Overview of Intracranial Stereotactic Radiosurgery Introduction Brain cancer is usually divided into two categories; primary cancer, where

the tumor originates in the brain, and secondary brain cancer, where metastases from primary tumors in other parts of the body spread to the brain. The way in which the brain tumor can and should be treated depends on the stage of the disease, the type of tumor and its location, and whether the tumor is a primary tumor or a metastasis. The patients age is another factor. The treatment of brain cancer entails unique challenges due to what is known as the bloodbrain barrier, which prevents external substances from permeating into the brain. This makes the use of cytotoxic (chemotherapy) treatment more difficult than for cancer in other parts of the body. The most frequently applied treatment to date for secondary brain cancer is radiation therapy for the entire brain. This method is currently increasingly being called into question in scientific publications, due to the risk of side effects. The treatment that is gaining most ground is instead is stereotactic radiosurgery, which is increasingly proving itself as a highly effective method with a considerably lower risk of side effects. A growing number of studies are showing that stereotactic radiosurgery generates better results, either independently or in combination with other forms of treatment. Radiosurgery System, with its high level of precision and automation, is particularly well-suited for the treatment of brain metastases, even for patients with multiple tumors. With the use of Stereotactic Radiosurgery, it has become increasingly common to apply treatments where many metastases can be eliminated during a single treatment, with benefits for both the patient and the hospital. For well chosen patients, the clinical outcome of stereotactic radiosurgery are better than those of open surgery. This offers the prospect of a technology that is Cheaper per treatment, More acceptable to patient, and More effective than the existing treatment Stereotactic Radiosurgery is a minimally invasive procedure. Recovery to post operative lifestyle is more rapid and minimum hospitalisation is required. Usually, the patient leaves the hospital the sameday as Stereotactic Radiosurgery was performed, or on the following day. There are fewer complications and none of the traditional complications associated with open surgery.

This unusual combination of advantages means that Stereotactic Radiosurgery has gained a high degree of clinical acceptance with improved cost effectiveness fewer complications shoter hospital stays faster patient recovery better quality of life for the patient less psychological trauma

Stereotactic Radiosurgery SRS is : the delivery of a single high dose of radiation to a small and critically loacted intra-cranial volume without opening the skull. SRS is a treatment for serious diseases in the brain and associated strructures in the skull. It is particularly valuable when the lesion is close to critical structures. SRS aims at irradiating precisely, in a single shot treatment, one or several intra cerebral lesions to stop growth of tumors, to introduce changes in blood vessels in the brain( arterovenous malformations), or to alter function ( eg., hormone producing tumors in the pituitary gland, pain sensations in trigeminal nerve) Radiation from Stereotactic Radiosurgery system is tightly focussed, using very fine beams, on a small target. By focusiing these high energy particles so precisely, the system can deliver very high doses of radiation with minimal damage to the normal brain tissue surrounding the problem area. SRS uses a frame and standard imaging procedure to establish the exact 3 dimensional spatial co-ordinates of the problem area, so that the radion can be precisely targetted. Not only the system is able to focus beam on a very small target, it is also able to build up a radiation field so that it conforms closely to the shape of the tumor or the AVM. This is done using the advanced computer software which works out precise instructions to allow the shape to be created out of smaller elements. Beams are targeted on different points within the lesion. These isocentres are spheres which, when taken together can create a spoherical shape. Multiple isocentres require very accurate co-ordinates to be recalculated for each shot.

Which beamns to be block, to make the shape of the radiation field no spherical which collimators to use. A collimator is a device for making beams thinner and therefore more focussed.

The technique is simple, quick and painless. It avoids opening the skull, with favourable consequences for the patients quality of life, for costs and for clinical outcomes and complications. The treatment is carried out in a single session. There is no intensive care and the patients often go home immediately after treatment. People typically return to their preoperative daily activity within a day or two, instead of covalesing for weeks after an operation. In summary, Stereotactic Radiosurgery is a non invasive, virtually painfree alternative to conventional open surgery and whole brain radiotherapy for selected indications.High selectivity is achieved by using narrow radiation beams and multiple isocentres. This ensures optimal target dose and minimal irradiation of healthy tissue. Latest developments in computing and patient positioning systems continue to improve further the ability of Radiosurgery system to mould/ sculpt the radiation field more effectively and precisesly. Radiosurgery offers an unusual combination of improved patient experience, improved clinical outcomes, and graeter cost effectiveness. Because Radiosurgery is effective and has low level of side effects, it is emerging as the treatment of choice for intracerebral lesions of limited volume (less than 3 cm in diameter), with well defined contours, especially the locations wheret the removal by open surgery is risky. Radiosurgery allows the doctor to reach and treat lesions located deep in the brain that were previously considered inoperable because the approach was too difficult. Unlike traditional raditherappy, Radiosurgery can be repeated if necessary because the radiation is deposited in the area of concern the tumor while avoiding the normal barin. In some some circumstances Radiosurgery is used in conjunction with other treatment modalities. for example to target small areas of residual tumor after surgery or as a boost after conventional radiotherapy. Radiosurgery is a multidisciplinary activity involving coordinated input from neurosurgeons radiation oncologists physists and engineers. Although Radiosurgery systems uses radiation, it does so, in a quiet a different way from radiotherapy and for different purposes. Intracranial Radiosurgery is a

surgical tool which uses radiation as an invisible scalpel. It is more natural, for Intracranial Radiosurgery to be seen as an alternative method of providing neurosurgical care than as an addition technique for radiotherapy

Indications Cerebral ArterioVenousMalformations are tangles of abnormal blood vessels in which blood passes between arteries and veins, bypassing the normal capillary system. These blood vessels are not as strong as normal blood vessels and a relatively high volume of blood passes through them. This can cause strokes, epileptic seizures and progressive neurological problems such as paralysis or loss of speech, memory or vision. AVMs , may also, like a tumor, compress or destroy normal tissues. Vestibular schwannoma (acoustic neuromas) are beningn tumors that originate from schwann cells ( schwann cell area specialised type of cell supporting the neuronal cells which carry signals) of the VIIIth cranial neve, the vestitubular nerve. They are often inseperable from the acousitc nerve which we need for hearing. The majority of patients present with progressive unilateral hearing loss and possibly also a malfunction in one or more

adjoining nerves (tinnitus, ataxia, facial numbness or mild facial palsy). The growth of the tumor will eventually lead to increased pressure inside the skull leading to more general symptoms. The aim of the treatment is to prevent the functional disorders that result from increasing tumor volume. Meningiomas are slow growing benign tumors arising from meninges, the sheets of tissue covering the brain. The problems which result depend on the increased pressure within the skull. Owing to its slow growth rate, the developments of symptoms can be very gradual and some tumors are not diagnosed until they have reached a significant size. The purpose of Radiosurgery is to achieve stabilisation of lesion or even reduction of volume taking into account that therauptic effect is a very slow process taking place over more than 5 years. Pituitary tumors cause problems either because they produce hormones or products which have hormonal effects or visual defects resulting from pressure effects on the nearby optic nerve. The therauptic choices and outcomes differ depending on the type of tumor and size. The pitutiatrty is located in the central part of the brain and tumors in this hormone producing structure are harder to access by open surgey. If a tumor originates in a hormone producing cell this multiplication also results, secondarily in drastic increase in the actual hormone production which leads to hormone induced disesaes (ie. acromegaly with extreme body growth, cushings disease with moon face and truncal obesity and Nelsons disease). In 25 % cases the tumor does not produce hormone and is then said to be non functional. Here the first symptom is often visual defect. The treatmrnt of choice depends on the size of tumor and type of hormone over production. Trigeminal neuralgia (tig douloureux) is a disorder of the VIth cranial nerve,the trigeminal nerve.It is characterized by brief attacks of severe pain(with rapid onset and abrupt end)lasting seconda to minutes or even hourss in the scalp,forehead,face ,mouth or teeth of the affected side. Many patients can experience areas of increased sensitivity around the mouth and nose,which when,touched many bring on an attack (trigger zones). Other things such as stumuli of cold, eating, brushing the hair may also cause attacks.The pains often described as similar to an electric shock and many occur in one or all of the areas supplied by the trigeminal nerve.Over time it tends to involve progressively in more parts on one side.Patients with trigeminal neuralgia almost invariably stop talking, sit still,and protect their face from touch during the attacks. Trigeminal neuralgia is generally considered to be the most painful affliction known to adult men or women.A significant proportion of patients with

trigeminal neuralgia commit suicide, The patients can experience pain for several consecutive weeks or months followed by an interval when the patient is symptom free.During common periods of remission,the patient may be completely pain free, but in a state of high anxiety over fear of the next attack. The cause is not known. The pain from trigeminal neuralgia also causes a great deal of suffering and limitation in every day activities. Hygiene and psychological problems often isolate patients. In addition. weight loss is common because oral triggers prevent affected individuals from eating enough to maintain adequate nutrition. Brain metastateses are nodules of cancer that have spread from sites of malignancy in the body through the bloodstream to deposit and grow in the brain,The brain is a common site of metastatic tumour.metastases to the brain are found in 23-35% of all cancer patients.Almost 50% of the patients with cerebral metastases have one lesion; 20% have two lesions. Effective palliation is available for most patients with brain metastases,but many will die within six months,usually from prograssive systemic tumour .However , in a substantial proportion of patients,a vigorous therapeutic approch using surgery, radiotherapy , and possibly chemotherapy can product significant benefits.There is an increasing tendency for treatment of brain metastases to be more active than was the case in the past. Clinical management decisions regarding the treatment of brain metastases is the subject of widely differing social and ethical views,as well as being clinical and technical . Some doctors feel thar patients with cerebral metastases should only be treated palliatevely to make them more comfortable in their final days or weeks,because the prognosis for patients with metastases is generally poor. The overall median survival time after surgery followed by radiation therapy for a solitary lesion is 9 to 23 months.The prognosis in patients with multiple metastases and or progressive systemic cancer is much worse. However, some patients a vigourous therauptic approach leads to years of productive life and even where it does not, it may lead to a useful remission of the neurological symptoms and may both enhance the quality of partients life and prolong survival. other indications are parkinsons disease, epilepsy , tumors of the pineal body (germinal, non secreting tumors), low grade glioma, childrens tumors (ependymoma and medulloblastoma), craniopharyngioma, psycho surgery

Incidence

(based on a study conducted in Europe in 2000)

The number of patients who can be treated with SRS can be estimated with reasonable accuracy using the published epidemiology of indications, the percentage of these indications that are currently believed to be treatable with SRS, and the population base in question, from sources related to research with leading clinicians in the fields of open surgery and radiation oncology. The data given below is from a study in Europe in 2000 The objective has been to calculate projected patient volume by using published information from peer reviewed literature, consensus studies by recognized scientific groups, and currently accepted practice in the eld of neurosurgery. When ranges were given in published data, a conservative approach was taken which may result in low end estimations of the actual potential volume of patients. a summary of epidemiological information. Cerebral AVMs The incidence of new symptomatic AVMs presenting to surgeons is estimated to be 12 patients per million per year. In addition, it is estimated that approximately 7 new asymptomatic cases per million are discovered incidentally when imaging studies are done for other reasons. Of these 19 new cases it is estimated that 70% will be suitable for treatment with Intracranial Radiosurgery . This results in approximately 13.3 cases per million per year. Meningiomas The incidence of meningiomas is reported as 78 per million per year, but only 20-25% of these are symptomatic (16-20cases per million per year). Looking only at symptomatic cases, the patients whose meningiomas are suitable for Intracranial Radiosurgery can be grouped into two categories. First, there are patients whose meningiomas are suitable for Radiosurgery as a primary treatment at the time of diagnosis, without any open surgical procedure. This number can be derived from large series of operated meningiomas, based on location and size. From these figures, it is estimated

that approximately 3.2 cases per million per year (or 20% of the symptomatic tumour incidence) fall into this first category. Second, there are patients whose meningiomas are residual orrecurrent and who stand a reasonable chance of benefiting from SRS as an adjuvant treatment. Based on studies on the rate of recurrence following operation, 30%-40% of meningiomas which are treated with open surgery are likely to benefit from Radiosurgery for recurrence or residual tumour at some point. This gives a figure of 4.8 per million per year. The total projected patient volume for Radiosurgery for meningiomas is therefore 8 per million per year. Pituitary adenomas Total incidence of pituitary adenomas is about 70 per million per year. In the best hands the expected success rate in open surgery of these primary treatments is 80%, with a recurrence rate of 20%. The tumour control rate with larger tumours is less good being reported between 36%-50%. Using a treatment failure rate of 20% as a reasonable estimate, this would imply 2.8 patients/million per year. To this may be added 50% of patients with Cushing's Disease. These cases would increase the numbers by 1.08 per million, giving a total of 3.9 per million. Finally, while 20% is the failure rate in the best hands, considerably higher failure rates have been reported. Even if the failure rate were as low as 30%, this would increase the number of patients expected to benefit from Radiosurgery to 5.4 per million p.a. The annual incidence of symptomatic pituitary adenomas is approximately 21 patients per million. Approximately 75% of pituitary tumours produce hormones. Almost all patients need treatment. Open surgery is, in many cases, the treatment of first choice because it has a high cure rate and its effects are evident within a few days after surgery. However, it is estimated that about 22% of all patients previously operated on by open surgery (7% persisting + 15% recurring) will sooner or later need Radiosurgery or an equivalent procedure. This is equivalent to about 4 per million. Vestibular schwannoma Five studies in centres where Radiosurgery was not then available (to avoid distorting the findings) reported a total of 1,671 tumours were reported, of which 1,057 were 3 cm. in the largest dimension. This suggests that 63% of the cases are suitable for treatment with Radiosurgery. This figure is supported by analysis of data available since 1987 regarding the number of cases for which Radiosurgery was performed. These data were used to predict the number of patients with vestibular schwannoma who will be treated with Radiosurgery in the future. If the current trend continues, an equal number of patients will undergo surgical resection and Radiosurgery between 2005 and 2010 and by 2020, two-thirds of the patients who are newly diagnosed with vestibular schwannomas will undergo Radiosurgery. The clinical prediction is that surgical resection for vestibular schwannoma

will be reserved for patients with large tumours associated with symptomatic brain stem compression. The incidence of vestibular schwannomas is 9.4 per million. This gives a projected vestibular schwannoma patient volume for Radiosurgery of 6 cases per million per year. Trigeminal neuralgia The incidence of trigeminal neuralgia is 43 per million per year. First line treatment has traditionally been medication. However, publications suggest that while Radiosurgery has been used most for cases that have failed open procedures and providescomparable results to those of open procedures, it is increasingly used as an effective non-invasive first line of treatment. 90% of clearly diagnosed patients are treatable with Radiosurgery. Assuming that medication may continue to provide long term pain relief in many patients, it is estimated that 50% would be suitable for Radiosurgery, i.e. 21 patients per million per year. In addition so-called secondary trigeminal neuralgia due to tumours, vascular malformations or multiple sclerosis may also be successfully treated with Radiosurgery, but are not included in this calculation. Brain metastases As mentioned earlier, there are differences of view about whether patients with cerebral metastases should be treated other than with palliation to make them more comfortable in their final days or weeks. The proportion of patients with cerebral metastases who might be offered Intracranial Radiosurgery treatment depends on the view of the individuals or the payor. A consensus conference on the treatment of brain metastasis noted that approximately 25% of brain metastases patients qualified for - and should receive more aggressive therapy. In this document, we use the rate that this implies, i.e. 157 per million per year. For suitable patients, Radiosurgery generally costs much less than the alternatives, with results as good as or better than - current treatments, and patient factors (such as quality of life, return to pre-operative activities etc.) strongly favour Radiosurgery over open surgery. Open surgery of many lesions is very difficult, and any partof the AVM or tumour left behind will potentially lead to a recurrence or worsening of symptoms in the future. With Radiosurgery there is no general anaesthetic with its risks of cardiorespiratory problems, no risk of infection, low complications, no fear, no hospital stay, and a rapid return to work. Radiosurgery will certainly not replace open surgery, and is not intended to: they are complementary rather than competing therapeutic options. Some

lesions are more suited to Radiosurgery, others to open surgery. In other cases, both may have a part to play. For example, planned staged procedures may be used for larger tumours: in these procedures, open surgery is used to reduce the volume of the lesion, and Radiosurgery used subsequently to treat residual tumour which cannot be removed because of its location. As noted earlier, SRS is now the alternative to microsurgery in the treatment of vestibular schwannoma, cerebral metastasis, meningioma of the base and arteriovenous malformations and is the only treatment available for AVMs located in functional and/or deep areas. Incidence of other indications like parkinsons disease, epilepsy etc are not included..
Annual Incidence per million 19 20 21 9 12 43 630 % indicated for radiosurgery 70% 40% 20% 70% 25% 50% 25% Annual cases suitable for radiosurgery 13 8 4 6 3 21 157 212

Indication Vascular AVMs Benign Tumors Meningimas pituitary Adenomas Vestibular Schwannoma other tumors functional Disorders trigeminal neuralgia malignant Tumors metastases Total cases /million/year

A typical open surgical treatment Open surgery involves making a suitably located hole in the skull which is big enough to allow a surgeon to View the lesion, and to use a scalpel, or a laser, to remove the lesion and, in some circumstances, place sutures in the material being left behind. Open surgery involves direct visual and physical access to the lesion. If the lesion is deep in brain tissue, it is necessary to cut through or retract this

normal tissue in order to get at the lesion. Once the normal brain tissue has been cut through or damaged by retraction, it will not repair itself. It is often impossible to gain access to the lesion without cutting through areas of brain which fulfil important functions (for example: sight, hearing, movement). These cases are considered as being at high surgical risk. On occasions, it may be impossible to gain access to the lesion without the risk of destroying vital areas and these cases are inoperable. When the lesion is accessed, it may be difficult to remove the diseased material with the level of accuracy that can be achieved with high quality imaging and Radiosurgery. The surgeon may either err on the side of caution and spare normal tissue but run the risk of recurrence, or be more radical and run a greater risk of damaging surrounding normal tissue. Patients who are not in good overall condition, especially those with cardiovascular or respiratory problems, may not be able to tolerate the general anaesthetic normally required for open surgery. It may not be possible to consider open surgery for unfit people, even if the lesion itself is operable. Brain surgery is difficult and demanding on both surgeon and patient. Open surgery takes a long time. In one study, the average duration of open surgery for vestibular schwannoma was 7 hours. It is common for patients to spend time after the operation in an Intensive Care Unit or a High Dependency Unit (2.4 days in van Roijens study). This is usually followed by a lengthy stay in hospital (10.5 days after surgery for vestibular schwannoma (also in van Roijens study), and a prolonged period of convalescence and recovery at home. Complications Complications of open surgery in the skull are frequent because of the difficult conditions in which the neurosurgeon has to operate. For example, in the case of vestibular schwannoma illustrated above, complications include: bleeding; infection; the development of facial weakness which will require the patient to return for plastic surgery or facial hypoglossal anastomosis (open surgery to connect the facial nerve to another nerve to improve appearance); up to 25% develop cerebrospinal fistula, requiring further open surgery to reopen the operation wound and plug the hole. In the case of complications, hospital stay may be prolonged. If the patient has to return to the operating theatre for a second major procedure, they may go back to the beginning of the sequence

A typical Radiosurgery treatment Radiosurgery describes the application of high doses of finely focused radiation beams focused on a small and precisely located target within the skull. The radiation successfully destroys or alters the function of deep-brain structures without opening the skull: it thereby avoids the risk of bleeding, infection, spreading cancer tumors, or destruction of surrounding (normal) tissue. The technique is performed in a single session. Intracranial Radiosurgery uses radiation like a very fine surgical knife. In this respect it is quite different from radiotherapy, which aims to irradiate wider fields, almost always with a view to shrinking cancerous tumours and generally suppressing nodules of secondary cancer which may be too small to see. The lesion is mapped out in 3-D space, the coordinates being plotted in relation to reference points on a frame fixed to the head. Intracranial Radiosurgery moulds radiation fields in a way that conforms closely to the shape and size of the target lesion. This, together with the precision of the beams, allows high doses of radiation to be delivered to the target without damaging the surrounding tissue. This conformality and selectivity are particular features of Radiosurgery. It is this ability to generate zones of very high radiation close to zones of very low radiation which distinguishes Radiosurgery from stereotactic radiotherapy. Radiosurgery can be described as a surgical procedure without the downsides of open surgery. There are fewer complications and none of the traditional complications associated with open surgery, because the problems of accessing lesions located deep in the brain. The patient often does not need to stay in hospital, even overnight. Patients prefer Radiosurgery because of its lack of sideeffects: they can go home immediately, and can get back to their pre-operative lifestyle very quickly. This minimal hospitalisation and insignificant post-operative care also reduce costs. Radiosurgery involves the use of very capital-intensive technology. However, although the capital cost is high, the cost per patient treatment is much lower than the average cost of treating patients currently. This is because Radiosurgery requires much less intensive resource inputs (other than the capital costs of the Intracranial Radiosurgery unit itself) itself than open surgery, Purchasing an Intracranial Radiosurgery system is a classic case of capital investment yielding benefits in terms of lower revenue costs. Radiosurgery is unusual in offering: clinical outcomes that are as good as, or better than, current alternatives; lower costs per treatment than current spending;

overwhelming advantages in terms of patient acceptability.

Many new technologies give planners a problem: where will the funds come from to fund treatments for problems which previously were not treated or were treated using simple, old, and cheap technologies. Radiosurgery, however, offers the prospect of reducing revenue costs, as well as delivering a better patient service. Radiosurgery substitutes for existing, more expensive, open surgery.

Patient throughput is critical to the average patient treatment cost. Whatever the capital and running costs are for a specific centre, and what ever depreciation method is used, increasing the throughput from 200 patients t0 300 patients will more or less halve average patient costs, because the marginal cost of treating patients in this range is very small. This is because the only significant variable cost for the SRS centre is the cost of staff. If staff are employed full time at the centre, the marginal cost of staff is zero within the range of throughput these staff can handle. Since other costs are largely fixed, within the range that can be handled by a given complement of staff, additional patients are treated without increasing the budget. The intensity of use is expressed as as the number of patients treated per treatment per day. With a single shift the operation time is eight hours per day. Experience has shown that preparatory treatment for the next radiological intervention can be carried out concurrently with the actual irradiation of a patient. This enables at least two patients to be treated every second treatment day, giving an average of 1.5 patients per day.
The maximum practicable operation is expressed by the number of treatment days per year effectively possible. There are 52 weeks a year and excluding holidays and other planned activities for personnel,it is estimated that there are 44 weeks, five days a week, for treatments. This number is limited to normal staffing patterns rather than to limitation of the machine. This represents the reasonable theoretical capacity of one unit working with one full time team which is around 330 patients per year ( 44 weeks x 5 days x 1.5 patients per day)

Cost of sustaing the equipment The useful lifetime of any piece of heavy equipment is, to some extent, a matter of opinion. The Intracranial Radiosurgery unit is extremely robust and does not wear out. The radiation sources decay at the natural rate of

cobalt-60, and treatment times gradually lengthen, although the machine continues to function in exactly the way intended however far the decay process goes. There is no fixed time to change the sources: as treatment times lengthen, throughput falls, and the cost per patient treatment rises. At some point, which can be calculated specifically for each installed machine, the marginal increase in patient treatment costs exceeds the marginal extra cost of purchasing the reload. This point will not be the same for every machine. Reloading cobalt-60 is straightforward, and once this is done the machine is restored to its original specification. Reloading is typically carried out after 7 years, so the cost of a machine and one reload would give it a life of 14 years. Running costs Although the cost of buying an Intracranial Radiosurgery unit is high, the unit is very economic to run. The structure of the Intracranial Radiosurgery is simple, robust, and massive. They have low maintenance costs, which is associated with a very low proportion of scheduled or unscheduled downtime. This means that throughput can be kept high, spreading the capital cost across a larger number of patients. Because of their robust structure, and the integrated nature of the Intracranial Radiosurgery system (the radiation unit and all the peripherals), it needs very limited quality assurance procedures to assure patient safety.