Articles

Case-based illustrations of clinical flow and practical aspects of DPD-deficiency screening in Belgium

BJMO - volume 16, issue 3, may 2022

L. Crapé MD, K.P. Geboes MD, PhD, V. Casneuf MD, A.G. Verstraete MD, PhD, K.B.M. Claes PhD, M. van den Eynde MD, PhD, I. Borbath MD, PhD, Y. Verheezen MD, W. Demey MD, J. Van der Meulen MD, V. Haufroid PhD

SUMMARY

Fluoropyrimidines are frequently used as anti-cancer treatment for gastro-intestinal malignancies, breast, head and neck cancer and others. The enzyme dihydropyrimidine dehydrogenase (DPD) is crucial in the first and rate limiting enzyme step of 5-fluorouracil (5-FU) catabolism. Reduced or complete deficiency leads to severe and even fatal toxicity. The Belgian Group of Digestive Oncology (BGDO) has agreed upon a recommendation on screening for DPD deficiency before starting treatment, which was endorsed by the Belgian Society of Medical Oncology (BSMO), the College of Genetics (CG), and the Toxicological Society of Belgium and Luxembourg (BLT). This article focuses on the clinical flows and practical recommendations. Both targeted germline genotype testing and phenotyping are supported. It was suggested to use a stepwise approach, with a phenotype testing upfront because of higher sensitivity and lower societal cost. In patients with uracil levels above 14 ng/ mL, targeted germline genotype screening should follow. Fluoropyrimidines are contra-indicated in patients with complete DPD deficiency and starting dose recommendations have been validated for patients with partial deficiency.

(BELG J MED ONCOL 2022;16(3):119–24)

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Genetic and molecular biology in pancreatobiliary cancers: Testing for pancreatobiliary cancer in the context of the Belgian NGS convention

BJMO - 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, PhD, 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

SUMMARY

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)

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Algorithms for molecular testing in solid tumours

BJMO - 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

SUMMARY

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)

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Molecular test algorithms for digestive tumours

BJMO - 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, 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 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 , 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)

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The Belgian next generation sequencing guidelines for haematological and solid tumours

BJMO - volume 11, issue 2, march 2017

Ir 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 MD, 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

SUMMARY

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:

  1. facilitate the implementation of the required quality metrics for the detection of somatic variants by next generation sequencing in oncology and haemato-oncology in the Belgian laboratories,
  2. harmonise test validation and verification,
  3. harmonise clinical interpretation and reporting of variants and,
  4. assure and maintain optimal test performance by establishing procedures and modalities for internal quality control and external quality assessments.

(BELG J MED ONCOL 2017;11(2):56–67)

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