Advantages of radiation therapy

The indications for radiation therapy for vestibular schwannomas have evolved over the years. The initial indications for radiation therapy for vestibular schwannomas included elderly patients, patients who had significant medical conditions precluding microsurgery, or patients who refused microsurgical removal. Recently, the indications for radiation therapy have expanded to include all patients who wish to have radiosurgery or radiotherapy for their vestibular schwannoma. Although some physicians will treat all vestibular schwannomas with radiation therapy, others recommend that there should be documented tumor growth before radiosurgery or radiotherapy. Because the goal of radiation therapy is to stop tumor growth, these physicians believe that the tumor should demonstrate growth before having the risk associated with radiation therapy. Many vestibular schwannomas do not grow and, therefore, a watch-and-wait policy can be recommended before undergoing radiation therapy.

The main advantage of radiation therapy is that it is less invasive compared with microsurgery. Radiosurgery or radiotherapy is considered less invasive, as the treatment usually is performed as an outpatient procedure, or requires only a one-night hospital stay. The patient may return back to work much faster following this type of treatment when compared with microsurgery. Radiosurgery or radiotherapy often results in preservation of facial nerve function, although facial nerve paralysis can occur. The risks of significant immediate adverse effects are low. Radiation therapy offers the ability to preserve hearing in tumors whose size normally would be considered a contraindication for a hearing preservation type of microsurgery. As an example, tumors larger than 2 cm in size have a poor prognosis for hearing preservation with microsurgery. The possibility of preserving hearing can be considered with radiation for tumors larger than 2 cm. Hearing preservation after microsurgery and radiation therapy will be discussed later in this article.

Disadvantages of radiation therapy

The main disadvantage of radiation therapy for vestibular schwannoma is that the tumor is still present after treatment and, therefore, the long-term control rate is unknown. As long as the tumor is still present there is always the possibility for tumor growth. Patients treated with radiation therapy must undergo routine MRI scans for the remainder of their lives. It is known that tumors swell initially after radiation therapy and, therefore, a size limit of 2.5 to 3.0 cm is recommended as the maximum treatment size. Tumors larger than 2.5 to 3.0 cm can swell, causing the patient to have significant intracranial complications such as brainstem compression requiring medical or microsurgical intervention. Therefore, most centers will not treat patients who have tumors larger than 2.5 to 3.0 cm in size. Radiation treatment also includes a risk to the cranial nerve’s seventh and eighth complexes. This risk includes partial or complete loss of hearing. Most studies have demonstrated that hearing may be preserved in the immediate months following radiation treatment; however, there is a definite decrease in the rate of hearing preservation the longer the patient is followed. Facial nerve complications can include temporary or permanent paralysis.

Facial nerve spasm is also a symptom that is associated with postradiation treatment. Patients can have significant hemifacial spasm that can be quite disabling. In some cases, the hemifacial spasm is severe enough to warrant microsurgical excision of the tumor. Botox therapy also may be used to treat the hemifacial spasm. New-onset or worsening preexisting dizziness or ataxia may develop following radiation treatment. Vestibular rehabilitation with physical therapy may help in some cases, but in other cases, the dizziness or ataxia can be so severe that the patient is at significant risk of falls. Two percent to 10% of patients treated with radiation therapy have tumors that continue to grow and that may require microsurgical treatment. Microsurgical treatment may consist of insertion of a ventricular peritoneal shunt for hydrocephalus or microsurgical excision of the tumor.

The long-term effects of radiation therapy for vestibular schwannomas are not known. The earliest reported series from within the United States used a higher dose of radiation to treat vestibular schwannomas than is used currently. This higher rate of radiation was associated with a higher rate of radiation-induced complications; therefore the total dose to the tumor has been reduced over the past 10 years. The long-term effect of lowering the treatment dose with respect to tumor control will be assessed only with time. There are very few reports on the long-term effects after 15 years from stereotactic radiation treatment. Radiation poses the risk of possible malignant transformation of the tumor or the risk of inducing additional tumor formation within the radiation field. This risk of malignancy associated with stereotactic radiation has been estimated to be approximately 1%. More information regarding malignancy risk is available elsewhere in this issue. Other radiation treatment modalities have been associated with an increase incidence of tumor formation 15 to 30 years after treatment. The risk of subsequent tumor formation is thought to be higher for younger patients, as they have a longer life expectancy following radiation treatment and therefore have more time to develop additional tumors. Meningioma formation and vestibular schwannoma have been associated in patients who have experienced external beam radiation therapy 15 to 30 years before the presentation and diagnosis of these tumors.

Disadvantages of radiation therapy

The main disadvantage of radiation therapy for vestibular schwannoma is that the tumor is still present after treatment and, therefore, the long-term control rate is unknown. As long as the tumor is still present there is always the possibility for tumor growth. Patients treated with radiation therapy must undergo routine MRI scans for the remainder of their lives. It is known that tumors swell initially after radiation therapy and, therefore, a size limit of 2.5 to 3.0 cm is recommended as the maximum treatment size. Tumors larger than 2.5 to 3.0 cm can swell, causing the patient to have significant intracranial complications such as brainstem compression requiring medical or microsurgical intervention. Therefore, most centers will not treat patients who have tumors larger than 2.5 to 3.0 cm in size. Radiation treatment also includes a risk to the cranial nerve’s seventh and eighth complexes. This risk includes partial or complete loss of hearing. Most studies have demonstrated that hearing may be preserved in the immediate months following radiation treatment; however, there is a definite decrease in the rate of hearing preservation the longer the patient is followed. Facial nerve complications can include temporary or permanent paralysis.

Facial nerve spasm is also a symptom that is associated with postradiation treatment. Patients can have significant hemifacial spasm that can be quite disabling. In some cases, the hemifacial spasm is severe enough to warrant microsurgical excision of the tumor. Botox therapy also may be used to treat the hemifacial spasm. New-onset or worsening preexisting dizziness or ataxia may develop following radiation treatment. Vestibular rehabilitation with physical therapy may help in some cases, but in other cases, the dizziness or ataxia can be so severe that the patient is at significant risk of falls. Two percent to 10% of patients treated with radiation therapy have tumors that continue to grow and that may require microsurgical treatment. Microsurgical treatment may consist of insertion of a ventricular peritoneal shunt for hydrocephalus or microsurgical excision of the tumor.

The long-term effects of radiation therapy for vestibular schwannomas are not known. The earliest reported series from within the United States used a higher dose of radiation to treat vestibular schwannomas than is used currently. This higher rate of radiation was associated with a higher rate of radiation-induced complications; therefore the total dose to the tumor has been reduced over the past 10 years. The long-term effect of lowering the treatment dose with respect to tumor control will be assessed only with time. There are very few reports on the long-term effects after 15 years from stereotactic radiation treatment. Radiation poses the risk of possible malignant transformation of the tumor or the risk of inducing additional tumor formation within the radiation field. This risk of malignancy associated with stereotactic radiation has been estimated to be approximately 1%. More information regarding malignancy risk is available elsewhere in this issue. Other radiation treatment modalities have been associated with an increase incidence of tumor formation 15 to 30 years after treatment. The risk of subsequent tumor formation is thought to be higher for younger patients, as they have a longer life expectancy following radiation treatment and therefore have more time to develop additional tumors. Meningioma formation and vestibular schwannoma have been associated in patients who have experienced external beam radiation therapy 15 to 30 years before the presentation and diagnosis of these tumors.

Tumor changes after radiation

There are consistent changes that occur following radiation therapy for vestibular schwannomas. These changes include an increase in size of the tumor 6 to 9 months after treatment and loss of central MRI enhancement. Pollock and colleagues found in 208 patients that the median time for tumor enlargement was 9 months. The median volume was increased by 75%. A loss of MRI central enhancement was noted in 93% of tumors at the time of tumor expansion. The increase in size of the tumor is presumed to be caused by swelling of tumor tissue. The tumors typically increase in size 6 to 12 months following treatment and then decrease in size over the 12 to 24 months following treatment. Reduction of MRI signal intensity and the time it takes for the tumor to reach maximum swelling following treatment have been associated with the total tumor dose. The higher tumor dose is associated with a more rapid swelling and more central MRI changes.

Pollock describes three types of growth patterns that may occur following stereotactic radiosurgery for vestibular schwannomas. Type 1 is seen most commonly. The vestibular schwannoma usually will enlarge by several millimeters within 9 to 12 months after stereotactic radiotherapy. This enlargement is followed by a volume reduction that reverts back to the initial tumor size. The type 2 pattern includes tumors that enlarge and remain larger than the size before radiosurgery. This occurs in approximately 30% of cases. Although these tumors may be larger, they do not cause any additional symptoms. The type 3 pattern consists of vestibular schwannomas that progressively grow in serial imaging. These are usually the tumors that require treatment when symptoms change or develop.

Long-term follow-up of type 1 tumors reveals that they are very stable. The type 2 tumors require long-term follow-up, because these tumors may continue to grow and fall into the type 3 category. It is possible that the increase in size and stabilization of type 2 tumors may represent the natural history of the benign tumor that has spontaneous periods of growth arrest.

Tumor size may increase after radiation therapy because of three factors: (1) solid expansion of the tumor, (2) tumor necrosis, or (3) tumor cyst formation.

Tumor cyst formation may result from increased extracellular proteins that leak from the blood vessel walls in the tumor. This can result in a multiseptated cyst associated with the tumor. Cyst formation following radiation therapy is not uncommon. This theory of cyst formation is supported by the fact that cerebrospinal fluid (CSF) protein levels are higher in patients who have tumor enlargement requiring ventriculo–peritoneal (VP) shunts after radiation therapy of their vestibular schwannomas.

In the early experience of stereotactic radiation therapy for vestibular schwannomas, the swelling found after treatment was thought to represent tumor growth, indicating the radiation did not work; therefore microsurgery was undertaken for the growth. This resulted in some patients undergoing microsurgery, which was probably unnecessary. In addition, in the early use of stereotactic radiation therapy for vestibular schwannomas, larger tumors were treated. Unfortunately, many of the patients with these large tumors had normal swelling that occurred following radiation therapy, and they developed hydrocephalus or brainstem compression. This has led to size constraints for patients who are candidates for radiation therapy.