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Policy Proposal for Gamma Knife Stereotactic Radiosurgery

______________________________________________________________________

Lookman AlliTamara Djuretic

September 2009_______________________________________________________________________

Policy Lead: Tamara DjureticDate of policy: September 2009 (Version 3)Date of review: September 2010

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Table of Contents

1. Recommendations-------------------------------------------------------------------------------------3

2. Introduction--------------------------------------------------------------------------------------------- 5

3. Trigeminal neuralgia (TN)----------------------------------------------------------------------------5

4. Brain (cerebral) metastasis--------------------------------------------------------------------------7

5. Arteriovenous malformations (AVMs)------------------------------------------------------------8

6. Meningiomas-------------------------------------------------------------------------------------------- 3

7. Appendix------------------------------------------------------------------------------------------------- 3

9. References----------------------------------------------------------------------------------------------- 3


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1. Recommendations

In the absence of very high quality evidence on the effectiveness of gamma-knife surgery for treating the following conditions, it is recommended that this service is not routinely commissioned by NHS Haringey. It is therefore proposed that NHS Haringey should fund requests for stereotactic radio-surgery with Gamma Knife where the following criteria are met and in carefully selected patients in whom the procedure will most likely be beneficial:

a. Trigeminal NeuralgiaNHS Haringey should fund requests for stereotactic radio-surgery with Gamma Knife for the treatment of trigeminal neuralgia if the following conditions are met:

Pain is very severe affecting the quality of life of the patient; First line treatment using medications has failed; Other convectional treatments have also failed or are inappropriate to use. The clinician should ensure that patients understand the potential

complications of the procedure and the uncertainty about its efficacy in the long term.

Arrangements for audit and clinical governance should also be in place.

b. Cerebral metastasis

Treatment with conservative surgery is contraindicated or considered clinically inappropriate;

The patient has a Karnofsky Performance Score (KPS) of greater than 70 (Appendix I);

There is no active extracranial cancer; The patient is clinically fit to undergo the procedure; There are no more than two cerebral metastatic lesions. Whole brain radiotherapy (WBRT) has already been tried; The lesions should be equal to or less than 3 cm in size. The clinician should ensure that patients understand the potential

complications of the procedure and the uncertainty about its efficacy and safety.

Arrangement for audit and clinical governance should also be in place.

c. Arteriovenous malformations (AVMs) Treatment with surgery or embolisation followed by surgery is

contraindicated or considered clinically inappropriate; The size of the lesion is equal to or less than 3cm; Treatment is not aimed to be fractionated; The lesion is Grade III or less on the Spetzler- Martin Grading Scale; The lesion is compact (and not a diffuse malformation).


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d. Meningiomas If treatment with surgery is contraindicated or considered clinically

inappropriate; The size of the lesion is equal to or less than 3.5 cm; Treatment is not aimed to be fractionated; The lesion is benign and typical; The lesion belongs to World Health Organisation (WHO) Grading I where the

histology is known. There are no more than 2 lesions.

Patients who are not eligible for treatment under this policy may be considered on an individual basis where their GP or consultant believes exceptional circumstances exist that warrant deviation from the rule of this policy. Those cases may be reviewed at the Individual Cases Panel making sure that the following above conditions are met.


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2. Introduction

2.1 The procedureGamma knife is a complex machine that uses an element known as cobalt 60 as its energy source, and is able to focus a precise intersection of beams of gamma rays to perform radio-surgery. Radio-surgery radiation treatment utilizes a precisely focused beam of radiation to treat a small, defined, target lesion while minimizing irradiation of adjacent normal structures. The procedure is at most minimally invasive and, is now being used in the treatment of conditions such as trigeminal neuraligia, primary and secondary brain tumours (metastases), arteriovenous malformations (AVMs), vestibular schwannoma and so on.

The target for the radio-surgery is usually clearly defined through prior use of high-resolution computerised tomography (CT) and Magnetic Resonance Imaging (MRI) scans.

2.2 Current providers of stereotactic radiosurgery using Gamma KnifeThere are a few specialist units across England and Wales and, among them are:

- Barts & The London Hospital (where NHS Haringey has a case by case service level agreement (SLA).

- Sheffield Teaching Hospital and;

- The Cromwell Hospital

All treatment requests are currently considered through the Individual Cases Panel (ICP) for decision and the number of requests is increasing. The panel considered a total of 4 requests for funding treatment with Gamma Knife radiosurgery in 2008 and another 4 have been considered in 2009.

3. Trigeminal neuralgia (TN)Trigeminal neuralgia is a condition characterised by sudden bursts of facial pain, which may be triggered by touch; talking; eating, or brushing teeth. The pain occurs in the areas supplied by the trigeminal nerve such as the cheeks, jaw, teeth, gums, lips and, less often, around the eye or forehead. Trigeminal neuralgia is rare in occurrence; the mean annual incidence is 4.7 per 100 000 population.1

Some people with mild symptoms recover without treatment but most people have bursts of severe pain indefinitely. Where treatment is indicated, the first line

1 J.N.W. Lim, L. Ayiku. The clinical efficacy and safety of stereotactic Radio-surgery (gamma knife) in the treatment of trigeminal neuralgia. January 2004 (on behalf of NICE)


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treatment for trigeminal neuralgia is medication such as Carbamazepine, Phenytoin and Baclofen. Approximately 70% of trigeminal neuralgia patients are well-controlled by non-operative means. Surgery is considered for people who experience severe pain despite medication, or who have side effects from medication. Other treatments for severe trigeminal neuralgia include: glycerol injection into trigeminal nerve under x- ray guidance; radiofrequency radio-surgery, balloon micro-compression, which involves inflating a balloon near the nerve. All of these are minimally invasive surgical procedures. Another form of treatment is microvascular decompression, which is a more invasive procedure involving opening the skull.Error: Reference source not found

3.1 Clinical Efficacy & Safety

Radio-surgery for the treatment of trigeminal neuralgia was a subject of a systematic review commissioned by the National Institute of Clinical Excellence (NICE) in 2004. The review reported that between 33% and 90% of patients achieved complete initial pain relief after stereotactic radiosurgery using the gamma knife. After a mean follow-up period of 18 months, the proportion of patients with recurrence of pain ranged from 0% to 34%, with an average of 14%.Error: Reference source not found

A careful interpretation suggests that in typical trigeminal neuralgia, gamma knife radiosurgery offers similar clinical efficacy, in terms of initial and short –term pain relief as microvascular decompression, percutaneous radiofrequency thermocoagulation rhizotomy, percutaneous glycerol rhizolysis and percutaneous balloon compression. Error: Reference source not found

A reported zero rate of operative mortality, a low rate of major complication risk, and only minor complications were reported in review commissioned by NICE.Error:Reference source not found The most common complication reported was facial numbness, affecting 8% (139/1757) of patients. New or worsened trigeminal nerve dysfunction was reported in 4% (66/1757) of patients. Facial paraesthesia occurred in 2% (33/1757) of patients. Less commonly reported complications included troublesome dysaesthesia, loss of taste, corneal numbness and deafness. There is a lack of long-term data and the condition can recur. Although the recurrence rate appears to be higher after stereotactic radiosurgery than after other treatments, the patient groups reported were not comparable. Relapse is most common in patients with multiple sclerosis and atypical neuralgia.Error: Reference source not found

3.2 Local cost implicationsThe mean annual incidence of trigeminal neuralgia is 4.7 per 100 000 population, suggesting that Haringey would expect approximately 11 new cases of trigeminal neuralgia each year. Of this, three to four cases would not respond to medications and would require other modalities of treatment.


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The cost of treatment of trigeminal neuralgia using Gamma Knife Radio surgery is £7,9902. If we assume that two patients with TN would eventually need to be treated with Gamma Knife per year that would result in total cost of £15,908.

3.3 Existing guidelines/ positions professional groupsNICE Interventional Procedure Guidance (IPG 85) published in 2004 states that the ‘current evidence on the safety and efficacy of stereotactic radiosurgery for trigeminal neuralgia using the gamma knife appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance’3

4. Brain (cerebral) metastasisMetastasis to the brain common occurs from primary cancers in lung, breast and gastrointestinal tract. In general 15-30% of cancer cases develop cerebral metastasis per year. In general terms, once brain metastases are diagnosed, the median survival is less than a year; however, timely therapy could restore neurological function and prevent further neurological complications of cancer for the duration of a patient's survival.5

Treatment modalities for cerebral metastasis include surgery, radiotherapy and, supportive care with drugs like corticosteroids. Surgery provides the best therapy, especially in patients with good prognostic features, but results are still not encouraging because even patients with the best prognostic indicators often die within 18 to 24 months.4 The common agreed factors for poor prognosis in cerebral metastasis include poor performance status on the Karnofsky Performance Scale (KPS) score, old age, and active extracranial disease.5

4.1 Clinical Efficacy & SafetyA systematic review of evidence to assess the efficacy of gamma knife radiosurgery in the treatment of brain metastasis (and other conditions such as arteriovenous malformations, acoustic neuroma, cerebral metastases and trigeminal neuralgia) shows there is no benefit for Gamma Knife radiosurgery compared to whole brain radiotherapy (WBRT), when employed as first line radiation treatment. None of the studies considered showed that surgical excision is better than WBRT alone.6 No RCT comparing GKS with surgical resection was found; however a retrospective case- controlled study suggested that there was no statistically significant improvement in median survival between surgery and GKS.7

4 Alexander E 3rd, Loeffler JS. The case for radiosurgery. Clin Neurosurg. 1999;45:32-40

5 Gaspar L, Scott C, Rotman M, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastasis trials. Int J Radiat Oncol Biol Phys 1997;37:745-751


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Evidence from small RCT found that there may be slightly improved local control for patients treated with radiosurgery plus WBRT compared with WBRT alone. There was, however, no survival benefit for these patients. The results of uncontrolled case series generally supported those of the randomised trial.8

Another study evaluated the role of stereotactic radio-surgery (SRS) in 83 patients with multiple brain metastases who underwent SRS between 1991 and 1999 by analyzing prognostic factors that predict survival. All 83 patients were included in the calculation of overall survival. The overall survival was 22% at one year and 13% at two years, and a median survival of 5.4 months (range, 0.3-28.8 months) was demonstrated.

Variables that predicted survival were Karnofsky Performance Scale (KPS) score, extracranial disease status, and the number of intracranial metastases. Median survival in patients with a KPS score greater than as compared with less than 70 was 9.1 and 2.7 months, respectively (p = 0.002). Median survival, when comparing absence and presence of extracranial disease, was 9.9 and 4.1 months, respectively (p = 0.02). Median survival in patients harbouring two, three, or four or more lesions was 6.6 months, 5.4 months, and 2.7 months, respectively (p = 0.02). In patients with a KPS score greater than or equal to 70 and with three or fewer lesions, median survival was 7 months or longer.9

4.2 Local cost implicationsThere were 694 cancers in Haringey in 2007.10 Of those, 15-30% would develop cerebral metastasis. Hence, we would expect between 104- 264 new cases of cerebral metastasis per year in Haringey. A proportion of these cases could be considered for Gamma Knife radiosurgery however it is difficult to determine the exact number of cases that would meet the proposed set of criteria .

The cost of a Gamma Knife procedure is £7,990 excluding anaesthesia and other materials.

4.3 Existing guidelines/ Positions of Professional groups The Guidance of Cancer Service: Improving Outcomes for People with Brain and Other CNS Tumours published by NICE in June 2006 advise as follows:

‘Complete surgical excision should be considered in patients with single metastases where the risk of unacceptable complications is low. Postoperative radiotherapy following the resection of solitary metastases may reduce the likelihood of intracranial relapse in appropriately selected patients.

Stereotactic radiotherapy can be considered as an alternative to surgery in small lesions (< 3 cm) when the histopathological diagnosis is known. Occasionally it may be considered in patients with more than one lesion. The role of further treatment with

10 Thames Cancer Registry January 2007.


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radiotherapy to the brain following stereotactic radiotherapy is uncertain, although it may prevent intracranial relapse.’

The American Society for Therapeutic Radiology and Oncology (ASTRO) in their review of the role of radiosurgery for brain metastases in 2005 reported that ‘there is insufficient evidence as to the clinical benefit/risks radiosurgery used in the setting of recurrent or progressive brain metastases, although radiographic responses are well-documented’.11

5. Arteriovenous malformations (AVMs)

Arteriovenous malformations (AVMs) are tangled web of abnormal arteries and veins connected by abnormal corridors (fistulas). They are generally thought to be present from birth and most commonly occur in the brain. AVM lesions are graded using the Spetzler-Martin Grading Scale, which is based on the lesion’s diameter, location and venous drainage. (see Appendix I)

The prevalence of arteriovenous malformation is estimated at approximately 0.01% of the general population, but reported rates range from 0.001% to 0.52%12. The annual incidence rate is around 1.1 (95%CI 0.9 to 1.4) per 100,000 adults per year.13

Brain arteriovenous malformations (AVMs) are the single most common cause of intracerebral haemorrhage in young adults occurring in 42 to 72% of clinically apparent arteriovenous malformations. After an initial hemorrhage, the annual risk of a subsequent hemorrhage has been reported to range from 4.5 to 34.4%; the best estimate is approximately 6% during the first year, with a return to the baseline risk afterward. AVMs can also cause seizure(s) and focal neurological deficits, migraine or an epileptic seizure in the absence of haemorrhage.

Several characteristics specific to arteriovenous malformation may also predict an increased risk of hemorrhage such as the presence of aneurysms, drainage into the deep venous sinuses, deep location (i.e., basal ganglia, internal capsule, thalamus, or corpus callosum), a single draining vein, and venous stenosis. Some data also suggest that risk increases with decreasing diameter of the malformation.Error: Reference source not found

Treatment options include neurosurgical excision, endovascular, and staged combinations of these interventions can be used to treat brain AVMs.14 Radio-surgery is also an option- it avoids a craniotomy (opening the skull via surgery), but there is a lag period of approximately one to three years from the time of treatment to potentially complete obliteration of the arteriovenous malformation, during which time there continues to be a risk of hemorrhage.Error: Reference source not found Trials directly comparing these approaches with one another or with observation are

12 Robert M. Friedlander. Arteriovenous Malformations of the Brain. The New England Journal of Medicine. Boston: Jun 28, 2007. Vol. 356, Iss. 26; pg. 270413 Source: Scottish Intracranial Vascular Malformation Study (SIVMS)


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lacking, and information on outcomes derives largely from case series. A randomised trial of unruptured brain AVMs (ARUBA) is currently underway to evaluate long-term outcome of best possible standard interventional therapy as compared to the natural history risk in a prospective multidisciplinary international study (www.arubastudy.org).

5.1 Clinical Efficacy & Safety A systematic review to assess the effects of stereotactic radiosurgery compared with conventional neurosurgery or whole brain radiotherapy on functional outcomes and survival in people with secondary brain tumours, acoustic neuromas or arteriovenous malformations found no level 1 studies. The studies identified suggest that stereotactic radiosurgery may be beneficial in the treatment of brain metastases, AVMs and acoustic neuromas. 15 The conclusion from another systematic review to assess the effectiveness of stereotactic radiosurgery (SRS) treatment in a range of conditions was that SRS should be regarded as a complementary option, with surgery being preferred if the lesion could be excised safely.16

A follow- up study to investigate cure rate after gamma knife radiosurgery treatment performed on 300 patients with AVMs with size ranging from 0.15 to 28.6 cm (median, 3.9 cm) found that obliteration was achieved in 222 (74%) patients after the first round of radiosurgery and in 47 (69%) after the second. The overall chance of cure was 92% (269 patients). Final angiography verified complete obliteration by 12 to 96 months (median, 25 months) after initial radiosurgery. Smaller volume AVMs and the application of a higher radiation dose resulted in a higher chance of obliteration. The risk of rebleeding after radiosurgery was 2.1% annually until full obliteration and the overall mortality from rebleeding was 1%. The risk of permanent morbidity after the first and second radiosurgery treatments were 2.7 and 2.9%, respectively. The cumulative risk of morbidity in both groups of patients was 3.4%.17

A prospective study of 500 patients followed up for a median of 7.8 years reported the cure rates for radiosurgery as ranging from 81 to 90% for lesions less than 3 cm in diameter, with lower cure rates for larger lesions. The risk of hemorrhage was reduced by 88% after obliteration by radiosurgery.

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In general, there is a 5% to 7% risk of treatment-related complications with radiosurgery. Over a 3-year period, the patient has a 14% to 19% risk of complication or hemorrhage in addition to possible incomplete obliteration.19 Early complications include seizures, nausea, vomiting, and headaches, most of which are self-limited.

18 Maruyama K, Kawahara N, Shin M, et al. The risk of hemorrhage after radiosurgery for cerebral arteriovenous malformations. N Engl J Med 2005;352:146-53.

19 AHA Scientific Statement Recommendations for the Management of Intracranial Arteriovenous Malformations. A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Stroke Association. Circulation. 2001;103:2644-2657


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Delayed complications, which can occur weeks to years after treatment, include seizures, hemorrhage, radionecrosis, progressive edema, and venous congestion; in rare cases, these can be life-threatening.Error: Reference source not found

5.2 Cost EffectivenessAn economic study comparing surgical resection with GKS for small an operable brain AVMs notes that surgical resection confers a larger clinical benefit over GKS by protecting patients earlier from haemorrhage. Surgical resection was found to confer a 0.98 quality-adjusted life year (QALY) advantage over GKS. The incremental cost-effectiveness ratio is $7100 per QALY for a patient treated surgically. The result was also found to be sensitive to surgical morbidity and surgical mortality only. The preferred treatment strategy favouring GKS only at the extreme high end of the

3 NICE. Stereotactic radiosurgery for trigeminal neuralgia using the gamma knife. Interventional Procedure Guidance 85. August 2004

6 Ontario Ministry of Health and Long-Term Care. Health Technology Assessment Database 2008 Issue 3

7 P. Charles Garell1, Patrick W. Hitchon1, B. Chen Wen2, David E. Mellenberg2 and James Torner3Stereotactic Radiosurgery Versus Microsurgical Resection for the Initial Treatment of Metastatic Cancer to the Brain. Journal of Radiosurgery.Volume 2, Number 1 / March, 1999.9 Cho KH, Hall WA, Gerbi BJ, Higgins PD. The role of radiosurgery for multiple brain metastases. Neurosurg Focus. 2000 Aug 15;9(2):e2

11 Mehta MP, Tsao MN, Whelan TJ, Morris DE, et al. The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys. 2005 Sep 1;63(1):37-46.

14 Al-Shahi R, Warlow CP. Interventions for treating brain arteriovenous malformations in adults. Cochrane Database of Systematic Reviews: Reviews. DOI: 10.1002/14651858.CD003436.pub2. John Wiley & Sons, Ltd. 2006 Issue 1

15 Michell A W. Stereotactic radiosurgery for brain tumours and arteriovenous malformations. London: Bazian Ltd (Editors), Wessex Institute for Health Research and Development, University of Southampton. 2001, 11. STEER: Succint and Timely Evaluated Evidence Reviews 1(13)16 Hailey D. Stereotactic radiosurgery: an update. Edmonton, AB, Canada: Alberta Heritage Foundation for Medical Research. 2002, 102 ISBN 1896956564

17 Liscák R, Vladyka V, Simonová G, Urgosík D, Novotný J, Janousková L, Vymazal J.Arteriovenous malformations after Leksell gamma knife radiosurgery: rate of obliteration and complications. Neurosurgery 2007 Jun;60(6):1005-14; discussion 1015-6.2 Source: Cromwell Hospital


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http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Simonov%C3%A1%20G%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Tsao%20MN%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Higgins%20PD%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Gerbi%20BJ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus

http://www.springerlink.com/content/epdbb3pa8d0t/?p=62a10d5772d644cd87d1743a65dec464&pi=0

http://www.springerlink.com/content/epdbb3pa8d0t/?p=62a10d5772d644cd87d1743a65dec464&pi=0

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possible range for these variables, when the rate of permanent neurological morbidity resulting from surgery exceeds 12% or the surgical mortality rate exceeds 4%.20

5.3 Existing guidelines/ Positions of Professional bodies - A report on Gamma Knife radiosurgery by the Society for British Neurological Surgeons in 2001 noted that it is ‘less suitable for larger (> 3cm) targets’ and also ‘not suited to fractionated treatments’.21

- Stroke Council of the American Stroke Association recommends ‘Strong consideration of surgery is recommended for lesions of Spetzler-Martin grade I and grade II, and consideration of endovascular embolization followed by microsurgery is recommended for grade III lesions. Consideration of radiosurgery is recommended for lesions that may be associated with an increased rate of surgical complications, owing to their anatomical location or feeding-vessel anatomy, in particular for lesions in eloquent tissue. Because of the risks of treatment, grade IV and grade V lesions are generally not treated.’Error: Reference source not found

5.4 Local cost implicationsThe in- patient cost for stereostatic radiology treatment for AVMs is £6,16822

(excluding other costs)

An estimated three patients would develop AVMs in Haringey per year; of those an estimated 23% would potentially be treated by stereostatic radiology per year.Error:Reference source not found Hence, an estimated one patient in two years would require treatment by gamma knife for AVM in Haringey.

6. MeningiomasMeningiomas are primary intracranial tumours arising from the Arachnoid, the fibrous covering of the brain and the spinal cord. They are the second most common primary tumor of the brain accounting for about one-fifth of all primary intracranial tumors.23

Population-based studies in the USA indicate an overall incidence of 2.3 cases per 100,000.24 An estimated 1200 new cases develop in the United Kingdom per year.Error:Reference source not found

Meningiomas are generally benign and usually slow growing; as they grow, they compress the normal brain. Eighty percent (80%) of people with slow- growing meningiomas will live more than 5 years. For those with high grade, malignant meningiomas, less that 6 out of 10 will live for 5 years.25 Seizures occur in approximately 50% of cases. Increased intracranial pressure (headache, blurred vision) are common.26

8 Centre for Reviews and Dissemination. Database of Abstracts of Reviews of Effects 2008 Issue 3. 2008 University of York. Published by John Wiley & Sons, Ltd


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Where feasible, craniotomy and complete removal of the tumours and its dural base has been the preferred treatment.Error: Reference source not found In large single-institution series, gross-total resection has been reported to achieve 5-, 10-, and 15-year recurrence-free survival rates of approximately 90, 80, and 70%, respectively. 27

Stereotactic radiosurgery is an option to surgery for meningiomas in locations, such as the skull base, where operative manipulation may be particularly difficult.28 Other options include radiotherapy and chemotherapy.

6.1 Clinical Efficacy & Safety

A systematic review of consecutive series of 309 meningiomas treated with gamma knife stereotactic radiosurgery by Malik I et al29 over a 6- year period found that the 5-year control rates was 87% for typical meningiomas, 49% for atypical tumours and 0% for malignant lesions. It was also found that tumour type (histology) was the main determinant of growth control (p < 0.001). In this study, there was an extreme selection bias towards lesions unfavourable for surgery, which was determined by the patients referred for treatment. Complications were reported in 3% of tumours, and were most frequently trigeminal and eye movement disturbances.Error: Referencesource not found

Another review of the literature on benign adult brain tumors using evidence-based standards and focusing on meningiomas and a few other benign primary brain tumours found that there is a level 3 evidence that radiosurgery is effective as an alternative to surgery in small to medium-sized meningiomas. The efficacy of drugs in therapy of meningiomas recurring after surgery was difficult to interpret due to lack of uniform criteria in the studies.30

Results from a follow-up study31 of 972 radio-surgically treated patients with 1045 intracranial meningiomas managed during an 18-year period showed that the overall control rate (described as tumour regression or size unchanged) for patients with benign meningiomas (World Health Organization Grade I) was 93%. Control rate for patients with World Health Organization Grade II and III tumors, tumor control was 50 and 17%, respectively. After 10 years, Grade 1 tumors were controlled in 91% (n = 53); in those without histology, 95% (n = 22) were controlled.

In those without previous histological confirmation (primary radiosurgery) and, receiving radio-surgery as the primary treatment (n = 482), tumor control rate was 97% at a median of 4 years. Of those whose neurological examination results were available, 93% either improved neurologically (n=87) or remained unchanged (n = 380). Past 10 years, 16 patients were stable, three were improved and, three were worse. Follow- up imaging past 8 and 10 years were obtained for 49 ad 22 tumours with control rates of 94 and 95% respectively. Delayed resection after radio-surgery was necessary in 51 patients (5%) at a mean of 35 months due to local tumour growth or increased symptoms. Additional radiotherapy was performed in 2.9% at an average of 32 months. Further radio-surgery was performed in 41 (4%) at 49 months due to new tumours. Eight of the patients later received chemotherapy (0.8%).


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Further analysis showed that worse overall survival significantly correlated with increasing age, increasing WHO grade from 0-III (0 for no tissue diagnosis) and increasing tumour volume. Worse disease survival was found to be significantly associated with WHO grade from 0-III, increasing age, and multiple tumours. In this study the overall morbidity rate attributable to radio-surgery was 7.7% at an average time of 11 months.

6.2 Existing guidelines/ Positions of Professional bodies NICE, in their Guidance of Cancer Service: Improving Outcomes for People with Brain and Other CNS Tumours published in June 2006 advise as follows32:

’Resection may be appropriate for patients with skull vault meningiomas. It can prevent further disease progression and the associated deterioration in neurological function although recurrence may occur. Radiotherapy may be considered followinghistopathological confirmation of the diagnosis in patients with the following features:• a WHO histopathological grade 2/3 tumour• invasion by tumour of adjacent brain or extensive invasion of other tissues• a second or subsequent relapse• a contraindication to surgery.

Stereotactic radiotherapy and radiosurgery may be useful in selected patients although the value of these approaches is still uncertain. There is no clearly established role for chemotherapy, hormonal therapy and radiolabelled treatments in the management of these patients.’

6.3 Local cost implicationsIncidence of brain meningioma is 2.3 per 100,000 population per year. Haringey would expect approximately five new cases of meningioma per year; an estimated 33.3% of these cases would potentially require treatment with radiosurgery. Hence, potentially two patients from Haringey would require the treatment per year at cost of £15,980.


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7. Appendix Appendix I


Appendix II

Spetzler-Martin Grading Scale for Arteriovenous Malformation*Feature Score

Maximum diameter

< 3 cm 1

3-6 cm 2

> 6 cm 3

Location

Non eloquent cortex tissue 0

In or adjacent to eloquent cortex tissue 1Venous drainage

Superficial only 0

Deep 1

The sum of the scores is equal to the grade*


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8. References

20 Porter, PJ. MD et al. Surgery versus Stereotactic Radiosurgery for Small, Operable Cerebral Arteriovenous Malformations: A Clinical and Cost Comparison. Neurosurgery: October 1997 - Volume 41 - Issue 4 - pp 757-766

21 Society for British Neurological Surgeons. Report on Stereotactic Radiosurgery/ Radiotherapy Workshop. April 2001.

22 Source: National Centre for Streotactic Radiology, Sheffield

23 International Radiosurgery Association. Meningioma. http://www.irsa.org/meningioma.html (viewed on 07/01/09)

25 CancerResearch United Kingdom . Statistics and outlook for brain tumours @ http://www.cancerhelp.org.uk/help/default.asp?page=5296#mening1 (viewed on 07/01/09)

26 Johns Hopkins University. Johns Hopkins Medicine Radiostatic Surgery (http://www.radonc.jhmi.edu/radiosurgery/disorders/meningioma.asp) viewed on 07/01/09

27 Rogers L,Mehta M. Role of radiation therapy in treating intracranial meningiomas.Neurosurgical Focus, 2007, vol./is. 23/4(E4), 1092-0684 (Abstract).

28 Elia AE,Shih HA,Loeffler JS. Stereotactic radiation treatment for benign meningiomas. Neurosurgical Focus, 2007, vol./is. 23/4(E5), 1092-0684.

29 Malik I,Rowe JG,Walton L,Radatz MW,Kemeny AA.The use of stereotactic radiosurgery in the management of meningiomas.British Journal of Neurosurgery, Feb 2005, vol./is. 19/1(13-20), 0268-8697.(Abstract)

30 Aghi M,Barker FG. Benign adult brain tumors: an evidence-based medicine review. Progress in Neurological Surgery, 2006, vol./is. 19/(80-96), 0079-6492.24 Medscape. e-medicine, Meningioma @ http://emedicine.medscape.com/article/1217466-overview (viewed on 07/01/09)


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http://www.radonc.jhmi.edu/radiosurgery/disorders/meningioma.asp

http://www.cancerhelp.org.uk/help/default.asp?page=5296#mening1

http://emedicine.medscape.com/article/1217466-overview

http://www.irsa.org/meningioma.html

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31 Kondziolka D,Mathieu D,Lunsford LD,Martin JJ,Madhok R,Niranjan A,Flickinger JC.Radiosurgery as definitive management of intracranial meningiomas. Neurosurgery, Jan 2008, vol./is. 62/1(53-8; discussion 58-60), 1524-4040.32 NICE. Guidance of Cancer Service: Improving Outcomes for People with Brain and Other CNS Tumours. June 2006. Policy Lead: Tamara DjureticDate of policy: September 2009 (Version 1)Date of review: September 2010

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