Johan Vansteenkiste

Universitair Ziekenhuis Leuven, Louvain, Flanders, Belgium

Are you Johan Vansteenkiste?

Claim your profile

Publications (238)1215.66 Total impact

  • Els Wauters, Johan Vansteenkiste
    Journal of thoracic disease. 06/2014; 6(6):574-7.
  • Source
    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
  • Johan F Vansteenkiste
    Future oncology (London, England). 05/2014;
  • Source
  • [Show abstract] [Hide abstract]
    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. · 51.66 Impact Factor
  • [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    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
    [Show abstract] [Hide abstract]
    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
    [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    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; · 2.62 Impact Factor
  • Sarah Declerck, Johan Vansteenkiste
    [Show abstract] [Hide abstract]
    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
  • Source
    [Show abstract] [Hide abstract]
    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
  • Source
    [Show abstract] [Hide abstract]
    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
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSETo detect a pretreatment gene expression signature (GS) predictive of response to MAGE-A3 immunotherapeutic in patients with metastatic melanoma and to investigate its applicability in a different cancer setting (adjuvant therapy of resected early-stage non-small-cell lung cancer [NSCLC]). PATIENTS AND METHODS Patients were participants in two phase II studies of the recombinant MAGE-A3 antigen combined with an immunostimulant (AS15 or AS02B). mRNA from melanoma biopsies was analyzed by microarray analysis and quantitative polymerase chain reaction. These results were used to identify and cross-validate the GS, which was then applied to the NSCLC data.ResultsIn the patients with melanoma, 84 genes were identified whose expression was potentially associated with clinical benefit. This effect was strongest when the immunostimulant AS15 was included in the immunotherapy (hazard ratio [HR] for overall survival, 0.37; 95% CI, 0.13 to 1.05; P = .06) and was less strong with the other immunostimulant AS02B (HR, 0.84; 95% CI, 0.36 to 1.97; P = .70). The same GS was then used to predict the outcome for patients with resected NSCLC treated with MAGE-A3 plus AS02B; actively treated GS-positive patients showed a favorable disease-free interval compared with placebo-treated GS-positive patients (HR, 0.42; 95% CI, 0.17 to 1.03; P = .06), whereas among GS-negative patients, no such difference was found (HR, 1.17; 95% CI, 0.59 to 2.31; P = .65). The genes identified were mainly immune related, involving interferon gamma pathways and specific chemokines, suggesting that their pretreatment expression influences the tumor's immune microenvironment and the patient's clinical response. CONCLUSION An 84-gene GS associated with clinical response for MAGE-A3 immunotherapeutic was identified in metastatic melanoma and confirmed in resected NSCLC.
    Journal of Clinical Oncology 05/2013; · 18.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSEThe MAGE-A3 protein is expressed in approximately 35% of patients with resectable non-small-cell lung cancer (NSCLC). Several immunization approaches against the MAGE-A3 antigen have shown few, but often long-lasting, clinical responses in patients with metastatic melanoma.Patients and methodsA double-blind, randomized, placebo-controlled phase II study was performed assessing clinical activity, immunologic response, and safety following immunization with recombinant MAGE-A3 protein combined with an immunostimulant (13 doses over 27 months) in completely resected MAGE-A3-positive stage IB to II NSCLC. The primary end point was disease-free interval (DFI).ResultsPatients were randomly assigned to either MAGE-A3 immunotherapeutic (n = 122) or placebo (n = 60). After a median postresection period of 44 months, recurrence was observed in 35% of patients in the MAGE-A3 arm and 43% in the placebo arm. No statistically significant improvement in DFI (hazard ratio [HR], 0.75, 95% CI, 0.46 to 1.23; two-sided P = .254), disease-free survival (DFS; HR, 0.76; 95% CI, 0.48 to 1.21; P = .248), or overall survival (HR, 0.81; 95% CI, 0.47 to 1.40; P = .454) was observed. Corresponding analysis after a median of 70 months of follow-up revealed a similar trend for DFI and DFS. All patients receiving the active treatment showed a humoral immune response to the MAGE-A3 antigen, although no correlation was observed with outcome. No significant toxicity was observed. CONCLUSION In this early development study with a limited number of patients, postoperative MAGE-A3 immunization proved to be feasible with minimal toxicity. These results are being investigated further in a large phase III study.
    Journal of Clinical Oncology 05/2013; · 18.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract BACKGROUND: Prior to the approval of the first erythropoiesis-stimulating agent (ESA) in the early 1990s, red blood cell transfusions were the primary means of treating severe chemotherapy-induced anemia (CIA), with little recourse for those with more mild forms of the condition. The introduction of the ESAs allowed treatment of mild-to-moderate CIA in patients with cancer. It has been a decade since darbepoetin alfa (DA), a second-generation ESA with a longer half-life, became available to patients with CIA. OBJECTIVE AND METHODS: We present a review of studies on DA in CIA, from its development through to the present day. Medline was searched for randomized clinical trials on DA. Additional trials and meta-analyses on ESAs were incorporated into this review when relevant. RESULTS: The first publications on DA generally focused on optimal dosing, efficacy and tolerability. In these, it was shown that DA is an effective and well tolerated treatment option to achieve hematopoietic response, regardless of dosing interval. Subsequently, the focus shifted towards meta-analyses on survival data of all ESAs. These reported conflicting results regarding mortality and/or disease progression. However, guidelines for ESA use were updated and, when followed, these make ESAs a well-tolerated and effective tool for managing CIA. CONCLUSIONS: As the past decade has broadened our knowledge on the benefits and risks of CIA management, continued high-quality studies will help to optimize treatment with ESAs in order to maximize quality of life for these patients. The limitation of a literature review of this nature is the complete reliance on previously published research and the availability of these studies using the methodology outlined above.
    Current Medical Research and Opinion 01/2013; · 2.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Four randomized phase II/III trials investigated the addition of cetuximab to platinum-based, first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis was performed to examine the benefit/risk ratio for the addition of cetuximab to chemotherapy. Materials and methods The meta-analysis included individual patient efficacy data from 2018 patients and individual patient safety data from 1970 patients comprising respectively the combined intention-to-treat and safety populations of the four trials. The effect of adding cetuximab to chemotherapy was measured by hazard ratios (HRs) obtained using a Cox proportional hazards model and odds ratios calculated by logistic regression. Survival rates at 1 year were calculated. All applied models were stratified by trial. Tests on heterogeneity of treatment effects across the trials and sensitivity analyses were performed for all endpoints. Results The meta-analysis demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival (HR 0.88, p = 0.009, median 10.3 vs 9.4 months), progression-free survival (HR 0.90, p = 0.045, median 4.7 vs 4.5 months) and response (odds ratio 1.46, p < 0.001, overall response rate 32.2% vs 24.4%) compared with chemotherapy alone. The safety profile of chemotherapy plus cetuximab in the meta-analysis population was confirmed as manageable. Neither trials nor patient subgroups defined by key baseline characteristics showed significant heterogeneity for any endpoint. Conclusion The addition of cetuximab to platinum-based, first-line chemotherapy for advanced NSCLC significantly improved outcome for all efficacy endpoints with an acceptable safety profile, indicating a favorable benefit/risk ratio.
    Lung cancer (Amsterdam, Netherlands) 01/2013; · 3.14 Impact Factor

Publication Stats

8k Citations
1,215.66 Total Impact Points

Institutions

  • 1996–2013
    • Universitair Ziekenhuis Leuven
      • • Department of Thoracic surgery
      • • Department of General medical oncology
      • • Department of Nuclear Medicine
      Louvain, Flanders, Belgium
    • The Catholic University of America
      Washington, Washington, D.C., United States
  • 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
    • Catholic University of Louvain
      Walloon Region, Belgium
  • 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
  • 1991–2006
    • KU Leuven
      • • Division of Nuclear Medicine and Molecular Imaging
      • • Department of Clinical and Experimental Medicine
      Leuven, VLG, Belgium
  • 2004
    • University of Santiago, Chile
      CiudadSantiago, Santiago, Chile
  • 2002
    • Algemeen ziekenhuis Sint-Maarten
      Flanders, Belgium
  • 1998
    • Psychiatrisch Ziekenhuis Sint-Norbertus
      Flanders, Belgium