BJMO - volume 15, issue 6, october 2021
L. Decoster MD, PhD
The identification of clinically relevant driver mutations has reshaped the therapeutic landscape of non-small cell lung cancer (NSCLC). In the past year, the activation of the mesenchymal-to-epithelial transition (MET) pathway has gained importance because of the recent development of selective and effective MET inhibitors. In NSCLC, MET dysregulation may be caused either by mutation or amplification and is associated with poor prognosis. In addition, the optimal first-line treatment is currently undetermined since data from different trials suggest limited activity of immune checkpoint inhibitors, indicating a high medical need. In phase II trials, MET inhibitors have shown promising response rates (41–65%) and duration of response in MET exon 14 mutated NSCLC. First-line trials are currently ongoing. In de novo MET amplified NSCLC, the activity of these inhibitors seems limited to tumours with a high level amplification. As in other oncogene driven NSCLC, resistance mechanisms do appear ultimately and future research should focus on this in order to optimise treatment options for MET dysregulated NSCLC.
(BELG J MED ONCOL 2021;15(6):278-82)
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D. Schrijvers MD, PhD, W. Teurfs MD, S. Van Wambeke MD
BRCA mutations play an important role in prostate cancer. All patients with high-risk localised or metastatic prostate cancer should be tested for somatic mutations and, if present, for germline mutations. BRCA muta-tions translate in a more aggressive prostate cancer with a worse prognosis. If these mutations are present, PARP inhibitors may be part of the treatment strategy.
(BELG J MED ONCOL 2021;15(6):283-5)
Read moreBJMO - 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
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)
Read moreBJMO - volume 15, issue 4, june 2021
R. de Putter MD, B. De Laere PhD, P. Ost MD, PhD, K.B.M. Claes PhD
Mutations in DNA damage repair (DDR) genes are relatively common in prostate cancer (PC), and may guide therapy selection. Approximately half of somatic DDR mutations are also present in the germline and lead to a heritable cancer predisposition syndrome (CPS), which informs on future risk, prostate cancer prognosis, and therapeutic options. In germline carriers, genetic counselling is essential to help psychosocial coping and to provide pre-symptomatic testing in relatives, who upon carrier identification can opt for intensified surveillance or – in some cases – prophylactic surgery.
(BELG J MED ONCOL 2021;15(4):156-63)
Read moreBJMO - volume 15, issue 4, june 2021
L. Dirix MD
Deoxyribonucleic acid (DNA) recombination between homologous chromosomes is essential in the process of meiosis as it drives genetic diversity and assures accurate segregation. In somatic cells, a substantial machinery is involved in DNA damage repair (DDR). Failure to repair DNA damage has many consequences, including cancer predisposition. Insights in DDR mechanisms and the prevalence of defects in DDR in tumours has resulted in the fundamental insight of the presence of DDR defects as a chemosensitising biomarker for alkylating agents in high-grade serous ovarian cancer, non-small-cell lung cancer and glioblastoma. Increasing the DDR defect by PARP inhibition in this context of pre-existing DDR impairment, can result in catastrophic DNA damage and cancer cell death. In patients with mCRPC and demonstrated intratumoural DDR defect, PARP inhibition represents a valuable new treatment option.
(BELG J MED ONCOL 2021;15(4):164-9)
Read moreBJMO - 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, 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, PhD, S. Metsu PhD, A. Demols MD, PhD, J-L. van Laethem MD, PhD
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)
Read moreBJMO - volume 15, issue 3, may 2021
A. Iabkriman MD, J. Collignon MD, F.P. Duhoux MD, PhD
The phosphatidylinositol-3-kinases (PI3Ks) play a critical role in cellular metabolism and proliferation, as well as in the development of cancer. Several mutations in the genes coding for PI3Ks have been identified in a large proportion of tumours at different rates, depending on the tumour type. Therapies targeting PI3Ks have been developed in the last years and initially used in hematological malignancies. In medical oncology, a number of trials have tried to prove the efficacy of these compounds, but most of them have been confronted with very important toxicities and only a modest benefit in progression-free survival. Recent trials using more selective treatments have shown good efficacy with an acceptable toxicity profile. The aim of this article is to review the current knowledge about PI3K inhibitors, their potential use in medical oncology and their toxicities.
(BELG J MED ONCOL 2021;15(3):96-103)
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