Radiosurgery of Central Nervous System Tumors

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Chapter 46 Radiosurgery of Central Nervous System Tumors

Douglas Kondziolka, Ajay Niranjan, L. Dade Lunsford, John C. Flickinger

Clinical Pearls

• Randomized clinical trials confirm the survival benefit of stereotactic radiosurgery for patients with single brain metastases and the local control benefit for patients with multiple (two to four) tumors.

• Four matched cohort studies (class II evidence) that compare Gamma Knife radiosurgery to resection for patients with acoustic neuromas less than 2.5 cm in diameter show improved outcomes after radiosurgery with lower morbidity rate. Indications for microsurgery at institutions with radiosurgery expertise include disabling symptomatic brainstem compression, severe headache, hydrocephalus, trigeminal neuralgia, and patient choice.

• Long-term data are available over the past 10 years from numerous institutions on the value of stereotactic radiosurgery for different benign intracranial tumors.

Stereotactic radiosurgery (SRS) has become one of the most important concepts in the management of patients with central nervous system tumors. The neurosurgeon uses SRS to destroy a tumor using precise, image-guided ionizing irradiation in a single procedure.¹ Over the past two decades, radiosurgery has supplanted fractionated radiation therapy in the care of many tumors, and has forced an evolution of thinking regarding the roles of resection or observation. At a biological level, radiosurgery can halt cell division, cause vascular occlusion, induce apoptosis or necrosis, and affect blood-brain barrier integrity.²^–⁶

Radiosurgical devices include the cobalt-60 Gamma Knife, modified linear accelerator systems, and charged particle generators.⁷^–¹⁰ Although initially designed for functional neurosurgery, the use of brain tumor radiosurgery took off in the era of higher-resolution parenchymal brain imaging with magnetic resonance imaging (MRI). Now robotic devices such as the Perfexion or model 4C gamma units or the Cyberknife facilitate dose planning and delivery.^11,¹² For use in the brain, accuracy and reliability are crucial. At present no pharmacological agents are used to modify the target response to radiosurgery.^13,¹⁴ A listing of indications is shown in Table 46.1.

TABLE 46.1 Applications for Gamma Knife Radiosurgery for Brain Tumors ^∗

Diagnosis	Number of Procedures
Vestibular schwannoma	1439
Trigeminal schwannoma	45
Other schwannomas	65
Meningioma	1377
Pituitary tumor	300
Craniopharyngioma	76
Hemangioblastoma	50
Hemangiopericytoma	41
Glomus tumor	24
Pineocytoma	16
Malignant pineal tumor	13
Chordoma	31
Chondrosarcoma	25
Choroid plexus papilloma	12
Hemangioma	7
Glioblastoma multiforme	349
Anaplastic astrocytoma	134
Fibrillary astrocytoma	43
Mixed glioma	78
Pilocytic astrocytoma	89
Ependymoma	74
Medulloblastoma	24
CNS lymphoma	12
Hypothalamic hamartoma	6
Brain metastasis	3264
Invasive skull base tumor	32
Other tumors	66
Total	7692

CNS, central nervous system.

∗ Data from clinical series at the University of Pittsburgh: total procedures = 10,158; total brain tumors = 7692.

The first two patients treated with the Gamma Knife in Sweden had tumors (a craniopharyngioma and a pituitary adenoma). Typically, radiosurgery has been used for smaller tumors that do not cause significant disability from mass effect. The question of maximum tumor size is asked commonly. The answer depends not only on the tumor volume, often estimated by tumor diameter, but on the degree of mass effect and any related symptoms. A dose reduction used for a larger tumor may lead to a relatively ineffective total dose. On the other hand, failure to decrease the dose for larger volumes can lead to an unacceptable risk of adverse radiation effects (ARE).

Not all radiosurgery systems are the same and they differ in both hardware and software. One should seek a system that allows the surgeon to efficiently create highly conformal and selective volumetric dose plans for irregular lesion volumes, because tumors are rarely “spherical.”¹⁵ The steep falloff of radiation into the surrounding structures (selectivity) helps to achieve safety. The location of many tumors either within or adjacent to critical brain or nerve makes the requirement for conformal and selective radiosurgery paramount.

Radiosurgery or radiotherapy?

Fractionated stereotactic irradiation has been used by some centers to treat benign tumors,^16,¹⁷ and of course, large-field conventional or whole-brain radiotherapy has been used for decades. Any advantage for the use of fractionated radiotherapy becomes important when large volumes of sensitive surrounding normal tissue need to be included in the treatment volume, such as with the standard 2-cm margin around a malignant glioma. If the volume of normal tissue irradiated inside or outside the target volume is small, then fractionated radiation may be of no additional value. Certain tumors appear to be more resistant to traditional radiotherapy and include meningiomas, schwannomas, and some metastatic tumors such as melanoma, sarcoma, and renal cell carcinoma. The radiobiological response can be addressed with the α/β ratio. A lower number refers to later responding tissue.¹⁸^–²⁰

Vestibular Schwannomas

The goals of vestibular schwannoma radiosurgery are to prevent tumor growth, preserve cochlear and other cranial nerve function, maintain general function and quality of life, and avoid the risks associated with open surgical resection. Available long-term data have established radiosurgery as an important alternative to resection. Radiosurgery was first offered to patients who were elderly or medically infirm, but with experience, was found ideal for patients of all ages.²¹^–²⁴ We have found consistent results across age groups.^21,²⁵

To date we have managed 1397 patients with vestibular schwannomas using Gamma Knife radiosurgery (Fig. 46.1). The mean patient age in our series was 57 years (range, 12 to 95). Eight percent had neurofibromatosis (93 patients). Symptoms before radiosurgery included hearing loss (92%), balance symptoms or ataxia (51%), tinnitus (43%), or other neurological deficit (19.5%). Thirty-four percent of our patients had useful hearing, Gardner-Robertson grade I (speech discrimination score ≥70%; pure tone average ≤30 dB) or grade II (speech discrimination score ≥50%; pure tone average ≤50 dB). Since 1992, the average dose prescribed to the tumor margin was 13 Gy. The 50% isodose line was used in 90% of patients.

FIGURE 46.1 Magnetic resonance imaging (MRI) showing a Gamma Knife radiosurgery dose plan for a left vestibular schwannoma. The patient received a tumor margin dose of 12.5 Gy.

Our long-term study documented a 98% clinical tumor control rate (no requirement for surgical intervention) at 5 to 10 years.^21,²³ Since the institution of MRI-guided dose planning, there has been a significant reduction in morbidity.^26,²⁷ Currently, the risk for any grade delayed facial nerve dysfunction is below 1%.^26,²⁷ Patients with useful hearing before radiosurgery continue to report an approximate 75% overall rate for maintenance of useful hearing, depending on tumor size, with even better results for intracanalicular tumors.²⁷^–²⁹ In comparison studies, radiosurgery has been shown to be a cost-effective alternative to microsurgery for these patients.

For smaller tumors, it is likely that more patients now receive radiosurgery as primary care. No randomized clinical trials have been conducted, but there are now four matched cohort studies (class II evidence). These studies evaluated patients with similar sized tumors, and evaluated clinical, imaging, and quality of life outcomes. All showed better results after radiosurgery for most clinical measures, similar results for the symptoms of tinnitus and imbalance, and similar freedom from tumor progression rates.³⁰^–³³ It is important to tell patients that there can sometimes be a transient expansion of the tumor capsule after radiosurgery and that it usually can be observed without further treatment.^34,³⁵ The value of radiosurgery in neurofibromatosis type 2 has been studied.³⁶ Based on these data, we believe that there are few remaining indications for surgical resection in a patient with a small to moderate size tumor. These indications include disabling symptomatic brainstem compression, severe headache, hydrocephalus, trigeminal neuralgia, and patient choice. Radiosurgery has also been performed and evaluated for patients with other cranial nerve schwannomas (Fig. 46.2).

FIGURE 46.2 Magnetic resonance imaging (MRI) at Gamma Knife radiosurgery using the Perfexion unit showing a left jugular foramen schwannoma with intracranial and extracranial extension. The patient presented with mild vocal cord dysfunction. Cranial nerve function was preserved in follow-up.

Meningiomas

Radiosurgery has transformed the management of intracranial meningiomas, particularly for tumors of the skull base.³⁷ As for most indications, radiosurgery was first considered for residual or recurrent tumors after prior resection.³⁸ The steep radiation falloff can be directly conformed to the well-defined tumor margin. The role of aggressive skull base surgery has waned as reports showing excellent clinical outcomes for small basal tumors have been published.^39,⁴⁰ Larger tumors with mass effect benefit from subtotal resection followed by radiosurgery if complete resection is not feasible. However, because of their more aggressive nature, atypical or anaplastic/malignant meningiomas (WHO [World Health Organization] grade II or III) are best managed with complete resection followed by fractionated radiotherapy because of their tendency to extend beyond the borders seen on imaging.⁴¹ Radiosurgery also is of value in the setting of incomplete resection.

Our 22-year experience includes 1302 intracranial meningiomas. Recently, we published data from 972 patients with 1045 meningiomas (Fig. 46.3).⁴² Half of the patients had undergone a prior resection and the average age was 57 years. Tumor locations included middle fossa (351 patients), posterior fossa (307), convexity (126), anterior fossa (88), parasagittal region (113), or other sites (115). Follow-up over the past 5, 7, 10, and 12 years was obtained in 327, 190, 90, and 41 patients, respectively.