Complications of stereotactic radiosurgery

Stereotactic radiosurgery is a technique that utilizes multiple convergent beams to deliver a high single dose of radiation to a radiographically discrete treatment volume. Although initially developed for the treatment of benign tumors and vascular malformations, it is being increasingly used for malignant disease, particularly metastatic intracranial lesions.

The complications of cerebral stereotactic radiosurgery will be reviewed here.

TYPES OF REACTIONS — In general, there are fewer complications associated with stereotactic radiosurgery compared with standard fractionation cranial irradiation. This is because of the limited field of treatment, and the methodology of strict stereotactic localization and immobilization. In addition to varying with time from treatment, the incidence and type of complications from stereotactic radiosurgery are a function of the type of underlying lesion and the location of the lesion within the brain. In general, the complications of stereotactic radiosurgery are divided into three categories based upon the time of onset following treatment:

  bullet Acute
  bullet Subacute
  bullet Delayed

Acute reactions — The symptoms associated with acute reactions are due to transient swelling that occurs 12 to 48 hours after therapy. One study reviewed the immediate side effects (ISE) following stereotactic treatment of 78 adult patients with a variety of intracranial lesions. ISE, defined as those occurring during and up to two weeks after therapy, developed in 35 percent. Most of the ISE (87 percent) were mild, and consisted of nausea, dizziness or vertigo, seizures, and new persistent headache. Two patients had worsening neurologic deficit and two others required hospitalization for seizure or worsening neurologic deficit.

The location of the treated lesion may impact on the incidence of posttreatment seizures. In one report, seizures following radiotherapy were more common in patients whose lesions were located in the motor cortex than elsewhere in the brain (66 versus 16 percent).

Other suggest that acute reactions are rare. In one series that included 835 consecutive patients undergoing gamma knife radiosurgery,18 (2.2 percent) had a neurologic event (new focal deficits or seizure) or death (n = 3) within seven days of treatment.

Acute reactions do not predict for the development of delayed side effects. Routine administration of short duration steroids around the time of radiosurgery may prevent or delay the clinical signs.

Subacute reactions — Subacute reactions occur 3 to 10 months following therapy (later than the subacute reactions following conventionally fractionated radiotherapy) and may be reversible, or progress to permanent sequelae. These are probably due to tumor swelling from treatment and associated edema in the surrounding normal parenchyma. This tumor swelling is indicative of radiation-induced damage and it has not been reported following conventionally-fractionated radiotherapy. Tumor shrinkage occurs later, with subsidence of the surrounding edema, and this phenomenon may therefore be regarded (paradoxically) as a good prognostic sign. Contrast enhancement in the tumor perimeter, as defined by cranial magnetic resonance imaging (MRI) or computed tomography (CT) reflects a reactive response and not tumor activity.

Delayed reactions — Persistent clinical neurologic symptoms or signs, and MRI changes (best seen on the T2-weighted sequences) can persist beyond two years, indicating delayed damage. About one to 24 months following radiosurgery, increased T2 signal is seen in 10 to 30 percent of patients treated for arteriovenous malformation (AVM) and about 5 to 10 percent of those with benign tumors (see below).

These late normal tissue reactions (particularly permanent late sequelae) are universally referred to as "necrosis." These areas usually represent scarring or focal coagulative necrosis without mass effect. Areas of low signal with mass effect and significant surrounding edema usually indicate coagulative necrosis, and surgical decompression is occasionally needed.

Posttreatment cranial neuropathies also represent late or delayed reactions. In one series, all new or worsened deficits occurred within 28 months of treatment.

COMPLICATIONS OF RADIOSURGERY FOR PRIMARY INTRACRANIAL TUMORS — Radiosurgery is a reasonable treatment option for selected benign or low grade intracranial tumors such as meningioma or acoustic neuroma.

Meningioma — Posttherapy complications occur in less than 10 percent of patients undergoing radiosurgery for meningioma:

  bullet In a prospective series of 88 consecutive patients who underwent radiosurgery for skull base meningiomas, there was no treatment-induced visual loss, and nine patients (10 percent) developed new trigeminal neuropathy; six of these had received locoregional doses >19 Gy.

  bullet In a second report that included 107 patients with 118 meningiomas (54 percent in the skull base), worsening symptomatic peritumoral edema without tumor growth followed treatment in 1 of 49 (2 percent) skull-base tumors and in 4 of 39 (10 percent) non-basal tumors.

Although rare, secondary brain tumors have been reported following radiosurgery for meningioma

Acoustic neuroma — Radiosurgery is a reasonable treatment option for selected patients with smaller tumors (<3 cm) or for patients with enlarging tumors who are not candidates for surgery. After radiosurgery for acoustic neuromas, hearing loss, and facial or trigeminal nerve dysfunction are significant neurologic complications.

The incidence of cranial nerve complications after radiosurgery is a function of dose, with the risk being highest at tumor margin doses greater than or equal to18 Gy. This was illustrated in a prospective study in which 40 consecutive patients were treated with standard tumor margin doses of 20, 18, and 16 Gy for tumor diameters of 2 cm or less, 2.1 to 3 cm, and 3.1 to 4 cm respectively. The subsequent 40 consecutive patients were treated with a reduced dose protocol providing 16, 14, and 12 Gy for tumor volumes of 4.2 cm3 or less, 4.2 to 14.1 cm3, and more than 14.1 cm3 respectively. The incidence of facial and trigeminal neuropathy at two years was significantly lower with the reduced dose protocol compared to the standard dose protocol (facial neuropathy, 8 versus 38 percent; trigeminal neuropathy, 15 versus 29 percent).

  Hearing loss — Variable rates of hearing loss are reported in different studies due in part to differences in delivered dose, variable rates of pretreatment hearing loss, and to the definition of hearing outcome. The following illustrates the range of findings:

  bullet In a large study with long term outcomes that included 162 patients, only 32 (20 percent) had useful hearing preoperatively, only one-half of whom maintained this level of hearing posttreatment.

  bullet Patients with pretreatment hearing deficits may improve following therapy. As an example, in one report, 38 patients were treated with stereotactic radiosurgery to a total dose of 20 Gy; 16 tumors were greater than or equal to3 cm in greatest dimension. Among the patients with diminished but clinically useful hearing pretreatment, hearing was improved in 25 percent, stable in 50 percent, and reduced in 25 percent after treatment.

  bullet Radiation dose is an important predictor of posttherapy hearing impairment. This was illustrated in a series of 29 patients with intracanalicular acoustic tumors,15 of whom had preradiosurgery hearing assessment. Long term followup demonstrated serviceable hearing preservation in all 10 patients who received doses to the tumor margin of less than or equal to14 Gy, but in only one of five who received >14 Gy

The only significant risk factor for hearing loss in a retrospective study involving 125 patients undergoing stereotactic radiosurgery for acoustic neuroma was underlying neurofibromatosis type 2 (NF2)

  Facial and trigeminal nerve dysfunction — In the study of 162 patients referred to above, the overall results relative to facial and trigeminal nerve dysfunction were:

  bullet Normal facial nerve function was preserved in 85 percent of patients who had normal function preoperatively. No patient with initial normal function developed complete facial weakness, and there was no facial sensory dysfunction in patients with intracanalicular tumors.

  bullet Trigeminal nerve function was preserved in 84 percent of patients with normal preoperative function.

However, it is important to note that several changes were made in technique during the study which diminished the rate of complications. The average dose delivered to the tumor margin was reduced and dose planning was done by MRI rather than CT. With these refinements, the rate of cranial nerve morbidity decreased significantly; the incidence of facial nerve and trigeminal nerve side effects was <7 percent for extracanalicular tumors and <2 percent for intracanalicular tumors.

Similar low rates of cranial neuropathy were observed in a prospective study of 37 consecutive patients at a mean followup period of 25 months. The actuarial rate of freedom from trigeminal nerve palsy at five years was 97 percent. No patient developed facial nerve dysfunction.

Risk factors for facial palsy and trigeminal neuropathy include the presence of NF2, higher dose of radiation to the tumor margin large transverse tumor diameter, the number of isocenters used for treatment, history of prior resection (for facial palsy), and in one series, female sex (for trigeminal neuropathy). Treatment includes supportive care and possibly nerve grafting.

COMPLICATIONS OF RADIOSURGERY FOR BRAIN METASTASES — A growing body of evidence suggests that radiosurgical treatment of single or multiple brain metastases may result in equivalent survival and fewer complications when compared to historical results from resection or whole brain radiotherapy

Acute side effects from radiosurgery occur in 10 to 20 percent of patients. They are generally mild and consist of nausea, headache, and mild seizures.

Delayed side effects, occurring several months after treatment, are uncommon. Symptoms include increased seizures, headaches, or worsening neurologic deficits, and corticosteroid treatment is usually beneficial . However, 5 to 10 percent of such patients develop severe symptomatic necrosis and may require surgical resection. In one large series of patients treated with radiosurgery for brain metastases, mass effect necessitating surgery, and treatment-related cranial neuropathies were found in 7 and 1 percent of the patients respectively. In a second report of 97 patients suffering from multiple brain metastases peritumoral edema occurred in 5 patients and necrosis in one.