Kristiaan Nackaerts

Erasmus Universiteit Rotterdam, Rotterdam, South Holland, Netherlands

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Publications (34)239.57 Total impact

  • American Journal of Respiratory and Critical Care Medicine 08/2014; 190(4):e12-3. · 11.04 Impact Factor
  • Kevin Lamote, Kristiaan Nackaerts, Jan P van Meerbeeck
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    ABSTRACT: Past and present asbestos use will reflect in increasing numbers of mesothelioma cases in the next decades, diagnosed at a late stage and with a dismal prognosis. This stresses the need for early detection tools which could improve patient's survival. Recently, breath analysis as a non-invasive and fast diagnostic tool has found its way into biomedical research. High-throughput breathomics uses spectrometric, chromatographic and sensor techniques to diagnose asbestos-related pulmonary diseases based upon volatile organic compounds (VOCs) in breath. This article reviews the state-of-the-art available breath analyzing techniques and provides the insight in the current use of VOCs as early diagnostic or prognostic biomarkers of mesothelioma in order to stimulate further research in this field.
    Cancer Epidemiology Biomarkers &amp Prevention 04/2014; · 4.56 Impact Factor
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    ABSTRACT: To evaluate the diagnostic accuracy of dynamic contrast-enhanced (DCE) magnetic resonance (MR) and diffusion-weighted imaging (DWI) sequences for defining benignity or malignancy of solitary pulmonary lesions (SPL). First, 54 consecutive patients with SPL, clinically staged (CT and PET or integrated PET-CT) as N0M0, were included in this prospective study. An additional 3-Tesla MR examination including DCE and DWI was performed 1 day before the surgical procedure. Histopathology of the surgical specimen served as the standard of reference. Subsequently, this functional method of SPL characterisation was validated with a second cohort of 54 patients. In the feasibility group, 11 benign and 43 malignant SPL were included. Using the combination of conventional MR sequences with visual interpretation of DCE-MR curves resulted in a sensitivity, specificity and accuracy of 100 %, 55 % and 91 %, respectively. These results can be improved by DWI (with a cut-off value of 1.52 × 10(-3) mm(2)/s for ADChigh) leading to a sensitivity, specificity and accuracy of 98 %, 82 % and 94 %, respectively. In the validation group these results were confirmed. Visual DCE-MR-based curve interpretation can be used for initial differentiation of benign from malignant SPL, while additional quantitative DWI-based interpretation can further improve the specificity. • Magnetic resonance imaging is increasingly being used to help differentiate lung lesions. • Solitary pulmonary lesions (SPL) are accurately characterised by combining DCE-MRI and DWI. • Visual DCE-MRI assessment facilitates the diagnostic throughput in patients with SPL. • DWI provides additional information in inconclusive DCE-MRI (type B pattern).
    European Radiology 10/2013; · 4.34 Impact Factor
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    ABSTRACT: Evaluation of: National Lung Screening Trial Research Team, Church TR, Black WC, Aberle DR et al. Results of initial low-dose computed tomographic screening for lung cancer. N. Engl. J. Med. 368, 1980-1991 (2013). In 2011, the US NLST trial demonstrated that mortality from lung cancer can be reduced by using low-dose computed tomography (LDCT) screening rather than chest x-ray (CXR) screening. This paper from the US NLST research team focuses on the results of the initial round of LDCT for lung cancer. A total of 53,439 participants were included and randomly assigned to LDCT screening (n = 26,715) or CXR screening (n = 26,724). In total, 27.3% of the participants in the LDCT group and 9.2% in the CXR group had a positive screening result. As a result, 3.8% (LDCT group) and 5.7% (CXR group) of these subjects were diagnosed with lung cancer. The sensitivity (93.8%) and specificity (73.4%) for lung cancer were higher for LDCT compared with CXR screening; 73.5 and 91.3%, respectively.
    Journal of comparative effectiveness research. 09/2013; 2(5):433-6.
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    ABSTRACT: OBJECTIVE. The purpose of this article is to retrospectively evaluate the technical and clinical outcomes of large-bore nitinol stents for treating malignant superior vena cava syndrome. In addition, we analyzed factors potentially influencing the outcome. MATERIALS AND METHODS. Over a 7-year period, 78 consecutive patients presented with superior vena cava syndrome related to primary lung tumor (n = 62) or malignant lymphadenopathies (n = 16). The factors analyzed were Kishi score at admission, tumor type, and need for an additional balloon-expandable stent. RESULTS. Technical success was obtained in all but one patient (99%), who presented with a stent migration immediately after insertion. In 17 patients (22%), an additional balloon-expandable stent was needed for complete expansion of the nitinol stent. For patients with symptomatic malignant lymphadenopathies or primary lung tumor, overall survival rates were 50% (n = 8) and 54% (n = 34), respectively, at 6 months and 19% (n = 3) and 34% (n = 21), respectively, at 12 months (p = 0.376). There was no difference in survival as a function of the Kishi score (p = 0.80) or of the placement of an additional balloon-expandable stent (p = 0.35). Finally, reocclusion events were noted in patients both with (n = 1) and without (n = 7) a balloon-expandable stent. CONCLUSION. Large-bore nitinol stents are highly effective for malignant superior vena cava syndrome. The survival rates of patients with caval vein stenosis due to either the primary tumor or secondary enlarged adenopathies were equal. An additional balloon-expandable stent was required in 22% of cases owing to incomplete expansion of the nitinol stent but was not associated with higher thrombosis rate.
    American Journal of Roentgenology 09/2013; 201(3):667-74. · 2.90 Impact Factor
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    ABSTRACT: Several medical associations recommended lung cancer screening by low-dose computer tomography (LDCT) scanning for high-risk groups. Counselling of the candidates on the potential harms and benefits and their lung cancer risk is a prerequisite for screening.In the NELSON trial, screenings are considered positive for (part) solid lung nodules with a volume >500 mm(3) and for (part) solid or non-solid nodules with a volume-doubling time <400days. For this study, the performance of the NELSON strategy in three screening rounds was evaluated and risk calculations were made for a follow-up period of 5.5 years.458 (6%) of the 7.582 screened participants had a positive screen result and 200 (2.6%) were diagnosed with lung cancer. The positive screenings had a predictive value of 40.6% and only 1.2% of all scan results were false-positive. In a period of 5.5 years, the risk of screen-detected lung cancer strongly depends on the result of the first scan: 1.0% after a negative baseline result, 5.7% after an indeterminate baseline and 48.3% after a positive baseline.The screening strategy yielded few positive and false-positive scans with a reasonable positive predictive value. The 5.5-year lung cancer risk calculations aid clinicians in counselling candidates for lung cancer screening with LDCT.
    European Respiratory Journal 07/2013; · 6.36 Impact Factor
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    ABSTRACT: RATIONALE: The NELSON trial is with 15,822 participants the largest European lung cancer computer tomography screening trial. A volumetry-based screening strategy, stringent criteria for a positive screening and an increasing length of the screening interval are particular features of the NELSON trial. OBJECTIVES: To determine the effect of stringent referral criteria and increasing screening interval on the characteristics of the screen-detected lung cancers, and to compare this across screening rounds, between genders and with other screening trials METHODS: All NELSON participants with screen-detected lung cancer in the first three rounds were included. Lung cancer stage at diagnosis, histological subtype, and tumor localization were compared between the screening rounds, the genders and with other screening trials. MEASUREMENTS AND MAIN RESULTS: In the first three screening rounds, 200 participants were diagnosed with 209 lung cancers. 70.8% of the lung cancers were diagnosed at stage I, 8.1% at stage IIIB-IV and 51.2% were adenocarcinomas. There was no significant difference in cancer stage, histology or tumor localization across the screening rounds. Women were diagnosed at a significantly more favorable cancer stage than men. Compared to other trials, the screen-detected lung cancers of the NELSON trial were relatively more often diagnosed at stage I and less often at stage IIIB-IV. CONCLUSIONS: Despite stringent criteria for a positive screening, an increasing length of the screening interval and few female participants, the screening strategy of the NELSON trial resulted in a favorable cancer stage distribution at diagnosis, which is a prerequisite for the effectiveness of our screening strategy.
    American Journal of Respiratory and Critical Care Medicine 01/2013; · 11.04 Impact Factor
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    ABSTRACT: Several randomized trials on maintenance therapy (MT) for metastatic non-small-cell lung cancer (NSCLC) have demonstrated benefit in progression-free survival. More recently, a study with pemetrexed and one with erlotinib also showed significant gains in overall survival (OS). Yet, in this palliative treatment setting, the benefit has to be weighed against the potential burden of treatment, and thus patients' preferences should be taken into account. In the absence of data on this topic, we undertook a pilot survey with 10 questions covering the overall patient attitude toward MT, the benefit expected by patients, and the acceptance of side effects or modes of administration. Included patients had stage IV NSCLC and were planned to start first-line platinum-based doublet chemotherapy. The questionnaire was submitted at the start of and after two and four cycles of chemotherapy. Thirty patients were included. Overall, patients had a positive attitude toward MT. At baseline, it was considered worthwhile by 83%, 67%, and 43% of patients for an OS benefit of 6, 3, or 1 month, respectively, with some decrease over time. Effects on symptom control were crucial for about 90% of the patients. There was a slight preference for oral versus intravenous administration. Side effects were accepted by most patients as long as they were mild to moderate. Our pilot survey showed that metastatic NSCLC patients in general are in favor of MT. They expect either an OS benefit of at least several months, or better symptom control, in balance with mild-to-moderate side effects.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2012; 7(8):1291-5. · 4.55 Impact Factor
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    ABSTRACT: To investigate the use of diffusion-weighted (DW) imaging for differentiating benign lesions from malignant pleural disease (MPD) and to retrospectively assess dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging acquisitions to find out whether combining these measurements with DW imaging could improve the diagnostic value of DW imaging. This study was approved by the local ethics committee, and all patients provided written informed consent. Thirty-one consecutive patients with pleural abnormalities suspicious for MPD underwent whole-body positron emission tomography (PET)/computed tomography (CT) and thorax MR examinations. Diagnostic thoracoscopy with histopathologic analysis of pleural biopsies served as the reference standard. First-line evaluation of each suspicious lesion was performed by using the apparent diffusion coefficient (ADC) calculated from the DW image, and the optimal cutoff value was found by using receiver operating characteristic curve analysis. Afterward, DCE MR imaging data were used to improve the diagnosis in the range of ADCs where DW imaging results were equivocal. Sensitivity, specificity, and accuracy of PET/CT for diagnosis of MPD were 100%, 35.3%, and 64.5%. The optimal ADC threshold to differentiate benign lesions from MPD with DW MR imaging was 1.52 × 10(-3) mm(2)/sec, with sensitivity, specificity, and accuracy of 71.4%, 100%, and 87.1%, respectively. This result could be improved to 92.8%, 94.1%, and 93.5%, respectively, when DCE MR imaging data were included in those cases where ADC was between 1.52 and 2.00 × 10(-3) mm(2)/sec. A total of 20 patients had disease diagnosed correctly, nine had disease diagnosed incorrectly, and two cases were undetermined with PET/CT. DW imaging helped stage disease correctly in 27 patients and incorrectly in four. The undetermined cases at PET/CT were correctly diagnosed at MR imaging. DW imaging is a promising tool for differentiating MPD from benign lesions, with high accuracy, and supplementation with DCE MR imaging seems to further improve sensitivity.
    Radiology 04/2012; 263(3):884-92. · 6.34 Impact Factor
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    ABSTRACT: To assess the complication rate in participants of the screen arm of the NELSON lung cancer screening trial who underwent surgical resection and to investigate, based on a literature review, whether the complication rate, length of hospital stay, re-thoracotomy and mortality rates after a surgical procedure were different from those of the non-screening series, taking co-morbidity into account. Between April 2004 and December 2008, 198 subjects underwent thoracic surgery. Co-morbid conditions were retrieved from the medical records. Postoperative complications were classified as minor and major. In total, 182 thoracotomies, 5 thoracotomies after video-assisted thoracoscopic surgery (VATS) and 11 VATS procedures were performed. In these patients, 36% had chronic obstructive lung disease, 16% coronary artery disease, 14% diabetes mellitus and 11% peripheral vascular disease. Following thoracotomy, 47% (88/187) had ≥1 minor (7-57% in literature) and 10% (18/187) ≥1 major complication (2-26% in literature); following VATS, 38% (6/16) had ≥1 minor complication, but no major complications. Seventeen per cent (3/18) of major complications and 21% (20/96) of minor complications were seen in subjects operated for benign disease. The re-thoracotomy rate was 3% and there was no 30-day mortality after thoracotomy or VATS (0-8.3% in literature). The mortality rate of 0% after surgical procedures is low when compared with the non-screening series (0-8.3%); the rate of complications (53%) is within range when compared with the non-screening series (8.5-58%). In conclusion, mortality rates after surgical procedures are lower in the NELSON lung cancer screening trial than those in the non-screening series. The rate of complications is within the same range as in the non-screening series. Trial registration number: ISR CTN 63545820.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 04/2012; 42(3):420-9. · 2.40 Impact Factor
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    ABSTRACT: Mesothelin is currently considered the best available serum biomarker of malignant pleural mesothelioma. To examine the diagnostic accuracy and use of serum mesothelin in early diagnosis, we performed an individual patient data (IPD) meta-analysis. The literature search identified 16 diagnostic studies of serum mesothelin, measured with the Mesomark enzyme-linked immunosorbent assay. IPD of 4,491 individuals were collected, including several control groups and 1,026 patients with malignant pleural mesothelioma. Mesothelin levels were standardized for between-study differences and age, after which the diagnostic accuracy and the factors affecting it were examined with receiver operating characteristic (ROC) regression analysis. At a common diagnostic threshold of 2.00 nmol/L, the sensitivities and specificities of mesothelin in the different studies ranged widely from 19% to 68% and 88% to 100%, respectively. This heterogeneity can be explained by differences in study population, because type of control group, mesothelioma stage, and histologic subtype significantly affected the diagnostic accuracy. The use of mesothelin in early diagnosis was evaluated by differentiating 217 patients with stage I or II epithelioid and biphasic mesothelioma from 1,612 symptomatic or high-risk controls. The resulting area under the ROC curve was 0.77 (95% CI, 0.73 to 0.81). At 95% specificity, mesothelin displayed a sensitivity of 32% (95% CI, 26% to 40%). In patients suspected of having mesothelioma, a positive blood test for mesothelin at a high-specificity threshold is a strong incentive to urge further diagnostic steps. However, the poor sensitivity of mesothelin clearly limits its added value to early diagnosis and emphasizes the need for further biomarker research.
    Journal of Clinical Oncology 03/2012; 30(13):1541-9. · 18.04 Impact Factor
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    ABSTRACT: Up to 50% of the participants in CT scan lung cancer screening trials have at least one pulmonary nodule. To date, the role of conventional bronchoscopy in the workup of suspicious screen-detected pulmonary nodules is unknown. If a bronchoscopic evaluation could be eliminated, the cost-effectiveness of a screening program could be enhanced and the potential harms of bronchoscopy avoided. All consecutive participants with a positive result on a CT scan lung cancer screening between April 2004 and December 2008 were enrolled. The diagnostic sensitivity and negative predictive value were calculated at the level of the suspicious nodules. In 95% of the nodules, the gold standard for the outcome of the bronchoscopy was based on surgical resection specimens. A total of 318 suspicious lesions were evaluated by bronchoscopy in 308 participants. The mean ± SD diameter of the nodules was 14.6 ± 8.7 mm, whereas only 2.8% of nodules were > 30 mm in diameter. The sensitivity of bronchoscopy was 13.5% (95% CI, 9.0%-19.6%); the specificity, 100%; the positive predictive value, 100%; and the negative predictive value, 47.6% (95% CI, 41.8%-53.5%). Of all cancers detected, 1% were detected by bronchoscopy only and were retrospectively invisible on both low-dose CT scan and CT scan with IV contrast. Conventional white-light bronchoscopy should not be routinely recommended for patients with positive test results in a lung cancer screening program.
    Chest 02/2012; 142(2):377-84. · 5.85 Impact Factor
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    ABSTRACT: In patients with lung cancer, bone is one of the most frequent sites of distant spread, with approximately 30% of patients developing skeletal metastases. About half of these patients will experience a skeletal-related event, the occurrence of which not only affects quality of life, but is also associated with poor prognosis. Bisphosphonates are currently the mainstay for treating bone metastases in patients with lung cancer, with proven beneficial effects on prevention and delay of skeletal complications. Their role in preventing the development of skeletal metastases, their anti-tumoral properties and their effect on survival remain to be elucidated. Other bone-targeted therapies are being investigated in phase II and III clinical trials and might expand the therapeutic arsenal in the near future.
    Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer 01/2012; 192:93-108.
  • Kristiaan Nackaerts, Johan Vansteenkiste, Philippe Nafteux
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2011; 6(12):2143-4; author reply 2144-5. · 4.55 Impact Factor
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    ABSTRACT: In computed tomography lung cancer screening programs, up to 30% of all resections are futile. To investigate whether a preoperative positron emission tomography (PET) after a conclusive or inconclusive nonsurgical workup will reduce the resection rate for benign disease in test-positive participants of a lung cancer screening program. ¹⁸F-Fluorodeoxyglucose-PET scans were made in 220 test positives. Nodules were classified as positive, indeterminate, or negative based on visual comparison with background activity. Gold standard for a positive PET was the presence of cancer in the resection specimen or the detection of cancer during more than 2 years follow-up. Sensitivity, specificity, positive predictive value, and negative predictive value (NPV) were calculated at participant level and 95% confidence intervals (CIs) constructed. The sensitivity of PET to detect cancer was 84.2% (95% CI: 77.6-90.7%), the specificity 75.2% (95% CI: 67.1-83.3), the positive predictive value 78.9% (95% CI: 71.8-86.0), and the NPV 81.2% (95% CI: 73.6-88.8). The resection rate for benign disease was 23%, but 26% of them had a diagnosis with clinical consequences. A preoperative PET after an inconclusive nonsurgical workup reduced the resection rate for benign lesions by 11 to 15%, at the expense of missing 12 to 18% lung cancer cases. A preoperative PET after a conclusive nonsurgical workup reduced the resection rate by 78% at the expense of missing 3% lung cancer cases. A preoperative PET scan in participants with an inconclusive nonsurgical workup is not recommended because of the very low NPV, but after a conclusive nonsurgical workup, the resection rate for benign disease can be decreased by 72%.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2011; 6(10):1704-12. · 4.55 Impact Factor
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    ABSTRACT: Soluble mesothelin (SM), megakaryocyte potentiating factor (MPF), and osteopontin (OPN) are blood biomarkers of mesothelioma. This study evaluates their use as markers of response to therapy and outcome. Sixty-two patients with malignant pleural mesothelioma were included in an observational multicenter study. Blood samples and matched computed tomography scans were collected at diagnosis and, when possible, during and after therapy. For each patient, the best overall radiological response was compared with the changes in serum SM, MPF, and plasma OPN levels across corresponding time points. In five patients, blood sampling was done shortly before and after extrapleural pneumonectomy. SM and MPF levels markedly decreased after surgery, whereas OPN levels showed a median increase. Fifty-seven patients were surveilled during (and after) chemotherapy, of whom 27 (47%) had stable disease, 14 (25%) partial response, and 16 (28%) progressive disease. In patients with stable disease, SM and MPF levels did not change significantly across the corresponding time points, whereas OPN levels significantly decreased. In those with partial response, SM and MPF levels significantly decreased, whereas OPN levels showed no significant change. In patients with progressive disease, all three biomarker levels significantly increased. Patient responses correlated with a 15% change in all three biomarkers, although SM and MPF appeared more accurate than OPN. Low baseline OPN levels were independently associated with favorable progression-free survival and overall survival. Neither SM nor MPF showed prognostic value. SM and MPF levels were more closely associated with disease course than OPN and might prove useful in monitoring patient response in mesothelioma. Baseline OPN levels were an independent negative predictor of survival. These promising results require further validation.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2011; 6(11):1930-7. · 4.55 Impact Factor
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    ABSTRACT: Soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF) are serum biomarkers of mesothelioma. This study examined the effect of clinical covariates on biomarkers levels and their diagnostic and prognostic value. Five hundred ninety-four participants were enrolled in a multicenter study, including 106 patients with mesothelioma and 488 control subjects. Multiple linear regression analyses were used to identify which covariates were independently associated with SM and MPF levels. The effect of these covariates on the diagnostic accuracy was evaluated with receiver operating characteristics curve analysis. In patients with mesothelioma, survival analysis was performed with Cox regression. SM and MPF levels were independently associated with age, glomerular filtration rate (GFR), and BMI in control subjects and with GFR and tumor stage in patients with mesothelioma. The diagnostic accuracy of SM and MPF was significantly affected by the distribution of these covariates in the study population. The patients with mesothelioma were best discriminated from the control subjects with either the youngest age, the highest GFR, or the largest BMI. Furthermore, the control subjects were significantly better differentiated from stage II to IV than from stage I mesothelioma. MPF, not SM, was an independent negative prognostic factor, but only if adjusted for the biomarker-associated covariates. SM and MPF levels were affected by the same clinical covariates, which also had a significant impact on their diagnostic and prognostic value. To improve the interpretation of biomarker results, age, GFR, and BMI should be routinely recorded. Approaches to account for these covariates require further validation, as does the prognostic value of SM and MPF.
    Chest 07/2011; 141(2):477-84. · 5.85 Impact Factor
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    ABSTRACT: To evaluate the long-term impact of locoregional breast radiotherapy (RT) on pulmonary function tests (PFTs). This study included 75 women who underwent postoperative locoregional breast RT. PFTs were performed before RT and 3, 6, and 12 months and 8 to 10 years after RT. By use of univariate and multivariate analyses, the impact of treatment- and patient-related factors on late changes in PFTs was evaluated. During the first year after RT, all PFTs significantly worsened at 3 to 6 months after RT (p < 0.05). At 12 months, forced vital capacity (FVC), vital capacity (VC), and forced expiratory volume in 1 second (FEV(1)) recovered almost to baseline values, whereas total lung capacity (TLC) and diffusion capacity of carbon monoxide (DL(CO)) recovered only slightly and were still found to be decreased compared with baseline (p < 0.05). At 8 to 10 years after RT, mean reductions in FEV(1) of 4% (p = 0.03) and in VC, DL(CO), and TLC of 5%, 9%, and 11% (all p < 0.0001), respectively, were observed compared with pre-RT values. On multivariate analysis, tamoxifen use negatively affected TLC at 8 to 10 years after RT (p = 0.033), whereas right-sided irradiation was associated with a late reduction in FEV(1) (p = 0.027). For FEV(1) and DL(CO), an early decrease was predictive for a late decrease (p = 0.003 and p = 0.0009, respectively). The time course of PFT changes after locoregional RT for breast cancer follows a biphasic pattern. An early reduction in PFTs at 3 to 6 months with a partial recovery at 12 months after RT is followed by a late, more important PFT reduction up to 8 to 10 years after RT. Tamoxifen use may have an impact on this late decline in PFTs.
    International journal of radiation oncology, biology, physics 03/2011; 82(2):701-7. · 4.59 Impact Factor
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    ABSTRACT: Soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF) are serum biomarkers of mesothelioma. This study aims to examine the longitudinal behavior of SM and MPF in controls to gain insight in the optimal use of these biomarkers in screening. Asbestos-exposed individuals, with no malignant disease at inclusion, were surveilled for 2 years with annual measurements of SM and MPF. Fixed thresholds were set at 2.10 nmol/L for SM and 13.10 ng/ml for MPF. Longitudinal biomarker analysis, using a random intercept model, estimated the association with age and glomerular filtration rate (GFR), and the intraclass correlation. The latter represents the proportion of total biomarker variance accounted for by the between-individual variance. A total of 215 participants were included, of whom 179 and 137 provided a second sample and third sample, respectively. Two participants with normal SM and MPF levels presented afterward with mesothelioma and lung cancer, respectively. Participants with elevated biomarker levels were typically older and had a lower GFR. During follow-up, biomarker levels significantly increased. Longitudinal analysis indicated that this was in part due to aging, while changes in GFR had a less pronounced effect on serial biomarker measurements. SM and MPF had a high intraclass correlation of 0.81 and 0.78, respectively, which implies that a single biomarker measurement and fixed threshold are suboptimal in screening. The longitudinal behavior of SM and MPF in controls indicates that a biomarker-based screening approach can benefit from the incorporation of serial measurements and individual-specific screening rules, adjusted for age and GFR. Large-scale validation remains nevertheless mandatory to elucidate whether such an approach can improve the early detection of mesothelioma.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 02/2011; 6(5):889-95. · 4.55 Impact Factor
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    ABSTRACT: This study evaluates the relationship of six polymorphisms found in the CHRNA3, DRD2 and COMT genes with nicotine dependence, the ability to quit smoking and the occurrence of withdrawal symptoms after short-term use of nicotine patch in hospitalized patients. The study included 233 participants from a double-blind, placebo-controlled trial of nicotine patch substitution with a 6-month follow-up period. Nicotine dependence was assessed by the Fagerström Test for Nicotine Dependence (FTND) questionnaire, withdrawal symptoms by the Minnesota Nicotine Withdrawal Scale questionnaire and smoking cessation by self-reported abstinence at 1 week, 1 month and 6 months after treatment. After correcting for multiple testing, three polymorphisms in the DRD2 gene (Taq1A, Taq1B and Pro319Pro) were significantly associated with nicotine dependence (p = 0.018, p = 0.048 and p = 0.006, respectively). Using a cutoff point for the FTND score, the CHRNA3 Tyr215Tyr (rs1051730) polymorphism was also associated with nicotine dependence (p = 0.037 and p = 0.074 after correction for multiple testing). No association of any of the studied polymorphisms was observed with either smoking cessation or the occurrence of withdrawal symptoms. This study confirms the reported association of the CHRNA3 locus with nicotine dependence and shows the involvement of two independent DRD2 polymorphisms in nicotine dependence.
    Pharmacogenomics 08/2010; 11(8):1053-63. · 3.86 Impact Factor

Publication Stats

700 Citations
239.57 Total Impact Points


  • 2013
    • Erasmus Universiteit Rotterdam
      • Department of Public Health (MGZ)
      Rotterdam, South Holland, Netherlands
  • 2007–2013
    • Erasmus MC
      • Research Group for Public Health
      Rotterdam, South Holland, Netherlands
    • Universitair Ziekenhuis Leuven
      • Department of Radiology
      Leuven, VLG, Belgium
  • 2012
    • Medical University of Vienna
      Wien, Vienna, Austria
  • 2010–2012
    • Universitair Ziekenhuis Ghent
      Gand, Flanders, Belgium
  • 2005
    • University of Leuven
      Louvain, Flanders, Belgium