LINAC-Based Stereotactic Radiosurgery and Stereotactic Radiotherapy for Parasagittal, Skull-Base, and Convexity Meningiomas

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CHAPTER 53 LINAC-Based Stereotactic Radiosurgery and Stereotactic Radiotherapy for Parasagittal, Skull-Base, and Convexity Meningiomas

Naren Raj Ramakrishna

INTRODUCTION

Gross total surgical resection (GTR) remains the mainstay of treatment for meningiomas.¹ GTR, however, may not be appropriate for a significant proportion of meningiomas, particularly those involving the skull base or parasagittal region, or large or invasive tumors involving the convexity. Skull-base tumors are often challenging to access, and may involve the brain stem, cranial nerves, hypothalamus, or vascular structures. The risk of postoperative morbidity after resection is approximately 30% to 40%.²^–⁵ For subtotally resected tumors, the risk of recurrence is substantial with a 55% risk. Even for total resections, there is a 20% to 23% risk of recurrence at 10 years.^4,⁶ Given the substantial long-term risk of recurrence after subtotal or even ostensibly complete resection, there has been great interest in improving local control with radiation treatment.

External beam radiation treatment was shown in the 1970s and 1980s to be an effective modality for primary or adjuvant treatment of meningioma. Large retrospective series revealed that radiation after a subtotal resection would result in long-term progression-free survival (PFS) of 82% to 88%, similar to that expected after a gross total resection.⁶^–⁸ For medically or surgically inoperable tumors, the use of radiation alone was shown to be associated with long-term local control similar to that with GTR.⁹ These data established the efficacy of radiation treatment for inoperable tumors, after subtotal resection, or at the time of recurrence. In addition, these data supported the notion that for sites associated with high operative morbidity, that a subtotal resection aimed at preserving function could be combined with radiation treatment to achieve tumor control comparable to total resection but with decreased risk of complications.^6,¹⁰

The development of stereotactic radiosurgery (SRS) ushered in an important new era in radiation treatment with greatly improved treatment precision and dose shaping. It was possible with the advent of the Gamma Knife® to treat tumors of up to 3.5 cm with doses to adjacent normal brain tissue significantly diminished relative to conventional external beam radiation treatment (EBRT).¹¹ In the late 1980s, effective methods were devised to adapt linear accelerators (LINACs) used for conventional radiation treatment to SRS.¹² The widespread availability and lower cost of LINACs broadened the availability of radiosurgery for meningioma patients. In addition, it offered the possibility of fractionated stereotactic radiation treatment (FSRT), using relocatable noninvasive stereotactic immobilization.¹³ FSRT combines the precise dose delivery and sharp dose gradients of SRS with the biological benefits to normal tissue sparing of dose fractionation from EBRT, allowing for the possibility of stereotactic treatment for meningiomas of virtually any shape or size.

In the last two decades, LINAC-based SRS and FSRT have emerged as effective and versatile treatment options for meningiomas. LINAC-based SRS has shown a high efficacy similar to that observed with Gamma Knife radiosurgery. For large meningiomas, or skull-base tumors in close proximity to dose-limiting structures such as the optic apparatus, FSRT has emerged as a safe and effective alternative to EBRT, providing a vital option in multimodality treatment. This chapter summarizes the results of LINAC-based SRS and FSRT for skull-base, convexity, and parasagittal meningiomas.

LINAC-SRS

Meningiomas represent a favorable tumor type for focused treatment such as radiosurgery. They are encapsulated, noninvasive in their benign form, and rarely metastasize. The focused treatment of brain tumors such as meningioma has benefitted greatly from development of computed tomography (CT)- and magnetic resonance (MR)-based imaging to define tumor volumes accurately,⁸ advanced treatment planning and dose shaping devices such as the micro-multileaf collimator,¹⁴ and precise methods for stereotactic tumor localization and radiation delivery.¹⁵

Stereotactic radiosurgery (SRS) refers to the delivery of large single doses of radiation to targets that have been localized using the process of stereotaxy. SRS also utilizes advanced dose shaping to create a steeply declining dose gradient beyond the tumor margin, which minimizes the volume of adjacent normal brain receiving radiation. SRS has become an important modality for primary and adjuvant treatment for tumors in high operative risk locations such as parasagittal and skull-base meningiomas where the likelihood of subtotal resection is highest. In addition, it has been an important treatment option for medically inoperable patients.

Unlike the Gamma Knife, which utilizes 201 fixed Co-60 sources in a hemispherical array, LINAC-based SRS treatment units rely on a gantry or robotic arm-mounted linear accelerator that creates gamma rays by accelerating electrons toward a metal target. This results in beam energies of 6 to 15 MeV versus 1.25 MeV for Co-60. Dose delivery for gantry-mounted LINACs is accomplished by either rotating the gantry in five or more arcs, or using multiple fixed fields all centered on the tumor location. Dose shaping for LINAC-based SRS is performed using circular collimators or a micro-multileaf collimator; intensity modulated radiosurgery is also possible for complex dose shaping. For gantry-mounted LINAC-SRS, treatment is generally delivered to a single isocenter, whereas Gamma Knife treatment relies on multiple isocenters for dose shaping. The robot-mounted CyberKnife LINAC treats via a non-isocentric method.

The physical characteristics of the radiation treatments using either the Gamma Knife or LINAC-based SRS are both highly conformal. In general, LINAC-SRS plans may have a slightly shallower dose gradient in normal tissue but also have greater dose homogeneity within the tumor.¹⁶ The increased dose inhomogeneity within the tumor associated with Gamma Knife treatment may result in increased risk or morbidity to interspersed normal tissue such as intratumoral cranial nerves.¹⁷

LINAC-based SRS systems are technically capable of radiosurgery to larger lesions than the Gamma Knife, owing to the larger potential radiation field size. However, the size of treated lesions for single-fraction intracranial radiosurgery, regardless of platform, is generally limited to approximately less than 4.0 cm owing to the increase in risk of normal tissue injury when tumor dimensions are greater.

Image-guided frameless stereotactic systems are an important recent development in radiosurgery. Both the Gamma Knife and LINAC-SRS may utilize an invasive head frame for stereotactic localization and patient immobilization. With the advent of image-guided stereotaxy, LINAC-based systems may forego an invasive head frame and utilize thermoplastic masks to immobilize the patient, while relying on X-ray image-based stereotaxy to position the patient accurately.¹⁸ Frameless SRS systems include the Novalis™ system (BrainLab, Heimstetten, Germany) and the CyberKnife (Accuray, Sunnyvale, CA). Each system acquires stereoscopic X-ray imaging of skull anatomy at the time of treatment. These images are then automatically fused with a reference treatment planning CT dataset. The deviation of the treatment position from the reference position is calculated and either the patient is shifted robotically (Novalis), or the robotically-mounted LINAC source is retargeted (CyberKnife). Stereoscopic imaging may be repeated during treatment to verify patient position and correct for patient movements.^19,²⁰ Another frameless radiosurgery system that may be added on to any LINAC system utilizes a bite-block to which is fixed an infrared target array. The position of the target array is used as a reliable surrogate for patient position through a system of infrared cameras that can precisely track the array position.¹⁸ In addition to improving patient comfort, the use of image-guided frameless radiosurgery allows flexibility in treatment scheduling as patients may undergo mask fabrication, treatment planning, and treatment on different days.

Ultimately, the adoption of image-guided LINAC-SRS will be hastened as further centers obtain the necessary equipment and develop clinical experience. Reports evaluating both the Novalis and CyberKnife platforms indicate system accuracy of image-guided frameless LINAC-radiosurgery systems to be comparable to that of frame-based systems.^19,²¹ In critical applications, where treatment tolerance and immobilization must be insured, the combined use of image-guidance together with frame-based treatment may allow for the detection of frame slippage, which may be more difficult to ascertain using conventional methods such as a depth-helmet.²²

LINAC-SRS RESULTS

There are relatively fewer published series on LINAC-based radiosurgery compared to Gamma Knife radiosurgery. Based on the similar precision and dose shaping characteristics, the LINAC and Gamma Knife SRS systems would be expected to have similar results. The largest LINAC-SRS treatment series since 1998 are summarized in Table 53-1. The median follow-up ranged from 23 months to 74.5 months.²³^–²⁸ The median doses employed for LINAC-based SRS range from 12.7 Gy²⁶ to 16 Gy.²³ The local control rate with LINAC-SRS of 89% to 100% is comparable to the range of local control observed with Gamma Knife radiosurgery of 86% to 98%.²⁹^–³¹ Regression of tumor after LINAC-SRS was observed in 32.4% to 43% of cases,^24,²⁶ while Gamma Knife series have reported rates of regression of 28% to 69.7%.^29,³⁰ The rate of late complications associated with SRS ranged from 3%²⁶ to 9.3%.²³ Overall, these results indicate that LINAC-SRS is comparable in both efficacy and toxicity to Gamma Knife SRS.

TABLE 53-1 LINAC-SRS series

The LINAC-SRS series of Hakim and colleagues included 155 tumors in 127 patients of which 31 involved the convexity, 39 were parasagittal/falcine, and 71 involved the skull base. SRS was the initial treatment in 31% of patients, for persistent disease in 17.5%, and for tumor regrowth in 52%. The median tumor volume treated was 4.1 cc. The 5-year actuarial tumor control was 89.3% for patients with benign meningioma.²⁵ They found no significant difference in tumor control between the skull base and the remaining locations. Six patients experienced permanent complications of SRS occurring at a median time of 10.3 months after treatment. The complications included blindness in one eye, unilateral hearing loss, leg weakness, hemiparesis, and two deaths. Complications were related to larger tumor volumes and proximity of the tumor to critical structures.

Shafron and colleagues reported on the initial results of LINAC-SRS at the University of Florida at Gainesville in 1999.²⁶ This experience was updated by Friedman and colleagues in 2005 and comprises the largest LINAC-based SRS report to date.²⁸ In this study, 210 patients, including 18 with atypical and 11 with malignant meningioma were followed for at least 2 years postradiosurgery. The most common radiosurgery peripheral dose for benign meningiomas was 12.5 Gy and the median dose was 13.14 Gy (range 10–20Gy). The median treatment volume was 7 cc. The mean imaging follow up was 39 months and the mean clinical follow-up was 56 months. As expected, benign tumors displayed better local control, with 100% control at both 1 and 2 years, and 96% at 5 years, whereas atypical/malignant tumors displayed 100%/100% control at 1 and 2 years but decreased to 77%/19% at 5 years. While the majority of patients had skull-base tumors, 22 patients treated had convexity tumors, and 50 patients had falcine/parasagittal tumors. Temporary complications were observed in 6.2% of patients and all resolved with steroid therapy. Age was the only variable shown to significantly increase the risk of temporary complications with each year of age above a mean of 59 years, resulting in an 8% increase in complication rate. Permanent complications were seen in only 2.3% of patients, and all 5 patients had malignant tumors. These patients were all treated with a combination of high-dose fractionated radiotherapy in addition to radiosurgery, with the high combined dose likely contributing to the increased complication rate.

LINAC-SRS series by Chuang and colleagues ²³ and Deinsberger and colleagues²⁴ reported results of radiosurgery for skull-base meningiomas of 5.68 and 5.9 cc volume, respectively. In the study by Chuang and colleagues, 43 patients with skull-base meningiomas were treated with LINAC-SRS using a median dose of 16 Gy. The median follow-up was 74.5 months and the 7-year local control rate was 89.7%. For patients receiving SRS alone as primary treatment, the 7-year local control rate was 100%. Reduction in tumor volume following LINAC-SRS was observed in 37.2% of patients. A 7% late complication rate was noted in this study including a patient with new left hemiparesis after treatment of a portion of brain stem to 16.2 Gy. Deinsberger and colleagues reported on the outcome of LINAC-SRS for 37 patients with skull-base meningioma.²⁴ With 66-month median follow-up, a 97.2% local control rate was achieved. A decrease in tumor volume was observed in 32.4% of tumors after treatment. Late complications were observed in 5.4% of patients. One patient developed a hemiparesis 8 months after LINAC-SRS for a petroclival meningioma. As in the report by Chuang, the affected patient received a 16-Gy dose to the surface of the brain stem. The hemiparesis responded to corticosteroids and only a slight residual hemiparesis was present at 2 years postradiosurgery.