Brain : Acoustic Neuroma : Cyberknife Radiosurgery Preserving Hearing

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J Neurosurg / Volume 111 / October 2009

J Neurosurg 111:863873, 2009

863

Acoustic neuromas, also known as vestibularschwannomas, are benign tumors arising fromthe vestibulocochlear nerve sheath. In recent

years ANs have been diagnosed more frequently and atearlier stages of presentation because of the widespreadavailability of MR imaging. The tumor location may beintracanalicular only or extend outside the IAC. There isvariable extension of the tumor along the course of thevestibular nerve.1,19 The most frequent presenting symp-

toms include tinnitus, hearing loss, gait disturbances,facial numbness, and weakness.3 Common hypothesesfor the development of hearing loss include direct com-pression of cochlear nerve bers by an adjacent AN, thedevelopment of a conduction block followed by the de-generation of nerve bers, compression and/or thrombo-sis of the internal auditory artery, and/or ischemic injuryto the cochlea.3,12

Therapeutic options include observation, microsur-gical removal, SRS, SRT, or other forms of fractionatedradiation therapy. Presently, radiosurgery is a well-estab-lished alternative to microsurgical removal of an AN.10

In a recent study in which Gamma Knife surgerywas utilized, Paek et al.21 suggested that the maximum

Predictors of hearing preservation after stereotacticradiosurgery for acoustic neuroma

Clinical article

Hideyuki kano, M.d., PH.d.,1,3 douglas kondziolka, M.d., F.R.C.s.(C),1,3aFtab kHan, M.d.,1,3JoHn C. FliCkingeR, M.d.,2,3and l. dade lunsFoRd, M.d.1,3

Departments of1Neurological Surgery and2Radiation Oncology, and the 3Center for Image-Guided

Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Object. Many patients with acoustic neuromas (ANs) have hearing function at diagnosis and desire to maintainit. To date, radiosurgical techniques have been focused on conformal irradiation of the tumor mass, with less attentionto inner ear structures for which there was scant radiobiological information. The authors of this study evaluated tu-mor control and hearing preservation as they relate to tumor volume, imaging characteristics, and nerve and cochlearradiation dose following stereotactic radiosurgery (SRS) using the Gamma Knife.

Methods. Seventy-seven patients with ANs had serviceable hearing (Gardner-Robertson [GR] Class I or II) andunderwent SRS between 2004 and 2007. This interval reected more recent measurements of inner ear dosimetryduring the authors 21-year experience. The median patient age was 52 years (range 2282 years). No patient hadundergone any prior treatment for the ANs. The median tumor volume was 0.75 cm3 (range 0.077.7 cm3), and themedian radiation dose to the tumor margin was 12.5 Gy (range 1213 Gy). At diagnosis, a greater distance from thelateral tumor to the end of the internal auditory canal correlated with better hearing function.

Results. At a median of 20 months after SRS, no patient required any other additional treatment. Serviceablehearing was preserved in 71% of all patients and in 89% (46 patients) of those with GR Class I hearing. Signicantprognostic factors for maintaining the same GR class included (all pre-SRS) GR Class I hearing, a speech discrimi-nation score (SDS) 80%, a pure tone average (PTA) < 20 dB, and a patient age < 60 years. Signicant prognostic

factors for serviceable hearing preservation were (all pre-SRS) GR Class I hearing, an SDS 80%, a PTA < 20 dB,a patient age < 60 years, an intracanalicular tumor location, and a tumor volume < 0.75 cm 3. Patients who received aradiation dose of < 4.2 Gy to the central cochlea had signicantly better hearing preservation of the same GR class.Twelve of 12 patients < 60 years of age who had received a cochlear dose < 4.2 Gy retained serviceable hearing at 2years post-SRS.

Conclusions. As currently practiced, SRS with the Gamma Knife preserves serviceable hearing in the majorityof patients. Tumor volume and anatomy relate to the hearing level before radiosurgery and inuence technique. A lowradiosurgical dose to the cochlea enhances hearing preservation. (DOI: 10.3171/2008.12.JNS08611)

key WoRds acoustic neuroma cochlea Gamma Knife

hearing preservation stereotactic radiosurgery vestibular schwannoma

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Abbreviations used in this paper: AN = acoustic neuroma; GR =Gardner-Robertson; IAC = internal auditory canal; PTA = pure toneaverage; SDS = speech discrimination score; SRS = stereotacticradiosurgery; SRT = stereotactic radiotherapy.


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dose delivered to the cochlear nucleus in the brainstemwas the only signicant prognostic factor for hearing de-terioration. Massager et al.16,17 showed that hearing lossfollowing SRS was related to the volumetric and dosimet-ric parameters of the intracanalicular tumor and that thedose to the cochlea, rather than the cochlear nucleus, isrelevant. We studied tumor anatomy, radiosurgical plan-ning, and the radiation dose delivered to the inner earstructures to dene a relationship between radiosurgicaltechnique, tumor extent, hearing function at presentation,and later outcome.

Methods

Patient Population

The University of Pittsburgh Institutional ReviewBoard approved this retrospective study. Between Octo-ber 2004 and March 2007, 248 consecutive patients withpreviously untreated unilateral ANs underwent SRS with

the Gamma Knife (Elekta Instruments) at the Universi-ty of Pittsburgh. For this series of patients, we excludedthose with neurobromatosis Type II, unserviceable hear-ing (GR Class IIIV) at the time of SRS, and < 6 monthsof radiological and audiological follow-up data (8 patientswith GR Class I, and 2 with GR Class II hearing). Twelvepatients with GR Class III hearing, 4 with GR Class IV,and 20 with GR Class V were excluded. The demographiccharacteristics of this study population of 77 patients arelisted in Table 1.

There were 40 men and 37 women with a medianage of 52 years (range 2282 years). Audiography re-sults were evaluated according to the GR classication.8

Serviceable hearing (useful hearing) was dened as GRClass III (SDS 50% and PTA 50 dB). Before SRS,46 patients had GR Class I hearing (SDS 70% and PTA

30 dB) and 31 patients had GR Class II (SDS 6950%and PTA 3150 dB). Radiological results were evaluatedaccording to the Koos system of classication:11 Grade I,28 patients (GR Class I in 22 patients, GR Class II in 6);Grade II, 18 patients (GR Class I in 8 patients, GR ClassII in 10); Grade III, 25 patients (GR Class I in 12 patients,GR Class II in 13); and Grade IV, 6 patients (GR Class Iin 4 patients, GR Class II in 2).

Radiosurgery Technique

Radiosurgery was performed using a Model C or4-C Leksell Gamma Knife (Elekta, Inc.). Our radiosur-gical technique has been described in detail in previousreports.5 The procedure began with the application of aModel G Leksell stereotactic frame after inducing con-scious sedation and applying a local scalp anesthetic, ex-cept in younger children in whom general anesthesia wasinduced. The tumor was then visualized using high-reso-lution 3D spoiled gradient recalled acquisition in steadystate sequence MR imaging after intravenous contrast en-

hancement. Fast spin echo T2-weighted MR images wereacquired to evaluate tumor extent and inner ear structures.We obtained images of the cochlea, vestibule, and semi-circular canals using T2-weighted volume-acquisitionMR imaging divided into axial images at 1- to 1.5-mmintervals. Figures 1 to 4 show the cochlear modiolus, in-dicated by a cruciform mark. Images were exported toa computer workstation for dose planning with LeksellGammaPlan software. In all tumors the radiosurgery vol-ume conformed to the enhancing tumor volume.

The median tumor volume was 0.75 cm3 (0.077.7cm3). The median prescription dose delivered to the tu-mor margin was 12.5 Gy (1213 Gy). The prescription

isodose was 50% in 65 cases. The maximum radiationdose varied from 18.6 to 26 Gy (median 25 Gy). All pa-tients received an intravenous dose of 2040 mg methyl-

TABLE 1: Summary of characteristics in 77 patients with AN

Characteristic GR Class I GR Class II Entire Series

no. of patients 46 31 77

median age in yrs (range) 51 53 52 (2282)

no. of men 22 18 40

no. of women 24 13 37

median PTA in dB (range) 16 (030) 40 (1849) 24 (049)median SDS in % (range) 98 (76100) 84 (56100) 92 (56100)

median dose to central cochlea in Gy (range) 4.5 (1.16.9) 4.6 (1.58.2) 4.5 (1.18.2)

median distance from tumor to IAC in mm (range) 2.7 (09.0) 2.1 (08.8) 2.5 (09.0)

Koos grade (no. of patients)

I 22 6 28

II 8 10 18

III 12 13 25

IV 4 2 6

median target vol in cm3 (range) 0.47 (0.096.7) 1.1 (0.077.7) 0.75 (0.077.7)

median tumor margin dose in Gy (range) 12.5 (1213) 12.5 (1212.5) 12.5 (1213)

median max radiation dose in Gy (range) 25 (18.626) 25 (20.825) 25 (18.626)


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prednisolone after radiosurgery, and all were dischargedfrom the hospital within 2 hours.

Patient Follow-Up

Patients were instructed to undergo clinical and imag-ing assessments after radiosurgery at 6 months, annuallyfor 2 years, and at less frequent intervals thereafter (every4 years past Year 10). If a new neurological symptom orsign (especially hearing deterioration) developed, the pa-tient was evaluated for audiological deterioration, tumorprogression, or any adverse radiation effect, and new au-

diological testing and MR imaging were performed. Allpatients had a minimum of 6 months of follow-up (range640 months, median 20 months). Thirty-three patientshad follow-ups 24 months. Tumor control was assessedin 2 ways. Radiologically demonstrated tumor progres-sion was strictly dened as any temporary or sustainedincrease in tumor diameter of at least 1 mm in 2 dimen-sions or 2 mm in any direction.

We assessed hearing preservation with follow-up au-diography, using the end points of preserving a specicGR hearing class (Class III) or serviceable hearing.

Based on MR images of each radiosurgical plan, wedened the dose to the central cochlea (modiolus), at thevestibule, and in the middle of the horizontal semicircular

canal, as well as the distance from the end of the tumorto the end of the IAC (Figs. 14). Radiation doses at thesepoints were derived using Leksell GammaPlan software.

Statistical Analysis

For statistical analysis we constructed Kaplan-Meierplots for GR class of hearing function, serviceable hear-ing preservation, and progression-free survival using thedate of SRS, follow-up audiological tests or MR images,and last follow-up data. Results were calculated from theday of SRS using the Kaplan-Meier method. Univariate

analysis of the Kaplan-Meier curves was performed usingthe log-rank statistic, with a probability level < 0.05 set assignicant. The Fisher exact test was applied to study therelationship between the number of patients who experi-enced hearing deterioration and a number of other specicvariables, with a probability level < 0.05 set as signicant.A comparison of continuous variables was performed us-ing the Mann-Whitney 2-sample t-test, again with a prob-ability level < 0.05 set as signicant. Multivariate analysiswas performed with the Cox proportional hazards model,with a probability level < 0.10 set as signicant. Standardstatistical processing software (SPSS, version 15.0, SPSS,Inc.) was used.

Fig. 1. A and B: Axial T2-weighted MR images obtained in a 67-year-old woman, showing a right AN (Koos Grade III at thetime of SRS). C and D: Axial T1-weighted contrast-enhanced MR images showing a right AN. One-sided arrowindicates thewell-visualized cochlea;cruciformmarks indicate the center of the cochlea, or the modiolus (dose = 3.1 Gy); and thedouble-sidedarrowshows the distance from the lateral end of tumor to the end of the IAC (3.9 mm). The radiosurgery plan is shown to deliver12.5 Gy to the tumor margin.


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Results

No patient has required any other procedure since theSRS. Tumor control was achieved in 75 (97.4%) of the 77patients at the last follow-up. Two patients demonstrateda small expansion (2 mm) of the extracanalicular tumorcomponent on early imaging after SRS.

Hearing Function Before SRS

Twenty-two of 46 patients with GR Class I hear-ing had an intracanalicular tumor only (Koos Grade I),whereas 6 of 31 patients with GR Class II hearing had an

intracanalicular tumor (p = 0.009, Fisher exact test). Themean and median age of patients with GR Class I hear-ing were 49.4 and 51.0 years, respectively, whereas thosefor patients with GR Class II were 55.7 and 53.0 years,respectively (p = 0.017, Mann-Whitney t-test). The meanand median tumor volume of patients with GR Class Ihearing were 1.20 and 0.47 cm3, respectively, whereasthose of patients with GR Class II hearing were 1.91 and1.1 cm3, respectively (p = 0.030, Mann-Whitney t-test).The median radiation dose to the center of the vestibule inpatients with GR Class I and II hearing were 6.3 and 7.3Gy, respectively (respective mean distance 6.57 2.48 vs7.35 2.55, p = 0.193, Mann-Whitney t-test). The medianradiation dose to the semicircular canal in patients with

GR Class I and II were both 3.8 Gy (respective mean dis-tance 3.78 0.93 vs 4.13 1.44, p = 0.238, Mann-Whit-ney t-test). The distance from the lateral end of the tumorto the end of the IAC (lateral extent) was not a predictorof hearing preservation; however, it was signicantly as-sociated with the GR class before SRS (mean distance forGR Class II vs 2: 3.44 2.29 vs 2.32 2.10, p = 0.0025,Mann-Whitney t-test). In addition, the distance from thelateral end of the tumor to the end of the IAC (lateral ex-tent) was associated with the GR class before SRS (meandistance for GR Class III vs Class IIIV: 2.89 2.28 vs2.10 2.40, p = 0.045, Mann-Whitney t-test; GR Class I,

II, and III vs V: p = 0.001, 0.026, and 0.007, respectively,Mann-Whitney t-test).Thus, GR Class I was signicantly associated with an

intracanalicular tumor location, a younger age, a smallertumor volume, and a longer segment of the IAC free oftumor.

Fifty-seven (36 with GR Class I and 21 with GR ClassII) of 77 patients had tinnitus before radiosurgery. Afterradiosurgery, tinnitus improved in 7 patients, worsened in5, and remained unchanged in 45. Twenty other patientsremained tinnitus free after radiosurgery.

Hearing Preservation After SRS

The last audiological examination revealed that 45

Fig. 2. A and B: Axial T2-weighted MR images obtained in a 54-year-old man, demonstrating a right AN (Koos Grade II atthe time of SRS). C and D: Axial T1-weighted contrast-enhanced MR images showing a right AN.Arrowindicates the cochlea,cruciform markshows the cochlear modiolus (dose = 2.6 Gy), anddouble-sided arrowshows the distance from the lateral end ofthe tumor to the end of the IAC (2.5 mm). The Gamma Knife surgery plan is shown.


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patients (58.4%) retained the same (pre-SRS) GR hear-ing class after SRS. Two patients (2.6%) had improvedhearing from GR Class II to I. Thirty patients (39.0%) ex-perienced some reduction in hearing after SRS. Hearingwas reduced by 1 GR class in 23 patients (8 patients fromGR Class I to II and 15 patients from GR Class II to III),by 2 classes in 4 patients (all 4 patients from GR Class Ito III), by 3 classes in 2 patients (both from GR Class IIto V), and by 4 classes in 1 patient (from GR Class I toV). Audiological tests in 22 patients (28.6%) showed dete-rioration to unserviceable hearing (GR Class IIIV) afterSRS; thus, 55 (71.4%) of 77 patients maintained service-able hearing (GR Class III) following SRS (Table 2).

Eighty-four and 56.5% of patients maintained thesame GR class at 1 and 2 years post-SRS, respectively.The median time for dropping to a lower GR class afterSRS was 25.0 5.1 months (mean SD). At 1 and 2 yearsafter SRS, 89.3 and 66.8% of respective patients had pre-served hearing. Among those whose hearing became un-serviceable, the mean time for unserviceable hearing todevelop was 31.1 3.5 months.

Statistical Analysis

We performed univariate analysis using the log-rankand Fisher exact test to assess factors that might inu-ence hearing preservation (remaining within the same

GR class or retaining serviceable hearing). The followingvariables were assessed: sex (male vs female), age ( vs< 60 years), prescription SRS target volume ( vs < 0.75cm3), radiation dose to tumor margin ( vs < 12.5 Gy),Koos grade (Grade III vs IIIIV), intracanalicular tu-mor only (yes vs no), radiation dose to the central cochlea( vs < 3.8, 4.0, 4.2, and 4.5 Gy), GR hearing class beforeSRS (Class I vs II), SDS before SRS ( vs < 70, 80, 90,and 100%), PTA before SRS ( vs < 20 and 30 dB), anddistance from the lateral end of the tumor to the end ofthe IAC ( vs < 2 and 4 mm). On univariate testing forthe entire series, pre-SRS factors associated with an im-

proved rate of hearing preservation (remaining within thesame GR class) included a younger age, GR Class I hear-ing, a higher SDS, and a lower PTA. The pre-SRS factorsassociated with an improved rate of serviceable hearingpreservation included a younger age, an intracanaliculartumor only, a smaller tumor volume, GR Class I hearing,higher SDS, and lower PTA (Table 3). In addition to thefactors associated with a better chance of preserving theGR class, the Fisher exact test showed that a radiationdose < 4.2 Gy to the central cochlea was signicantly as-sociated with better odds of preserving hearing function(p = 0.022).

We performed multivariate analysis using the Coxproportional hazards model to assess factors that might

Fig. 3. A and B: Axial T2-weighted MR images obtained in a 51-year-old man, revealing a right AN (Koos Grade III at thetime of SRS). C and D: Axial T1-weighted contrast-enhanced MR images showing a right AN.Arrowindicates the cochlea,cruciform markshows the modiolus (dose = 4.1 Gy), and double-sidedarrowdemonstrates the distance from the lateral end ofthe tumor to the end of the IAC (3.2 mm).


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inuence the rates of hearing preservation. The followingvariables were assessed: radiation dose to the central co-chlea, tumor volume, distance from the lateral end of thetumor to the end of the IAC, and GR hearing class beforeSRS. On multivariate analysis, the only factor associatedwith improved odds of preserved hearing (same GR classor serviceable hearing preservation) was GR Class I hear-ing before SRS (p = 0.014 and p = 0.0001, respectively).

Predictors of Hearing Outcome

Patients with GR Class I hearing before SRS had a

signicantly better chance of remaining within the sameGR class (p = 0.029, log-rank test; p = 0.013, Fisher exacttest) and retaining serviceable hearing (p = 0.012, log-ranktest; p = 0.070, Fisher exact test). Patients with a PTA < 20dB before SRS remained within the same GR class (p =0.00017, log-rank test; p = 0.00025, Fisher exact test) andhad better odds of maintaining serviceable hearing (p =0.00025, log-rank test; p = 0.001, Fisher exact test).

Fourteen (93.3%) of 15 patients with a pre-SRS SDS< 80% exhibited some deterioration in hearing (any dropin GR class) compared with 15 (25.0%) of 60 patients

TABLE 2: Hearing outcome after SRS

No. (%)

GR Class Preserved Hearing

Variable Improved Stable Worse Serviceable Unserviceable

pre-SRS 2 (2.6) 45 (58.4) 30 (39.0) 55 (71.4) 22 (28.6)

GR class

I 0 (0) 33 (71.7) 13 (28.3) 41 (89.1) 5 (10.9)

II 2 (6.5) 12 (38.7) 17 (54.8) 14 (45.2) 17 (54.8)

age


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with an SDS 80% before SRS. Among patients with anSDS 80% before SRS, 96.3 and 67.8% maintained the

same GR class at 1 and 2 years, respectively, after SRS.Thus, patients with an SDS 80% had signicantly betterodds of maintaining the same GR class (p < 0.0001, log-rank test; p < 0.0001, Fisher exact test) as well as service-able hearing (p < 0.0001, log-rank test; p < 0.0001, Fisherexact test; Table 3).

Relationship Between Patient Age and HearingPreservation

Eighteen patients (23.4%) were older than 60 years,and 59 patients (76.6%) were 60 years or younger. Twelve(66.7%) of 18 older patients exhibited some hearing dete-rioration (any drop in GR class) compared with only 18(30.5%) of 59 younger patients. Overall, 94.4 and 69.6%of younger patients maintained the same GR class at 1and 2 years after SRS, respectively; older patients did notfare as well (48.9 and 17.5%, respectively). Thus, a pa-tient age < 60 years was signicantly associated with themaintenance of a GR class (p = 0.001, log-rank test; p =0.011, Fisher exact test; Table 3).

Inuence of Cochlear Radiation Dose on HearingPreservation

Both the mean and median radiation dose to the cen-tral cochlea in this study were 4.5 Gy (range 1.18.2).Although not signicantly different (p = 0.843, Mann-

Whitney t-test), the median radiation dose to the centralcochlea was slightly higher in patients with hearing dete-

rioration (4.55 vs 4.40 Gy). Overall, patients who received< 4.2 Gy to the central cochlea had signicantly betterodds of maintaining the same GR class (p = 0.022, Fisherexact test).

Among patients < 60 years old, only 3 (13.6%) of 22who had received < 4.2 Gy to the central cochlea exhibitedsome hearing deterioration (any drop in GR class) com-pared with 15 (40.5%) of 37 patients who had received aradiation dose 4.2 Gy. Among patients with a cochleardose < 4.2 Gy, 94.7 and 86.8% maintained the same GRclass at 1 and 2 years after SRS, respectively. Only 66.1%of patients who had received a higher cochlear dose (4.2 Gy) maintained the same GR class at 2 years post-

SRS (Fig. 5A). The median time for hearing deteriora-tion to a lower GR class was 25.0 months among patientswho had received a cochlear dose 4.2 Gy. Similarly,patients who had received the lower cochlear dose (< 4.2Gy) had better odds of both maintaining a GR class ( p =0.032, log-rank test; p = 0.024, Fisher exact test;) and pre-serving serviceable hearing ( p = 0.027, log-rank test; p =0.031, Fisher exact test; Fig. 5B and Table 4).

On multivariate testing of patients < 60 years old, 2factors were associated with improved hearing preserva-tion: GR Class I before SRS (p = 0.014 and p = 0.0001 forsame GR class or serviceable hearing, respectively) and acentral cochlear dose < 4.2 Gy (p = 0.028 and p = 0.059for same GR class or serviceable hearing, respectively).

TABLE 3: Statistical analysis of hearing preservation for entire series*

Maintaining Same GR Class Serviceable Hearing Preservation

Parameter Log-Rank Test Fisher Exact Test Log-Rank Test Fisher Exact Test

dose to central cochlea

vs < 4.0 Gy 0.140 0.057 0.122 0.080

vs < 4.2 Gy 0.084 0.022* 0.100 0.058

vs < 4.5 Gy 0.326 0.214 0.605 0.612

distance from lat end of tumor to end of IAC

or < 2 mm 0.289 0.252 0.340 0.331

or < 4 mm 0.916 0.844 0.970 0.904

age, vs < 60 yrs 0.001* 0.011* 0.012* 0.070

Koos grade, Grade III vs IIIIV 0.248 0.165 0.164 0.108

intracanalicular tumor, yes vs no 0.177 0.153 0.015* 0.006*

target vol, vs < 0.75 cm3 0.138 0.062 0.014* 0.003*

GR class before SRS, Class I vs II 0.029* 0.013* < 0.001*


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Best Opportunity for Hearing Preservation

Among patients < 60 years old with GR Class I hear-ing before SRS, only 2 (16.7%) of 12 who had received acentral cochlear dose < 4.2 Gy exhibited any GR classdeterioration, compared with 6 (27.3%) of 22 patients whohad received a higher dose. Ninety-three percent of thepatients who had received the lower cochlear dose main-tained their GR class at 2 years post-SRS. In addition,all 12 patients < 60 years and treated with a cochleardose < 4.2 Gy maintained serviceable hearing at 2 years

post-SRS. Although not enough patients were treatedto reach statistical signicance, 80% of the 22 patientsyounger than 60 years who had received a cochleardose 4.2 Gy were able to maintain serviceable hearingat 2 years after SRS (Table 5).

DiscussionTreatment options for patients with serviceable hear-

ing despite an AN include observation, surgical lesionremoval, SRS, and fractionated radiotherapy.9,13,18,22,23,26For many patients, choosing a specic form of therapycan be difcult. Physicians vary in their advice, pub-lished data can be difcult to interpret, and the Internetprovides many confusing and unconrmed opinions. Al-though hearing preservation was rarely offered as a goalto patients treated before 1990, this objective is now dis-cussed with virtually all patients who have some level ofhearing at diagnosis. In the past, radiosurgical techniqueshave been focused on conformal irradiation of the tumor

mass, usually visualized with high-resolution contrast-enhanced MR imaging. Less attention was directed at in-ner ear structures, which were poorly seen utilizing suchsequences and for which there was scant radiobiologicalinformation.

Yamakami et al.26 collected data from conservativemanagement over a 3-year period and found that one-halfof ANs showed growth, one-third of the patients lost use-ful hearing, and 20% of ANs ultimately required surgicalintervention. In a prospective study of radiosurgery ver-sus resection, Pollock et al.22 have reported that patientswho underwent radiosurgery with the Gamma Knife hadbetter results according to a health status questionnaire

compared with patients in the resection group, includinghearing preservation, normal facial movement, physicalfunctioning, role limitation due to physical health, ener-gy/fatigue, and overall component.

Stereotactic Radiosurgery for ANs

A recent analysis of our current experience with ra-diosurgery for ANs has indicated lower morbidity with asimilar tumor control rate compared with those from ourrst experience between 1987 and 1992.4,6,10 We have re-ported a 6-year clinical tumor-control rate of 98.1% afterGamma Knife surgery performed with a median tumormargin dose of 13 Gy. In that study, the overall hearing

preservation rate remained 70.3%. In previous studieswith higher tumor margin doses, we found that cranialneuropathy seemed to occur within 2 years of SRS.5 Ra-diosurgery at the current margin doses of 1213 Gy pro-vides a high rate of tumor control and low morbidity, andfacial neuropathy is rare.

Hearing Preservation After SRS

With all forms of therapeutic management, hearingpreservation has been the greatest challenge.5 Commonhypotheses for hearing deterioration after irradiation in-clude damage to cochlear primary sensory cells, injuryto the cochlear nerve by the tumor, injury to the cochlearnerve by radiation, and compression or thrombosis of the

Fig. 5. Upper: Kaplan-Meier curves comparing the maintenance ofthe same GR hearing class with a radiation dose < vs 4.2 Gy in themiddle of the cochlea in patients < 60 years old. A radiation dose < 4.2Gy was significantly associated with better odds of remaining withinthe same GR hearing class (p = 0.032). Lower: Kaplan-Meier curvescomparing the maintenance of serviceable hearing with a radiationdose < vs 4.2 Gy in the middle of the cochlea in patients < 60 yearsold. Again, patients who had received a radiation dose < 4.2 Gy hadsignificantly better odds of retaining serviceable hearing (p = 0.027).


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internal auditory artery, leading to ischemic injury of thecochlea.3,12

Chang et al.1

have reported on therapeutic outcomesin 61 patients treated using 3-stage radiosurgery withmore than 36 months of follow-up. These authors report-ed useful hearing preservation in 74% of their patients,which they reported as a crude rate as opposed to a 10-year actuarial rate. In our previous series of 110 patientswith testable hearing and > 3 years of follow-up, crudehearing preservation rates were 78% for retaining the ex-

act same GR hearing class (Classes IIV) and 77% forserviceable hearing (starting with GR Class I or II hear-

ing and preserving at least Class II).2

In the present studycrude hearing preservation rates were as follows: 61% ofpatients remained within the exact same GR class and71.4% retained serviceable hearing.

Predictors of Hearing Preservation

This study had a mean follow-up of 20 months (range

TABLE 4: Statistical analysis of hearing preservation for patients < 60 years*

Mainta ining Same GR Class Serviceable Hearing Preservation

Parameter Log-Rank Test Fisher Exact Test Log-Rank Test Fisher Exact Test

dose in central cochlea

> vs < 3.8 Gy 0.228 0.158 0.126 0.093

> vs < 4.0 Gy 0.038* 0.035* 0.022* 0.024*

> vs < 4.2 Gy 0.032* 0.024* 0.027* 0.031*

> vs < 4.5 Gy 0.105 0.127 0.134 0.224

distance from lat end of tumor to end of IAC

> or < 2 mm 0.652 0.553 0.867 0.773

> or < 4 mm 0.813 0.940 0.822 0.889

Koos grade, Grade III vs IIIIV 0.072 0.054 0.070 0.058

intracanalicular tumor, yes vs no 0.067 0.036* 0.016* 0.005*

target vol, > vs < 0.75 cm3 0.104 0.032* 0.021* 0.004*

GR class before SRS, Class I vs II 0.114 0.036* 0.008* 0.002*

SDS before SRS

> vs < 70% 0.152 0.060 0.045* 0.025*

> vs < 80% 0.002* vs < 90% 0.007* 0.009* 0.007* 0.013*

100% vs < 100% 0.101 0.042* 0.133 0.073

PTA

> vs < 20 dB 0.234 0.114 0.033* 0.018*

> vs < 30 dB 0.067 0.036* 0.016* 0.005*

* Statistically significant.

TABLE 5: Hearing preservation in patients < 60 years of age in GR Class I *

CentralCochlear

Dose(Gy)

Maintaining Same GR Class Serviceable Hearing Preservation

No.Worse/NoChange

CrudeRate (%)

2-Yr HPR(%)

Log-RankTest

FisherExactTest

No.Worse/NoChange

CrudeRate (%)

2-Yr HPR(%)

Log-RankTest

FisherExactTest

< 3.8 1/8 87.5 90.0 0.694 0.164 0/8 100 100 0.280 0.156

3.8 7/30 76.7 70.0 4/30 86.7 85.5

< 4.0 1/12 91.8 92.3 0.195 0.259 0/12 100 100 0.096 0.071

4.0 6/22 73.1 66.9 4/26 84.6 81.7

< 4.2 2/16 87.5 92.9 0.279 0.259 1/16 93.8 100 0.283 0.452

4.2 6/22 72.7 65.0 3/22 86.4 79.6

< 4.5 1/8 87.5 83.3 0.214 0.484 1/16 93.8 100 0.242 0.452

4.5 7/30 72.7 75.3 3/22 86.4 78.2

* HPR = hearing preservation rate.


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H. Kano et al.


6.040 months), which is relatively short in terms of com-menting on tumor control rates and long-term toxicity.Nevertheless, a similar criticism can be made about mostof the other published studies on SRS, SRT, and resection.It is generally accepted that almost all cases of postradio-surgery facial, trigeminal, and auditory neuropathy occur124 months after SRS, with a median onset of 6 monthspost-SRS.14,15,20 Most cranial nerve dysfunction after SRTalso occurs in the rst few months after treatment, withmost researchers suggesting that treatment-related toxic-ity occurs primarily during the rst 36 months.7,24,25

In our study the signicant pre-SRS prognostic fac-tors for retaining the same GR hearing class were GRClass I hearing, SDS 80 and 90%, pre-SRS PTA 20 dB from 3 to 24 months afterSRS. The only signicant prognostic factor for hearingdeterioration was the maximum radiation dose deliveredto the cochlear nucleus (hearing unchanged vs hearingworsened: 9.1 4.4 Gy vs 7.8 2.6 Gy). The dose to thecochlea was not specied. Massager et al.17 have reportedthat hearing preservation after SRS is signicantly as-sociated with the intracanalicular tumor volume and theintegrated dose delivered across that volume. The averagedose delivered to the cochlea was 3.70 Gy in patients withaudiological preservation and 5.33 Gy in those with wors-ening hearing after SRS. In our study, patients who hadreceived a radiation dose < 4.2 Gy to the central cochleahad signicantly better odds of maintaining the same GR

hearing class (p = 0.022, Fisher exact test). In the groupof patients < 60 years old, the 4.2-Gy radiation dose tothe central cochlea was associated with signicantly bet-ter odds of maintaining the same GR class (p = 0.032,log-rank test) as well as serviceable hearing (p = 0.027,log-rank test); younger patients tended to be inuenced bythe radiation dose to the central cochlea. We can reducethe dose to the central cochlea by using a beam-blockingtechnique without reducing the tumor margin dose.

Conclusions

Among patients < 60 years old with GR Class I hear-ing, 93 and 100% of those who had received a radiation

dose < 4.2 Gy to the central cochlea retained the sameGR class and serviceable hearing, respectively, at 2 yearspost-SRS. Such data are provocative and may support ear-lier radiosurgery in younger patients with high-level hear-ing. Many such patients are currently being observed forimaging-demonstrated tumor growth or hearing deterio-ration. Thus, we suggest that radiosurgery with the Gam-ma Knife be considered for younger patients with smallerANs in an attempt to preserve functional hearing.

Disclosure

Drs. Lunsford and Kondziolka are consultants with Elekta AB.Dr. Lunsford is a stockholder in Elekta AB. The work described inthis report was funded by a grant (H.K.) from the Osaka MedicalResearch Foundation for Incurable Diseases.

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Manuscript submitted June 8, 2008.Accepted December 5, 2008.Please include this information when citing this paper: published

online March 13, 2009; DOI: 10.3171/2008.12.JNS08611.Address correspondence to: Douglas Kondziolka, M.D.,

F.R.C.S.(C), University of Pittsburgh, Suite B-400, UPMC Pres-byterian, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213. email:[email protected].

Brain : Acoustic Neuroma : Cyberknife Radiosurgery Preserving Hearing

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