Tilburg, Netherlands
Tilburg, Netherlands

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Bing Oei S.,Verbeeten Institute
Cancer | Year: 2012

BACKGROUND: The objective of this study was to evaluate the role of reirradiation and hyperthermia in the treatment of radiation-associated sarcoma (RAS) in the thoracic region, which is an increasing, yet extremely rare condition with a poor prognosis. METHODS: Between 1979 and 2009, 16 patients with RAS in the thoracic region were treated in the Academic Medical Center and the Institute Verbeeten with reirradiation and hyperthermia. In 13 patients, this treatment was given for unresectable disease and 3 times after resection as adjuvant treatment. The median latency period between the original malignancy diagnosis and the RAS diagnosis was 86 months (range 19-212 months). Histology was angiosarcoma in 11 patients (69%). The literature on reirradiation with or without hyperthermia for RAS was reviewed. RESULTS: The median survival was 15.5 months (range, 3-204 months). Four patients were not evaluable for response. The response rate for the remaining 12 patients was 75% (7 complete responses and 2 partial responses). Six patients remained free of local failure until death (5 months and 7 months) or last follow-up (8 months, 11 months, 39 months, and 68 months). CONCLUSIONS: The current study indicates that combined reirradiation and hyperthermia for RAS in the thoracic region is feasible. The high response rate and the possibility of durable local control suggest that this treatment is promising. Copyright © 2011 American Cancer Society.


Van Den Heuvel M.M.,Netherlands Cancer Institute | Uyterlinde W.,Netherlands Cancer Institute | Vincent A.D.,Netherlands Cancer Institute | De Jong J.,Netherlands Cancer Institute | And 6 more authors.
Radiotherapy and Oncology | Year: 2014

Background Modest benefits from concurrent chemoradiotherapy in patients with locally advanced NSCLC warrant further clinical investigations to identify more effective treatment regimens. Cetuximab, a monoclonal antibody against the epidermal growth factor receptor has shown activity in NSCLC. We report on the safety and efficacy of the combination of daily dose Cisplatin and concurrent radiotherapy with or without weekly Cetuximab. Patients and methods Patients received high dose accelerated radiotherapy (66 Gy in 24 fractions) and concurrent daily Cisplatin (6 mg/m2) without (Arm A) or with (Arm B) weekly Cetuximab (400 mg/m2 loading dose one week prior to radiotherapy followed by weekly 250 mg/m2) the primary endpoint of the trial was objective local control rate (OLCR) determined at 6-8 weeks after treatment. Toxicity was reported as well. Results Between February 2009 and May 2011, 102 patients were randomized. Median follow up was 29 months the OLCR was 84% in Arm A and 92% in Arm B (p = 0.36) the one-year local progression free interval (LPFI) and overall survival (OS) were 69% and 82% for Arm A and 73% and 71% for Arm B, respectively (LPFI p = 0.39; OS p = 0.99). Toxicity compared equally between both groups. Conclusion The addition of Cetuximab to radiotherapy and concurrent Cisplatin did not improve disease control in patients with locally advanced NSCLC but increased treatment related toxicity. © 2013 Elsevier Ireland Ltd. All rights reserved.


PubMed | Verbeeten Institute, Comprehensive Cancer Center Netherlands Netherlands Cancer Registry, Catharina Hospital and St Elisabeth Hospital
Type: Journal Article | Journal: Acta oncologica (Stockholm, Sweden) | Year: 2016

We assessed the use of external beam radiotherapy, brachytherapy chemoradiotherapy and chemotherapy in patients with metastatic esophageal cancer and evaluated the effect on overall survival.We included all patients diagnosed with synchronous metastatic esophageal cancer in the south of the Netherlands between 1 January 1994 and 31 December 2013. Proportions of patients treated with external beam radiotherapy, brachytherapy, chemoradiotherapy and chemotherapy were described with respect to the period of diagnosis, patient and tumor characteristics. Independent risk factors for death were discriminated.A total of 1020 patients were included, 61.5% of these patients received palliative treatment with external beam radiotherapy, chemoradiotherapy, brachytherapy and/or chemotherapy. The use of external beam radiotherapy decreased from 44.5% in 1994 to 22.2% in 2013 (p=0.0001), whereas the use of chemoradiotherapy increased from 2.9% in 1994 to 19.1% in 2013 (p<0.0001). The prescription of systemic chemotherapy as single modality increased from 13.9% to 30.5% (p<0.0001). The use of brachytherapy decreased from 20.9% in 1994 to 7.4% in 2013 (p=0.0013). The odds of receiving external beam radiotherapy, brachytherapy, chemoradiotherapy and chemotherapy were influenced by different tumor and patient characteristics, such as age, gender, histologic subtype and number of metastatic sites. The median overall survival in patients with metastatic esophageal cancer significantly improved over time from 18 weeks (one-year survival rate 14.4%) in 1994-1998 to 25 weeks (one-year survival rate 22.4%) in 2009-2013. Patients treated with chemoradiotherapy had the most favorable prognosis, followed by patients treated with chemotherapy as a single modality.The median overall survival of patients diagnosed with metastatic esophageal cancer improved from 18 weeks in 1994-1998 to 25 weeks in 2009-2013. Although this increase could be attributed to stage migration, our population-based study suggests that major changes in treatment strategies and appropriate patient selection might have played a role as well.


PubMed | Erasmus Medical Center, Verbeeten Institute, Haga Hospital, Netherlands Cancer Institute and MC Haaglanden
Type: Clinical Trial, Phase II | Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology | Year: 2016

Radiation dose escalation using hypofractionation might improve overall survival (OS). We investigated OS in a phase II multicenter study in locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with hypofractionated concurrent chemoradiotherapy.A 2-armed phase II, multi-center study (NTR2230) was performed with the aim to assess the effect of cetuximab to concurrent chemoradiotherapy in LA-NSCLC patients (stage II/IIIA/B). Arm A received high dose radiotherapy (24 2.75 Gy) and concurrent daily low-dose cisplatin (6 mg/m(2)). Arm B received an identical treatment regimen with additional weekly cetuximab. Kaplan-Meier survival curves and 1-, 2- and 5-year OS proportions were calculated.Between February 2009 and May 2011, 102 patients were randomly allocated in two arms. Median OS was 31.5 months (range 12.8-52.3), not significantly different between arms A and B; 33.0 (range 17.0-57.0) and 30.0 (11.0-52.0) months. 1-, 2- and 5-year OS rates were 74.5%, 59.4% and 37.3%, respectively. In multivariate analyses, worse performance score, V35 of the esophagus and the existence of comorbidities were significantly (P-value<0.05) associated with a shorter OS.In this phase II trial, the median OS for the entire group was remarkably high; 31.5 months. Furthermore, 5-year OS was still 37.3%. Hypofractionation might contribute to improved OS in LA-NSCLC patients.


Shapiro J.,Erasmus University Rotterdam | van Lanschot J.J.B.,Erasmus University Rotterdam | van Hagen P.,Erasmus University Rotterdam | Wijnhoven B.P.L.,Erasmus University Rotterdam | And 21 more authors.
The Lancet Oncology | Year: 2015

Background: Initial results of the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) comparing neoadjuvant chemoradiotherapy plus surgery versus surgery alone in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus or oesophagogastric junction showed a significant increase in 5-year overall survival in favour of the neoadjuvant chemoradiotherapy plus surgery group after a median of 45 months' follow-up. In this Article, we report the long-term results after a minimum follow-up of 5 years. Methods: Patients with clinically resectable, locally advanced cancer of the oesophagus or oesophagogastric junction (clinical stage T1N1M0 or T2-3N0-1M0, according to the TNM cancer staging system, sixth edition) were randomly assigned in a 1:1 ratio with permuted blocks of four or six to receive either weekly administration of five cycles of neoadjuvant chemoradiotherapy (intravenous carboplatin [AUC 2 mg/mL per min] and intravenous paclitaxel [50 mg/m2 of body-surface area] for 23 days) with concurrent radiotherapy (41·4 Gy, given in 23 fractions of 1·8 Gy on 5 days per week) followed by surgery, or surgery alone. The primary endpoint was overall survival, analysed by intention-to-treat. No adverse event data were collected beyond those noted in the initial report of the trial. This trial is registered with the Netherlands Trial Register, number NTR487, and has been completed. Findings: Between March 30, 2004, and Dec 2, 2008, 368 patients from eight participating centres (five academic centres and three large non-academic teaching hospitals) in the Netherlands were enrolled into this study and randomly assigned to the two treatment groups: 180 to surgery plus neoadjuvant chemoradiotherapy and 188 to surgery alone. Two patients in the neoadjuvant chemoradiotherapy group withdrew consent, so a total of 366 patients were analysed (178 in the neoadjuvant chemoradiotherapy plus surgery group and 188 in the surgery alone group). Of 171 patients who received any neoadjuvant chemoradiotherapy in this group, 162 (95%) were able to complete the entire neoadjuvant chemoradiotherapy regimen. After a median follow-up for surviving patients of 84·1 months (range 61·1-116·8, IQR 70·7-96·6), median overall survival was 48·6 months (95% CI 32·1-65·1) in the neoadjuvant chemoradiotherapy plus surgery group and 24·0 months (14·2-33·7) in the surgery alone group (HR 0·68 [95% CI 0·53-0·88]; log-rank p=0·003). Median overall survival for patients with squamous cell carcinomas was 81·6 months (95% CI 47·2-116·0) in the neoadjuvant chemoradiotherapy plus surgery group and 21·1 months (15·4-26·7) in the surgery alone group (HR 0·48 [95% CI 0·28-0·83]; log-rank p=0·008); for patients with adenocarcinomas, it was 43·2 months (24·9-61·4) in the neoadjuvant chemoradiotherapy plus surgery group and 27·1 months (13·0-41·2) in the surgery alone group (HR 0·73 [95% CI 0·55-0·98]; log-rank p=0·038). Interpretation: Long-term follow-up confirms the overall survival benefits for neoadjuvant chemoradiotherapy when added to surgery in patients with resectable oesophageal or oesophagogastric junctional cancer. This improvement is clinically relevant for both squamous cell carcinoma and adenocarcinoma subtypes. Therefore, neoadjuvant chemoradiotherapy according to the CROSS trial followed by surgical resection should be regarded as a standard of care for patients with resectable locally advanced oesophageal or oesophagogastric junctional cancer. Funding: Dutch Cancer Foundation (KWF Kankerbestrijding). © 2015 Elsevier Ltd.


Vermeltfoort I.A.C.,Verbeeten Institute | Teule G.J.J.,Verbeeten Institute | van Dijk A.B.,Verbeeten Institute | Muntinga H.J.,Tweesteden Hospital | Raijmakers P.G.H.M.,VU University Amsterdam
Netherlands Heart Journal | Year: 2012

Aims Follow-up studies of patients with cardiac syndrome X (CSX) generally report good prognosis. However, some recent studies report an adverse outcome for women. Methods and results Structured literature search and metaanalysis for studies regarding prognosis of cardiac syndrome X patients. We identified 85 studies, ultimately selecting 16 for inclusion. Meta-analysis yielded a pooled major cardiac event percentage of 1.5% per 5 years and a pooled vascular event percentage of 4.8% per 5 years (n=16 studies, n=1694 patients). Fourteen studies reported upon the recurrence rate of angina pectoris: the pooled percentage of angina recurrence was 55% (n=1336 patients). Conclusion The present review of recent archival literature demonstrates an overall major cardiac event rate of 1.5% per 5 years. Although this is an excellent prognosis for CSX patients, the quality of life is impaired because of the high recurrence rate of angina pectoris (55%). © The Author(s) 2012.


Kunneman M.,Leiden University | Marijnen C.A.M.,Leiden University | Rozema T.,Verbeeten Institute | Ceha H.M.,Radiotherapy Center West | And 4 more authors.
British Journal of Cancer | Year: 2015

Background: For shared decision making to be successful, patients should receive sufficient information on possible benefits and harms of treatment options. The aim of this study was to evaluate what information radiation oncologists provide during the decision consultation about preoperative radiotherapy with rectal cancer patients. Methods: Decision consultations of 17 radiation oncologists with 81 consecutive primary rectal cancer patients, eligible for short-course radiotherapy followed by a low-anterior resection, were audio taped. Tapes were transcribed and analysed using the ACEPP (Assessing Communication about Evidence and Patient Preferences) coding scheme. Results: A median of seven benefits/harms were addressed per consultation (range, 2-13). This number ranged within and between oncologists and was not clearly associated with the patient's characteristics. A total of 30 different treatment outcomes were addressed. The effect of radiotherapy on local control was addressed in all consultations, the effect on survival in 16%. The most important adverse effects are bowel and sexual dysfunction. These were addressed in 82% and 85% of consultations, respectively; the latter significantly less often in female than in male patients. Four out of five patients did not initiate discussion on any benefits/harms. Conclusions: Our results showed considerable inconsistency between and within oncologists in information provision, which could not be explained by patient characteristics. This variation indicates a lack of clarity on which benefits/harms of radiotherapy should be discussed with newly-diagnosed patients. This suboptimal patient information hampers the process of shared decision making, in which the decision is based on each individual patients' weighing of benefits and harms. © 2015 Cancer Research UK.


Cai L.,University of Lausanne | Cai L.,Sun Yat Sen University | Stauder M.C.,Mayo Medical School | Zhang Y.-J.,Sun Yat Sen University | And 12 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with Stages I and II PBL. Patients and Methods: Thirteen Rare Cancer Network (RCN) institutions enrolled 116 consecutive patients with PBL treated between 1987 and 2008 in this study. Eighty-seven patients underwent chemoradiotherapy (CXRT) without (78) or with (9) surgery, 15 radiotherapy (RT) without (13) or with (2) surgery, and 14 chemotherapy (CXT) without (9) or with (5) surgery. Median RT dose was 40 Gy (range, 4-60). The median number of CXT cycles was six (range, 2-8). Median follow-up was 41 months (range, 6-242). Results: The overall response rate at the end of treatment was 91% (complete response [CR] 74%, partial response [PR] 17%). Local recurrence or progression was observed in 12 (10%) patients and systemic recurrence in 17 (15%). The 5-year overall survival (OS), lymphoma-specific survival (LSS), and local control (LC) were 76%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for OS and LSS were International Prognostic Index (IPI) score ≤1 (p = 0.009), high-grade histology (p = 0.04), CXRT (p = 0.05), CXT (p = 0.0004), CR (p < 0.0001), and RT dose >40 Gy (p = 0.005). For LC, only CR and Stage I were favorable factors. In multivariate analysis, IPI score, RT dose, CR, and CXT were independently influencing the outcome (OS and LSS). CR was the only predicting factor for LC. Conclusion: This large multicenter retrospective study confirms the good prognosis of early-stage PBL treated with combined CXRT. An adequate dose of RT and complete CXT regime were associated with better outcome. © 2012 Elsevier Inc. All rights reserved.


PubMed | Leiden University, Verbeeten Institute, Radiotherapy Center West and Reinier Of Graaf Group
Type: Journal Article | Journal: British journal of cancer | Year: 2015

For shared decision making to be successful, patients should receive sufficient information on possible benefits and harms of treatment options. The aim of this study was to evaluate what information radiation oncologists provide during the decision consultation about preoperative radiotherapy with rectal cancer patients.Decision consultations of 17 radiation oncologists with 81 consecutive primary rectal cancer patients, eligible for short-course radiotherapy followed by a low-anterior resection, were audio taped. Tapes were transcribed and analysed using the ACEPP (Assessing Communication about Evidence and Patient Preferences) coding scheme.A median of seven benefits/harms were addressed per consultation (range, 2-13). This number ranged within and between oncologists and was not clearly associated with the patients characteristics. A total of 30 different treatment outcomes were addressed. The effect of radiotherapy on local control was addressed in all consultations, the effect on survival in 16%. The most important adverse effects are bowel and sexual dysfunction. These were addressed in 82% and 85% of consultations, respectively; the latter significantly less often in female than in male patients. Four out of five patients did not initiate discussion on any benefits/harms.Our results showed considerable inconsistency between and within oncologists in information provision, which could not be explained by patient characteristics. This variation indicates a lack of clarity on which benefits/harms of radiotherapy should be discussed with newly-diagnosed patients. This suboptimal patient information hampers the process of shared decision making, in which the decision is based on each individual patients weighing of benefits and harms.


PubMed | Leiden University, Verbeeten Institute, Amsterdam Medical Center and Radiotherapy Group Deventer
Type: Journal Article | Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology | Year: 2015

The shared decision making (SDM) model states that patients values and preferences should be clarified to choose a strategy that best fits the patient. This study aimed to assess whether values and preferences of rectal cancer patients are voiced and considered in deciding about preoperative radiotherapy (PRT), and whether this makes patients feel more involved in treatment decision making.Pre-treatment consultations of radiation oncologists and patients eligible for PRT were audiotaped (N=90). Tapes were transcribed and coded to identify patients values and treatment preferences. Patients filled in a post-consultation questionnaire on their perceived involvement in decision making (N=60).Patients values were voiced for 62/611 of benefits/harms addressed (10%), in 38/90 consultations (42%; maximum 4 values per consultation), and most often related to major long-term treatment outcomes. Patients treatment preferences were discussed in 20/90 consultations (22%). In 16/90 consultations (18%), the oncologists explicitly indicated to consider patients values or preferences. Patients perceived a significantly more active role in decision making if their values or preferences had been voiced or considered.Patients values and treatment preferences are voiced or considered in a minority of consultations. If they are, this increases patients perceived involvement in the decision making process.

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