Ruud Houben

Maastricht University, Maestricht, Limburg, Netherlands

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Publications (99)

  • [Show abstract] [Hide abstract] ABSTRACT: Background and purpose: Isolated nodal failures (INF) are rare after 3D-conformal radiotherapy (3D-CRT) for stage III non-small cell lung cancer (NSCLC). Since incidental nodal irradiation doses are lower with Intensity Modulated Radiation Therapy (IMRT) than with 3D-CRT, INF may be higher after IMRT. We therefore investigated the incidence of INF after IMRT in stage III NSCLC patients. Materials and methods: Stage III NSCLC patients undergoing radical radiotherapy using IMRT in the period January 2010 till March 2012 were included. The primary endpoint was the rate of INF, secondary endpoints included patterns of failure, progression free survival (PFS), overall survival (OS) and toxicity. Results: 183 stage III NSCLC patients were enrolled. With a median follow-up of 58.0months 2.2% of patients had an INF. The median PFS was 15.0months, the median OS 19.5months. Patterns of recurrence: 2.2% INF, 11.5% local and 2.7% loco-regional recurrence, 26.8% distant metastases only, 18.0% a combination of local/loco-regional and distant metastases, and 38.3% patients without recurrence. One INF was out of field, in adjacent lymph nodes. Acute toxicity was limited. Discussion: Selective nodal irradiation using IMRT in stage III NSCLC patients results in a low in-field incidence of INF (2.2%), similar to 3D-CRT, and may thus be considered safe.
    Article · Nov 2016 · Radiotherapy and Oncology
  • Lucas J. Poort · Charlotte C. Kiewiet · Jack P.M. Cleutjens · [...] · Peter A.W.H. Kessler
    [Show abstract] [Hide abstract] ABSTRACT: Objectives The aim of this study was to compare the influence of implant surface treatment and irradiation dose on implant stability and osseointegration of 144 extraoral implants in irradiated frontal bone of minipigs. Material and methods 144 implants with 3 different surface treatments (machined, etched and HAVD-coated) were implanted in the frontal bone of 16 Göttingen minipigs. Three groups of four pigs received radiation with equivalent doses of 25, 50 and 70 Gy, and one group served as control. Resonance frequency analysis (RFA) was performed recording Implant Stability Quotients (ISQ) at implant placement and 3 months thereafter. Removal torque was measured whilst removing specific implants after 3 months. In addition, the bone-to-implant contact (BIC) was analyzed. Results Evaluation of ISQ, BIC-values showed no significant difference between the different surface treatments in irradiated and non-irradiated bone. Removal torque revealed statistically significant differences between machined and HAVD-coated implants in the irradiated bone. Conclusions Implant stability and osseointegration, based on Removal Torque showed significant higher results for the HAVD-coated implants. No significant difference was observed between the irradiated and non-irradiated animals. This study shows that HAVD-coated extraoral implants can potentially be used for craniofacial rehabilitation in non-irradiated and irradiated bone.
    Article · Aug 2016 · Journal of Cranio-Maxillofacial Surgery
  • J. Paulissen · C. Offermann · R. Houben · [...] · K. Smits
    Article · Apr 2016
  • P. Simons · R. Houben · H. Backes · [...] · M. Jacobs
    Article · Apr 2016
  • Simon J. A. van Kuijk · Ala Yaromina · Ruud Houben · [...] · Ludwig J. Dubois
    [Show abstract] [Hide abstract] ABSTRACT: Hypoxia is a characteristic of many solid tumors and an adverse prognostic factor for treatment outcome. Hypoxia increases the expression of carbonic anhydrase IX (CAIX), an enzyme that is predominantly found on tumor cells and is involved in maintaining the cellular pH balance. Many clinical studies investigated the prognostic value of CAIX expression, but most have been inconclusive, partly due to small numbers of patients included. The present meta-analysis was therefore performed utilizing the results of all clinical studies to determine the prognostic value of CAIX expression in solid tumors. Renal cell carcinoma was excluded from this meta-analysis due to an alternative mechanism of upregulation. 958 papers were identified from a literature search performed in PubMed and Embase. These papers were independently evaluated by two reviewers and 147 studies were included in the analysis. The meta-analysis revealed strong significant associations between CAIX expression and all endpoints: overall survival [hazard ratio (HR) = 1.76, 95% confidence interval (95%CI) 1.58–1.98], disease-free survival (HR = 1.87, 95%CI 1.62–2.16), locoregional control (HR = 1.54, 95%CI 1.22–1.93), disease-specific survival (HR = 1.78, 95%CI 1.41–2.25), metastasis-free survival (HR = 1.82, 95%CI 1.33–2.50), and progression-free survival (HR = 1.58, 95%CI 1.27–1.96). Subgroup analyses revealed similar associations in the majority of tumor sites and types. In conclusion, these results show that patients having tumors with high CAIX expression have higher risk of locoregional failure, disease progression, and higher risk to develop metastases, independent of tumor type or site. The results of this meta-analysis further support the development of a clinical test to determine patient prognosis based on CAIX expression and may have important implications for the development of new treatment strategies.
    Article · Mar 2016 · Frontiers in Oncology
  • Simon J. A. van Kuijk · Ala Yaromina · Ruud Houben · [...] · Ludwig J. Dubois
    File available · Data · Mar 2016
  • Simon J. A. van Kuijk · Ala Yaromina · Ruud Houben · [...] · Ludwig J. Dubois
    File available · Data · Mar 2016
  • Simon J. A. van Kuijk · Ala Yaromina · Ruud Houben · [...] · Ludwig J. Dubois
    File available · Data · Mar 2016
  • Simon J. A. van Kuijk · Ala Yaromina · Ruud Houben · [...] · Ludwig J. Dubois
    File available · Data · Mar 2016
  • Simon J. A. van Kuijk · Ala Yaromina · Ruud Houben · [...] · Ludwig J. Dubois
    File available · Data · Mar 2016
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    [Show abstract] [Hide abstract] ABSTRACT: Objectives: The aim of this study was to assess the effect of early weight loss before the onset of radiation esophagitis on overall survival (OS) in patients with non-small cell lung cancer treated with concurrent chemoradiotherapy. Methods: Characteristics (e.g., patient weight, radiation esophagitis score, sex, World Health Organization performance status, chemotherapy dose, nodal status, and gross tumor volume) of 151 patients who received concurrent chemoradiotherapy (in 2006-2013) were retrospectively correlated with OS. Early weight loss was defined as weight loss of more than 5% between the start and third week of radiotherapy in patients whose weight was stable before treatment initiation. Results: In 17% of the patients early weight loss was observed. Median OS (95% confidence interval [CI]) was significantly shorter in the early weight loss group (OS = 13.0 months, 95% CI: 2.0-24.0) versus in the non-early weight loss group (OS = 23.0 months, 95% CI: 14.7-31.3) (hazard ratio [HR] = 1.8, 95% CI: 1.12-2.96, p = 0.017). On multivariate analysis sex (HR = 2.1, 95% CI: 1.33-3.29, p = 0.001), World Health Organization performance status (HR = 1.9, 95% CI: 1.20-2.97, p = 0.006), nodal status (HR = 2.9, 95% CI: 1.38-6.01, p = 0.005), and early weight loss (HR = 1.9, 95% CI: 1.10-3.19, p = 0.022) were associated with OS. Conclusions: Early weight loss in patients with non-small cell lung cancer was found to be associated with worse prognosis. These data warrant further investigation into the efficacy of tailored intervention to prevent early weight loss.
    Full-text available · Article · Feb 2016 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
  • [Show abstract] [Hide abstract] ABSTRACT: Background and purpose: The aim was to investigate whether the use of metformin during concurrent chemoradiotherapy (cCRT) for locally advanced non-small cell lung cancer (NSCLC) improved treatment outcome. Material and methods: A total of 682 patients were included in this retrospective cohort study (59 metformin users, 623 control patients). All received cCRT in one of three participating radiation oncology departments in the Netherlands between January 2008 and January 2013. Primary endpoint was locoregional recurrence free survival (LRFS), secondary endpoints were overall survival (OS), progression-free survival (PFS) and distant metastasis free survival (DMFS). Results: No significant differences in LRFS or OS were found. Metformin use was associated with an improved DMFS (74% versus 53% at 2years; p=0.01) and PFS (58% versus 37% at 2years and a median PFS of 41months versus 15months; p=0.01). In a multivariate cox-regression analysis, the use of metformin was a statistically significant independent variable for DMFS and PFS (p=0.02 and 0.03). Conclusions: Metformin use during cCRT is associated with an improved DMFS and PFS for locally advanced NSCLC patients, suggesting that metformin may be a valuable treatment addition in these patients. Evidently, our results merit to be verified in a prospective trial.
    Article · Feb 2016 · Radiotherapy and Oncology
  • [Show abstract] [Hide abstract] ABSTRACT: Objectives When evaluating anti-tumor treatment response by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) it is necessary to assure its validity and reproducibility. This has not been well addressed in lung tumors. Therefore we have evaluated the inter-reader reproducibility of response classification by DCE-MRI in patients with non-small cell lung cancer (NSCLC) treated with bevacizumab and erlotinib enrolled in a multicenter trial. Materials and methods: Twenty-one patients were scanned before and 3 weeks after start of treatment with DCE-MRI in a multicenter trial. The scans were evaluated by two independent readers. The primary lung tumor was used for response assessment. Responses were assessed in terms of relative changes in tumor mean trans endothelial transfer rate (Ktrans) and its heterogeneity in terms of the spatial standard deviation. Reproducibility was expressed by the inter-reader variability, intra-class correlation coefficient (ICC) and dichotomous response classification. Results: The inter-reader variability and ICC for the relative Ktrans were 5.8% and 0.930, respectively. For tumor heterogeneity the inter-reader variability and ICC were 0.017 and 0.656, respectively. For the two readers the response classification for relative Ktrans was concordant in 20 of 21 patients (k = 0.90, p < 0.0001) and for tumor heterogeneity in 19 of 21 patients (k = 0.80, p < 0.0001). Conclusions: Strong agreement was seen with regard to the inter-reader variability and reproducibility of response classification by the two readers of lung cancer DCE-MRI scans.
    Article · Dec 2015 · Lung Cancer
  • [Show abstract] [Hide abstract] ABSTRACT: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is an orphan disease and few data are available on its clinical characteristics. Therefore, we analysed LCNEC registered in the Netherlands Cancer Registry, and compared data with small cell lung carcinoma (SCLC), squamous cell carcinoma (SqCC) and adenocarcinoma (AdC).Histologically confirmed LCNEC (n=952), SCLC (n=11 844), SqCC (n=19 633) and AdC (n=24 253) cases were selected from the Netherlands Cancer Registry (2003-2012). Patient characteristics, metastasis at diagnosis (2006 or later), overall survival (OS) including multivariate Cox models and first-line treatment were compared for stage I-II, III and IV disease.The number of LCNEC cases increased from 56 patients in 2003 to 143 in 2012, accounting for 0.9% of all lung cancers. Stage IV LCNEC patients (n=383) commonly had metastasis in the liver (47%), bone (32%) and brain (23%), resembling SCLC. Median OS (95% CI) of stage I-II, III and IV LCNEC patients was 32.4 (22.0-42.9), 12.6 (10.3-15.0) and 4.0 (3.5-4.6) months, respectively. Multivariate-adjusted OS of LCNEC patients resembled that of SCLC patients, and was poorer than those of SqCC and AdC patients. However, frequency of surgical resection and adjuvant chemotherapy resembled SqCC and AdC more than SCLC.Diagnosis of LCNEC has increased in recent years. The metastatic pattern of LCNEC resembles SCLC as does the OS. However, early-stage treatment strategies seem more comparable to those of SqCC and AdC.
    Article · Nov 2015 · European Respiratory Journal
  • [Show abstract] [Hide abstract] ABSTRACT: Purpose The aim of this study was to investigate local blood flow changes in the mandibular bone compared to the os frontale after irradiation in various doses. Materials and methods This study used an animal experiment with 16 female Göttingen minipigs. Three groups of four animals were irradiated with equivalent doses of 25, 50 or 70 Gray on the mandible and os frontale and four animals served as control. Three months after irradiation laser Doppler flowmetry (LDF) was used to record local blood flow on the left mandible and in the irradiated area on the os frontale. At 6 months measurements were repeated. Descriptive and univariate analyses were conducted and p-values lower than 0.05 were considered statistically significant. Results Local blood flow measurements in the mandible were significantly higher compared to the os frontale. In the os frontale and mandible there was no significant change in the measurements with increasing irradiation dose. Conclusion We found a non-significant decrease in LDF values with an increase in radiation dose in the mandible and non-significant changes in the os frontale at 3 and 6 months. We consider this to represent the process of on-going fibrosis affecting the local blood flow in the mandible. © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
    Article · Oct 2015 · Journal of Cranio-Maxillofacial Surgery
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    [Show abstract] [Hide abstract] ABSTRACT: Background: Trials are vital in informing routine clinical care; however, current designs have major deficiencies. An overview of the various challenges that face modern clinical research and the methods that can be exploited to solve these challenges, in the context of personalised cancer treatment in the 21st century is provided. Aim: The purpose of this manuscript, without intending to be comprehensive, is to spark thought whilst presenting and discussing two important and complementary alternatives to traditional evidence-based medicine, specifically rapid learning health care and cohort multiple randomised controlled trial design. Rapid learning health care is an approach that proposes to extract and apply knowledge from routine clinical care data rather than exclusively depending on clinical trial evidence, (please watch the animation: http://youtu.be/ZDJFOxpwqEA ). The cohort multiple randomised controlled trial design is a pragmatic method which has been proposed to help overcome the weaknesses of conventional randomised trials, taking advantage of the standardised follow-up approaches more and more used in routine patient care. This approach is particularly useful when the new intervention is a priori attractive for the patient (i.e. proton therapy, patient decision aids or expensive medications), when the outcomes are easily collected, and when there is no need of a placebo arm. Discussion: Truly personalised cancer treatment is the goal in modern radiotherapy. However, personalised cancer treatment is also an immense challenge. The vast variety of both cancer patients and treatment options makes it extremely difficult to determine which decisions are optimal for the individual patient. Nevertheless, rapid learning health care and cohort multiple randomised controlled trial design are two approaches (among others) that can help meet this challenge.
    Full-text available · Article · Sep 2015 · Acta oncologica (Stockholm, Sweden)
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    [Show abstract] [Hide abstract] ABSTRACT: To analyse the prognostic impact on overall survival (OS) of single versus multiple organ metastases, organ affected, and local disease status in a population based stage IV non-small cell lung cancer (NSCLC) cohort. In this observational study, data were analysed of all histologically confirmed stage IV NSCLC patients diagnosed between 1 January 2006 and 31 December 2012 registered in the Netherlands Cancer Registry. Location of metastases before treatment was registered. Multivariable survival analyses [age, gender, histology, M-status, local disease status, number of involved organs, actual organ affected] were performed for all patients and for an (18)fluorodeoxyglucose-positron emission tomography ((18)FDG-PET)-staged subgroup. 11,094 patients were selected: 60% male, mean age 65years, 73% adenocarcinoma. Median OS for 1 (N=5676), 2 (N=3280), and ⩾3 (N=2138) metastatically affected organs was 6.7, 4.3, 2.8months, respectively (p<0.001). Hazard ratio (HR) for 2 versus 1 organ(s) was 1.33 (p<0.001), for ⩾3 versus 1 organ(s) 1.91 (p<0.001). Results were confirmed in the (18)FDG-PET-staged cohort (N=1517): patients with single organ versus 2 and ⩾3 organ metastases had higher OS (8.6, 5.7, 3.8months, HR 1.40 and 2.17, respectively, p<0.001). In single organ metastases, OS for low versus high TN-status was 8.5 versus 6.5months [HR 1.40 (p<0.001)]. (18)FDG-PET-staged single organ metastases patients with low TN-status had a superior OS than those with high TN-status (11.6 versus 8.2months, HR 1.62, p<0.001). Patients with single organ metastases stage IV NSCLC have a favourable prognosis, especially in combination with low TN status. They have to be regarded as a separate subgroup of stage IV disease. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text available · Article · Aug 2015 · European journal of cancer (Oxford, England: 1990)
  • Cary Oberije · Dirk De Ruysscher · Ruud Houben · [...] · Philippe Lambin
    File available · Data · Jul 2015
  • Cary Oberije · Dirk De Ruysscher · Ruud Houben · [...] · Philippe Lambin
    File available · Data · Jul 2015
  • Cary Oberije · Dirk De Ruysscher · Ruud Houben · [...] · Philippe Lambin
    File available · Data · Jul 2015