BJMO - volume 17, issue 6, october 2023
M. Piccart MD, PhD, J. Vansteenkiste MD, PhD, H. Prenen MD, PhD, F. Duhoux MD, PhD, A. Janssens MD, PhD, M. Delforge MD, PhD, A. Awada MD, PhD, P. Neven MD, PhD, A. Sibille MD, B. Neyns MD, PhD
The oncological treatment landscape is evolving at a very rapid pace with a continuous stream of novel treatment options. To fully leverage these therapeutic advances in clinical practice it is important to facilitate a rapid access to innovative anticancer drugs for patients. Specifically for Belgium, the delay from EMA approval to reimbursement for anticancer drugs is very long, with an average of almost 600 days, and a substantial proportion of innovative drugs never make it to the patient. The stringent focus of the Belgian Commission for Reimbursement of Medicines (CRM) on overall survival (OS) data in reimbursement decisions is believed to be an important contributor to this situation. However, the ever-increasing pace at which new anticancer therapies are being developed in combination with an earlier detection of cancer will make it increasingly difficult to present mature OS data at the time of regulatory approval in the years to come. As such, there is an urgent need for a debate with the regulators to consider more readily available endpoints in their reimbursement assessments. In fact, when a strong treatment effect is seen on an intermediate endpoint such as disease-free or progression-free survival, a benefit in OS is quite likely. As such, our reimbursement system needs to be adapted to better align with the scientific progress in oncology. In this, a temporary reimbursement decision based on intermediate endpoints could give Belgian patients earlier access to promising lifesaving medicines. In this, we as oncologists, including specialists in haematology, respiratory oncology, and gastrointestinal cancer, strongly encourage the CRM to use the grading provided by the ESMO magnitude of clinical benefit scale to evaluate the clinical added value of future cancer treatments. This will not only facilitate a faster patient access to innovative therapies, but will also help policy-makers in advancing ‘accountability for reasonableness’ in their resource allocation deliberations.
(BELG J MED ONCOL 2023;17(6):211–5)
Read moreBJMO - volume 17, issue 6, october 2023
M. Machiels MD, PhD, R. Oulkadi MD, T. Tramm MD, PhD, S.R. Stecklein MD, PhD, N. Somaiah MD, PhD, A. De Caluwé MD, J. Klein MD, PhD, W.T. Tran MD, PhD, R. Salgado MD, PhD
Radiation therapy (RT) has long been fundamental for the curative treatment of breast cancer. While substantial progress has been made in the anatomical and technological precision of RT delivery, and some approaches to de-escalate or omit RT based on clinic-pathologic features have been successful, there remain substantial opportunities to refine individualised RT based on tumour biology. A major area of clinical and research interest is to ascertain the individualised risk of loco-regional recurrence to direct treatment decisions regarding escalation and de-escalation of RT. Patient-tailored treatment with RT is considerably lagging behind compared with the massive progress made in the field of personalised medicine that currently mainly applies to decisions on the use of systemic therapy or targeted agents.
Herein we review select literature surrounding the use of tumour genomic biomarkers and biomarkers of the immune system, including tumour-infiltrating lymphocytes (TILs), within the management of breast cancer, specifically as they relate to progress in moving toward analytically validated and clinically tested biomarkers utilised in RT.
(Belg J Med Oncol 2023;17(6):216–29)
Read moreBJMO - volume 17, issue 4, june 2023
L. Hendrickx MD, L. Van Mileghem MD, P. Vermeulen MD, L. Dirix MD
Cancer is a leading cause of morbidity and mortality worldwide. The process of metastasis involves many steps, with circulating tumour cells (CTCs) playing an essential role. This literature review examines the role of neutrophil extracellular traps (NETs) in the survival and implantation of CTCs in secondary organs. CTCs get to secondary organs primarily through the bloodstream and can then extravasate into the parenchyma of these organs. NETs are formed by various stimuli, including cancer. They can occur in primary tumours, but are most commonly present in metastatic tumour sites. They make the blood vessels of both primary organs and secondary organs more permeable, allowing CTCs to enter the bloodstream and extravasate from the bloodstream into the secondary organs, respectively. NETs also protect CTCs from degradation by the immune system and can trap CTCs in the microvasculature of secondary organs, allowing CTCs to be more numerous in the vasculature before entering these organs. This contributes to the formation of micrometastases and, subsequently, macrometastases. It also appears that this metastatic cascade is more easily initiated after surgery of the primary tumour, due to an increase in inflammation and, thus, increased formation of NETs. NETs can also awaken dormant tumour cells, which promotes metastasis as well. In short, NETs play an important role in the different stages of the life cycle of CTCs. Treatments against NETs may, therefore, offer important advances in fighting cancer.
(BELG J MED ONCOL 2023;17(4):112–7)
Read moreBJMO - volume 17, issue 3, may 2023
L. Van Mileghem MD, L. Hendrickx MD, W. Seuntjens MD, P. Vermeulen MD, L. Dirix MD
The main cause of death in patients with breast cancer is the spread and outgrowth of tumour cells at distant sites. The presence of disseminated tumour cells (DTCs) in the bone marrow at diagnosis is a predictor for metastasis. This is an updated analysis of a prospective study in 100 patients with operable breast cancer on the long term-significance of bone marrow micrometastasis. The follow-up time ranges between one and 242 months, with a mean of 131 months and a median of 141 months. Bone marrow aspirates were analysed for the presence of DTCs by real-time polymerase chain reaction (RT-PCR) for cytokeratin 19 (CK19) and mammaglobin (MAM), as well as immunocytochemistry (ICC) for cytokeratin (CK). The aim of this study was to confirm the association between DTCs and disease-specific survival (DSS), as well as distant metastasis-free survival (DMFS).
CK19 positivity did not reach statistical significance for DSS (p=0.065) or DMFS (p=0.233). However, MAM positivity was significantly prognostic for DSS (HR: 5.583, p<0.001), but only borderline trending for DMFS (p=0.064). The combination of CK19 and MAM positivity, however, did confer a significantly increased risk for both DSS (HR: 3.073, p=0.003) and DMFS (HR: 3.150, p=0.023). ICC CK positivity significantly predicted DSS (HR: 3.868, p=0.040) or DMFS (HR: 3.868, p=0.040) when using a cut-off of ≥1 DTC. Stratifying the quantitative data also gave a significant result for DSS and DMFS (OR: 2.974, p=0.008). Combining both detection measurements using a cut-off of ≥1 DTC in immunochemical detection showed a significant association with DSS (HR: 3.213, p=0.089) and DMFS (HR: 4.984, p=0.015). Three negative parameters significantly predicted DSS (HR: 0.368, p= 0.017), but not DMFS. There was no statistically significant association of DTCs with organ-specific metastasis. This study supports the role of DTCs as a negative, prognostic factor in patients with operable breast cancer. The combination of multiple DTCs could be useful in identifying this increased risk.
(BELG J MED ONCOL 2023;17(3):71–84)
Read moreBJMO - 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
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)
Read moreBJMO - volume 17, issue 2, march 2023
C. Isnard-Bagnis MD, PhD, J. Nortier MD, PhD, C. Vulsteke MD, PhD, C. Hermans MD, PhD, S. Treille De Grandsaigne MD, P. Clement MD, PhD, A. Awada MD, PhD
Chronic kidney disease (CKD) and cancer are intertwined in many ways. In fact, cancer can cause CKD either directly or indirectly through the treatment adverse effects, while CKD may conversely be a risk factor for cancer. According to the Belgian Renal Insufficiency and Anticancer Medications (BIRMA) study, 64% of patients with cancer had a glomerular filtration rate (GFR) <90 ml/min/1.73m2 and 16% of them presented with a mildly to severely decreased GFR (i.e.; <30 ml/min/1.73m2 or 30–60 ml/min/1.73m2). As many anticancer drugs are predominantly excreted in the urine, tailoring the drug dose to the renal function of the individual patient is a crucial consideration. Furthermore, patients with cancer and CKD are also at an increased risk of thrombosis. Therefore, safe and effective drugs for the treatment and prevention of thrombotic events are necessary.
(BELG J MED ONCOL 2023;17(2):46–51)
Read moreBJMO - volume 17, issue 1, january 2023
B. Depreitere MD, PhD, S. Schelfaut MD, F. Sinnaeve MD, H. Wafa MD, M. Lambrecht MD, PhD, M. Christiaens MD, PhD, M. Delforge MD, PhD, F.J. Sherida H. Woei-A-Jin MD, PhD, P. Brys MD, M. Renard MD, R. Sciot MD, PhD, J-F. Daisne MD, PhD
Primary bone tumours of the spine are relatively rare when compared to metastatic lesions and haematopoietic neoplasms. This often results in misdiagnosis leading to a high incidence of inadvertent intralesional surgery, which is associated in many cases with worse progression-free survival and overall survival. Based on evidence and consensus, a protocol was designed at the University Hospitals Leuven, intended to guide all possibly involved caregivers in different clinical situations. The protocol raises awareness of potentially suspicious situations and provides expert input to avoid unfortunate decisions, even in situations with alarming neurological deficits.
(BELG J MED ONCOL 2023;17(1):4–10)
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