BJMO - volume 13, issue 7, november 2019
A. Hébrant PhD, M. Lammens MD, PhD, C. Van den Broecke MD, N. D’Haene MD, PhD, J. Van den Oord MD, PhD, A. Vanderstichele MD, PhD, A. Dendooven MD, PhD, P. Neven MD, PhD, K. Punie MD, PhD, G. Floris MD, PhD, J. Van der Meulen PhD, HA. Poirel MD, PhD, C. Dooms MD, PhD, S. Rottey MD, PhD, T. Boterberg MD, PhD, L. Brochez MD, PhD, M.C. Burlacu MD, G. Costante MD, D. Creytens MD, PhD, P. De Paepe MD, PhD, R. De Pauwn MD, B. Decallonne MD, PhD, F. Dedeurwaerdere MD, H. Denys MD, PhD, L. Ferdinande MD, PhD, R. Forsyth MD, PhD, M. Garmyn MD, PhD, T. Gevaert MD, PhD, J. De Grève MD, PhD, E. Govaerts MD, E. Hauben MD, PhD, J. Kerger MD, PhD, O. Kholmanskikh Van Criekingen MD, PhD, V. Kruse MD, PhD, Y. Lalami MD, L. Lapeire MD, PhD, P. Lefesvre MD, PhD, J.P. Machiels MD, PhD, B. Maes MD, PhD, G. Martens MD, PhD, M. Remmelink MD, PhD, I. Salmon MD, PhD, R. Sciot MD, PhD, S. Tejpar MD, PhD, K. Van de Vijver MD, PhD, L. Van de Voorde MD, I. Van den Berghe MD, A. Van den Bruel MD, K. Vandecasteele MD, PhD, L. Vanwalleghem MD, K. Vermaelen MD, PhD, R. Salgado MD, PhD, E. Wauters MD, B. Weynand MD, PhD, E. Van Valckenborgh PhD, G. Raicevic PhD, M. Van den Bulcke PhD, P. Pauwels MD, PhD
In order to advise the Federal Government on the reimbursement of molecular tests related to Personalised Medicine in Oncology, the Commission of Personalised Medicine (ComPerMed), represented by Belgian experts, has developed a methodology to classify molecular testing in oncology. The different molecular tests per cancer type are represented in algorithms and are annotated with a test level reflecting their relevance based on current guidelines, drug approvals and clinical data. The molecular tests are documented with recent literature, guidelines and a brief technical description. This methodology was applied on different solid tumours for which molecular testing is a clear clinical need.
(BELG J MED ONCOL 2019;13(7):286–95)
Read moreBJMO - volume 13, issue 2, march 2019
A. Hébrant PhD, K. Punie MD, PhD, F.P. Duhoux MD, PhD, C. Colpaert MD, PhD, G. Floris MD, PhD, K. Lambein MD, PhD, P. Neven MD, PhD, M. Berlière MD, PhD, R. Salgado MD, PhD, M. Chintinne MD, PhD, K. Dahan MD, PhD, S. Dedeurwaerdere MD, J. De Grève MD, PhD, A. de Leener MD, PhD, H. Denys MD, PhD, R. de Putter MD, PhD, L. Desmyter PhD, M. Baldewijns MD, PhD, D. Feret MD, C. Fontaine MD, C. Galant MD, PhD, P. Hilbert PhD, J. Janssens MD, PhD, D. Larsimont MD, PhD, P. Lefesvre MD, PhD, T. Sticca PhD, M-D. Tkint de Roodenbeke MD, G. Van Den Eynden MD, PhD, I. Vanden Bempt PhD, C. Van den Broecke MD, I. Vandernoot MD, C. Sotiriou MD, PhD, J. van Dorpe MD, PhD, H.A. Poirel MD, PhD, E. Van Valckenborgh PhD, G. Raicevic PhD, M. Van den Bulcke PhD, P. Aftimos MD
In order to advise the Federal Government on all matters related to personalised medicine in oncology, including the reimbursement of molecular tests, the Commission of Personalized Medicine (ComPerMed) has applied, for the breast tumours, the same methodology as previously applied for the digestive tumours. Meaning, the different molecular tests, represented in the shape of algorithms, are annotated with test levels — which aim to reflect their relevance based on current available data and to define the reimbursement — and are documented with recent literature, guidelines and a brief technical description.
(BELG J MED ONCOL 2019;13(2):40–45)
Read moreBJMO - volume 13, issue 9, february 2019
T. Feys MBA, MSc, J. De Grève MD, PhD
Chimeric antigen receptor (CAR) T-cell therapy is a new cancer immunotherapy targeting specific cell surface antigens. This type of adoptive cell immunotherapy has been a breakthrough in the treatment of aggressive B-cell lymphoma and B-cell precursor acute lymphoblastic leukaemia (ALL) and is currently being studied in other cancer types, including multiple myeloma and chronic lymphocytic leukaemia. With the unprecedented success of CAR T cells in haematological malignancies, a growing number of (pre)clinical studies are focusing on translating this treatment to solid tumours. However, response rates to CAR T-cell therapy have so far been much less favourable in non-haematologic malignancies, mainly due to a paucity of unique tumour target antigens, limited CAR T-cell trafficking to tumour sites, tumour heterogeneity, antigen loss, the presence of an immune suppressive tumour microenvironment and recognition of normal cells expressing the targeted antigen. A broad range of strategies is currently being explored to overcome these hurdles. For example, TCR-CAR-T hybrids have been developed that can also target intracellular antigens which broadens the potential scope of the CAR-T cell strategy. This article reviews completed and ongoing CAR T-cell trials in solid tumours and discusses the strategies to improve the efficacy of this treatment modality in solid tumours, including accelerated production flows. CAR-T’s might very well be the upcoming major advance in cancer treatment.
Read moreBJMO - volume 13, issue 1, february 2019
A. Hébrant PhD, Ir , A. Jouret-Mourin MD, PhD, G. Froyen PhD, J. Van der Meulen PhD, M. De Man MD, R. Salgado MD, PhD, M. van den Eynde , N. D’Haene MD, PhD, G. Martens MD, PhD, E. van Cutsem , H.A. Poirel MD, PhD, S. Tejpar MD, PhD, J.L. van Laethem MD, PhD, K. Geboes MD, PhD, P. Pauwels MD, PhD, F. Dedeurwaerdere MD, B. Maes MD, PhD, J. De Grève MD, PhD, J. Vanhuysse , P. Peeters MD, L. Vanacker MD, M. Gomez-Galdon , M. Chintinne MD, PhD, A. Hendlisz MD, PhD, G. de Hertogh , X. Sagaert MD, PhD, M. Peeters MD, PhD, P. Vannuffel , P. Lefesvre MD, PhD, J. Vermeij , M. Simoens , T. Van den Mooter MD, N. van Damme , M. Van den Bulcke PhD
The Belgian Commission of Personalized Medicine has been created to advise the federal government on all matters related to personalised medicine in oncology, including the reimbursement of molecular tests. Here, we propose the Belgian strategy for molecular testing in the digestive tumours within a scientific-based framework. For each tested biomarker, a clinical test level is attached, which is key to establish the relevance of the test and to define the reimbursement. For each digestive tumour type, the different molecular tests are represented as decision trees with its test utility, test level and a brief technical test description.
(BELG J MED ONCOL 2019;13(1):4–10)
Read moreBJMO - volume 13, issue 1, february 2019
A. Noeparast PhD, I. Umelo , E. Teugels PhD, J. De Grève MD, PhD
In three sequential studies, we pre-clinically investigated several previously unexplored lung cancer-derived BRAF mutations as well as a HER3 mutation and their response to clinically available targeted therapeutics. During the FIELT I clinical study at UZ Brussel, in which 229 non-small-cell lung carcinoma patients were prospectively investigated at the genomic level, twelve patients (5.2%) were identified to harbour a BRAF mutation in their tumour and one patient found to harbour a novel HER3 mutation. As opposed to melanoma, 75% of these non-small-cell lung carcinoma-derived BRAF mutations were non-V600. RAF inhibitors have only been clinically developed against BRAF V600 mutations because of concerns of paradoxical effect in non-V600 mutant cancers. The status of non-V600 mutations with regards to BRAF inhibition effects was unknown. We functionally analysed thirteen of such tumour-derived BRAF non-V600 mutations and demonstrated that all types of BRAF mutations cause pathway activation and are sensitive to clinically relevant doses of a combination of type I RAF-inhibitor (dabrafenib) and that paradoxical pathway activation is abrogated by MEK-inhibition (trametinib). This entails that dual inhibition of non-V600 mutations is effective and safe. Further, we investigated the comparative efficacy of two modes of RAF inhibition (type I vs type II) in suppressing mutant BRAF-induced ERK signalling. Our preclinical findings in non-V600 BRAF expressing cellular models suggest that the type II RAF-inhibition (AZ628) has more potential than the type I RAF-inhibition (dabrafenib), both as single agent and combined with MEK inhibition in suppressing the ERK pathway independent of the BRAF mutation type. We also explored a novel somatic lung cancer-derived V855 HER3 mutation. Our study provided evidence for oncogenicity of V855 HER3 in a HER2 and ligand-dependent manner, in murine and human cell lines. Further, we showed that the given V855A HER3 mutation predicts sensitivity to the clinically available HER-targeting therapeutic afatinib. Our findings support the clinical investigation of non-V600 BRAF mutated lung or other cancers with dual RAF and MEK inhibition and HER3 mutant cancers with afatinib.
(BELG J MED ONCOL 2019;13(1):31–34)
Read moreBJMO - 12, issue 3, february 2018
A. Noeparast PhD, J. De Grève MD, PhD, S. De Brakeleer PhD, P. Giron , C. Eggermont , R.B. Shahi MSc, E. Teugels PhD
BJMO - 12, issue 3, february 2018
P. Giron , C. Eggermont , E. Teugels PhD, G. Gutierrez , J. De Grève MD, PhD
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