This article describes in detail the uses of and distinctions between stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) for vestibular schwannoma (VS). The authors discuss devices and techniques used in SRS and SRT and, additionally, present readers the approach used by surgeons at Mayo Clinic. They discuss indications and results for both approaches in patients with vestibular schwannoma. Treatment of small and large tumors is discussed, along with cystic tumors and NF2-associated VS. Repeating SRS for vestibular schwannoma is also mentioned.
| MS | Microsurgery |
| NF2 | Neurofibromatosis 2 |
| PTA | Pure tone audiometry |
| QOL | Quality of life |
| SDS | Speech discrimination score |
| SRS | Stereotactic radiosurgery |
| SRT | Stereotactic radiotherapy |
| VS | Vestibular schwannoma |
Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) are similar but distinctly different techniques to treat vestibular schwannomas (VSs). These techniques have evolved over the past 50 years as alternatives to microsurgery (MS) of VS, with the common goal of providing long-term tumor control with minimal treatment-related morbidity. The Swedish neurosurgeon Lars Leksell is deservedly credited as the father of SRS. He tested a variety of radiation delivery techniques in the 1950s before putting his primary efforts into a fixed cobalt 60 (Co 60) source unit. SRS combines stereotactic localization with radiation physics to distribute energy (photons, protons) to an imaging-defined target in 1 to 5 sessions. SRT uses similar principles but delivers the radiation dose in more than 5 sessions, depending on the technique and indication. Effective SRS relies on conformal radiation dose plans with steep radiation falloff to minimize injury to adjacent normal tissues, whereas SRT typically does not use the same dose conformality as SRS, but a similar degree of safety is achieved by dose fractionation.
SRS
SRS can be performed using a variety of devices that have been continually improved over the past several decades.
Leksell Gamma Knife
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The Leksell Gamma Knife (Elekta Instruments, Norcross, GA, USA) uses either 201 (models U, B, C, 4-C) or 192 (model Perfexion) fixed Co 60 radiation sources that can be collimated to radiation beams of 4 to 18 mm (16 mm with Perfexion).
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Dose plans generally consist of several weighted isocenters to create a conformal 3-dimensional volume to cover the desired target.
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A stereotactic headframe is used to provide reference fiducials for stereotactic accuracy and fixation in the device.
Linear Accelerator
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Multiple linear accelerator (LINAC) systems have also been developed during the second half of the last century. These include X-knife (Radionics Inc, Burlington, MA, USA), Novalis (BrainLAB, Heimstetten, Germany), and Cyberknife (Accuray Inc, Sunnyvale, CA, USA), which are commercially available.
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Rather than relying on multiple fixed radiation sources collimated to a set point, the radiation source moves around the patient usually as multiple arcs with the radiation entering the skull through many different points.
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Various techniques have been developed to improve dose conformality, including dynamic techniques, in which both the patient couch and arc radiation delivery system move to shape target volume, and the addition of minileaf or microleaf collimators.
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These systems are also used in conjunction with a stereotactic headframe.
Cyberknife
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The Cyberknife uses a LINAC mounted on a 6-axis robot. The robot positions the LINAC at different beam positions, always aiming the center of the radiation beam at the target.
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This technology does not require a stereotactic headframe but relies on orthogonal radiographs and an optical tracking system that scans the patient multiple times throughout the treatment, and any patient movement is detected and dose delivery corrected by the robot in real time.
Proton beam
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Charged particles, mainly in the form of protons, have the advantage of delivering most of their energy at a fixed point, the Bragg peak, with minimal entry and exit radiation compared with photon-based radiation delivery systems.
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This technology is theoretically appealing when treating intracranial targets surrounded by sensitive critical structures such as the brainstem or cochlea. However, the cost of charged particle centers is much greater than that of other technologies, and its application to VS is fairly limited.
This article reviews the technique, indications, and results of SRS and SRT for the treatment of VS.
Technique
SRS
The precise technique of SRS varies based on the device used as detailed earlier. The general principles, however, are very similar. Our experience at the Mayo Clinic, Rochester, MN, USA, has been with the Leksell Gamma Knife and the associated software (GammaPlan) that allows the rapid creation of conformal 3-dimensional dose planning.
SRS is typically performed as an outpatient procedure.
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After administration of low-dose oral benzodiazepine, the patient’s head is cleaned with alcohol.
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The Leksell Model G stereotactic headframe is applied using 4-point fixation after the infiltration of local anesthesia. This is generally well tolerated in patients older than 14 years. For younger patients, the procedure is done under general anesthesia. We have encountered very few superficial pin site infections in more than 5000 headframe applications using this technique, and the pins do not leave any permanent marks on the skin once removed.
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Detailed stereotactic imaging of the VS and adjacent critical temporal bone structures is then performed using magnetic resonance imaging (MRI) and computed tomography (CT). A postgadolinium axial spoiled gradient recalled acquisition in the steady state, MRI with 1 mm thick, volumetrically acquired slices (28–60 images) is performed to encompass the tumor and surrounding pertinent anatomy. The patient is then taken to the CT scanner where a noncontrast axial CT scan of the temporal bones is obtained with 1-mm thick slices. This imaging is directly transferred to the computer workstation. MRI and CT can also be fused using the Gamma Plan software (Elekta Instruments, Norcross, GA, USA).
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A conformal radiation dose plan is then developed by using a combination of isocenters using various-sized collimators and differential weighting. The Perfexion model divides 192 Co 60 radiation sources into 8 sectors of 24 sources each. Each sector can be completely blocked from contributing to the isocenter or collimated to sizes of 4, 8, or 16 mm. Previous models only resulted in ovoid isocenters of radiation using collimator helmets of 4, 8, 14, or 18 mm. The Perfexion allows for more complex-shaped isocenters by varying the sizes or blocking different combinations of the 8 sectors. See Box 1 for evolution of dose planning and treatment at Mayo Clinic
Box 1
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Dose planning and treatment evolved significantly during the first decade of experience at Mayo Clinic. Between 1990 and 1993, 44 VSs were treated with a mean tumor margin dose of 18 Gy (range, 16–20 Gy). The mean number of isocenters used was 5 (range, 1–12). The tumor control rate was excellent, and most tumors showed a dramatic decrease in size on follow-up imaging. However, there was a rate of new facial weakness of 21% and a chance of trigeminal paresthesias or sensory loss of 36%, and 75% of patients with serviceable hearing before SRS had hearing loss.
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To reduce the cranial nerve morbidity associated with VS SRS, the prescribed tumor margin dose was reduced in 1994 and then again in 1996.
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Between 1997 and 2000, 84 patients were treated with a mean tumor margin dose of 13 Gy (range, 12–16 Gy). In addition, the mean number of isocenters used increased to 8 (range, 2–20), reflecting the overall improved dose conformality. Over this interval, there were no cases of new facial weakness, trigeminal symptoms occurred in less than 4% of patients, and hearing loss was reduced to 23%.
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At present at Mayo Clinic, we typically prescribe 12 to 13 Gy for patients with serviceable hearing and 13 to 14 Gy for patients with poor hearing. Most cases are treated using the 50% to 60% isodose line, which maintains a high intratumoral dose with a steep radiation falloff. Single-fraction SRS using LINAC-based units is very similar, except that the tumor margin dose of 12 to 14 Gy is usually prescribed to the 80% or 90% isodose line. This results in a more homogeneous radiation distribution, but the maximum dose is less than typically used in Gamma Knife procedures. Hypofractionated (multisession) SRS procedures for patients with VS generally use 18 to 21 Gy in 3 daily fractions up to 20 to 25 Gy in 5 daily fractions.
Dose planning and treatment of SRS
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Patients typically tolerate the noiseless painless delivery of the radiation well and are discharged from the outpatient observation ward of the hospital within several hours of completing treatment. They can resume all daily activities after treatment with no restrictions.
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Patients are requested to take follow-up audiograms and MRI scans at 6-month intervals for the first year, then yearly for the next several years, eventually moving to MRI imaging every 3 to 4 years if no evidence of tumor growth is detected.
SRT
Several fractionation schemes have been used and reported in the literature to treat VS.
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Typical fractionation schemes in radiation oncology involve delivering 1.8 to 2.0 Gy per fraction with a maximum dose of 45.0 to 57.6 Gy. This dose has historically been proven to be safe for adjacent normal tissues and allows for total doses in excess of 50 Gy to be delivered over a course of approximately 6 weeks.
- •
To allow repeatable radiation delivery over several weeks, a molded mask and bite block is created for each patient. Similar fractionation schemes have been developed for proton beam SRT with the radiation dose being expressed as cobalt Gray equivalents (CGE). These doses have ranged from 1.8 to 2.0 CGE per fraction delivered in 30 to 33 fractions with a maximum dose of 54 to 60 CGE for patients with useful hearing before treatment.
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Follow-up after treatment is similar to SRS, with MRIs and audiograms being performed at roughly 6-month intervals initially and less frequent examinations after several years.
Technique
SRS
The precise technique of SRS varies based on the device used as detailed earlier. The general principles, however, are very similar. Our experience at the Mayo Clinic, Rochester, MN, USA, has been with the Leksell Gamma Knife and the associated software (GammaPlan) that allows the rapid creation of conformal 3-dimensional dose planning.
SRS is typically performed as an outpatient procedure.
- •
After administration of low-dose oral benzodiazepine, the patient’s head is cleaned with alcohol.
- •
The Leksell Model G stereotactic headframe is applied using 4-point fixation after the infiltration of local anesthesia. This is generally well tolerated in patients older than 14 years. For younger patients, the procedure is done under general anesthesia. We have encountered very few superficial pin site infections in more than 5000 headframe applications using this technique, and the pins do not leave any permanent marks on the skin once removed.
- •
Detailed stereotactic imaging of the VS and adjacent critical temporal bone structures is then performed using magnetic resonance imaging (MRI) and computed tomography (CT). A postgadolinium axial spoiled gradient recalled acquisition in the steady state, MRI with 1 mm thick, volumetrically acquired slices (28–60 images) is performed to encompass the tumor and surrounding pertinent anatomy. The patient is then taken to the CT scanner where a noncontrast axial CT scan of the temporal bones is obtained with 1-mm thick slices. This imaging is directly transferred to the computer workstation. MRI and CT can also be fused using the Gamma Plan software (Elekta Instruments, Norcross, GA, USA).
- •
A conformal radiation dose plan is then developed by using a combination of isocenters using various-sized collimators and differential weighting. The Perfexion model divides 192 Co 60 radiation sources into 8 sectors of 24 sources each. Each sector can be completely blocked from contributing to the isocenter or collimated to sizes of 4, 8, or 16 mm. Previous models only resulted in ovoid isocenters of radiation using collimator helmets of 4, 8, 14, or 18 mm. The Perfexion allows for more complex-shaped isocenters by varying the sizes or blocking different combinations of the 8 sectors. See Box 1 for evolution of dose planning and treatment at Mayo Clinic
Box 1
- •
Dose planning and treatment evolved significantly during the first decade of experience at Mayo Clinic. Between 1990 and 1993, 44 VSs were treated with a mean tumor margin dose of 18 Gy (range, 16–20 Gy). The mean number of isocenters used was 5 (range, 1–12). The tumor control rate was excellent, and most tumors showed a dramatic decrease in size on follow-up imaging. However, there was a rate of new facial weakness of 21% and a chance of trigeminal paresthesias or sensory loss of 36%, and 75% of patients with serviceable hearing before SRS had hearing loss.
- •
To reduce the cranial nerve morbidity associated with VS SRS, the prescribed tumor margin dose was reduced in 1994 and then again in 1996.
- •
Between 1997 and 2000, 84 patients were treated with a mean tumor margin dose of 13 Gy (range, 12–16 Gy). In addition, the mean number of isocenters used increased to 8 (range, 2–20), reflecting the overall improved dose conformality. Over this interval, there were no cases of new facial weakness, trigeminal symptoms occurred in less than 4% of patients, and hearing loss was reduced to 23%.
- •
At present at Mayo Clinic, we typically prescribe 12 to 13 Gy for patients with serviceable hearing and 13 to 14 Gy for patients with poor hearing. Most cases are treated using the 50% to 60% isodose line, which maintains a high intratumoral dose with a steep radiation falloff. Single-fraction SRS using LINAC-based units is very similar, except that the tumor margin dose of 12 to 14 Gy is usually prescribed to the 80% or 90% isodose line. This results in a more homogeneous radiation distribution, but the maximum dose is less than typically used in Gamma Knife procedures. Hypofractionated (multisession) SRS procedures for patients with VS generally use 18 to 21 Gy in 3 daily fractions up to 20 to 25 Gy in 5 daily fractions.
Dose planning and treatment of SRS
- •
- •
Patients typically tolerate the noiseless painless delivery of the radiation well and are discharged from the outpatient observation ward of the hospital within several hours of completing treatment. They can resume all daily activities after treatment with no restrictions.
- •
Patients are requested to take follow-up audiograms and MRI scans at 6-month intervals for the first year, then yearly for the next several years, eventually moving to MRI imaging every 3 to 4 years if no evidence of tumor growth is detected.
SRT
Several fractionation schemes have been used and reported in the literature to treat VS.
- •
Typical fractionation schemes in radiation oncology involve delivering 1.8 to 2.0 Gy per fraction with a maximum dose of 45.0 to 57.6 Gy. This dose has historically been proven to be safe for adjacent normal tissues and allows for total doses in excess of 50 Gy to be delivered over a course of approximately 6 weeks.
- •
To allow repeatable radiation delivery over several weeks, a molded mask and bite block is created for each patient. Similar fractionation schemes have been developed for proton beam SRT with the radiation dose being expressed as cobalt Gray equivalents (CGE). These doses have ranged from 1.8 to 2.0 CGE per fraction delivered in 30 to 33 fractions with a maximum dose of 54 to 60 CGE for patients with useful hearing before treatment.
- •
Follow-up after treatment is similar to SRS, with MRIs and audiograms being performed at roughly 6-month intervals initially and less frequent examinations after several years.
Indications and results for SRS and SRT for VS
The debate regarding the role of SRS and SRT in the management of patients with VS with small to medium-sized tumors has been fairly contentious. Advocates for or against using radiation to treat VS have even reached opposite conclusions after reviewing the same body of literature. However, increasing evidence regarding the safety and efficacy of SRS has been established, initially from retrospective case series (level 4 evidence) and case-control series (level 3 evidence) up to more recent prospective cohort studies (level 2 evidence).
The best evidence (levels 2 and 3) shows improved cranial nerve outcomes in short-term follow-up (<5 years) for patients with VS using SRS compared with MS. Two prospective studies have shown that MS is associated with a decline in quality-of-life (QOL) measures, whereas SRS did not affect patients’ day-to-day living in a significant manner. Conversely, one prospective study found no difference in QOL measures for patients with VS undergoing observation, MS, or radiation treatment (included were patients who underwent either SRS or SRT).
Sporadic VS
In the 1980s and early 1990s, the primary indications for VS SRS were recurrent tumors after prior MS resection, patients with neurofibromatosis type 2 (NF2), and patients considered poor candidates for general anesthesia. As our and other academic centers gained more experience, SRS became a popular treatment option for all patients with small to medium-sized VSs ( Table 1 ).
| Indication | Number of Patients (Percentage of Series [%]) |
|---|---|
| Sporadic VS | 526 (94) |
| NF2 (bilateral) a | 28 (5) |
| NF2 (unilateral) | 6 (1) |
a Patients who have undergone SRS on both sides, but procedures performed at different times.
At our institution between 2000 and 2002, patients being evaluated for newly diagnosed sporadic VS smaller than 3 cm in posterior fossa diameter were offered to participate in a prospective observational outcome analysis comparing MS and SRS. Data were collected preoperatively and at 3 months, 1 year, and last follow-up. Mean follow-up was 3.5 years. Facial nerve outcome was assessed by an independent observer in a blinded review of photographs of the patients (at rest, eye closure, eyebrow raising, smiling, frowning) taken at each time interval. Hearing was assessed by an independent blinded audiologist reviewing pure tone audiometry (PTA) and speech discrimination scores (SDS) on preoperative and follow-up audiograms. Patients completed questionnaires evaluating dizziness, tinnitus, headache, and general QOL. Forty-six patients were in the SRS cohort, and no patient withdrew from the study.
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The only facial weakness seen in this group occurred in 2 patients who required salvage MS for continued tumor growth after SRS, for a treatment failure and new facial nerve weakness rate of 4%.
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Sixty-three percent of patients maintained serviceable hearing (PTA<50 dB, SDS>50%) at last follow-up.
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One patient (2%) developed new trigeminal neuralgia after SRS, requiring medication.
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The SRS group had no decline at 3 months, 1 year, or last follow-up on any component of the health status questionnaire compared to prior to treatment.
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There was no difference in tinnitus or headache at any time comparing SRS and MS.
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At last follow-up, patients who underwent SRS had a lower dizziness handicap inventory score.
Table 2 reviews some of the prospective and retrospective data available in the literature regarding the use of SRS to treat patients with VS. The results of LINAC-based SRS on tumor control and facial nerve weakness are comparable to published Gamma Knife reports, but less information is available to compare hearing preservation. Advocates of dose fractionation have posited that SRT may provide better hearing outcomes than single-fraction SRS ( Table 3 ). However, multiple reports on VS SRT have relied on patients’ subjective hearing perception and not objective comparison of audiometry performed before and after treatment. In addition, both single-center experiences using both SRT and SRS and a recent review of the SRT literature found that hearing preservation rates for conventional and hypofractionated schemes are no better than what has been reported for single-session SRS. Proton beam radiotherapy seems to have similar tumor control and facial nerve outcomes, with hearing preservation rates reported from 31% to 42%.
