Towards updated understanding of brain metastasis

Abstract

Brain metastasis (BM) is a common complication in cancer patients with advanced disease and attributes to treatment failure and final mortality. Currently there are several therapeutic options available; however these are only suitable for limited subpopulation: surgical resection or radiosurgery for cases with a limited number of lesions, targeted therapies for approximately 18% of patients, and immune checkpoint inhibitors with a response rate of 20-30%. Thus, there is a pressing need for development of novel diagnostic and therapeutic options. This overview article aims to provide research advances in disease model, targeted therapy, blood brain barrier (BBB) opening strategies, imaging and its incorporation with artificial intelligence, external radiotherapy, and internal targeted radionuclide theragnostics. Finally, a distinct type of BM, leptomeningeal metastasis is also covered.

Keywords: Brain metastasis; artificial intelligence; blood-brain barrier; imaging; model; nuclear medicine; targeted therapy.

Figure 1

Schematic illustration of blood-brain barrier (BBB) and action sites of the strategy for increasing drug penetration.

Figure 2

Exemplified rodent case of intracranial tumour treated with Regadenoson and a vascular disrupting agent CA4P, studied on a 3.0T clinical magnet. CE-T1WI anatomical scans (A) before treat-ment, one hour and eight hours after combinatory treatment. T2 relaxation map (B), T1 relaxation map (C), CE T1 relaxation map (D), T1 ratio map (E) and AUC30 (F) display at time points of before treatment, one hour, and eight hours after combinatory treat-ment. Abbreviations: CE: contrast enhancement, AUC30: area under curve for the first 30 seconds.

Figure 3

Two example cases treated with a vascular disrupting agent (CA4P) monitored by ultra-high field MRI for therapeutic effect at 24 hours after treatment. Intraindividual comparison of intracranial (red arrow) and extracranial (yellow arrow) efficacy of CA4P showed much stronger vascular shutdown effect in extracranial lesion (A). However, CA4P did not work well in the BM of lower row case (B). Postmortem nanoCT angiography was performed on day 5 after treatment. Robust angiogenesis after VDA treatment is also observed in both BM cases of a single-artery supplied tumor (asterisk) (A) in contrast with a BM of multiple arterial blood supply (asterisks) (B).