Dodd Spine Neurosurg 2006

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CLINICAL STUDIES

CYBERKNIFE RADIOSURGERY FOR BENIGN INTRADURALEXTRAMEDULLARY SPINAL TUMORS

Robert L. Dodd, M.D., Ph.D.

Department of Neurosurgery,Stanford University

School of Medicine,Stanford, California

Mi-Ryeong Ryu, M.D., Ph.D.

Department of Radiation Oncology,

Kangnam St. Marys Hospital,Seoul, Korea

Pimkhuan Kamnerdsupaphon,

M.D.Division of Therapeutic Radiologyand Oncology,

Faculty of Medicine,Chiang Mai University,

Chiang Mai, Thailand

Iris C. Gibbs, M.D.

Department of Radiation Oncology,Stanford UniversitySchool of Medicine,

Stanford, California

Steven D. Chang, Jr., M.D.

Department of Neurosurgery,Stanford University

School of Medicine,Stanford, California

John R. Adler, Jr., M.D.

Department of Neurosurgery,

Stanford UniversitySchool of Medicine,Stanford, California

Reprint requests:John R. Adler, Jr., M.D.,Department of Neurosurgery,

Stanford UniversitySchool of Medicine,

Stanford, CA 94305.Email: [email protected]

Received, July 20, 2005.

Accepted, December 7, 2005.

OBJECTIVE: Microsurgical resection of benign intradural extramedullary spinal tumorsis generally safe and successful, but patients with neurofibromatosis, recurrent tumors,multiple lesions, or medical problems that place them at higher surgical risk maybenefit from alternatives to surgery. In this prospective study, we analyzed our pre-liminary experience with image-guided radiosurgical ablation of selected benignspinal neoplasms.

METHODS: Since 1999, CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery wasused to manage 51 patients (median age, 46 yr; range, 1286 yr) with 55 benign spinaltumors (30 schwannomas, nine neurofibromas, 16 meningiomas) at Stanford Univer-sity Medical Center. Total treatment doses ranged from 1600 to 3000 cGy delivered in

consecutive daily sessions (15) to tumor volumes that varied from 0.136 to 24.6 cm3

.RESULTS: Less than 1 year postradiosurgery, three of the 51 patients in this series (onemeningioma, one schwannoma, and one neurofibroma) required surgical resection oftheir tumor because of persistent or worsening symptoms; only one of these lesionswas larger radiographically. However, 28 of the 51 patients now have greater than 24months clinical and radiographic follow-up. After a mean follow-up of 36 months, allof these later lesions were either stable (61%) or smaller (39%). Two patients died fromunrelated causes. Radiation-induced myelopathy appeared 8 months postradiosurgeryin one patient.

CONCLUSION: Although more patients studied over an even longer follow-up periodare needed to determine the long-term efficacy of spinal radiosurgery for benignextra-axial neoplasms, short-term clinical benefits were observed in this prospective

analysis. The present study demonstrates that CyberKnife radiosurgical ablation ofsuch tumors is technically feasible and associated with low morbidity.

KEY WORDS: CyberKnife, Image guidance, Meningioma, Neurofibroma, Radiosurgery, Schwannoma,Spinal tumors

Neurosurgery 58:674-685, 2006 DOI: 10.1227/01.NEU.0000204128.84742.8F www.neurosurgery-online.com

Stereotactic radiosurgery (SRS) has be-come an important tool for managing arange of benign intracranial and cranial

base tumors. Although similar tumor histolo-gies can be found in and around the spine, the

first generation of radiosurgical instrumentswas, by virtue of being frame-based, unable totreat such extracranial targets. The more re-cent emergence of image-guidance technologynow makes it possible to use radiosurgicalmethods to ablate lesions throughout the bodyincluding in the spine (1, 45, 56). There arenow several published studies that describeoutcome in series of patients treated with spi-nal radiosurgery, primarily for metastases (9,

10, 14, 41, 45). Although these preliminarystudies demonstrate safety and efficacy,follow-up is relatively short because these pa-tients tend to die early from their underlyingmalignancies.

The safety and effectiveness of microsurgi-cal resection of most benign spinal neoplasmsis well documented (8, 15, 24, 37, 48, 49). Nev-ertheless, certain patients are less than idealcandidates for standard surgical resection be-cause of age, medical comorbidities, the recur-rent nature of their tumor, or because multiplelesions occur in the setting of one of the famil-ial phakomatoses. It is in such clinical circum-stances that radiosurgery could be an attrac-

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tive clinical option. Despite this theoretical attraction, theliterature on malignant spinal metastases provides an insuffi-cient basis for judging the possible benefits of radiosurgicalablation of benign spine tumors. Because patients with suchlesions have prolonged life expectancies, the potential fordelayed and possibly catastrophic radiation myelopathy is a

special concern. In addition, benign spine tumors have theirown unique presentation, spatial relationship to the spinalcord, and radiobiologic response to radiosurgery, any ofwhich could present unique challenges to the safe and effec-tive application of radiosurgical ablation.

Image-guided robotic radiosurgery, the CyberKnife (Ac-curay, Inc., Sunnyvale, CA), was introduced at Stanford Uni-versity Medical Center in 1994 (1), and in 1997, the first patientwith a benign spinal lesion (a hemangioblastoma) was treated.Since that time, 101 patients with a variety of benign spinaltumors and vascular malformations have undergone radiosur-gical ablation at our institution. Among this group were 51patients with meningioma, neurofibroma, or schwannoma

who now have at least 6 months follow-up. In this report, weprovide a prospective analysis of this cohort. Our primaryobjectives were to 1) document the relative safety of thisprocedure and 2) develop a preliminary understanding of therange of potential treatment doses and outcome measures thatare appropriate for patients with benign spine tumors.

PATIENTS AND METHODS

Fifty-one patients with 55 benign intradural extramedullaryspinal tumors (16 meningiomas, 30 schwannomas, nine neu-rofibromas) were treated at Stanford University Medical Cen-ter from 1999 to 2005 as part of a protocol for spinal tumors

approved by our institutional review board. A multidisci-plinary team of specialists that included neurosurgeons, radi-ation oncologists, and neuroradiologists evaluated all patients.Spinal radiosurgery was only offered to patients for whommicrosurgical resection was contraindicated because of med-ical comorbidities, underlying neurofibromatosis (NF) thatresulted in multiple lesions developing over time, or, occa-sionally, strong patient preference. Selected cases also hadwell-circumscribed lesions, no evidence of overt spinal insta-bility, and generally minimal compromise of spinal cord func-tion (i.e., myelopathy). Several of the NF patients in this serieshad an aggressive form of this illness that resulted at the timeof presentation in significant neurological compromise. Alltumors were known or presumed to be spinal meningioma,neurofibroma, or schwannoma on the basis of prior patholog-ical confirmation, characteristic appearance on contrast mag-netic resonance imaging (MRI) scans, or history of NF.

The general clinical characteristics for the 51 patients in thisseries are summarized in Tables 13. After signing an institu-tional review board-approved consent form, the image-guidedCyberKnife radiosurgical system was used to administer spi-nal radiosurgery in every case. This instrument has been de-scribed previously in detail by Adler et al. (1). The deviceconsists of a 6 MV linear accelerator mounted on a computer-

controlled robotic arm, which is coupled to an x-ray trackingsystem that monitors and adjusts in near real time on the basisof changes in the targets position. Image-guidance eliminatesthe need for skeletal rigid immobilization.

The process of CyberKnife spinal radiosurgery begins withan outpatient procedure that inserts small stainless steel mark-ers percutaneously into vertebral segments above and belowthe radiosurgical target (45). Next, a custom alpha cradle moldis fabricated for the supine patient (Smithers Medical Prod-ucts, Inc., Akron, OH). This device is used to noninvasivelyimmobilize the spine during computerized tomographic (CT)imaging (used later in treatment planning) and also to restrictpatient movement during the radiosurgery itself. For those

tumors that enhanced poorly with iodinated contrast or whensevere allergy precluded the acquisition of an enhanced CTimaging, a contrast MRI scan of the relevant spine was alsoacquired and fused to the pretreatment CT scan.

Treatment planning begins with the treating neurosurgeondefining the target volume and critical structures within theCT/MRI scans using software tools provided on the Cy-berKnife workstation (Fig. 1, DF). On imaging studies, thespinal cord volume was delineated as the primary criticalstructure beginning 1 cm cephalad to and ending 1 cm belowthe targeted lesion. A proprietary inverse planning computeralgorithm uses the above inputs to determine the number,direction, and duration of treatment beamlets so as to opti-mize dose conformality and minimize irradiation of criticalstructures (Fig. 1G). Visual inspection and analysis of dosevolume histograms for the target region and adjacent criticalanatomy are used to of find the best radiosurgical solution.

Just before the administration of radiosurgery, a library ofdigitally reconstructed radiographs (i.e., computer simulatedx-rays) are calculated from the perspective of a pair of x-raysources and cameras used throughout the operation. Thisarray of images encompasses those vertebral elements, alongwith embedded fiducials, that are in close proximity to theradiosurgical target. During radiosurgery, the patient lies su-

TABLE 1. Characteristics of patientsa

Age (yr)

Mean 46.5

Range 12.686.5

Sex, n (%)Female 23 (45)

Male 28 (55)

Previously resected (%)

Subtotal 24 (47)

Gross total 2 (4)

NF1 7 (14)

NF2 10 (20)

Previously radiated (%) 4 (8)

a NF, neurofibromatosis.

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pine on the operating table in the alpha cradle mold. Sequen-tial paired digital radiographs of the target region are thenobtained by ceiling-mounted, orthogonally directed, rigidlyfixed x-ray tubes. A computer workstation performs rapidimage-to-image correlation between the acquired images andthe previously calculated digitally reconstructed radiographs.

Before each beamlet of radiation is administered, the x-rayimaging system determines target location and communicatesthe answer to the robot. The robot adjusts for small patientmovements by automatically realigning the treatment beamwith submillimeter accuracy (5).

Postradiosurgical follow-up, typically performed at 3months, 6 months, 1 year, and then annually thereafter, in-cluded clinical evaluation, physical examination, and radio-graphic imaging. The formula for an idealized ellipsoid, Vol 4/3 (length width height) was used to estimate tumorvolume on contrast MRI scans. Pain was qualitatively assessedby patient report as either improved, stable, or worse andsemiquantitatively by recording a patients analgesia require-

ment. This information was placed into a prospectively main-tained computer database. The median follow-up after radio-surgery for the entire series was 23 months (mean, 25 mo;range, 673 mo). Similarly, the median follow-up for eachhistological subtype was 25, 23, and 21.5 months in meningi-oma, schwannoma, and neurofibroma, respectively (mean,27.2, 26, and 19.9 mo, respectively).

RESULTS

Fifty-one patients (28 men, 23 women; median age, 46 yr;age range, 1286 yr) with 55 intradural extramedullary benignspinal tumors were treated with multisession radiosurgery

using the CyberKnife radiosurgical system (Table 1). A femalepredominance was observed among spinal meningiomas,whereas the male to female ratio in schwannomas and neuro-fibromas was 1.6:1 and 2:1, respectively. Twenty-six (51%)patients had undergone a previous surgical resection andwere being treated for residual or recurrent tumor. Four pa-tients developed tumors in radiation fields for other cancers(e.g., Hodgkins lymphoma, breast adenocarcinoma). One pa-tient developed a traumatic schwannoma (22, 43, 55) aftersurgery for removal of a synovial cyst. Seventeen patientscarried a diagnosis of either NF Type 1 (NF1) or NF2. Tumorswere observed throughout the entire spinal axis (Table 2) andvaried in configuration from entirely intraspinal to dumbbellshaped to predominantly foraminal. Presenting symptoms(pain, radiculopathy, and myelopathy) varied depending onspinal location and the precise relationship between the tumorand adjoining nerves/spinal cord (Table 3). Very few patientshad significant spinal cord compression and myelopathy be-fore radiosurgery. Furthermore, most patients presenting withmyelopathy developed this neurological deficit as a conse-quence of either previous tumor-related cord compression orspinal surgery. Eight (15%) asymptomatic patients underwentpreemptive radiosurgical ablation because of the size, loca-tion, or growth of their tumor on serial MRI scans.

Radiosurgical Doses and Fractionation

The specific fractionation schedule (median of two sessions;range, 15) was based on the size and volume of the treatedtumor as well as the length and total dose administered to the

spinal cord. For intracranial meningiomas and nerve sheathtumors, it is widely accepted that an effective single dose canrange from 12 to 18 Gy depending on the size of the lesion (6).Because with spinal lesions there is added concern about thedose tolerance of the spinal cord, and because of our previouslack of experience with paraspinal radiosurgery, we incorpo-rated staging in our dose selection for a substantial number ofthese tumors. The choice of dose and staging schedule wasselected to minimize the risk of spinal cord injury. With use ofthe concepts of the linear quadratic model, the biologicalequivalent dose (BED) is estimated by the following formula:BED nd(1 d//). Multisession radiosurgical regimenswere devised that achieved a BED of 53 to 180 Gy, dependingon the proximity to the spinal cord, history of prior spinal cordirradiation, and total tumor volume. These BED values com-pare favorably with the single fraction guidelines. (60126 Gy)for benign brain tumors. In most patients, radiosurgery wasdelivered in one (37%) or two sessions (42%). However, addi-tional daily sessions were administered in three (eight pa-tients), four (two patients), or five sessions (1 patient). Acutetoxicity was rare and limited to short-lived nausea.

Table 4 summarizes the radiosurgical dosimetry used in thisseries. Target volumes ranged from 0.136 to 24.6 cm3 (mean4.29 cm3; median 2.18 cm3). Treatment plans were designed to

TABLE 2. Characteristics of lesions

No. of lesions (%)

Level

Cervical 38 (69)

Thoracic 7 (13)Lumbar 8 (15)

Sacral 2 (4)

Histology

Schwannoma 16 (29)

Neurofibroma 9 (16)

Meningioma 30 (54)

TABLE 3. Presenting symptoms

Local or radicular pain 34 (63%)

Radicular sensory loss 26 (48%)Radicular weakness 22 (41%)

Myelopathic weakness 12 (22%)

Axial sensory loss 4 (7%)

Bladder paresis 3 (6%)

Asymptomatic 8 (15%)

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deliver 1600 to 3000 cGy to an average 80th percentile isodoseline as defined at the margin of the treated tumor; the corre-

sponding maximum intratumoral dose ranged from 1950 to3435 cGy (mean, 2506 cGy). Similar amounts of radiation weredelivered to all three tumor histologies because the / wasbelieved comparable for these slow-growing benign lesions.The major limitation to maximizing tumor dose was the desireto limit the risk of injury to the adjacent spinal cord. Somewhat

arbitrarily, but drawing from established optic nerve toleranceto radiosurgery, an attempt was made to construct treatmentplans that limited the volume of irradiated spinal cord receiv-ing more than a maximum single fraction dose of 1000 cGy toless than 0.2 cm3 (28, 52, 54). When this criterion could not bemet, we opted to fractionate the radiosurgery over two to fivesessions. In these situations, care was taken to limit the 80%reference dose per fraction to the spinal cord to below 800 cGy.Consistent with this objective, the volume of the spinal cordthat received 80% of the prescribed dose was generally lessthan 0.4 cm3 (0.2 0.06 cm3; mean standard error of themean), and the volume that received 50% of the prescribeddose was generally less than 1.4 cm3 (0.9 0.15 cm3; mean

standard error of the mean).

Clinical Symptoms at Presentation

After radiosurgery, most clinical symptoms either remainedstable or improved. Unfortunately, the small sample size forvarious symptoms precluded any significant findings, exceptfor pain. Across all tumor histologies, pain (both local andradicular) was the most common presurgical clinical com-plaint. The treated spinal tumors were painful in 78, 66, and53% of patients with neurofibromas, schwannomas, and me-ningioma, respectively. Collectively, 25 to 50% of patientsreported significant reduction in pain 12 months after Cy-berKnife SRS. The next most frequent symptoms in this serieswere radicular weakness and sensory loss, present in one thirdand two thirds of patients, respectively. The likelihood ofthese symptoms was similar across all three tumor histologies.Treated spinal tumors caused radicular weakness in 67, 35,and 34% of patients with neurofibromas, meningiomas, andschwannomas, respectively; similarly, radicular sensory losswas observed in 67%, 53%, 41%, respectively. Trends towardmodest improvements in these signs were also observedthroughout postradiosurgical follow-up.

Twenty-eight of the 55 lesions had greater than 24 monthsfollow-up (one, 6 yr; three, 5 yr; three, 4 yr; three, 3

FIGURE 1. MRI scans showing temporal response to radiosurgery is demon-strated in a patient with C7/T1 schwannoma treated with 19 Gy to the marginaldose in two sessions. A, sagittal T1 postcontrast MRI scan before SRS. Com-

parable images at 12 (B) and 40 months (C) after SRS also shown. Artifact fromimplanted fiducials is also noted in posttreatment images. Axial (D), sagittal (E),and coronal (F) postcontrast CT images used in treatmentplanning. Tumor (redlines, with or without solid squares), 83% isodose (solid green lines), and50% isodose curves (purple lines). Spinal cord (green line with squares) isidentified as a critical structure. Three-dimensional reconstruction of actual beam

paths used in treatment (G).

TABLE 4. CyberKnife treatment dosimetry characteristicsa

Meningioma Neurofibroma Schwannoma All

Average tumor volume, TV (cm3) 2.44 (0.14 7.57) 4.31 (0.6114.5) 5.72 (0.68 24.6) 4.53

Average prescribed dose, TD (cGy) 2031 (1600 3000) 1978 (1800 2100) 1870 (1700 2200) 1960

Average dose/session, Df (cGy) 1188 (500 1800) 1061 (700 2000) 1264 (500 2100) 1208

Average maximum tumor dose, Dmax (cGy) 2631 (19753435) 2646 (21682985) 2399 (19503000) 2507

a TV, tumor volume; TD, prescribed treatment dose; Df, treatment dose per session; Dmax, maximum dosage.




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yr; and 18 2 yr). The mean follow-up interval in this groupwas 36 months (median, 29 mo; range, 2473 mo). All lesionsin this group were either stable (61%) or smaller (39%) (Figs. 1and 2). No tumor in this group increased in size.

Post-SRS Tumor Enlargement and Surgical ResectionAmong the entire group of tumors treated in this series,

three enlarged on MRI scans by less than 10% at either 6 (twopatients) or 12 months (one case) on follow-up imaging. Theformer two lesions also demonstrated typical loss of centralenhancement when contrast was administered and regressedin volume on subsequent MRI scans. Given this temporalcourse, tumor enlargement was deemed transient and incon-sequential. The third tumor (a neurofibroma) was surgicallyremoved (at 13 mo) with the primary goal of decompressingthe spinal cord and reversing a pre-existing myelopathy.

Analogous to the treatment of benign tumors of the brain, itis worth noting that radiosurgery was not very effective at

reversing mass effect produced by intraspinal lesions. Al-though not enlarged on follow-up MRI scans, two lesions (onemeningioma, one schwannoma) were resected (at 10 and 13mo) because of persistent myelopathy. None of the surgeonsreported anything unusual about these resections.

Radiosurgical Complications

The only direct treatment-related complication occurred ina 29-year-old woman with a CyberKnife treated recurrentC7/T1 spinal meningioma, who developed the new onset ofposterior column dysfunction 8 months after radiosurgery(Fig. 3). In this case of presumed radiation myelopathy, theperipheral dose was 2400 cGy, administered in three sessionsto a tumor volume of 7.56 cm3, and a maximum dosage of 3435cGy. The dose volume histogram revealed that approximately

1.7 cm3 of the spinal cord received greater than 800 cGy perfraction.

Posttreatment neurological deterioration also occurred in a38-year-old patient with NF1 and multiple large cervical neu-rofibromas who underwent CyberKnife SRS to a large C2neurofibroma secondary to neck and scapula pain. He had

minimal response both clinical and radiographically to thetreatment at 6 and 12 months. Fifteen months postradiosur-gery, this patient suffered a fall that resulted in a complete C5quadriparesis. The worsening neurological function in thispatient was not counted as a complication of SRS.

Two patients died from causes unrelated to their tumors.One was an 82-year-old woman who died from respiratoryfailure complicating a long history of chronic pulmonary ob-structive disease, 7 months after radiosurgery for a C1 menin-gioma. A second patient with severe NF2 died 6 months aftertreatment of a C5 schwannoma. This 49-year-old woman ex-perienced bilateral vocal cord paralysis and chronic aspirationbefore radiosurgery, a condition that finally led to her death.

Histopathological examination of this patients postmortemtumor revealed hyalinized tumor vessels and central necrosis.Similar histology was observed after the removal of a neuro-fibroma in another patient 13 months after treatment (Fig. 4).

DISCUSSION

Radiosurgery delivered with image-guided robotics is aminimally invasive method for ablating almost any smallvolume of pathological tissue that can be visualized on med-ical imaging studies. Its accuracy, short-term safety, and effi-cacy have been previously reported for patients with malig-nant lesions of the spine (1, 5, 10, 36, 45). Because the lifeexpectancy of most of these patients is measured in monthsand because radiation injury can take years to manifest, the

FIGURE 2. MRI scans showing temporal response to radiosurgery inpatient with recurrent T9 schwannoma treated with 22 Gy in three ses-sions. A, pretreatment sagittal T1 postcontrast MRI scan. B, 6-month

sagittal postcontrast MRI scan illustrating slight change in pattern ofenhancement pattern. C, 24- and 73-month (D) sagittal postcontrast MRIscans illustrating size reduction and further loss of central enhancement.

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longer-term efficacy and safety of spinal radiosurgery is yet tobe established. A primary objective of the current investiga-tion was to clarify the risk of this procedure for spinal menin-giomas, schwannomas, and neurofibromas, tumors that tendto occur in patients with prolonged life expectancies. The closeproximity of these lesions to the spinal cord makes this ques-tion particularly relevant and was directly linked to our initialdeep-seated apprehension about the potential for radiation

FIGURE 4. Hematoxylin-eosin stained specimen from a surgicallyremoved C6 neurofibroma 13 months after CyberKnife radiosurgery.

Despite 20 Gy delivered in two sessions, this patient experienced persis-tent pain and worsening myelopathy, necessitating surgical decompression.

Hyalinized tumor vessels (A, arrows) and necrosis (B, arrows) are bothobserved (original magnification, 20).

FIGURE 3. CT and MRI scans showing treatment plan of a patient withC7/T1 recurrent meningioma treated with 24 Gy to the marginal dose in threesessions A, axial, sagittal, and coronal postcontrast CT images used in treatment

planning. Tumor (red lines, with or without solid squares), 71% isodose(solid green lines), and 50% isodose curves (purple lines). Spinal cordidentified as a critical structure (green line with squares). Three-dimensionalreconstructionof actualbeam paths used in thetreatment is shown. Pretreatment(B) sagittal and axial T1 postcontrast MRI scans along with posttreatment (C)sagittal and axial T2 images demonstrate location and size of ventral cervico-thoracic tumor (B, arrow) as well as intramedullary spinal cord injury (C,arrow) observed 8 months after radiosurgery.




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myelopathy. Despite our concern, only one patient in thisseries developed delayed radiation-induced injury to the spi-nal cord. The following discussion will review the pertinentclinical attributes of benign spinal tumors, summarize ourtreatment rationale, and discuss our experience with both theclinical benefits and radiation toxicity.

Rationale for using Radiosurgery to Treat Benign SpinalTumors

The majority of spinal meningiomas, schwannomas, andneurofibromas are noninfiltrative and can be completely andsafely resected by experienced surgeons. Because advancedoperative techniques provide surgical access to and the meansfor stabilizing nearly every spinal region (33, 34), even ventraland lateral tumors can now be removed with modest morbid-ity and mortality (2, 12, 37). When complete tumor removal isachieved, recurrence is unlikely (7, 8, 37, 46). Although surgi-cal resection is the mainstay for managing benign spinal neo-

plasms, there are also sporadic accounts of radiation therapybeing used successfully as a surgical adjuvant in small num-bers of patients (15, 44).

Since its conception, SRS has played an increasingly importantrole in the management of patients with intracranial meningiomaand schwannoma (4, 30), particularly in cases of difficult toaccess cranial-based tumors, where the risks to the brainstem andadjacent cranial nerves from standard microsurgical resection aregreatest. Kondziolka et al. (26) recently reported that the long-term tumor control rate in 85 benign intracranial tumor patientstreated with SRS at the University of Pittsburgh was 93%, with53% of lesions decreasing in size. Other studies have shownsimilar or better efficacy of SRS for cranial-based meningiomas,

along with low rates of radiation injury (3, 26, 29). Althoughvestibular schwannoma are histologically distinct, the long-termrate of growth control (9598% at 10 yr) after radiosurgical abla-tion is also excellent; up to 73% decrease in size (25, 39).

Given their pathological similarities, one would expect benignspinal lesions to respond to radiosurgery much the same asintracranial counterparts. Armed with image-guided radiosurgi-cal technologies, investigators have recently reported prelimi-nary results for treating small numbers of benign neoplasms ofthe spine with radiosurgery. Ryu et al. (45) published the firstdescription of SRS being used to treat such lesions. Their reportof 16 spinal lesions included 2 schwannomas, one meningioma,and a hemangioblastoma. Subsequently, there was a series of 15benign spinal tumors treated with the CyberKnife, 9 of whichwere either neurofibroma, schwannoma, or meningioma. Al-though no tumor progression was reported in either study, theminimum follow-up in both reports was only 6 months, and themean follow-up period in the latter study was a mere 12 months.In DeSalles et al.s (9) recent series of 14 patients, there wereindividual cases of neurofibroma and schwannoma, both ofwhich were stable in size after a mean follow-up of 6 months.The small number of patients and the very short follow-up, forsuch a group of relatively slow-growing lesions make it impos-sible to conclude from these studies anything other than that

spinal radiosurgery is feasible. The larger number of patients andlonger follow-up in the present study make it unique.

Spinal Meningiomas

Spinal meningiomas occur less frequently than intracranial

lesions, account for approximately 7.5 to 12.7% of all meningio-mas (50), and represent 25 to 46% of tumors of the spine (18).Most meningiomas arise from arachnoid cap cells embedded indura near the nerve root sleeve and as a result, are predomi-nantly lateral in location and have meningeal attachments (38).When they lie anterior to the spinal cord, particularly in thethoracic area, meningiomas provide a significant surgical chal-lenge. Forty percent of the 16 meningiomas in the present studywere anteriorly placed. Presenting symptoms were pain (53%),radicular sensory loss (53%), and radicular weakness (35%). Themean radiosurgical treatment dose across all meningioma in thisseries was 2031 cGy (range 16003000 cGy), which was admin-istered to a mean tumor volume of 2.441 cm3 (range, 0.1367.569cm3), using an average of two sessions (range, 15). The meanfollow-up interval in this cohort was 27.2 months (median, 25mo). After radiosurgery, the majority of patients reported im-provement in pain and strength but were without change insensory loss. However, in 30% of cases, a minor degree of wors-ening in pain, numbness, or subjective weakness was describedafter radiosurgical ablation.

Fifteen of the 16 meningioma patients in the current serieshad radiographic follow-up. The size of the treated lesionswas either stable (67%) or decreased (33%) at last follow-up.Importantly, no tumor increased in size. However, the lengthof follow-up is still far from adequate to establish the durabil-ity of radiosurgery in this population. In this regard, theprobability of recurrence after surgery or progression may be

lower in cases involving meningiomas of the spine than forintracranial sites (23). Among a group of operated spinalmeningioma patients followed for 7 years, Cohen-Gadol et al.(7) found a reoperation rate of only 5% in their older cohortbut a rate of 22.5% in younger patients, leading them tospeculate that the later may be innately more aggressive.Schick et al. (46) reported 8.6% of 81 operated spinal menin-giomas recurred on average 5.25 years after surgery. Riskfactors for recurrence included subtotal resection, youngerage, location anterior to the spinal cord, extradural extension,calcification, en plaque appearance, and NF2. Postoperativemortality ranged between 0 and 3% (37), and morbidityranged between 0 and 6% (37, 46), consisting mainly of wound

infections and cerebrospinal fluid leakage. These studies serveto categorize temporal progression in symptomatic patients,delineate at-risk populations of asymptomatic patients, andsuggest the minimum follow-up intervals required to assesstumor control after SRS.

Spinal Schwannomas

Schwannomas are the most common spinal tumor, account-ing for almost one-third of primary spinal neoplasms (49).Because spinal schwannomas typically arise from the poste-

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riolaterally placed dorsal root, their removal via laminectomyis fairly routine. Nevertheless, the risks of surgery are likelyincreased in elderly patients and for some recurrent lesions. Inthe current study, 30 patients with schwannoma were treatedwith a mean dose of 1870 cGy, using an average of tworadiosurgical sessions. The mean follow-up interval in this

cohort was 26 months (median 23 mo). Forty-one percent weretreated for recurrent or residual disease after surgical resec-tion, 1 (3%) had undergone prior radiation, and 16 (53%)underwent radiosurgery as their primary treatment option.

Twelve (40%) of the CyberKnife-treated schwannomas inthe present series occurred within a setting of NF2, a group ofpatients who are routinely confronted with a succession ofmultiple brain and spine lesions over the course of their lives.As is typical for spinal schwannomas, the presenting symp-toms in this series were pain (66%), radicular sensory loss(41%), or radicular weakness (34%). After radiosurgery, themajority of patients reported stabilization of their clinicalsymptoms, with one third describing improvement in pain,

weakness, or improved sensation. However, 18% reportedbeing clinically worse off than before treatment. Within therelatively short follow-up period of this study, tumor growthcontrol was observed in all but one radiosurgically ablatedspinal schwannoma; tumor was either stable (56%) or reduced(40%) in size. When the axial neck pain in a single patient witha slightly larger 3.4 cm C3 tumor was not improved by 13months, he underwent an uncomplicated surgical resection. Itis unclear whether the enlargement observed in this patientwould have been transient if not resected (as observed in somevestibular schwannoma).

Similar to other benign neoplasms, recurrence is unlikely (012.3%) when a spinal schwannoma is extirpated completely (8,

37, 46, 49). However, it is important to note that spinal schwan-noma, similar to their biological kin acoustic neuroma, have avariable rate of growth (21, 27, 49). Such intermittent growth isparticularly relevant to postoperative and postradiosurgicalfollow-up. In a series of 65 resected schwannomas, 5 (7.7%)recurrences only became apparent after 57 months (46).

NF is a significant risk factor for tumor recurrence. Despiteevidence that schwannomas of patients with and without NF2are indistinguishable histologically, tumors in patients withNF2 tend to behave much more aggressively (24). NF2 ischaracterized by an alteration of the gene sited on chromo-some 22q that predisposes patients to the development ofmultiple tumors of the central and peripheral nervous sys-tems. When the entire spine is scanned with MRI, spinal nervesheath tumors will be found in approximately 90% of NF2patients (32). Schwannomas are the most common type ofneoplasm that occurs in these patients (17). The natural historyof NF2-associated tumors is believed to differ from that oftheir sporadic counterparts, and data from Evans et al. (11)demonstrate that the NF2 genotype influences the number ofspinal tumors per patient. The clinical course of NF2 patientsharboring spinal schwannomas is as varied as their pheno-typic expression of the NF2 gene, and Mautner et al. (32)reported that only 33% of spinal tumors actually cause symp-

toms. Symptomatic schwannomas occurring in associationwith NF2 tend to grow faster, are more likely to infiltratenerve roots, tend to progress to severe neurological deficitssooner, and recur more frequently after resection (24). Kle-kamp and Samii (24) report a recurrence rate of 10.7% at 5years and 28.2% at 10 years in patients without NF2. However,

for patients with NF2, these investigators describe a recur-rence rate at 5 years of 39.2%, and all of their patients experi-ence recurrence by 9 years. Therefore, patients with NF2 needto be followed more vigilantly and may represent a cohort ofpatients for whom SRS may be particularly beneficial.

Spinal Neurofibromas

Neurofibromas are benign nerve-sheath tumors consistingof axons, Schwann cells, fibroblasts, perineural cells, mastcells, and collagen fibrils surrounded by extracellular myxoidmatrix. These tumors can arise from either peripheral or spinalnerve roots and are common in the setting of NF1, an autoso-

mal dominant disorder with highly variable expression. TheNF1 gene, which is located in the pericentromeric area onchromosome 17, codes for a tumor suppressor that, wheninactivated in both alleles, leads to tumorigenesis. Seppala etal. (49) found that spinal neurofibroma constitute approxi-mately 3.5% all spinal tumors, but less than 2% are symptom-atic.

In the present study, seven NF1 patients underwent radio-surgical ablation of nine spinal neurofibromas with a meandose of 1978 cGy and an average of two fractions. Follow-uptime ranged from 7 to 29 months with a mean of 19.9 months(median, 21.5 mo). Fifty-six percent of these patients weretreated for recurrent or residual disease after surgical resec-

tion, one (11%) had undergone previous radiation, and three(33%) had upfront radiosurgery as their primary treatment.The predominant presenting symptoms among NF1 patientswere pain (78%), sensory loss (67%), or weakness (67%). How-ever, it is important to note that a significant percentage ofthese cases presented with myelopathy, which in a few pa-tients was significant. No NF1 patient was asymptomatic.Unlike the other pathologies treated in this study, radiosur-gery did not improve preoperative clinical symptoms. Half ofthe NF1 patients described a worsening in pain, weakness, ornumbness at last follow-up. However, the treated neurofi-broma in six of the seven patients who underwent postoper-ative MRI were stable in size at last follow-up. One NF1patient with significant pretreatment myelopathy required mi-crosurgical resection at 13 months to decompress the spinalcord. Although the size of the tumor in this case had beencontrolled, this was insufficient for improving her symptoms.

Interestingly, our experience with radiosurgical ablation ofspinal neurofibroma correlates with the microsurgical litera-ture. Seppala et al. (49) reported that only one of 16 patients ina series of such tumors were free of symptoms after surgicalresection, and in all other cases pain, sensory deficits, or motorweakness persisted. This phenomenon may stem from theinfiltrating nature of neurofibroma, whereby the tumor itself




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is intermingled with the native nerve root. In such a situation,neither surgical removal nor radiosurgical ablation is specificenough for tumor alone.

Halliday et al. (17) have shown that the spinal nerve roottumors that occur in a setting of NF1 are typically neurofibro-mas, as compared with NF2 where schwannomas predomi-

nate. In contrast with NF2, where spinal tumors are a diag-nostic hallmark and often lead to neurological deficits (3040%), neurofibroma are less clinically significant in NF1 (24,53). Spinal tumors can be detected in 40% of NF1 patients byMRI scans, but they cause neurological symptoms in only 2%(53). Topographical classification of the neurological deficits isoften difficult because of the multiplicity of lesions along asingle nerve root and the often large number of affected roots.As a result, when confronted with a symptomatic NF1 patient,we typically resorted to treating either the largest lesion, thelesion with documented growth, or the lesion judged to bemost closely associated with the clinical symptoms. However,the poorer overall improvement in symptoms that we ob-

served in this patient cohort may stem in part from our in-ability to correctly identify the offending spinal tumor.

Consistent with the literature, we found that spinal neuro-fibromas often present at a younger age (48) compared withspinal schwannoma. This phenomenon likely contributes tothe overall poor outlook for these patients, which, in at leasttwo studies, manifests itself as a reduction in life expectancy(48, 51). Because spinal neurofibromas are typically multiple,are associated with persistent symptoms even after surgicalremoval, have an increased likelihood of recurrence, and oc-cur in a setting of lower life expectancy, an alternative treat-ment to surgical excision is potentially quite attractive.

Radiation Injury

One patient in the current series experienced a radiation-induced spinal cord injury. To the best of our knowledge, thisseems to be the first published case of radiation-induced myelop-athy after SRS. By the standards of the present study, this wom-ans treatment was not especially aggressive. The volume oftumor, dose, and fractionation were unremarkable. The onetreatment variable that may have contributed to her injury, how-ever, was the volume of spinal cord irradiated. Approximately1.7 cm3 of spinal cord was irradiated with slightly more than 6Gy per fraction and 18 Gy over all three sessions. Although thisdid not seem unusual at the time of surgery (given our experi-ence treating vertebral metastasis), this volume of irradiatedspinal cord does represent an outlier in the current study. Al-though this certainly gives us pause, there were other patientswho received more radiation to their spinal cord without se-quela. It is also reasonable to speculate that the trauma from twoprior surgical resections may have predisposed this womansspinal cord to subsequent radiation injury. Furthermore, it isworth noting that this complication did not occur in the water-shed region of the midthoracic region where spinal cord injury ofall kinds, especially radiation induced, is most frequent. The onlyother radiosurgery patients at Stanford who have developed

radiation-induced spinal cord injury (among more than 100 ma-lignant spinal neoplasm) suffered this complication in themidthoracic region.

The literature indicates that the main factors associated witha risk of radiation-induced myelopathy are the total dose andfraction size, length of spinal cord irradiated and total dura-

tion of treatment (19, 40, 47). Delayed radiation myelopathyfrom conventional radiation therapy typically has a timecourse between 6 to 24 months (31, 40, 47). The traditionaldose tolerance of the normal spinal cord to conventional frac-tionated external beam radiotherapy is often quoted to be 45 to50 Gy delivered in 1.8 to 2 Gy fractions (19, 31, 40). However,other studies examining the incidental irradiation of the cer-vical spinal cord during radiotherapy for head and neck can-cer suggest even greater radiation tolerance (31). Overall, thepublished literature suggests that a realistic estimate of a 5%risk of myelopathy at 5 years requires 57 to 61 Gy delivered in2 Gy fractions (47). The present limited experience (with onlyone complication) is insufficient for determining the absolute

threshold for developing spinal cord damage after multises-sion radiosurgery. Longer follow-up is also needed to assessthe ultimate risk of spinal radiosurgery.

Response of Symptoms to Spinal Radiosurgery

The most common presenting symptom of spinal tumors waspain, and reasonable success at pain alleviation was achievedwithin the time frame of this study. Although tolerable doses ofradiosurgery have been shown to be effective for managing painsecondary to spinal metastasis, the ultimate rate of tumor controlremains to be defined (10, 14, 42). Interestingly, the specificpathophysiological mechanisms of pain relief after irradiation of

all spinal tumors remain poorly defined. In the case of vertebralmetastasis without compression fractures, stretching of perios-teum by tumor expansion, mechanical stress of the weakenedbone, activation of pain receptors by the release of chemical painmediators/cytokines from the tumor and the inflammatory re-sponse to it, and nerve entrapment/nerve root infiltration by thetumor are all potential pain mechanisms (35). The analgesicaction of radiotherapy for bone metastases is possibly mediatedvia tumor shrinkage and inhibition of the release of chemicalpain mediators (20). The sometimes rapid initial pain relief ob-served after only a single-fraction may suggest an effect onchemical mediators of the inflammatory response (20). Becausemany patients in this study reported pain relief without radio-graphic evidence of tumor acquiescence, it seems reasonable thatsimilar processes occur after radiosurgical ablation of benignhistologies.

In the present series, approximately 70 and 50% of patientswith spinal meningioma or schwannoma, respectively, re-ported significant improvement and, in many cases, completerelief of their pain. In general, no correlation was observedbetween pain relief and the number of multisession treatmentsor the amount of radiation delivered. The time course of painamelioration varied from a few weeks to months, althoughone patient reported complete pain abatement after only 6

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days. Some patients reported a temporary increase in radicu-lar symptoms 2 to 3 weeks after radiosurgery, which im-proved with corticosteroids and later resolved without addi-tional analgesia. This phenomenon is hypothesized to besecondary to radiation-induced tumor swelling, which mightcorrelate with the slight transient increase in tumor size occa-

sionally observed at 6 to 8 months. Many patients first re-ported improved symptoms at their 12 month assessment, andno patient who achieved complete pain relief has reportedrecurrence. The pain response therefore appears durable.

Not all patients experienced pain relief. Several patients, whoin retrospect likely had postsurgical pain, not surprisingly didnot improve. Patients with NF1 (unlike those who carry thediagnosis of NF2) also often failed to attain analgesic or othersymptomatic relief, possibly because of nerve infiltration or ourinability to accurately identify which of their tumors was respon-sible for symptoms. In addition, persistent pain was observed inNF cases where new lesions arose and in a small number ofpatients who had larger tumors that, after SRS, were less likely to

shrink appreciably in the short term. This last limitation alsoapplies to the use of radiosurgical ablation for larger intraspinaltumors that cause significant myelopathy.

Slow-growing, benign, intradural extramedullary tumorspresumably cause radicular and myelopathic symptoms ofweakness and numbness from gradual nerve root and spinalcord compression. Interestingly, improvement in these symp-toms was often observed without radiographic evidence oftumor shrinkage. Seven of the 16 patients with spinal schwan-noma who initially presented with complaints of weakness orsensory loss reported some form of symptom improvementafter radiosurgery. More interesting, only one of those sevenwas among the 25% of schwannomas that were reduced in

size. Similarly, 8 of the 16 patients with spinal meningiomathat exhibited clinical weakness or sensory loss describedsymptom improvement after CyberKnife treatment. Four ofthese patients had tumors that decreased in size after radio-surgery, whereas four patients had tumors that remainedstable. The mechanism responsible for clinical improvement inthese cases remains as enigmatic as the analgesic action ofradiation. Importantly, no neurological symptoms developedas a result of treatment in any asymptomatic patient.

Because, as described above, the growth of benign spinal tu-mors can take several years, the length of follow-up in the cur-rent study is insufficient to establish the long-term efficacy ofspinal radiosurgery for these lesions (46). Nonetheless, long-termstudies in patients with benign brain tumors who were treatedwith radiosurgery suggests that tumor control at 3 years is verylikely to be durable (26). Ultimately, longer follow-up will beneeded to definitively establish the safety, and even more so, theefficacy, of radiosurgery for benign spinal tumors.

CONCLUSION

At the start of this study, we harbored grave concerns thatradiosurgical ablative doses could prove injurious to the ad-jacent spinal cord. Selection of doses and fraction number

were based on our own and published experience with intra-cranial ablation, which in hindsight may have been moreconservative than needed. As we have gained experience andconfidence in the overall safety of spinal radiosurgery, doseshave been gradually escalated and the number of fractionsdecreased. Thus, the dose-fraction regimens described here

should not be viewed as optimal but merely as useful startingpoints for future investigation. Nevertheless, this study dem-onstrates both the relative safety, and early evidence of effi-cacy, for spinal radiosurgery and provides a rough frameworkfor treating patients going forward. Given the average lengthof follow-up to date, it is not possible to say anything defini-tive about long-term efficacy of spinal radiosurgery for benigntumors; this topic will remain the subject of ongoing investi-gation at our institution. Nevertheless, the present study doessuggest that CyberKnife SRS could someday serve as a usefuladjunct to the neurosurgical armamentarium for managingselected benign spinal tumors.

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COMMENTS

The authors not only provide clinical and radiosurgical details on thelargest series of benign spinal tumors treated with radiosurgery todate, but they also thoroughly discuss the particularly relevant questionsfor this relatively new addition to the clinical armementarium. Althoughlonger follow-up of this cohort will be necessary, the length of clinicaland radiological follow-up in this series serves as a basis for compellingclinical information, especially in view of the low morbidity after signif-icant cumulative doses of radiation to the spinal cord. The prospectivemanner of data collection allows for an optimal reliability in terms ofclinical assessment, especially for complaints of pain.

As is not uncommon in radiosurgical series, the diagnosis is notalways pathologically confirmed. In the present series, the diagnosiswas established based on magnetic resonance imaging in a certainpercentage of patients, underscoring the need for careful clinical andradiological follow-up.

Perhaps one of the most worrisome issues for practitioners relatesto the extent of spinal cord compression that would limit this form ofnonsurgical treatment. While it is stated in this report that very fewpatients had significant spinal cord compression, future reports focus-ing on this radiological parameter will be necessary. In this regard, itis interesting to note that many of the tumors in this series did notdecrease in size.

Attention should also be drawn to the data relative to the volume ofspinal cord receiving significant doses of radiation; less than 0.4 cm2

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received 80% of the prescribed dose and less than 1.4 cm 2 received50% of the prescribed dose. These volumes represent a significantpotential for neurological deterioration, yet the morbidity noted inthis series remained low.

Notably, while only one tumor (1/55) actually enlarged radiologi-cally, surgery for persistence or worsening of symptoms was required

in 3 patients from the entire cohort. Despite only 3 patients requiringsubsequent surgery, a greater percentage of patients still reportedincreased symptoms, and this issue, while disappointing, has beenaddressed in the discussion.

While only one convincing radiation-induced complication is re-ported in this series, it would seem reasonable to also consider as apossible radiation-induced complication the patient who was radiatedfor a C2 tumor and died 7 months after treatment with respiratoryinsufficiency.

Overall, this report from one of the pioneering groups in the field isinformative and the results are encouraging.

Jack P. Rock

Detroit, Michigan

This paper represents an important landmark in the development ofradiosurgery. This group of investigators should be commendedfor their courage in aggressively pursuing this new indication forradiosurgery. Prior investigations regarding spinal radiosurgery haveconcentrated primarily on treatment of metastasis disease to the spine.This report, by contrast, addresses treatment of benign intraduralspinal disease. The long overall life expectancy of the subjects, as wellas the technical constraints in regards to limiting spinal cord exposureto radiation, increases the potential for risk.

Evaluation of outcomes for these patients is difficult due to the longfollow-up periods required in order to determine disease control,neurological function, and radiation-induced side effects. This paperanalyzes a sizeable number of patients with fairly heterogeneouspathology, including several different tumor types and sizes, varyingdegrees of cord compression, and varying histories of prior surgical

resection. Such limitations do not, however, take away from theprimary observations of technical feasibility and overall safety of theprocedure. The median follow-up length in this report is sufficient tomake some basic conclusion regarding early outcomes. As such, thispaper serves as an important starting point for further investigationsinto the application of radiosurgery in the treatment of benign intra-dural spinal tumors. The present information in the literature, how-ever, is deficient primarily in its description of the long-term toleranceof the spinal cord to specific dose and fractionation regimens. Groupsinterested in pursuing this form of treatment should understand thecurrent lack of understanding in regards to the therapeutic window ofefficacy and safety when treating for this indication.

The authors have demonstrated that the early risk of complications fromhypofractionated stereotactic radiotherapy is low, and the rate of tumorcontrol is respectable. Nevertheless, the overall role of spinal conformalradiotherapy for benign intradural tumors in specific circumstances remainsto be determined. Its utilization in the clinical setting should be tempered bythe availability of highly safe and effective open surgical treatment. In thesetting of a neurological deficit due to a compressive myelopathy, surgeryshould continue to be recommended as the first-line treatment of choice.Radiosurgery in such instances should be discouraged. While the use ofspinal radiosurgery at present should be restricted to patients who are poorsurgical risks or who refuse surgery in the setting of adequate and completeinformed consent, continued accrual of clinical data may ultimately change

this recommendation. This has been the case for a variety of cranial indica-tions where radiosurgery has assumed the role of treatment of first choice.

Michael R. Girvigian

Radiation OncologistJoseph C.T. Chen

Los Angeles, California

Dodd et al. have presented the outcomes of 51 patients with benignspinal tumors having CyberKnife treatment. These early resultsare encouraging, with less than 10% of patients requiring operative

resection after the radiation treatments. This approach is especiallyattractive for patients with neurofibromatosis and for patients with

recurrent tumors after prior surgery.

Bruce E. Pollock

Rochester, Minnesota

Stereotactic radiosurgery is becoming an important new technique for themanagement of a variety of spinal tumors. While there is an increasingbody of evidence supporting the role of radiosurgery for malignant spinaltumors, there is much less experience and more controversy regarding its

use for benign tumors of the spine. Indeed, less than 15% of our total spinalradiosurgery experience has been for benign tumors, mostly neurofibromas,

schwanommas, and meningiomas. This is somewhat different than theintracranial radiosurgery experience at most centers.

In this study, the authors have attempted to carefully analyze their

experience with radiosurgery for benign intradural extramedullary spi-nal tumors in what is the largest published series to date on this subject.

The authors have organized their analysis based on tumor histology.While a relatively small clinical series, their results mirror radiographic

tumor control rates for these histologies when treated within the cra-

nium. As is often the case with such new technologies, patient selectionis often due to the fact that they are not candidates for more conventional

treatments, namely open surgical techniques. Many of these patients arereferred for spinal radiosurgery either because they cannot or wish not to

undergo open surgery. In other cases, radiosurgery is used as a salvagetechnique after post-surgical tumor recurrence.

There are several limitations to this study. It represents a cohort of quite

different patients with a wide variety of differently sized (0.136 to 24.6 cm 3)and shaped tumors. There was also quite a difference in radiosurgical

technique employed between patients. Total treatment doses range from 16to 30 Gy delivered in one to five fractions. This makes it somewhat more

difficult for the reader to extrapolate the best dose and fractionation scheme

to use on his or her own patients. The authors did their best to explain theirrationale for dose prescription. As the authors state, the dose-fraction reg-

imens described here should not be viewed as optimal but merely as usefulstarting points for future investigation.

I believe that the authors statement that the study demonstrates both therelative safety and early evidence of efficacy for spinal radiosurgery for

benign intradural extramedullary spinal neoplasms has been validated bythis manuscript. Our own experience with a comparable number of patients

has alsobeenequallyencouraging. I would hopethatfuture standardizationof fractionation schemes, as well as doses, will allow for the more useful

comparison between clinical series. I expect for spinal radiosurgery to be anexciting new development in the treatment of these potentially very chal-

lenging cases.

Peter Gerszten

Pittsburgh, Pennsylvania



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