Stereotactic and microsurgery for acoustic neuroma: The controversy continues Antonio A. F. De Salles, Leonardo Frighetto, Michael Selch. International Journal of Radiation Oncology-Biology-Physics, 2003: 56: 5: 1215-1217 Resection has been the traditional treatment for acoustic neuroma. Modern microsurgery practiced by ear, nose, and throat specialists and neurosurgeons have reached high levels of complete resection and low morbidity. Large modern surgical series report facial and trigeminal neuropathy below 7%, and a hearing preservation between 33–81%. These results are directly related to the tumor volume. Similar results were reported by the early radiosurgery series, again dependent on tumor volume at time of treatment . Surgery of acoustic neuroma is, however, a challenge, requiring years of training and experience to achieve the results reported by the major series. A more standardized approach allowing true information to the patient to what is to be expected became justified. The current state of imaging of these lesions confirms histology with certainty. This, coupled with the recent radiosurgery reported results, questions the need for surgical intervention of these lesions. Only in situations of substantial mass effect accompanied by symptoms of brainstem compression is surgery necessary. The growing body of literature in favor of stereotactic radiation supports this statement. During the past 10 years, there has been rapid progress in the application of stereotactic radiosurgery (SRS) to the treatment of acoustic neuroma. Since the pioneer publication from the Karolinska group with unacceptable morbidity, improvements on stereotactic radiation techniques have provided a broad experience in patients with 5- to 10-year follow-up. Tumor control of at least 95% accompanied by remarkably low treatment-related morbidities has finally established stereotactic radiation as the treatment of choice by patients and even seasoned neurosurgeons. The demand for complete function preservation requires, however, that one refuses the less-than-desirable 1.1–36% facial, 2.6–25% trigeminal, and 19–67% rate of hearing deterioration reported in the major SRS and stereotactic radiotherapy (SRT) series. Theoretical radiobiologic models suggest a direct relationship between late normal tissue damage and dose per treatment delivered to critical structures. Consequently, recent reports from an ever-increasing number of institutions have debated the best approach to stereotactic radiation to preserve function and afford tumor control superior to that offered by microsurgery and SRS. We believe the real message of the Amsterdam experience is that stereotactic regimens using one or a very few fractions, while equally efficacious for tumor control, are also equally damaging to normal tissue, particularly cranial nerve VIII. That no difference was detected by Meijer and colleagues does not mean such a difference does not exist for appropriately fractionated SRT. Any potential clinical impact of dose fractionation was likely obscured by choosing a fractionation scheme that did not fully exploit the biologic capacity of late reacting normal tissues to repair sublethal cellular damage from ionizing irradiation. In the 72 patients with retention of useful pretreatment hearing, function was preserved in 75% after SRS and 61% after SRT. The authors did not perform sequential audiometry, but considered ability to use a telephone as proof of useful hearing. Although the results agree well with the retention of hearing in the recent University of Pittsburgh low-dose SRS experience and those of other hypofractionated SRT trials , both rates are inferior to those of centers employing more protracted, and perhaps more biologically meaningful, fractionation schemes. Fuss et al., using a median of 57 Gy in 23 fractions, reported 5-year actuarial retention of useful hearing in 85% of patients . The rate of hearing retention among those without neurofibromatosis (NF)-2 was 100%. Andrews et al., in the other single-institution comparison trial cited previously, reported retention of useful hearing in 81% after 50 Gy in 25 fractions compared with 33% in those receiving SRS . This group used serial audiometry to evaluate hearing function. Although a small series of hypofractionated SRT report excellent retention of hearing , these results must be viewed cautiously. In the preliminary experience from Amsterdam with the first 17 SRT patients, the 3-year actuarial rate of useful hearing retention was 70%. In a larger experience, Williams treated 125 patients with either 25 Gy in 5 fractions or 30 Gy in 10 fractions . The actuarial 2-year rates of hearing retention were 90% and 100%, respectively. Of note, however, is that there was no suggestion of a plateau on the hearing retention curve for the five-fraction patients compared with the more protracted fractionation patients. Gamma knife radiosurgery of acoustic neurinomas. Bertalanffy A, Dietrich W, Aichholzer M, Brix R, Ertl A, Heimberger K, Kitz K.   Acta Neurochir (Wien) 2001;143(7):689-95 Department of Neurosurgery, University of Vienna, Medical School, Austria. The maximal axial tumour diameter ranged from 6 to 33 mm (median: 25 mm), the maximal transverse tumour diameter ranged from 7 mm to 36 mm (median: 16 mm). The dose distributed to the tumour margin was 10 to 17 Gy (median: 12 Gy) by enclosing the tumour with the 40% to 95% isodose line (median: 50% isodose line) and using 1 to 12 isocenters (median: 5 isocenters). Central loss of contrast enhancement was observed in 78% of the patients within six to 12 months after radiosurgery. Thirty-two patients were observed over a minimum follow up period of at least 36 months, 9 patients were lost to follow up as they died of unrelated causes or refused further check-ups. Within the follow up period of up to seven years, magnetic resonance imaging (MRI) control scans revealed the tumour diameter stable or decreased in 29 cases and increased in three tumours. Of 14 patients with useful hearing before treatment, 9 patients were examined in addition to pure tone audiogramm by measurement of brainstem auditory evoked potentials (BAEPs) one to four years after radiosurgery. None of these patients showed a postoperative loss of the cochlea function. According to slight alterations of the cochlea function (cochlea summating action potential), pure tone audiometry of those patients revealed only slight changes of the hearing level (HL) within a maximum range of +/-15 Decibel (dB). The hearing threshold improved in two, was stable in four and deteriorated in three patients, respectively. We observed postradiosurgical aggravation of a pre-existing facial weakness in two out of 13 patients, a new occurrence of facial palsy was seen in two cases (four years after treatment), one of them was previously operated on and both suffered from cystic degeneration with mass effect. Tinnitus improved in six out of 13 patients, deteriorated in two and never appeared as a new permanent sequela. Trigeminal hypaesthesia did also not appear as a new permanent symptom, improved in three out of 9, and deteriorated in one out of 9 patients. Vertigo increased in six out of 23, was stable in 8 and decreased in nine out of 23 patients each. GKRS proves to be a safe and highly satisfactory therapeutical option or addition to open surgery, especially for radiologically verified regrowing residual ACNs, but also as primary treatment in selected patients. A high rate of tumour control can be achieved with an acceptable rate of neurological deficits. Dose and diameter relationships for facial, trigeminal, and acoustic neuropathies following acoustic neuroma radiosurgery. Flickinger JC, Kondziolka D, Lunsford LD.   Radiother Oncol 1996 Dec;41(3):215-9 Department of Radiation Oncology, University of Pittsburgh School of Medicine, PA 15213, USA. Two hundred and thirty-eight patients with unilateral acoustic neuromas who underwent Gamma knife radiosurgery between 1987-1994 with 6-91 months of follow-up (median 30 months) were studied. Minimum tumor doses were 12-20 Gy (median 15 Gy). Transverse tumor diameter varied from 0.3-5.5 cm (median 2.1 cm). The relationships of dose and diameter to the development of cranial neuropathies were delineated by multivariate logistic regression. RESULTS: The development of post-radiosurgery neuropathies affecting cranial nerves V, VII, and VIII were correlated with minimum tumor dose and transverse tumor diameter (P < 0.01 for all except Dmin for VIII where P = 0.10). A comparison of the dose-diameter response curves showed the acoustic nerve to be the most sensitive to doses of 12-16 Gy and the facial nerve to be the least sensitive. CONCLUSION: The risks of developing trigeminal, facial, and acoustic neuropathies following acoustic neuroma radiosurgery can be predicted from the transverse tumor diameter and the minimum tumor dose using models constructed from data presently available. Results of acoustic neuroma radiosurgery: an analysis of 5 years' experience using current methods. Flickinger JC, Kondziolka D, Niranjan A, Lunsford LD.   J Neurosurg 2001 Jan;94(1):1-6 Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pennsylvania, USA. jflickin@pop.pitt.edu One hundred ninety patients with previously untreated unilateral acoustic neuromas (vestibular schwannomas) underwent gamma knife radiosurgery between 1992 and 1997. The median follow-up period in these patients was 30 months (maximum 85 months). The marginal radiation doses were 11 to 18 Gy (median 13 Gy), the maximum doses were 22 to 36 Gy (median 26 Gy), and the treatment volumes were 0.1 to 33 cm3 (median 2.7 cm3). The actuarial 5-year clinical tumor-control rate (no requirement for surgical intervention) for the entire series was 97.1+/-1.9%. Five-year actuarial rates for any new facial weakness, facial numbness, hearing-level preservation, and preservation of testable speech discrimination were 1.1+/-0.8%, 2.6+/-1.2%, 71+/-4.7%, and 91+/-2.6%, respectively. Facial weakness did not develop in any patient who received a marginal dose of less than 15 Gy (163 patients). Hearing levels improved in 10 (7%) of 141 patients who exhibited decreased hearing (Gardner-Robertson Classes II-V) before undergoing radiosurgery. According to multivariate analysis, increasing marginal dose correlated with increased development of facial weakness (p = 0.0342) and decreased preservation of testable speech discrimination (p = 0.0122). CONCLUSIONS: Radiosurgery for acoustic neuroma performed using current procedures is associated with a continued high rate of tumor control and lower rates of posttreatment morbidity than those published in earlier reports. Gamma knife radiosurgery for acoustic tumors: multivariate analysis of four year results. Flickinger JC, Lunsford LD, Linskey ME, Duma CM, Kondziolka D.  Radiother Oncol 1993 May;27(2):91-8 Department of Radiation Oncology, University of Pittsburgh, School of Medicine, Pennsylvania. In order to evaluate the results of radiosurgery for acoustic tumors and to identify optimum treatment parameters, an analysis of tumor control, as well as incidences of hearing loss, facial and trigeminal neuropathies was undertaken. Between August 1987 and August 1991, 134 patients with 136 acoustic tumors received stereotactic gamma knife radiosurgery at the University of Pittsburgh. Median follow-up was 24 months (range: 6-56 months). Tumor volumes ranged from 0.10 to 17.00 cm3 (median = 2.75 cm3). From one to ten isocenters were utilized per tumor treated (median = 3). Minimum tumor doses varied from 12 to 20 Gy (median = 17 Gy). The 4-year actuarial tumor control rate was 89.2 +/- 6.0%. Some degree of hearing (by pure tone audiometry) was preserved in 71.0 +/- 4.4% of patients. The actuarial rates for preservation of either pretreatment hearing level or useful hearing were 34.4 +/- 6.6% and 35.1 +/- 97% respectively. Respectively, the actuarial incidences of postradiosurgery facial and trigeminal neuropathies were 29.0 +/- 4.4% and 32.9 +/- 4.5%, respectively. No significant factors affecting tumor control were identified. Multivariate analysis identified a significantly increased risk of hearing loss in patients with neurofibromatosis (p = 0.0003) as well as decreased risks of facial and trigeminal neuropathies with both decreasing tumor diameter (p = 0.001) and increasing number of isocenters treated (p = 0.003). Radiosurgery is a safe and effective treatment for acoustic neuromas with acceptable morbidity that may be lowered by the use of multiple isocenter treatment techniques and by earlier treatment of small tumors. Analysis of risk factors associated with radiosurgery for vestibular schwannoma. Foote KD, Friedman WA, Buatti JM, Meeks SL, Bova FJ, Kubilis PS. J Neurosurg 2001 Sep;95(3):440-9 Department of Neurosurgery, University of Florida, Gainesville, USA. From July 1988 to June 1998, 149 cases of VS were treated using linear accelerator radiosurgery at the University of Florida. In each of these cases, the patient's tumor and brainstem were contoured in 1-mm slices on the original radiosurgical targeting images. Resulting tumor and brainstem volumes were coupled with the original radiosurgery plans to generate dose-volume histograms. Various tumor dimensions were also measured to estimate the length of cranial nerve that would be irradiated. Patient follow-up data, including evidence of cranial neuropathy and radiographic tumor control, were obtained from a prospectively maintained, computerized database. The authors performed statistical analyses to compare the incidence of posttreatment cranial neuropathies or tumor growth between patient strata defined by risk factors of interest. One hundred thirty-nine of the 149 patients were included in the analysis of complications. The median duration of clinical follow up for this group was 36 months (range 18-94 months). The tumor control analysis included 133 patients. The median duration of radiological follow up in this group was 34 months (range 6-94 months). The overall 2-year actuarial incidences of facial and trigeminal neuropathies were 11.8% and 9.5%, respectively. In 41 patients treated before 1994, the incidences of facial and trigeminal neuropathies were both 29%, but in the 108 patients treated since January 1994, these rates declined to 5% and 2%, respectively. An evaluation of multiple risk factor models showed that maximum radiation dose to the brainstem, treatment era (pre-1994 compared with 1994 or later), and prior surgical resection were all simultaneously informative predictors of cranial neuropathy risk. The radiation dose prescribed to the tumor margin could be substituted for the maximum dose to the brainstem with a small loss in predictive strength. The pons-petrous tumor diameter was an additional statistically significant simultaneous predictor of trigeminal neuropathy risk, whereas the distance from the brainstem to the end of the tumor in the petrous bone was an additional marginally significant simultaneous predictor of facial neuropathy risk. The overall radiological tumor control rate was 93% (59% tumors regressed, 34% remained stable, and 7.5% enlarged), and the 5-year actuarial tumor control rate was 87% (95% confidence interval [CI] 76-98%). Analysis revealed that a radiation dose cutpoint of 10 Gy compared with more than 10 Gy prescribed to the tumor margin yielded the greatest relative difference in tumor growth risk (relative risk 2.4, 95% CI 0.6-9.3), although this difference was not statistically significant (p = 0.207). CONCLUSIONS: Five points must be noted. 1) Radiosurgery is a safe, effective treatment for small VSs. 2) Reduction in the radiation dose has played the most important role in reducing the complications associated with VS radiosurgery. 3) The dose to the brainstem is a more informative predictor of postradiosurgical cranial neuropathy than the length of the nerve that is irradiated. 4) Prior resection increases the risk of late cranial neuropathies after radiosurgery. 5) A prescription dose of 12.5 Gy to the tumor margin resulted in the best combination of maximum tumor control and minimum complications in this series. Stereotactic radiosurgery using the gamma knife for acoustic neuromas. Foote RL, Coffey RJ, Swanson JW, Harner SG, Beatty CW, Kline RW, Stevens LN, Hu TC.   Int J Radiat Oncol Biol Phys 1995 Jul 15;32(4):1153-60 Mayo Clinic, Division of Radiation Oncology, Rochester, MN 55905, USA. PURPOSE: To assess the efficacy and toxicity of stereotactic radiosurgery using the gamma knife for acoustic neuromas. METHODS AND MATERIALS: Between January 1990 and January 1993, 36 patients with acoustic neuromas were treated with stereotactic radiosurgery using the gamma knife. The median maximum tumor diameter was 21 mm (range: 6-32 mm). Tumor volumes encompassed within the prescribed isodose line varied from 266 to 8,667 mm3 (median: 3,135 mm3). Tumors < or = 20 mm in maximum diameter received a dose of 20 Gy to the margin, tumors between 21 and 30 mm received 18 Gy, and tumors > 30 mm received 16 Gy. The dose was prescribed to the 50% isodose line in 31 patients and to the 45%, 55%, 60%, 70%, and 80% isodose line in one patient each. The median number of isocenters per tumor was 5 (range: 1-12). RESULTS: At a median follow-up of 16 months (range: 2.5-36 months), all patients were alive. Thirty-five patients had follow-up imaging studies. Nine tumors (26%) were smaller, and 26 tumors (74%) were unchanged. No tumor had progressed. The 1- and 2-year actuarial incidences of facial neuropathy were 52.2% and 66.5%, respectively. The 1- and 2-year actuarial incidences of trigeminal neuropathy were 33.7% and 58.9%, respectively. The 1- and 2-year actuarial incidence of facial or trigeminal neuropathy (or both) was 60.8% and 81.7%, respectively. Multivariate analysis revealed that the following were associated with the time of onset or worsening of facial weakness or trigeminal neuropathy: (a) patients < age 65 years, (b) dose to the tumor margin, (c) maximum tumor diameter > or = 21 mm, (d) use of the 18 mm collimator, and (e) use of > five isocenters. The 1- and 2-year actuarial rates of preservation of useful hearing (Gardner-Robertson class I or II) were 100% and 41.7% +/- 17.3, respectively. CONCLUSION: Stereotactic radiosurgery using the gamma knife provides short-term control of acoustic neuromas when a dose of 16 to 20 Gy to the tumor margin is used. Preservation of useful hearing can be accomplished in a significant proportion of patients. Radiosurgery: a minimally interventional alternative to microsurgery in the management of acoustic neuroma. Forster DM, Kemeny AA, Pathak A, Walton L.   Br J Neurosurg 1996 Apr;10(2):169-74 Royal Hallamshire Hospital, Sheffield, UK. We report the results of treatment with radiosurgery of 29 tumours in 27 patients with acoustic neuromas between 1986 and 1989. The median follow-up was 6.6 years. The treatment appears to be an effective alternative to surgery for patients with tumours of 3 cm diameter or less. The mortality and morbidity of the treatment and the presentation of cranial nerve function is comparable to the very best surgical results. Every patient with an acoustic neuroma should be informed about this alternative to direct surgery. Gamma Knife radiosurgery for acoustic schwannoma: effects of low radiation dose and functional prognosis. Hirato M, Inoue H, Zama A, Ohye C, Shibazaki T, Andou Y.   Stereotact Funct Neurosurg 1996;66 Suppl 1:134-41 Department of Neurosurgery, Gunma University School of Medicine, Hidaka Hospital, Maebashi, Japan. The effects of relatively low dose Gamma Knife irradiation on acoustic schwannoma were evaluated in 29 patients followed over 2 years after treatment. The mean dose delivered to the tumor periphery was 12.1 Gy. Lowering of the magnetic resonance signal intensity in the tumor center appeared in 69% and signs of tumor shrinkage appeared in 59% of cases. The cyst in the tumor enlarged in 3 cases, and 2 cases developed hydrocephalus. The percentage of pure-tone hearing preservation was 82% at 3 months, 73% at 6 months, 68% at 12 months. 64% at 18 months and 59% at 24 months in 22 out of 29 cases. Relatively low dose Gamma Knife radiosurgery was effective in suppressing tumor growth, with preservation of hearing. Risk factors for neurological complications after acoustic neurinoma radiosurgery: refinement from further experiences. Ito K, Shin M, Matsuzaki M, Sugasawa K, Sasaki T.   Int J Radiat Oncol Biol Phys 2000 Aug 1;48(1):75-80 Department of Otolaryngology, Faculty of Medicine, University of Tokyo,Tokyo, Japan. itoken-tky@umin.ac.jp Between June 1990 and September 1998, 138 patients with acoustic neurinomas underwent stereotactic radiosurgery at Tokyo University Hospital. Of these, 125 patients who received medical follow-up for 6 months or more entered the present study. Patient ages ranged from 13 to 77 years (median, 53 years). Average tumor diameter ranged from 6.7 to 25.4 mm (mean, 13. 9 mm). Maximum tumor doses ranged from 20 to 40 Gy (mean, 29.8 Gy) and peripheral doses from 12 to 25 Gy (mean, 15.4 Gy). One to 12 isocenters were used (median, 4). Follow-up period ranged from 6 to 104 months (median, 37 months). The potential risk factors for neurological complications were analyzed by two univariate and one multivariate actuarial analyses. Neurological complications examined include hearing loss, facial palsy, and trigeminal nerve dysfunction. Variables included in the analyses were four demographic variables, two variables concerning tumor dimensions, and four variables concerning treatment parameters. A variable with significant p values (p < 0.05) on all three actuarial analyses was considered a risk factor. RESULTS: The variables that had significant correlation to increasing the risk for each neurological complication were: Neurofibromatosis Type 2 (NF2) for both total hearing loss and pure tone threshold (PTA) elevation; history of prior surgical resection, tumor size, and the peripheral tumor dose for facial palsy; and the peripheral tumor dose and gender (being female) for trigeminal neuropathy. In facial palsies caused by radiosurgery, discrepancy between the course of palsy and electrophysiological responses was noted. CONCLUSION: Risk factors for neurological complications seem to have been almost established, without large differences between institutions treating a large number of patients by radiosurgery. Radiosurgical doses and tumor dimensions were considered the two important risk factors for the 7th and 5th nerve injuries. Neurofibromatosis Type 2 was an important factor for hearing loss. Gamma knife treatment of acoustic neurinoma. Kwon Y, Kim JH, Lee DJ, Kim CJ, Lee JK, Kwun BD. Stereotact Funct Neurosurg 1998 Oct;70 Suppl 1:57-64 Department of Neurological Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea. The results of treatment of acoustic neurinomas using Gamma Knife radiosurgery (GKR) during a 6-year period in our center were reviewed. Since May 7, 1990, we treated 88 cases of acoustic neurinoma with GKR. During a 52-month mean follow-up period, MRI was obtained in 63 patients. Reduction in tumor size occurred in 34 (54%) cases, and another 27 (42.8%) tumors showed no change. The tumor control rate was thus 95%. Tumor size increased in 3 (4.8%) cases, but one case is still in early follow-up. Two cases were operated after GKR. Histological examination of the tumors removed at surgery 8 months after GKR were obtained. The examinations showed enlargement of nucleoli and cytoplasm and proliferation of endothelial cells due to delayed radiation changes. Post-GKR facial neuropathy was noted in 7 (8.8%) patients, of which 4 recovered during the follow-up period. The tumor volume, margin dose, number of isocenters and marginal isodose did not have any statistically significant relationship with the development of facial neuropathy. Transient trigeminal neuropathy were noted in 3 patients. Hearing was preserved in 2 of 3 hearing patients. In conclusion, our GKR results for acoustic neurinomas were very similar to the previously reported series, which makes GKR for acoustic tumors an excellent treatment modality for small- to medium-sized tumors with or without microsurgical tumor removal. Radiologic and histopathologic changes after Gamma Knife radiosurgery for acoustic schwannoma. Kwon Y, Khang SK, Kim CJ, Lee DJ, Lee JK, Kwun BD.   Stereotact Funct Neurosurg 1999;72 Suppl 1:2-10 Department of Neurological Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea. ykwon@www.amc.seoul.kr Gamma knife radiosurgery (GKRS) is a widely used treatment option for acoustic schwannomas, 3 cm in diameter or less. Between May 1990 and February 1998, 102 acoustic tumors in 101 patients were treated with GKRS. There are 77 patients with a follow-up period of more than six months (mean 55, range 7 to 90 months). Seventy (91%) of these tumors have remained unchanged or reduced in volume. After GKRS there was an increase in volume in seven cases. In four the volume increase affected solid tumour. Among these, three patients were in stable condition and are being observed. One of these patients developed brain stem compression symptoms and was operated. In another three cases, cysts with multiple septa developed medial to the tumor and compressed the brain stem and fourth ventricle, thus necessitating post-GKRS surgery. In these three patients, MRI had shown loss of central contrast enhancement followed by its return. Histological findings at surgery before and after GKRS were compared for these four tumours. In spite of the MRI changes, there were no definite histological findings after GKRS which could be attributed to radiation induced changes. The development of cysts occurred after the treatment of larger tumors. Decrease in cranial nerve complications after radiosurgery for acoustic neuromas: a prospective study of dose and volume. Miller RC, Foote RL, Coffey RJ, Sargent DJ, Gorman DA, Schomberg PJ, Kline RW.   Int J Radiat Oncol Biol Phys 1999 Jan 15;43(2):305-11 Division of Radiation Oncology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. PURPOSE: To determine whether tumor control can be maintained, and cranial nerve complications decreased by reducing the radiosurgical dose to acoustic neuromas. METHODS AND MATERIALS: Forty-two consecutive patients with acoustic neuromas were treated prospectively using an initial standard-dose protocol in which the tumor-margin dose (50% isodose) was 20, 18, and 16 Gy for tumor diameters < or =2 cm, 2.1-3 cm, and 3.1-4 cm, respectively. After analysis of tumor control and complications, the next 40 patients were treated using a reduced-dose protocol in which the tumor-margin dose was 16, 14, and 12 Gy for tumor volumes < or =4.2 cm3, 4.2-14.1 cm3, and > or =14.1 cm3, respectively. RESULTS: Median follow-up was 2.3 years (range 0.1-6) for 80 of 82 patients. The actuarial incidence (Kaplan-Meier) of facial neuropathy at 2 years was 38% (95% confidence interval [CI], 23-53%) for the standard-dose protocol and 8% (95% CI, 0-17%) for the reduced-dose protocol (p = 0.006). Univariate analysis revealed an association between risk of facial neuropathy and use of CT planning, higher radiosurgical dose, and neurofibromatosis, type 2. Multivariate analysis revealed that the only factor associated with increased risk of post-treatment facial neuropathy was a tumor margin dose > or =18 Gy. The incidence of trigeminal neuropathy at 2 years was 29% (95% CI, 15-43%) for the standard-dose protocol and 15% (95% CI, 3-27%) for the reduced-dose protocol (p = 0.17). Univariate analysis revealed an association between maximal tumor diameter and increased risk of trigeminal neuropathy; multivariate analysis revealed no additional statistically significant associations between tumor and dosimetric and patient characteristics and risk of trigeminal neuropathy. Two tumors in the standard-dose protocol required salvage surgery for progression. To date, no tumor in the reduced-dose protocol has shown progression. CONCLUSION: Our analysis suggests that a tumor margin dose of > or =18 Gy is the most significant risk factor for facial nerve complications after acoustic neuroma radiosurgery. Patients receiving a minimal tumor dose of < or =16 Gy are at significantly lower risk for permanent facial neuropathy after radiosurgery. Longer follow-up is required before definitive conclusions can be made about the ultimate rate of tumor control using reduced radiosurgical doses. Dose distribution and shrinkage of acoustic neurinomas 2 years after Gamma Knife treatment. Nagano H, Tanohata K, Kato E, Nakayama S, Fujino H, Matsubara S.  Stereotact Funct Neurosurg 1996;66 Suppl 1:146-56 Department of Radiology, Yokohama Rosai Hospital, Japan. To examine the relationship between dose distribution and tumor shrinkage of acoustic neurinomas, correlation coefficients between distribution probabilities of some dose areas and residual tumor ratios of 21 cases were studied at 2 years. Approximating a dose-volume histogram to beta-distribution, two essential dose areas for tumor control were extracted: a dose area from 14.2 to 24.7 Gy contributed to tumor shrinkage, whereas a dose area from 27.3 to 29.4 Gy was contraindicated. Given that there are at least two different dose areas with reverse characters, a formula with two opposing logistic components is proposed to predict tumor control. With this formula, Gamma Knife treatment of acoustic neurinomas may be optimized Serial follow-up MR imaging after gamma knife radiosurgery for vestibular schwannoma. Nakamura H, Jokura H, Takahashi K, Boku N, Akabane A, Yoshimoto T.  AJNR Am J Neuroradiol 2000 Sep;21(8):1540-6 Department of Neurosurgery, Tohoku University School of Medicine, Sendai, Japan. BACKGROUND AND PURPOSE: Gamma knife radiosurgery has become an important treatment option for vestibular schwannoma. The effect of treatment can be assessed only by neuroimaging. We analyzed the evolution of follow-up MR imaging findings after gamma knife radiosurgery to provide information for the clinical management of these tumors. METHODS: Changes in tumor volume and enhancement were assessed visually on 341 follow-up MR studies obtained in 78 of 86 consecutive patients with unilateral vestibular schwannoma who underwent gamma knife radiosurgery. RESULTS: Follow-up MR studies were obtained between 10 and 63 months (mean, 34 months) after treatment. Tumor control rate was 81%. Changes in tumor volume were classified as temporary enlargement (41%), no change or sustained regression (34%), alternating enlargement and regression (13%), or continuous enlargement (12%). Temporary enlargement occurred within 2 years after radiosurgery. Changes in tumor enhancement were classified as transient loss of enhancement (84%), continuous increase in enhancement (5%), or no change in enhancement (11%). There was no significant correlation between changes in tumor volume and tumor enhancement. Areas of T2 hyperintensity in adjacent brain tissue appeared in 31% of patients. CONCLUSION: Dynamic changes in vestibular schwannoma are seen on serial follow-up MR studies obtained after gamma knife radiosurgery. An increase in tumor size up to 2 years after radiosurgery is likely to be followed by regression. Changes in contrast enhancement are not predictive of clinical outcome. Neuroimaging follow-up is recommended. Gamma knife surgery in acoustic tumours. Noren G, Greitz D, Hirsch A, Lax I.   Acta Neurochir Suppl (Wien) 1993;58:104-7 Department of Neurosurgery, Karolinska Hospital, Stockholm, Sweden. Presentation of the experiences with 254 acoustic neurinomas, treated at the Karolinska Gamma Knife Center from 1969 to 1991, with a minimum follow-up of 12 months. Early loss of contrast enhancement on CT or MRI was seen in 70%. Unilateral tumours showed size decrease in 55%, no change in 33%, and increase in 12%. NF 2 tumours had decrease in 33%, no change in 43%, and increase in 24%. Some degree of facial weakness was seen after 17% of treatments, but always with later improvement of function. The incidence of trigeminal neuropathy was 19%. Preservation of hearing was 77%. Gamma knife treatment is as efficient as microsurgery, but without risk of infection, bleeding or CSF leak. It requires no hospitalisation. The patient can go back to work after a few days. It therefore should be offered as an alternative to every acoustic neurinoma patient Preservation of hearing in acoustic neuromas treated by gamma knife surgery. Thomassin JM, Epron JP, Regis J, Delsanti C, Sarabian A, Peragut JC, Pellet W.    Stereotact Funct Neurosurg 1998 Oct;70 Suppl 1:74-9 Federation of Oto-neurosurgery, CHU TIMONE, Marseille, France. 138 acoustic schwannomas were treated by Gamma Knife surgery from July 1992 to May 1994. Cases with neurofibromatosis were excluded because of differences in the patterns of growth and development of tumors in these cases. Hearing was evaluated by tonal and vocal audiometry and classified using the Gardner and Robertson score. 104 patients were observed at 3 years after treatment. Hearing studies, the relation of tumor volume to hearing, central and marginal dose, number of shots and preoperative brain-stem-evoked responses (BER) were all recorded. 70% of patients with normal hearing maintained a useful hearing, and 50% of patients with useful hearing maintained serviceable hearing. No correlation was found between hearing preservation and tumor volume, central and marginal dose and number of shots. Gamma Knife surgery seems to be superior to microsurgery with regard to preservation of useful hearing. Tumour response and morphological changes of acoustic neurinomas after radiosurgery. Valentino V, Raimondi AJ.    Acta Neurochir (Wien) 1995;133(3-4):157-63 Centro di Radiochirurgia, Clinica Flaminia, Rome, Italy. Twenty-seven of the 1560 patients treated by radiosurgery during the period 1984-1993 had acoustic neurinomas. Four cases were excluded from this study because they had a follow-up of less than 2 years. There were 24 neurinomas treated in 23 patients as one patient had a bilateral tumour. Seven patients underwent radiosurgery for a recurrent tumour (already operated on once or twice), while it was the first treatment for 16 patients. The tumour volume ranged from 1.99 cm3 to 18.30 cm3, and the patient follow-up was from 2 to 8 years. To determine the target on CT/NMR for linear accelerator stereotactic irradiation, the Greitz-Bergstrom non-invasive head fixation device was used. It was again adopted for subsequent serial imaging, and for repeat radiosurgery when necessary. The total peripheral tumour dose ranged from 12 to 45 Gy. In 9 patients there was a reduction in tumour volume varying from 39 to 100%, while 14 of the neurinomas appeared stable after an average follow-up of 3 years. In one patient there was an increase in size of the tumour. Variable morphological changes were present in 66% of the neurinomas treated. Radiosurgery is indicated as an alternative to microsurgery for inoperable patients and for those who refuse surgery, for recurrent tumours, and as a post-operative complementary treatment for partially removed tumours. A gradual approach to radiosurgery, depending on tumour response, allows a greater efficacy with minimal risk. In the present series no complications were observed. Hearing was preserved at almost the same level as that prior to radiosurgery in all patients. Management of benign cranial nonacoustic schwannomas by fractionated stereotactic radiotherapy. Zabel A, Debus J, Thilmann C, Schlegel W, Wannenmacher M.    Int J Cancer 2001 Dec 20;96(6):356-62 Department of Radiotherapy, German Cancer Research Center, Heidelberg, Germany. A.Zabel@dkfz.de Schwannomas are the most common tumors of cranial nerves. Nonacoustic schwannomas are very rare tumors, accounting for approximately 10% of intracranial schwannomas. Standard treatment is complete surgical resection if possible. The role of fractionated stereotactic radiotherapy remains to be defined. Thirteen patients with cranial nonacoustic schwannomas underwent fractionated stereotactic radiotherapy. Seven patients had trigeminal schwannomas, three schwannomas of the lower cranial nerves, and three located in the cerebellopontine angle without involvement of the acoustic nerve. Treatment included primary or adjuvant radiotherapy in progressive disease. Tumor volume ranged from 4.5 to 76.0 cc (median 19.8 cc). Median dose was 57.6 Gy with 1.8 Gy/fraction. Median follow-up was 33 months (range 13-70 months). Local tumor control rate was 100% (13/13). Tumor size remained stable in nine patients and decreased in four. Improvement of preexisting neurological deficits was seen in four cases. No patient developed new cranial nerve or brain stem deficits. No patient showed clinically significant complications of irradiation. Fractionated stereotactic radiotherapy is an effective and well-tolerated noninvasive treatment for cranial nonacoustic schwannomas with excellent tumor control rates. It is an option for patients at higher risk for microsurgical resection or in residual and recurrent tumors.