.J.,Daniel Den Hoed Cancer Center | And 2 more authors.
British Journal of Cancer | Year: 2012

Background: We have recently demonstrated that expression profiling is a more accurate and objective method to classify gliomas than histology. Similar to most expression profiling studies, our experiments were performed using fresh frozen (FF) glioma samples whereas most archival samples are fixed in formalin and embedded in paraffin (FFPE). Identification of the same, expression-based intrinsic subtypes in FFPE-stored samples would enable validation of the prognostic value of these subtypes on these archival samples. In this study, we have therefore determined whether the intrinsic subtypes identified using FF material can be reproduced in FFPE-stored samples.Methods: We have performed expression profiling on 55 paired FF-FFPE glioma samples using HU133 plus 2.0 arrays (FF) and Exon 1.0 ST arrays (FFPE). The median time in paraffin of the FFPE samples was 14.1 years (range 6.6-26.4 years). Results: In general, the correlation between FF and FFPE expression in a single sample was poor. We then selected the most variable probe sets per gene (n17 583), and of these, the 5000 most variable probe sets on FFPE expression profiles. This unsupervised selection resulted in a better concordance (R 2 0.54) between expression of FF and FFPE samples. Importantly, this probe set selection resulted in a correct assignment of 87% of FFPE samples into one of seven intrinsic subtypes identified using FF samples. Assignment to the same molecular cluster as the paired FF tissue was not correlated to time in paraffin. Conclusion: We are the first to examine a large cohort of paired FF and FFPE samples. We show that expression data from FFPE material can be used to assign samples to intrinsic molecular subtypes identified using FF material. This assignment allows the use of archival material, including material derived from large-randomised clinical trials, to determine the predictive and/or prognostic value of intrinsic glioma subtypes on Exon arrays. This would enable clinicians to provide patients with an objective and accurate diagnosis and prognosis, and a personalised treatment strategy. © 2012 Cancer Research UK. Source

Van Putten E.H.,Erasmus Medical Center | Dirven C.M.,Erasmus Medical Center | Van Den Bent M.J.,Erasmus Medical Center | Van Den Bent M.J.,Daniel Den Hoed Cancer Center | Lamfers M.L.,Erasmus Medical Center
Future Oncology | Year: 2010

The field of gene therapy for malignant glioma has made important advances since the first gene transfer studies were performed 20 years ago. Multiple Phase I/II trials and two Phase III trials have been performed and have demonstrated the feasibility and safety of intratumoral vector delivery in the brain. Sitimagene ceradenovec is an adenoviral vector encoding the herpes simplex thymidine kinase gene, developed by Ark Therapeutics Group plc (UK and Finland) for the treatment of patients with operable high-grade glioma. In preclinical and Phase I/II clinical studies, sitimagene ceradenovec exhibited a significant increase in survival. Although the preliminary results of a Phase III clinical study demonstrated a significant positive effect of sitimagene ceradenovec treatment on time to reintervention or death when compared with standard care treatment (hazard ratio: 1.43; 95% CI: 1.06-1.93; p < 0.05), the European Committee for Medicinal Products for Human Use did not consider the data to provide sufficient evidence of clinical benefit. Further clinical evaluation, powered to demonstrate a benefit on a robust end point, is required. This article focuses on sitimagene ceradenovec and provides an overview of the developments in the field of gene therapy for malignant glioma. © 2010 Future Medicine Ltd. Source

Osman S.O.S.,Daniel Den Hoed Cancer Center | Astreinidou E.,Leiden University | Levendag P.C.,Daniel Den Hoed Cancer Center | Heijmen B.J.M.,Daniel Den Hoed Cancer Center
Acta Oncologica | Year: 2014

Purpose. To investigate the robustness of single vocal cord intensity modulated radiation therapy (IMRT) treatment plans for set-up errors, respiration, and deformation. Material and methods. Four-dimensional computed tomography (4D-CT) scans of 10 early glottic carcinoma patients, previously treated with conventional techniques, were used in this simulation study. For each patient a pre-treatment 4D-CT was used for IMRT planning, generating a reference dose distribution. Prescribed PTV dose was 66 Gy. The impact of systematic set-up errors was simulated by applying shifts of ± 2 mm to the planning CT scans, followed by dose re-calculation with original beam segments, MUs, etc. Effects of respiration and deformation were determined utilizing extreme inhale and exhale CT scans, and repeat scans acquired after 22 Gy, 44 Gy, and 66 Gy, respectively. All doses were calculated using Monte Carlo dose simulations. Results. Considering all investigated geometrical perturbations, reductions in the clinical target volume (CTV) V95%, D98%, D2%, and generalized equivalent uniform dose (gEUD) were limited to 1.2 ± 2.2%, 2.4 ± 2.9%, 0.2 ± 1.8%, and 0.6 ± 1.1 Gy, respectively. The near minimum dose, D98%, was always higher than 89%, and gEUD always remained higher than 66 Gy. Planned contra-lateral (CL) vocal cord DMean, gEUD, and V40 Gy were 38.2 ± 6.0 Gy, 43.4 ± 5.6 Gy, and 42.7 ± 14.9%. With perturbations these values changed by -0.1 ± 4.3 Gy, 0.1 ± 4.0 Gy, and -1.0 ± 9.6%, respectively. Conclusions. On average, CTV dose reductions due to geometrical perturbations were very low, and sparing of the CL vocal cord was maintained. In a few observations (6 of 103 simulated situations), the near-minimum CTV-dose was around 90%, requiring attention in deciding on a future clinical protocol. © 2014 Informa Healthcare. Source

De Bruijne M.,Daniel Den Hoed Cancer Center | Holt B.V.D.,Erasmus University Rotterdam | Van Rhoon G.C.,Daniel Den Hoed Cancer Center | Van Der Zee J.,Daniel Den Hoed Cancer Center
Strahlentherapie und Onkologie | Year: 2010

Background and Purpose: Prospective use of the CEM43°CT90 thermal dose parameter has been proposed for hyperthermia treatments. This study evaluates the CEM43°CT90 parameter by means of a retrospective analysis of recurrent breast cancer patients receiving reirradiation plus hyperthermia. Material and Methods: CEM43°CT90 was calculated for 72 patients who received 8 × 4 Gy reirradiation plus 8 × 1 h hyperthermia for adenocarcinoma recurrences at the chest wall. Associations of prognostic factors CEM43°CT90 and tumor maximum diameter with endpoints complete response (CR), duration of local control (DLC), and overall survival (OS) were determined. Results: A highly significant inverse association between CEM43°CT90 and tumor maximum diameter (ρ = -0.7, p < 1e-6) was found. The association between CR and CEM43°CT90 was not significant (p ≥ 0.7). CEM43°CT90 was associated with DLC. Both CEM43°CT90 and tumor maximum diameter had a significant association with survival (p > 0.01). The association with thermal dose, when adjusted for tumor maximum diameter, was not significant for either CR, DLC, or OS (p > 0.2). Conclusion: In this retrospective study, no clear CEM43°CT90 thermal dose targets or associations with clinical endpoints could be established. © 2010 Urban & Vogel, Muenchen. Source

Geisler C.H.,Rigshospitalet | Van t'Veer M.B.,Daniel Den Hoed Cancer Center | Jurlander J.,Rigshospitalet | Walewski J.,Center of Oncology of Poland | And 10 more authors.
Blood | Year: 2014

The randomized Haemato Oncology Foundation for Adults in The Netherlands 68 phase 3 trial compared front-line chemotherapy with chemotherapy plus the CD52 monoclonal antibody alemtuzumab for high-risk chronic lymphocytic leukemia, defined as at least 1 of the following: unmutated immunoglobulin heavy chain genes, deletion 17p or 11q, or trisomy 12. Fit patients were randomized to receive either 6 28-day cycles of oral FC chemotherapy (days 1 through 3: fludarabine 40 mg/m2 per day and cyclophosphamide 250 mg/m2 per day: n = 139) or FC plus subcutaneous alemtuzumab 30 mg day 1 (FCA, n = 133). FCA prolonged the primary end point, progression-free survival (3-year progression-free survival 53 vs 37%, P = .01), but not the secondary end point, overall survival (OS). However, a post hoc analysis showed that FCA increased OS in patients younger than 65 years (3-year OS 85%vs 76%, P = .035). FCA also increased the overall response rate (88 vs 78%, P = .036), and the bone marrow minimal residual disease-negative complete remission rate (64% vs 43%, P = .016). Opportunistic infections were more frequent following FCA, but without an increase in treatment related mortality (FCA: 3.8%, FC: 4.3%). FCA improves progression-free survival in high-risk chronic lymphocytic leukemia. As anticipated, FCA ismore immunosuppressive than FC, but with due vigilance, does not lead to a higher treatment-related mortality. This study was registered at www.trialregister.nl as trial no. NTR529. © 2014 by The American Society of Hematology. Source

Discover hidden collaborations