Articles

Tumour mutational burden: a review

BJMO - volume 14, issue 1, january 2020

J. Brauns MD, P. Pauwels MD, PhD

SUMMARY

Immunotherapeutics, like immune checkpoint blockade (ICB), have demonstrated therapeutic efficacy in a variety of human cancers. Even among the tumour types described as responsive, immunotherapy is only efficient in a minority of the patients. To maximise therapeutic benefits, a biomarker to identify ICB-responders is needed. Tumour mutational burden would correlate with the efficacy of immune checkpoint inhibitors. Clinical evidence for TMB as biomarker already exists in metastatic melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). In this review an update about tumour mutational burden (TMB) is given.

(BELG J MED ONCOL 2020;14(1):4–7)

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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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Unravelling the immunotherapeutic potential of CD70 as a target in solid malignancies

BJMO - volume 13, issue 2, march 2019

J. Jacobs PhD, T. Flieswasser MSc, F. Lardon PhD, E. Smits PhD, P. Pauwels MD, PhD

SUMMARY

Under normal conditions, CD70, member of the tumour necrosis factor family, is only transiently expressed on activated T and B cells. Instead, constitutive expression of CD70 has been described on malignant cells in a range of solid and haematological malignancies. Through its receptor, CD27, the expression of CD70 can facilitate evasion of the immune system by three important mechanisms: induction of T cell apoptosis, T cell exhaustion and increasing the amount of suppressive regulatory T cells. The general aim of this thesis was to investigate the role of CD70 in solid tumour types and explore promising combination strategies for anti-CD70 therapy. Thereby, we focused on the role of CD70 in non-small cell lung cancer and colorectal cancer.

(BELG J MED ONCOL 2019;13(2):54–59)

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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 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)

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PD-L1 Testing for Non-Small Cell Lung Cancer: Belgian Guidelines

BJMO - 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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How to overcome resistance to epidermal growth factor receptor tyrosine kinase inhibitors in patients with advanced epidermal growth factor receptor mutated non-small-cell lung cancer?

BJMO - volume 12, issue 2, march 2018

J. Raskin , B.I. Hiddinga MD, A. Janssens MD, PhD, P. Pauwels MD, PhD, J.P. Van Meerbeeck MD, PhD

Summary

Targeted therapies have transformed the management of non–small-cell lung cancer and placed an increased emphasis on stratifying patients on the basis of the presence of oncogenic drivers. The best characterised molecular driver to date is epidermal growth factor receptor. Selective oral inhibitors of epidermal growth factor receptor that are superior to chemotherapy have become available in clinical practice. Unfortunately progression develops after a median of ten to twelve months. This article provides a framework for understanding clinically relevant resistance mechanisms to epidermal growth factor receptor-tyrosine kinase inhibitors and strategies to delay or overcome resistance, both those clinically available and those in development.

(BELG J MED ONCOL 2018;12(2):68–74)

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Second-line treatment of non-small cell lung cancer adenocarcinoma patients not harbouring an oncogene driver mutation anno 2017–2018: A consensus group meeting

BJMO - volume 12, issue 2, march 2018

P-E. Baugnée , L. Bosquée MD, PhD, C. Compère MD, N. D’Haene MD, PhD, I. Demedts MD, PhD, D. Galdermans MD, P. Germonpré , M. Gustin , V. Ninane MD, PhD, S. Ocak , P. Pauwels MD, PhD, T. Pieters MD, PhD, A. Sadowska MD, A. Sibille MD, V. Surmont MD, PhD, J. Vansteenkiste MD, PhD

Summary

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)

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