Articles

Value of testing for homologous recombination repair deficiency in newly diagnosed advanced-stage epithelial ovarian cancer: Recommendations for Belgian physicians

BJMO - volume 17, issue 2, march 2023

C. Gennigens MD, PhD, H. Denys MD, PhD, S. Altintas MD, PhD, J. Kerger MD, J-F. Baurain MD, PhD, V. Bours MD, PhD, S. Henry MD, K. Van de Vijver MD, PhD, D. Lambrechts PhD, I. Vergote MD, PhD

SUMMARY

Epithelial ovarian cancer (EOC) is the most frequent form of OC, a disease with a poor prognosis and high lethality, as most patients are diagnosed at advanced stages. To successfully battle EOC, it is crucial to identify reliable biomarkers and use personalised therapies in patient subgroups. A common feature of high-grade serous and endometrioid OC is homologous recombination repair deficiency (HRD), which frequently stems from the inactivation of the breast cancer susceptibility (BRCA) genes. Poly-(adenosine diphosphate [ADP])-ribose polymerase inhibitors (PARPi) were, therefore, developed for their lethality against HRD tumour cells. While patients with non-HRD tumours may also benefit from PARPi therapy in the recurrent EOC setting, recent phase III trials on newly diagnosed advanced-stage EOC have shown that PARPi treatment benefit is greater in patients with HRD tumours. These findings open new avenues for the use of PARPi as maintenance therapy in HRD-positive patients who had received first-line chemotherapy. This manuscript provides recommendations for Belgian physicians on how to approach HRD testing and incorporate it into treatment decisions of patients with newly diagnosed advanced-stage EOC.

(BELG J MED ONCOL 2023;17(2):38–45)

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Update to the Belgian follow-up guidelines for abnormal cervical screening results

BJMO - volume 16, issue 2, march 2022

C. Bourgain MD, PhD, B. Weynand MD, PhD, K. Van de Vijver MD, PhD, S. Shahebali MD, PhD

SUMMARY

The Belgian Society for Clinical Cytology elaborated updated guidelines for the follow-up of abnormal cervical cytology results in Belgium, according to a review of the literature and current reimbursement of the screening tests. A proposal for the follow-up in the setting of primary HPV screening for cervical cancer is added.

(BELG J MED ONCOL 2022;16(2):60–9)

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Standard of care in 2021 for patients with ovarian cancer in Belgium

BJMO - volume 15, issue 6, october 2021

I. Vergote MD, PhD, H. Denys MD, PhD, J. De Grève MD, PhD, C. Gennigens MD, PhD, K. Van de Vijver MD, PhD, J. Kerger MD, P. Vuylsteke MD, J-F. Baurain MD, PhD

SUMMARY

Ovarian cancer is often diagnosed at an advanced stage, which is associated with worse survival outcomes and more limited therapeutic options. Over the last years, knowledge regarding the molecular features of ovarian cancer has advanced considerably, enabling the development of several options for diagnosis and treatment in a patient-tailored approach. Identification of homologous recombination deficiency (such as mutations of the BRCA1 and BRCA2 genes, or genomic instability) affecting DNA repair, has become essential in guiding treatment decisions, especially after the development of targeted agents. Therapeutic decisions take into consideration the cancer subtype, its molecular features and disease stage. Fundamental principles of good treatment for women with ovarian cancer include debulking surgery (to reduce the tumour to no residual disease whenever possible), along with appropriate systemic treatment (chemotherapy and targeted agents). To aid Belgian physicians in developing the best individual medical strategies for patients with primary and recurrent ovarian cancer, we present here standard of care applicable in Belgium, that also includes recently developed targeted agents and currently applicable reimbursement criteria.

(BELG J MED ONCOL 2021;15(6):286-91)

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PIK3CA in breast cancer: a Belgian practical testing guideline

BJMO - 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

SUMMARY

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)

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Guidelines for the detection of NTRK fusions. A report from the Belgian Molecular Pathology Working Group

BJMO - 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)

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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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