Acoustic neuroma Clinical Article

Experience with radiosurgery now extends to over thirty years. During the late 1980s and early 1990s, patients and their doctors chose radiosurgery or resection based mainly on early outcomes data from limited patient series. In 1987 we began a prospective assessment of the response of patients with acoustic tumors to Gamma Knife radiosurgery.

At our last review, 827 patients underwent stereotactic radiosurgery for an acoustic tumor (vestibular schwannoma) at the University of Pittsburgh over a 15-year interval. These included 765 patients with solitary tumors and 62 with neurofibromatosis type II, a hereditary disease characterized by bilateral acoustic neuromas. Fifty percent of tumors were on the left side of the brain and fifty percent were on the right side, and half of the patients were female. The patient age range was 12 to 95 years (mean, 56 years). Twenty percent had undergone prior surgery. "Useful" hearing before radiosurgery was noted by 33% of patients.

One hundred ninety-two patients had radiosurgery between 1992 and 1997 and were eligible for extended follow-up. The maximum follow-up in this cohort was 65 months. The median tumor margin dose was 13 Gy. Five-year actuarial rates of developing problems were: facial weakness, 1%; facial numbness, 2.6%; hearing level preservation, 71%; preservation of testable speech discrimination, 91%. At a tumor margin dose of =13 Gy, the rate of facial neuropathy was 0%, and above 13 Gy, 2.5% (usually mild and transient). Neuropathy refers to malfunctioning nerves, and symptoms can include weakness, numbness and pain. Tumor diameter did not significantly affect results.

We continue to evaluate a cohort of patients who were treated before 1992 who are a minimum of ten years out from their procedure (n=162). This study represented results of our initial techniques. Approximately 70% of irradiated acoustic tumors decreased in size over time. Nine patients had tumors that increased in size and all were identified within the first three years after radiosurgery. Enlargement represented either true neoplastic tumor growth (n=4) or tumor death (n=5) with an expansion of the tumor margins as the central portion of the tumor became necrotic. In the latter group, patients' subsequent imaging studies confirmed tumor volume regression. Four patients underwent resection. No further increase in tumor volume was identified in any patient with further follow-up. Patients returned to their routine activities immediately. In our five to ten year review, three patients developed hydrocephalus and required a ventriculoperitoneal shunt. All new or worsened post-radiosurgery deficits occurred within 28 months of radiosurgery and no patient described a treatment-related problem after the third year. We continue to tell patients that 2% of them may require tumor resection in the future, a number that is consistent with other groups.

There have been a number of patient-based surveys to study outcomes after acoustic neuroma management. One of the first was a survey of 541 patient members of the Acoustic Neuroma Association who provided data on tumor resection between 1973 and 1983. Sixty-two percent reported facial weakness, 84% reported eye-related problems, and depression, sleep disturbance and speech or swallowing difficulties were reported by 38%, 26% and 16%, respectively. More recently, a larger survey of 1579 resections performed between 1989 and 1994 found improved results that included a 44% rate of facial weakness, an 11% rate of cerebrospinal fluid leakage, and persistent balance problems after one year in 9%. Approximately 8% had recurrent or residual tumor on follow-up imaging.

Better results following resection have been documented since that time. Samii et al. and Gormley et al. found that complete tumor removal was a frequent outcome. However, neurologic and systemic morbidity (complications) remained present with 1% mortality rates and cerebrospinal fluid fistula rates of 9.2% (Samii) and 15% (Gormley). The study by Barker et al. evaluated patient death following resection and found a rate of 1 in 200, even amongst surgeons with the most experience. However, for patients with large acoustic tumors (over 3 cm in extracanalicular diameter) and those with progressive neurologic deficits that require brainstem decompression, total or subtotal surgical resection is the preferred option. We believe that a complete resection should be performed in such patients if possible, but not at the expense of lost neurologic function. Stereotactic radiosurgery can be considered for patients with intracanalicular, small or medium-sized acoustic tumors since most such patients do not have a rapidly progressive neurologic syndrome. The initial symptoms caused by most acoustic tumors are not improved by resection.

A recent United Kingdom report by Martin et al. (Table 1) evaluated quality of life in patients after tumor resection. They found a disparity between the patient's report and the physician's assessment of function, with decreases in physical functioning, general health, and social functioning after surgery. More severe balance functions led to worse social functioning.

The long-term effects of both resection and radiosurgery must be documented to assist physician and patient decision making. Surprisingly little information has been published on long-term imaging-based outcomes after resection. Cerullo et al. noted a 10% recurrence rate after 10 years had passed following resection. In their series of over 100 patients in which hearing preservation was attempted during resection, Mazzoni et al. reported that the overall tumor recurrence rate was 8.1%. These papers are often criticized for their results, but they represent an honest evaluation of longer-term imaging results. All groups should strive to obtain serial imaging studies on their own patients. Post et al. found that 4 of 56 patients (7%) had an incomplete resection when hearing preservation was attempted and that three had regrowth of the tumor within three years. In the largest series, Samii et al. reported a complete resection in 98% of patients and found later recurrence in 6 of 880 who did not have neurofibromatosis type II. In our radiosurgery series, 98% of patients required no further surgery and 94% had imaging confirmation of persistent tumor control. Tumors that increased in size in the first year or two after radiosurgery did so usually in association with central tumor necrosis, with a small expansion of the tumor capsule. Most such tumors then regressed below baseline in size with longer follow-up. Such transient expansion may be associated with temporary ear region discomfort, perhaps from regional dural inflammation.

In the last several years, a number of groups have used fractionated radiation therapy to treat patients with acoustic neuromas. This technique developed when several centers who used linear accelerator irradiation technology were not satisfied with the results or accuracy of their devices after single fraction irradiation (radiosurgery). In order to decrease the cranial nerve morbidities they were observing, they began to deliver radiation over multiple sessions (fractionation). The goal of this approach is to weaken the effect of each radiation administration and try to maintain brain or nerve function. Correspondingly this also weakens the effect of the radiation on the tumor target.

Williams et al. reported 80 patients who had fractionated stereotactic radiotherapy. Median follow-up after radiotherapy was 2.9 years. Seventy patients received 25 Gy in five fractions and ten patients received 30 Gy in ten fractions. The treatment was delivered using CT targeting which is limited in evaluating the intracanalicular portion of the tumor. Only 19 of 80 patients had Gardner-Robertson grade 1 or 2 hearing ("serviceable" to "excellent" hearing) at the time of treatment. Hearing levels were preserved in 82% (actuarial data). Two patients had transient trigeminal neuropathies and no patient had a significant facial neuropathy. There is little data on this approach in the peer-reviewed literature that includes diligent outcomes and follow-up. Standardization with linear accelerator machines, which are made by many manufacturers, does not exist. Therefore, research results with this technology are not as comparable among researchers as with Gamma Knife which is identical throughout the world.

Optimally, appropriate doses of radiation should be delivered precisely to the tumor and regional brain structures should be spared radiation. This is not the case with fractionated techniques where larger volumes of regional tissue are irradiated. We believe that any advantage of fractionation in limiting toxicity only makes sense if the target volume contains normal brain or nerves. Sophisticated stereotactic radiosurgical instruments allow regional brain or nerves to be spared through frame-based, single-session image guidance. We do not believe that fractionated radiotherapy provides any useful advantage over radiosurgical techniques that have been in use for the last 10 years.

A survey was mailed to members of the Congress of Neurological Surgeons in July 2002. Six hundred sixty-three surgeons responded to the survey. The survey included two questions about acoustic neuroma. Forty-one percent of responders were between the ages of 40 and 50. Eighty percent of neurosurgeons surveyed had either performed radiosurgery on a patient with an acoustic neuroma or had referred a patient for neurosurgery (n=530).

 
Question One
Question: You are a 37 year-old neurosurgeon who presents with mild decreased hearing on one side. You have no tinnitus, no balance problems and facial function is normal. An MRI scan shows an intracanalicular acoustic neuroma and serial scans have shown a small amount of growth. Which management strategy would you choose for yourself? (Observation, stereotactic radiosurgery, surgical resection or fractionated radiotherapy.)

Response: The majority of surgeons (43%; n=283) stated that they would choose stereotactic radiosurgery for management of their small acoustic tumor. Only 122 surgeons (18%) stated that they would choose surgical resection of their tumor. Fractionated radiotherapy was chosen by 2% of responders. Interestingly, 240 surgeons (36%) stated that they would continue to observe their tumor rather than undergoing any specific treatment at the present time. It had been stated in the case presentation that serial scans had already shown a small amount of growth. This tumor had been observed and was increasing in volume. Nevertheless, approximately one-third of responders continued to choose observation for a 37 year-old patient with a small but growing tumor. This case reflected the care of an actual neurosurgeon who had Gamma Knife radiosurgery. He remains well 18 months after his procedure and maintains a full practice. He has had no facial weakness or change in hearing.

Table 1. Comparison of Patient Survey Data for Vestibular Schwannomas

¹ Martin HC, Sethi J, Lang D, et al. Patient-assessed outcomes after excision of acoustic neuroma: postoperative symptoms and quality of life. J Neurosurg 2001;94(2):211-216. 
² Kondziolka D, Lunsford LD, McLaughlin MR, Flickinger JC. Long-term outcomes after radiosurgery for acoustic neuromas. New Engl J Med 1998;339:1426-1433.

Question Two
Question: You are a 50 year-old neurosurgeon who presents with mild decreased hearing on one side. You have tinnitus but no balance problems and facial function is normal. An MRI shows a 2.2 cm left acoustic neuroma. Which management strategy would you choose for yourself? (Observation, stereotactic radiosurgery, surgical resection or fractionated radiotherapy.)

Response: In this scenario, the neurosurgeon had a medium size acoustic tumor that indented the side of the brainstem but did not compress the fourth ventricle. The minority of surgeons recommended continued observation for a tumor of this size (6%). Surgical resection was recommended by 347 surgeons (52%), whereas radiosurgery was chosen by 261 surgeons (39%). Fractionated radiotherapy was only chosen by 3%. When the results were stratified by age, resection was the most popular choice across the groups between the ages of 30 and 60. However, radiosurgery became more popular with advancing age of the survey group, surpassing resection as the most popular choice when the neurosurgeon is over age 60. It appears that surgeons chose to have a resection because of the larger volume of the tumor with indentation of the lateral surface of the brain stem. This patient was also a real neurosurgeon who had radiosurgery. He remains well 18 months after the procedure with a decrease in the size of the tumor, and his facial function remains normal.

When we evaluate patients with acoustic tumors, many ask the following two questions. First, is the tumor more difficult to resect if radiosurgery fails? The answer to this is not clear. Few patients have required resection after radiosurgery, and the opinions of the surgeons we have asked indicated that some tumors were less difficult, some were about the same, and some were more difficult to resect. In a report on this issue that included thirteen patients who had resection after radiosurgery, eight were thought to be more difficult. However, five of the eight patients had failed resection before they had radiosurgery. In a recent report, Regis et al. noted that most tumors were not more difficult to resect after radiosurgery than the typical untreated tumor.

Second, patients inquire about the risk of delayed malignant transformation. Malignant schwannomas are rare, but have been reported to occur spontaneously, after prior resection, and after irradiation. We answer that delayed malignant transformation is always a risk after irradiation, but the risk should be very low. We have not yet seen this in any of our 6400 patients during our first 17 years of experience with radiosurgery, but quote patients a risk of 1 in 1000 over the next 5–30 years of their life. We believe the risk of developing a tumor years after radiosurgery is much less than the risk of mortality immediately after a resection, and likely less than the risk of the patient developing another tumor on his own in another body location.

We have conducted detailed evaluations for Gamma Knife radiosurgery in patients with tumors due to neurofibromatosis type II. Imaging studies of 45 tumors over a median 36-month follow-up (range, 6–120 months) found that 16 tumors (36%) had regressed, 28 tumors (62%) remained unchanged in size, and one tumor (2%) demonstrated progression. Loss of central contrast within the tumor was observed in some patients and was thought to reflect tumor necrosis.

At our last detailed review, the mean period of clinical follow-up was 41 months (range, 6–120). Thirty patients (67%) maintained a stable exam and 15 patients (33%) demonstrated some degree of clinical deterioration. Two patients (4%) died during the follow-up period due to unrelated illnesses. The median Karnofsky score after radiosurgery was 80. The Karnofsky score reflects a person's ability to perform common tasks. Thirty-five patients (78%) were able to carry out normal daily activities at the time of the last examination (Karnofsky score =80).

Of the 14 tumors associated with useful hearing (Gardner-Robertson grades 1 or 2) at the time of radiosurgery, six (43%) demonstrated no change in hearing class during the follow-up period.

In tumors managed since 1992, nine patients with useful hearing underwent radiosurgery. Six of the patients (67%) had hearing preservation at the time of last examination. Thirty-one tumors (69%) were associated with intact facial nerve function (House-Brackmann grade 1) at the time of radiosurgery. Three patients (8%) experienced trigeminal distribution sensory loss at a mean five months (range, 4–5 months) after radiosurgery.