Disclosure
Over the last decade, the efficacy and utilization of stereotactic radiation has increased dramatically because of improvements in medical imaging, computer technology, and advanced delivery devices. As a result, stereotactic radiation has become a viable and useful primary management alternative for patients with cerebellopontine angle and/or skull base tumors, including acoustic neuromas, meningiomas, and paragangliomas. In addition, stereotactic radiation is increasingly used for secondary management of recurrent or planned residual disease, ie, in patients in whom a tumor is specifically left on cranial nerves to avoid loss of function. Contemporary neurootological/neurosurgical teams must have an understanding of this tool and use this information for the benefit of patients. This article is intended to be a concise resource for the neurootologist; it provides a basic introduction of the technology available, the applications in the management of acoustic neuromas (including the role of the neurootologist in treatment planning), and the controversies regarding the use of radiation for the management of these tumors.
In most instances, traditional external beam radiation therapy (EBRT) is generated by a photon unit or a cobalt 60 unit. The radiation beam is then delivered through a collimator, which shapes the beam. In traditional EBRT, the field or treatment area is defined by the size and shape of the collimator, and usually 2 or 3 portals or fields are used to direct the radiation beam to the tumor and the surrounding tissue. Some variation in beam intensity, location, angle, and shielding can be used to protect surrounding tissue, but, in general, the entire field receives the treatment dose. Because healthy tissues are typically more resistant to the effects of radiation, tumor cells are killed while the surrounding tissue eventually recovers. Although traditional EBRT is useful for certain tumors, in the past, results using traditional EBRT were often complicated by adverse effects associated with treatment, particularly loss of function of adjacent healthy tissues. Furthermore, some tumors were said to be resistant to radiation, often because of dose limitations of the surrounding or adjacent tissues. As a side note, meningiomas and acoustic neuromas were not treated with traditional radiation therapy because they were thought to be radiation resistant and because of their proximity and contact with the brain stem. Stereotactic radiation is the term used to define the method of delivery of a precise dose of high-energy radiation through stereotactically directed narrow beams. Lars Leksell, MD, formulated the term stereotactic radiosurgery for this method, and in the literature, stereotactic radiosurgery is the term used for single-dose stereotactic radiation treatment. Today, through the use of sophisticated imaging devices and 3-dimensional treatment-planning computers, stereotactic radiation allows much more specific targeting of a lesion, with significantly less radiation delivered to surrounding healthy tissues. Stereotactic radiation allows dynamic beam shaping and intensity modulation, providing flexibility and optimal tumor dosing. Furthermore, specialized collimators and treatment plans have been developed for a variety of unusual and rare tumors. As a consequence, much higher doses can be delivered accurately to the tumor, resulting in greater control and cure rates and decreased complications. In the past, stereotactic radiation could only be delivered in a single dose. The first step in the single-dose procedure is to attach the patient's head to a fixation head ring or stereotactic head frame, which establishes a reference frame with a coordinate system for target determination and a means of precise patient positioning. Next, a series of images are taken with the head ring in place; typically used are CT, MRI, single-photon emission computed tomography (SPECT), or positron emission tomography (PET). The images are transferred with the underlying coordinate system to the computer workstation. Each scan has specific reference coordinates attached to it. The physician, working on the virtual tumor on the computer, then prescribes an individual treatment plan by carefully outlining the lesion(s) to be treated, using the computer mouse in a paintbrush fashion. The role of the neurootologist is to analyze the cross-sectional anatomy of the scans, determine the tumor area to be treated, and note the vital or significant structures nearby that should be avoided. This may include avoidance of the facial nerve in the lateral portion of the internal auditory canal or the brain stem, for example. Those in the workstation then process the treatment plan, including the isocenters and the optimal dose to the lesion. One recent technological advance in stereotactic radiation is the development of 3-dimensional images of the tumor and surrounding tissues. Sophisticated software and workstations take 3-mm cuts from either CT or MRI scans and convert them into 3-dimensional images. Three-dimensional treatment planning achieves better results than 2-dimensional planning. It delivers a high-precision dose to the tumor with sparing of healthy tissue. Notably, continued evolution in this technology will directly translate to improvements in accuracy and predictability of 3-dimensional stereotactic radiation. Irradiation is delivered to the patient only after final verification methods have ensured the accuracy of the beam angle and dose. Final verification is performed with a target positioner, and a trial run is performed on the positioner before treating the patient. Several types of target positioners are available, including simple stereotactic hardware with radiographic film, laser-guided systems, and newer electronic detector systems. A collimator is then selected and attached to the radiation unit. In some cases, conformal blocks are placed inside the collimator to further shape the beam. Recently, disease-specific collimators and software programs have been developed; these are available for purchase by treatment facilities. Finally, the patient is placed in the radiation unit, the head frame and the patient's head are secured into position, and necessary monitors are applied. The planned radiation treatment is then administered.
Today, because of noninvasive fixation devices, single-treatment delivery of stereotactic radiation is no longer mandatory. Because the treatment plan can now be reliably duplicated day to day, multiple fractionated doses or fractionated stereotactic radiation can be delivered. For acoustic neuromas, 5-30 fractionated treatments are typically administered. The main advantage of fractionation is that it allows higher doses to be delivered to the tumor because of increased tolerance of the surrounding healthy tissues to these smaller fractionated doses. In other words, whereas single-dose stereotactic radiation takes advantage of differences in the pattern of radiation given, fractionated stereotactic radiation takes advantage of the pattern and, more importantly, of the differing radiosensitivities of healthy and surrounding tissues. Another advantage is so-called iterative treatment, meaning the shape and intensity of the treatment plan can be modified during the course of therapy. Radiation therapy planning currently takes 2 forms, beam first or dose first. Beam-first therapy means that the target volume of radiation is determined first, and then the surrounding tissue volume is planned. Also known as forward planning, this works extremely well in patients in whom the tumor has a regular or spherical shape. Alternatively, dose-first or inverse planning determines the safe dose for the surrounding healthy tissues first, and then the computer workstation determines the required beam intensity and shape for each portion of the field. Inverse planning works very well for irregularly shaped lesions and allows for modulating the intensity of treatment to the lesion. This method is often referred to as the Peacock plan or Peacock tomotherapy. Beam-first (2-dimensional and 3-dimensional planning) and dose-first (inverse planning) radiotherapy have become standard at both academic and community centers. A number of alternatives in noninvasive fixation devices are available, including frameless technology and masks/head immobilizers. Frameless technology uses implanted 2-mm gold fiducial markers, which are readily inserted around the head to provide a coordinate system. Image detectors use these markers and the patient's bony skeleton as a reference frame for localization. The computer updates the treatment plan based on this reference. Newer systems have online continuous updating of the patient's position during the treatment. Mask systems use a meshed thermotransformable material to create an individual mask molded for each patient. The patient's head is placed in a horseshoe-shaped frame, and the forehead and maxilla are secured first with snug plastic strips. The nasal bridge is then firmly secured using the mask. The mask system gives reproducible positioning with less than 1-mm variation between sessions for a cooperative patient and less than 2-mm variation for a noncooperative patient. Head immobilizers use vacuum-attached markers to secure the upper jaw and the occiput into a stable position. |
|
||||||||||||||||||||||||||||||||||||||||||
Three methods are used to deliver stereotactic radiation: (1) high-energy photon irradiation produced by linear accelerator (LINAC) systems, (2) gamma irradiation from a fixed-array cobalt 60 source, and (3) heavy charged particles including protons. All 3 systems are based on the procedures described above, ie, stereotactic reference and positioning devices, imaging, 3-dimensional target and treatment-planning computers, and delivery of the radiation with specialized collimators. With respect to the different types of irradiation energy, each has similar and predictable effects on tumors. Proton beams provide the best control of penetration depth compared to photon or gamma irradiation. LINAC systems are by far the most frequently used (67% of patients) because most radiation oncology departments either have modified existing equipment or have purchased less expensive dedicated units. Gamma knife units, which are considerably more expensive, represent most of the remainder. LINAC systems achieve radiation targeting and rapid dose fall-off by rotating the patient and the treatment unit gantry simultaneously. Specialized dynamic collimators and beam intensity modulation enable hundreds of sources to be aimed at the tumor through a series of noncoplanar arcs. Conversely, gamma knife units have 201 fixed cobalt 60 sources aimed precisely at the center of the unit; collimators are placed near the treatment unit and in a collimator helmet surrounding the patient's head. Gamma units are thought to have superior mechanical precision versus LINAC units, but, to date, this has not been demonstrated to offer a clinically meaningful advantage. While no radiation unit is entirely comfortable, gamma units are inherently less comfortable because of the unusual angle of the head during treatment. Recently, gamma knife units have been adapted for fractionated multi-dose treatments. One disadvantage to fractionated stereotactic radiation using a LINAC system or gamma knife is that multiple patient visits are required, although this provides the significant advantage of higher dosing to the tumor.
Certain terminology is used in the radiation oncology literature to denote specific target volumes for treatment. Gross tumor volume (GTV) is the term used for all known disease, including adjacent nodes, visible on CT or MRI scans. Clinical tumor volume (CTV) is the term for GTV plus the surrounding tissue that presumably harbors microscopic disease. Planning target volume (PTV) provides a margin around CTV to allow for movement and treatment setup variation. Most radiation therapists include a small additional margin around PTV to allow for machine beam characteristics. The goals of performing stereotactic radiation are to achieve the highest probability of local tumor control with the lowest achievable incidence of adverse effects, to prolong the life of the patient, and to provide the best quality of life with as few anatomic and physiologic defects as possible. Following stereotactic radiation of an acoustic neuroma, little change is detected over the first 6 months. By 12 months postradiation, follow-up MRI scans show the loss of central enhancement of the tumor, which usually indicates a favorable response. During the initial 12 months, the tumor may exhibit initial swelling or edema, but this process declines over time. These patients are usually treated with supportive measures, including steroid administration or ventriculoperitoneal shunting if indicated. By 2 years postradiation, partial involution of the tumor is often noted. Stereotactic radiation can completely eradicate the tumor, but in most patients, residual enhancing tumor is noted on an MRI scan. This residual tumor usually remains stable for long periods, and this is often reported as local control in the radiation oncology literature. Acoustic neuroma growth is controlled by 2 main mechanisms, direct cellular injury and vascular fibrosis. In the higher-dose central region, tumor histopathology has revealed necrosis, decreased tumor cell population, and fibrosis. In the lower-dose peripheral region, vascular occlusion, macrophage infiltration, fibrin deposits, and thrombus formation have been identified. In general, apoptosis is the mechanism of cellular death and tumor control.
Reports by Perez indicate a close relationship between the dose of radiation given and the probability of tumor control. The effects of radiation on most healthy tissues, including the interrelationship of total dose, fractions used, volume and function of the organ irradiated, and mechanisms of cellular repair, have been well documented. Although a number of studies have reported the radiation tolerance of healthy tissues, the data preceded 3-dimensional planning and fractionated treatments and thus must be viewed cautiously. Assuming that accurate stereotactic radiation will lead to a higher probability of tumor control is reasonable, but imprecise systems could lead to problems with necrosis of surrounding tissues. Kondziolka et al reported their results in the treatment of 162 consecutive patients with acoustic neuroma treated from 1987-1992 using single-fraction gamma knife radiation. Patients were evaluated using serial imaging tests, clinical evaluations, and a survey 5-10 years postprocedure. The average dose of radiation to the tumor margin was 16 Gy, and the mean transverse diameter of the tumor was 22 mm (range, 8-39 mm). Resection had been performed previously in 42 patients (26%); in 13 patients, the tumor represented a recurrence of disease after a previous total resection. The rate of tumor control (with no resection required) was 98%. Of the tumors, 100 (62%) became smaller, 53 (32.5%) remained unchanged in size, and 9 (5.5%) became slightly larger. Resection was performed in 4 patients (2.5%) within 4 years of radiation. These authors report hearing loss in 49% of patients, facial palsy in 21%, and trigeminal nerve problems in 27%. Of patients working at the time of treatment, 31% were no longer working after treatment. No new neurologic deficits occurred later than 28 months after treatment. Of patients in whom stereotactic radiation was the primary treatment, 95% believed it was successful. At least 1 complication was described by 36 of 115 patients (31%); 56% of complications resolved. Some of the criticisms of the report by Kondziolka et al include failure to analyze age as a variable, a lack of detail regarding tumor size and preoperative growth rates, inclusion of previously operated tumors in the study group (which underreports the frequency of facial palsy and hearing loss because they were preexisting), actual evaluation of just 38 patients 7-8 years after treatment, failure to use a validated instrument to determine health status, use of a change in size of 2 mm as a measure of outcome, and failure to mention the risk of cancer after treatment. Many of these criticisms have been addressed in the literature. Noren et al reported 254 patients (193 of whom had a unilateral tumor) who underwent single-treatment gamma radiation at Karolinska Institute. In the unilateral cases, 55% of tumors shrank, 33% were unchanged, and 12% continued to enlarge at least temporarily. Those that enlarged did so over 6-18 months posttreatment and then either shrank or stabilized. This study indicates a control rate of 94% at 1 year. Noren et al reported a 15% prevalence of facial palsy and a 33% prevalence of hearing preservation. Miller et al have reported their findings in a prospective study of 82 patients with acoustic neuroma. The first 42 patients were treated in a high-dose single-treatment protocol, and the next 40 were treated with a reduced-dose protocol. The researchers found that a tumor margin dose 18 Gy or greater is the most significant risk factor for facial and trigeminal nerve complications. Tumor margin doses of 16 Gy or less pose a significantly lower risk of permanent facial palsy. Interestingly, 2 of the patients undergoing a higher-dose protocol continued to progress and required microsurgical decompression. Flickinger et al reported similar findings; tumors treated with less than 14 Gy had 0% prevalence of facial palsy, and those treated with 16-20 Gy had an prevalence of 53%. Many patients had permanent palsies at House-Brackmann grade 5 or 6. As noted in these prior reports, unchanged tumor size was considered evidence of tumor control. Pitts and Jackler and Yamamoto et al have questioned whether this assertion is correct. These authors note that 50-60% of patients demonstrate either no growth or slow growth before treatment, and therefore no or slow growth after treatment does not necessarily represent control. The authors have performed salvage microsurgery on 1 patient following single-dose stereotactic radiation. In this previously unreported case, a large cyst developed more than 1 year after treatment. This cyst protruded from the wall of the tumor and compressed the brain stem. Histopathology of the tumor showed no specific effect from the radiation. Clearly, longer follow-up study is needed to be certain that unchanged size indeed represents long-term control. Because the brain has serial architecture, damage to even a small area could have significant repercussions. Werner-Wasik et al found that one third of patients undergoing stereotactic radiation had an immediate posttreatment adverse effect, including nausea, headache, and dizziness. Rarely, acute swelling of the tumor occurs, necessitating supportive therapies such as ventriculoperitoneal shunting, steroid administration, and seizure control. Dizziness and vertigo occurred in 4 of 12 patients with acoustic neuroma, and this complication did not appear to be related to dose or technique. Flickinger et al reported that the acoustic nerve was the most sensitive cranial nerve to radiation doses of 12-16 Gy, while the facial nerve was the least sensitive. Finally, most reports indicate that serviceable hearing is preserved in 60-65% of patients with single-dose protocols.
Fractionated stereotactic radiation for acoustic tumors developed primarily because of the incidence of trigeminal and facial nerve palsies that occurred after treatment with single-dose stereotactic radiation. Lederman et al reported no permanent facial or trigeminal nerve problems in 39 acoustic tumors managed with 20 Gy given in weekly fractions of 4-5 Gy. Among smaller tumors (<3 cm), 61% shrank in size, and the remaining 39% showed no growth over 27 months. Among larger tumors (>3 cm), 81% shrank in size, and the remainder showed no further growth. Only 1 patient had a transient facial palsy. These authors concluded that fractionated stereotactic radiation offers high control rates while avoiding the morbidity frequently observed after single-dose stereotactic radiation or microsurgery. Song and Williams reported similar data managing 31 acoustic tumors using a total dose of 25 Gy given in 5 consecutive daily fractions of 5 Gy. The tumor shrank in 29% of patients and was unchanged in 71%. No facial palsies developed, but 2 patients developed trigeminal neuropathy. Balance improved in 3 patients, was unchanged in 20, and was markedly worse in 7 patients. Of the 12 patients with serviceable hearing before treatment, 9 (75%) retained useful hearing after therapy. Of 25 patients with any hearing before treatment, 2 improved, 10 were unchanged, and 13 were worse. Although this protocol may provide good control of the acoustic neuroma, it has a much greater incidence of cranial nerve dysfunction than the protocol of Lederman et al. Poen et al reported results in 33 patients receiving 21 Gy in 3 fractions over 24 hours. Tumor control was documented over 2 years in 97% of patients. The single patient with tumor progression remains asymptomatic and does not require surgery. With this protocol, 16% of patients developed trigeminal neuropathy, and 3% developed mild facial palsy. All patients with serviceable hearing maintained it after therapy. Fractionated therapy is considered to be associated with fewer cranial nerve complications than single-dose treatment. Furthermore, the various reports tend to indicate that the use of multiple smaller-dose fractions over a longer period perhaps gives the greatest possibility of hearing preservation, avoidance of facial palsy, and tumor control. However, use of multiple-dose fractionated radiation therapy results in large areas receiving multiple low doses of radiation, which may carry a long-term risk of carcinogenesis.
Comparing stereotactic radiation with microsurgery, studies show substantially less cost for radiation treatment of acoustic tumors smaller than 3 cm in diameter and comparable results in terms of postoperative outcomes. Fractionated stereotactic radiation is a reasonable method to manage some acoustic neuromas, but patients must be willing to undergo careful follow-up care, including MRI scans over a long period. The author always recommends this treatment modality in older patients and medically infirm patients, such as those who are taking anticoagulants or have other significant illnesses. The author also recommends this treatment in only-hearing ears. In patients with serviceable hearing, fractionated stereotactic radiation is the preferred treatment, particularly in small but enlarging intracanalicular tumors, intracochlear tumors, and cerebellopontine angle tumors that are 2 cm or smaller, ie, those that barely touch the brain stem or smaller. The author currently uses 2 protocols, depending on the convenience and distance the patient lives from the facility. The first protocol uses 10 fractions for a total of 30 Gy over 2 weeks. The second protocol uses 30 fractions for a total of 54 Gy, usually over 5 weeks. The author has treated 11 patients with intracanalicular tumors less than 1.1 cm in size; 10 have had no change in hearing at 1 year, and 5 demonstrate central necrosis with shrinkage of tumor. The author has also treated 9 patients with cp angle tumor not compressing the brainstem. Three of the cp angle tumors (the larger ones of the series) demonstrated significant hearing loss. The author does not usually recommend fractionated stereotactic radiation in patients with small tumors and poor hearing, preferring the transtemporal translabyrinthine surgical approach in these individuals. Furthermore, because brainstem compression by acoustic tumor is not improved by radiation, surgery is the preferred option in these patients. However, the author uses fractionated stereotactic radiation in the management of planned residual or recurrent acoustic neuroma. Pollock et al have reported that 94% of residual tumors are controlled by single-dose stereotactic radiation. Finally, the condition of patients with significant dysequilibrium or recurrent vertigo is not improved by fractionated stereotactic radiation to the tumor and may worsen, thus this circumstance is a specific contraindication in the author's opinion. However, patients who are not candidates for fractionated stereotactic radiation should be informed of the availability of the therapy and told why they are not candidates in thephysician's opinion. In summary, patients who have serviceable hearing, no vertigo, and an acoustic tumor 2 cm in diameter or smaller are preferred candidates for this treatment. With these criteria, the author recommends fractionated stereotactic radiation as primary treatment in approximately 40% of patients. If the patient chooses to have fractionated stereotactic radiation, the author actively participates in treatment planning with the radiation oncologists and then carefully monitors a posttreatment protocol for clinical examination, repeat imaging, audiovestibular testing, and management. Although the author does not have any long-term follow-up data with fractionated stereotactic radiation, he has observed none of the acute or immediate effects that were experienced with single-dose protocols in 24 patients.
Fractionated Stereotactic Radiation for Acoustic Neuroma excerpt | |||||||||||||||||||||||||||||||||||||||||||
){kind=small}
