Radiosurgery is presently a well-established alternative to microsurgical resection of acoustic neuroma (vestibular schwannoma). Many patients prefer radiosurgery to surgical resection because of the lower morbidity of the procedure and similar rates of long-term tumor control. Although lower than with microsurgery, we reported significant rates of subsequent facial weakness (21%), facial numbness (27%), and decreased hearing (49%) in our first 5 years of experience with acoustic neuroma radiosurgery using marginal tumor doses on the order of 16 Gy. Since that time, we reduced marginal tumor dose prescriptions to reduce complications. Treatment techniques have also improved with the substitution of high-resolution stereotactic magnetic resonance imaging over computed tomography. In addition, treatment-planning software became more refined, faster, and easier to use. Large numbers of isocenters could be more easily used in plans to achieve greater conformality and sharper dose fall-off.

Analysis of our more recent experience over the last decade with improved techniques indicated lower morbidity with similar tumor control compared with our initial experience from 1987 to 1992. The use of lower marginal doses has lead to questions of whether high tumor control rates and reduced treatment morbidity will be maintained with longer follow-up. A number of studies looking at outcomes after radiosurgical treatment for acoustic schwannomas have concluded that cranial nerve morbidity related to the procedure will generally manifest itself within 3–5 years of treatment. We recently reported our summary of experience in 829 cases of acoustic schwannomas treated between 1987 and 2002, whereby our experience with treatment-related cranial nerve morbidity was generally seen within 5 years after radiosurgery. This article seeks to better define the long-term outcomes with stereotactic radiosurgery as primary treatment of acoustic neuroma using clinically relevant techniques and dosing.

Between May 1992 and June 2000, 216 consecutive patients with previously untreated unilateral acoustic neuromas (vestibular schwannomas) underwent Gamma Knife radiosurgery at the University of Pittsburgh with doses of 12 to 13 Gy. The median follow-up was 68 months (maximum follow-up, 143 months). Forty-one patients had follow-up >96 months. Follow-up magnetic resonance scans were normally obtained every 6 months for the first 2 years after radiosurgery, and then yearly thereafter. The median patient age was 56.5 years (range, 22–88 years). One hundred sixteen patients were male and 100 were female. Audiogram results were evaluated according to the Gardner-Robertson classification (7). Serviceable hearing (useful hearing) was defined as Gardner-Robertson (GR) Class 1–2 (speech discrimination >50% and pure tone average <50 dB). Before radiosurgery, 106 patients had GR Class 1–2 hearing (useful or serviceable hearing), 57 patients had Class 3–4 hearing, and 38 patients had no discernible speech discrimination (Class 5). Eighteen patients (8.3%) had trigeminal nerve symptoms (facial numbness, paresthesia, or pain) before radiosurgery.

Radiosurgery was performed with the Model B, C, or U Leksell Gamma Knife (Elekta, Atlanta GA). We used stereotactic magnetic resonance imaging for target definition in all cases. Marginal tumor doses were 12 Gy (n = 21), 12.5 Gy (n = 11), or 13 Gy (median dose, n = 184). Maximum dose varied from 20 to 26 Gy (median, 26 Gy). The marginal tumor dose was prescribed to the 50% isodose volume in 199 patients, 55% in 12, 60% in 4, and 65% in 1 patient. The number of isocenters treated per patient varied from 1 to 16 (median, 6 isocenters). Tumor volume varied from 0.08 to 37.5 cm3 (median, 1.3 cm3).

Our long-term evaluation of tumor control using marginal doses of 12 to 13 Gy with modern radiosurgery techniques in this series was favorable. The actuarial 10-year clinical tumor control rate (no requirement for surgical intervention) for this current series was 98.3% ± 1.0%. This compares to a long-term resection-free clinical tumor control rate of 98% among the patients treated to higher doses (median dose, 16 Gy) in our first 5 years of experience. It also compares favorably to other series using radiosurgery, fractionated radiotherapy, or microsurgical resection to manage acoustic neuroma.  Although most patients in this series showed some evidence of recent progression of symptoms or increase in tumor size, these were not used as absolute selection criteria for treatment in this series. We did not record how many patient seemed to have “quiescent” tumors at the time of radiosurgery in this study. It is possible that comparisons of short-term tumor control rates could be biased between centers that observe all acoustic tumors before treating after undisputed tumor progression and other centers that are more liberal in their selection criteria. Because of the natural tendency for all acoustic schwannomas to eventually grow, it should make less of a difference with longer follow-up.

We found acceptable rates for preservation of facial and trigeminal nerve function in this series. Facial nerve preservation was 100%. Normal trigeminal nerve function was preserved in 94.9% of patients. The rates of facial and trigeminal nerve dysfunction were in line with our experience from 1992 to 1997, as well as our initial series of patients treated with marginal doses of 12 to 13 Gy. We found in our earlier experience with higher marginal doses that all of the cranial neuropathies seemed to occur within 2, or at most 3 years after radiosurgery. Regarding hearing preservation, we were surprised to discover continued hearing loss beyond 5 years of follow-up. Although we found 6-year actuarial rates that were somewhat similar to the overall preservation rates of Gardner-Robertson and useful hearing, the 10-year rates had lessened. In this series, tumor control continues to remains high with long-term follow up, whereas hearing loss and trigeminal nerve dysfunction (for larger tumors that indent the trigeminal root) continue to occur. Certainly, careful exploration of lower marginal doses seems reasonable in trying to reduce cranial nerve complications. On the basis of the data from this series, it is possible that even with the use of lower marginal doses, hearing preservation may continue to suffer in the long term.

Chang recently reported on treatment outcomes of 61 patients treated with Cyber Knife radiosurgery with more than 36 months of follow-up. They reported an imaging-defined tumor control rate of 98%. Useful hearing preservation was possible in 74% of their patients, which they reported as a crude rate as opposed to a 10-year actuarial rate. Our crude rate of useful hearing preservation in patients with more than 3 years of follow-up was similar at 74%. Chang et al. found no evidence of permanent facial or trigeminal neuropathy. Large long-term studies examining the efficacy of this modality of radiosurgery with respect to tumor control rates and cranial nerve preservation are needed.

There have been a number of recent studies examining long-term outcomes in patients treated with Gamma Knife radiosurgery or fractionated stereotactic radiotherapy (FSRT). With respect to FSRT, Combs  recently reported results of 106 patients treated at their institution. Using a median dose of 57.6 Gy given in 1.8 Gy per day, they treated 106 patients with a median follow-up period of 48.5 months. Actuarial tumor control rates from that study were 94.3% and 93% at 3 and 5 years, respectively. They reported “actual” hearing rate preservation of 94% at 5 years. This was ascertained through telephone follow-up and questionnaires rather than audiograms in the majority of patients. They reported facial and trigeminal nerve damage in 3.4% and 2.8% of patients, respectively. They concluded that FSRT allowed for a lower incidence of late morbidity, including facial palsy, trigeminal nerve palsy, or hearing loss due to the beneficial effect of fractionation compared with single fraction radiosurgery, while maintaining high rates of tumor control. This is in contrast to a comparison of observation vs. FSRT in 77 patients performed by Shirato . After a mean follow-up period of 35 months in the observation group and 31 months in the FSRT group, they were able to find a statistically significant improvement in tumor control in the latter but no difference in the Gardner-Robertson class preservation curves for 5 years after initial presentation.

A recent study reported by Hasegawa  looked at 317 patients treated with Gamma Knife stereotactic radiosurgery with a minimum follow-up period of 5 years and a median follow-up period of 7.8 years. They reported 5- and 10-year progression-free survival rates of 93% and 92%, respectively. In subgroup analysis of patients treated with 13 Gy or less, they found a hearing preservation rate of 68%, facial numbness in 2%, and a 10-year progression-free survival rate of 94%. With respect to their hearing preservation data, the median follow-up was not noted in the study. Their long-term findings with respect to tumor control concur with the data we have presented here.

This series provides a relatively long follow-up of patients treated with clinically relevant marginal tumor doses, with 41 patients followed for more than 8 years and 11 patients followed for more than 10 years. It is generally accepted that almost all cases of postradiosurgery facial, trigeminal, and auditory neuropathy occur within the first 3 years after treatment, and this would seem to bear out with our current analysis, except for continued hearing loss in this series of patients beyond 5 years. We hypothesize that with lower marginal doses and longer follow-up hearing loss may continue through a number of mechanisms, including direct radiation effects, vascular effects, and changes in the tumor remnant. It would be interesting to compare these hearing preservation rates with those seen in patients who have undergone observation or fractionated radiotherapy with audiometric follow-up for more than 5 years.

Acoustic neuroma radiosurgery with marginal doses of 12 to 13 Gy is associated with a high rate of tumor control with minimal facial and trigeminal morbidity. These observations remain durable in long-term follow-up for most patients.