Johan Vansteenkiste

University of Leuven, Louvain, Flanders, Belgium

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Publications (244)1273.49 Total impact

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    ABSTRACT: ESMO consensus recommends EGFR mutation testing in never/former light smokers (<15 pack-years) or patients with non-squamous NSCLC. The aim of this work was to determine the frequency and clinical predictors of EGFR mutations, and the role of specimen sampling tests, in Caucasian standard practice setting.
    Translational respiratory medicine. 12/2014; 2(1):9.
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    ABSTRACT: The Lungscape project was designed to address the impact of clinical, pathological, and molecular characteristics on outcome in resected non-small- cell lung cancer (NSCLC). A decentralized biobank with fully annotated tissue samples was established. Selection criteria for participating centers included sufficient number of cases, tissue microarray building capability, and documented ethical approval. Patient selection was based on availability of comprehensive clinical data, radical resection between 2003 and 2009 with adequate follow-up, and adequate quantity and quality of formalin-fixed tissue. Fifteen centers contributed 2449 cases. The 5-year overall survival (OS) was 69.6% and 63.6% for stages IA and IB, 51.6% and 47.7% for stages IIA and IIB, and 29.0% and 13.0% for stages IIIA and IIIB, respectively (p < 0.001). Median and 5-year relapse-free survival (RFS) were 52.8 months and 47.3%, respectively. Distant relapse was recorded for 44.4%, local for 26.0%, and both for 16.9% of patients. Based on multivariate analysis for the OS, RFS, and time to relapse, the factors significantly associated with all of them are performance status and pathological stage. The aim of this report is to present the results from Lungscape, the first large series reporting on NSCLC surgical outcome measured not only by OS but also by RFS and time to relapse and including multivariate analysis by significant clinical and pathological prognostic parameters. As tissue from all patients is preserved locally and is available for detailed molecular investigations, Lungscape provides an excellent basis to evaluate the influence of molecular parameters on the disease outcome after radical resection, besides providing an overview of the molecular landscape of stage I to III NSCLC.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 11/2014; 9(11):1675-84. · 4.55 Impact Factor
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    ABSTRACT: Background: Biomarker-driven clinical trials in advanced non-small cell lung cancer (NSCLC) usually accept biopsy specimens only, as cytology specimens are supposed to be more challenging due to low neoplastic cell content and suboptimal DNA quantity. Objectives: We aimed to evaluate 2 aspects of bronchoscopic biopsy and cytology specimens: (1) the proportion of neoplastic cells and quantity of DNA extracted, and (2) the detection limit of the Scorpion amplification refractory mutation system on endoscopic samples obtained in daily clinical practice. Methods: We screened 679 patients with advanced-stage NSCLC for the presence of an activating EGFR mutation according to the guidelines of the European Society of Medical Oncology. Their diagnostic tumour tissue samples were characterized. A dilution experiment was performed to determine the minimal proportion of neoplastic cells for a reliable test result. Results: Surgical biopsies, bronchoscopic forceps biopsy samples and needle aspiration cytology specimens exhibited a median tumour cell proportion of 70 versus 30 versus 20% and a DNA quantity of 2,500 versus 1,610 versus 1,440 ng, respectively. The overall EGFR mutation rate was 11%, with no differences between different sample types. Dilution experiments showed that the detection limit depends on the type of mutation. A neoplastic cell content of at least 10 and 25% for exon 19 deletions and exon 21 L858R point mutation, respectively, was required for a true negative result. Conclusions: Bronchoscopic forceps biopsy and needle aspiration cytology specimens are suitable for accurate EGFR mutation analysis using single-gene quantitative real-time polymerase chain reaction. Technologies with a better analytical sensitivity are evolving and should consider these endoscopic tumour specimens. © 2014 S. Karger AG, Basel.
    10/2014;
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    ABSTRACT: Purpose To evaluate the diagnostic accuracy of the visual assessment of malignant pleural mesothelioma (MPM) on magnetic resonance (MR) images by using two known visual markers (mediastinal pleural thickness and shrinking of the lung) and a newly introduced one (pleural pointillism). Materials and Methods With the approval of the local ethics committee, 100 consecutive patients (mean age, 61.4 years; age range, 18-87 years; 75 men, 25 women) suspected of having MPM pleural abnormalities underwent positron emission tomography/computed tomography and MR imaging, including diffusion-weighted (DW) MR imaging, followed by explorative thoracoscopy or guided biopsy with histopathologic confirmation. Because visual assessment is still the preferred method of image interpretation, the diagnostic accuracy of mediastinal pleural thickening, shrinking lung (hemithorax volume decrease due to fibrosis), and pleural pointillism were examined. Pleural pointillism was denoted by the presence of multiple, hyperintense pleural spots on high-b-value DW images. Histopathologic findings in the surgical specimen served as the reference standard. McNemar tests with Bonferroni correction were used to assess differences in accuracy among the three examined markers. Results Of 100 patients, 33 had benign pleural alterations, and 67 had malignant pleural diseases (MPDs); 57 of 67 had MPM. A total of 78 patients received a correct diagnosis (benign vs malignant) on the basis of mediastinal pleural thickening (sensitivity, 81%; specificity, 73%; accuracy, 78%); and 66 patients, on the basis of shrinking lung (sensitivity, 60%; specificity, 79%; accuracy, 66%). The correct diagnosis was indicated on the basis of pleural pointillism in 88 patients (sensitivity, 93%; specificity, 79%; accuracy, 88%). Conclusion Visual assessment of pleural pointillism on high-b-value DW images is useful to differentiate MPD from benign alterations, performing substantially better than mediastinal pleural thickness and shrinking lung, and might obviate unnecessary invasive procedures for MPM. © RSNA, 2014.
    Radiology 09/2014; · 6.34 Impact Factor
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    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 06/2014; 9(6):897-9. · 4.55 Impact Factor
  • Els Wauters, Johan Vansteenkiste
    Journal of thoracic disease. 06/2014; 6(6):574-7.
  • Johan F Vansteenkiste
    Future oncology (London, England). 05/2014;
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    ABSTRACT: Non-small-cell lung cancer (NSCLC) harboring the anaplastic lymphoma kinase gene (ALK) rearrangement is sensitive to the ALK inhibitor crizotinib, but resistance invariably develops. Ceritinib (LDK378) is a new ALK inhibitor that has shown greater antitumor potency than crizotinib in preclinical studies. In this phase 1 study, we administered oral ceritinib in doses of 50 to 750 mg once daily to patients with advanced cancers harboring genetic alterations in ALK. In an expansion phase of the study, patients received the maximum tolerated dose. Patients were assessed to determine the safety, pharmacokinetic properties, and antitumor activity of ceritinib. Tumor biopsies were performed before ceritinib treatment to identify resistance mutations in ALK in a group of patients with NSCLC who had had disease progression during treatment with crizotinib. A total of 59 patients were enrolled in the dose-escalation phase. The maximum tolerated dose of ceritinib was 750 mg once daily; dose-limiting toxic events included diarrhea, vomiting, dehydration, elevated aminotransferase levels, and hypophosphatemia. This phase was followed by an expansion phase, in which an additional 71 patients were treated, for a total of 130 patients overall. Among 114 patients with NSCLC who received at least 400 mg of ceritinib per day, the overall response rate was 58% (95% confidence interval [CI], 48 to 67). Among 80 patients who had received crizotinib previously, the response rate was 56% (95% CI, 45 to 67). Responses were observed in patients with various resistance mutations in ALK and in patients without detectable mutations. Among patients with NSCLC who received at least 400 mg of ceritinib per day, the median progression-free survival was 7.0 months (95% CI, 5.6 to 9.5). Ceritinib was highly active in patients with advanced, ALK-rearranged NSCLC, including those who had had disease progression during crizotinib treatment, regardless of the presence of resistance mutations in ALK. (Funded by Novartis Pharmaceuticals and others; ClinicalTrials.gov number, NCT01283516.).
    New England Journal of Medicine 03/2014; 370(13):1189-97. · 54.42 Impact Factor
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    ABSTRACT: Lung cancer is the commonest cause of cancer-related death worldwide and poses a significant respiratory disease burden. Little is known about the provision of lung cancer care across Europe. The overall aim of the Task Force was to investigate current practice in lung cancer care across Europe.The Task Force undertook four projects: 1) a narrative literature search on quality management of lung cancer; 2) a survey of national and local infrastructure for lung cancer care in Europe; 3) a benchmarking project on the quality of (inter)national lung cancer guidelines in Europe; and 4) a feasibility study of prospective data collection in a pan-European setting.There is little peer-reviewed literature on quality management in lung cancer care. The survey revealed important differences in the infrastructure of lung cancer care in Europe. The European guidelines that were assessed displayed wide variation in content and scope, as well as methodological quality but at the same time there was relevant duplication. The feasibility study demonstrated that it is, in principle, feasible to collect prospective demographic and clinical data on patients with lung cancer. Legal obligations vary among countries.The European Initiative for Quality Management in Lung Cancer Care has provided the first comprehensive snapshot of lung cancer care in Europe.
    European Respiratory Journal 03/2014; · 6.36 Impact Factor
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    ABSTRACT: To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, early stage disease and locally-advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early stage disease.
    Annals of Oncology 02/2014; · 7.38 Impact Factor
  • Valerie Adam, Isabelle Wauters, Johan Vansteenkiste
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    ABSTRACT: Introduction: Lung cancer is a common health problem with a bad prognosis, despite recent advances in its treatment. Antigen-specific immunotherapy implies the administration of tumor-specific antigens with an immunostimulant to induce a powerful antitumor immune response, which has shown to be capable of eliminating tumor cells. Melanoma-associated antigen (MAGE) A3 is a good antigen to use in antigen-specific immunotherapy, since it is aberrantly expressed in cancer cells, but not expressed in normal tissue, except in germline and placental cells. Areas covered: Trials have been performed with the MAGE-A3 vaccine in the adjuvant setting after resection of non-small-cell lung cancer. They have shown that the MAGE-A3 vaccine is safe and well tolerated, with promising signs of clinical benefit, especially in patients expressing a specific gene signature. Outcome data are currently expected of a large Phase III randomized controlled trial in the same setting. Expert opinion: The future is hopeful for antigen-specific immunotherapy in general and MAGE-A3 vaccine in specific. Further research needs to identify new tumor-specific antigens, more potent adjuvants and genetic profiles suggestive of a better response toward antigen-specific immunotherapy. The MAGE-A3 vaccine has to be investigated in other settings than the adjuvant one and in other tumor types expressing MAGE-A3.
    Expert opinion on biological therapy 01/2014; · 3.22 Impact Factor
  • Kristof Cuppens, Johan Vansteenkiste
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    ABSTRACT: Recent advances in our understanding of cancer immunology resulted in the development of promising therapeutic agents for either nonantigen-specific immunotherapy, for example, monoclonal antibodies targeting immune checkpoints on the T-cell lymphocyte, and antigen-specific immunotherapy or vaccination. Here, we review the recently reported results from randomized controlled trials (RCTs) with the latter approach. Several trials indicated feasibility, safety, and potential for better patient outcomes. In resected early stage nonsmall cell lung cancer, a phase II RCT with the MAGE-A3 vaccine showed a trend for improved disease-free interval (hazard ratio 0.75), now further evaluated in the large MAGRIT (MAGE-A3 as Adjuvant NSCLC Immunotherapy Trial) study. In stage III after chemoradiotherapy, the phase III START (Stimulating Targeted Antigenic Responses to NSCLC) trial with L-BLP25 vaccine resulted in a remarkable 10-month improvement in median survival in the concurrent chemoradiotherapy subgroup. In the advanced setting, the phase III study with the allogeneic tumor cell vaccine belagenpumatucel-L did not improve survival in the whole study, but interesting effects were seen in subgroups. Recent nonsmall cell lung cancer vaccination trials did not meet their primary endpoint, but showed clear patient benefits in subgroup analyses. Confirmatory trials and identifying patients who will benefit using predictive factors, will hopefully bring these approaches in the clinic in the near future.
    Current opinion in oncology 01/2014; · 4.09 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: Background: Pulmonary function may decline after induction chemotherapy and predict perioperative complications in non-small cell lung cancer (NSCLC). The influence of adjuvant chemotherapy is largely indeterminate. Objective: To assess whether adjuvant chemotherapy alters pulmonary function and impacts on treatment-related adverse events. Methods: In a trial on adjuvant chemotherapy (the TREAT trial), 132 patients with R0-resected NSCLC were randomised to 4 cycles of cisplatin-vinorelbine (CVb, n = 65) or cisplatin-pemetrexed (CPx, n = 67). Pulmonary function tests (forced expiratory volume in 1 s, FEV1, forced vital capacity, FVC, total lung capacity, TLC, diffusing capacity for carbon monoxide, DLCO, and blood gas analyses, BGA) were analysed before and 30 days after the last chemotherapy, and changes were calculated (Δ = mean differences). Results: Overall, FVC increased significantly (Δ +290 ml, n = 76; p < 0.0001), while TLC did not change (Δ +220 ml, n = 41; p = 0.174). For CPx, FEV1 increased significantly (Δ +150 ml, n = 47; p = 0.0017), but not for CVb (Δ +30 ml, n = 30). DLCO decreased only for CVb (-8%, n = 6) but not for CPx (-0.39%, n = 17; p = 0.58). BGA did not change (p = 0.99). In a Cox regression analysis, baseline pulmonary function did not influence treatment failure. Conclusions: Adjuvant chemotherapy seems not to result in a decrease of pulmonary function parameters. A significant FVC increase was probably due to ongoing postoperative improvement. Decline of DLCO was noted with CVb but not with CPx. Pulmonary function does not impact on treatment failure. © 2013 S. Karger AG, Basel.
    Respiration 10/2013; · 2.92 Impact Factor
  • Sarah Declerck, Johan Vansteenkiste
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    ABSTRACT: Modulation of a patient's immune system so that it acts against lung cancer cells has not been successful in the past decades. Advances in our understanding of the immune response to tumors resulted in the development of different kinds of novel immunotherapeutic agents. This has resulted in the development of two major approaches. First, antigen-specific immunotherapy or cancer vaccination, with the MAGE-A3 vaccine in resected early-stage non-small-cell lung cancer (NSCLC), the L-BLP25 vaccine in locally advanced NSCLC after chemoradiotherapy and belagenpumatucel-L and the TG4010 vaccine in advanced-stage NSCLC. Second, non-antigen-specific immunotherapy or cancer immunomodulation is reviewed, including how monoclonal antibodies modulate the interaction between antigen-presenting cells, T-lymphocytes and tumor cells (e.g., antibodies against CTLA-4, or against PD-1 receptor or its ligands). Recent Phase II trials with these treatments have shown promising results of efficacy and tolerability, which has led to testing in several large Phase III trials. Some of these are fully recruited, while others are still ongoing, and important results are be expected in the near future.
    Future Oncology 10/2013; · 3.20 Impact Factor
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    ABSTRACT: We hypothesized that modern postoperative radiotherapy (PORT) could decrease local recurrence (LR) and improve overall survival (OS) in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC). To investigate the effect of modern PORT on LR and OS, we identified published phase III trials for PORT and stratified them according to use or non-use of linear accelerators. Non-individual patient data were used to model the potential benefit of modern PORT in stage IIIA-N2 NSCLC treated with induction chemotherapy and resection. Of the PORT phase III studies, eleven trials (2387 patients) were included for OS analysis and eight (1677 patients) for LR. PORT decreased LR, whether given with cobalt, cobalt and linear accelerators, or with linear accelerators only. An increase in OS was only seen when PORT was given with linear accelerators, along with the most significant effect on LR (relative risk for LR and OS 0.31 (p=0.01) and 0.76 (p=0.02) for PORT vs. controls, respectively). Four trials (357 patients) were suitable to assess LR rates in stage III NSCLC treated with surgery, in most cases after induction chemotherapy. LR as first relapse was 30% (105/357) after 5years. In the modeling part, PORT with linear accelerators was estimated to reduce LR rates to 10% as first relapse and to increase the absolute 5-year OS by 13%. This modeling study generates the hypothesis that modern PORT may increase both LR and OS in stage IIIA-N2 NSCLC even in patients being treated with induction chemotherapy and surgery.
    Radiotherapy and Oncology 10/2013; · 4.52 Impact Factor
  • Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2013; 8(10):1339-40. · 4.55 Impact Factor
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    ABSTRACT: Background. Radiation-induced lung damage (RILD) is an important problem. Although physical parameters such as the mean lung dose are used in clinical practice, they are not suited for individualised radiotherapy. Objective, quantitative measurements of RILD on a continuous instead of on an ordinal, semi-quantitative, semi-subjective scale, are needed. Methods. Hounsfield unit (HU) changes before versus three months post-radiotherapy were correlated per voxel with the radiotherapy dose in 95 lung cancer patients. Deformable registration was used to register pre- and post-CT scans and the density increase was quantified for various dose bins. The dose-response curve for increased HU was quantified using the slope of a linear regression (HU/Gy). The end-point for the toxicity analysis was dyspnoea ≥ grade 2. Results. Radiation dose was linearly correlated with the change in HU (mean R(2) = 0.74 ± 0.28). No differences in HU/Gy between groups treated with stereotactic radiotherapy, conventional radiotherapy alone, sequential or concurrent chemo- radiotherapy were observed. In the whole patient group, 33/95 (34.7%) had dyspnoea ≥ G2. Of the 48 patients with a HU/Gy below the median, 16 (33.3%) developed dyspnoea ≥ G2, while in the 47 patients with a HU/Gy above the median, 17 (36.1%) had dyspnoea ≥ G2 (not significant). Individual patients showed a nearly 21-fold difference in radiosensitivity, with HU/Gy ranging from 0 to 10 HU/Gy. Conclusions. HU changes identify objectively the whole range of individual radiosensitivity on a continuous, quantitative scale. CT density changes may allow more robust and accurate radiogenomics studies.
    Acta oncologica (Stockholm, Sweden) 08/2013; · 2.27 Impact Factor
  • E Govaerts, J Vansteenkiste
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 06/2013; 8(6):e52-3. · 4.55 Impact Factor

Publication Stats

8k Citations
1,273.49 Total Impact Points

Institutions

  • 1991–2014
    • University of Leuven
      • • Division of Nuclear Medicine and Molecular Imaging
      • • Department of Clinical and Experimental Medicine
      Louvain, Flanders, Belgium
  • 1996–2013
    • Universitair Ziekenhuis Leuven
      • • Department of Thoracic surgery
      • • Department of General medical oncology
      • • Department of Nuclear Medicine
      Louvain, Flanders, Belgium
  • 2012
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 2008–2012
    • Medical University of Vienna
      • Institut für Sozialmedizin
      Wien, Vienna, Austria
    • Western Health
      Melbourne, Victoria, Australia
  • 1994–2012
    • The Catholic University of America
      Washington, Washington, D.C., United States
  • 2011
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
  • 2010
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2009
    • Università degli Studi di Torino
      • Dipartimento di Scienze Cliniche e Biologiche
      Torino, Piedmont, Italy
  • 2007
    • Memorial Sloan-Kettering Cancer Center
      • Thoracic Service
      New York City, NY, United States
  • 2004
    • University of Santiago, Chile
      CiudadSantiago, Santiago, Chile
  • 2002
    • Algemeen ziekenhuis Sint-Maarten
      Flanders, Belgium
  • 1998
    • Psychiatrisch Ziekenhuis Sint-Norbertus
      Flanders, Belgium