Abstract
Brain metastases (BM) are frequently detected during the follow-up of patients with malignant tumors, particularly in those with advanced disease. Despite a major progress in systemic anti-cancer treatments, the average overall survival of these patients remains limited (6 months from diagnosis). Also, cognitive decline is regularly reported especially in patients treated with whole brain external beam radiotherapy (WBRT), due to the absorbed radiation dose in healthy brain tissue. New targeted therapies, for an earlier and/or more specific treatment of the tumor and its microenvironment, are needed. Radioimmunotherapy (RIT), a combination of a radionuclide to a specific antibody, appears to be a promising tool. Inflammation, which is involved in multiple steps, including the early phase, of BM development is attractive as a relevant target for RIT. This review will focus on the (1) early biomarkers of inflammation in BM pertinent for RIT, (2) state of the art studies on RIT for BM, and (3) the importance of dosimetry to RIT in BM. These two last points will be addressed in comparison to the conventional EBRT treatment, particularly with respect to the balance between tumor control and healthy tissue complications. Finally, because new diagnostic imaging techniques show a potential for the detection of BM at an early stage of the disease, we focus particularly on this therapeutic window.
Highlights
Current Management of Brain MetastasesOwing to advances in primary cancer control, the incidence of brain metastases (BM) is increasing [1]
Even in cases where control of the primary cancer has a favorable impact on the overall survival (OS), a significant proportion of patients die as a result of BM [3], with an average OS of 6 months
225Ac coupled to a monoclonal antibody directed against monomeric vascular endothelial cadherin, which is expressed on the tumour neovasculature (E4G10), induces vascular remodelling in a preclinical model of glioblastoma [15]. This remodelling impacted the biodistribution of a systemic treatment, with an increase of dasatinib (TKI) concentration observed within the tumour when given in combination with the RIT agent
Summary
Owing to advances in primary cancer control, the incidence of brain metastases (BM) is increasing [1]. This remodelling impacted the biodistribution of a systemic treatment, with an increase of dasatinib (TKI) concentration observed within the tumour when given in combination with the RIT agent. A novel MRI contrast agent, comprised of microparticles of iron oxide (MPIO) conjugated to anti-VCAM-1 antibodies (VCAMMPIO), has been proposed as a diagnostic tool for the detection of early BM [23], and has been shown to enable detection of BM from breast, lung, and melanoma human cancers in preclinical models [24] For these reasons, RIT targeted to BM via VCAM-1 may be promising, as it allows the targeting of the very early phase of BM. Biomarkers (study reference) RAD51, HDGF and TPR gene overexpression in primary cancer cells [8] Tyrosine kinase inhibitors [2] av-integrin [9] VEGF [12] VCAM-1 [21]
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