Transcript
Stereotactic radiosurgery for trigeminal neuralgia has really become a very well accepted treatment modality and this technique of course, was pioneered by our colleagues in the Gamma Knife community. But the introduction of hardware and methods allowing for the use of LINAC radiosurgery for this application has been a more recent development. We've used the LINAC method over the last six years or so and the results from our group using frame-based SRS for trigeminal neuralgia treatment really mirrors the best available reports from the Gamma Knife community. So from the standpoint of the frame-based methods, I think that the Novalis LINAC device is equivalent essentially to Gamma Knife radiosurgery.
But the new frontier is IGRS, and image-guided methods have resulted in a large paradigm shift in the way that we conceive of radiosurgery treatments. And there are a number of different devices now that have been available for this, including the CyberKnife device, the Novalis device as well as the newer concept of onboard imaging as exemplified by Trilogy and Novalis Tx.
Now, the considerations for precision IGRS for trigeminal neuralgia revolve around a comprehensive quality control management that my colleague spoke about earlier. And for this issue, we have to understand that essentially, the imaging, fiducialization, dose planning, the geometric accuracy of the gantry, and the LINAC dose calibration is identical to the methods that we use for frame-based treatments. The issue here lies entirely upon the issue of patient immobilization and patient positioning, and whether these components are adequate for trigeminal neuralgia treatment. And on the basis of our quality control analysis, it does appear to be adequate.
But of course, the phantom testing is not treating a patient. And eventually, we have to see whether these methods are applicable to an actual patient who's breathing and in some cases squirming. There are patients that have tremors and there are patients that have habitus issues such as, morbid obesity or, you know, thoracic kyphosis that may make them difficult to treat.
Now, our colleagues in the CyberKnife groups have reported a multicenter trial involving Stanford, Colorado, at Boulder as well as Carlo Besta in Milan, and they recently reported their results in the Neurosurgery Red Journal a couple of months ago. But what's interesting in this IGRS paper is how much they departed from the relatively standardized techniques that we use for treatment of radiosurgery trigeminal neuralgia. First of all, they radiated much longer lengths of nerve and they typically used either 5- or 7-millimeter cones. As you can see, their target was placed fairly far interiorly virtually into Meckel's cave. So therefore, the targeted volume is not necessarily what we would do using classic radiosurgery methods which is a purely retrogasserian lesioning, but rather this is something that radiates probably substantial amounts of the gasserian ganglion.
And while they had very rapid relief of pain and a fairly high pain-free outcome, this was counter-weighted by substantial risks of complication in their series. So out of 95 patients that they treated, they counted approximately 18% complication rate, but serious complications included diplopia, limb weakness, and these are essentially complications that I've not encountered up to this time in my practice now treating over 250 patients with the radiosurgery technique. In addition, their hypoesthetic complications were very high, numbering approximately 45% and in our series our complication rate as far as hypoesthesia of any severity at all is somewhere between 10% and 15%, and they reported about 12% severe hypoesthesia. So at least using this method, the complication rate compares unfavorably to RF, percutaneous glycerol rhizolysis, let alone frame-based SRS.
So we commissioned ExacTrac, actually version 5 in late 2006 and the cranial frameless package was installed in mid-2007 corresponding with the final release of Novalis Robotics and then we began IGRS treatments for trigeminal neuralgia in mid to late 2007. And the selection criteria we've reported before, but generally speaking, unilateral face pain, patients with a prior history of injury to the nerve or post-herpetic neuralgia, or symptoms consistent with a typical facial pain were excluded from consideration for treatment. All of the 15 patients were either first-time patients or had recurrence of facial pain after a previous successful radiosurgery.
Oops, wrong way. Our method has been described before. We use a high-resolution MRI imaging, employing 3d-SPGR and 3d-FIESTA sequences using a 512x512 matrix, and 1-millimeter slice thickness. We use the BrainLAB frameless stereotactic mask immobilizer which is a bivalve mask as opposed to univalve style mask. CT scan, following fitting of the mask was accomplished using GE LightSpeed, 16RT with 512x512 matrix, and 1.25-millimeter-thick slices with the BrainLAB head and neck fiducial localizer.
Now as far as the dose planning, I like to use a 4-millimeter circular collimator against 7 circular non-coplanar arcs and 90 Gy to the isocenter. I've moved where I usually treat to the distal cisternal segment of the trigeminal nerve. We had previously analyzed our data and found essentially no difference whether the isocenter is placed more proximally or more distally in regards to the success of the radiosurgery using this technique at 90 Gy. Now out of the 15 patients, the median age was 63. There were six female, nine males. Again, 13 were initial treatments and 2 were for recurrence of pain following initially successful SRS. Twelve of these patients had so called idiopathic trigeminal neuralgia, but three were associated multiple sclerosis.
Following treatment, the patients underwent follow-up examinations at four weeks following treatment and then every two to three months until an effect could be ascertained. A standard battery was administered at each of these follow-up visits including a Barrow Neurological Institute pain scale score.
So this is the only data I have to present which is the results. The Level I patients are essentially patients that are pain-free, off of medication, and we achieved 27%. Level II is pain-free or rather, very minimal pain not requiring medications, 13%. Level IIIa is patients who are pain-free, but requiring medications, 27%. And level IIIb are patients who feel that although they do still have pain, they've had substantial meaningful reduction of pain and do not require further treatment too. Three patients failed and one of these patients had multiple sclerosis. The other two patients were extremely difficult cases which I attempted to salvage using glycerol rhizolysis in one, which resulted in some slight reduction in pain and then he was treated again with SRS, and now has a relatively good result. The last of the 15, I've performed 2 additional glycerol rhizolysis on this patient without any improvement in his pain. So I believe that he's certainly one of these terribly refractive patients.
As far as complications, none yet but the follow-up is relatively short. So in conclusion, we believe that IGRS with Novalis ExacTrac 6D is a promising method to achieve high precision radiosurgery. Our preliminary results with IGRS appear to at present closely mirror results with frame-based methods, and thus far, we have not encountered any complications from treatment yet. One remark as well, BNI 3b results and better appear to be close what we've achieved with frame-based methods. We have had fewer BNI level 1 results than would be expected, but this is likely to change with longer follow-up. And further patient accrual is necessary to make definitive comparisons with frame-based methods. Thank you very much.
But the new frontier is IGRS, and image-guided methods have resulted in a large paradigm shift in the way that we conceive of radiosurgery treatments. And there are a number of different devices now that have been available for this, including the CyberKnife device, the Novalis device as well as the newer concept of onboard imaging as exemplified by Trilogy and Novalis Tx.
Now, the considerations for precision IGRS for trigeminal neuralgia revolve around a comprehensive quality control management that my colleague spoke about earlier. And for this issue, we have to understand that essentially, the imaging, fiducialization, dose planning, the geometric accuracy of the gantry, and the LINAC dose calibration is identical to the methods that we use for frame-based treatments. The issue here lies entirely upon the issue of patient immobilization and patient positioning, and whether these components are adequate for trigeminal neuralgia treatment. And on the basis of our quality control analysis, it does appear to be adequate.
But of course, the phantom testing is not treating a patient. And eventually, we have to see whether these methods are applicable to an actual patient who's breathing and in some cases squirming. There are patients that have tremors and there are patients that have habitus issues such as, morbid obesity or, you know, thoracic kyphosis that may make them difficult to treat.
Now, our colleagues in the CyberKnife groups have reported a multicenter trial involving Stanford, Colorado, at Boulder as well as Carlo Besta in Milan, and they recently reported their results in the Neurosurgery Red Journal a couple of months ago. But what's interesting in this IGRS paper is how much they departed from the relatively standardized techniques that we use for treatment of radiosurgery trigeminal neuralgia. First of all, they radiated much longer lengths of nerve and they typically used either 5- or 7-millimeter cones. As you can see, their target was placed fairly far interiorly virtually into Meckel's cave. So therefore, the targeted volume is not necessarily what we would do using classic radiosurgery methods which is a purely retrogasserian lesioning, but rather this is something that radiates probably substantial amounts of the gasserian ganglion.
And while they had very rapid relief of pain and a fairly high pain-free outcome, this was counter-weighted by substantial risks of complication in their series. So out of 95 patients that they treated, they counted approximately 18% complication rate, but serious complications included diplopia, limb weakness, and these are essentially complications that I've not encountered up to this time in my practice now treating over 250 patients with the radiosurgery technique. In addition, their hypoesthetic complications were very high, numbering approximately 45% and in our series our complication rate as far as hypoesthesia of any severity at all is somewhere between 10% and 15%, and they reported about 12% severe hypoesthesia. So at least using this method, the complication rate compares unfavorably to RF, percutaneous glycerol rhizolysis, let alone frame-based SRS.
So we commissioned ExacTrac, actually version 5 in late 2006 and the cranial frameless package was installed in mid-2007 corresponding with the final release of Novalis Robotics and then we began IGRS treatments for trigeminal neuralgia in mid to late 2007. And the selection criteria we've reported before, but generally speaking, unilateral face pain, patients with a prior history of injury to the nerve or post-herpetic neuralgia, or symptoms consistent with a typical facial pain were excluded from consideration for treatment. All of the 15 patients were either first-time patients or had recurrence of facial pain after a previous successful radiosurgery.
Oops, wrong way. Our method has been described before. We use a high-resolution MRI imaging, employing 3d-SPGR and 3d-FIESTA sequences using a 512x512 matrix, and 1-millimeter slice thickness. We use the BrainLAB frameless stereotactic mask immobilizer which is a bivalve mask as opposed to univalve style mask. CT scan, following fitting of the mask was accomplished using GE LightSpeed, 16RT with 512x512 matrix, and 1.25-millimeter-thick slices with the BrainLAB head and neck fiducial localizer.
Now as far as the dose planning, I like to use a 4-millimeter circular collimator against 7 circular non-coplanar arcs and 90 Gy to the isocenter. I've moved where I usually treat to the distal cisternal segment of the trigeminal nerve. We had previously analyzed our data and found essentially no difference whether the isocenter is placed more proximally or more distally in regards to the success of the radiosurgery using this technique at 90 Gy. Now out of the 15 patients, the median age was 63. There were six female, nine males. Again, 13 were initial treatments and 2 were for recurrence of pain following initially successful SRS. Twelve of these patients had so called idiopathic trigeminal neuralgia, but three were associated multiple sclerosis.
Following treatment, the patients underwent follow-up examinations at four weeks following treatment and then every two to three months until an effect could be ascertained. A standard battery was administered at each of these follow-up visits including a Barrow Neurological Institute pain scale score.
So this is the only data I have to present which is the results. The Level I patients are essentially patients that are pain-free, off of medication, and we achieved 27%. Level II is pain-free or rather, very minimal pain not requiring medications, 13%. Level IIIa is patients who are pain-free, but requiring medications, 27%. And level IIIb are patients who feel that although they do still have pain, they've had substantial meaningful reduction of pain and do not require further treatment too. Three patients failed and one of these patients had multiple sclerosis. The other two patients were extremely difficult cases which I attempted to salvage using glycerol rhizolysis in one, which resulted in some slight reduction in pain and then he was treated again with SRS, and now has a relatively good result. The last of the 15, I've performed 2 additional glycerol rhizolysis on this patient without any improvement in his pain. So I believe that he's certainly one of these terribly refractive patients.
As far as complications, none yet but the follow-up is relatively short. So in conclusion, we believe that IGRS with Novalis ExacTrac 6D is a promising method to achieve high precision radiosurgery. Our preliminary results with IGRS appear to at present closely mirror results with frame-based methods, and thus far, we have not encountered any complications from treatment yet. One remark as well, BNI 3b results and better appear to be close what we've achieved with frame-based methods. We have had fewer BNI level 1 results than would be expected, but this is likely to change with longer follow-up. And further patient accrual is necessary to make definitive comparisons with frame-based methods. Thank you very much.