286 Algorithms for molecular testing in solid tumours A. Hébrant, Ir, PhD1, M. Lammens, MD, PhD2, C. Van den Broecke, MD3, N. D’Haene, MD, PhD4, J. Van den Oord, MD, PhD5, A. Vanderstichele, MD, PhD6, A. Dendooven, MD, PhD7,8, P. Neven, MD, PhD6,9, K. Punie, MD, PhD10, G. Floris, MD, PhD7,11,12, J. Van der Meulen, Ir, PhD13, HA. Poirel, MD, PhD14, C. Dooms, MD, PhD15, S. Rottey, MD, PhD16, T. Boterberg, MD, PhD17, L. Brochez, MD, PhD18, MC. Burlacu, MD19, G. Costante, MD20, D. Creytens, MD, PhD8,21, P. De Paepe, MD, PhD22, R. De Pauwn, MD23, B. Decallonne, MD, PhD24, F. Dedeurwaerdere, MD25, H. Denys, MD, PhD16, L. Ferdinande, MD, PhD8,21, R. Forsyth, MD, PhD26, M. Garmyn, MD, PhD27, T. Gevaert, MD, PhD28,29, J. De Greve, MD, PhD30, E. Govaerts, MD31, E. Hauben, MD, PhD5,11, J. Kerger, MD32, O. Kholmanskikh Van Criekingen, MD, PhD33, V. Kruse, MD, PhD16, Y. Lalami, MD32, L. Lapeire, MD, PhD16,21, P. Lefesvre, MD, PhD34, JP. Machiels, MD, PhD35, B. Maes, MD, PhD36, G. Martens, MD, PhD37, M. Remmelink, MD, PhD4, I. Salmon, MD, PhD4, R. Sciot, MD, PhD11, S. Tejpar, MD, PhD38, K. Van de Vijver, MD, PhD8,21, L. Van de Voorde, MD39, I. Van den Berghe, MD22, A. Van den Bruel, MD40, K. Vandecasteele, MD, PhD17,21, L. Vanwalleghem, MD22, K. Vermaelen, MD, PhD41, R. Salgado, MD, PhD42, E. Wauters, MD, PhD15, B. Weynand, MD, PhD5, E. Van Valckenborgh, PhD1, G. Raicevic, PhD1, M. Van den Bulcke, PhD1, P. Pauwels, MD, PhD2 1Cancer Centre, Sciensano, Brussels, 2Department of Pathology, Antwerp University Hospital, and Centre for Oncological Research (CORE), University of Antwerp, Antwerp, 3Department of Pathology, AZ Sint-Lucas Ghent, Ghent, 4Department of Pathology, Hôpital Erasme - Université Libre de Bruxelles (ULB), Brussels, 5Department of Pathology, KU Leuven- University Hospitals Leuven, Leuven, Belgium, 6Department of Oncology, KU Leuven, Leuven, 7Department of Pathology, UZ Antwerp; MIPRO/LEMP, University of Antwerp, Antwerp, 8Department of Pathology, UZ Gent, Ghent, 9Department of Gynecology and Obstetrics, University Hospitals Leuven, Leuven, 10Department of General Medical Oncology. University Hospitals Leuven, 11Department of Imaging and Pathology, KU Leuven- University of Leuven, Leuven, 12Laboratory of Translational Cell & Tissue Research, Leuven, 13Molecular Diagnostics Ghent University Hospital (MDG), Ghent University Hospital, Ghent, 14Belgian Cancer Registry, Brussels, 15Department of Respiratory Diseases and Respiratory Oncology Unit, KU Leuven, Leuven, 16Department of Medical Oncology, Ghent University Hospital, Ghent, 17Department of Radiation Oncology, Ghent University Hospital, Ghent, 18Dermatology University Hospital Ghent, Cancer Research Institute Ghent (CRIG), Ghent, 19Department of Endocrinology, Cliniques Universitaires St-Luc, Brussels, 20Endocrinology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, 21Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, 22Department of Pathology, AZ Sint-Jan Brugge-Oostende, 23Department of Pulmonology, AZ Sint-Jan Brugge-Oostende, 24Department of Endocrinology, University Hospitals Leuven, 25Department of Pathology, AZ Delta, Roeselare, 26Department of Pathology, University Hospital Brussels and Experimental Pathology, Vrije Universiteit Brussel, Brussels, 27Department of Dermatology, University Hospitals Leuven, Leuven, 28Organs Systems, KU Leuven, Leuven, 29Department of Pathology, AZ Klina, Brasschaat, 30Department of Medical Oncology, Oncologisch Centrum, UZ Brussel, Vrije Universiteit Brussel, Brussels, 31Department of pneumology, AZ Sint-Lucas Hospital, Ghent, 32Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, 33Federal Agency for Medicines and Health Products, Brussels, 34Department of Anatomic Pathology, UZ Brussel, Brussels, 35Department of medical oncology, Cliniques universitaires Saint-Luc, Brussels, 36Department of Clinical Biology, Jessa Hospital, Hasselt, 37Department of Laboratory Medicine, AZ Delta, Roeselare, 38Molecular Digestive Oncology, Kuleuven, Leuven, 39Department of Radiation Oncology, AZ Sint-Lucas, Ghent, 40Department of Internal Medicine, Endocrinology, AZ Sint Jan Brugge- Oostende, 41Departement of Pulmonary Medicine, Ghent University Hospital, Ghent, 42Department of Pathology GZA-ZNA, Antwerp. Please send all correspondence to: A. Hébrant, Ir, PhD, Rue Juliette Wytsman 14, 1050 Brussels, Belgium, tel: +32 2 642 57 32, email: aline. [email protected]. Conflict of interest: K. Punie declares to receive honoraria for consulting/advisory from Astra Zeneca, Novartis, Pfizer, Roche and Vifor Pharma as well as speaker fees from Novartis and Pfizer. Honoraria and fees were paid to the institution. Keywords: brain cancer, endometrium cancer, head and neck cancer, lung cancer, melanoma, molecular tests, NGS, oncology, ovarian cancer, soft tissue tumours, thyroid tumours. Acknowledgements: The authors would like to acknowledge all the ComPerMed experts. VOLUME13NOVEMBER2019 PRACTICE GUIDELINES 287 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 rele- vance 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) INTRODUCTION type, the corresponding working group of the ComPerMed The clinical management of patients with cancer has become (Table 1) started with a systematic evaluation of all molecular more challenging with the advent of numerous innovative tests currently performed in clinical routine in Belgium, tak- molecular tests giving the opportunity to the care givers to ing into account their test utility (diagnostic, prognostic or tailor the patient’s management by fine-tuning the diagno- therapeutic), and then assigned, for each of them, a test lev- sis or by predicting the resistance or response to a thera- el. Three test levels (Table 2) were defined, with level 1 rep- py. In addition, test results may also provide information resenting the highest priority of implementation of the test on prognosis. by the policy makers. These test levels are assigned based on In order to advise the Federal Government on the reimburse- their use in clinical guidelines, expert opinions and on reim- ment of molecular tests related to Personalised Medicine in bursement rules for drugs in Belgium. This test level scale al- Oncology, the Belgian Commission of Personalised Medi- lows easy implementation of common biomarker testing into cine (ComPerMed) was created in 2016. This commission clinical practice. Furthermore, it facilitates the development includes representatives of all professional organisations di- of reimbursement criteria. rectly involved in personalised medicine, including experts In this paper, the methodology has been applied for lung, from the College of Genetics, the College of Oncology, the melanoma, brain, endometrium, ovarian, head and neck, soft Commission of Anatomic Pathology, the Commission of tissue, and thyroid tumours. Clinical Biology and different working groups with Belgian oncologists, haematologists, pathologists, clinical biologists, ALGORITHMS geneticists and other scientists. The ComPerMed is organised To design the molecular test algorithms, only tests with a lev- in different working groups according to the tumour type. el of 1 or 2A were retained. However, some tests with level 2B The ComPerMed advises the Platform Companion Diagnos- were also added to the algorithm if the expert group estimat- tics (CDx platform) from the Belgian reimbursement agency ed that they will become a test level 1 or 2A in the near future. National Institute for Health and Disability Insurance (NIH- For lung, melanoma, brain, endometrium, ovarian, head and DI) or RIZIV/INAMI on decision making related to the reim- neck, soft tissue and thyroid tumours, the different molecu- bursement of diagnostic tests in personalised medicine. The lar tests used in Belgium are sequentially represented in the CDx platform, launched in January 2016, aims to evaluate shape of algorithms (Figures 1-8). These algorithms are pub- the reimbursement of a molecular test and the correspond- lished on the ComPerMed website www.compermed.be/ with ing patient management in personalised medicine. additional information, such as tumour incidence (provid- The ComPerMed has set up a methodology in order to sys- ed by the Belgian Cancer Registry), and, for each molecular tematically evaluate and prioritise, for different tumour types, test, its utility (diagnostic, prognostic or therapeutic utility), the molecular tests currently performed in Belgium in clini- its corresponding test level and a brief technical test descrip- cal routine or in research phase.1 tion. In case of next generation sequencing (NGS) testing, the genes and regions that have to be analysed at minimum are METHODOLOGY also described. These algorithms will be reviewed annual- The methodology has been previously described and applied ly. Additional updates of the gene tests are possible when re- for digestive and breast