Stereotactic radiosurgery and radiation therapy in British Columbia

Introduction

The ability of conventional external beam radiation therapy to control both malignant and benign lesions may be limited by the radiation dose that can be administered, which, in turn, is limited by the tolerance of the volume of normal tissue that is also irradiated. Stereotactic irradiation attempts to overcome these limitations through the accurate delivery of irradiation to targets precisely localized in three dimensions.[1]

Stereotactic irradiation differs from external beam radiation therapy primarily in the dimensions of tissue irradiated. While targets irradiated with external beam radiation therapy are never less than 5 cm and range up to 40 cm or more in size, with stereotactic irradiation, targets treated almost always have a maximum dimension of less than 4 cm. The treatment of small targets is achieved by using special small apertures to restrict radiation beams. The apertures are generally circular but may be a different shape when lesions are not spherical. Conventional external beam radiation therapy frequently includes a significant volume of surrounding normal tissue in the treatment volume. Conversely, with stereotactic irradiation, restricted apertures and the specialized use of multiple radiation beams enable the target volume to be conformal to the lesion.

In stereotactic irradiation, the lesion to be treated must be localized to within 1 mm with a suitable imaging procedure, specifically CT scanning and, sometimes, digital subtraction angiography and MRI, depending on the lesion to be treated; immobilization during both imaging and treatment is required. To achieve this level of accuracy, the treatment is currently limited almost entirely to intracranial lesions, which are subject to little or no internal motion. The head is immobilized with a device that can be rigidly fixed to the couch for both imaging and treatment. In addition, a box is attached to define a three-dimensional coordinate system.

Stereotactic radiosurgery

The term stereotactic radiosurgery refers to stereotactic irradiation delivered in a single session or fraction. It is not a surgical procedure as understood in the conventional sense. There is no general anesthetic and no incision is made to the head. However, stereotactic radiosurgery may achieve similar results as a classical surgical procedure in that a lesion is targeted and treated in one sitting, although the actual eradication usually occurs in a delayed fashion. Thus evolved the concept of high-dose radiation therapy as a surgical event: radiosurgery. Stereotactic radiosurgery is often referred to as laser surgery by patients and the popular media, but it is X-rays, photons of a much higher energy than is used in lasers, that are the weapons that attack the lesion.

Two technical feats create the foundation for stereotactic radiosurgery. The first is the ability to precisely target intracranial lesions with an accuracy of ± 1 mm. This is achieved with the application of a fixed stereotactic head frame (Figure 1), a well-established neurosurgical technique. The second is the ability, through careful computerized treatment planning (Figure 2), to deliver a high dose of radiation to a volume that conforms tightly to a target with near exclusion of the surrounding brain tissue. Combining these two technologies has allowed stereotactic radiosurgery to reach its present success.

Although there are no randomized studies comparing stereotactic radiosurgery to conventional microsurgery, it is currently accepted that radiosurgery provides an excellent management option for cerebral arteriovenous malformations, selected metastatic tumors, and acoustic neuromas. Acknowledging some opinion to the contrary, the gold standard treatment for all three of these diseases remains microsurgery. However, there are a number of variables that can make stereotactic radiosurgery a better option, including poor general medical health, lesions in areas of the brain that are essential for neurological function, and strong patient preference.

The benefits of stereotactic radiosurgery include its performance in a day-care setting, the avoidance of a general anesthetic, and the absence of physical manipulation of the head or brain apart from the application of the frame. The risks are twofold. First, normal tissue complications due to irradiation can occur. Second, the effect of treatment may be delayed. For example, in the case of arteriovenous malformations, it can take up to 3 years for the blood vessels to completely occlude, and thus for the lesion to be obliterated. Although radiosurgery leads to complete obliteration in 65% to 90% of cases, until such obliteration occurs, the patient retains a significant risk of bleeding. Thus a patient may undergo treatment only to find it has failed some years later. In contrast, microsurgery presents more “up front” risk. However, with the avoidance of perioperative complications, following surgery the patient can generally expect to leave the hospital free of the brain disease and its attendant complications.

A wide range of intracranial pathologies have been treated with radiosurgery.[1] This includes malignant gliomas, meningiomas, cavernous angiomas, arteriovenous fistulas, glomus tumors, pituitary adenomas, craniopharyngiomas, primitive neuro-ectodermal tumors, various nerve sheath tumors, developmental venous anomalies, hemangioblastomas, and low-grade gliomas. Trigeminal neuralgia, thalamic pain syndromes, Parkinson’s disease, and epilepsy have also been managed with stereotactic radiosurgery. However, like many new, seemingly low-risk treatments, the merits of application remain to be seen. Although the literature is replete with reports of radiosurgical use, firm evidence of its efficacy in the treatment of various diseases and tumors is more difficult to find. Suffice it to say that this technology has a significant role in the definitive treatment for a variety of neurologic disorders, arteriovenous malformations, brain metastases, and acoustic neuromas among them. But its appropriate application in many other instances is not yet proven.

Stereotactic radiosurgery became available to British Columbians in 1997. It has led to better management of many neurologic disorders, several of which were previously considered not treatable or referred elsewhere in North America for definitive care. It is anticipated that the current use of the technology will grow in the near future.

Stereotactic radiation therapy

Conventional external beam radiation therapy is delivered using fractionation, in which treatment is delivered in daily fractions over a period of several weeks, a technique well known to protect normal tissues from radiation damage. In stereotactic radiosurgery, sparing of normal tissue is achieved by the rapid dose fall-off and conformality of the irradiated volume to the lesion. Nevertheless, even when using stereotactic technique, fractionation holds appeal for lesions intimately associated with particularly radiation-sensitive normal structures like the optic chiasm, and for some neoplastic lesions that are larger than 25 mm in diameter and/or are in the growing brain of a young child. Although the fixation of a stereotactic head ring used in stereotactic radiosurgery confers accuracy, it also presents one of the major limitations of the technique, since the ring is generally only left in place for a period of less than 24 hours. To allow fractionation of stereotactic irradiation, several devices that provide a relocatable coordinate system have been developed.[2,3] Generally, these are based on mask and/or bite block systems, which are associated with a slight decrease in accuracy in target localization (Figure 3). By convention, fractionated stereotactic irradiation is termed stereotactic radiation therapy. The role that stereotactic radiation therapy may play remains the subject of ongoing study, and is discussed below.

Stereotactic irradiation technologies

Stereotactic irradiation may be delivered using either protons or photons. Currently, the only two centres capable of stereotactic proton irradiation in North America are in Boston[4] and Loma Linda.[5] Although proton beams offer some advantage in dose reduction at depths greater than the target, the prohibitive cost of a suitable clinical facility precludes their use in all but a few centres. More commonly, stereotactic irradiation is delivered by high-energy photons, either from a purpose-built, commercial unit using 201 individual cobalt-60 sources, which is marketed as the Gamma Knife (Elekta Medical)[6] or from a linear accelerator (linac),[7] like the one used to administer stereotactic radiosurgery and stereotactic radiation therapy at the British Columbia Cancer Agency. Although the initial cost is similar for both, the former is a single-purpose unit restricted to circular apertures less than 18 mm in diameter, and it cannot be used to deliver stereotactic radiation therapy. Since linacs are widely available and used in external beam radiation therapy, they provide the most flexible alternative. Linac stereotactic treatment is usually delivered through multiple, non-coplanar arcs with beam entry spread over the superior part of the head, which ensures that the dose to surrounding tissue is minimized. Although there has been controversy regarding the relative merits of the two photon stereotactic radiosurgery technologies,[8,9] there is no convincing evidence that one is superior to the other. Irrespective of the technology employed, both stereotactic radiosurgery and stereotactic radiation therapy require the diligent efforts of health care professionals from radiation oncology, neurosurgery, neuroradiology, medical physics, and radiation therapy to ensure appropriate patient selection and accuracy in imaging, treatment planning, and treatment delivery.

Future developments

An important area for development in stereotactic photon irradiation lies in stereotactic radiation therapy for both intracranial and extracranial lesions. Although the initial focus has been on intracranial and skull base tumors,[10] devices to enable immobilization and stereotactic localization of head and neck[11] and other extracranial lesions[12] have been developed, but clinical experience with these is still in its infancy. Recently, computer-controlled systems for accurate frameless stereotactic localization and treatment have been developed;[13] work continues to confirm whether these systems possess sufficient accuracy for stereotactic irradiation. Treatment of all sites will be facilitated by the advent of computer-controlled beam-shaping systems, including micromultileaf collimators, dynamic collimation, and intensity-modulated radiotherapy,[14] and by treatment planning software with complex algorithms that optimize radiation dose delivery to conform treatment to irregular target lesions.[15]

Since the physical properties of stereotactic irradiation are already excellent, future efforts should also be focused on potential clinical opportunities. The first is the prospect of escalation of radiation dose. Tumors for which this might be of benefit would be those with a predominance of local failure after conventional radiotherapy, a low metastatic potential, and evidence in the literature for a radiation dose-response relationship (for example, locally advanced nasopharyngeal carcinomas, paranasal sinus tumors, chordomas, and chondrosarcomas arising from the skull base). The ability of stereotactic radiation therapy to conform to the target volume is significant, since these tumors are often located close to radiation-sensitive critical structures, such as the optic apparatus and the brain stem. The second clinical opportunity is the ability of stereotactic radiation therapy to reduce integral radiation dose to surrounding normal tissues when conventional radiation doses are given, relative to external beam radiation therapy; this should minimize the probability of long-term sequelae. Stereotactic radiation therapy may be beneficial in young adults with small benign tumors such as pituitary adenomas or craniopharyngiomas, since the long life expectancy that many of these patients enjoy is associated with a significant lifetime risk of developing radiation-related neuropsychological effects. In this respect, stereotactic radiation therapy may be of particular benefit in children, in whom a developing central nervous system is particularly sensitive to the long-term effects of irradiation. An additional benefit may be a decrease in radiation-induced second malignancy, especially in those with a known predisposition to this, such as retinoblastoma or Ewing’s sarcoma.

For stereotactic radiation therapy, studies are required to compare competing technologies with respect to physical benefits, ease of delivery, and costs. However, perhaps the greatest future challenges lie in the determination of which clinical settings are appropriate for both stereotactic radiosurgery and stereotactic radiation therapy, and in the establishment and completion of prospective clinical trials.

UBC’s Stereotactic Radiosurgery/Radiotherapy Program

The Stereotactic Radiosurgery/Radiotherapy Program is a joint venture of the Radiation Therapy Program at the British Columbia Cancer Agency, Vancouver Cancer Centre, and the Division of Neurosurgery at the Vancouver General Hospital. It is overseen by the Stereotactic Radiation Therapy Operations Working Group, which consists of representatives from radiation oncology, neurosurgery, neuroradiology, medical physics, radiation therapy, and nursing. All patients to be considered for treatment are discussed by the group at the Stereotactic Radiation Therapy Disposition Conference. Table 1 summarizes the patients discussed to date; almost two-thirds of them were referred by neurosurgeons. Table 2 summarizes patients treated.

Research is important for the program. Medical physicist members of the group remain hard at work on the development and implementation of new stereotactic irradiation techniques, including the evaluation of a system to enable immobilization and location for stereotactic radiation therapy of extracranial tumors in the head and neck. Our Working Group has participated in prospective clinical trials of stereotactic irradiation within the Radiation Therapy Oncology Group in the United States, and will continue to do so.

Conclusions

The UBC provincial stereotactic radiosurgery/stereotactic radiation therapy program is available to accept referrals of patients who might be eligible for stereotactic irradiation. Since research is an important mandate for the program, the development of new techniques and participation in prospective clinical trials are both important areas of activity.

Table 1. Patients presented at UBC Stereotactic Radiation Therapy Disposition Conference (as of 7 March 2001)

Table 2. Patients treated at UBC Stereotactic Radiosurgery/Stereotactic Radiation Therapy program. 

Michael R. McKenzie, MD, FRCPC, Roy Ma, MD, FRCPC, Brenda Clark, PhD, and Brian Toyota, MD, FRCSC

Dr McKenzie is a clinical associate professor in the Division of Radiation Oncology at the University of British Columbia and practises as a radiation oncologist at the British Columbia Cancer Agency, Vancouver Cancer Centre. Dr Ma is a clinical assistant professor in the Division of Radiation Oncology at UBC, chairs the British Columbia Cancer Agency’s Neurooncology Tumour Site Group, and practises as a radiation oncologist at the British Columbia Cancer Agency, Vancouver Cancer Centre. Dr Clark is an adjunct professor in the Department of Physics and Astronomy at UBC and practises as chief physicist at the British Columbia Cancer Agency, Vancouver Cancer Centre. Dr Toyota is an assistant professor in the Division of Neurosurgery at UBC and practises as a neurosurgeon at Vancouver General Hospital.