Cyberknife Radiosurgery for Trigeminal Neuralgia

Background: We present preliminary results using Cyberknife radiosurgery as a noninvasive treatment for trigeminal neuralgia (TN). Methods: Ten patients with medically refractory TN who were deemed unsuitable for conventional surgery underwent Cyberknife radiosurgery using CT cisternography for localization. Results: Pain relief was achieved in 7 patients, in 5 of them within 24–72 h after irradiation. Conclusion: Cyberknife radiosurgery can achieve early-onset pain relief in a subset of TN patients. Improvements using this technique include the absence of a stereotactic ring, potentially improved targeting accuracy produced by CT cisternography and improved dose homogeneity.


Introduction
The median time to achieve more than 50% pain relief after gamma knife radiosurgery for trigeminal neuralgia (TN) was about 2 months in one of the largest series published [1]. Acutely ill patients are rarely treated with gamma knife radiosurgery because immediate pain relief can be achieved with more invasive treatments, including microvascular decompression, radiofrequency rhizotomy and balloon compression. A much shorter delay in the development of analgesia has been observed in a small cohort of patients undergoing Cyberknife radiosurgery for TN. The Cyberknife exploits the highly maneuverable robotic arm of an image-guided LINAC to deliver conformal irradiation without a rigid frame. A combination of factors including potentially improved targeting accuracy due to CT cisternography, improved treatment planning due to the absence of the stereotactic ring, conformal irradiation and treatment of an extended length of the nerve could be responsible for such an early response to treatment.

Patient Selection
Cyberknife radiosurgery was offered to patients with medically refractory TN who failed or refused surgery or were not suitable candidates for invasive intervention due to age or medical contraindications to surgery.

CT Cisternography
To obtain an accurate distortion-free localization of the trigeminal nerve, a CT cisternography was performed by injecting 5 ml of Omnipaque-300 into the thecal sac and keeping the patient in Trendelenburg's position for about 30 min. A thin-section CT scan (175 slices, thickness 1.25 mm) was made through the entire head, showing the anatomy of the basal cisterns.

Treatment Planning
The CT images were networked to the Cyberknife workstation, where the trigeminal nerve was outlined. The most proximal point of the nerve identified for the purposes of treatment planning was 3 mm away from the brainstem. The 80% isodose line was prescribed in a conformal fashion to an 8-mm length of the nerve, sparing the proximal 3 mm ( fig. 1).

Image-Guided Radiosurgery
A compact 6-MV X-ray LINAC was accurately positioned by a robotic arm that can move and point the LINAC with six degrees of freedom [2,3]. Two X-ray imaging devices based on amorphous silicon detectors were positioned on either side of the patient and acquired real-time digital radiographs of the skull at repeated intervals during treatment. The images were automatically registered to digitally reconstructed radiographs derived from the treatment planning CT. This registration process allowed the position of the skull (and thus the treatment site) to be translated to the coordinate frame of the LINAC. A control loop between the imaging system and the robotic arm adjusted the pointing of the LINAC therapeutic beam to the observed position of the treatment anatomy (target). If the patient moved, the change was detected during the next imaging cycle and the beam was adjusted and realigned with the target.

Results
Preliminary results from a cohort of 10 patients undergoing Cyberknife radiosurgery for TN showed that pain relief was achieved in 5 patients within the first 72 h after the treatment. The average dose delivered at the 80% isodose line was 64.3 Gy. These 5 patients received doses between 66 and 70 Gy. Three patients reported overnight onset of pain relief and maximal effect within 48 h. One patient had onset of pain relief after 48 h with complete relief within 72 h, and another had onset of pain relief after 72 h and complete relief within 7 days after the treatment. Four of these patients are now pain free and medication free after a 6-month follow-up period. One patient was pain free for 2 months, then developed bothersome dysesthesias.
The next 5 patients were treated with a reduced 80% isodose of 60-64 Gy to avoid similar complications. Two of these patients developed a response to radiosurgery after about 2 months. Three have not yet developed pain relief after 3 months.

Discussion
There are several possible explanations for the fast onset of pain relief after Cyberknife radiosurgery. First, the targeting technique based on positive contrast CT cisternography could be more accurate than conventional MR-based targeting, due to the lack of image distortion. Second, the absence of a frame avoids any restriction to the treatment planning and delivery of radiation. Third, improved dose homogeneity allows irradiation of an extended length of the nerve.
The clinically relevant accuracy of the Cyberknife radiosurgery system is based on the accuracy of the beam delivery, which is a combination of the robot and the camera image tracking system, and the target localization accuracy, which is a combination of CT imaging and treatment planning. A phantom study revealed an average radial error of 1.14 B 0.3 mm using a CT slice thickness of 1.25 mm [4]. In contrast, MR-based stereotactic systems can produce a localization error of up to 5 mm [5]. An additional factor improving the radiation delivery to the nerve is the treatment conformality of Cyberknife radiosurgery. To treat nonspherical targets, isocentric radiosurgical methods rely on multiple overlapping spherical dose volumes, a method which results in target dose heterogeneity. The elongated shape of the trigeminal nerve is sometimes suboptimally treated with a single spherical irradiation and may require repeated irradiation using a second isocenter, usually located more anteriorly along the nerve. This approach may increase morbidity [6]. The conformal irradiation provided by the Cyberknife is especially convenient for the treatment of an elongated structure such as the TN because it can produce homogeneous irradiation along an extensive length of the nerve.

Conclusion
Cyberknife radiosurgery can induce early-onset pain relief in a subset of TN patients. A combination of conformal irradiation and increased targeting accuracy due to CT cisternography could explain this interesting phenomenon. Larger patient samples are necessary to validate these findings.