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Stereotactic radiosurgery: brain surgery without the knife

Andras A Kemeny
1 July, 2006  

Andras A Kemeny
FRCS MD
National Centre for Stereotactic
Radiosurgery
Sheffield, UK
E: a.kemeny@shef.ac.uk

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.

Indications

Vascular abnormalities
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.

Benign tumours
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.

[[HHE06_fig1_R22]]

Metastases
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.

Functional indications
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.

Future trends
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.

References

  1. Kemeny AA, Radatz MW, Rowe JG, et al  Acta Neurochir  Suppl 2004;91:55-63.
  2. Metellus P, Regis J, Muracciole X, et al.Neurosurgery  2005;57:873-86.
  3. Rowe JG, Radatz MW, Walton L, et al. J Neurol  Neurosurg Psychiatry 2003;74:1536-42.