Andras A Kemeny
National Centre for Stereotactic
In radiosurgery high-dose ionising radiation is used to penetrate the skull all the way to the target. In order to minimise the effects on the surrounding brain, radiation is delivered from different directions using multiple beams. The overwhelming majority of the radiation energy ends up within the desired volume. The rapid fall-off of radiation dose – within a few millimetres away from the tumour surface the normal brain gets a minimal amount of radiation – is the key principle of this technique. It has brought an entirely new philosophy to radiotherapy. Radiobiology of these treatments is entirely new compared to fractionated regimes and it utilises predominantly the vascular effects of ionising radiation. This, in turn, broadened the spectrum of pathologies for which radiation can be used (eg, benign tumours and functional indications).
Standard for stereotactic radiosurgery is performed using several different methodologies
Proton beams are produced by ionising hydrogen gas and accelerating the resulting protons in a synchrocyclotron. The physical properties of these charged particles are particularly attractive. If the energy of the particles is precisely known, the depth of penetration into the brain is predictable. This way a very uniform radiation dose can be delivered into the target with a virtual absence of dose beyond the target. The difficulty is that the equipment is cumbersome and expensive.
Linear accelerators have been used for several decades, beginning in the late 1970s, when several groups modified their radiotherapy equipment to produce narrow beams for radiosurgical treatment from a large number of angles. This inevitably resulted in including some normal tissue in the spherical high-dose volume. Therefore multiple targets (so-called isocentres) had to be prescribed, which caused computational and practical difficulties. More recently, linear accelerators were fitted with miniature multileaf collimators (mMLC). The principle of this method is that the therapeutic radiation beams are shaped to match the shape of the tumour as seen from the direction of the beam (“bird’s eye view”). This is achieved by multiple metal “leaves” that are positioned and moved under computer control in order to conform to irregularly shaped targets. The original 3–5mm leaf width utilised in conventional radiotherapy was replaced by ever-thinner components, which improved the quality of shape matching. Computer control of the mMLC allows even dynamic movement of the leaves while the radiation source moves along. In combination with modulating the intensity of the beam (IMRT) quite complex treatment volumes can be achieved. The increasing complexity of these treatments required increasing computer power and it remains time-consuming.
The Gamma Knife is a purpose-built tool for intracranial targets. Two hundred and one Co(60) sources are arranged over a sector of a sphere within a precision-engineered fixed array. This allows very high precision and reproducibility of radiation delivery. The simplicity of dose delivery and dose planning with Gamma Knife systems made it the most successful technique and established it as the gold standard for stereotactic radiosurgery (SRS). The latest model of Gamma Knife, Perfexion™ (Elekta), contains an even higher level of automation, and it is expected that this will enable an easier and quicker treatment for several patients on the same day.
Fractionated stereotactic radiotherapy
High-quality and quality-assured imaging (CT scan and MRI scan) shows up the abnormality with increasing clarity but still requires a fixed three-dimensional coordinate system. In traditional radiotherapy where a plastic cast is used, accuracy is about 5–10 millimetres at best, which is inappropriate for single-fraction high-dose delivery, and often close to very sensitive structures.
To reduce the invasiveness of stereotactic frame application, “noninvasive” frames can be attached to the head using a plastic mould fitted to the upper set of teeth (“bite blocks”). The accuracy of these systems is much lower (in the order of a few millimetres). Although the precision may not be up to the standard used in radiosurgery, if the radiation is delivered in smaller daily doses, the neighbouring normal brain is protected. According to most experts noninvasive frames do not allow sufficient precision for use in radiosurgery, but it is superior to conventional radiotherapy. Bite blocks are tiring, unpleasant and unsuitable for the edentulous older age group who often present with the kind of pathology that requires this treatment.
During the last few years new image guidance systems have been introduced, which can be used for radiation delivery without the need for an external coordinate system, increasing the acceptability of fractionated stereotactic radiotherapy (FSRT). In the first technique, dual auxiliary X-rays “observe” the patient, while the radiation delivery system adapts to the position of the head. CyberKnife(®) (Accuray, Inc) is an industrial robot holding a linear accelerator head that delivers radiation from different angles to achieve a cross-firing effect. A limitation of this technique is that treatment for a complex shape takes a long time and the patient’s head is exposed to imaging X-ray during the whole procedure. There are also concerns that the patient may be able to move the head in the time between the last X-ray and the onset of the radiation beam.
The second principle technique combines the benefits of axial imaging (CT scan) with stereotactically localised treatment. TomoTherapy Hi-Art II® (TomoTherapy, Inc) combines a helical CT and the radiation source. Localisation of the lesion is limited to what one can see on a CT scan, but this system allows a daily review of any changes within the tumour as the patient is scanned again at the beginning of each treatment day. Patient movement may cause a similar problem for this technology.
Comparison of different FSRT technologies is difficult due to the large number of factors that need to be taken into account (eg, anatomy of the patient and target, the choice of immobilisation, the number of beams used, the choice and quality of collimation of the beams, whether the beams are static or intensity modulated). Experts have not even agreed on choosing the best formulae for comparing the quality of dose plans. Whether homogeneity within the lesion is an important factor or not is still open to debate with some suggesting that inhomogeneity (giving higher radiation dose within certain parts of the tumour) may be quite beneficial and may even improve the success of the treatment. This view would have been anathema only a few years ago. A true comparison would be meaningful if compared with the actual outcome using different modalities. However, for most pathologies the outcome cannot be assessed for several years, by which time technology and practice will have changed. This makes “evidence-based” assessment difficult. Decisions choosing one or other machine for FSRT are usually taken with practicalities in mind. At the end what truly matters is patient selection and high-level institutional and personal expertise.
Arteriovenous malformations (AVM) may present with, for example, brain haemorrhage and epilepsy. Unfortunately, open operation has a high risk of neurological complications. Radiosurgery successfully treats these life-threatening “birthmarks” in the brain with 80–90% success rate, in a single day’s treatment. With previous embolisation even very large malformations can be reduced to suitable size for Gamma Knife surgery.
With the broad availability of MRI scanning, very large number of patients were found to have another “birthmark”, so-called cavernomas, which may manifest with headaches, epilepsy or a stepwise worsening neurological deficit. An increasing number of these patients undergo radiosurgery as the risk of further trouble from these lesions is reduced.
Approximately 30% of benign meningiomas are not resectable due to their location, particularly on the skull base or in the cavernous sinus. On the other hand, for discrete small- to medium-size tumours (up to 30–35mm) a single-fraction radiosurgery treatment is convenient and effective. A progression-free survival rate of 86–98% is comparable to the results of apparently total surgical excision for these tumours. Radiosurgery is safe, with less than 5% risk of complications in experienced hands. For the rare large tumours and those growing around the optic nerve, FSRT is safer. There is no advantage of fractionated schedules for the overwhelming majority of meningiomas.
Vestibular schwannomas (acoustic neuromas)
These are benign tumours of cranial nerves responsible for balance or hearing, next to the brain stem. Despite significant improvements in microsurgery, most patients would avoid open surgery where possible. Further intervention can be avoided in 97–98% of patients with Gamma Knife radiosurgery. Reduction in tumour size may occur over several years after the treatment (Figure 1). Hearing is preserved in 75% of patients if the treatment is done by experienced radiosurgery teams. This is a particular bonus, because open surgery is almost invariably associated with rendering the patient deaf. The good reputation of radiosurgery led to more patients asking for treatment at an early stage when there is still hearing to be preserved.
Adding radiosurgery to whole brain radiotherapy is now the standard for up to three cancer deposits in the brain. Several centres are pushing the boundaries further, accepting patients for focused radiation treatment without an upper limit. If all patients with brain metastases were receiving such treatment, approximately 1.5 million would be treated annually in Europe alone. Therefore, prediction of outcome (eg, recursive partitioning analysis [RPA]) is important. In Sheffield we select patients with high performance status, absent or controlled primary and secondary extracranial disease.
Radiosurgery for previously untreated trigeminal neuralgia has 85–90% chance of a cure. Salvage procedures after previous operations are effective only in 65–70%. However, it is very safe, and only facial numbness develops occasionally.
The history of neurosurgery is that of the history of its tools. The relentless march of minimally invasive interventions is going to continue. An increasing proportion of neurosurgical work will be carried out using closed focused radiation techniques.The convenience and exquisite precision of the Gamma Knife appears to rule stereotactic radiosurgery. The demand to treat larger tumours with FRST generates considerable excitement and investment. Over the last few years a plethora of new machines have been developed and introduced for FSRT. Strong marketing may give an advantage to some, but it would appear that most could deliver a safe treatment with similar outcome.
- Kemeny AA, Radatz MW, Rowe JG, et al Acta Neurochir Suppl 2004;91:55-63.
- Metellus P, Regis J, Muracciole X, et al.Neurosurgery 2005;57:873-86.
- Rowe JG, Radatz MW, Walton L, et al. J Neurol Neurosurg Psychiatry 2003;74:1536-42.