Stereotactic Radiosurgery of Skull Base Tumors

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Chapter 65 Stereotactic Radiosurgery of Skull Base Tumors

P. Ashley Wackym, Christina L. Runge-Samuelson, David R. Friedland

Management of many skull base tumors has shifted in recent years away from surgical resection and towards control of growth. This is particularly true for vestibular schwannomas, i.e., acoustic neuromas, and is increasingly applicable to glomus jugulare tumors. The principal modality for such treatment is gamma knife surgery although other conformal radiation treatment systems are available. Gamma knife surgery is advantageous in requiring a single session for treatment of most skull base lesions, which increases its appeal to both surgeon and patient. This chapter will focus primarily on the methods used in treating skull base tumors with gamma knife surgery.

Gamma knife surgery, similar to microsurgery, has advantages and disadvantages which must be thoroughly discussed with the patient.^1,² For the patient it is alluring to undergo an outpatient procedure rather than microsurgical management that requires a much longer period of care. Further, gamma knife outcomes show excellent tumor control and, with current methods, low cranial nerve morbidity. Gamma knife surgery is a viable treatment modality for the appropriate patient as defined by age, medical history, tumor characteristics and physical findings. As such, many neurotologists now offer gamma knife surgery as part of their armamentarium for managing vestibular schwannomas and glomus tumors.³

Several institutions world-wide offer training courses for physicians and radiation physicists at centers having the Leksell Stereotactic System or Leksell Gamma Knife. To date more than 1500 neurotologists, neurosurgeons, physicists, and radiation oncologists have received such training. In addition, the parent company, Elekta Instrument AB (Stockholm, Sweden), offers basic and advanced training courses and workshops. Courses typically consist of didactic lectures, observation of patient treatment, and practical hands-on training. Further, all new installations of Leksell Gamma Knife are accompanied by a one-week on-site start-up training for the neurotologists, neurosurgeons, radiation oncologists, and physicists comprising the gamma knife treatment team.

PATIENT SELECTION

Opting for gamma knife surgery over observation or microsurgical resection is a complex decision. There are the preferences of the informed patient, the comfort and experience of the surgeon, the patient’s medical history and condition, and the characteristics of the tumor. While there are no definitive measures defining or restricting the use of gamma knife surgery, particular guidelines can inform the decision making process.

Although a tissue diagnosis is not typically acquired prior to gamma knife treatment, radiographic and clinical diagnoses of vestibular schwannoma and glomus jugulare are sufficient to initiate a discussion of gamma knife surgery. Other potential neoplasms amenable to gamma knife treatment by the neurotologist are cerebellopontine angle meningiomas, posterior fossa and jugular foramen non-vestibular schwannomas, temporal bone metastatic lesions and primary vascular neoplasms. An absolute contraindication to gamma knife treatment would be tumors extending too far inferiorly to enable placement into the centrum of the collimator helmet. Gamma knife surgery is also contraindicated in large tumors causing life-threatening brainstem and central aqueduct compression. Such large tumors, in the absence of clinically significant problems, provide a relative contraindication to gamma knife surgery as post-treatment swelling may cause obstructive hydrocephalus requiring emergent intervention. Typically, vestibular schwannomas greater than 2.5 cm in the cerebellopontine angle should be cautiously approached if gamma knife proves the best option given other medical concerns. Most surgeons will not treat vestibular schwannomas greater than 3.0 cm in maximum axial dimension within the cerebellopontine angle because of the risk of post-treatment obstructive hydrocephalus.

Other guidelines for gamma knife surgery require clinical judgment as to the medical condition of the patient, the expected growth and potential morbidity of the tumor, the functional status of the patient, audiometric and vestibular performance, age and expected life-span of the patient. Individualized treatment plans depend on a frank and thorough dialogue between physician and patient as to the options available, risks and benefits of each approach, and expected outcomes based upon evidence-based reviews or an analysis of each institution’s outcomes.

PREOPERATIVE COUNSELING

Informed consent for gamma knife surgery requires the surgeon to discuss alternative options such as observation and microsurgical resection.² The risks and benefits of these alternatives should be frankly described and compared to gamma knife treatment. Many patients have received information from the Internet or from physicians with limited experience with gamma knife and may have erroneous information. Common misconceptions include the expectation that gamma knife surgery completely removes the tumor and that hearing will improve, or conversely that cranial nerve morbidities are significant. These need to be addressed with evidence-based reports and information.

One statistic, which is particularly alarming to patients considering gamma knife surgery is that there have been eight cases of malignancy within vestibular schwannomas (as of 2002).⁴ Four of these patients had been previously treated with radiosurgery. While it remains possible that these four malignancies developed after the radiation treatment, it is more likely that these malignant tumors were misdiagnosed as benign at the outset of evaluation and treatment.

Delayed development of radiation-induced neoplasms was addressed by Pollock and colleagues in 1998.⁵ They reviewed more than 20,000 patients treated with radiosurgery worldwide and found no increased incidence of new neoplasm development (i.e., benign or malignant). A retrospective cohort study comparing the Sheffield, England radiosurgery patient database with the national mortality and cancer registries identified a single new astrocytoma among those treated.⁶ Based on their national incidence figures, 2.47 cases would have been predicted. The risk of radiosurgery induced malignancy in patients with neurofibromatosis type 2 (NF2) and von Hippel-Lindau disease was similarly studied.⁷ Of 118 NF2 and 19 von Hippel-Lindau disease patients, totaling 906 and 62 patient-years of follow-up data, respectively, only two cases of intracranial malignancy were found. Both of these were in NF2 patients. One was thought to have arisen before the radiosurgery; the other was a glioblastoma diagnosed three years after radiosurgery. Gliomas may occur in as many as 4% of NF2 patients and the single case may not represent an increased risk. It was suggested that the late risk of malignancy arising after irradiation must be put in the context of the condition being treated, the treatment options available to these individuals, and their life expectancy.

Despite the findings of the studies just reviewed, it is important to counsel patients about the possibility of malignant transformation or induction. A handful of tumors suggestive of radiation induced malignancy have been reported among the tens of thousands who have undergone gamma knife treatment. Lustig and colleagues reported the development of a squamous cell carcinoma following radiation treatment of vestibular schwannoma.⁸ Hanabusa and colleagues reported the malignant transformation of a vestibular schwannoma following gamma knife surgery.⁹ There was histologic evidence of vestibular schwannoma following a retrosigmoid resection. Four years after this resection, recidivistic tumor was identified, and the patient was subsequently treated with gamma knife surgery. Six months post-treatment, the tumor had grown, and the patient underwent surgical resection via a combined retrosigmoid-translabyrinthine approach. Abnormal mitotic figures were observed on histologic sections, and the diagnosis of malignancy was assigned.

SURGICAL TECHNIQUE

The Gamma Knife Unit

The first gamma knife unit (Elekta Instrument AB, Stockholm, Sweden) was installed in Stockholm, Sweden in 1968, and it was not until 1987 that the first gamma knife (model U) was installed in the United States at the University of Pittsburgh. The gamma knife model B (1996) is the unit currently most used throughout the United States. The gamma knife model C was introduced three years later and the major upgrade consisted of an automatic positioning system (APS). The unit is otherwise quite similar to the model B and both contain 201 radioactive isotope cobalt 60 (⁶⁰Co) sources and beam channels. Due to physical restraints these units can only treat lesions intracranially or along the skull base. During 2008, a completely redesigned gamma knife unit, named Perfexion, is being introduced. It uses 192 ⁶⁰Co sources, has a single collimator helmet with variable diameters, and can treat lesions within the entire head and neck, down to the level of the clavicles.

The basic principle of gamma knife surgery is to provide focused radiation to the tumor while minimizing radiation delivery to surrounding tissues. As such, a semicircular shield called the collimator helmet is used to generate approximately 200 individual gamma radiation “beams.” In the center of the helmet, where the beams meet, radiation delivery is maximal, but along each individual radiation tract tissue exposure is relatively low. When the collimator helmet is locked into position, the 201 openings of the collimator helmet coincide with the cobalt sources. There is a shielded chamber within which the ⁶⁰Co sources are contained, and stainless steel shielding doors protect the treatment room from the ⁶⁰Co sources. There is a treatment couch with an adjustable mattress that slides into the gamma knife unit together with the collimator helmet and the patient. Figure 65-1 schematically shows the orientation of the components of the gamma knife model, Leksell Gamma Knife® 4C and Figure 65-2 shows the overall appearance of the gamma knife model, Leksell Gamma Knife® 4C.

Figure 65-1 Gamma knife surgery. Schematic illustration of the Leksell Gamma Knife 4C which utilizes the automatic positioning system.

Figure 65-2 Leksell Gamma Knife 4C.

When treatment is initiated, the treatment couch is automatically moved from its idle position into the treatment unit together with patient and helmet. Once the couch is docked in its treatment position, the helmet collimator and corresponding collimators in the unit form a beam channel, allowing the radiation that is continuously emitted by the sources to reach the patient. At the end of each irradiation “shot,” the couch is automatically withdrawn, either to its idle position or to a position outside the radiation focus to reposition the patient for the next irradiation shot. There are four interchangeable helmets by means of which the size of the collimator (that part of the treatment unit that shapes the beam) can be changed between 4 mm, 8 mm, 14 mm and 18 mm. The combination of four different sized collimators and repositioning the patient in the three-dimensional space defined by the stereotactic headframe are effective to deliver the radiation dose selectively and conformally to radiosurgical targets of any shape.

Frame Attachment

The stereotactic head frame is used to coordinate the location of the tumor within the collimator helmet. As such, proper placement is of utmost importance to providing adequate treatment. There are two general principles guiding head frame placement for gamma knife surgery. First, the target should be as close to the center of the frame as possible. This prevents possible collisions of the frame with the sides of the collimator helmet especially when trying to align laterally extended tumors in the center of the unit. Second, the frame attachment should be stable. This prevents movement and ensures accuracy and correlation among the pre-treatment imaging study, workstation treatment plan, and delivery of focused radiation. These principles should be addressed at the time of frame attachment. In lateral targets, such as vestibular schwannomas or glomus tumors, the frame should be shifted toward the tumor side. In skull base tumors the frame should also be positioned lower than for treatment of more superior intracranial lesions. Anterior-posterior alignment should also be accounted for and can be adjusted by varying the lengths of the pins used to secure the frame. To ensure stability, avoid screw fixation in bone flaps, cranioplasty materials, burr holes, or skull defects.

The method of anesthesia used during frame placement is surgeon and patient dependent. In our program, either sedation with versed and fentanyl, or monitored anesthesia with propofol, followed by injection of local anesthetic at the pin sites is used. Figure 65-3A shows the typical array of tools used for the frame attachment. A variety of screw lengths allow the surgeon to choose those ideally suited for the individual location of the posts and tumor. The placement of the frame should begin with an accurate orientation of the location of the target within the patient’s head. Ideally, the target should be located within the fiducial range and placed centrally within the frame thereby avoiding later collisions with the collimator helmet and granting sufficient accuracy for the stereotactic target definition.

Figure 65-3 A, Stereotactic headframe at the time of assembly. Pins used for fixation prior to imaging, treatment planning, and gamma knife radiosurgery are seen in the foreground. B, With a towel placed on the vertex of the head, the magnetic resonance imaging (MRI) fiducial box is balanced on the head while topical anesthetic is infiltrated at the pin sites. C, While the headframe and attached plastic MRI fiducial box is secured to the skull using the pins, an assistant stabilizes the assembly in place. Note the tightening of pins in opposing vectors. D, After the frame has been secured to the skull, measurements are taken through defined entrance points in a plastic dome representing the size and position of the collimator helmet relative to the frame, head and face. These values are incorporated into the treatment planning software to create a wire grid representing the patient’s head. The post height and pin length are also measured and are inputted into the treatment planning software. These values are used in the calculations used to predict collisions between the collimator helmet and the stereotactic headframe.

The stereotactic frame is assembled and preliminarily supported by using external auditory canal support pins, a Velcro band, or a stereotactic fiducial box. When using a fiducial box to facilitate frame placement, it is important to use the MRI fiducial box, rather than the CT or angiography fiducial box, since this is the smallest of the three plexiglass fiducial boxes (Figs. 65-3B and 65-3C). Asymmetric frame placements are possible and do not impair the accuracy of imaging. The frame can be shifted from side to side or can be moved as far as possible to the front or back to facilitate centering of the tumor. The frame is stabilized against the patient by an assistant and the surgeon should adjust the lengths of the posts to maintain relative tumor position. A low position of the anterior posts can help avoid anterior collisions with the collimator helmet for skull base posterior fossa tumors. In critical positions, collisions can sometimes be avoided by using the curved posts in the anterior position.

Once post position is determined the screws can be inserted. The surgeon and assistant should work on diagonally opposing screws to provide the best stability without changing the desired frame position. For asymmetric frame placement apply the longest screws first, thereby defining the desired distance of the target to the frame. Protrusion of the screws from the posts should be kept to a minimum to avoid collisions. Approximately 8 to 10 mm is considered to be sufficient but at our institution we prefer to limit this projection to 4 to 6 mm. If a screw extends further it should be exchanged for a shorter screw.

Measurements of the frame and placement are then performed to allow the computer to identify any potential collisions after the plan is formulated. These measurements are required for the frame and skull section in Leksell GammaPlan treatment planning software. Measurements include the length of the four posts and the length of the screws that protrude from the posts. Additionally, the volume of the head is measured using the plastic collimator bubble, simulating the relationship of the frame to the treatment collimator helmet (Fig. 65-3D). This concludes frame placement and the patient may proceed to imaging.

Imaging

Treatment planning requires imaging of the tumor with respect to the frame as determined by specific fiducial boxes. The MRI fiducial box clips to the frame and care should be taken to ensure that it is flush and square during imaging. The MRI fiducial box has a Z-shaped channel on each side filled with copper sulfate to generate position markers for each axial slice. The box should be checked prior to each use to ensure the channels are filled with solution and no air bubbles are present. The patient, with head frame and fiducial box, is secured into the head holder on the MRI sliding table. For imaging acoustic neuromas and glomus tumors we typically order axial 3D SPGR (spoiled gradient recalled) acquisition with T1 weighting and double dose IV contrast. Before the patient leaves the scanner images are reviewed and the distance between fiducial registration markers is validated for accuracy.

Many centers acquire only MRI scans for treatment planning. We prefer to also acquire a non-contrast CT scan through the temporal bone to aid in planning. There is evidence of distortion of MR images and correlation with CT scans at the time of planning can aid in reducing radiation delivery to critical structures such as the cochlea and facial nerve.¹⁰ A CT fiducial box is affixed to the frame, the patient secured in the holder attached to the table, and an axial scan through the temporal bone and skull base acquired. Both CT and MR images are imported into the Gamma Knife workstation. Axial scans are defined, and coronal and sagittal reconstructions generated for each.

Treatment Planning

Leksell GammaPlan is the dedicated software treatment planning system for Leksell Gamma Knife. Dose planning for gamma knife surgery means precisely conforming the isodose distribution to the target. The isodose distribution is built up by a number of individual shots or isocenters. The Leksell GammaPlan software is designed to help the operator as much as possible to perform this procedure and is quite straightforward to use.

Currently, for vestibular schwannomas, the routine prescription is 12 to 14 Gy delivered to the 50% isodose line. The 50% isodose line shows where 50% of the prescribed dose lies. In the case of gamma knife treatments the dose is frequently prescribed to the 50% isodose line. This ensures that the periphery of the tumor will receive at least the prescribed dose, that the dose will be higher than the prescribed dose inside the tumor, and that the dose will fall off rapidly outside the tumor thus sparing critical structures.

Dose planning using Leksell GammaPlan involves composing shots to develop a conformal isodose. By definition, this includes the whole target but spares the surrounding healthy tissue. Figure 65-4 shows an example of a vestibular schwannoma. The target is well positioned on the screen and magnified for good visibility. When the shot menu is opened, one can select the size of the collimators. The size of the collimator is selected based on the tumor shape and the gaps in coverage of the 50% isodose line displayed over the tumor. Shots are placed sequentially to cover the target as effectively as possible. Changing the position of the shots, adding additional shots, and adjusting the relative weight of shots quickly leads to a conformal dose plan.