Ruud Houben

Maastricht University, Maestricht, Limburg, Netherlands

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Publications (78)299.11 Total impact


  • No preview · Article · Feb 2016
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    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.
    No preview · Article · Dec 2015
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    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.
    No preview · Article · Nov 2015 · European Respiratory Journal
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    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.
    No preview · Article · Oct 2015 · Journal of Cranio-Maxillofacial Surgery
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    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 · Article · Sep 2015 · Acta oncologica (Stockholm, Sweden)
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    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 · Article · Aug 2015 · European journal of cancer (Oxford, England: 1990)
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    ABSTRACT: Recent studies suggest that the use of metformin is associated with reduced cancer incidence and improved prognosis in patients with oesophageal cancer. We explored the relationship between the use of metformin and outcome (pathologic response rate, distant metastasis-free and overall survival) in our mono-institutional cohort of patients treated for oesophageal cancer. Between 2008 and 2014, a total of 196 patients with oesophageal cancer (ages ranged from 37 to 82 years) eligible for curative treatment entered the study. Patients were categorized as non-diabetic (n = 172), diabetic not taking metformin (n = 5) or diabetic taking metformin (n = 19). The majority of patients were treated with trimodality therapy (n = 189). Pathologic response was graded according to Mandard's tumour regression score at the time of surgery. Distant metastasis-free and overall survival were calculated using the Kaplan-Meier method with log rank comparisons performed to determine significance. The overall pathologic complete response rate for the study population was 26%. It was 25% for patients not using metformin and 39% for diabetics taking metformin (p = 0.260). The two-year overall survival rate for the whole group was 59%. Use of metformin was associated with a significantly better distant metastasis-free survival rate (p = 0.040) or overall survival rate (p = 0.012). Multivariate analysis using Cox regression found that metformin treatment significantly prolonged survival (p = 0.043). In our population-based study, the use of metformin was associated with an improved overall and distant metastasis-free survival rate in patients with oesophageal cancer. These data are complementary to one other clinical study and warrant further prospective study. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Jun 2015 · European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
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    ABSTRACT: Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability (www.predictcancer.org). The data set can be downloaded at https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048. Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.
    Full-text · Article · Apr 2015 · International journal of radiation oncology, biology, physics
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    ABSTRACT: To realize safe, high-quality treatment, employees should behave according to patient safety standards. Periodic measurement of safety behavior could provide management-relevant information to adjust the implementation of interventions and maximize improvement. Therefore, we constructed a factorial survey measuring safety awareness and intentions for behavior. Cross-sectional results of the factorial survey were compared with results from the Hospital Survey on Patient Safety Culture, distributed in MAASTRO radiotherapy in 2010 to 2011. Respondents were presented 20 scenarios about incidents, randomly varying on work pressure, person causing incident, whether patient level was reached, severity of harm, notification by patient, and management support. After each scenario, questions were asked about safety awareness and behavior. χ and multilevel regression analyses were used. Response rates were 64% (n = 54) for the culture survey and 62% (n = 52) for the factorial survey on intentions. The culture survey reflected positive opinions regarding nonpunitive response and incident reporting, in accordance with high scores (factorial survey) on safety awareness (9.0; scale, 1-10) and reporting intentions (8.7). Whether an incident reached the patient level predicted safety awareness and intentions for safety behavior (β = -1.3/-3.08) most strongly. Severity of harm showed minimal additional effects (β = -0.24/-0.42). The factorial survey presented practical information on safety awareness and intentions for behavior. Therefore, it created additional opportunities for improving safety interventions. Because behavior is expected to change before values, one could hypothesize that factorial surveys would be more sensitive to change than culture surveys. Longitudinal research should further study the surveys' sensitivity to measure changes.
    No preview · Article · Apr 2015 · Journal of Patient Safety
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    Full-text · Article · Apr 2015 · Annals of Oncology
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    ABSTRACT: Objectives: To simultaneously improve patient care processes and clinical research activities by starting a hypothesis-driven reorganisation trajectory mimicking the rigorous methodology of a prospective clinical trial. Methods: The design of this reorganisation trajectory was based on the model of a prospective trial. It consisted of 1) listing problems and analysing their potential causes, 2) defining interventions, 3) defining endpoints and 4) measuring the effect of the interventions (i.e. at baseline and after one and two years). The primary endpoint for patient care was the number of organisational root causes of incidents/ near incidents; for clinical research it was the number of patients in trials. There were several secondary endpoints. We analysed the data using two sample z-tests, chi square, a Mann Whitney U test and the one-way ANOVA with Bonferroni correction. Results: The number of organisational root causes was reduced by 27% (p<0.001). There was no effect on the percentage of patients included in trials. Conclusions: The reorganisational trajectory was successful for the primary endpoint of patient care and had no effect on clinical research. Some confounding events hampered our ability to draw strong conclusions. Nevertheless, the transparency of this approach can give medical professionals more confidence in moving forward with other organisational changes in the same way. Advances in knowledge: This paper is novel because managerial interventions were set up similarly to a prospective clinical trial. This study is the first of its kind in radiotherapy and this approach can contribute to discussions about the effectiveness of managerial interventions.
    Full-text · Article · Feb 2015 · British Journal of Radiology

  • No preview · Article · Dec 2014 · Radiotherapy and Oncology

  • No preview · Article · Dec 2014 · Radiotherapy and Oncology
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    ABSTRACT: Stereotactic ablative body radiotherapy (SABR) is a non-invasive treatment option for inoperable patients or patients with irresectable liver tumors. Outcome and toxicity were evaluated retrospectively in this single-institution patient cohort. Between 2010 and 2014, 39 lesions were irradiated in 33 consecutive patients (18 male, 15 female, median age of 68 years). All the lesions were liver metastases (n = 34) or primary hepatocellular carcinomas (n = 5). The patients had undergone four-dimensional respiration-correlated PET-CT for treatment simulation to capture tumor motion. We analyzed local control with a focus on CT-based response at three months, one year and two years after treatment, looking at overall survival and the progression pattern. All patients were treated with hypofractionated image-guided stereotactic radiotherapy. The equivalent dose in 2 Gy fractions varied from 62.5 Gy to 150 Gy, delivered in 3-10 fractions (median dose 93.8 Gy, alpha/beta = 10). The CT-based regression pattern three months after radiotherapy revealed partial regression in 72.7% of patients with a complete remission in 27.3% of the cases. The site of first progression was predominantly distant. One- and two-year overall survival rates were 85.4% and 68.8%, respectively. No toxicity of grade 2 or higher according to the NCI Common Terminology Criteria for Adverse Events v4.0 was observed. SABR is a safe and efficient treatment for selected inoperable patients or irresectable tumors of the liver. Future studies should combine SABR with systemic treatment acting in synergy with radiation, such as immunological interventions or hypoxic cell radiosensitizers to prevent distant relapse. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Full-text · Article · Nov 2014 · European Journal of Surgical Oncology
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    ABSTRACT: Purpose: Increased tumor metabolism and hypoxia are related to poor prognosis in solid tumors, including non-small cell lung cancer (NSCLC). PET imaging is a noninvasive technique that is frequently used to visualize and quantify tumor metabolism and hypoxia. The aim of this study was to perform an extensive comparison of tumor metabolism using 2[(18)F]fluoro-2-deoxy-d-glucose (FDG)-PET and hypoxia using HX4-PET imaging. Experimental design: FDG- and HX4-PET/CT images of 25 patients with NSCLC were coregistered. At a global tumor level, HX4 and FDG parameters were extracted from the gross tumor volume (GTV). The HX4 high-fraction (HX4-HF) and HX4 high-volume (HX4-HV) were defined using a tumor-to-blood ratio > 1.4. For FDG high-fraction (FDG-HF) and FDG high-volume (FDG-HV), a standardized uptake value (SUV) > 50% of SUVmax was used. We evaluated the spatial correlation between HX4 and FDG uptake within the tumor, to quantify the (mis)match between volumes with a high FDG and high HX4 uptake. Results: At a tumor level, significant correlations were observed between FDG and HX4 parameters. For the primary GTV, the HX4-HF was three times smaller compared with the FDG-HF. In 53% of the primary lesions, less than 1 cm(3) of the HX4-HV was outside the FDG-HV; for 37%, this volume was 1.9 to 12 cm(3). Remarkably, a distinct uptake pattern was observed in 11%, with large hypoxic volumes localized outside the FDG-HV. Conclusion: Hypoxic tumor volumes are smaller than metabolic active volumes. Approximately half of the lesions showed a good spatial correlation between the PET tracers. In the other cases, a (partial) mismatch was observed. The addition of HX4-PET imaging has the potential to individualize patient treatment.
    Full-text · Article · Oct 2014 · Clinical Cancer Research
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    ABSTRACT: PURPOSE: The importance of a safety culture to maximize safety is no longer questioned. However, achieving sustainable culture improvements are less evident. Evidence is growing for a multifaceted approach, where multiple safety interventions are combined. Lean management is such an integral approach to improve safety, quality and efficiency and therefore, could be expected to improve the safety culture. This paper presents the effects of lean management activities on the patient safety culture in a radiotherapy institute. METHODS: Patient safety culture was evaluated over a three year period using triangulation of methodologies. Two surveys were distributed three times, workshops were performed twice, data from an incident reporting system (IRS) was monitored and results were explored using structured interviews with professionals. Averages, chi-square, logistical and multi-level regression were used for analysis. RESULTS: The workshops showed no changes in safety culture, whereas the surveys showed improvements on six out of twelve dimensions of safety climate. The intention to report incidents not reaching patient-level decreased in accordance with the decreasing number of reports in the IRS. However, the intention to take action in order to prevent future incidents improved (factorial survey presented β: 1.19 with p: 0.01). CONCLUSIONS: Due to increased problem solving and improvements in equipment, the number of incidents decreased. Although the intention to report incidents not reaching patient-level decreased, employees experienced sustained safety awareness and an increased intention to structurally improve. The patient safety culture improved due to the lean activities combined with an organizational restructure, and actual patient safety outcomes might have improved as well.
    No preview · Article · Sep 2014 · European journal of oncology nursing: the official journal of European Oncology Nursing Society
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    ABSTRACT: Purpose To realize safe radiotherapy treatment, processes must be stabilized. Standard operating procedures (SOP's) were expected to stabilize the treatment process and perceived task importance would increase sustainability in compliance. This paper presents the effects on compliance to safety related tasks of a process redesign based on lean principles. Method Compliance to patient safety tasks was measured by video recording of actual radiation treatment, before (T0), directly after (T1) and 1.5 years after (T2) a process redesign. Additionally, technologists were surveyed on perceived task importance and reported incidents were collected for three half-year periods between 2007 and 2009. Results Compliance to four out of eleven tasks increased at T1, of which improvements on three sustained (T2). Perceived importance of tasks strongly correlated (0.82) to compliance rates at T2. The two tasks, perceived as least important, presented low base-line compliance, improved (T1), but relapsed at T2. The reported near misses (patient-level not reached) on accelerators increased (P < 0.001) from 144 (2007) to 535 (2009), while the reported misses (patient-level reached) remained constant. Conclusions Compliance to specific tasks increased after introducing SOP's and improvements sustained after 1.5 years, indicating increased stability. Perceived importance of tasks correlated positively to compliance and sustainability. Raising the perception of task importance is thus crucial to increase compliance. The redesign resulted in increased willingness to report incidents, creating opportunities for patient safety improvement in radiotherapy treatment.
    No preview · Article · Sep 2014
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    ABSTRACT: Objective: The aim of this review is to investigate the effect of timing of the reconstruction and radiotherapy, with respect to complication rate and cosmetic outcome, with a special focus on the timing of the placement of the definite implant. Methods: PubMed was searched for publications between January 2000 and December 2012. Of 37 eligible studies, timing of reconstruction, type, and incidence of complications were recorded. First, we calculated the weighted mean including confidence intervals for complications and cosmetic outcome overall, and for the following subgroups: (1) Autologous reconstruction after radiotherapy; (2) Definite implant reconstruction after radiotherapy; (3) Autologous reconstruction before radiotherapy; (4) Definite implant reconstruction before radiotherapy. A second analysis was performed using only studies that directly compared group 1 versus 3 and 2 versus 4. Results: A large variation in complication rates (8.7-70.0%) and in acceptable cosmetic outcome (41.4-93.3%) was reported. The first analysis showed more complications and a higher revision rate if an implant reconstruction was performed after radiotherapy; for autologous reconstruction fibrosis occurred more often if reconstruction was applied first. The second analysis showed no significant differences in total complication rate. Only implant failure occurred more often if applied after radiotherapy (odds ratio (OR) 3.03 [1.59-5.77]). No differences were found in both patient and physician satisfaction. Conclusions: A definite implant reconstruction placed before radiotherapy limits the rate of complications. For autologous reconstruction, less fibrosis is seen if reconstruction is performed after radiotherapy, but timing had no significant impact on total complication rate.
    No preview · Article · Aug 2014 · European journal of cancer (Oxford, England: 1990)
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    ABSTRACT: Purpose: To realize safe radiotherapy treatment, processes must be stabilized. Standard operating procedures (SOP's) were expected to stabilize the treatment process and perceived task importance would increase sustainability in compliance. This paper presents the effects on compliance to safety related tasks of a process redesign based on lean principles. Method: Compliance to patient safety tasks was measured by video recording of actual radiation treatment, before (T0), directly after (T1) and 1.5 years after (T2) a process redesign. Additionally, technologists were surveyed on perceived task importance and reported incidents were collected for three half-year periods between 2007 and 2009. Results: Compliance to four out of eleven tasks increased at T1, of which improvements on three sustained (T2). Perceived importance of tasks strongly correlated (0.82) to compliance rates at T2. The two tasks, perceived as least important, presented low base-line compliance, improved (T1), but relapsed at T2. The reported near misses (patient-level not reached) on accelerators increased (P < 0.001) from 144 (2007) to 535 (2009), while the reported misses (patient-level reached) remained constant. Conclusions: Compliance to specific tasks increased after introducing SOP's and improvements sustained after 1.5 years, indicating increased stability. Perceived importance of tasks correlated positively to compliance and sustainability. Raising the perception of task importance is thus crucial to increase compliance. The redesign resulted in increased willingness to report incidents, creating opportunities for patient safety improvement in radiotherapy treatment.
    No preview · Article · Jun 2014 · European journal of oncology nursing: the official journal of European Oncology Nursing Society
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    ABSTRACT: In this open-label phase I study, the maximum-tolerated dose of cetuximab with concurrent chemoradiotherapy (C-CRT) in stage III non-small-cell lung cancer together with individualized, isotoxic accelerated radiotherapy (RT) was investigated. Patients with stage III non-small-cell lung cancer, World Health Organization performance status 0-1, forced expiratory volume in 1 second more than 50%, carbon monoxide diffusing capacity more than 50%, weight loss less than 10%, and no severe comorbidity were enrolled. Patients without progression after one to two cycles of gemcitabine-carboplatin were included and treated with cetuximab 400 mg/kg d7 and 250 mg/kg weekly together with RT and cisplatin (50 mg/m d1, 8; 40 mg/m d22)-vinorelbine for 5 weeks. Vinorelbine was escalated in three steps; (1) 10 mg/m d1, 8 and 8 mg/m d22, 29; (2) 20 mg/m d1, 8 and 8 mg/m d22, 29; (3) 20 mg/m d1, 8; 15 mg/m d22, 29. An individualized prescribed RT dose based on normal tissue dose constraints was applied (e.g., mean lung dose 19 Gy). The primary endpoint was the maximum-tolerated dose 3 months after the end of C-CRT; secondary endpoints were toxicity and metabolic response as assessed by positron emission tomography. Between September 2007 and October 2010, 25 patients (12 men, 13 women, mean age 59 years) were included. The mean RT dose was 62 ± 6.6 Gy. The vinorelbine dose could be escalated to dose level 3. Twelve of 25 patients experienced greater than or equal to grade 3 toxicity (esophagitis 3, rash 1, diarrhea 1, cough 1, dyspnea 1, vomiting 1, and pulmonary embolism 1). No dose-limiting toxicities were observed. One patient with a complete pathological response in dose level 3 developed a fatal hemoptysis 4 months after RT. Metabolic remissions were observed in 19 of 22 patients. C-CRT with cetuximab and cisplatin-vinorelbine is safe to deliver at full dose. The recommended phase II dose is therefore cetuximab 400 mg/m d7 and 250 mg/m weekly, cisplatin 50 mg/m d1, 8; 40 mg/m d22 and vinorelbine 20 mg/m d1, 8; 15 mg/m d22, 29 for 5 weeks together with RT.
    Full-text · Article · May 2014 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer

Publication Stats

1k Citations
299.11 Total Impact Points

Institutions

  • 2001-2015
    • Maastricht University
      • • GROW School for Oncology & Developmental Biology
      • • Department of Clinical Psychological Science
      Maestricht, Limburg, Netherlands
  • 2007-2014
    • Maastricht Universitair Medisch Centrum
      • Central Diagnostic Laboratory
      Maestricht, Limburg, Netherlands
  • 2007-2011
    • Maastro Clinic
      Maestricht, Limburg, Netherlands