Stereotactic Radiosurgery with the Gamma Knife Part 2

Brain Metastases

More than 100,000 patients are diagnosed with brain metastasis annually. The management of brain metastasis patients remains a challenge for oncologists, radiation oncologists, and neurosurgeons. Traditional therapy of single metastasis has been either resection or whole brain radiation (WBRT), with a boost to the affected region, or combined surgery with whole brain radiation. The surgical resection of solitary metastasis with WBRT has been shown to improve survival compared to WBRT alone [7]. The complications of whole brain fractionated radiation include memory loss, alopecia, dementia, and radiation necrosis.

Stereotactic radiosurgery is changing the long-standing management of brain metastasis. Radiosurgery can achieve many of the same goals as resection, (tumor control, reduced mass effect), one of the goals of fractionated radiation therapy (the treatment of multiple lesions), and effectively treat deeply located tumors that are not considered for resection. For patients with solitary metastasis, radiosurgery may allow the avoidance of WBRT and its potential complications. In conjunction with WBRT, radiosurgery can provide rapid improvement in peritumoral edema, local tumor control, and prolonged survival compared with WBRT alone [8]. Radiosurgery provides nearly equivalent tumor control rates for breast, lung, and renal cell carcinoma, as well as melanoma. With control of brain metastasis, the management of systemic disease becomes the survival limiting factor. Radiosur-gery has the additional benefits of 1- to 2-day hospital stays and low costs (Fig. 4).

OTHER LESIONS

Stereotactic radiosurgery can be used to manage effectively other intracranial lesions, such as chordomas, chondrosarcomas, gliomas, and cavernous malformations (CM). Stereotactic radiosurgery is an adjuvant therapy, providing a radiation boost to the enhancing component of malignant glial neoplasms. We have also obtained good results in the treatment of juvenile pilocytic astrocytomas in children. Cavernous malformations are treated with radio-surgery after a second symptomatic hemorrhage using the same dose algorithm applied to AVMs. The baseline risk of hemorrhage for CMs is approximately 1% annually; however, the natural history of CMs suggests that those with a second symptomatic hemorrhage have an increased tendency toward hemorrhage (> 30% annually).

FUNCTIONAL RADIOSURGERY

Lars Leksell originally designed the Gamma Knife in 1967 to create functional lesions for the treatment of psychiatric disorders. Today, radiosurgery is used to treat trigeminal neuralgia, essential tremor, parkinsonian tremor, and selected psychiatric or epileptic disorders. In trigeminal neuralgia, a maximum dose of 80 Gy is targeted to the proximal trigeminal nerve just anterior to the pons, using a single 4-mm isocenter. Radiosurgical thala-motomy (ventral intermediolateral thalamic nucleus) is performed with anatomical MRI localization. Tremor is improved in most patients after a latency interval of 2 to 6 months.

Figure 4 A 56-year-old woman presented with this solitary metastasis, 2 years after a mastectomy for breast cancer. The dose plan was created with two 14-mm isocenters and three 8-mm isocenters. The maximal dose was 32 Gy. The marginal dose was 16 Gy.

CRITICISMS OF RADIOSURGERY

Radiosurgery was initially viewed as a competitor to traditional neurosur-gical techniques. Common criticisms of radiosurgery included the following: (1) The tumor is not removed; (2) There is no rapid reduction in mass effect; (3) Future surgery will be more difficult; (4) Additionally, patients may have a false sense of cure. It is true that the tumors often are not eliminated, but the goal of radiosurgery is tumor control, not extirpation. A rapid reduction in mass effect is often not required, and edema is often significantly reduced after radiosurgery. It is unlikely that radiosurgery complicates future operations. One study of arteriovenous malformations that were resected after radiosurgery found they were less vascular and easier to remove. One mi-crosurgeon has noted that three of four tumors that he resected after radio-surgery were no more difficult to remove compared with the average tumor. Finally, patient misconceptions are addressed with education and long-term follow-up. We obtain MRI scans at 6, 12, 24, 48 and 96 months after treatment of benign lesions, and every 3 years or so thereafter. We obtain more frequent follow-up for patients with malignant diseases.

COMPLICATIONS OF RADIOSURGERY

It is true that there are almost no immediate complications of radiosurgery, but complications do occur. Such problems include small patches of alopecia for tumors adjacent to the scalp, brain edema, radiation necrosis, neurological deficits, and failure to achieve the intended goal. The risk of complications is a function of the tissue volume being treated, the dose delivered, the location, and prior radiation treatments.

There is no absolute maximal tolerated dose that important neuroan-atomical structures, such as the optic nerve, can tolerate, but our general guidelines are included in Table 2. The maximum volume treated also depends on the location, the radiosurgical indication, and prior therapies. Large volumes are more easily treated in the frontal lobe, as compared with the brainstem. In general, treating volumes larger than 10 cm3 increase the risk of complications. A study by Flickinger et al. found that complications after AVM radiosurgery varied dramatically with location and the volume of tissue receiving greater than 12 Gy [9]. Locations in order of increasing risk for radiosurgery complications were frontal, temporal, intraventricular, parietal, cerebellar, corpus callosum, occipital, medulla, thalamus, basal ganglia, and pons/midbrain. Oncologic indications may dictate the use of higher doses, accepting higher risk, than nononcological indications.

Table 2 Potential Complication Limits

Location	Dose
Scalp—temporary epilation	3 Gy
Scalp—main erythema	6 Gy
Scalp—permanent epilation	7 Gy
Scalp—desquamation/atrophy
Scalp—ulceration/necrosis
Ocular lens	0.08 Gy
Optic nerve	8 Gy
Brainstem	14 Gy

The risk-benefit ratio weighs heavily in favor of radiosurgery. In our experience treating more than 3500 cases with the Gamma Knife, the risk of significant morbidity is approximately 3%. The chance of successful tumor control is more than 90% for most lesions. Long-term results now demonstrate that radiosurgery is an important therapeutic alternative for patients who are ineligible for surgery because of deep-seated lesions or serious medical conditions, or for patients who would like to avoid the risks of microsurgery.