BJMO - volume 16, issue 7, november 2022
S. Verbeke MD, PhD, S. Verschuere MD, PhD, M-D. Martín-Martinez MD, B. Lelie MD, L. Libbrecht MD, PhD, M. Baldewijns MD, PhD, S. Rorive MD, PhD, G. Beniuga MD, J. Eben MD, M-A. van Caillie MD, N. D’Haene MD, PhD, C. Gabriel MD, F. Dedeurwaerdere MD, Ir A. Hébrant PhD, H.L. Gijs , K.B.M. Claes PhD, D. De Maeseneer MD, B. Tombal MD, PhD, P. Pauwels MD, PhD
The recent approval of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) harbouring pathogenic variants of BRCA2 or BRCA1 marks the start of molecularly guided precision medicine in prostate cancer. In parallel with this approval comes the need to embed molecular diagnostics in the clinical management of patients with mCRPC. To date, however, there are no established protocols in Belgium for the use of mutation testing in this setting. This article will therefore provide practical guidance for sample preparation and handling, pre-analytic processing, and pathogenic variant analysis in mCRPC. Across the different phases of this process, a multidisciplinary approach involving urologists, oncologists, radiologists, pathologists, molecular biologists, technicians, nurses, and geneticists will be key to safeguard adequate sample selection to perform molecular analyses at the time of metastatic disease. It will also facilitate high-quality molecular testing with a minimal failure rate. Only by optimising this process will physicians be able to adequately select mCRPC patients that are most likely to benefit from PARP inhibition, or other future targeted therapies, allowing to use these agents in the correct patient groups.
(BELG J MED ONCOL 2022;16(7):343–54)
Read moreBJMO - volume 15, issue 6, october 2021
G. Broeckx MD, Ir A. Hébrant PhD, N. D’Haene MD, PhD, K. Van de Vijver MD, PhD, J. Van Huysse MD, I. Vanden Bempt MD, PhD, P. Aftimos MD, P. Neven MD, PhD, P. Pauwels MD, PhD
The PI3K/AKT pathway plays an important role in the oncogenesis of breast cancer. Activating mutations in PI3K, more specifically in the p110α catalytic unit of the class IA PI3K isoform (encoded by the PIK3CA gene), lead to an increased conversion of phosphatidylinositol-4,5-biphosphate (PIP2) to phosphatidylinositol-3,4,5-triphosphate (PIP3) inducing a cell signalling cascade for cell proliferation and cell survival. PIK3CA mutations are found in 20–32% of all breast cancers (BC), particularly in hormone sensitive (HR+) BC. In breast cancer, activation of the PI3K pathway coexists with the activation of the oestrogen receptor pathway. Inhibition of one of these pathways may lead to compensatory activation of the other pathway. Therefore, mono-therapy with PI3K inhibitors has limited activity in HR+ BC. On the other hand, this explains the efficacy of a PI3K/ER dual blockade. This dual blockade is researched in the phase III SOLAR-1 trial. In the PIK3CA-mutated cohort of this study, there is an improved outcome for patients with advanced or metastatic HR+ HER2- BC, harbouring activating hotspot mutations in PIK3CA and previously treated with an aromatase inhibitor and no more than one line of endocrine therapy for MBC, who received fulvestrant (a selective oestrogen receptor degrader) and alpelisib (a p110α-isoform specific inhibitor) in comparison to the patients that received fulvestrant and placebo. Based on these results, a medical need program for alpelisib in a heavily pre-treated setting and an amendment were approved by the EMA and the Belgian FAMHP. Supporting this data, we propose the mutational analysis of PIK3CA, preferably by next generation sequencing on FFPE tumour material, in advanced or metastatic HR+ HER2- BC, previously treated with three lines of systemic therapy.
(BELG J MED ONCOL 2021;15(6):304-14)
Read moreBJMO - volume 15, issue 4, june 2021
Ir A. Hébrant PhD, H. Antoine-Poirel MD, PhD, K.B.M. Claes PhD, F. Dedeurwaerdere MD, J. Van der Meulen MD, F. Lambert MD, J. Van Huysse MD, G. Martens MD, PhD, N. D’Haene MD, PhD, K. Geboes MD, P. Pauwels MD, PhD, A. Jouret-Mourin MD, PhD, P. Peeters MD, M. van den Eynde MD, PhD, R. Salgado MD, PhD, P-J. Van Dam MD, P. Lefesvre MD, PhD, X. Sagaert MD, S. Metsu PhD, A. Demols MD, PhD, J-L. van Laethem MD, PhD
Pancreatobiliary cancers (PBC) group pancreatic and biliary tract cancers and are among the cancers with the lowest survival rate. Emerging data suggest that novel biomarker-specific targeted therapies can be proposed for selected populations with survival benefit. This review summarises the scientific evidence to test for these biomarkers in order to optimise the management of pancreatobiliary cancers, within the context of the Belgian NGS convention.
(BELG J MED ONCOL 2021;15(4):170-6)
Read moreBJMO - volume 15, issue 3, may 2021
P. Pauwels MD, PhD, G. Broeckx MD, F. Dedeurwaerdere MD, C. Galant MD, Ir A. Hébrant PhD, I. Vanden Bempt MD, PhD, K. Van de Vijver MD, PhD, J. Van Huysse MD, B. Weynand MD, PhD, N. D’Haene MD, PhD
(BELG J MED ONCOL 2021;15(3):112-6)
Read moreBJMO - volume 13, issue 7, november 2019
Ir 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, G. Floris MD, PhD, J. Van der Meulen MD, 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, 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, PhD, 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 1, february 2019
Ir A. Hébrant PhD, Ir , A. Jouret-Mourin MD, PhD, G. Froyen PhD, J. Van der Meulen MD, M. De Man MD, R. Salgado MD, PhD, M. van den Eynde MD, PhD, N. D’Haene MD, PhD, G. Martens MD, PhD, E. van Cutsem MD, PhD, H.A. Poirel MD, PhD, S. Tejpar MD, PhD, J-L. van Laethem MD, PhD, K. Geboes MD, 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 MD, X. Sagaert MD, M. Peeters MD, PhD, P. Vannuffel , P. Lefesvre MD, PhD, J. Vermeij , M. Simoens , T. Van den Mooter MD, N. van Damme PhD, 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 12, issue 5, september 2018
P. Pauwels MD, PhD, M. Remmelink MD, PhD, D. Hoton MD, J. van Dorpe MD, PhD, K. Dhaene MD, PhD, F. Dome MD, A. Jouret-Mourin MD, PhD, B. Weynand MD, PhD, N. D’Haene MD, PhD
In recent years, the outcome of patients with non-small cell lung cancer (NSCLC) has improved thanks to the development of targeted therapies. Currently, the introduction of immunotherapy for lung cancer patients offers new treatment opportunities. The pathologist is now asked to provide the most accurate possible diagnosis in association with theranostic information in order to provide the best therapeutic option. For immunotherapy, programmed death receptor ligand 1 (PD-L1) status is, at the present, the required biomarker for patient stratification, at least in first line treatment. Different international societies have already underlined the importance of guidelines for managing samples of non-small cell lung cancer NSCLC. With the goal of adapting these international recommendations to the Belgian landscape, Belgian guidelines were published in 2016. This update integrates immunotherapy into the previously published guidelines.
(BELG J MED ONCOL 2018;12(5):233–238)
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