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Intracranial arteriovenous.qxd

Radiosurgery Practice Guideline Initiative
Stereotactic Radiosurgery for Patients with
Practice Guideline Report #2-03
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. Summary
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
Consensus Statement
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 Group Composition
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; Consensus Process
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 Conclusions
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 Stereotactic Radiosurgery
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.
Imaging Studies
Intracranial Arteriovenous Malformation:
Patients are identified by high resolution neurodiagnosticimaging including CT and MRI scans supplemented by Overview
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 [3]. 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 [4]. 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 [41]. 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 CLINICAL ALGORITHM
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 DEVELOPER COMMENT:
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 COMMITTEE:
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 GROUP COMPOSITION:
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, OUTCOMES CONSIDERED:
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 DISEASE/CONDITION:
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:
Hand Searches of Published Literature (PrimarySources); Hand Searches of Published Literature CATEGORY:
(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 INTENDED USERS:
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.
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 REVIEW METHODS:
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 TARGET POPULATION:
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 MAJOR RECOMMENDATIONS:
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 POTENTIAL BENEFITS:
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 GUIDELINE STATUS:
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 PATIENT RESOURCES:
procedures and the lower risk potential of bleeding fromsurgical incisions, anesthesia problems, infections and Patient resources are available on line at, side effects which may include transient or permanent by email at or by calling +717-260- SUBGROUP(S) MOST LIKELY TO BENEFIT:
See "publications" for patient resources for arteriovenousmalformations: Patients with brain or dural arteriovenous malformations Brain Talk® Volume 8, No. 1; Volume 6, No. 1; considered unsuitable for complete excision by surgical Another Perspective® Volume 4, No. 3; Volume 4, No. 2 craniotomy or complete obliteration by endovascular Brochure on AVMs available by mail. COPYRIGHT STATEMENT:
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


Hp122-03-review (07p).p65

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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Home Page > Newsroom > News Releases > PECO > News Release News Releases October 14, 2004 - UC GREEN, PECO & OTHERS TEAM UP TO PLANT 50 TREES IN UNIVERSITY CITY WHAT: Hundreds of volunteers and representatives from local corporations and agencies gather together to not only plant trees -- but also plant the Fact Sheet right tree in the right p

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