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Radiosurgery Practice Guideline Initiative
Stereotactic Radiosurgery for Patients with
Practice Guideline Report #2-03
ORIGINAL GUIDELINE: September 2003
MOST RECENT LITERATURE SEARCH: September 2003
This practice guideline, together with a report on "Intracranial ArteriovenousMalformations (AVM): Overview" is an original guideline approved by the IRSA®(International RadioSurgery Association) Board of Directors and issued in September 2003.
The IRSA® (International RadioSurgery Association) Radiosurgery Practice Guideline Initiative aims to improve
outcomes for intracranial arteriovenous malformations by assisting physicians and clinicians in applying research
evidence to clinical decisions while promoting the responsible use of health care resources.
This guideline is copyrighted by IRSA (2003) and may not be reproduced without the written permission of IRSA. IRSA
reserves the right to revoke copyright authorization at any time without reason.
This guideline is not intended as a substitute for professional medical advice and does not address specific treatments or
conditions for any patient. Those consulting this guideline are to seek qualified consultation utilizing information specific
to their medical situation. Further, IRSA does not warrant any instrument or equipment nor make any representations
concerning its fitness for use in any particular instance nor any other warranties whatsoever.
KEY WORDS • arteriovenous malformations • AVM • vascular malformation • stereotactic radiosurgery
• Gamma Knife® • linear accelerator • proton beam • Bragg peak proton therapy • irradiation
group provided formal written comments that wereincorporated into the preliminary draft of the statement.
No significant disagreements existed. The final
To develop a consensus-based radiosurgery practice
statement incorporates all relevant evidence obtained by
guideline for treatment recommendations to be used by
the literature search in conjunction with final consensus
medical and public health professionals for patients with
recommendations supported by all working group
the diagnosis of brain or dural arteriovenous
The Radiosurgery Guidelines Committee is comprised of
The working group included nine physicians and one
neurological surgeons, radiation oncologists, and
physicist, all of whom staff a major medical center that
medical physicists. Community representatives did not
participate in the development of this guideline.
Names of Group Members:
L. Dade Lunsford, M.D.,
The first author(s) (LDL/AN) conducted a literature
Neurosurgeon, Chair; Douglas Kondziolka, M.D.,
search in conjunction with the preparation of this
Neurosurgeon; Ajay Niranjan, M.B.B.S., M.Ch.,
document and development of other clinical guidelines.
Neurosurgeon; Christer Lindquist, M.D., Neurosurgeon;
The literature identified was reviewed and opinions were
Jay Loeffler, M.D., Radiation Oncologist; Michael
sought from experts in the diagnosis and management of
McDermott, M.D., Neurosurgeon; Michael Sisti, M.D.,
brain AVMs, including members of the working group.
Neurosurgeon; John C. Flickinger, M.D., RadiationOncologist; Ann Maitz, M.S., Medical Physicist;
The initial draft of the consensus statement was a
Interventional Radiologist; Tonya K. Ledbetter, M.S.,
synthesis of research information obtained in the
M.F.S., Editor; Rebecca L. Emerick, M.S., M.B.A.,
evidence-gathering process. Members of the working
Many AVMs are identified because of the sudden onset
Specific recommendations are made regarding target
of bleeding within the brain, which can be fatal or merely
population, treatment alternatives, interventions and
lead to serious headache with or without new
practices and additional research needs. Appropriate use
neurological deficits. Deep-seated AVMs frequently
of radiosurgery in those with AVM following medical
present with hemorrhage. Hemorrhage may occur in the
subarachnoid space, the intraventricular space or, mostcommonly, the brain parenchyma. The overall risk of
This guideline is intended to provide the scientific
intracranial hemorrhage in patients with known AVM is
foundation and initial framework for the person who has
2-4% per year. Specific angiographic features of the
been diagnosed with a brain or dural arteriovenous
AVM increase the risk of hemorrhage. These include a
malformation. The assessment and recommendations
small and only deep venous drainage, and relatively high
provided herein represent the best professional judgment
arterial and venous pressures within the AVM nidus.
of the working group at this time, based on research data
Hemorrhage recurs in 15-20%, usually within the first
and expertise currently available. The conclusions and
year after the initial bleeding incident. Subcortical lobar
recommendations will be regularly reassessed as new
AVMs may also present with seizures, progressive
neurological deficits, or intractable vascular (migraine)headaches. Seizures occur as the presenting symptom in
25-50% of patients with AVM. These may be focal orsecondary generalized seizures. Headache occurs in 10-50% of patients with AVM. Refractory headaches may
Brain stereotactic radiosurgery involves the use of
be a presenting symptom if seizures or hemorrhages do
precisely directed closed skull single fraction (one
not occur. The headache may be typical for migraine or
surgical session) radiation to create a desired
may be present with a less specific complaint of more
radiobiologic response within the brain with minimal
generalized head pain. Rarely, a progressive neurological
effects to surrounding structures or tissues. In the case of
deficit may occur over a few months to several years.
an arteriovenous malformation a relatively high dose of
The neurological deficits may be explained by the mass
focused radiation is delivered precisely to the AVM,
effect of an enlarging AVM or venous hypertension in the
under the direct supervision of a radiosurgery team, in
draining veins. In the absence of mass effect deficit
one surgical session. The irradiated vessels gradually
could occur due to the siphoning of blood flow away
occlude over a period of time. In Centers of Excellence,
from adjacent brain tissue (the "steal phenomenon").
the radiosurgery team is composed of a neurosurgeon,radiation oncologist, physicist and registered nurse.
Intracranial Arteriovenous Malformation:
Patients are identified by high resolution neurodiagnosticimaging including CT and MRI scans supplemented by
complete cerebral angiography. High-quality MRI isessential for initial diagnosis of AVMs. AVMs appear as
Pathophysiology and Incidence
irregular or globoid masses anywhere within thehemispheres or brain stem. AVMs may be cortical,
Intracranial arteriovenous malformations (AVM)
subcortical, or in deep gray or white matter. Small,
constitute relatively rare and usually congenital vascular
round, low-signal spots within or around the mass on T1,
anomalies of the brain [1, 2]. AVMs are composed of
T2, or fluid-attenuated inversion recovery (FLAIR)
complex connections between the arteries and veins that
sequences are the "flow voids" of feeding arteries,
lack an intervening capillary bed. The arteries have a
intranidal aneurysms, or draining veins. If hemorrhage
deficient muscularis layer. The draining veins often are
has occurred, the hematoma may obscure other
dilated and tortuous due to the high velocity of blood
diagnostic features, requiring angiogram or follow-up
flow through the fistulae. No genetic, demographic, or
MRI. Dark signal of extracellular hemosiderin may be
environmental risk factor has been associated with
seen around or within the AVM mass, indicating prior
cerebral AVMs. Rarely inherited disorders, such as the
hemorrhage. Aneurysms within the AVM or on feeding
Osler-Weber-Rendu syndrome (hereditary hemorrhagic
arteries may be identified occasionally.
telangiectasia), Sturge-Weber disease, neurofibromatosis,
Cerebral angiography is required to assess morphology
and von Hippel-Lindau syndrome are associated in a small
and hemodynamics, which are essential for planning
minority of AVM patients. It is estimated that 10,000 to
treatment. Important features include feeding arteries,
12,000 new patients are diagnosed in the United States on
venous drainage pattern, and arterial and venous
aneurysms. Ten to fifty-eight percent of patients withAVM have aneurysms located in vessels remote from the
AVM, in arteries feeding the AVM, or within the nidus of
the AVM itself. Intranidal aneurysms may have a higherrisk of rupture than those outside the bounds of the AVM.
Although AVMs are considered congenital, the clinicalpresentation most commonly occurs in young adults (20-
Once identified, arteriovenous malformations may be
40 years). Brain hemorrhage or seizure as an incident
suitable for one or more of four management strategies:
event may occur in young children or adults over 40. A
observation, surgical excision, stereotactic radiosurgery
history of subtle learning disorders is elicited in 66% of
or endovascular embolization . AVM management
depends on risk of subsequent hemorrhage, which is
determined by the anatomical (MRI and angiography),
Symptoms and Signs
historical, and demographic features of the individualpatient. Young age, prior hemorrhage, small AVM size,
AVM patients may present with brain hemorrhage,
deep venous drainage, and high flow makes subsequent
seizures, headache or progressive neurological deficit.
Observation may be most appropriate for large volume
full years have elapsed. If angiography after three years
AVMs (average diameter 4-5 cm), especially for patients
demonstrates that the AVM nidus is not obliterated,
who have never bled. Studies of the natural history of
repeat stereotactic radiosurgery is recommended [27,
AVMs suggest an annual hemorrhage rate of 2-4% with
an annual 1% mortality rate from AVM bleeding. Asecond strategy is endovascular embolization, which is
Dose volume guidelines for AVM management have
often used as an adjunct preceding surgical removal of
been extensively published [29-32]. AVM outcomes are
the AVM via craniotomy and at times before stereotactic
best for those patients with small volume AVMs located
radiosurgery. Other vascular anomalies may be
in non-critical locations [21, 33-36]. Children may
associated with AVMs including the presence of
respond faster than adults in terms of the obliteration
proximal intracranial or intranidal aneurysms. Such
rate. Obliteration is a process resulting from endothelial
aneurysms may pose additional risk factors to patients.
proliferation within the AVM blood vessel walls,
Surgical management options are not part of this
supplemented by myofibroblast proliferation. This leads
discussion, although incomplete surgical obliteration
to contraction and eventual obliteration of the AVM
may prompt eventual radiosurgery. Embolization prior
blood vessels [37-39]. The process is cumulative, with
to radiosurgery is thought to be beneficial in some cases,
earliest obliterations noted within two to three months,
but in other cases may lead to less reliable recognition of
50% of the effect often seen within one year, 80% within
the target volume suitable for radiosurgery . Re-
two years, and 90% within three years. If at the end of
canalization of embolized AVM components may require
three years residual AVM is identified by imaging, repeat
subsequent re-treatment for portions of the AVM
radiosurgery may be considered (as may other
previously thought to be occluded by successful
management strategies designed to complete obliteration
Stereotactic radiosurgery is considered for patients with
Average marginal dose depends upon the technology
unresectable AVMs. Such patients may warrant
used. Commonly, the 50-70% isodose is used for photon
treatment based on age, location, volume, or medical
radiosurgery, and different doses are used for particle
history. Radiation technologies for stereotactic
beam radiosurgery using protons [29-31, 40]. Conformal
radiosurgery include Gamma Knife® radiosurgery, proton
radiosurgery is required in order to maximize dose within
beam radiosurgery, and linear accelerators (LINACs)
the three-dimensionally defined AVM volume while
modified at Centers of Excellence with extensive AVM
restricting dose to the surrounding brain.
experience [5-26]. Multi-modality management teamsare essential for proper patient selection and patient care.
Current studies indicate a success rate between 50-95%
Because of the delayed obliteration rate of AVMs after
at the end of three years of observation after a single
radiosurgery, comprehensive long-term management and
radiosurgery procedure [5-26]. The long-term result of
observational strategies are necessary. Patients usually
radiosurgery (5-14 year results after Gamma Knife®
receive a single dose (40 mg) of methylprednisolone at
radiosurgery) suggest that the majority of AVM patients
the conclusion of the radiosurgery procedure. They can
(73%) are protected from the risk of future hemorrhage
continue to take their other medications (antiepileptics,
and continue their normal daily activities after
analgesics, etc.) after the procedure as recommended by
radiosurgery . The identification of a patient with
their physicians. Postradiosurgical clinical examinations
brain or dural AVMs suitable for radiosurgery requires a
and MR studies are requested at six month intervals for
commitment to long-term follow-up care and a team
the first three years to assess the effect of radiosurgery on
management strategy using the talents of neurological
AVM (gradual obliteration). If MRI at the three-year
surgeons, radiation oncologists, neuro-imaging
mark suggests complete closure of the AVM nidus, an
specialists, and medical physicists. Additional
angiogram is obtained to confirm the obliteration. If the
management strategies include surgery, embolization,
MR imaging before three years suggests nidus
and radiosurgery alone or in combination [42-46].
obliteration, angiography is generally delayed until three
A number of factors are considered in making a
1. Patient's age2. Patient's medical condition
A broad outline of management algorithm is shown
below; however, the final recommendation is usually
influenced by the recommending neurosurgeon's
experience along with patient preference.
Intracranial Arteriovenous Malformation Management Algorithm
11. Kobayashi, T., et al., Gamma knife treatment of
AVM of the basal ganglia and thalamus. No to
Stein, B.M. and S.M. Wolpert, Arteriovenous
Shinkei - Brain & Nerve, 1996. 48(4): p. 351-6.
malformations of the brain. I: Current concepts and
12. Kondziolka, D. and L.D. Lunsford, The case for and
treatment. Archives of Neurology, 1980. 37(1): p. 1-5.
against AVM radiosurgery. Clinical Neurosurgery,
Wilkins, R.H., Natural history of intracranial
vascular malformations: a review. Neurosurgery,
13. Kurita, H., et al., Results of radiosurgery for brain
stem arteriovenous malformations. [comment].
Smith, J.L. and B. Garg, Treatment of arteriovenous
Journal of Neurology, Neurosurgery & Psychiatry,
malformations of the brain. Current Neurology &
Neuroscience Reports, 2002. 2(1): p. 44-9.
14. Levy, E.I., et al., Radiosurgery for childhood
Pollock, B.E., et al., Embolization and radiosurgery
intracranial arteriovenous malformations.
for AVMs.[comment]. Journal of Neurosurgery,
Neurosurgery, 2000. 47(4): p. 834-41; discussion
1997. 86(2): p. 319-20; author reply 320-1.
Crocco, A., Arteriovenous malformations in the
15. Maesawa, S., et al., Repeated radiosurgery for
basal ganglia region: Gamma Knife radiosurgery as
incompletely obliterated arteriovenous malformations.
first choice treatment in selected cases. Journal of
Journal of Neurosurgery, 2000. 92(6): p. 961-70.
Neurosurgical Sciences, 2002. 46(2): p. 43-54.
16. Massager, N., et al., Gamma knife radiosurgery for
Ellis, T.L., et al., Analysis of treatment failure after
brainstem arteriovenous malformations: preliminary
radiosurgery for arteriovenous malformations.
results. Journal of Neurosurgery, 2000. 93 Suppl 3:
Journal of Neurosurgery, 1998. 89(1): p. 104-10.
Flickinger, J.C., et al., Radiosurgical management of
17. Miyawaki, L., et al., Five year results of LINAC
intracranial vascular malformations. Neuroimaging
radiosurgery for arteriovenous malformations:
Clinics of North America, 1998. 8(2): p. 483-92.
outcome for large AVMs. International Journal of
Friedman, W.A., Radiosurgery for arteriovenous
Radiation Oncology, Biology, Physics, 1999. 44(5):
malformations. Clinical Neurosurgery, 1995. 42: p.
18. Nakanishi, A., et al., Linac-based stereotactic
Hadjipanayis, C.G., et al., Stereotactic radiosurgery
radiosurgery for arteriovenous malformations
for motor cortex region arteriovenous malformations.
(AVMs) in brain: estimation for efficacy of
Neurosurgery, 2001. 48(1): p. 70-6; discussion 76-7.
therapeutic response using angiography. Nippon
10. Karlsson, B., C. Lindquist, and L. Steiner, Prediction
Igaku Hoshasen Gakkai Zasshi - Nippon Acta
of obliteration after gamma knife surgery for cerebral
Radiologica, 1999. 59(4): p. 137-42.
arteriovenous malformations. Neurosurgery, 1997.
19. Nicolato, A., et al., Stereotactic radiosurgery for the
treatment of arteriovenous malformations in
childhood. Journal of Neurosurgical Sciences, 1997.
Neurosurgery, 2000. 93 Suppl 3: p. 96-101.
20. Pan, D.H., et al., Gamma knife radiosurgery as a
37. Chang, S.D., et al., Stereotactic radiosurgery of
single treatment modality for large cerebral
arteriovenous malformations: pathologic changes in
resected tissue. Clinical Neuropathology, 1997.
Neurosurgery, 2000. 93 Suppl 3: p. 113-9.
21. Pollock, B.E., et al., Factors associated with
successful arteriovenous malformation radiosurgery.
histopathology.[comment]. Journal of Neurosurgery,
Neurosurgery, 1998. 42(6): p. 1239-44; discussion
39. Schneider, B.F., D.A. Eberhard, and L.E. Steiner,
22. Pollock, B.E., Stereotactic radiosurgery for
Histopathology of arteriovenous malformations
arteriovenous malformations. Neurosurgery Clinics
after gamma knife radiosurgery.[comment]. Journal
of North America, 1999. 10(2): p. 281-90.
of Neurosurgery, 1997. 87(3): p. 352-7.
23. Ross, D.A., et al., Stereotactic radiosurgery of
40. Flickinger, J.C., et al., Complications from
cerebral arteriovenous malformations with a
multileaf collimator and a single isocenter.
multivariate analysis and risk modeling.
Neurosurgery, 2000. 47(1): p. 123-8; discussion
International Journal of Radiation Oncology,
Biology, Physics, 1997. 38(3): p. 485-90.
24. Schlienger, M., et al., Linac radiosurgery for
41. Pollock, B. E., Gorman, D. A., Coffey, R. J, Patient
cerebral arteriovenous malformations: results in 169
outcomes after arteriovenous malformation
patients. International Journal of Radiation
radiosurgical management: results based on a 5- to
Oncology, Biology, Physics, 2000. 46(5): p. 1135-
14-year follow-up study. Neurosurgery.
25. Shin, M., et al., Retrospective analysis of a 10-year
42. Jizong, Z., et al., Combination of intraoperative
experience of stereotactic radio surgery for
embolisation with surgical resection for treatment of
arteriovenous malformations in children and
giant cerebral arteriovenous malformations. Journal
adolescents.[comment]. Journal of Neurosurgery,
of Clinical Neuroscience, 2000. 7 Suppl 1: p. 54-9.
43. Martin, N.A., et al., Therapeutic embolization of
26. Young, C., et al., Radiosurgery for arteriovenous
arteriovenous malformations: the case for and
against. Clinical Neurosurgery, 2000. 46: p. 295-318.
experience. Canadian Journal of Neurological
44. Negoro, M., et al., Recent advances in AVM
embolization. No to Shinkei - Brain & Nerve, 2000.
27. Lunsford, L.D., et al., Black holes, white dwarfs and
supernovas: imaging after radiosurgery. Stereotactic
45. Tokunaga, K., et al., Curative treatment of cerebral
& Functional Neurosurgery, 1998. 70 Suppl 1: p. 2-
arteriovenous malformations by embolisation using
cellulose acetate polymer followed by surgical
28. Kihlstrom, L., et al., Magnetic resonance imaging of
resection. Journal of Clinical Neuroscience, 2000. 7
obliterated arteriovenous malformations up to 23
years after radiosurgery.[comment]. Journal of
46. Miyachi, S., et al., Embolisation of cerebral
Neurosurgery, 1997. 86(4): p. 589-93.
arteriovenous malformations to assure successful
29. Flickinger, J.C., et al., A dose-response analysis of
subsequent radiosurgery. Journal of Clinical
arteriovenous malformation obliteration after
Neuroscience, 2000. 7 Suppl 1: p. 82-5.
radiosurgery.[comment]. International Journal ofRadiation Oncology, Biology, Physics, 1996. 36(4):p. 873-9.
30. Flickinger, J.C., D. Kondziolka, and L.D. Lunsford,
Dose selection in stereotactic radiosurgery.
Neurosurgery Clinics of North America, 1999.
10(2): p. 271-80.
Stereotactic radiosurgery for patients with intracranial
31. Flickinger, J.C., et al., An analysis of the dose-
response for arteriovenous malformationradiosurgery and other factors affecting obliteration.
Radiotherapy & Oncology, 2002. 63(3): p. 347-54.
32. Mavroidis, P., et al., Prediction of AVM obliteration
after stereotactic radiotherapy using radiobiological
DEVELOPER AND FUNDING SOURCE:
modeling. Physics in Medicine & Biology, 2002.
47(14): p. 2471-94.
IRSA (International RadioSurgery Association)
33. Pollock, B.E., et al., Repeat stereotactic radiosurgery
of arteriovenous malformations: factors associated
with incomplete obliteration. Neurosurgery, 1996.
38(2): p. 318-24.
IRSA (International RadioSurgery Association) is a non-
34. Kwon, Y., et al., Analysis of the causes of treatment
profit entity dedicated to promoting the development of
failure in gamma knife radiosurgery for intracranial
scientifically relevant practice guidelines for stereotactic
radiosurgery. IRSA is a professional organization that
Neurosurgery, 2000. 93 Suppl 3: p. 104-6.
works to educate and provide support for physicians,
35. Friedman, W.A., et al., Analysis of factors predictive
of success or complications in arteriovenous
malformation radiosurgery. Neurosurgery, 2003.
52(2): p. 296-307; discussion 307-8.
The IRSA Medical Advisory Board Guidelines
36. Chang, J.H., et al., Factors related to complete
Committee and representatives in the industry
occlusion of arteriovenous malformations after
Dose selection to the arteriovenous malformation isrelated to AVM volume, location, and a predicted
The Radiosurgery Guidelines Committee is comprised of
obliteration rate within three years, as well as a
neurological surgeons, radiation oncologists, and
reasonably estimated adverse radiation risk to
surrounding brain. Minimal AVM doses in a singletreatment vary from 16 to 25 Gy, with volumetric
Names of Group Members:
L. Dade Lunsford, M.D.,
conformal radiosurgery designed to provide maximal
Neurosurgeon, Chair; Douglas Kondziolka, M.D.,
dose sparing to surrounding brain tissue.
Neurosurgeon; Ajay Niranjan, M.B.B.S., M.Ch.,Neurosurgeon; Christer Lindquist, M.D., Neurosurgeon,
European Co-Chair; Jay Loeffler, M.D., RadiationOncologist; Michael McDermott, M.D., Neurosurgeon;
Total obliteration of the arteriovenous malformation
Michael Sisti, M.D., Neurosurgeon; John C. Flickinger,
within three years is the primary end point of interest.
M.D., Radiation Oncologist; Ann Maitz, M.S., Medical
Additional outcome end points include resolution or an
Physicist; Michael Horowitz, M.D., Neurosurgeon and
improvement in seizure disorders if present, resolution or
Interventional Radiologist; Tonya K. Ledbetter, M.S.,
reduction in vascular headache syndromes, and
M.F.S., Editor; Rebecca L. Emerick, M.S., M.B.A.,
prevention of bleeding risks from the arteriovenous
malformation (estimated to vary between 1-10% per yeardepending upon prior bleeding history, location, and
volume). Improvement in the existing neurologicaldeficits is also considered. Maintenance of quality of
Arteriovenous malformations (AVM), brain (cerebrum,
life, employability, and prevention of adverse radiation
NUMBER OF REFERENCES:
METHODS TO COLLECT EVIDENCE:
Hand Searches of Published Literature (PrimarySources); Hand Searches of Published Literature
(Secondary Sources); Searches of Electronic Databases
DESCRIPTION OF METHODS TO COLLECT
MEDLINE and PUBMED searches were completed for
the years 1971 to September 2003. Search terms
included arteriovenous malformation, AVM, vascularmalformation, stereotactic radiosurgery, Gamma
Knife®, irradiation, Linac radiosurgery, proton beamradiosurgery, Bragg peak proton therapy, clinical trials,
research design, practice guidelines and meta-analysis.
Bibliographies from recently published reviews were
reviewed and relevant articles were retrieved.
METHODS TO ASSESS THE QUALITY AND
STRENGTH OF THE EVIDENCE:
To develop a evidenced and consensus-based stereotactic
METHODS TO ANALYZE EVIDENCE:
radiosurgery practice guideline for symptomatic patientswith imaging identified arteriovenous malformations of
the brain for treatment recommendations to be used bymedical and public health professionals. Such patients
may or may not be candidates for alternative
External peer review; internal peer review
management strategies that include observation, surgicalresection via craniotomy, and endovascular
DESCRIPTION OF REVIEW METHODS:
The recommendations were originally suggested by a
core group of four members. These recommendationswere mailed to all committee members. Feedback was
Men and women >2 years old with imaging identified
obtained through this mailed survey in order to revise the
congenital or acquired arteriovenous malformations of
proposed guidelines. Committee members were asked
the brain, including the cerebrum, cerebellum, brainstem
whether the recommendations should serve as a practice
and dura. Patients often are not considered candidates
guideline. No significant disagreements existed. The
for surgical resection based on size or anatomic location,
final statement incorporates all relevant evidence
or medical co-morbidities and advanced age.
obtained by the literature search in conjunction with thefinal consensus recommendations supported by all
INTERVENTIONS AND PRACTICES:
Stereotactic radiosurgery of cerebral arteriovenousmalformations is performed using single procedure or
occasionally staged procedure techniques based on
• Patients with intracranial arteriovenous
intraoperative stereotactic guidance, digitally acquired
malformations defined by modern neurodiagnostic
images (CT or MRI) and intracranial angiography.
imaging including CT, MRI scan, and cerebral
angiography constitute the study group. Such
a stable neurological recovery or plateau (generally
patients typically present with brain hemorrhage
within two to three months after the intracranial
(especially when located in deep anatomic
hemorrhage or prior surgery). The optimal time
locations of the brain), persistent seizures, vascular
between prior embolization and radiosurgery is not
headache syndrome or progressive neurological
known, but generally waiting for a period of
deficits. Arteriovenous malformations are
several weeks is considered beneficial in order to
considered suitable for four management strategies
reduce the likelihood of vascular ischemic
alone or in combination: observation only, surgical
excision, endovascular embolization (designed to
sometimes associated with embolization followed
reduce either a selected volume or flow through the
AVM), and stereotactic radiosurgery. Stereotacticradiosurgery is typically employed alone but also
• Postradiosurgical clinical examinations and MR
may be employed in combination with prior
studies are requested by referring physicians at six
month intervals for the first three years to assess
circumstances. Size ranges of average diameter
the effect of radiosurgery on AVM (gradual
are usually less than 3 cm (0.1-10 cm3).
obliteration). If MR at the three-year mark
Prospective stereotactic radiosurgery volumetric
suggests complete disappearance of the AVM
staging is frequently performed for those
nidus, an angiogram is obtained to confirm the
symptomatic patients with AVM volumes > 15
obliteration. If the MR imaging before three years
cm3 in the absence of other acceptable risk
suggests nidus obliteration, angiography is
management strategies and can be considered for
generally delayed until three full years have
elapsed. If angiography after three years
patients suitable for radiosurgery is dependent on
demonstrates that the AVM nidus is not obliterated,
the prior bleeding history, the age of the patient,
repeat stereotactic radiosurgery is recommended.
existing co-morbidities, anatomic location, andclinical history. Radiosurgery, a minimally
• Patients who have residual arteriovenous
invasive closed skull treatment strategy, may be
malformations identified by neurodiagnostic
especially suitable for patients in advanced age
imaging at three years (after radiosurgery) may be
groups or those with excessive medical co-
candidates for a second stereotactic radiosurgical
morbidity risk factors for surgical excision.
procedure. Alternatively, patients with largervolume AVMs (e.g., >10 cm3) may be considered
• The optimal dose range for volumetric conformal
suitable for up-front volumetric staging of AVMs
stereotactic AVM radiosurgery has been largely
by treating different anatomic components of the
established based on location and volume of the
AVM at intervals staged between three and six
AVM. Doses at the margin of the AVM typically
months. The interval for staging of radiosurgery
range from 16-25 Gy in a single fraction, wherein
prospectively is not established. Stereotactic
the volume of the AVM is defined by stereotactic
radiosurgery should not be considered as the
guidance during the procedure itself. Stereotactic
panacea for large volume AVMs unsuitable for
volumetric axial plane imaging (MRI or CT)
surgery or embolization. At selected centers with
experience, estimated obliteration rates after two
subtraction angiography is usually necessary for
radiosurgical procedures at five years approach 60-
complete conformal dose planning. Dose selection
depends on location, volume, estimated adverse
diameters < 3 cm3), estimated complete
radiation risks, pre-existing neurological
obliteration rates at three years after a single
conditions, and prior bleeding history. Depending
upon the technology used, the margin of the AVMdose is usually 50-70% of the central target dose
• Causes for failure of stereotactic radiosurgery have
within the AVM. Sharp fall-off of the radiation
dose outside of the target volume is required.
visualization of the target nidus, lack of
Current radiation delivery technologies for
intraoperative stereotactic 3-D (volumetric axial
volumetric stereotactic conformal single fraction
plane imaging), insufficient dose to achieve the
radiosurgery include Gamma Knife®, proton beam
obliterative response, compression of the AVM
using Bragg peak effect, and specially modified
visualization secondary to overlying vascularstructures. In a few cases selected radiobiological
• Patients usually receive a single dose (40 mg) of
resistance of undetermined etiology may be the
methylprednisolone at the conclusion of the
radiosurgery procedure. They can continue to taketheir other medications (antiepileptics, analgesics,
• At present, technologies delivered to provide
volumetric stereotactic radiosurgery are limited to
Gamma Knife®, modified linear accelerators atcenters supplemented by significant experience,
• Some AVM patients will have been previously
and proton beam facilities in the United States.
treated by embolization for volumetric reduction orflow reduction. Some patients may have had prior
• Stereotactic radiosurgery is defined as a relatively
intracranial surgery for blood clot (hematoma)
high dose of focused radiation delivered precisely
evacuation or partial AVM resection. The safe
to the malformation, under the direct supervision
interval between surgery and stereotactic
of a medical team (neurosurgeon, radiation
radiosurgery is not known, but it is reasonable to
oncologist, registered nurse, and medical
perform radiosurgery once the patient has achieved
physicist), in one surgical treatment session
TYPE OF EVIDENCE:
permanent new neurological deficits related to radiationin a large group of patients undergoing radiosurgery is 3-
Type I, II and III evidence (Bandolier) exists in support
5%. Late delayed potential risks of radiosurgery should
of stereotactic radiosurgery for arteriovenous
be assessed by MRI at five and ten years after
SUBGROUP(S) LIKELY TO BE HARMED:
All the published studies have shown a significant
Patients with large volume AVMs who are treated with
response of stereotactic radiosurgery for arteriovenous
large doses in a single fraction, especially if the AVM is
malformations including a high rate of AVM nidus
located in a deep brain area. Patients with large AVMs in
obliteration, concomitant improvement in seizure
a deep brain area, in whom the risk of bleeding over their
control, headache resolution, and a satisfactory (low) rate
expected lifetime is less than the risk of radiosurgery
of adverse radiation effect that might lead to additional
complications, will benefit least from radiosurgery.
neurological deficits. Complete obliteration of the AVMis considered necessary in order to definitely eliminate
the risk of future bleeding. To date, insufficient evidenceexists to establish whether bleeding rates are reduced
This is the full current release of the guideline
more than five years after AVM radiosurgery even inpatients who have had incomplete obliteration.
Electronic copies: Available in Portable Document
obliteration, symptomatic relief, no new neurological
deficits, no long term complications, and life-longprevention of bleeding risks.
Print copies: Available from IRSA, 3005 HoffmanStreet, Harrisburg, PA 17110
Literature has documented the cost savings benefit ofstereotactic radiosurgery versus invasive surgical
procedures and the lower risk potential of bleeding fromsurgical incisions, anesthesia problems, infections and
Patient resources are available on line at www.IRSA.org,
side effects which may include transient or permanent
by email at intouch@IRSA.org or by calling +717-260-
SUBGROUP(S) MOST LIKELY TO BENEFIT:
See "publications" for patient resources for arteriovenousmalformations: www.IRSA.org/publications.html/
Patients with brain or dural arteriovenous malformations
® Volume 8, No. 1; Volume 6, No. 1;
considered unsuitable for complete excision by surgical
® Volume 4, No. 3; Volume 4, No. 2
craniotomy or complete obliteration by endovascular
Brochure on AVMs available by mail.
Major adverse effects of radiosurgery are based onlocation, volume, dose, and flow, and these risks can beestimated based on published data and experience.
Individual risks are related to the anatomical location ofthe AVM. Currently, the estimated adverse risk of
Drug interactions with boceprevir and telaprevir. CONCISE REVIEW A review of drug interactions with boceprevir and telaprevir: implications for HIV and transplant patients Kyle J. Wilby,* Erica D. Greanya,† Jo-Ann E. Ford,‡ Eric M. Yoshida,§ Nilufar Partovi||* BSP, ACPR, Doctor of Pharmacy Candidate, Faculty of Pharmaceutical Sciences,The University of British Columbia, Vancouver,
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