Magnetic-resonance-guided Focused Ultrasound Surgery in the Treatment of Oncology Patients
below, other applications, including FDA studies for palliative treatment of bone metastases and breast cancer, are in phase II/III clinical trials. The Sonalleve Philips system received the CE mark for treatment of uterine fibroids in 2009. Published articles in oncology refer to the ExAblate MRgFUS system only.
Current Use in the Treatment of Painful Bone Metastases
Bone is the third most common organ of metastatic dissemination after the lungs and the liver, and 50–75% of patients with bone metastases present with severe pain. Palliation of associated symptoms is the primary objective of their treatment. Current options for pain management include both local and systemic therapies. Local options include radiotherapy, surgery and percutaneous ablation by radiofrequency. Systemic treatments comprise hormone therapy, analgesics, chemotherapy and bisphosphonates.2
MRgFUS treatment of bone metastases is based on the high acoustic absorption and low thermal conductivity of cortical bone, which allows the use of low energy levels (compared with treatment of soft tissues) to achieve temperatures >60°C at the target locations. This energy produces a coagulative necrosis without damaging the surrounding tissues, which otherwise would receive a sublethal dose.3,4
Two mechanisms have been postulated to explain the analgesic effect of MRgFUS: thermal denervation of the periosteum and ablation of the tumoral mass itself. In published studies, immediate pain relief is described, supporting the first hypothesis. Also, a maintained analgesic effect is found, which is explained by both mechanisms. Most treated patients present an improvement on pain scale and a reduced dose of opioids and other analgesics. Possible complications are of a thermal nature, including cutaneous burns and damage to nearby structures that are sensitive to heat, such as nerves or the intestinal wall. None of these side effects has been described in published studies, and realtime imaging control and temperature feedback through thermal mapping make such complications rare.5–7
This study is in the recruitment phase and is expected to include patients with osteolytic or osteoblastic lesions caused by certain clinical conditions.
Application to Breast Cancer
Breast cancer constitutes the second cause of cancer-related death in women in developed countries and is a global health issue.9,10 Conservative surgery followed by radiotherapy has become the gold standard in the treatment of localised breast cancer.11
This procedure
has a low mortality rate, but complications can occur, including bleeding (2–10%), infection (1–20%), seroma formation (10–80%) and chronic pain in the incision area (20–30%).12
Technical advances in
recent decades have allowed the emergence of minimally and non-invasive techniques such as cryotherapy, interstitial laser ablation, radiofrequency ablation or ultrasound ablation.13–16
MRgFUS
constitutes a potentially powerful new tool for the treatment of breast cancer.
EUROPEAN ONCOLOGY
MRgFUS treatment of painful bone metastases has CE mark approval and is currently used in Germany, Italy, Russia and Spain. A case example is shown in Figure 2. There is an ongoing FDA pivotal study to evaluate the effectiveness and safety of the ExAblate system in the palliative treatment of pain from metastatic bone and multiple myeloma tumours in patients who are not suitable candidates for radiotherapy.8
Figure 1: Closed-loop Strategy for Magnetic-resonance- guided Focused Ultrasound Surgery
3D planning • MR segmentation of target • Determination of sonication spots • Simulation of ultrasound beams
Feedback and control • Adjustment of sonication parameters
Treatment • Application of sonications • Realtime temperature mapping
Evaluation of outcome • Contrast MR • Evaluation of ablation and non-perfused volume
MR = magnetic resonance.
Figure 2: Case Example of Palliative Treatment Using Magnetic-resonance-guided Focused Ultrasound Surgery
AB
A. Magnetic resonance image (MRI) showing soft-tissue mass within the sacral area with bone destruction. B. Immediate post-treatment MR (T1w contrast-enhanced subtraction image) showing ablated area. The patient is a 72-year-old male with a diagnosis of urothelial carcinoma of the bladder followed by bone metastasis. MR-guided focused ultrasound surgery (MRgFUS) ablation of the coccyx lesion was applied. Before treatment, the patient’s pain score was 8 on a on a visual analogue scale (VAS) of 0–10. The same day he reported a very significant symptomatic improvement in pain down to a score of 3. The next day he reported disappeance of pain (VAS 0). After four-month follow-up, the patient reported no pain and continued improvement in general status. Source: Valero et al., 2010.50
The first experience with MRgFUS in the treatment of benign tumours was published by Hynynen and colleagues in 2001.17
In the same year,
Huber and colleagues published the first case of a malignant breast tumour treated using this technique.18
It is important to note that for a
non-invasive technique to be considered equivalent to surgical extirpation, it must show necrosis of 100% of the target tumour.19,20 Although there is no clearly established protocol, the combination of MR and biopsy is used as the procedure of choice for detecting residual tumour. To evaluate the safety of margin ablation, Furosawa and colleagues21
three months. Gianfelice22
scheduled a follow-up including MR and ultrasound every also used MR 10 days and one, three and six
months after the treatment as well as multiple biopsies of the affected area within six months. In cases of residual tumour, it is possible to re-treat with MRgFUS and perform a new biopsy one month later.
including a minimum distance between the tumour and the skin (to avoid skin burns) and between the tumour and the chest wall (to avoid heat accumulation in the ribs and lung). Also, the patient should be able to lie on her chest for several hours during the process. In certain cases, this positioning may become difficult. Although there are no exact recommendations regarding the size of the target lesion, breast tumours >5cm in diameter should not be selected for treatment with MRgFUS because of the increased treatment time and reduced probability of tumour necrosis.25
diameter show a 100% success rate.26 Patients with ductal carcinoma in
situ (DCIS) should also be excluded from treatment with MRgFUS because MR may under- or overestimate the extent of DCIS, which may
77
A number of factors must be considered when selecting candidates for the procedure,23,24
Patients with tumours ≤2cm in
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