Update of radiosurgery at the Royal Adelaide Hospital

Update of radiosurgery at the Royal AdelaideHospitalDE Roos,1 BP Brophy,2 MK Bhat3 and ES Katsilis4

Departments of 1Radiation Oncology, 2Neurosurgery, 3Medical Physics and 4Radiation Therapy, Royal Adelaide Hospital, Adelaide,

South Australia, Australia

SUMMARY

This is an update of the Royal Adelaide Hospital radiosurgery experience between November 1993 and December

2004 comprising 165 patients with 168 intracranial lesions. Including re-treatment, there were 175 treatment epi-

sodes (163 radiosurgery and 12 stereotactic radiotherapy) at an average of 1.3 per month. The commonest lesions

were acoustic neuroma (65), arteriovenous malformation (58), solitary brain metastasis (23) and meningioma (14).

The clinical features, treatment details and outcome are described. Our results continue to be well within the

range reported in the published work. Radiosurgery provides an elegant, non-invasive alternative to neurosurgery

and conventional external beam radiotherapy for many benign and malignant brain tumours.

Key words: brain; linac; radiosurgery; stereotactic radiotherapy.

INTRODUCTION

Radiosurgery (RS) is the use of single large doses of highly

focused ionizing radiation to treat small lesions localized by

stereotactic technology. All nine Australasian units are linac

based (there are no gamma knife or charged particle acceler-

ator systems at the time of writing). The Royal Adelaide Hos-

pital (RAH) commenced RS in 1993 using a German-designed

Fischer–Leibinger system (now Stryker–Leibinger), the only one

of its type in Australasia. Treatment has been restricted to

intracranial pathology, although RS is now commonly used

elsewhere for head and neck, and trunk tumours. Because of

resource constraints, fractionated RS, so-called stereotactic

radiotherapy (SRT), only commenced at the RAH in 2001.

An audit of our results for the first 65 treated lesions and a

subsequent update of 16 solitary brain metastasis patients

both confirmed outcomes consistent with those reported in

the published work to that time.1,2

The purpose of the current study is to review the overall

RAH RS/SRT experience up to December 2004. Data at pre-

sentation and follow up were prospectively gathered in our

weekly RS clinic, supplemented where necessary by phone or

written contact with the patients and their referring specialist or

general practitioner.

MATERIALS AND METHODS

Radiosurgery was initially carried out on a Siemens KD2 linac

(Siemens Medical Systems, Concord, CA, USA), but from

1998, a Varian 6/100 linac (Varian Medical Systems, Palo Alto,

CA, USA) was used. The procedure is as previously described.1

Briefly, the patient is admitted to the neurosurgical ward on the

morning of RS for fixation of the stereotactic head ring, followed

by angiography (for arteriovenous malformations (AVM) only)

and CT imaging of the brain for computer planning (all patients).

If MRI is required, this is usually arranged the preceding week,

with CT–MRI fusion carried out on the day of RS. Computer

planning is completed by late morning, and treatment takes

place mid to late afternoon (for logistics reasons) after which

the head ring is removed. Patients are generally observed over-

night, with discharge the following morning. Although not

essential for RS, inpatient management is convenient in view

DE Roos BSc(Hons), MD, FRANZCR; BP Brophy FRACS; MK Bhat MSc, M App Sc, Dip Rad Phys; ES Katsilis MIR.

Correspondence: Dr Daniel E Roos, Department of Radiation Oncology, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia.

Email: [email protected]

Submitted 9 February 2005; accepted 24 November 2005.

doi: 10.1111/j.1440-1673.2006.01560.x

RadiationOncology Australasian Radiology (2006) 50, 158–167

ª 2006 The AuthorsJournal compilation ª 2006 Royal Australian and New Zealand College of Radiologists

of the above scheduling. For patients having SRT, a relocatable

rigid fibreglass head cast is constructed during the preceding

week and treatment is on an outpatient basis.

The default beam arrangement is six equally dose-weighted,

non-coplanar arcs per isocentre using 140� gantry rotation per

arc and equal angular separation (30�) between the arcs. This

produces a spherical dose distribution that can be modified by

omitting arcs, varying their separation, gantry rotation or dose

weighting to conform to the lesion contour. Sometimes, a com-

bination of circular collimator sizes is used. The available colli-

mators have 80% isodose curve diameters at isocentre ranging

from 4 to 55 mm. Irregular lesions may require the use of more

than one isocentre, which can have different collimator sizes

and different dose weightings to optimize conformity. We do not

currently have the option of micromultileaf collimation.

Between November 1993 and December 2004, 165 patients

with 168 lesions were treated. Six AVM and one brain meta-

stasis required re-treatment. Hence, there were 175 treatment

episodes (RS 163 and SRT 12) at an average of 1.3 per month.

Table 1 summarizes the clinical characteristics and treat-

ment details for the four commonest tumour types. Follow-up

data extends to September 2005.

Acoustic neuroma

There were four patients with bilateral acoustic neuroma (AN)

due to neurofibromatosis type 2 (NF2). Their median age was

28 years (range 19–40 years), characteristically younger than

the 61 unilateral (sporadic) cases (median 62 years, range

21–81 years). Six of the sporadic cases had RS for recurrence

after surgery that was carried out a median of 11.5 years pre-

viously (range 2.5–32 years). Two of these recurrences were

detected on follow-up imaging, the other four were symptom-

atic. Three of the 59 de novo tumours were picked up inci-

dentally on scans carried out for other reasons; the commonest

symptoms for the other 56 were hearing loss (51 patients),

tinnitus (46), disequilibrium (34) and trigeminal neuropathy

(eight).

Of interest, for the sporadic cases, there was an excess

of left-sided lesions (39:22 = 1.77). This difference was statis-

tically significant (P = 0.04).

Follow-up MRI and audiometry were carried out at

12 months, yearly for 2–3 years, then two yearly thereafter

unless there were clinical indications to vary this schedule.

Maximum dimensions mediolaterally (including contrast-

enhancing extension into the internal auditory meatus), antero-

posteriorly (usually obliquely) and superoinferiorly were

recorded. Because of the difficulties inherent in measurements

from sequential imaging (e.g. interpolation from the centimetre

scale; variable slice width and angulation on successive scans),

sustained changes �2 mm were deemed significant.

Arteriovenous malformation

Each of the 56 patients had solitary AVM except a 13-year-

old woman with Rendu–Osler–Weber disease (familial haemor-

rhagic telangiectasia) and a 43-year-old man, both of whom had

RS for two AVM. Five patients had prior treatment elsewhere

Table 1. Summary of the clinical features and treatment details for the four commonest tumour types

Acoustic neuroma Arteriovenous malformation Metastasis Meningioma

No. patients 65 56 22 14

No. lesions treated 65 58 23 14

No. treatments 65 64 24 14

Age (years)

Range 19–81 5–69 36–83 14–75

Median 61 36.5 64 47.5

Male:female 38:27 24:32 12:10 5:9

Largest diameter (mm)

Range 11–40 5–70 3–34 17–35

Median 22 23 19 24.5

Site Left = 39† Cerebral hemisphere = 42 Cerebral hemisphere = 20 Base of skull = 10

Right = 22† Thalamocapsular = 7 Thalamus = 1 Tentorial = 1

Cerebellum = 5 Cerebellum = 1 Parasagittal = 1

Brainstem = 2 Brainstem = 1 Optic nerve sheath = 1

Basal ganglia = 2 Lateral ventricle = 1

Marginal dose (Gy), RS cases only

Range 12–14 12–23 15–23 14–18

Median 12 18 19 15

Isocentres (1:2:3) 54:11:0 55:9:0 22:2:0 11:2:1

Prescription isodose curve (%)‡

Range 70–90 70–90 60–90 70–90

Median 85 80 75 80

†Sporadic (unilateral) cases only (n = 61). ‡Single isocentre technique only. RS, radiosurgery.

RAH RADIOSURGERY UPDATE 159


(embolization plus RS, two; conventional external beam radio-

therapy (RT) plus gamma knife, one; RS alone, one and partial

excision, one). Eleven AVM were discovered incidentally on

imaging (six at the time of intracranial haemorrhage from other

lesions). The commonest presentations otherwise were haem-

orrhage from the AVM (19 patients), seizures (15), headache

(10) and neurological deficit (six); some patients had a com-

bination of these features.

Eight paediatric patients (age 5–15 years) required a gen-

eral anaesthetic lasting 5.5–12 h (median 9 h) for planning and

treatment.

Seven of the biggest lesions (40–60 mm) were treated with

SRT (30 Gy in 5 or 6 fractions); one other patient with a 70-mm

AVM was offered ‘volume fractionation’ but failed to attend after

two of the three components had been treated.

Our policy was to monitor AVM regression with 12 monthly

MRI. Angiography was carried out as the gold standard to con-

firm apparent obliteration on MRI, or in any case at approxi-

mately 3 years (this being the time when re-treatment needs

to be considered in the event of nonobliteration because of the

continuing risk of haemorrhage).

Metastasis

Details for the first 16 patients have been previously de-

scribed.1,2 Six more have been treated subsequently, all with

MRI confirmed solitary (presumed) brain metastases. One

patient had RS for two metachronous lesions and another

had re-treatment of a brainstem metastasis at the time of symp-

tomatic recurrence. Thus, there were 24 RS treatments in all.

The commonest primaries were lung (12 patients) and mela-

noma (three), and the commonest presenting symptoms were

hemiparesis (10), headache (six) and visual field defect (five).

When classified by Radiation Therapy Oncology Group recur-

sive partitioning analysis (RPA) prognostic class (based upon

Karnofsky performance status, age and extracranial disease

status),3 four patients were in class 1, 16 in class 2 and two in

class 3.

Two patients had RS 12 and 31 months following excision

plus whole-brain radiotherapy (WBRT) for solitary brain meta-

stases at a different site. Of the other 20 patients, eight had

adjuvant WBRT (30 Gy in 10 or 36 Gy in 18 fractions) at the

time of the RS, two had subsequent WBRT for distant brain

relapse and one had focal (conventional) brain RT for local

relapse. The other nine patients (41%) did not receive conven-

tional brain RT in their remaining lifespan.

Meningioma

One meningioma was discovered incidentally on brain MRI car-

ried out for other reasons. Presenting symptoms for the other

13 patients were cranial neuropathy (10 patients), headache/

pain (five) and seizures (one). Ten patients had no prior treat-

ment, two had adjuvant RS after surgical debulking and two had

RS on progression 6 and 5 years after surgery (the latter also

had repeat surgery and conventional RT 3 years before the

RS). Nine patients had RS and the other five SRT (30 Gy in 6

fractions to 52.2 Gy in 29 fractions).

Miscellaneous

The clinical features and treatment details for eight patients with

various other lesions are summarized in Table 2.

RESULTS

Non-specific acute side-effects

The majority of patients experienced no acute side-effects.

Vomiting was recorded for six patients only (3.6%). In some

cases, analgesia and/or anaesthesia may have contributed.

This low incidence may reflect our policy of routine premedica-

tion with dexamethasone 8 mg i.v. and metoclopramide 10 mg

i.v. A few patients developed minor toxicity related to the head

ring pins (haematoma, infection, transient focal scalp tingling or

numbness). Many showed temporary 1- to 1.5-cm patches of

alopecia at the two posterior pin sites, thought to be due to

pressure ischaemia of the adjacent hair follicles. This was of

no cosmetic consequence as it was obscured by surrounding

hair. Reversible circular or ellipsoidal alopecia also developed

predictably in the case of subcranial lesions because of un-

avoidable irradiation of the overlying scalp. Several patients

reported lethargy for a week or two after the RS. One patient

with a medullopontine AVM developed facial flushing and fever

(38–39�C) the morning after RS. There was no obvious infec-

tion, and the symptoms settled conservatively.

Treatment outcome and site-specific side-effects are as

follows.

Acoustic neuroma

One patient died at 5 months from an unrelated cause and two

others await their first follow-up scan and audiometry at the time

of writing, leaving 62 evaluable patients.

A transient increase in tumour size associated with central

necrosis was observed in nine patients (16%) at a median of

12 months from RS (range 4–25 months). This typically per-

sisted for 1–2 years. The median increase was 4 mm (range

2–5 mm) (Fig. 1b).

Tumour control (defined as stable or reduced dimensions

on follow-up imaging relative to baseline) was achieved in 59 of

the 62 evaluable patients (95%) over a median observation

period of 48 months (range 12–134 months). Seventeen tumours

were stable over 12–85 months; 42 decreased by 2–12 mm

(median 4 mm) over 13–134 months (Fig. 1c). One of the three

patients whose tumour progressed had palliative RS to part

of a recurrent multicystic AN excised 32 years previously. The

cystic component increased at 26 months after RS, associated

with further distortion of the brainstem, but this has not required

surgical intervention after a further 7 years. The second had

160 DE ROOS ET AL.


Table

2.

Clinicalfeatures,treatm

entdetails

andoutcomeformiscellaneouslesions

Lesion

Site

Age(y)/sex

Priortreatm

ent

Symptoms

Dim

ensions(m

m)

Marginaldose

Outcome

1.Glomustumour

(recurrent)

Leftjugularbulb

45/F

Excised7ypreviously

Nonewsymptoms

133

133

11

18Gyto

75%

Stable

onMRIto

99mo

2.Subependymoma

(recurrent)

Fourthventricle

43/M

Subtotalexcision

41mopreviously

Episodic

vertigo,

disequilibrium,

nausea

203

203

20

12.5

Gyto

80%

Shrinkagefor31mo,then

slowregrowth

to403

393

26mm

by93mo.

Salvagesurgery

3.Arteriovenous

fistula

Lefttentorialedge

45/M

Nil

Atypicalheadaches

113

63

620Gyto

90%

Partialresponseon

angiographyat

29and38mo,temporarily

lostto

follow

up,still

patentonangiographyat

76mo.Salvage

embolization/surgery

4.Arteriovenous

fistula

Rightcavernous

sinus

65/F

Nil

Diplopia,retroorbital

pulsations

183

173

17

15Gyto

80%

Symptomsresolved.

Obliterationconfirm

ed

onangiographyat5mo

5.Haemangioblastoma

(recurrent)

Leftcerebellum

56/F

Excised13mopreviously

Headaches,vertigo

173

133

918Gyto

70%

Recurrentnodule

along

lefttentorialedgeanterior

totreatedsiteat48mo.

Repeatsurgery

6.Pituitary

adenoma

(recurrent)

Pituitary

fossa

47/F

Transsphenoidal

enucleation

13ypreviously,

ketoconazole

RecurrentCushing’s

syndrome

63

53

325Gyto

65%

Curedbiochemically

by

5moafterRS.

Panhypopituitarism

by36mo

7.Pinealtumour

(?pineocytoma)

Pineal

53/F

Nondiagnostic

stereotactic

biopsy2mopreviously

Gazepalsy

303

273

27

30Gyin

6fr

to85%

Stable

imagingat12mo,

stable

symptomsat

22mo

8.Prolactinoma

(recurrent)

Pituitary

fossa

59/M

Surgery

1RT8y

previously,

bromocriptine/cabergoline,

repeatsurgery

6mo

previously

Visualfield

defect

223

163

14

45Gyin

25frto

80%

Stable

onMRIat20mo.

Significantprolactin

response

fr,fractions;mo,months;RS,radiosurgery;RT,(conventional)radiotherapy;SRT,stereotacticradiotherapy;y,years.



salvage RS for recurrence 4.5 years after excision but developed

symptomatic progression 2 years following the RS. Pathology

at reoperation confirmed (benign) AN. The third patient’s

tumour was stable for 3 years after primary RS but increased

by 2–3 mm over the next 3 years without new symptoms. This

appears to be a delayed recurrence but further follow up will be

needed for confirmation. The current rate of freedom from sur-

gical salvage for patients treated with primary RS is thus 100%

and for the whole series 64/65 (98.5%).

With respect to hearing outcome, two of the four NF2

patients were functionally deaf before RS. The other two had

some hearing on the treated side but lost this by 2 months

Fig. 1. Coronal MRI images showing an enhancing left acoustic neuroma. (a) Before radiosurgery with pre-existing ventriculomegaly. (b) At

11 months, central necrosis associated with transient 3-mm enlargement. (c) At 24 months, progressive hydrocephalus requiring elective shunting.

(d) At 45 months, 5-mm shrinkage with resolution of the hydrocephalus.

162 DE ROOS ET AL.


(14 Gy) and 8 months (12 Gy). All six of the patients with post-

operative recurrences were deaf on that side. Of the other 55

(sporadic) cases, 19 (35%) had no useful ipsilateral hearing at

presentation (defined as pure tone average .50 dB or patient

report to that effect where audiometry was borderline). At the

time of writing, two of the 36 patients with initially useful hearing

await first follow-up audiogram. This leaves 34 assessable

patients, of whom 18 (53%) lost useful hearing by 8–77 months

(median 24 months), whereas 16 (47%) retained it over 20–

108 months (median 60 months) of follow up.

Nausea was reported by five patients after RS, lasting for

1.5–4 weeks. This was associated with vomiting in one patient

and vertigo requiring bedrest in another who developed a pul-

monary embolus at 2.5 weeks. Worsened disequilibrium also

occurred in five patients at 1, 2, 4, 5 and 7 months each requir-

ing temporary corticosteroids and brief admission for two of

them.

Mild/partial trigeminal neuropathies developed in seven

patients (two of whom also developed facial neuropathies).

Four of these were new (numbness, dysaesthesia or hyper-

aesthesia) at 4, 6, 12 and 20 months; the other three patients

developed trigeminal neuralgia in a distribution of pre-existing

numbness at 2, 6 and 41 months. Mild facial neuropathies

developed in four patients (facial weakness in three and

impaired ipsilateral taste in one). Three of these were new at

4, 6 and 7 months (one associated also with minor hemifacial

spasms reported at 42 months) and the other was transient

worsening of pre-existing facial nerve weakness at 4 months.

Significantly, when considered together, these V and VII neu-

ropathies affected four of eight patients (50%) receiving 14 Gy

but affected only five of the 57 patients (9%) receiving 12 Gy.

Ventriculoperitoneal shunting for hydrocephalus was re-

quired in three patients at 5, 6 and 27 months. However, in

two of these, ventriculomegaly preceded treatment and it is

unclear whether RS contributed to the natural history of this

known complication of untreated AN (Fig. 1c). The rate of de

novo hydrocephalus after RS was thus 1/63 (1.6%).

No second tumour has occurred at the treated site, but six

patients so far have developed distant neoplasms 6–56 months

after the RS, three fatal, namely contralateral parietal glio-

blastoma multiforme, contralateral suprasellar meningioma,

squamous cell carcinoma (SCC) of the lung, uterine leiomyo-

sarcoma, disseminated adenocarcinoma (unknown primary)

and ipsilateral metastatic parotid SCC (skin primary). None of

these would satisfy the criteria for radiation-induced tumours.


Of the five previously treated AVM, angiography confirmed

obliteration in three at 27, 31 and 57 months (the latter patient

failing to pursue earlier angiography); one poorly compliant

patient had a persistent diffuse vascular abnormality at

6.5 years but declined selective angiogram and further follow

up thereafter; the other has had a partial response on MRI after

2 years.

Fifty-three AVM were treated with primary RS (47) or SRT

(six). Six patients failed to continue follow up or declined con-

firmatory angiography, and 13 patients await 3-year angio-

graphy at the time of writing, leaving 34 assessable AVM.

Obliteration without any further treatment was confirmed in 25

of these (74%) at 12–56 months (median 26 months). Five

of the partially obliterated AVM went on to have repeat RS or

SRT at a median of 40 months after initial treatment (range 37–

47 months). Subsequent obliteration has so far been confirmed

in one of these 19 months after re-treatment; another had inde-

terminate angiograms (stable dysplastic vessels without early

draining vein) at 14, 25 and 36 months after re-treatment

(coded conservatively as nonobliteration). Hence, the crude

‘cure’ rate with primary RS/SRT (one or two treatments) stands

at 26/34 (76%). Two partially obliterated AVM required surgery,

one for haemorrhage at 36 months and the other for radionec-

rosis at 63 months.

There were three complications of angiography (haemor-

rhage at groin puncture site, presumed femoral artery throm-

bosis and vertebral artery occlusion), each of which resolved

conservatively without sequelae.

Two patients, both of whom were already on anticonvul-

sants for grand mal epilepsy, had partial seizures within a few

days of the RS, whereas a third had increased frequency and

severity of pre-existing hemisensory seizures during the first

few weeks after RS; one patient had a first generalized seizure

at 2 months, with, in retrospect, a history of partial seizures for

7–8 years before the RS; another developed complex partial

seizures from about 6 months, which subsequently became

intractable (related to radionecrosis) but had initially presented

with temporal lobe haemorrhage associated with one grand mal

and several focal seizures. Thus, there has been no case of

post-RS seizures developing in the absence of a history of

seizure disorder.

Six patients required dexamethasone for 1–4 months be-

cause of symptomatic oedema around the AVM at a median

of 6.5 months (range 6–20 months) after RS. Of interest, four of

these had been treated with a two isocentre technique (which

is associated with higher central dose). Two patients with

large, deeply seated AVM (left thalamic 47 mm, right basal

ganglia 60 mm) developed progressive hemiparesis from about

6 months after SRT but have been able to continue working

2–3 years later. One paediatric patient with a midbrain/thalamic

AVM required shunting for hydrocephalus at 21 months, al-

though it is unclear whether this was a complication of the RS.

Two patients (4%) have had nonfatal haemorrhages at the

site of the treated AVM, one at 36 months (mentioned above),

the other 9 years after initial RS elsewhere, and 58 and

59 months after repeat RS despite angiographically confirmed

obliteration at 57 months.



Metastasis

The estimated median survival from RS for the 22 patients was

10.1 months (95% CI 2.4–34.7 months), with the estimated

2-year survival being 35% (95% CI 18–58%). The actuarial

overall survival curve is shown in Figure 2a, and by RPA class

in Figure 2b. Despite the small number of patients, there was

a statistically significant difference in survival by RPA class

(P = 0.013, log–rank test). As far as could be determined, the

cause of death for the 17 deceased patients was central

nervous system disease (seven), systemic disease (five) and

both (five).

Meningioma

Thirteen of the 14 patients have had at least one MRI scan to

assess response. At a median radiologic follow up of 36 months

(range 7–123 months), six lesions have regressed (median

shrinkage 5.5 mm, range 2–10 mm), six have remained stable

and one has progressed. The latter patient had two operations

and conventional external beam RT for a parietal meningioma

within 5 years before the RS, which was given with palliative

intent to the solid component of a mixed cystic/solid recurrence.

He required further surgery after 9 months, pathology confirm-

ing transformation to atypical meningioma and he died at

19 months because of complications from his tumour. Another

patient who had RS for a recurrent lateral ventricle meningioma

excised 5 years previously developed a new site of disease

on the other side of the resection track (outside the high dose

region) at 28 months. He is asymptomatic at 10 years, but

although the treated site remains controlled, the new lesion

continues to grow (Fig. 3).

Five patients developed side-effects attributable to the treat-

ment: transient worsening of ipsilateral facial paraesthesiae

from a cavernous sinus meningioma at 18 months; partial

ipsilateral VI nerve palsy from a petroclival meningioma at

14 months (corrective eye surgery had to be revised subse-

quently because of recovery); transient contralateral hemisen-

sory loss from a parietal meningioma at 6 months; decreased

visual acuity during SRT for an optic nerve sheath meningioma

resolving with steroids, subsequent intermittent steroids for epi-

sodes of visual blurring and orbital pain; worsening ipsilateral

trigeminal neuralgia from a cerebellopontine angle meningioma

at 3 months resolving with steroids. These cases presumably

reflect temporary oedema due to the radiation.

Miscellaneous

Outcomes for the remaining eight patients are shown in

Table 2. Two patients with lesions within or adjacent to the

brainstem (cases 2 and 5) required dexamethasone because

of transient oedema following RS, but subsequently recovered

to pretreatment level of functioning. At the time of writing, five of

these lesions remain controlled with RS.

DISCUSSION

Acoustic neuroma

The optimal management of small to moderate-sized AN

(�3 cm) is controversial because of the absence of randomized

trials. Radiosurgery is certainly a viable alternative to micro-

surgery, but debate continues in the published work about the

relative merits of RS versus SRT, with a wide range of fraction-

ation schedules reported for the latter (20 Gy in 4–5 fractions up

to 45–59.4 Gy in 25–33 fractions).4,5 Tumour control rates are

similar with all three treatment options (.90–95%), and the

unacceptably high incidence of V and VII neuropathies reported

in early RS series has greatly improved as doses have progres-

sively decreased to ,14 Gy.6 Hearing preservation rates vary

enormously between series reflecting differing selection factors

(age, tumour size, degree of loss pretreatment), length of follow

up and definitions of ‘useful’ hearing.

0

20

40

60

80

100(a)

(b)

0 1 2 3 4 5 6 7

Number at risk

0 1 2 3 4 5 6 7

Number at risk

22 9 6 3 2 2 1 0

0

20

40

60

80

100

4162

441

420

300

200

200

100

000

Class 1Class 2Class 3

P = 0.013

Fig. 2. Actuarial survival curves for the 22 solitary brain metastases

patients treated with radiosurgery: (a) overall and (b) by recursive par-

titioning analysis class. ( ), RPA class 1; ( ), RPA class 2; ( ),

RPA class 3.

164 DE ROOS ET AL.


We have so far chosen to use RS (only) for AN, although two

NF2 patients were referred interstate for SRT before this option

became available at the RAH. Of significance, after we

reduced our marginal dose from 14 to 12 Gy, there have been

only two (mild) VII neuropathies, one motor, one gustatory

(2/57 = 3.5%), and four V neuropathies (4/57 = 7%), three of

which were transient, the fourth (trigeminal neuralgia) well

controlled with carbamazepine. Two of the four patients with

V neuropathies had pre-existing trigeminal dysfunction.

The freedom from surgical salvage rate for patients treated

with primary RS stands currently at 100%. Our preservation of

useful hearing rate of 47% at a median of 60 months is well

Fig. 3. Enhanced axial CT and MRI images showing a recurrent right lateral ventricle meningioma adjacent to the surgical defect. (a) Before

radiosurgery, maximum dimensions 20 · 20 mm. (b) At 28 months, shrinkage to 12 · 8 mm, but development of a tiny enhancing lesion on the

other side of the resection track. At (c) 78 and (d) 111 months, the treated site remains controlled, but the adjacent lesion continues steady growth to

18 · 16 mm. It is asymptomatic and the patient has so far declined further intervention.



within the 33–81% range found in the major RS and SRT

series.4 Three out of the 65 patients (4.6%) required shunting

for hydrocephalus after RS, but two of these had pre-existing

ventriculomegaly (de novo hydrocephalus rate 1/63 = 1.6%).

These figures are similar to the 2–3% shunting rate typically

reported.6

It is interesting to speculate whether the previously noted

excess of left-sided sporadic lesions (P = 0.04) may be associ-

ated with mobile phone use, either causally or by unmasking

early hearing loss preferentially on that side. Recent Swedish

data showed an increased risk of AN on the side where the

phone is usually held (but not on the other side) after 10 or more

years of analogue mobile phone use. However, in that study,

the excess of tumours and phone use was on the right,7 and in

the context of many previous negative population studies, the

association remains highly uncertain.8 We do not have prospec-

tive data on mobile phone behaviour for our patients, and the

observed left-sided dominance may simply be because of

chance.


Similar to the situation with AN, there are no randomized trials

comparing surgery with RS (with or without embolization) for

AVM. Surgery offers the possibility of immediate cure, whereas

obliteration after RS can take 2–3 years, during which time the

risk of haemorrhage persists. Incomplete obliteration requires

further treatment in order to eliminate this risk. However, RS

may be the only option for deep-seated (inoperable) lesions,

and where patients decline surgery or are medically inoperable.

Obliteration rates are typically in the range of 60–90%, and

are a function of marginal dose rather than AVM size per se.9

Large (.3–4 cm) AVM can be treated with (hypofractionated)

SRT10 or ‘staged-volume’ RS where components of the AVM

are sequentially treated with single fractions several months

apart.11

Our overall obliteration rate for assessable patients treated

with primary RS is 76%. Evaluation of the efficacy of our SRT

fractionation is pending as only one of the seven patients has

had follow-up angiography at the time of writing.

Haemorrhage after RS is reported to occur at an annual rate

of 3–4% per year until obliteration, with no statistical alteration

from the natural history of untreated AVM. This typically trans-

lates to an approximately 5% bleeding risk.12 However, there

are case reports of haemorrhage after angiographic obliteration

thought to be because of recanalization of thrombi that have not

evolved to stable scar tissue at the time of the angiogram.13 So

far, two of our patients (3.6%) have had nonfatal bleeds after

RS, one following angiographic obliteration.

Metastasis

The management issues have been addressed previously.2

In brief, there is randomized evidence of survival benefit for

the addition of surgery or RS to WBRT alone, at least for good

prognosis patients with solitary brain metastases. The addition

of WBRT to surgery or RS improves local and distant brain

control, but does not increase survival. There have been no pub-

lished randomized trials directly comparing surgery with RS

(one is in progress at the RAH), although nonrandomized data

suggest similar efficacy but superior cost effectiveness for RS.

We have restricted RS to patients with solitary brain meta-

stases and generally to RPA class 1 or 2 (two class 3 patients

were treated on the above-mentioned randomized trial). The

overall median survival of 10.1 months is typical of recent multi-

institutional reviews.14 Our results also illustrate the prognostic

validity of the RPA concept.3

Meningioma

The role of radiation in any form for benign meningioma is con-

troversial, particularly the issue of timing in the postoperative

setting. Radiosurgery and SRT are no exception to this ob-

servation.15 Accordingly, our indications are broad, including

primary treatment of inoperable lesions (e.g. cavernous sinus,

optic nerve sheath), adjuvant treatment after debulking surgery

where symptomatic progression is likely (e.g. young patient with

base of skull meningioma), or for postoperative recurrence

as an alternative to repeat surgery. Stereotactic radiotherapy

is favoured for large meningiomas (.3–3.5 cm) or because

of proximity to sensitive structures (e.g. optic pathway,

brainstem).16

Control rates of more than 90% are usually reported with

stereotactic radiation techniques.17 However, prolonged fol-

low up (10–20 years) is required for a true indication of tumour

control, so our 100% rate for the 12 assessable lesions trea-

ted with ‘curative’ intent with a median radiological follow up

of 36 months must be regarded as very preliminary. The rate

is 92% if the adjacent recurrence discussed above is counted

as a marginal failure. This case illustrates a disadvantage of

RS relative to conventional RT, namely the risk that highly

focused radiation may inadequately treat nearby microscopic

disease.

Complication rates are a function of tumour volume, dose

and location. Each of the five cases of (probable) treatment-

related toxicity described above were transient and/or episodic.

In only two patients were these symptoms new.

CONCLUSION

Radiosurgery and SRT provide elegant non-invasive alterna-

tives to microsurgery for many benign and malignant intra-

cranial tumours. Our more mature follow-up data confirm

outcomes that continue to be well within the range reported in

the world literature. Subject to provision of the necessary fund-

ing, we are planning to upgrade the current system to one

based upon micromultileaf collimation and including the option

166 DE ROOS ET AL.


of recent advances in stereotactic radiation techniques, namely

intensity-modulated stereotactic RS.

ACKNOWLEDGEMENTS

The support of the Royal Adelaide Hospital physics, radi-

ation therapy, radiology and nursing staff are all gratefully

acknowledged. Many thanks to Dr Jennifer Smith for statistical

analysis of the brain metastasis outcomes.

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Update of radiosurgery at the Royal Adelaide Hospital