Dr Bernard Verbeeten Institute

Tilburg, Netherlands

Dr Bernard Verbeeten Institute

Tilburg, Netherlands

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Rades D.,University of Lübeck | Rades D.,University of Hamburg | Dziggel L.,University of Lübeck | Nagy V.,Oncology and Radiotherapy Institute | And 5 more authors.
Radiotherapy and Oncology | Year: 2013

Background and purpose Survival scores for patients with brain metastasis exist. However, the treatment regimens used to create these scores were heterogeneous. This study aimed to develop and validate a survival score in homogeneously treated patients. Materials and methods Eight-hundred-and-eighty- two patients receiving 10 × 3 Gy of WBRT alone were randomly assigned to a test group (N = 441) or a validation group (N = 441). In the multivariate analysis of the test group, age, performance status, extracranial metastasis, and systemic treatment prior to WBRT were independent predictors of survival. The score for each factor was determined by dividing the 6-month survival rate (in %) by 10. Scores were summed and total scores ranged from 6 to 19 points. Patients were divided into four prognostic groups. Results The 6-month survival rates were 4% for 6-9 points, 29% for 10-14 points, 62% for 15-17 points, and 93% for 17-18 points (p < 0.001) in the test group. The survival rates were 3%, 28%, 54% and 96%, respectively (p < 0.001) in the validation group. Conclusions Since the 6-month survival rates in the validation group were very similar to the test group, this new score (WBRT-30) appears valid and reproducible. It can help making treatment choices and stratifying patients in future trials. © 2013 Elsevier Ireland Ltd. All rights reserved.


Rades D.,University of Lübeck | Dziggel L.,University of Lübeck | Haatanen T.,University of Hamburg | Veninga T.,Dr Bernard Verbeeten Institute | And 2 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2011

Purpose: To create and validate scoring systems for intracerebral control (IC) and overall survival (OS) of patients irradiated for brain metastases. Methods and Materials: In this study, 1,797 patients were randomly assigned to the test (n = 1,198) or the validation group (n = 599). Two scoring systems were developed, one for IC and another for OS. The scores included prognostic factors found significant on multivariate analyses. Age, performance status, extracerebral metastases, interval tumor diagnosis to RT, and number of brain metastases were associated with OS. Tumor type, performance status, interval, and number of brain metastases were associated with IC. The score for each factor was determined by dividing the 6-month IC or OS rate (given in percent) by 10. The total score represented the sum of the scores for each factor. The score groups of the test group were compared with the corresponding score groups of the validation group. Results: In the test group, 6-month IC rates were 17% for 14-18 points, 49% for 19-23 points, and 77% for 24-27 points (p < 0.0001). IC rates in the validation group were 19%, 52%, and 77%, respectively (p < 0.0001). In the test group, 6-month OS rates were 9% for 15-19 points, 41% for 20-25 points, and 78% for 26-30 points (p < 0.0001). OS rates in the validation group were 7%, 39%, and 79%, respectively (p < 0.0001). Conclusions: Patients irradiated for brain metastases can be given scores to estimate OS and IC. IC and OS rates of the validation group were similar to the test group demonstrating the validity and reproducibility of both scores. © 2011 Elsevier Inc.


Rades D.,University of Lübeck | Rades D.,University of Hamburg | Evers J.N.,University of Lübeck | Veninga T.,Dr Bernard Verbeeten Institute | And 2 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2011

Purpose: Many patients with brain metastases receive whole-brain radiotherapy (WBRT) alone. Using 10 × 3 Gy in 2 weeks is the standard regimen in most centers. Regarding the extraordinarily poor survival prognosis of elderly patients with multiple brain metastases, a shorter WBRT regimen would be preferable. This study compared 10 × 3 Gy with 5 × 4 Gy in elderly patients (≥65 years). Methods and Materials: Data from 455 elderly patients who received WBRT alone for brain metastases were retrospectively analyzed. Survival and local (= intracerebral) control of 293 patients receiving 10 × 3 Gy were compared with 162 patients receiving 5 × 4 Gy. Eight additional potential prognostic factors were investigated including age, gender, Karnofsky performance score (KPS), primary tumor, number of brain metastases, interval from tumor diagnosis to WBRT, extracerebral metastases, and recursive partitioning analysis (RPA) class. Results: The 6-month overall survival rates were 29% after 5 × 4 Gy and 21% after 10 × 3 Gy (p = 0.020). The 6-month local control rates were 12% and 10%, respectively (p = 0.32). On multivariate analysis, improved overall survival was associated with KPS ≥ 70 (p < 0.001), only one to three brain metastases (p = 0.029), no extracerebral metastasis (p = 0.012), and lower RPA class (p < 0.001). Improved local control was associated with KPS ≥ 70 (p < 0.001), breast cancer (p = 0.029), and lower RPA class (p < 0.001). Conclusions: Shorter-course WBRT with 5 × 4 Gy was not inferior to 10 × 3 Gy with respect to overall survival or local control in elderly patients. 5 × 4 Gy appears preferable for the majority of these patients. © 2011 Elsevier Inc.


Van Schil P.E.,University of Antwerp | Baas P.,Netherlands Cancer Institute | Gaafar R.,Cairo University | Maat A.P.,Erasmus University Rotterdam | And 6 more authors.
European Respiratory Journal | Year: 2010

The European Organisation for Research and Treatment of Cancer (EORTC; protocol 08031) phase II trial investigated the feasibility of trimodality therapy consisting of induction chemotherapy followed by extrapleural pneumonectomy and post-operative radiotherapy in patients with malignant pleural mesothelioma (with a severity of cT3N1M0 or less). Induction chemotherapy consisted of three courses of cisplatin 75 mg·m-2 and pemetrexed 500 mg·m-2. Nonprogressing patients underwent extrapleural pneumonectomy followed by postoperative radiotherapy (54 Gy, 30 fractions). Our primary end-point was "success of treatment" and our secondary end-points were toxicity, and overall and progression-free survival. 59 patients were registered, one of whom was ineligible. Subjects' median age was 57 yrs. The subjects' TNM scores were as follows: cT1, T2 and T3, 36, 16 and six patients, respectively; cN0 and N1, 57 and one patient, respectively. 55 (93%) patients received three cycles of chemotherapy with only mild toxicity. 46 (79%) patients received surgery and 42 (74%) had extrapleural pneumonectomy with a 90-day mortality of 6.5%. Post-operative radiotherapy was completed in 37 (65%) patients. Grade 3-4 toxicity persisted after 90 days in three (5.3%) patients. Median overall survival time was 18.4 months (95% CI 15.6-32.9) and median progression-free survival was 13.9 months (95% CI 10.9-17.2). Only 24 (42%) patients met the definition of success (one-sided 90% CI 0.36-1.00). Although feasible, trimodality therapy in patients with mesothelioma was not completed within the strictly defined timelines of this protocol and adjustments are necessary. Copyright©ERS 2010.


Rades D.,University of Lübeck | Kueter J.D.,University of Lübeck | Gliemroth J.,University of Lübeck | Veninga T.,Dr Bernard Verbeeten Institute | And 2 more authors.
Strahlentherapie und Onkologie | Year: 2012

Background. The optimal treatment for patients with a single brain metastasis is controversial. This study investigated the value of a radiation boost given in addition to neurosurgerical resection and whole-brain irradiation (WBI). Patients and methods. In this retrospective study, outcome data of 105 patients with a single brain metastasis receiving metastatic surgery plus WBI (S + WBI) were compared to 90 patients receiving the same treatment plus a boost to the metastatic site (S + WBI + B). The outcomes that were compared included local control of the resected metastasis (LC) and overall survival (OS). In addition to the treatment regimen, eight potential prognostic factors were evaluated including age, gender, performance status, extent of metastatic resection, primary tumor type, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from first diagnosis of cancer to metastatic surgery. Results. The LC rates at 1 year, 2 years, and 3 years were 38%, 20%, and 9%, respectively, after S + WBI, and 67%, 51%, and 33%, respectively, after S + WBI + B (p = 0.002). The OS rates at 1 year, 2 years, and 3 years were 52%, 25%, and 19%, respectively, after S + WBI, and 60%, 40%, and 26%, respectively, after S + WBI + B (p = 0.11). On multivariate analyses, improved LC was significantly associated with OP + WBI + B (p = 0.006) and total resection of the metastasis (p = 0.014). Improved OS was significantly associated with age ≤ 60 years (p = 0.028), Karnofsky Performance Score > 70 (p = 0.015), breast cancer (p = 0.041), RPA class 1 (p = 0.012), and almost with the absence of extracerebral metastases (p = 0.05). Conclusion. A boost in addition to WBI significantly improved LC but not OS following resection of a single brain metastasis. © Springer-Verlag 2012.


Rades D.,University of Lübeck | Veninga T.,Dr Bernard Verbeeten Institute | Bajrovic A.,University of Hamburg | Karstens J.H.,Leibniz University of Hanover | Schild S.E.,Mayo Medical School
Strahlentherapie und Onkologie | Year: 2013

Purpose: This study aimed to develop and validate a scoring system to identify long-term survivors after conventional radiotherapy (RT) for metastatic spinal cord compression (MSCC). Patients and methods: Data from 1,125 patients who had received long-course RT for MSCC were included in this study. Of these patients, 344 survived for over 12 months and 781 died within a year following RT. Based on differences between the distributions of patient characteristics in the two groups, a scoring system was developed. Scores ranged from 0 to 18 points and 15 points was selected as the cutoff for identifying long-term survivors. Data from the 1,125 long-course RT patients (test group) were compared to data from 773 patients receiving short-course RT (validation group). Results: A score of ≥ 15 points was associated with a 94 % proportion of long-term survivors. The 15-point cutoff resulted in a specificity of 98 % and a positive predictive value of 94 % for identification of long-term surviving patients. The proportions of long-term survivors for each scoring point in the validation group were very similar to those in the test group. Conclusion: This new scoring system enabled identification of long-term survivors after RT for MSCC with very high specificity and positive predictive value. The score proved to be valid and reproducible. © 2013 Urban & Vogel.


Rades D.,University of Lübeck | Veninga T.,Dr Bernard Verbeeten Institute | Hornung D.,University of Hamburg | Wittkugel O.,University of Lübeck | And 2 more authors.
Cancer | Year: 2012

Background: The current study was conducted to compare neurosurgical resection (NR) followed by whole-brain irradiation (WBI) (NR + WBI) with WBI followed by radiosurgery (WBI + RS) in patients with a single brain metastasis. Methods: The outcome of 41 patients treated with WBI + RS was retrospectively compared with 111 patients who received NR;+ WBI with respect to local control of the treated metastasis and survival. Eleven additional potential prognostic factors were investigated, including WBI schedule, patient age, patient gender, Karnofsky performance score (KPS), primary tumor type, extracerebral metastases, recursive partitioning analysis (RPA) class, interval between the first diagnosis of cancer to the treatment of brain metastasis, metastatic site, maximum diameter of the metastasis, and graded prognostic assessment (GPA) score. Results: The 1-year local control rates were 87% after WBI + RS and 56% after NR + WBI (P =.001). Using the Cox proportional hazards model, the treatment regimen remained significant (risk ratio [RR], 2.46; 95% confidence interval [95% CI], 1.29-5.17 [P =.005]). On the multivariate analysis, local control was also found to be associated with the maximum diameter of the metastasis. The 1-year survival rates were 61% after WBI + RS and 53% after NR + WBI (P =.16). Acute and late toxicities were similar in both groups. On the multivariate analysis, KPS, extracerebral metastases, RPA class, and the GPA score were found to be independent predictors of survival. Conclusions: The use of WBI + RS resulted in significantly better local control of the treated metastasis than NR + WBI. Survival was not found to be significantly different in either group. Because WBI + RS is less invasive than NR + WBI, it appears to be preferable for many patients with a single brain metastasis. These results should be confirmed in a randomized trial. © 2011 American Cancer Society.


Rades D.,University of Lübeck | Douglas S.,University of Lübeck | Veninga T.,Dr Bernard Verbeeten Institute | Schild S.E.,Mayo Clinic Scottsdale
BMC Cancer | Year: 2012

Background: This multicenter study aimed to create and validate a scoring system for survival of patients with metastatic spinal cord compression (MSCC) from non-small cell lung cancer (NSCLC).Methods: The entire cohort of 356 patients was divided in a test group (N = 178) and a validation group (N = 178). In the test group, nine pre-treatment factors including age, gender, Eastern Cooperative Oncology Group performance status (ECOG-PS), number of involved vertebrae, pre-radiotherapy ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, and the time developing motor were retrospectively analyzed.Results: On multivariate analysis, survival was significantly associated with ECOG-PS, pre-radiotherapy ambulatory status, visceral metastases, and the time developing motor deficits. These factors were included in the scoring system; the score for each factor was determined by dividing the 6-month survival rate (in %) by 10. The risk score represented the sum of the scores for each factor. According to the risk scores, which ranged from 6 to 19 points, three prognostic groups were designed. The 6-month survival rates were 6% for 6-10 points, 29% for 11-15 points, and 78% for 16-19 points (p < 0.001). In the validation group, the 6-month survival rates were 4%, 24%, and 76%, respectively (p < 0.001).Conclusions: Since the survival rates of the validation group were similar to those of the test group, this score can be considered reproducible. The scoring system can help when selecting the individual treatment for patients with MSCC from NSCLC. A prospective confirmatory study is warranted. © 2012 Rades et al.; licensee BioMed Central Ltd.


Rades D.,University of Lübeck | Hornung D.,University of Hamburg | Veninga T.,Dr Bernard Verbeeten Institute | Schild S.E.,Mayo Medical School | Gliemroth J.,University of Lübeck
Cancer | Year: 2012

BACKGROUND: Neurosurgical resection is considered the standard treatment for most patients with a single brain metastasis. However, radiosurgery (RS) is a reasonable alternative. It was demonstrated that whole-brain radiotherapy (WBRT) in addition to RS improves local control of 1-3 brain metastases. Little information is available regarding WBRT in addition to RS for a single lesion. METHODS: Data of 63 patients who received RS alone for a single brain metastasis were retrospectively compared with 39 patients treated with WBRT+RS for local control of the treated metastasis, distant intracerebral control, and survival. Seven additional potential prognostic factors were investigated including age, sex, Karnofsky performance score, tumor type, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to irradiation. RESULTS: The 1-year local control rates were 49% after RS and 77% after WBRT+RS (P =.040). The 1-year distant control rates were 70% and 90%, respectively (P =.08). The 1-year survival rates were 57% and 61%, respectively (P =.47). On multivariate analysis, improved local control was associated with WBRT+RS (risk ratio [RR], 1.95; P =.033) and interval from tumor diagnosis to irradiation >15 months (RR, 1.88; P =.042). Improved distant control was almost associated with WBRT+RS (RR, 2.24; P =.05) and age (RR, 2.20; P =.05). Improved survival was associated with KPS 90-100 (RR, 1.73; P =.040), no extracerebral metastases (RR, 1.88; P =.013), RPA class 1 (RR, 2.06; P =.005), and interval from tumor diagnosis to irradiation >15 months (RR, 1.98; P =.009). CONCLUSION: The addition of WBRT to RS was associated with improved local control and distant intracerebral control but not survival. Copyright © 2011 American Cancer Society.


Cutuli B.,Institute du Cancer Courlancy | Poortmans P.,Dr Bernard Verbeeten Institute
Radiotherapy and Oncology | Year: 2014

Often considered an "indolent" disease for which a treatment de-escalation is advocated, ductal carcinoma in situ (DCIS) of the breast has been recently shown to be associated with a significant increase in long-term mortality in case of invasive local recurrence (LR). The publication of data from four randomised trials did not prevent the continuation of the debates about the pros and cons of postoperative radiation therapy (PORT) for optimal DCIS management. Actually only partial answers regarding the impact of PORT on local control had been brought by these randomised trials among others due to differences in pathological assessment among these controlled studies. A biologically heterogeneous disease, DCIS is characterised by a large variation in clinical behaviour, which hampers the identification of those patients for whom PORT might be considered as an overtreatment. At the light of the most recent biological and clinical studies, this review tries to identify accurately the LR risks associated with both tumour- and patient-related factors and to analyse the treatment-related parameters impacting significantly on the patient outcome. © 2014 The Authors. Published by Elsevier Ireland Ltd.

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