By Simone Peschillo
Malignant brain tumours are among the most feared types of cancer, not only for their poor prognosis, but also because of the direct repercussions on quality of life and cognitive functions. Malignant gliomas are the most common type of primary malignant brain tumour, accounting for 80% of patients and an annual incidence of 5.26 per 100,000 population, or 17,000 new cases diagnosed per year.
These numbers are for mass pathology, with a significant impact on the lives of the people who are affected, their families and also on the economy and social life of the community. The pathology brings multiple effects, involving concentric circles of individuals ranging from the patient who is directly involved, their relational network and the environment in which they live. If we then consider the total number of patients affected by the disease and the size of those concentric circles, it is clear that the consequences on the economy and society of a country may be relevant.
The onset of a neuro-oncological disease is not just an individual problem; it involves the whole family, upsets relationships, daily routines and interrupts social interaction.
Glioblastoma is a highly vascular cerebral tumour that expresses vascular endothelial growth factor, a key regulator of angiogenesis and tumour blood vessel permeability. Bevacizumab, which has recently been introduced as an intravenous chemotherapeutic agent in the treatment of high-grade gliomas with encouraging results, is a monoclonal antibody which binds to vascular endothelial growth factor (VEGF). Bevacizumab reduces brain tumour oedema, ‘normalises’ tumour blood vessels and is an effective anti-tumor agent alone or in combination with chemotherapy. It blocks the formation of new blood vessels in tumours but also affects existing vasculature. Several monoclonal antibodies whose target was the VEGF have been shown to inhibit the growth of glioblastoma in vitro and in vivo. Intravenous bevacizumab monotherapy has been proven effective for recurrent glioblastoma in extending progression-free survival and improved patient quality of life in various clinical trials.
The advent of modern devices used by endovascular neurosurgeons made it possible to proceed with the release of chemotherapeutic agents in an ultra-selective mode by means of superselective intra-arterial cerebral infusion (SIACI).
Some authors have proposed the use of bevacizumab by cerebral infusion after phase I studies. This method would have considerable advantages compared with intravenous treatment demonstrated in studies. The concentration delivered to the tumour by intra-arterial injection compared with intravenous administration of chemotherapeutic agents is five times higher than hydrosoluble drugs and up to 50 times higher with liposoluble drugs. Furthermore, intra-arterial chemotherapy results in a more localised delivery than intravenous administration which is suitable for the treatment of primary brain malignancies as these tumours rarely metastasise and most recurrences are local. Bevacizumab is well suited for delivery to brain tumours using SIACI because of its ability to selectively target the tumour tissue and because of its reduced toxicity with respect to the systemic modality of delivery.
In our article (Peschillo et al, Journal of NeuroInterventional Surgery 2014) we reviewed all recent published works on cerebral infusion of brain tumours with chemotherapy drugs. We found that the initial experience with bevacizumab administered by cerebral infusion, anticipated by the destruction of the blood-brain barrier, has shown good outcomes. The treatment produced a stable disease and an improvement was observed.
At our institution we have started a new research project with nano-particles addressed by SIACI to the tumour hoping to maximise the effectiveness of chemotherapy drugs.
If this initial experience with bevacizumab administered by cerebral infusion is confirmed by further phase II studies, this paradigm may significantly alter the way chemotherapies are delivered to patients with both diffusely infiltrating low- and high-grade malignant brainstem gliomas, opening a new endovascular era.
Simone Peschillo is with the Department of Neurology and Psychiatry, Endovascular Neurosurgery/Interventional Neuroradiology, “Sapienza” University of Rome, Italy