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 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 12, issue 2, march 2018
P-E. Baugnée , L. Bosquée MD, PhD, C. Compère MD, N. D’Haene MD, PhD, I. Demedts , D. Galdermans , P. Germonpré , M. Gustin , V. Ninane , S. Ocak , P. Pauwels MD, PhD, T. Pieters MD, A. Sadowska MD, A. Sibille MD, V. Surmont MD, PhD, J. Vansteenkiste MD, PhD
The treatment landscape for patients with advanced non-small cell lung cancer, who do not harbour an oncogenic driver abnormality, has changed dramatically over the last years. Second-generation antiangiogenic agents, such as nintedanib and ramucirumab, and particularly PD-1/PD-L1 inhibitors, such as nivolumab, pembrolizumab and atezolizumab have shown to prolong survival in pretreated non-small cell lung cancer patients. Immune checkpoint inhibition in the treatment of advanced non-small cell lung cancer comes with the promise of durable responses in responding patients. Nevertheless, one must appreciate that the average response rate seen with these PD-1/PD-L1 targeting agents is only about 20%. While PD-L1 testing may be used as an enrichment biomarker, a substantial proportion of patients still do not benefit from these agents. They could benefit from alternative therapeutic options, including novel anti-angiogenic agents. In this paper, a treatment algorithm is proposed that aims to optimise the second-line treatment choice for patients with lung adenocarcinoma, based on the available clinical data.
(BELG J MED ONCOL 2018;12(2):61–66)
Read moreBJMO - volume 11, issue 5, september 2017
C. Dooms MD, PhD, B. Colinet MD, I. Demedts , N. D’Haene MD, PhD, V. Ninane , T. Pieters MD, J. Vansteenkiste MD, PhD, B. Weynand MD, PhD, P. Pauwels MD, PhD
Somatic sensitising mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) are detected in approximately 10% of patients with advanced non-squamous non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (EGFR-TKIs) are the first-line treatment option for patients with an actionable EGFR mutation. Despite initial responses, the majority of patients progress within one to two years after EGFR-TKIs treatment initiation.
The most common mechanism of resistance is the development of an additional EGFR-T790M mutation in exon 20, found in 50–60% of EGFR-mutant NSCLC patients who were rebiopsied on EGFR-TKI treatment. Phase II and III trials with osimertinib, a third-generation EGFR-TKI, demonstrated an objective response rate (ORR) of 60–70% and median progression-free survival (mPFS) of 10–11 months in EGFR-T790M-positive tumours.
A tissue biopsy of a progressing lesion for confirmation of histology and molecular characterisation is a critical consideration. However, a repeat tissue biopsy is not possible for every patient. Therefore, a liquid biopsy can be considered for EGFR-T790M mutation testing. Indeed, clinical trials testing osimertinib have shown similar clinical outcomes (ORR and mPFS on osimertinib) in patients with T790M-positive plasma versus T790M-positive tumour tissue.
Osimertinib clearly expands relapse treatment options for advanced stage EGFR-mutant NSCLC. Testing for EGFR-T790M at acquired resistance should become a standard component of patient care in EGFR-mutant tumours. In this manuscript, we propose and discuss two possible clinical diagnostic algorithms that could be used for the therapy-orienting testing of EGFR-TKI-resistant NSCLC patients. Tissue and liquid biopsies involve challenges in terms of specific clinical role, safety, logistics, and cost.
(BELG J MED ONCOL 2017;11(5):226–233)
Read moreBJMO - volume 11, issue 2, march 2017
A. Hébrant PhD, G. Froyen PhD, B. Maes MD, PhD, R. Salgado MD, PhD, M. Le Mercier PhD, N. D’Haene MD, PhD, S. De Keersmaecker PhD, K. Claes PhD, J. Van der Meulen PhD, P. Aftimos MD, J. Van Houdt PhD, K. Cuppens MD, K. Vanneste PhD, E. Dequeker PhD, S. Van Dooren PhD, J. Van Huysse MD, F. Nollet PhD, S. Van Laere PhD, B. Denys MD, V. Ghislain , C. Van Campenhout PhD, M. Van den Bulcke PhD
Targeted next generation sequencing is a complex procedure including the ‘wet bench’ and ‘dry bench’ parts. Both parts are composed of many steps for which optimal assay conditions and settings must be determined.
The aim of these guidelines is to provide generic, platform independent, recommendations for targeted next generation sequencing tests to detect acquired somatic mutations in DNA, in (haemato)-oncology that are complementary to the ISO 15189 norm (medical laboratories) in order to:
(BELG J MED ONCOL 2017;11(2):56–67)
Read moreBJMO - volume 10, issue 4, july 2016
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 management of patients with non-small cell lung cancer has been modified thanks to the development of targeted therapies. The pathologist is now asked to give the most accurate possible diagnosis in association with theranostic information in order to provide the best therapeutic option.
Different international societies have already underlined the importance of guidelines for managing samples of non-small cell lung cancer. These Belgian guidelines have the goal of adapting these international recommendations to the Belgian landscape.
(BELG J MED ONCOL 2016;10(4):123–131)
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BJMO - volume 9, issue 7, december 2015
M. Le Mercier PhD, N. De Nève MSc, O. Blanchard MSc, M. Remmelink MD, PhD, B. Weynand MD, PhD, I. Salmon MD, PhD, N. D’Haene MD, PhD
The successes of targeted agents in patients with molecularly defined tumours and improvements in genomic technology have generated enthusiasm for incorporating genomic profiling into clinical cancer practice and molecular testing has now become a standard of care for lung cancer. International guidelines recommend testing for EGFR mutations and ALK gene rearrangement to guide patient selection for therapy. However, different potentially targetable oncogenes, such as KRAS, PIK3CA, BRAF, ERBB2 or MET, for which agents are being evaluated, have been proposed as valuable for managing patients with lung cancer. Recently, the development of next generation sequencing has enabled simultaneous detection of many clinically relevant mutations in different genes in a single test. In this study, we have evaluated the clinical utility of targeted next generation sequencing, using a 22 genes panel, for patients with lung cancer on 234 samples, including cytology, biopsies and surgical resections, from two different institutions tested in routine daily practice since validation and accreditation of the method (BELAC ISO15189). On the 234 samples tested, only one case could not be sequenced due to an insufficient quantity of available tissue. Among the 233 cases tested, 223 (95.7%) samples were sequenced successfully. The median turnaround time between reception of the sample in the laboratory and report release was one week. The most frequent mutations were found in TP53 (42.1%) and KRAS (35.9%). Of successfully sequenced cases, 137 potentially actionable mutations were identified in 130 patients (58.3%), including 80 KRAS mutations, 26 EGFR mutations, fourteen BRAF mutations, eight PIK3CA mutations, three PTEN mutations, two ERBB2 insertions, two NRAS mutations and two MAP2K1 mutations. Overall, next generation sequencing can be applied in daily practice even for small samples, such as lung biopsies or cell blocks. Moreover, it provides clinically relevant information for lung cancer patients.
(BELG J MED ONCOL 2015;9(7):272–78)
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