Johan Vansteenkiste

Universitair Ziekenhuis Leuven, Louvain, Flanders, Belgium

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Publications (209)1378.03 Total impact

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    ABSTRACT: Background Unplanned hospital admissions (UHAs) are frequent in lung cancer, but literature on this topic is scarce. The aim of this study is to gain insight in the demographics, patterns of referral, causes, presenting symptoms, and final outcome of these UHAs. A strategy to improve quality of care and reduce the number and cost of UHAs was suggested based upon these findings. Patients and methods In retrospective analysis of all consecutive UHAs in a 6-month period in a tertiary center, demographics, pattern of referral, clinical data, tumor control status, final diagnosis, duration of hospitalization, and outcome were examined. Results Two hundred seven UHAs were recorded. Male/female ratio was 185/62, mean age 65.5 years, performance status (PS) on admission 0–1 in 32 %, 2 in 37.2 %, and 3–4 in 30.8 % of patients. Patient referral occurred by general practitioner in 33.6 % or specialist in 25.5 % and in 40.9 % on own initiative. UHAs were therapy-related in 23.9 %, cancer-related in 47.4 %, comorbidity-related in 19.4 %, or of unclear nature in 9.3 %. Most frequent causes were infections (21.9 %) and respiratory problems (17.0 %). Mean length of stay was 9.5 days. Final outcome was 10.1 % mortality, 6.9 % hospice care transfers, and 79.4 % home returns (including 18.2 % same day returns). Conclusion UHAs in lung cancer were more cancer- than therapy-related. Majority of patients (2/3) were not seen by their general practitioner. A significant number of same day returns were noted. UHAs in patients with poor PS, uncontrolled cancer and cancer-related events had the worst outcome. This work is a first step in identifying specific characteristics of UHAs in lung cancer patients, which may lead to strategies to reduce the burden of UHAs.
    No preview · Article · Jan 2016 · Supportive Care Cancer
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    ABSTRACT: Purpose: Limited data are available to describe the effectiveness of darbepoetin alfa (DA) in terms of hemoglobin (Hb) and transfusion outcomes when initiated at Hb ≤10 g/dL (the threshold specified in the summary of prescribing characteristics). We assessed DA, initiated according to current labeling (Hb ≤10 g/dL), in chemotherapy-induced anemia (CIA). Methods: Data for patients with cancer and CIA who initiated DA at Hb ≤10 g/dL were extracted from a database of Amgen-sponsored trials. A comparative analysis was limited to randomized, controlled trials in patients treated with DA or control (placebo/best supportive care). Data for the DA arm(s) of randomized, multiple-arm, or prospective, single-arm trials were also extracted (DA-only analysis; non-front-loaded studies only). Outcomes included Hb increase ≥1 g/dL or ≥2 g/dL during the first 12 weeks of treatment. Crude and Kaplan-Meier proportions of patients who experienced each outcome and time (days) to each outcome were summarized by treatment arm. Meta-analysis (fixed-effects inverse-variance method) was performed to compare outcomes for DA with control. Findings: The comparative analysis included 4 studies (2 in lung cancer, 1 in lymphoproliferative disease, and 1 in non-myeloid malignancy: DA, n = 261; control, n = 273). The DA-only analysis included 15 studies (n = 3768). In comparative analyses, more patients who received DA than placebo achieved Hb increase of ≥1 g/dL (fixed-effects hazard ratio [HR] = 2.07; 95% CI, 1.62-2.63) or ≥2 g/dL (HR = 2.91; 95% CI, 2.09-4.06). Median times to ≥1 g/dL or ≥2 g/dL increase were 43 or 78 days for DA (not evaluable for placebo). Transfusions were less common in patients who received DA (HR = 0.58; 95% CI, 0.44-0.77). Addition of 2 dose-finding studies did not change the findings of the main comparative analysis. Results were similar in the DA-only analyses. Implications: This is the first patient-level meta-analysis, to our knowledge, to evaluate the efficacy in terms of Hb response of DA treatment when initiated according to current product labeling in patients with CIA. Limitations include the small number of studies and patients eligible for inclusion in the comparative analyses and the absence of non-Amgen trials of DA. The results of the comparative analysis confirm that DA is more effective than placebo at increasing serum Hb levels and at reducing the need for transfusion in patients with CIA when treatment is initiated at Hb ≤10 g/dL, as per current product labeling.
    No preview · Article · Jan 2016 · Clinical Therapeutics
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    ABSTRACT: Somatic mutations found within the tyrosine kinase domain (TKD) of the human epidermal growth factor (HER) family of receptors have been implicated in the development and progression of non-small cell lung cancer (NSCLC). However, no conclusive reports have described pathogenic mutations in kinase-impaired HER3. Here, we report a case of an advanced chemotherapy-resistant NSCLC, harboring a novel HER3V855A somatic mutation homologous to the EGFRL858Ractivating mutation. Co-expression of HER3V855A and wild-type HER2 enhances ligand-induced transformation of murine and human cell lines, while HER-targeted inhibitors potently suppress mutant HER3 activity. Consistent with these observations, in silico computational modeling predicts that mutant V855A alters the kinase domain and c-terminal end of the HER3 protein. Taken together, these findings provide a basis for the clinical exploration of targeted therapies in HER3 mutant NSCLC and by extrapolation, in other cancers that more frequently carry somatic HER3 mutations.
    Preview · Article · Dec 2015 · Oncotarget
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    Preview · Article · Nov 2015
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    ABSTRACT: (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) complements conventional imaging for diagnosing and staging lung cancer. Two literature-based meta-analyses suggest that maximum standardised uptake value (SUVmax) on PET has univariate prognostic value in nonsmall cell lung cancer (NSCLC). We analysed individual data pooled from 12 studies to assess the independent prognostic value of binary SUVmax for overall survival.After searching the published literature and identifying unpublished data, study coordinators were contacted and requested to provide data on individual patients. Cox regression models stratified for study were used.Data were collected for 1526 patients (median age 64 years, 60% male, 34% squamous cell carcinoma, 47% adenocarcinoma, 58% stage I-II). The combined univariate hazard ratio for SUVmax was 1.43 (95% CI 1.22-1.66) and nearly identical if the SUV threshold was calculated stratifying for histology. Multivariate analysis of patients with stage I-III disease identified age, stage, tumour size and receipt of surgery as independent prognostic factors; adding SUV (HR 1.58, 95% CI 1.27-1.96) improved the model significantly. The only detected interaction was between SUV and stage IV disease.SUV seems to have independent prognostic value in stage I-III NSCLC, for squamous cell carcinoma and for adenocarcinoma.
    No preview · Article · Sep 2015 · European Respiratory Journal
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    ABSTRACT: Introduction: Non-small cell lung cancer (NSCLC) is a heterogeneous disorder consisting of distinct molecular subtypes each characterised by specific genetic and epigenetic profiles. Here, we aimed to identify novel NSCLC subtypes based on genome-wide methylation data, assess their relationship with smoking behaviour, age, COPD, emphysema and tumour histopathology, and identify the molecular pathways underlying each subtype. Methods: Methylation profiling was performed on 49 pairs of tumour and adjacent lung tissue using Illumina 450 K arrays. Transcriptome sequencing was performed using Illumina HiSeq2000 and validated using expression data from The Cancer Genome Atlas (TCGA). Tumour immune cell infiltration was investigated by immunohistochemistry. Results: Unsupervised hierarchical clustering of tumour methylation data revealed two subgroups characterised by a significant association between cluster membership and presence of COPD (p=0.024). Ontology analysis of genes containing differentially methylated CpGs (false discovery rate, FDR-adjusted p<0.05) revealed that immune genes were strongly enriched in COPD tumours, but not in non-COPD tumours. This COPD-specific immune signature was attributable to methylation changes in immune genes expressed either by tumour cells or tumour-infiltrating immune cells. No such differences were observed in adjacent tissue. Transcriptome profiling similarly revealed that genes involved in the immune response were differentially expressed in COPD tumours (FDR-adjusted p<0.05), an observation that was independently replicated using TCGA data. Immunohistochemistry validated these findings, revealing fewer CD4-positive T lymphocytes in tumours derived from patients with COPD. Conclusions: Lung tumours of patients with COPD differ from those of patients without COPD, with differentially methylated and expressed genes being mainly involved in the immune response.
    No preview · Article · Sep 2015 · Thorax

  • No preview · Article · Sep 2015 · Journal of Thoracic Oncology
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    ABSTRACT: Introduction: To assess the safety and immunogenicity of MAGE-A3 immunotherapeutic in patients with stage IB-III MAGE-A3-positive non-small-cell lung cancer (NSCLC) who were or were not undergoing standard cisplatin/vinorelbine chemotherapy. Methods: This open, prospective, multicenter, parallel-group phase I study (NCT00455572) enrolled patients with resected (cohorts 1-3) or unresectable (cohort 4) MAGE-A3-positive NSCLC. MAGE-A3 immunotherapeutic (300 g recombinant MAGE-A3 formulated with AS15) was administered (eight doses, 3 weeks apart) concurrent with (cohort 1), after (cohort 2), or without (cohort 3) standard-adjuvant chemotherapy, or after standard radiotherapy and/or chemotherapy (cohort 4). Results: Sixty-seven patients received greater than or equal to 1 dose of MAGE-A3 immunotherapeutic. Grade 3/4 adverse events (AEs) were reported for 16 out of 19 (84%), 2 out of 18 (11%), 5 out of 18 (28%), and 1 out of 12 (8%) patients in cohorts 1, 2, 3, and 4, respectively. Many grade 3/4 AEs in cohort 1 (e.g., neutropenia) were typical of chemotherapy. Six patients, including three in cohort 1, reported study treatment-related grade 3/4 AEs (injection-site reactions or musculoskeletal/back pain, which resolved within 5 days). One patient (in cohort 4) died, but this and the other serious adverse events were not study treatment related. MAGE-A3-specific antibody responses to immunotherapy were induced in all patients evaluated in all cohorts. MAGE-A3-specific CD4(+) T-cell responses to immunotherapy were detected in 4 out of 11 (36%), 4 out of 15 (27%), 2 out of 8 (25%), and 5 out of 6 (83%) evaluated patients in cohorts 1, 2, 3, and 4, respectively; and CD8(+) T-cell responses were only detected in four patients. Conclusion: In resected and unresectable NSCLC patients and irrespective of whether standard chemotherapy was concurrent or not, MAGE-A3 immunotherapeutic is well tolerated and induces MAGE-A3-specific immune responses.
    No preview · Article · Aug 2015 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
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    ABSTRACT: The phosphatidylinositol 3-kinase (PI3K) pathway promotes tumor growth and treatment resistance in non-small cell lung cancer (NSCLC). The aim of the open-label, two-stage, Phase II study BASALT-1 (NCT01820325) was to investigate the pan-PI3K inhibitor buparlisib (BKM120) in patients with PI3K pathway-activated, relapsed NSCLC. After pre-screening for PI3K pathway activation, patients with PI3K pathway-activated, metastatic, squamous or non-squamous NSCLC who had relapsed after prior systemic antineoplastic therapy, were enrolled. In Stage 1, patients received single-agent buparlisib (100 mg/day). A futility analysis was performed independently in each histology group, based on the 12-week progression-free survival (PFS) rate for the first 30 patients treated in each group being <50%. Exploratory biomarker analyses were performed in archival tissue samples and circulating tumor DNA (ctDNA). Of 1242 pre-screened patients, 13.5% exhibited PI3K pathway activation. As of June 5, 2014, 63 patients (30 squamous and 33 non-squamous) were treated in Stage 1. The 12-week PFS rates were 23.3% (95% confidence interval [CI] 9.9-42.3) and 20.0% (95% CI 7.7-38.6) in the squamous and non-squamous groups, respectively. Stage 2 was therefore not initiated in either group. PI3K pathway mutations in ctDNA were more concordant with metastatic tissue than with primary biopsies. Despite preselecting patients for targeted treatment, BASALT-1 did not meet its primary objective during Stage 1. PI3K pathway activation can be detected using ctDNA, but may not be the main oncogenic driver in NSCLC. Combinations of PI3K inhibitors with other agents may demonstrate greater efficacy than monotherapy.
    No preview · Article · Jun 2015 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer

  • No preview · Article · Jun 2015

  • No preview · Article · Jun 2015
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    ABSTRACT: Treatment decisions in advanced non-small cell lung cancer rely on accurate analysis of the EGFR mutation status in small tissue samples. Sanger sequencing of PCR products is unbiased and cheap, but its detection threshold requiring 20 % infiltration by malignant cells is not optimal. Commercial kits, based on quantitative real-time PCR have better detection limits and can detect a wide spectrum of mutations but are considerably more expensive. We developed a wild-type blocking PCR for EGFR G719A/S/C (exon 18), exon 19 deletions, and exon 20 insertions using locked nucleic acid (LNA) probes. The amplification products of positive reactions were analyzed by Sanger sequencing. We retrospectively validated this assay by comparison of the EGFR mutation status as obtained with Fragment Length Analysis and the Therascreen EGFR RGQ PCR kit. The EGFR mutation status for exon 18 and 19 as obtained with the LNA-PCR/sequencing assay correlated adequately with the results obtained by the other independent methods. Due to the lack of structural consistency among the insertions in exon 20, the latter are less amenable for a LNA-PCR design. The LNA-PCR/sequencing assay presented here is specific, sensitive, and has a low detection threshold. In combination with allele-specific PCR reactions for T790M (exon 20) and L858R (exon 21), a wider scope of EGFR mutations can be assessed at a lower cost. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1272520418142748.
    Full-text · Article · May 2015 · Diagnostic Pathology
  • Johan Vansteenkiste · Julie Craps · Nele De Brucker · Isabelle Wauters
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    ABSTRACT: ABSTRACT In the past decade, the approach to patients with metastatic non-small-cell lung cancer has relied on chemotherapy and on targeted agents for molecularly selected subgroups of patients. Recent work has introduced immunotherapy as another area of progress, and likely as a new treatment paradigm in the near future. While the large Phase III studies with cancer vaccination with the current technologies remain at present disappointing, the immunomodulation strategies with immune checkpoint inhibitors have delivered remarkable results in expanded Phase I studies and are now intensively studied in large Phase III studies. This review summarizes the past decade of immunotherapy for non-small-cell lung cancer, gives an updated overview of trials in this field, and the context of future development in this exciting field.
    No preview · Article · May 2015 · Future Oncology
  • Valerie Adam · Christophe Dooms · Johan Vansteenkiste
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    ABSTRACT: Lung cancer is the most common solid tumor that requires admission to an intensive care unit (ICU). The overall perception about the value of ICU admission for lung cancer patients remains negative, given the poor overall prognosis of patients with advanced lung cancer. Recently developed highly effective targeted therapies for lung cancers with an oncogene driver have an expected rapid onset of action and a decreased risk of toxicity. Therefore, ICU care for lung cancer patients has to be reconsidered. We present an illustrative case of a young woman with stage IV ALK-translocated pulmonary adenocarcinoma. Her disease dramatically worsened while waiting for central confirmation of the ALK-translocation to start treatment in a clinical trial with ceritinib, a 2nd generation ALK tyrosine kinase inhibitor. She needed mechanical ventilation and veno-venous extracorporal membranous oxygenation, to have sufficient time to recover from overwhelming bilateral lung adenocarcinoma, while on treatment. She is now doing fine 1 year later. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · May 2015 · Lung cancer (Amsterdam, Netherlands)
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    ABSTRACT: This multicentre, open-label, randomized, controlled phase II study evaluated cilengitide in combination with cetuximab and platinum-based chemotherapy, compared with cetuximab and chemotherapy alone, as first-line treatment for patients with advanced NSCLC. Patients were randomized 1:1:1 to receive cetuximab plus platinum-based chemotherapy alone (control), or combined with cilengitide 2000 mg 1x/week i.v. (CIL-once) or 2x/week i.v. (CIL-twice). A protocol amendment limited enrolment to patients with epidermal growth factor receptor (EGFR) histoscore ≥200 and closed the CIL-twice arm for practical feasibility issues. Primary endpoint was progression-free survival (PFS; independent read); secondary endpoints included overall survival (OS), safety, and biomarker analyses. A comparison between the CIL-once and control arms is reported, both for the total cohorts, as well as for patients with EGFR histoscore ≥200. There were 85 patients in the CIL-once group and 84 in the control group. The PFS (independent read) was 6.2 vs. 5.0 months for CIL-once versus control (hazard ratio [HR] 0.72; P=0.085); for patients with EGFR histoscore ≥200, PFS was 6.8 versus 5.6 months, respectively (HR 0.57; P=0.0446). Median OS was 13.6 for CIL-once versus 9.7 months for control (HR 0.81; P=0.265). In patients with EGFR ≥200, OS was 13.2 versus 11.8 months, respectively (HR 0.95; P=0.855). No major differences in adverse events between CIL-once and control were reported; nausea (59% versus 56%, respectively) and neutropenia (54% versus 46%, respectively) were the most frequent. There was no increased incidence of thromboembolic events or haemorrhage in cilengitide-treated patients. αvβ3 and αvβ5 expression was neither a predictive nor prognostic indicator. The addition of cilengitide to cetuximab/chemotherapy indicated potential clinical activity, with a trend for PFS difference in the independent-read analysis. However, the observed inconsistencies across endpoints suggest additional investigations are required to substantiate a potential role of other integrin inhibitors in NSCLC treatment. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    No preview · Article · May 2015 · Annals of Oncology
  • Johan Vansteenkiste

    No preview · Article · Apr 2015 · Annals of Oncology
  • G.V. Scagliotti · P. Bironzo · J.F. Vansteenkiste
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    ABSTRACT: Chemotherapy is currently the standard of care for non-oncogene-driven advanced non-small cell lung cancer (NSCLC). Due to improvements in chemotherapeutic choices and supportive care, patients currently typically undergo multiple lines of chemotherapy as their disease progresses. Although treatments have improved over recent years, limited benefits are seen, especially in patients receiving later-line chemotherapy, as response rates can be low, response duration short and survival poor. Furthermore, only a small percentage of patients derive benefit from later-line therapy, with most experiencing deteriorating quality of life and significant toxicities. More recently, molecular targeted therapies have provided improvements in outcomes. However, these treatments only offer a clear benefit in subsets of tumours harbouring the appropriate genomic alteration (mutation, amplification, translocation). Most of the genomic abnormalities susceptible to therapeutic intervention are detected in adenocarcinoma, mainly in never smokers, while alterations in the genome of other histological subtypes are known but specific agents targeting these alterations have yet to be developed. Thus, the therapeutic management of these subtypes represents an ongoing challenge. Recent advances in immunotherapy have highlighted the potential of immuno-oncology based treatments for NSCLC, offering the potential to provide durable responses and outcomes regardless of histology or mutation status. This review discusses the current unmet medical needs in NSCLC, the limits of current first-line and later-line chemotherapy and targeted agents, and the emergence of new therapeutic strategies. Copyright © 2015. Published by Elsevier Ltd.
    No preview · Article · Apr 2015 · Cancer Treatment Reviews

  • No preview · Article · Apr 2015
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    ABSTRACT: Background: Accumulating evidence has shown that cancer cell metabolism differs from that of normal cells. However, up to now it is not clear whether different cancer types are characterized by a specific metabolite profile. Therefore, this study aims to evaluate whether the plasma metabolic phenotype allows to discriminate between lung and breast cancer. Patients and methods: The proton nuclear magnetic resonance spectrum of plasma is divided into 110 integration regions, representing the metabolic phenotype. These integration regions reflect the relative metabolite concentrations and were used to train a classification model in discriminating between 80 female breast cancer patients and 54 female lung cancer patients, all with an adenocarcinoma. The validity of the model was examined by permutation testing and by classifying an independent validation cohort of 60 female breast cancer patients and 81 male lung cancer patients, all with an adenocarcinoma. Results: The model allows to classify 99% of the breast cancer patients and 93% of the lung cancer patients correctly with an area under the curve of 0.96 and can be validated in the independent cohort with a sensitivity of 89%, a specificity of 82% and an area under the curve of 0.94. Decreased levels of sphingomyelin and phosphatidylcholine (phospholipids with choline head group) and phospholipids with short, unsaturated fatty acid chains next to increased levels of phospholipids with long, saturated fatty acid chains seem to indicate that cell membranes of lung tumors are more rigid and less sensitive to lipid peroxidation. The other discriminating metabolites are pointing to a more pronounced response of the body to the Warburg effect for lung cancer. Conclusion: Metabolic phenotyping of plasma allows to discriminate between lung and breast cancer, indicating that the metabolite profile reflects more than a general cancer marker.
    No preview · Article · Apr 2015 · Annals of Oncology
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    ABSTRACT: Modern imaging techniques that can provide functional information on tumor vascularization, metabolic activity, or cellularity have seen significant improvements over the past decade. However, most of these techniques are currently not broadly utilized neither in clinical trials nor in clinical routine, although there is a large agreement on the fact that conventional approaches for therapy response assessment such as Response Evaluation Criteria in Solid Tumors or World Health Organization criteria-that exclusively focus on the change in tumor size-are of less value for response assessment in modern thoracic oncology. The aim of this article comprises two parts: a short review of the most promising state-of-the-art imaging techniques that have the potential to play a larger role in thoracic oncology within the near future followed by a meeting report including recommendations of an interdisciplinary expert panel that discussed the potential of the different techniques during the Dresden 2013 Post World Congress of Lung Cancer (WCLC) - International Association for the Study of Lung Cancer (IASLC) meeting. It is intended to provide a comprehensive summary about ongoing trends and future perspectives on functional imaging in thoracic oncology.
    Full-text · Article · Feb 2015 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer

Publication Stats

14k Citations
1,378.03 Total Impact Points

Institutions

  • 1998-2016
    • Universitair Ziekenhuis Leuven
      • Department of Thoracic surgery
      Louvain, Flanders, Belgium
  • 1997-2015
    • University of Leuven
      • Division of Nuclear Medicine and Molecular Imaging
      Louvain, Flanders, Belgium
  • 2012
    • Hospital Universitario Virgen del Rocío
      • Medical Oncology Department
      Hispalis, Andalusia, Spain
  • 2007-2012
    • Universitair Ziekenhuis Ghent
      Gand, Flanders, Belgium
  • 1998-2012
    • The Catholic University of America
      Washington, Washington, D.C., United States
  • 2011
    • Groote Schuur Hospital
      Kaapstad, Western Cape, South Africa
  • 2002-2009
    • Catholic University of Louvain
      Лувен-ла-Нев, Walloon, Belgium
    • VU University Medical Center
      • Department of Nuclear Medicine and PET Research
      Amsterdamo, North Holland, Netherlands
  • 2008
    • Università degli Studi di Torino
      • Dipartimento di Scienze Cliniche e Biologiche
      Torino, Piedmont, Italy
  • 2007-2008
    • Charles University in Prague
      Praha, Praha, Czech Republic
  • 2005
    • Maastro Clinic
      Maestricht, Limburg, Netherlands