Bogdan: Hello, everyone, and welcome to a new Novalis Circle webinar focusing on clinical versatility of ExacTrac Dynamic. My name is Bogdan Valcu, I'm the director of Novalis Circle, and today I have the pleasure to welcome four distinguished speakers covering various aspects of IGRT and SGRT clinical applications. Today's webinar will focus on ExacTrac utilization for both traditional applications such as cranial or spinal radiosurgery but also cover new applications more in the conventional radiation space for the extracranial cancers. To begin, we have the pleasure to welcome Dr. Stefanie Corradini from Ludwig-Maximilians-University Hospital in Munich, Germany. Dr. Corradini will review her initial experience utilizing ExacTrac Dynamic for cranial radiosurgery.
Moving on, we have Dr. Thomas Kole from Valley Hospital in Paramus, New Jersey, who will review a more generalized clinical application for ExacTrac, focusing ultimately on new implementations for prostate SBRT treatments. We'll transition then to Dr. Joshua Silverman from NYU Langone, who will cover applications of ExacTrac in combination with Cone Beam CT for spine radiosurgery. And finally, the webinar will conclude with a lecture from Professor Mark de Ridder from UZ Brussels who will provide a clinical justification for the need of not only SGRT but also IGRT monitoring for patients with breast cancer.
As you may have noticed by now, we are utilizing a new platform for our webinars. As such, please locate your GoToWebinar control panel for resizing your application, refreshing your application, or should you want to ask a question to any of our speakers, locate the questions interface to submit your inquiries. As this webinar precedes the ASTRO annual meeting, we look forward to welcome you to our booth as well as connect with you on any topics presented here. As always, should you choose to follow us on social media, please remember to utilize the #NovalisCircle. With that said, I'd like to turn it over to Dr. Corradini who will review her experience with ExacTrac for cranial applications.
Dr. Corradini: Thank you very much for the introduction. My name is Stefanie Corradini, I'm a radiation oncologist at LMU in Munich in Germany. And today I'm going to share our initial experience with the ExacTrac Dynamic system, which we use for patient positioning and monitoring for cranial radiosurgery. These are my disclosures. And as many of you may already know, the ExacTrac Dynamic system is an image guidance system, which is mainly used for frameless radiosurgery. And the big advantage is that you can use it also for non-coplanar treatments if you use different couch angles. It has also very high accuracy and precision as it uses X-rays for imaging. Now, the latest version, it's a seventh generation of the ExacTrac system, it's called the ExacTrac Dynamic.
And it not only has the extra information but additionally, it also has a surface guidance system and also a thermal camera. So, that's very unique for the system. Here is how the camera looks like. So, you have in the middle the projector which projects structured light on the surface of the patient, and then you have two cameras, which record just reprojections of the surface. And here below, you can see that's a very unique feature, it's an integrated thermal camera. So, here you can see how basically the images look like. This is an example of the abdomen of a patient. So, you can see here the surface data and then also the thermal information below. So, you can see the yellow and red areas which are more hot, and then the blue and green, which are colder areas.
And the system combines both these images and this is how it creates a very unique typography. So, as you can see here on the fused image, every surface point has also thermal information. That's why this is so precise. So, at LMU, we use the system for various indications, mainly for the multiple brain metastasis radiosurgery, but we also use it for fractionated treatments, which we can then do with open face masks. And this is very good for our patients as it has a high advantage. We also use the ExacTrac Dynamic spine SRS, and very recently also for the deep inspiration breath-hold module. So, this is our system. We have it on the ELEKTA platform, Versa HD, and the system is fully integrated with the Linac. It is also connected to the R&V system and the big advantage is that you also can send the shifts to do the repositioning of the patients to the robotic couch. So, in ELEKTA, that's a hexapod.
I'm going to briefly also show you the workflow which we use. So, first of all, you start with the pre-positioning of your patient. For this, you use surface and thermal cameras. So, here you see the patient and the reference which is used is from the planning CT, the outer contour, and then you use the surface information to position your patient in the isocenter. So, here is how it looks in real life. And so, you can see the patient on the couch and you can also see here, the structured light in the background. And this is how these images look like, so you have a surface image, but also the additional thermal information. So, you see the patient, it's warm and it's more yellow and red, and you see in the background, the gantry, which is all blue, so a very cold area. And here is the image.
So, you can see the reference in gray, that's our CT, the outer contour, and then you'll see the actual position of your patient when you position him on the table. And then the system calculates the deviations which you have to your isocenter, and then the Rtts consent this shifts and the patient is then automatically positioned to your isocenter. Then you can select the area of interest, which is then used during the fraction for interfraction surface monitoring. Here, you can see an example of a patient with an open face mask, and, of course, we then select the face for the surface tracking. After this, you do the X-ray verification. In the ExacTrac Dynamic, you have the stereoscopic X-rays, which are taken. This is how it looks like. You then compare this to the DRS of your treatment plan and can do then a very precise X-ray-based positioning.
So, what you can see here is the interfraction monitoring. So, basically, you have a continuous surface and thermal monitoring of your patients, which you can see here in the green line and that's the area which is selected previously, so it's the face of the patient. And then you have the X-rays which are taken. In our case, we do that every 90 degrees, so you have additionally to the X-rays, also this continuous surface guidance, which makes the treatment really safe. Here are the tolerances which we use. So, for the X-rays, usually, we do or we use 1 millimeter and from the surface, 1.5 millimeters. In regular cranial treatments, however, in single fraction radiosurgery, we use smaller tolerances, so 0.5 millimeters and 0.5 degrees. In the beginning, when the system was very new, of course, our physics team did a lot of QA and testing.
And what we also found was the head phantom, which you can fill up with warm water so we could also test how much influence does the temperature has. In this analysis by Vanessa Mendez, what we compared was the data from the surface and thermal camera to the X-rays and then we found a really good correlation, so all values were below 0.1 millimeters. And what we also analyzed was the impact of the temperature. So, you can see the values for the cold...if the phantom was filled with cold water or warm water and actually, we did not find any statistical significance difference. So, that's really good, and the correlation of the surface and the X-ray was excellent. So, why is it so important to do a very precise patient positioning in SRS?
Basically, when you have multiple lesions and you use multiple isocenters, obviously, the patient has to come back also for multiple fractions, but you can control for every misalignment for every single lesion. On the other side, if you have a treatment technique where you use only one isocenter and treat multiple lesions at the same time, of course, also small deviations can have a high impact on the dose coverage which I will show later. So, here's an example. Basically, the lesion is away from the isocenter and also very small, translational or also rotational errors can have an impact on your target coverage but you can also have a higher dose, for example, at the organ at risk. So, here's a study which we did from Max Eder of the physics team.
This is an example of a woman, she was 72 years old, had five brain metastases, and we did a non-coplanar treatment with a single isocenter. And during the treatment, she had to be repositioned after couch angles at 60 degrees and 315 degrees. What we then did is that we did a dose comparison if you use ExacTrac to correct for this misalignment and if you would not do it. And what you can see here on this dose difference map is that in very small lesions which are not close to the isocenter, you can have a very large deviation of your dose, in this case, up to 5 gray. Here you can see the DVH of this patient. And as you can see here in this example on the right side, this was the PTV 1, you can see that your target coverage can be significantly reduced if you do not correct for intrafractional misalignments.
So, we did the same analysis in 20 patients and overall 75 metastasis. We used a median of six couch angles per patient and verified 86 couch rotations. And what we found that was very interesting was that in 23%, we had to do a repositioning of the patients after it exceeded our limits. And what we also found when we compared the dose coverage, as you can see here, the red dots are if you have ExacTrac and if you correct for intrafractional misalignments and blue is if you don't do it and you can see that your dose differs much more from your plan if you do not correct for it. So, it is highly significant also for the outcome of your patients. What we also did is that we analyze the intrafractional deviations in real patients, so not only phantoms, it was a preliminary analysis of 10 patients and 76 fractions where we analyze 328 X-rays.
This was only during beam on-time...when the beam was on, so not after the couch rotations. And what we did was we compared the surface data to the X-ray data. And also here, we found an excellent correlation of the two, so it was all in the sub-millimeter range and also below 0.5 degree for all rotations. So, overall, the surface information is really reliable during the intrafractional monitoring and maybe also you can reduce the X-rays, so not every 90 degrees in future. Briefly, I also want to share our results from the Stereobrain study that was a prospective Phase II study. Here, we included patients with 4 to 10 brain metastases up to 2.5 centimeters. We excluded histology of lymphomas or germinoma or small cell lung cancer.
And overall, we did 254 lesions and 65 patients. The results are recently also published by my colleague, Maximilian Niyazi and Rafael Bodensohn. And the dose which was prescribed was for smaller lesions, 20 gray on the 80% isodose, and for the larger lesions, 18 gray on the 80% isodose. And the mean total PTV volume, so all PTVs together was 4.5 cc, and the maximum was 12.7 cc. The results are really excellent. So, the local control rate at one year was 97.5%, we had four lesions which had radiation necrosis, otherwise, we had only very low grade one or two toxicity. Overall, 27.7% develop new metastases during the follow-up. Eight of them were treated with whole-brain radiotherapy, while eight patients received a second course of SRS.
What I wanted to share with you today here is that the total treatment time because that's always very interesting, how long do these treatments last. So, the median time was 23 minutes and the maximum time was 38 minutes, which was a very complex case as you can see here, which had four metastasis. However, also the patient where we treated 12 metastasis had lasted 35 minutes. So, that's a very reasonable time for these patients and these high-precision treatments. Here's a case example. So, this was a patient with breast cancer, she had three metastases, which you can here see in the upper panel.
We treated it with 18 to 20 gray to 80% isodose. As you can see here in the lower panel, really excellent result, the metastases are nearly disappeared. So, taking together, the ExacTrac Dynamic system offers sub-millimetric and sub-degree accuracy and precision for patient setup and also for intrafractional patient monitoring. The very large largest advantage is that you can use it also during non-coplanar techniques and during the entire fraction. We found a very good correlation between the X-ray information and the surface and thermal imaging.
And overall, we found that if you do these stereotactic treatments after the couch rotations, we frequently find that patient positioning exceeds our limits and you have to do repositioning. This is usually in angles where you cannot do, for example, a cone-beam CT, so it's highly relevant and we could also show you that it has an impact on the dose coverage to your targets and it could also have an impact on your organs at risk. Thank you very much for your attention. Here are my contact details, so if you have any questions, please let me know. Thank you very much.
Bogdan: Thank you for your great review, Dr. Corradini. And let's move on now to Dr. Kole from Valley Hospital who will present a more generalized application for ExacTrac Dynamic with a focus on prostate SBRT treatments.
Dr. Kole: Thank you for giving me the opportunity to speak today. I'm going to speak to you about the clinical versatility of ExacTrac Dynamic. These are my disclosures. So, at Valley-Mount Sinai radiation oncology, we have two Varian TrueBeam linear accelerators, both fitted with the six degrees-of-freedom couches, Varian real-time imaging, and Varian RPM gating. We also have a tomotherapy unit and a Gamma Knife Icon system. So, we use our Icon system for the majority of our SRS and we are looking to ExacTrac Dynamic not to enhance our SRS capabilities, but we are really in the market at the time for a surface guidance system. After doing a bunch of research, we found that...we felt that the ExacTrac Dynamic system is going to be the most versatile for our department.
And also outside of just the surface guidance, it's going to be able to enhance almost everything we're doing on our linear accelerators. So, we ultimately decided to upgrade both of our machines with the ExacTrac Dynamic system in March and April of this year and Brainlab was really great to minimize our machine downtime. We've performed the upgrade sequentially, with these machines only being down for a week at a time. Once we were up and running, we very quickly were trained and then began treating prostate, breast, brain, and spine cases using the new system. Very quickly after seeing the versatility of the system, we expanded to other disease sites such as neck, lung, upper and lower GI, extremity sarcoma, and GYN. And as of today, about 70% of our treatments are currently using some form of ExacTrac Dynamic with all of our linear accelerator treatments.
Once we got the system, you know, our physics really did the heavy lifting of putting together workflows for every disease site based upon the primary ExacTrac Dynamic workflows. So, the primary workflows within ExacTrac Dynamic include the standard where you have a surface-based pre-positioning followed by anatomic alignment using the ExacTrac Dynamic stereoscopic X-ray alignment to the planning DRR. And then for more soft tissue aligned sites, we have the CBCT workflow where we're doing, again, the surface-based pre-positioning followed by a soft tissue CBCT alignment. Once the CBCT iso is set, ExacTrac Dynamic takes over on the stereoscopic X-ray reference, and then subsequent verification is performed to that reference.
Then we have the implanted marker workflow, we're using that for the majority of prostate cases. There, again, we have a surface-based pre-positioning, and then we go into an ExacTrac Dynamic stereoscopic X-ray fiducial match to the planning DRR. What we did is we went through for every disease site and we use different combinations of these workflows, along with different imaging parameters to create separate workflows for every site. And so, what you're looking at here is sort of the work that our physics team put together along with our clinicians. And we have the prostate and pelvis workflows here, including our SBRT and conventional prostate treatments. We have cranial workflows that include the SBRT brain treatment that is performed on our linear accelerators, along with our conventional brain and head/neck treatments.
We then also have our breast, lung, spine, and sort of miscellaneous workflows to which we use for the remaining disease sites. Once we put all these workflows together, we then started building tables of tolerances for our ExacTrac Dynamic templates. And here you see this is sort of a living document that we have in our department. It contains all of the six-dimensional tolerances for X-ray shifts as well as surface tracking for each of our disease-specific workflows. This document is always changing, and we'd be happy to share it with any site that was interested. So, I'm going to take you through some of the setups that we've been using now for different disease sites and sort of what our experience has been like with the ExacTrac Dynamic.
For all of our patients, we're using six degrees-of-freedom couch, all patients received non-coplanar X-ray imaging before all the ExacTrac treatments. For the majority of our volumetric arc therapy patients, they're going to be having periodic stereoscopy X-ray verifications of the function angles. And then for our static fields, we have MU-triggered X-ray imaging. The first operation we're doing was our conventional brain case. This is a 74-year-old gentleman with glioblastoma, he had a gross total resection, which was then followed by adjuvant chemoradiation with temozolomide. He was prescribed 60 gray in 30 fractions which was planned using RapidArc IMRT with two arcs, and standard thermoplastic immobilization and 2 millimeter PTV margins were used.
Now, given the cranial nature of the disease, we're using the standard workflow to line the cranial bony anatomy. So, the patient is first pre-positioned to the surface. We perform a CBCT on the first day of these treatments just for volume verification. Especially with glioblastoma, we tend to find times where there's been some change in volume from the time of simulation to the time of treatments so we always verify with the CBCT on the first day. The ExacTrac Dynamic then takes over where we performed stereoscopic X-ray imaging and you can see with the red where the therapists have excluded portions of the cranial anatomy from alignment. The images are fused to the treatment plan in DRR and then a subsequent stereoscopic X-ray verification is performed.
During the course of the arc, we are monitoring the surface for motion, and then a stereoscopic X-ray verification is performed prior to the next arc. We also repeat a CBCT every fifth treatment, again, just for volume verification. For our head and neck patients, we're looking more for soft tissue alignment so there, we're using a CBCT-based workflow. This patient happened to be a 95-year-old gentleman with a locally advanced squamous cell carcinoma on the right tonsil. He was not a good candidate for combined modality therapy given his age and medical comorbidities, so he had to be treated with RT alone. He was getting some mild type of fractionation given the fact that he was only able to get chemotherapy prescribed at 66 gray in 30 fractions to sites of gross disease while simultaneously delivering 54 gray in 30 fractions to subclinical sites.
Again, it's planned using RapidArc IMRT with two arcs, standard thermoplastic immobilization, and we also use a vacloc up to the shoulders of this patient to help reproduce the setup daily. Again, 2 millimeter PTV margins. So, for this patient, after the surface pre-positioning, the CBCT is performed, the therapist then performed a soft tissue alignment once the CBCT isocenter is set. We then enable ExacTrac Dynamic for an X-ray reference, then we go into surface monitoring during the course of the arc. Prior to the next arc, a verification of stereoscopic X-rays is performed within a given surface tracking through the remainder of the treatment. For our breast treatments, we've been using the ExacTrac Dynamic now for the right breast, right whole breast.
This is the patient who's a 58-year-old female with a right stage IIA breast cancer. She had a partial mastectomy with negative margins and was then recommended to proceed with adjuvant whole breast RT using the moderately hypofractionated technique, opposed tangents with field-and-field. So, for this case, our target is the whole breast and therefore, lining up to the chest wall and using the standard-based workflow. So, the patient is pre-positioned using the surface. Currently, we are still using AP and lat simulation tattoos, however, we anticipate in the future to be discontinuing that as we spend more time using the system. We then indicate on the patient's surface the area for which we would like to monitor the surface during the course of the treatment.
And then ExacTrac uses the stereoscopic X-ray system to align the patient using six degrees of freedom to the treatment planning DRR. Once that alignment takes place, we perform an MV portal verification on the first day and then every fifth treatment. During the course of treatment, the patient is monitored with surface tracking and then periodic stereoscopic X-rays as a function of the monitoring unit as well as prior to each new field. For our lung treatments, again, we're now moving to, again, the soft tissue alignment so we're using a CBCT-based workflow. This patient here is an 83-year-old male with a medically unresectable stage IIB non-small cell lung cancer by virtue of a satellite nodule adjacent to his primary. The patient has very, very poor pulmonary function.
Given the location of the disease and the volume that needed to be encompassed, it was recommended that he had a modified stereotactic technique. He was simulated using a 4DCT with stereotactic fixation and abdominal compression, and was ultimately prescribed 60 gray in 10 fractions, again, using RapidArc IMRT with two arcs. For this patient, again, after surface pre-positioning, we enacted CBCT workflow where after a CBCT alignment was performed, the CBCT isocenter was set. The ExacTrac Dynamic then performed a stereoscopic X-ray reference and we then surface monitoring throughout the course of the arc. The patient then had a stereoscopic X-ray verification performed prior to the next arc against their surface monitoring throughout the course of treatment. By having this stereoscopic X-ray referenced before each arc as well as surface monitoring, it's given us a lot of confidence to decrease our margins from ITV to PTV.
For upper GI cancers, we're seeing also tremendous utility with ExacTrac Dynamic. This happens to be a patient with intrahepatic cholangiocarcinoma. She had a resection performed and was found to have positive lymph nodes. She completed adjuvant chemotherapy and then went on to receive adjuvant chemoradiation. Then because of the location, she had a 4DCT simulation through the respiratory motion and was ultimately prescribed 50.4 gray in 28 fractions which was delivered using RapidArc IMRT with four arcs. Given the soft tissue alignment, we went with a CBCT workflow. Once the CBCT isocenter is set, stereoscopic X-ray verification...stereoscopic X-ray referencing was performed and then surface monitoring throughout the course of the arc. X-ray verification was performed prior to the next arc, again, with surface monitoring throughout the arc.
What we find is that we've become very confident now in our setups for these patients because we're getting...not only are we monitoring during the course of their treatment on the surface, but we were able to verify their bony alignment in between each arc and make any sort of adjustments that we need to. So, that really helps with these multi-arc treatments with keeping these patients aligned and not significantly increasing the treatment time. Now, we get to the best part which I saved for last, which is prostate. As you are all well aware, conventional treatments for prostate are becoming increasingly rare these days, 1.8 to 2 gray per fraction treatments probably composed less than 5% of what we do for our prostate population here at Valley-Mount Sinai.
And so, as moderately hypofractionated or stereotactic body radiotherapy treatments become increasingly more prevalent, we really need to be taking into account intrafraction prostate motion as the dose per fraction is increasing. In the past, we were using the Varian real-time imaging system where we were doing fiducial monitoring using real-time 2D kV imaging. And what you're seeing here is some data from a manuscript that's in preparation where we're looking at the visual excursions during our prostate SBRT treatments. And what you see is more than 20%...or about 20% of our treatments have excursions of 3 millimeters or greater throughout the fraction SBRT that's been delivered. So, it's imperative that when we're delivering these high-dose per fraction treatments, we account for that prostate infraction motion.
So, what we're doing now with the ExacTrac Dynamic system is using the implanted marketing workflow and then we'll use additional workflows as necessary when we need to incorporate things like pelvic nodal coverage. We always perform a CBCT prior to the start of treatment, and this is mostly for anatomic verification, we want to verify [inaudible 00:32:27], but also we do an approximate CBCT fiducial alignment, which helps with the automatic marker detection with ExacTrac Dynamic. The other thing that CBCT does for us is it tells us whether or not we should proceed with the treatment the way it is. We've come up with some guidance for therapists during our prostate treatments to determine whether or not the patient needs to be really taken off the table, have some of their...having their rectum emptied or their bladder fill more.
And sometimes they just need to be re-setup and we use this by looking at the pitch required to approximately get the producible line in CBCT. And if we find that we're having problems, you know, over consecutive treatments, then maybe that's a patient that needs to be re-simulated. So, for our prostate SBRT treatments, again, we're using an implanted marker workflow. This happened to be a 60-year-old gentleman with intermediate-risk prostate cancer who wish to proceed with prostate SBRT. He had a standard gold fiducial in place along with SpaceOAR hydrogel prior to simulation with CT and MRI, and he was then prescribed 36.25 gray in 5 fractions which is usually delivered with 2 arcs of RapidArc IMRT and 6 arcs of flattening filter free mode, there's always stereotactic body fixation, and 3 millimeter PTV margins.
So, we perform an initial CBCT, we wanted to check for anatomical variations in the bladder and the rectum. We also then perform a rough alignment for fiducial. From there, ExacTrac Dynamic takes over where we perform stereoscopic X-rays and auto fiducial match is performed and then aligned to the treatment planning DRR. Throughout the course of the arc, we are monitoring the surface as well as performing stereoscopic verification X-rays at each cardinal angle of the arc with subsequent adjustment made depending on tolerances. Some of the more complicated treatments that we've been doing since getting ExacTrac Dynamic is actually incorporating pelvic nodal coverage into some of our moderately hypofractionated prostate treatment.
So, in moderate hypofractionation at our institution, we routinely prescribe 70 gray in 28 fractions to the prostate. In certain patients with a high-risk disease where we want to cover prophylactically the pelvic lymph nodes, we also want to deliver 50.4 gray in 28 fractions to the pelvic lymph node. The problem with this is that we're retreating two different volumes that really have two different references. If we line up to the prostate, there's a good chance that we'll be off of our pelvic lymph node. So, one solution is, okay, just increase the margin around the pelvic lymph node. The problem with that is that then you're increasing the volume of normal tissue that you're treating. So, the solution that we came up with is to deliver a daily composite plan, one where we're treating a volume that aligns to the pelvic bony anatomy and encompasses all of the tissue including the pelvic lymph nodes, the prostate, the seminal vesicles at the margin that would allow for a positive motion up to a total dose of 180 centigray.
We then deliver the prostate boost of 70 centigray, which is aligned to the prostate fiducial. So, this allows us to sort of cover everything we want while minimizing dose to the adjacent normal structures like the rectum and bladder. So, this is a case of a patient with Gleason 9 high-risk prostate cancer who is actually treated on NRG protocol GU009, and we treated him using the exact same approach that I just described. What we do with these patients is actually treat the prostate and seminal vesicle boost first, we perform a CBCT again for the anatomic verification and then rough fiducial alignment. We then go into the ExacTrac Dynamic implanted market workflow and deliver the first 70 centigray of treatment. We're monitoring the service during the course of treatment and then X-ray verification is performed every 180 degrees.
Once that plan has been delivered, we then move into the remaining portion of the treatment which encompasses all sites of disease, the pelvic lymph nodes, the remaining distal prostate, and seminal vesicles with a larger margin. For this, we then use the standard workflow. So, the ExacTrac Dynamic stereoscopic X-rays are now aligning to the treatment planning DRR of the pelvic bone, we perform X-ray verification at the start of each arc, and we monitor the surface throughout the course of treatment. So, in summary, we have found the ExacTrac Dynamic to be extremely versatile, and we have been applying it to nearly all of our EBRT treatments at this point.
We're very confident with the accuracy and precision now that we have been provided by ExacTrac Dynamic. We're able to decrease PTV margins very confidently in certain situations. And like I said, we're currently using ExacTrac Dynamic in some shape or form with 70% of our EBRT treatments at this point. One of the important things that we found is that overall treatment times have not significantly increased with ExacTrac Dynamic and surprisingly, we actually...or maybe not so surprisingly, our prostate SBRT treatment times have actually decreased. And this is really due to the fact that we're now in real-time able to verify fiducial position and make corrections without having to reset the gantry and perform additional CBCT, so this has been really beneficial for patients. That's all I have for today. Thank you.
Bogdan: Thank you for the extensive review, Dr. Kole, and let's transition now to the lecture from Dr. Silverman from NYU who will present their experience with ExacTrac for spine SBRT treatments.
Dr. Silverman: Thank you for the introduction and the opportunity to speak. The title of my talk today is, "Metastatic Spinal Tumors, Early Implementation of Brainlab ExacTrac Dynamic." I want to talk to you today about advances in treatment of metastatic spinal tumors and focus on a few concepts. The first is to establish clear indications and treatment recommendations for these patients. I want to emphasize the importance of a multidisciplinary team and then I want to focus on spine stereotactic body radiation therapy, SBRT, and importantly, focus on the workflow using the ExacTrac Dynamic system. The goals of therapy for managing patients with metastatic spinal tumors is to preserve neurologic function, ensure spinal stability, limit pain control, and have local tumor control as well as effects on overall survival.
There are many different treatment options in the modern armamentarium including systemic therapy options, radiation options, and surgical interventions as listed. The treatment has been evolving. On the left, you see an example of the radical surgeries that used to be done for these patients, leaving them quite debilitated. On the right is the more modern minimally invasive spine stereotactic radiation therapy plan. This is from my surgical colleagues demonstrating on the left the change from flap reconstructions to minimally invasive surgery and on the right, the use of smaller constructs and hardware. In order to think about managing spine metastatic patients, we talked about looking at the NOMS framework, the acronym. We focus first on the neurologic component with assessing the degree of myelopathy and functional radiculopathy in a patient, and we have a system for that.
There's basically a grading system that enables common communication for low-grade or high-grade ESCC, zero through three scales that I showed. Then we look at the oncologic components in terms of the tumor histology and relative sensitivity to radiation or chemotherapy. Histologies have been broken down and categorized in this very nice article, radiosensitive tumors respond well to conventional radiation and radioresistant tumors are relatively resistant to that treatment, requiring SBRT in the upfront setting. So, this demonstrates the evolution of going from conventional radiation therapy to stereotactic body radiation therapy involving less normal tissue and higher dose to tumors. Single-fraction radiation therapy to the spine and other tumors may involve new biologies, including endothelial apoptosis as well as overcoming stem cell resistance that gives it an advantage.
In terms of single-fraction SBRT, there's a suspicion and some evidence that higher dosing actually results in better tumor control. This slide shows an article which demonstrates that with single-fraction SBRT, the effects of histology are less important than they used to be. Whereas traditionally, there are wide differences, we see very little difference in the local control rates amongst histologies. This is a slide demonstrating another study looking at patients receiving spine SBRT, indicating that the durability of tumor response following SBRT. There's a one-year freedom from tumor progression of above about 85%, which is important in our patients who are more commonly living long term. It's important to note that single-fraction toxicity exists and you need to counsel patients properly about it.
In addition to the upfront setting for radio-resistant tumors, we also use SBRT in the spine to re-irradiate tumors that have already been treated. And so, this slide shows a summary table of this. So, this enables us to think critically and have a very tailored approach to our patients using conventional external beam radiation therapy for radiosensitive patients and incorporating spinal radiosurgery into radioresistant histologies and their management. We also need to take into account mechanical factors and that also has a grading system. And mechanical instability is very important because it affects patients' quality of life and how they perceive their disease. We use the standard SINS score, which is an acronym looking at different factors to score to determine whether patients have stable or unstable spines and also the need for surgical intervention, no amount of radiation is going to properly treat an unstable spine.
And so, for several factors, spine instability is important to be stabilized prior to SBRT, and working in a multidisciplinary group with neurosurgical teams is critically important. Lastly, we have to take into account the patient as a whole in terms of their systemic metastatic tumor burden as well as medical comorbidities. So, for example, additional workup needs to be done oftentimes and an active discussion with the patient's oncologist and potentially cardiologists and other specialists should be performed. I want to now come to the workflow for spine SBRT and talk about the role of the ExacTrac Dynamic system. But first, before you even get started, it's important to develop and have a multidisciplinary team that communicate with one another and work seamlessly.
These are the various members of the team including surgeons, radiation and medical oncology specialists, as well as radiologists, rehabilitation medicine, interventional neuroradiology, supportive oncology, and our nursing staff. It's important to acknowledge that communication is key. We then set about by seeing the patient and evaluating them thoroughly in consultation. And we discussed cases at a spine oncology tumor board, and this is important to set up because we want to optimize multidisciplinary care. Finally, we come to the SBRT planning for those patients where it's integrated. We usually use an immobilization set up with a standard commercial board. We use CT-myelogram in patients who have had post-operative cases as well as for most intact cases at our institution.
It's important to also use MRI fusion or simulation, the latter where available. It's important to also note that there is deformation in terms of MRI fusion because a patient's MRI of the spine may be performed in a position slightly different from the planning scan and the Brainlab fusion tool can help with that. In terms of treatment planning, we typically treat two to four arcs with periodic real-time X-rays for each arc using the ExacTrac system. And we also like to see automation in treatment planning. We've published a paper on automation in treatment planning using an open script with a common commercial planning system, but the Brainlab system does this automatically where you're able to generate plans quickly and efficiently.
In terms of contouring and target designation, it's important to use the consensus guidelines. We subscribe to these, this is a figure from the IntAct publication. There are similar publications for sacral tumors and also post-operative cases which we also follow. In terms of the workflow for spine SBRT delivery, we have the team assembly, a physician, physicist, and trained therapists are available at the start of treatment. We then set up with patient alignment and immobilization, take kV orthogonal images, perform a cone-beam CT scan for alignment, and then we use ExacTrac Dynamic for intrafraction monitoring. And this has two components which really ensure and give confidence to our high-dose refraction treatments, particularly near adjacent critical structures such as the spinal cord, cauda equina, and esophagus.
So, we use real-time X-ray tracking and 3D surface rendering and thermal imaging in four dimensions, essentially giving us multiple modalities to ensure that our patients are not moving during treatment. This is the equipment setup. Basically, the floorboards with cameras that give the cross X-rays up to the detectors, as well as the Brainlab detector device. This is some...this is a couple of screenshots of how the heads-up display looks like. On the left is a standard display for a brain case, and you can see the X-ray matching on the upper left and the infrared on the right. The bottom left shows the gantry angle and the bottom shows the tracking of the thermal imaging in real-time. The upper left middle panel shows the tracking of the X-ray, on the right, it shows that you can zoom in and verify the exact anatomic definition.
This is a spine case on the right. This is an example that's an important concept which is that the recording verification system can be used for image storage. So, this is a case that we treated, post-operative SBRT using the ExacTrac system and this is an example of images that were imported for verification and recording so we can keep records of the images that we take and review those. Also, this is a possible research tool. I want to present some unpublished evidence from our cases that we've observed with physics analysis looking at how good we're doing with the ExacTrac. This shows in the x-axis different patients being treated, and on the left is translation, on the right, rotational axis. And this is showing the difference between our pre-treatment cone beam and the ExacTrac measurements.
And as you can see, in the left panel, this is usually pretty accurate to within a millimeter or two in our experience. And on the right panel, usually within one degree of rotation. So, the conformality and accuracy and precision between the cone-beam CT and ExacTrac is quite good in our experience. And then this is the important data, which is that the intrafraction motion using ExacTrac Dynamic. In other words, how often are our patients moving while they're being treated, and do we have confidence in that? This shows the different cases. On the left is basically using X-ray tracking for translations, and you basically see that we're under a threshold of one millimeter. All the patients are within one millimeter except two treatments for our patient who is in pain.
And you can see on the right is the three dimensions of rotation, and similarly, we have no greater than one degree of rotation except for the one outlier patient. So, currently, we're treating with setting these as parameters to pause the treatment and retake a CBCT and realign the patient if they exceed that. So, in summary, I think the ExacTrac Dynamic system fits in very well to a spine SBRT program and really gives us a lot of confidence in terms of the precision and accuracy of intrafraction motion targeting for our spinal patients. Thank you for the opportunity to speak. I want to thank the NYU team and the team at Brainlab. Thank you.
Bogdan: Thank you Dr. Silverman for that great talk. For those of you intimate with Brainlab, you may know that we have an imminent release for a new version of ExacTrac Dynamic. And to build a case for the clinical requirements for IGRT for breast radiation therapy, we have a lecture from Professor de Ridder from UZ Brussels.
Prof. de Ridder: Good morning, afternoon, or evening. I, first of all, would like to thank Brainlab for the kind invitation. In the next 15 minutes, I'm going to talk about ultra-hypofractionated radiotherapy for breast cancer and I'm going to show you the need for image guidance. Deep inspiration breath hold increases the physical space between your heart and the left breast. Here you'll see a CT scan in shallow breathing where the heart almost touches the breast and here you'll see a CT scan in deep inspiration breath hold. And this decreases the mean heart dose by 40% to 50%. And that's very important as Taylor and colleagues showed a linear relationship between the relative risk of heart disease mortality and the mean heart dose. They found an excess relative risk per gray of 0.04.
Over the last decades, there have been changes in fractionation. At the end of the last century, we were using two gray fractions and treating whole-breast irradiation with 50 gray in five weeks. Afterwards, we have the START trials exploring a treatment in three weeks delivering fractions of 2.67 gray, and now more recently, we have the results of the FAST-Forward trial which is treating breast cancer in one week using 5.2 gray a fraction. Here you see the results of this UK FAST-Forward trial that's compared the treatment of whole breasts in five fractions delivering 26 or 27 gray in one week and it was compared to the standard of care, the 40 gray in 15 fractions. And the three arms were no inferior, note that the ipsilateral breast cancer relapse was very low in all arms.
When you look now to the adverse events in the breast, there's some difference between the three arms. When you look at the number of moderate or marked events in the 40 gray group where they're taking the treatment in three weeks, it was noted in 10.6% of the patients. In the 27 gray in one week, it was noted in almost 16% of the patients, and between 26 gray group in one week, it was noted in 12.2% of the patients. The 27 gray group did significantly worse than the 40 gray group, and the 26 gray group did significantly better than the 27 gray group. And this was confirmed by patient and photographic assessments that show a high normal tissue effects risk for 27 gray versus 40 gray, but not for 26 gray versus 40 gray. And based on these data, 5.2 gray whole-breast irradiation in one week became the standard of care in the UK and many other centers worldwide.
Meanwhile, we perform the feasibility study of pre-operative accelerated radiotherapy for early breast cancer, our POP-ART study. In this study, we delivered five fractions of 5 gray whole-breast irradiation with a simultaneous integrated boost of 6 gray on the tumor. And this was followed by breast-sparing surgery with sentinel node procedure two to eight days after the termination of radiotherapy. And this was technically feasible in the first 14 patients that we treated for 15 clinical early-stage breast cancers. When you look now at the adverse events in the breasts, we had one patient with a wound disruption, three patients needed antibiotics due to mastitis, and another patient developed a fistula needing a surgical intervention a couple of months after the end of radiotherapy.
So, because of this high number of adverse events in the breast, we decided not to go to a phase two trial. What about the potential drawbacks of ultra-hypofractionated radiotherapy? Well, first of all, the follow-up is still limited. If you want to assess long-term radiotherapy-induced iatrogenic effects for breast cancer, you need a follow-up of more than 10 years, especially about cardiovascular mortality and secondary lung cancer induction. We published a paper recently in "The Green Journal" about these two issues. And we took into account the score table, which gives us a 10-year risk of fatal cardiovascular diseases in normally irradiated patients and takes into account the systemic blood pressure, the smoking status, and cholesterol. We combine this with a known TCP and TCP models to come to a table which allows a patient individualized approach.
So, here you see the estimated absolute 10-year cardiovascular mortality in female breast cancer patients of radiotherapy and you can see important differences. For instance, if you have a 50-year-old woman at the consultation with a systolic BP of 140 millimeters of mercury and low cholesterol, despite the fact that she's smoking, she only has a 1% risk of a fatal cardiovascular event within the next 10 years. When you deliver a mean heart dose of 8 gray, which is much above what we normally do, you see that she still only has a 1.2% absolute risk of a fatal cardiovascular event. While on the other hand, if you have a 65-year-old woman with a BP of 180 and high cholesterol, you can see that the risk of developing a fatal cardiovascular event is already 19% and after radiotherapy, it is increased to 23%.
And with the same efforts to estimate the absolute 20-year lung cancer risk, here again, you see huge differences. For instance, if you're a non-smoking woman without a familial history of non-small cell lung cancer, she has only 0.1% risk without radiotherapy to develop lung cancer in the coming 20 years. When you give a mean heart dose of 8 gray, which again is very high, the risk is only increased to 0.2% absolute risk. While on the other hand, if you have a heavy smoker in consultation with a familial history of breast cancer, the base risk of developing lung cancer within the next 20 years is 15% and this risk is increased to 39% if you give a mean lung dose of 8 gray. Now, the second potential drawback is that our treatment time increases with the fraction dose, and if treatment time increases, your patient needs to do more DIBH cycles and you have a risk of drifting.
We studied this intrafraction drifting during DIBH, so we performed treatment monitoring for a series of DIBH patients using ExacTrac Dynamic and we started with an average of two fractions of patients. And you can see on the y-axis, the greatest deviation from 6D displacement is plotted against here on the x-axis, each motor unit. So, this was one irradiation field, the patient performed three DIBH cycles, and you can see that as we give more motor units, there is a drifting of the position of the patient. And this was confirmed by communication from our Dutch colleagues that showed that the mean displacements, the systemic error, and the random errors increase with fraction time.
And hence, if you don't use intrafraction image guidance, you need to adopt the largest margins when treating patients with higher fraction doses and hence, longer treatment times. And then we come to a third potential drawback of this ultra-hypofractionated radiotherapy. The impact of positional errors can lead to potential higher biological dose to the organs at risk, taking into account the higher fraction dose and the acceleration of the treatments. So, I want to conclude that there is a need for intrafraction image-guided radiotherapy if you want to safely deliver whole-breast radiotherapy within one week. Thank you for your attention.
Bogdan: Thank you, Professor de Ridder, and again, perfect segue for us to welcome you once again to join us during the live ASTRO meeting for in-person interaction and should you have the time to stop by our Brainlab booth, we would love to show you in greater details the products that we are bringing to the market. For those of you who submitted questions, please look for a personalized email response from our speakers. And as always, I'd like to thank not only our speakers for the great lectures but to all of you who have joined us online for this event. Thank you very much and have a good day.
