Articles

Algorithms for molecular testing in solid tumours

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

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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Belgian consensus guidelines for prostate core needle biopsy reporting

BJMO - volume 12, issue 6, october 2018

T. Gevaert MD, PhD, L. Libbrecht MD, PhD, E. Lerut MD, PhD, B. Weynand MD, PhD, M. Lammens MD, PhD, S. Verschuere , C. Mattelaer MD, B. Lelie MD, J. Eben , L. Martinez , M-A. van Caillie , S. Rorive MD, PhD, S. Verbeke , M. Baldewijns MD, PhD

The Belgian Working Group on Uropathology has agreed upon a dataset for prostate core needle biopsy reporting, based on existing international guidelines, recent scientific insights, national survey analysis and panel discussion, with the focus on a user- and receptor-friendly format. This dataset should encourage standardised structured reporting of prostate biopsies in the Belgian healthcare system, aiming to improve the quality of individual pathology reports and to provide real benefit for the clinical management of patients and secondary users. Therefore the Belgian Working Group on Uropathology recommends implementing this dataset in each Belgian pathology lab, in close consultation with the entire clinical team involved in the treatment of the prostate cancer patient.

(BELG J MED ONCOL 2018;12(6):279–286)

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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

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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Therapy-orienting testing of EGFR inhibitor-resistant non-small cell lung cancer

BJMO - 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

SUMMARY

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)

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Pathological diagnosis and molecular testing in non-small cell lung cancer: Belgian guidelines

BJMO - 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

Summary

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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Molecular diagnostics on tissue samples obtained through EBUS-TBNA: review on practice guidelines

BJMO - volume 10, issue 1, february 2016

C. Dooms MD, PhD, B. Weynand MD, PhD, S. Vander Borght PhD, L. Vliegen MSc, E. Verbeken MD, PhD, J. Vansteenkiste MD, PhD, P. Vandenberghe MD, PhD

Summary

Endobronchial ultrasonography is a minimally invasive endoscopic technique that enables a real time transbronchial needle aspiration. Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) specimens have a high diagnostic accuracy in the detection of intrathoracic lymph node metastasis for a variety of malignancies. Predictive biomarker testing is gaining wide importance to tailor the treatment with the largest benefit to the patient. Endobronchial ultrasound guided transbronchial needle aspiration also results in an accurate analysis of molecular alterations (by ImmunoHistoChemistry, Fluorescence In Situ Hybridisation, or gene sequencing) provided that the endoscopist takes sufficient tumour samples and a dedicated cytopathologist is involved in the mastery of the specimens.

Endobronchial ultrasound guided transbronchial needle aspiration samples can be handled in different ways. Liquid-based cytology and smears are mostly used. The choice of the testing method should be based primarily on the nature of the sample to be tested, testing laboratory’s expertise, and available equipment. ImmunoHistoChemistry, Fluorescence In Situ Hybridisation and targeted polymerase chain reaction-based sequencing can be performed on >80% of the endobronchial ultrasound guided transbronchial needle aspiration specimens, as the latter is more sensitive in terms of limit of detection than Sanger sequencing. The next step are the next generation sequencing assays, with only 10–20 ng of DNA sample input per gene mutation, which will minimise rejected samples due to insufficient sample quantity.

(BELG J MED ONCOL 2016;10(1):15–20)

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Clinical application of targeted next generation sequencing for lung cancer patients

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

Summary

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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