Radiology and Imaging lead to over- or, even worse, undertreatment.27 Furthermore, although


the anatomy of the lymphatic drainage of the breast may be altered by hyperthermal coagulative necrosis, published results show that the sentinel node procedure is not affected in 91% of cases, although the anatomy of the lymphatic drainage of the breast may be altered by hyperthermal coagulative necrosis.28,29


Initial Application in the Central Nervous System


Central nervous system (CNS) tumours include those that originate in the brain and in the spinal cord. They account for 9.2% of all neoplasms (malignancies) and represent the second leading cause of death from neurological disease after stroke. The incidence of CNS tumours increases in the seventh decade of life. All intracranial tumours, although properly differentiated and relatively benign, are potentially lethal due to their confinement in the skull. Brain tumours do not usually originate distant metastases due to the absence of lymphatic paths, although they may spread to the neuraxis or at the intracerebral level. Currently, the mainstay of their curative treatment is surgery. However, in a high proportion of cases surgical options are not possible because of tumour location, relationship with neighbouring vital structures and difficulties with ensuring adequate resection margins. In such cases, other procedures are considered, including chemotherapy, radiation therapy, a combination of both or even proton therapy. Thus, non- invasive treatment of brain tumours represents one of the potential areas of MRgFUS application that is generating the greatest interest.30 The safety of intracranial application of MRgFUS has been reported by Hynynen based on a pre-clinical study on primates where there was no need for bone opening thanks to the use of a novel helmet system.31


The


first non-invasive treatment of three human glioblastoma multiforme cases was recently published by McDannold and colleagues.32


The same


system was used for non-invasive thalamotomy for treatment of neuropathic pain, as published in 2009 by Martin and colleagues.33


The


results show the safety and accuracy of non-invasive deep brain lesioning. These data support ongoing research in this field with the aim of developing a truly non-invasive neurosurgical procedure. Other possible applications of MRgFUS in the CNS field arise in functional neurosurgery. Ablation of a path or a beam in the brain may be helpful to treat certain symptoms and diseases. Potential applications include treatment of epilepsy and psychiatric disorders and the thermal destruction of the spinothalamic tract for treatment of neuropathic pain. MRgFUS has also been used to treat acute brain infarction,34 this application will not be described in this article.


although


Initial Application in Prostate Cancer Prostate carcinoma is a public health problem worldwide, with an increasing incidence due to ageing of the population. It is estimated that in 2015, 450,000 new cases will be diagnosed in the US alone. Current treatments for prostate cancer include surgery, radiotherapy and brachytherapy. The most important complications related to radical prostatectomy include deep vein thrombosis, pulmonary embolism, urinary incontinence and impotence. Radiation therapy has similar complications plus gastrointestinal toxicity. The search for image-guided minimally/non-invasive methods with a low mortality rates is of great interest.35


New therapies include cryotherapy,36 photodynamic therapy37


and HIFU. The first results of application of HIFU to localised prostate carcinoma were published by Gelet et al.38


Pre-clinical MRgFUS trials


have been carried out in canine models. The key differences between MR-guided and ultrasound-guided systems is the ability of MR to yield realtime temperature mapping and procedure feedback during the


78


ablation. The possibility of performing treatment in a single session with a low complication rate and without the need to irradiate the patient explain the very high interest in using MRgFUS to treat prostate cancer.


Treatment of Hepatocellular Carcinoma As in other malignancies, the gold standard for the treatment of hepatocellular carcinoma is surgical resection. However, about 85% of patients are not suitable candidates for surgery, and the five-year survival rate is very low. This situation has fostered the development of novel minimally invasive techniques such as microwave and laser ablation, cryotherapy and radiofrequency ablation. The interest in using MRgFUS instead of these techniques is due to its true non-invasive character: since there is no need to insert any type of guide or needle into the hepatic parenchyma, the risk of surgical complications is eliminated. Starting with focused ultrasound, studies have been published on animal models and individual cases.39–41


There are still


some limitations to be overcome, including the ability to treat lesions behind the ribs and synchronise sonications with respiratory motion.42


Controlled liberation and activation of the drug by MRgFUS- induced hyperthermia would act specifically on the target tumour.44,45 Further studies are still needed to investigate suitable drugs and the exact mechanisms of deployment of therapeutic targets. Other future directions of MRgFUS research include the induction of antitumour immune response by activating dendritic cells46 induced hyperthermia.47–49


and gene transfer by Conclusions


Non-invasive MRgFUS constitutes a powerful new surgical tool with an increasing variety of applications in oncology, ranging from palliative pain treatment to tumour ablation. Its impact in the management of such health problems as breast, prostate, liver and brain tumours will became clear as data from ongoing trials emerge. The application of this technique to targeted drug delivery has the potential to reduce the side effects and increase the efficiency of oncology treatments. n


Pedro Valero is Director of Oncology at Hospital Infanta Luisa in Seville. In collaboration with the Instituto Cartuja and the University of Seville, his research focuses on applications of magnetic-resonance-guided focused ultrasound surgery in oncology. Dr Valero is an active member of several Spanish oncology research groups, including TDD (digestive tumours), GEICAM (breast cancer) and ONCAMI (medical oncology).


Emilio Gomez-Gonzalez is Director of the Group of Interdisciplinary Physics in the Department of Applied Physics III in the Engineering School of the University of Seville. His research focuses on advanced physics and technology in biomedical applications, with a current focus on non-invasive and image-guided surgery. He is a member of the Spanish Societies of Physics, Optics, Radiology, and Pediatric Neurosurgery.


Application to Targeted Drug Delivery The application of MRgFUS to targeted drug delivery is a potentially great innovation and advance in the field of medical oncology since it may help to prevent systemic toxicities and achieve increased intratumoral efficiency in the treatment of solid tumours. One method under development is encapsulated chemotherapy inside heat-sensitive liposomes that remain intact at temperatures around 37ºC. Since malignant tumours are associated with high neovascularisation rates, liposomes would preferably accumulate in the interstitium around the tumour.43


EUROPEAN ONCOLOGY


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