17.1 Introduction

Stereotactic radiosurgery (SRS) is a minimally invasive treatment modality that delivers a single session of radiation to a specific target while sparing surrounding tissue. Unlike conventionally fractionated radiotherapy, SRS does not maximally exploit the presumed higher radiosensitivity of brain lesions relative to normal brain (i.e., therapeutic ratio). Its selective destruction is dependent mainly on sharply focused high-dose radiation and a steep-dose gradient away from the defined target. The biological effect is irreparable cellular damage, presumably via irreparable DNA double-strand breaks, and delayed vascular occlusion within the high-dose target volume. Because a therapeutic ratio is not required, traditionally radioresistant lesions can be treated. Since ablative doses are used, however, any normal structure included in the target volume is subject to injury.

The basis for SRS was conceived over 60 years ago by Lars Leksell.s. Literatur He proposed the technique of focusing multiple beams of external Cobalt-60 gamma ray radiation on a stereotactically defined intracranial target. The confluence of these intersecting beams results in very high doses of radiation to the target volume, but low doses to nontarget tissues along the path of any given beam. His team’s implementation of this concept culminated in the development of the Gamma Knife. The modern Gamma Knife (Perfexion or Icon model) employs 192 Cobalt-60 radiation sources with a fixed circumferential array of collimators of varying size, such that all 192 gamma ray photon beams are focused on a single point or isocenter. The patient is stereotactically positioned in the Gamma Knife unit using a robotic treatment couch so that the intracranial target coincides with the isocenter of radiation. Using variable collimation, beam blocking, differential weighting of dose to each isocenter, and multiple isocenters, the radiation target volume is shaped to conform to the intracranial target. Further discussion regarding the Gamma Knife SRS platform can be found in Chapter 16.

An alternate radiosurgical solution using a linear accelerator (LINAC) was first described in 1984 by Betti and Derechinsky.s. Literatur Colombo et al described such a system in 1985,s. Literatur and LINACs have subsequently been modified in various ways to achieve the precision and accuracy required for radiosurgical applications.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur In 1986, a team composed of neurosurgeons, medical physicists, and software engineers began development of the University of Florida LINAC-based radiosurgery system.s. Literatur This system has been used to treat over 4,500 patients at the University of Florida since May 1988, and is in use at multiple sites worldwide. Many other commercial versions of radiosurgical systems are currently available, including the Brain Lab system (Novalis), the Radionics (X-knife) system, the Accuray (CyberKnife) system, among others.

Most LINAC radiosurgical systems rely on the same basic paradigm: A collimated X-ray beam is focused on a stereotactically identified intracranial target. The gantry of the LINAC rotates around the patient, producing an arc of radiation focused on the target (Fig. 17‑1 ). The patient couch is then rotated in the horizontal plane and another arc performed. In this manner, multiple non-coplanar arcs of radiation intersect at the target volume and produce a high target dose, with minimal radiation to surrounding brain. This dose concentration method is exactly analogous to the multiple intersecting beams of Cobalt-60 gamma ray radiation in the Gamma Knife.

The target dose distribution can be tailored by varying collimator sizes, eliminating undesirable arcs, manipulating arc angles, using multiple isocenters, and differentially weighting the dose to each isocenter.s. Literatur In our center, multiple isocenters are used to achieve highly conformal dose distributions, analogous to the Gamma Knife technique. Some LINAC systems use an alternative approach that relies upon a computer-driven multileaf collimator to generate nonspherical beam shapes, which are conformal to the beam’s eye view of the tumor. The multileaf collimator can be adjusted statically or dynamically as the LINAC gantry rotates. Intensity modulation can be used to achieve dose distributions that are close to those seen with multiple isocenters and treatment time can be reduced.

Achievable dose distributions are similar for LINAC-based and Gamma Knife–based systems. With both systems, it is possible to achieve dose distributions that conform closely to the shape of the intracranial target, thus sparing the maximum amount of normal brain. Recent advances in stereotactic imaging and computer technology for dose calculation and treatment planning, as well as refinements in radiation delivery systems, have led to improved efficacy, fewer complications, and a remarkable amount of interest in the various applications of SRS. Perhaps of equal importance is the fact that increasing amounts of scientific evidence have persuaded the majority of the international neurosurgical community that radiosurgery is a viable treatment option for selected patients suffering from a variety of challenging neurosurgical disorders. This chapter will present a brief description of LINAC radiosurgical technique, followed by a detailed review of the experience with vestibular schwannoma (VS) treatment. The interested reader can find an in-depth review of the CyberKnife system in Chapter 19.

17.2 LINAC Radiosurgery Technique

Although the details of radiosurgical treatment techniques differ somewhat from system to system, the basic paradigm is quite similar everywhere. The following is a detailed description of a typical radiosurgical treatment at the University of Florida.

Almost all radiosurgical procedures in adults are performed on an outpatient basis. The patient reports to the neurosurgical clinic the day before treatment for a detailed history and physical, as well as an in-depth review of images and treatment options. If radiosurgery is deemed appropriate, the patient is sent to the radiology department for a volumetric MRI scan. A radiosurgical plan can be generated, in advance, using this MRI study. The next morning, the patient arrives at 7:00 AM. A stereotactic head ring is applied under local anesthesia. No skin shaving or preparation is required. Subsequently, stereotactic CT scanning is performed. One millimeter slices are obtained throughout the entire head. The patient is then transported to an outpatient holding area where they wait until the treatment planning process is complete.

The stereotactic CT scan and the nonstereotactic volumetric MRI scan are transferred via Ethernet to the treatment-planning computer. The CT images are quickly processed so that each pixel has an anteroposterior, lateral, and vertical stereotactic coordinate, all related to the head ring previously applied to the patient’s head. Using image fusion software, the nonstereotactic MRI is fused, pixel for pixel, with the stereotactic CT. The “pre-plan” performed the day before is, likewise, fused to the stereotactic CT. Final treatment planning then begins and continues until the neurosurgeon, radiation oncologist, and medical physicist are satisfied that an optimal dose plan has been developed. A variety of options are available for optimizing the dosimetry. The fundamental goal is to deliver a radiation in high-dose volume that is precisely conformal to the lesion shape (Fig. 17‑2 ) while delivering a minimal dose of radiation to all surrounding neural structures.

When dose planning is complete, the radiosurgical device is attached to the LINAC. The patient then is attached to the device and treated. The head ring is removed and, after a short observation period, the patient is discharged. The radiosurgical device is disconnected from the LINAC, which is then ready for conventional radiotherapy utilization. Close clinical and radiologic follow-up is arranged at appropriate intervals depending on the lesion treated and the condition of the patient.

17.3 Radiosurgery for Vestibular Schwannomas

Among benign intracranial tumors, VS has been one of the most frequent targets for SRS. Leksell first used SRS to treat a VS in 1969.s. Literatur SRS is a logical alternative treatment modality for this tumor for several reasons. A VS is typically well demarcated from surrounding tissues on neuroimaging studies. The sharp borders of this noninvasive tumor make it a convenient match for the characteristically steep dose gradient produced at the boundary of a radiosurgical target. This allows the radiosurgeon to minimize radiation dose to normal tissue. Excellent spatial resolution on gadolinium-enhanced MRI facilitates radiosurgical dose planning. These tumors commonly occur in an older population that may be less fit for microsurgical resection under general anesthesia. Finally, the location of these tumors at the skull base in close proximity to multiple critical neurologic structures (i.e., cranial nerves, brainstem) can lead to appreciable surgical morbidity and very rare mortality even in expert hands. This makes the concept an effective, less invasive, less morbid alternative treatment that can be performed in a single day under local anesthesia attractive.

Certainly, the role of radiosurgery is limited by its inability to expeditiously relieve mass effect in patients for whom this is necessary. The radiobiology of SRS also requires lower, potentially less effective doses for larger target volumes in order to avoid complications. This limits the use of SRS to the treatment of smaller tumors (generally <25 mm in diameter). Despite these limitations, there is a growing body of literature that substantiates the claim that radiosurgery is a safe and effective alternative therapy for VSs.

The published experience using LINAC-based SRS for the treatment of VS is relatively limited compared to the Gamma Knife literature. Foote et als. Literatur performed an analysis of risk factors associated with SRS for VS at the University of Florida. The aim of this study was to identify factors associated with cranial neuropathy following SRS for VS and to determine how such factors may be manipulated to minimize the incidence of SRS complications while maintaining high rates of tumor control. From July 1988 to June 1998, a total of 149 cases of VS were treated using LINAC SRS 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 SRS targeting images. Resulting tumor and brainstem volumes were coupled with the original SRS 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 incidence rate of both facial and trigeminal neuropathies was 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 doses 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 (Fig. 17‑2 ). 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%; Fig. 17‑3 ). Based on this study, the authors currently recommend a peripheral dose of 12.5 Gy for almost all VSs, as this dose is most likely to yield long-term tumor control without causing cranial neuropathy. Since 1994, when the treatment dose was reduced to 12.5 Gy, less than 1% of patients have experienced facial or trigeminal neuropathy after treatment.

Spiegelmann et als. Literatur ^,​ s. Literatur reviewed their results of LINAC-based SRS in 44 patients with VSs who were treated between 1993 and 1997. CT scanning was selected as the stereotactic imaging modality for target definition. A single, conformally shaped isocenter was used in the treatment of 40 patients; two or three isocenters were used in four patients who harbored very irregular tumors. The radiation dose directed to the tumor margin was the only parameter that changed during the study period—in the first 24 patients who were treated, the dose was 15 to 20 Gy, whereas in the last 20 patients, the dose was reduced to 11 to 14 Gy. After a mean follow-up period of 32 months (range: 12–60 months), 98% of the tumors were controlled. The actuarial hearing preservation rate was 71% at 2 years. New transient facial neuropathy developed in 24% of the patients and persisted to a mild degree in 8%. Radiation dose correlated significantly with the incidence of cranial neuropathy, particularly in large tumors (≥4 cm³).

Several reports on smaller series of patients treated with LINAC-based SRS for VSs have been published in recent years. Martens et al reported on 14 patients with at least 1 year of follow-up after SRS on the LINAC unit in the University Hospital in Ghent, Belgium.s. Literatur A mean marginal dose of 19.4 Gy (range: 16–20) was delivered to the 70% isodose line with a single isocenter. Mean follow-up duration was 19 months (range: 12–24 months). During this relatively short follow-up interval, 100% radiographic tumor control has been achieved (29% regressed, 71% stable, 0% enlarged). Rates of delayed facial and trigeminal neuropathy were 21 and 14%, respectively, and two of three facial nerve deficits resolved. Preoperative hearing was preserved in 50% of cases.

Valentino and Raimondi reported on 23 patients treated with LINAC-based SRS or multisession hypofractionated radiotherapy in Rome, Italy.s. Literatur Five of these had neurofibromatosis type 2 and 7 (30%) had undergone previous surgery. Total radiation dose to the tumor margin ranged from 12 to 45 Gy (median: 30 Gy) and was delivered in one to five sessions. One or two isocenters were used and mean duration of follow-up was 40 months (range: 24–46 months). Results using this less conventional method of multisession hypofractionated radiotherapy were comparable to SRS techniques. Tumor control was achieved in 96% of patients (38% regressed, 58% stable, 4% enlarged), facial and trigeminal neuropathies each occurred at a rate of 4%, and “hearing was preserved at almost the same level as that of SRS in all patients.”

The use of LINAC-based SRS for VS is briefly discussed in reports by Delaney et als. Literatur and Barcia Salorio et al.s. Literatur In addition, conventionally fractionated (see Chapter 18) and hypofractionated stereotactic radiation therapy has been used as an alternative management for VS. This method is proposed as a way of exploiting the precision of stereotactic radiation delivery to minimize dose to normal brain, while employing lower fractionated doses with each session in an effort to minimize complications. Thus far, most radiosurgeons feel that optimal results can be achieved with highly conformal single-session SRS, while sparing the patient the inconvenience of a prolonged treatment course.