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    Bogdan: Hello, everyone, and welcome to a new Novalis Circle Symposium. My name is Bogdan Valcu, I am the director of Novalis Circle, and today I have the privilege to host this online event part of the ASTRO 2020 Industry-Expert Theater. For our presentations today, I am honored to introduce you to two groups, one from Ludwig Maximilian University in Munich and one from University Hospitals in Brussels that have put together an agenda of four talks highlighting clinical and technical considerations for spine and breast treatments.

    To begin, we'll have Dr. Maximilian Niyazi from LMU in Munich discuss disease considerations for spine radiosurgery. Dr. Niyazi is the vice-chair of the Department of Radiation Oncology and the deputy coordinator for the Neuro-Oncology Comprehensive Cancer Center. He will be followed by Dr. Philipp Freislederer who will discuss the first clinical applications of ExacTrac Dynamic. Dr. Freislederer will also discuss general commissioning and implementation considerations for ExacTrac Dynamic.

    We will follow his talk with Professor Mark De Ridder from University Hospitals in Brussels who will discuss general considerations for breast radiotherapy. Professor De Ridder is the head of the Radiotherapy Department, the vice-chairman in the board of directors, and also the vice president of the Medical Council. His talk will be followed by that of Professor Thierry Gevaert who will discuss both SGRT and IGRT considerations for breast setups. Dr. Gevaert is a professor and the coordinator of the Medical Physics Group in the Department of Radiation Oncology at UZ Brussels.

    And as it has become standard by now for online events, please remember to utilize either Google Chrome or Safari, and should you have any internet connection issues, simply refresh the webinar page. Use the chat interface to send us questions. We will answer your questions upon completion of the four lectures, monitor the polling interface for questions that we might like to ask you. And should you choose to follow us on social media, please use the #NovalisCircle. With this, I'd like to send it over to Professor Niyazi for the first lecture.

    Prof. Niyazi: Dear ladies and gentlemen, dear Bogdan, thank you so much for the invitation and the possibility to present the radiosurgical planning on spine disease and respective considerations with ExacTrac Dynamic. So, first of all, I would like to introduce our Department of Radiation Oncology. I'm the vice-chairman. The LMU Munich University Hospital has around 2,400 patients per year, has a standard equipment with Versa HDs with some additional tools like Clarity, C-Rad, and ViewRay MRIdian, some brachytherapy facilities, and, of course, a lot of staff because we need to implement all these techniques. And one of the novel issue is our ExacTrac Dynamic which has several capabilities, and, specifically, an optical surface scanner with structured light, a thermal camera that is included, the X-ray positioning system that you all know from the ExacTrac, and additional real-time tracking using surface-guided radiotherapy situations.

    And that's here a nice image of my dear colleagues, and as you can see, the thermal information adds a new dimension to the surface information itself, and that's what you can see here. You have the projector, you have the thermal camera, and you have the surface cameras that angulate the information from the surface of the patient and altogether add together a 3D to 4D view of the patient.

    And these are, like, these projected lines, and what you can see here is that you have a certain mesh on the surface. And this is recorded from the cameras, and then you add on the information from the thermal camera itself, and in the end, you have, let's say, a very nice view of the surface of the patient. And the good and key benefits of this new tool are, like, submillimetric accuracy in patients. You have the possibility to track both very large and small areas, you have a large field of view, you can do motion tracking. It's not too sensitive to room lighting or skin tone, and you have no really imager blocking of the cameras as you have just this one tool. And the accuracy of the tracking is not affected by baseline drifts and its unique matching algorithm that's integrated.

    So, since our first installation at the beginning in June 2nd this year, we could treat 30 patients so far, 26 cases with brain tumors and metastasis, 2 spine, and 2 head and neck cases. So how does the pre-positioning work? It's fully integrated with linac. It's an automated plan loading from R&V system, in this case MOSAIQ from Elekta. And the pre-positioning is done with the outer contour from the planning CT, and then the shifts are sent to linac. And at the beginning, you have the baseline image that's taken with the thermal information and the surface information. That is your new baseline for this treated patient.

    So the indications from the scratch were multiple brain mets, of course, within a prospective trial and every kind of hypofractionated SRS in the brain. With fractionated treatments with an open face mask, which was very comfortable for our patients, and, for example, in skull base meningioma. And the good thing was about replacing cone-beam workflow of it was, like, not fast enough for palliative cases. And we're now launching our spine SRS program as we were not eager to start that before we had these unique imaging capabilities and this high degree of precision, and, of course, bone oligometastatic disease anywhere else in the body.

    So I'll just introduce our spine SBRT program as to refer to conventional radiotherapy, for example, 3 gray times 10, 4 gray times 5, or even 1 times 8 gray. The target volume is normally the whole vertebral body including the cord, mostly in [inaudible 00:07:13] techniques with one vertebral body above and below, and still it's mostly 3D conformal radiotherapy. And it's somehow effective in 60% to 70% of cases, but the duration of response is mainly short and depends on histology. So we're thinking about that whether to proceed in this way or change it.

    There's nice work here from the Shizuoka Cancer Center. If you compare the one-year and two-year local control rates in patients with bulky tumor, you see that you lose, like, local control if you compare the non-mass to the mass lesions. It's around just one-third. So it's important to have, like, other treatment paradigms to [inaudible 00:07:55] disease problems. And the spine SBRT is here in the nice work from Finnigan, a potential to exclude the core, the cauda equina in this case, and to spare all the organs at risk around. And that's something we would like to adopt in this case, and this is a nice overview on all the different prospective and retrospective studies and trials that have been done.

    And Tseng published that in 2017 with the local control range ranging from [inaudible 00:08:27] to over 90% with a very favorable pain response, a very early pain response, actually. And even in the reirradiation setting, we have a very high local control rate now dropping a bit to around 70% to 80% but still high pain relief in this situation with really a considerable number of histologies as well on, of course, the so-called radio-resistant histologies as well. So that would be the way we would like to proceed with. And what you should know, of course, is that the cord tolerance in SBRT and radiosurgery is, of course, different to conventional fractionation, and that's here with the QUANTEC model. If you compare that to the Katsoulakis-Gibbs model, for example, and the Saghal model, then you at least see that according to these curves here, yo usee a steep increase of the risk about 15 gray, so you'd still keep your dose below these ranges here to be on the safe side.

    And the similar thing is about reirradiation, and you have nice data in this report in one to five fractions in different measure, for example, above the thecal sac if you try to keep the EQD, the equivalent dose with an alpha/beta of 2 gray, and 2 gray fractions below 70 gray, and a total of the 2 series. And, of course, there are some other rules to be applied like the thecal sac of the reirradiation should be around 25 gray EQD2. And the reirradiation SBRT, those compared to the cumulative one should not exceed 0.5. That means that you should not exceed the initial dose. And the minimum time interval should be at least five months. In some reports, it's around three months.

    And what could be a complication of this? It could be about the vertebral compression fracture, and the risk is high according to the lesion itself and according to the dose that you apply. And that's a situation with 24 gray plan from Cunha in 2013, so at least you should consider that. And one very good measure for the risk of instability of a SINS score, which is used in neurosurgery, it's actually defined from different parameters like location and like pain relief, bone lesion, radiographic spinal alignment, vertebral body collapse, and the posterolateral involvement. And if you add up these numbers, you end up with something, and this score, like, gives you stable or unstable lesions and potentially unstable lesions where you should at least consider to talk to your neurosurgeon.

    And this SINS score is also correlated somehow with a vertebral compression fracture. And this nice work published in the JCO shows that with considerable higher doses to the vertebral body itself, you increase the risk significantly to end up with a vertebral compression fracture. So dose is actually a limiting factor. And there has been a nice publication from Faruqi in 2018, a review on the pathophysiology and risk factors, and the rate was around 13.9%, and these risk factors were actually identified, like, dose per fraction how many of the vertebral body was involved, the age, deformity, and lytic disease. So, at least, you have some idea which factors to be considered.

    And one other important information is the Bilsky epidural disease grade which gives you the information whether a separation surgery makes sense. So if you have an abatement of the cord, for example, or a high compression and almost no CSF fluid, that's something where you should consult the neurosurgeon. And this nice work has been shown by Al-Omair in neuro-oncology, also a seven-years-old publication. And there's the local control for the entire cohort according to post-operative epidural disease in Bilsky grade. And as you can see here, the Bilsky grade increases, the local control gets lower. And if you consider this group that had the pre-op 2 to 3 grade and afterwards, like, had very low grade and mainly 2% and 10%, if you see these patients and they end up with a 0 or 1, they have this considerably higher local control. So this is something that should be noted and that's important that you have, like, NOMS criteria and talk to your neurosurgeon about the separation surgery.

    So we launched a study protocol which is called SPINES, so spine SRS, and the background is that the local anatomy of vertebral body, of course, is different according to the location within the spine. And what's important is that you can divide the vertebral body into these sectors, and that's important for planning as well. So if you have those spine processes or the transverse processes, laminae, or pedicles, or the wider body, it depends on what you would include into your target volume. And as you can see here, that's something provides a soft resolution from Brainlab as well. According to this international spine consortium, to define the target volume according to the lesion, which parts of the vertebral body are affected, and in that way, the software automatically contours this respective CTV.

    And what we did in the SPINES trial is that we used the common fractionation schedules like from 1 fraction to 5 fractions, so 6 gray times 5 to 16 to 24 gray times 1. And we had, like the BED to the tumor with a bit of three here, of course, rather radio-resistant. The histology is the same thing for normal tissue. As you can see here, like, you're going with the BED from values like 90 gray, 260 gray. That's far more that you would normally do with moderate conventional fractionation. And we're using SIB approach in order to reduce the cumulative equivalent uniform dose to the vertebral body in order to decrease the risk of compression fracture. And we're doing, like, the CDV elective in a way that is done, like, according to ISRS recommendations with a margin of two to three millimeters and boost the GTV plus-three but, of course, exclude spinal canal and thecal sac. And the cord is used with one millimeter additional margin of the cauda instead of the cord if we're in the lumbar and sacral region.

    So, as we can see here, the elective target volume is treated with, for example, 16 gray in 1 fraction, and the boost within the SIB is 24 gray, or in similar fashion in 2 fractions is 18 gray and 24 gray, so that's like 12 gray times 2 to the lesion itself and 9 gray times 2 to the elective PTV. The same thing is done, like, 9 gray times 3, 7 gray times 3, and here it's like 6 gray times 5, and 5 gray times 5. So, as you can see here, the equivalent doses are pretty much different, so it's not the biological effect of dose, and you really increase the dose up to 130 gray, so it's 2.5 times of this initial prescription. And then you can choose according to histology, to situation, to oncologic outcome which one to choose.

    And the inclusion criteria are pretty much the same given from ISRS. So, spinal and paraspinal metastases in smaller than three affected vertebral bodies, untreated, or if it's progressive of the conventional radiotherapy and oligometastatic disease if you have a stable spine with a SINS score of 36, low epidural involvement with a controlled extraspinal tumor, life expectancy over 3 months, and a Karnofsky score over 50. And the exclusion is pretty much the contrary of that, so uncontrolled disease, unstable spine, rather if you have a high degree of epidural involvement, consult your neurosurgeon if it's a radiosensitive histology. Would not choose that in previous SBRT if the life expectancy is very low or the spinal cord compression high.

    So, constraints that should be used are, for example, given the ASTRO guidelines, I'll just go through this very briefly. So 1 fraction is 12.2, 5 fraction is 25.3 here, but this is referring to the thecal sac, so you have to add on a margin to be considered for your cord, and that's the PRV. That's the important issue about the ExacTrac Dynamic in a way because then you can really achieve this high degree of precision. And as you can see here, that's the vertebral body that's automatically contoured, for example, in this Brainlab software tool. Then you can use the extra intelligence layer to deform your MRI and to fuse that to the CT scan. And the planning program actually can, for example, achieve, like, different prescriptions to the lesions and the algorithm uses the different segments of the vertebral body to apply the dose according to the substructures right here.

    That's an example of a clinical SRS case, a uterine leiomyosarcoma that was metastasized. It was initially presented in 2015, had resection and adjuvant chemo. It was in the piriforme muscle region and had sacral metastasis that were resected again in 2016. And a destructive metastasis of T9 underwent more hyperfractionated palliative radiotherapy, it's like 3 gray times 12. And seven months later, we had a progressive lesion in T9 and we retreated with 20 gray and 30 gray, actually, to the lesion with 5 fractions and we went down to the cord and thecal sac PRV to below 18 gray and, of course, had to spare all the structures around, like, the esophagus and the aorta here. And, of course, the cord itself and the thecal sac, that was really a very complex case, but we were able to manage that with the ExacTrac Dynamic.

    And the important issue here was that we had to choose high margins for the patient's surface. And my dear colleague, Philipp Freislederer, will show you the workflow afterwards in spine SRS, but here it was important to have not too much breathing motion that was detected. So, very tight margins for X-ray surveillance with 0.7 millimeters and 0.5 degrees, and the highest possible framerate for X-ray that was possible to only stereoscopic, 4 per arc. And we used the surveillance mainly with the X-ray images. The arms were up with no body fixation, no vacuum mattress, so it was very easy to place this patient and it worked pretty nicely. And these five fractions could be delivered within the range, and the ExacTrac gave us this confidence to make everything possible.

    So I would like to cordially thank you all for listening to that first part of the presentation, and I would like to hand over to my dear colleague, Philipp. Thank you so much.

    Bogdan: Thank you for the review of your spine program, Professor Niyazi, and let's go to Philipp Freislederer for a recap of the LMU experience with ExacTrac Dynamic for spine treatments.

    Dr. Freislederer: Well, hello, everyone. My name is Philipp Freislederer from LMU Clinic in Munich. I'm gonna start talking a little bit about the workflow for the ExacTrac Dynamic for spine patients and go a little bit into QA and commissioning details but not too much, and afterwards, summarize some of the benefits from the treatment and the treatment procedure from our side. So when it comes to the workflow, the system starts with a pre-positioning workflow. What you see here is the patient on the treatment couch, and you shift the patient now from the live position. But you can detect with the surface camera only the thermal information is not used in this case for the pre-positioning workflow to the planned position you arrived from your planning CT.

    And the software would look like this. So you have a CT outer contour, your treatment position, and your current position, and also your live surface here in orange, and you send the shift to your treatment couch. After you shifted your patient in, I think, the correct way from the pre-positioning workflow, you select an area of interest you want to track on this patient. So, you simply draw this area of interest for this specific patient for this specific treatment site, and if you confirm this, that's the moment where the thermal information of the fourth-dimension here is safe and tracked. So, from now on, you're not only using surface information but thermal information, too.

    Afterwards, you would start doing an x-ray acquisition. So you simultaneously acquire two X-rays, two orthogonal X-rays, and the thermal or the optical and thermal, so the 4D surface is captured and stored. If you send this shift to the linac, all of the shifts derived from the X-rays are applied also to the surface and the region of interest is transformed according to this information. This is what it would look like in the software. You have your contours drawn onto the DRRs and to your current X-rays, and you can check whether your fusion result is valid, whether you track the right position in the patient, and you afterwards send the shifts to your six-dimensional table.

    Why would you, in general, use a thermal camera in this case? So you see this is just a very nice Brainlab image, a marketing image of the camera where you have your structured light projector, and your data camera, and also integrated your thermal camera. What would it look like if you would look at sort of a flat surface on the patient? So if you look at the surface data only, this will look very flat and kind of hard to track for any kind of registration algorithm. In addition, this surface has some thermal information stored inside. If you combine those two together, this is what the surface would look like with a thermal topography plotted on them. This is not what you actually see in the software, but this is what the software inside or internally makes out of the two surface data and thermal data projections. This is something which is very easy for any registration algorithm to grab and to hold on.

    Before you start monitoring, you can always check if the patient moves differently than the applied couch shifts. That's what the surface information does, so that's a pretty easy use case. The RTT is positioning the patient, turns around, leaves the room, and then, afterwards, the patient starts stretching a little bit because he thinks he is not monitored during this time. But you see it, you track him using your surface camera and your thermal camera. And if you see any deviations, you could go back, acquire new X-rays, and reposition the patient again.

    Then you start with your monitoring workflow. In general, when there's some gantry blocking or some other blocking of one of the two X-ray sources or tubes, you can only acquire a monoscopic X-ray. But if you acquire a monoscopic X-ray, you do not update your reference surface. You only update the surface if you have stereoscopic X-rays because that's the only case where you have enough information to do a six-dimensional registration. So, as you can see here, there is no blocking of the gantry. You can take a stereoscopic X-ray image, and that's also when you update your surface image and your thermal image, your whole surface to the point where the body is tracked dependent on the X-ray internal information.

    What happens if a deviation is detected? So, if you simultaneously store the thermal surface and capture it in the background, if the internal anatomy from the X-ray is out of tolerance, there is a beam hold. No more radiation is applied, and you will have to go back to a repositioning of the patient because the patient has moved, and then you start with a repositioning workflow according to your X-rays. The fusion needs to be verified by the user. It provides you a very good six-dimensional fusion registration result between the DRR and the X-ray, but you need to verify it and to check it if you're doing everything right. If you send the shift or the fusion approval, also, as I said before, the shift is applied to the thermal or the 4D surface.

    What happens if not the X-ray is out of tolerance but your surface or a monoscopic X-ray is out of tolerance? In general, you can decide what you want to do depending on the patient's specific side. What's always a good idea is to have the beam on hold. You can also do automatic X-rays in this case. It really depends on how important it is for you to have a beam hold directly when a little bit of the surface is out of position, but it's always a good idea to put the beam on hold and think about if you need to do X-ray repositioning. Again, you need to verify this fusion after you reposition the patient.

    What is a pretty nice thing to have is a good template for each case. So if you import any patients, you have your specific template for each single use case with different tolerance levels, with different methods of beam hold or not, with different fusion and approval settings, and so on. So, in this case, there are some pretty nice details is if you wanna have beam hold control dependent on the patient surface or not, if you wanna have verification images of your X-rays for each couch angle, or if you have a verification for an initial correction image. This is what you can decide in each template. And the second thing is, obviously, you have different tolerance levels for X-ray and for surface between a cranial SRS case or a cranial spine case, or anything where larger deviations can be tolerated.

    There are two different methods of X-ray triggering. One is you can always decide that for yourself, for each patient again. One is an automatic triggering when the surface exceeds the tolerance, and the other one is an automatic triggering for static beams after a certain amount of monitor units is applied, or for dynamic beams for certain positions of the gantry. Now, briefly about the routine QA. Our daily check in this case is roughly or mostly less than five minutes in total. You do check for two different things. One is the deviation between the surface camera or the surface and the thermal camera and the X-ray position, so a so-called consistency check, and the second one is a deviation from your radiation isocenter. The second thing you need to do is a calibration of the thermal surface or the thermal camera to the 3D camera. This is done with a specifically designed phantom. We have to do it monthly, and it also takes at most five minutes.

    We do recommend a calibration of the radiation isocenter monthly. This is pretty simple, the placement of any ball bearing in the radiation isocenter. This could be a ball bearing inside an anthropomorphic phantom or also a Winston-Lutz pointer. We did some initial verification test because still the cone-beam CT is mostly considered a gold standard, and for a lot of the patients, we want to move from cone-beam CT treatments to positioning using ExacTrac Dynamic all the time in every fraction.

    So we wanted to see just for a phantom how those two systems interact. So we checked it with two anthropomorphic phantoms with different isocenter locations and did a verification between the initial correction for both of the systems. So, for the head phantom, pretty much in agreement a little bit more rotation difference between those two systems. For a pelvic phantom, 0.4 millimeters in deviation between the initial correction. When it comes to the verification after the applied shift, there is not really much of a deviation. So everything submillimetric between those systems. So this now just depends on which system you want to trust more.

    There are a lot of initial commissioning thoughts when we first got the system. For example, the static accuracy of the system, the dynamic accuracy of the system or the surface. This is something that's possible to measure, but at the moment, the data is only stored in Beam ON, but it's, again, possible. The impact of the region of interest is something which is more of a scientific rigor at the moment. The field of view is something that has changed quite drastically not only when it comes to the X-ray field of view, which has been enlarged quite a bit, but also here you can see the field of view on what surface you can track, which is quite a large one for any type of treatment side you want to treat with ExacTrac. If you want to have additional insight on some of the commissioning, I would like to refer on another webinar from our institution which is available on the Novalis Circle homepage.

    When it comes to the benefits of the new system, especially for the treatment not only of cranial treatments but also of spine or other treatment sites, we identified some already proven benefits and also some potential for the future. The first one is the integration of the system to the linac so you have either automatic or manual X-ray triggering if you have deviations between your planned and your actual patient surface. And you have direct repositioning, and this leads to an increase in time efficiency if you don't have to reposition the patient with a different system or do a whole cone-beam CT workflow and move the patient back and forth. In addition, you have a whole surface-guided radiation therapy workflow. So you monitor the surface motion throughout the entire fraction, which increases the patient safety quite dramatically because in automatic beam hold with a latency of roughly 200 to 300 milliseconds is always a little faster than the RTT if she or he doesn't have a hand over the radiation off button.

    What we decided to do for spine patients, you can see on the right-top picture, this is the entire surface we are monitoring for a spine patient in this case. So we don't incorporate a lot of breathing motion, but this is only the wide surface is monitored. And this surface provides enough information for us to see if the patient moves dramatically outside the intended planning or treatment window in this case. The ground tools for the spine treatments are always our X-rays. You will always have larger deviations if you look at surface only because there's some breathing motion inside. But at least this surface gives us a hint if you cannot shoot an X-ray at the moment because the gantry might block or something. You don't wanna shoot X-rays all the time. You still have a surface that can provide you with additional information for patient safety and for the actual position dependent on the X-rays before.

    Additionally, for more and more patients, we are moving to the ExacTrac Dynamic treatments. We're doing less cone-beam CT, so it's possible if you don't have to rely on soft-tissue contrast too much and if you can do a good match on the bony anatomy, and spine is a perfect case in here. So you have less dose and also a faster workflow. But you can see quite clearly the software already does a very nice automatic six-dimensional fusion of the X-rays in the DRR. And you just have to approve this fusion and check if you're at the right position, but the software has very good and quite smart methods of incorporating this fusion. This is maybe not so big on the spine topic, but, in general, you can reposition your patient at every couch angle and you can monitor the patient motions for all couch angles if you use them. This is maybe more for cranial, but, in some cases, eventually also good for other treatment sites.

    A big point in the surface-guided radiation therapy community is the reduction of skin marks or tattoos, also if you're using a cone-beam CT-only workflow. So you pre-position the patient on the patient surface and you can reduce the number of verification cone-beam CTs or even of initial cone-beam CTs. So the reduction of skin marks in this case, if you have a concept where you have surface guidance at your linac or an ExacTrac Dynamic at your linac, you do not need any skin marks because you perform everything with the optical surface camera and the thermal information.

    What we will do in the future, our outlook, we will replace the cone-beam CT workflows for palliative settings to increase the speed. If the soft tissue contract matters, we will reduce the frequency of cone-beam CTs and implement the ExacTrac Dynamic regularly. A big point will be the start of deep inspiration breath holds for left-sided cancer treatments. And in the future, we will start doing some liver and lung SBRT and breath hold where gating on the surface becomes feasible. I want to thank you for your attention. Also, thank you to Max Niyazi for the first part of this talk, and I'm ready and we are ready for your questions. Thank you very much.

    Bogdan: Great review, Dr. Freislederer, and we'll switch now to Professor De Ridder for a review of breast radiotherapy planning considerations.

    Prof. De Ridder: Good afternoon, dear colleagues. First of all, I would like to thank Brainlab for the kind invitation. I will present our work, breast radiotherapy towards a patient-tailored approach. What are the benefits of radiotherapy for patients with breast cancer? Well, whole-breast radiotherapy reduces the incidence of recurrence after breast-conserving surgery. We share a graph from Fisher and colleagues with on the Y-axis, the cumulative incidence of recurrence. You can see the patients undergoing lumpectomy have a 38% of cumulative recurrence incidence after 20 years. If you add all those radiotherapy to this, the local recurrences are reduced to 12%.

    Now, radiotherapy also improves disease-free survival and breast cancer-specific survival after breast-conserving surgery. When you look to the panel at the left, you see the any first recurrences on the Y-axis, and you see that after 10 years, patients undergoing breast-conserving surgery show 35% of recurrences. If you add radiotherapy, this is decreased to 19%, and this is translated into a benefit in cancer-specific survival. We see that the breast cancer deaths, 25.2% after the breast-conserving surgery and a reduction to 21.4% of breast cancer when you add radiotherapy.

    So we have an improved breast cancer-specific survival of 3.8%, and this number is important to remember if we go later on to discuss the late toxicity of breast cancer radiotherapy. A radiation boost to the tumor bed reduces the recurrence in the ipsilateral breast after whole-breast irradiation. This was nicely shown by Bartelink and colleagues, and you can see that they reported that 10% of cumulative incidence of local recurrences in the ipsilateral breast after whole-breast radiotherapy, and this was reduced to 6% at 8 years with the addition of irradiation boost to the tumor bed itself. But this radiation boost will increase radiation dose to the heart if the tumor is located in the lower inner quadrant of the left breast.

    Does internal mammary and medial supraclavicular lymph-node irradiation improve the outcome? To answer that question, we need to refer to the publication by Poortmans and colleagues in "The New England Journal of Medicine." They reported a randomized study with very broad inclusion criteria, namely centrally and medially located primary tumors irrespectively of axillary involvement, and patients with an externally located tumor with axillary involvement. And they reported an improved dysentery survival. So the dysentery survival without development of metastasis was 75% in the patients without regional irradiation, and it was improved to 78% when adding this regional irradiation to the internal mammary and medial supraclavicular regions, but this was not translated into a significant survival benefit.

    But we know that internal mammary irradiation will increase the radiation dose to the lung and to the heart, and we need to balance so the benefits against the toxicity. And that is what radiotherapy perception is all about. It's about balancing breast cancer-related benefits versus long-term iatrogenic events. And to do so, we recently published a paper in "The Green Journal" estimating lung cancer and cardiovascular mortality in female breast cancer patients receiving radiotherapy. And I think it was Darby and colleagues who reported in 2013 a linear effect between the increase in major coronary events and the mean radiation dose to the heart. You can see that women receiving a mean radiation to the heart of 8 gray have an up to 50% increase in rate of major coronary events.

    And Taylor and colleagues confirmed this linear relation between the relative risk of heart disease mortality and mean heart dose, and they reported an excess relative risk of 4.1% per gray mean heart dose. Now, these are relative risks. When you want to estimate the absolute risk, we first need to take a look at the SCORE tables. These are tables developed by the cardiologist and they describe the 10-year risk of fatal cardiovascular disease based on gender, on smoking status, on systolic blood pressure, and on the cholesterol levels. So what we did, we combined the relative risks from irradiation papers with the absolute risk in the SCORE table to estimate the absolute 10-year cardiovascular mortality in risk in female breast cancer patients based on mean heart dose, as you see here, based on smoking status, based on age, on systolic blood pressure, and on cholesterol levels. You can see important differences.

    If you, for instance, irradiate a 50-year-old woman who smokes with a BP systolic of 140 millimeters mercury and with a low cholesterol, you see that even a mean higher dose of 8 gray only increases the absolute risk of cardiovascular toxicity mortality from 1% to 1.2%. On the other hand, if you irradiate a 65-year-old woman with a high blood pressure and a high cholesterol, you have an increased absolute risk of cardiovascular mortality from 19% to 22.9%. Now, perhaps this 3.9% does not seem important to you, but it becomes important when you balance it again to 3.8% in survivability of radiotherapy that I reported at the beginning of this presentation.

    Now, Grantzau and colleagues reported in "The Green Journal" a model of excess risk of lung cancer according to the estimated radiation dose. You can see on the Y-axis the excess risk of lung cancer, and on the X-axis, the radiation dose in a certain region of the lungs. And you can see that the region of the lung receiving 10 gray that these patients are in that region and 85% excess risk of developing lung cancer. In order to translate this towards absolute risks, we use the data from the PLCO trial. In the PLCO trial, they describe the probability of smokers who develop lung cancer according to four parameters, namely the age of the patient, the pack-years smoked, and also the fact that the patients quitted smoking and since when they quitted smoking and if not whether they are still smoking and how many years they are smoking.

    So we combine this relative risk with this absolute risk from the PLCO trial, and we calculated the absolute 20-year lung cancer risk in female breast cancer patients. You can see huge differences. For instance, if you irradiate a 55-year-old non-smoking patient, even a mean bilateral lung dose of 8 gray increases the risk of developing lung cancer from 0.1% to 0.2%. But, on the other hand, if you irradiate a woman from the same age after 20 pack-years of continuous smoking, you see an increased risk in developing lung cancer from 15.1% to 39%. So, clearly, in this type of patients, you need to pay extra attention in keeping the lung dose as low as possible.

    So we developed this novel NTCP model for estimating lung cancer and cardiovascular mortality, and we propose to use it, first of all, for patient-tailored cardiovascular prevention and lung cancer screening strategies after breast radiotherapy. Second, it helped for individualized prescription of radiotherapy balancing breast cancer-related benefits versus long-term iatrogenic events. And, of course, it can be used to evaluate new radiation techniques that are dedicated to reduce the mean heart dose such as deep inspiration breath hold. Deep inspiration breath hold increases the physical space between the heart and the breast.

    Here, you see a CT scan of a patient in shallow breathing where the heart touches the breast. When this patient take a deep inspiration, you see clearly that the physical distance between the heart and the breast becomes much increased. And this deep inspiration breath hold decreases the mean heart dose. You see a patient receiving a 2-field radiotherapy, so radiation to the whole breast, and you can see that the 2 and the 4 gray isodoses are going through the heart. And you include an internal mammary lymph node irradiation. As I discussed in the previous trials, you see that this isodose are going further into the heart. When you use DIBH, you can spare the heart whether you irradiate the whole breast or whether you irradiate the whole breast and the mammary internal lymph nodes. But, of course, to do so, you need a very precise positioning and control of deep inspiration breath hold. And in order to go to this topic, I would like to give the floor to my colleague, Thierry Gevaert. I thank you for your attention.

    Bogdan: Thank you for your talk, Professor De Ridder, and we'll go next to Dr. Thierry Gevaert who will address a rather interesting exploratory outlook into extracranial applications of ExacTrac Dynamic.

    Dr. Gevaert: Good afternoon. First of all, I want to thank Brainlab for inviting me to talk about the ExacTrac Dynamic, and, of course, experience for breast irradiations. These are my disclosures. So when we speak about ExacTrac, we think directly about brain and spine, which we were using in the past to perform the positioning. So, basically, we were using the stereoscopic X-ray images, we have the submillimetric accuracy. And a couple of months ago, we installed the ExacTrac Dynamic and, of course, we started with brain cases as it was quite obvious, but we wanted also to see whether or not we can go beyond and treat other indications with the new software. So when we speak about ExacTrac Dynamic, as it was previously already shown, so it's a 4D surface guidance and then you have a triggering of the X-rays. It can be based on a gantry angle when you are using an arc, and when you are using static beams, you can use the surface or the monitor units to trigger your X-ray. So, that's a bit of the concept. So you have the SDRT, but it will be combined with an RGRT solution.

    So, again, as I was mentioning, so we started directly to treat our brain cases with the new software, and the ExacTrac Dynamic is working really well. It's very fluent for brain cases, but we wanted to see for extracranial indications whether or not we could use it already in the first version. So, as Professor De Ridder was already mentioning, the idea is basically to look whether or not we can do monitoring for breast cases and in this way also have an idea about the NTCP modeling and also to be sure that the dose will be deposit at the correct position.

    So, for breast cases, when we look in our department, we have kind of points of improvement where we think that maybe the ExacTrac Dynamic can help us out. So, first of all, we have the pre-positioning. We are still using the tattoo points, so it's a three-point alignment based on the lasers. Then, of course, during treatment, we don't do any kind of intrafraction motion monitoring, so maybe here we can also add the value of the ExacTrac Dynamic. And then, of course, for left-sided breast, the idea and the concept is you have a breath hold. So how stable is that breath hold during the whole treatment course? So these are the three points that we think that we may improve in our department with the use of the ExacTrac Dynamic.

    So let's first move forward with the SGRT solution. So it's an optical surface scanner, so, yeah, in the literature, you find already a lot of publications about it. I took the review of the LMUC. And so, yeah, we all know that it has a high spatial and temporal resolution. It's an important addition for patient positioning and monitoring. And there is already a broad agreement on the superiority of the surface scanning compared to the three-point laser alignment. So we know that it's working well in the literature, but as we are the very first to try it out with the ExacTrac Dynamic, we wanted to see whether or not it was also feasible with the ExacTrac Dynamic solution. So our idea is to go to a complete tattoo-free workflow. As for the patient, it's a constant reminder of the patient cancer treatment. We believe that getting rid of those tattoo points can be beneficial for the patient. And, secondly, of course, as it's completely automated, we may believe that we can have also a reduction in patient setup time.

    So let's first look about the pre-positioning. So the pre-positioning is based on the structured light. So at that moment that you will pre-position your patient, the thermal information will not be available. So, basically, once the structural light is seeing the patient, you will start the pre-positioning. And as you can see over here, you have the lateral, longitudinal, and vertical shifts and also the rotations. So, our idea is also here as you see the rotation directly on the screen, we believe that this can also be more easy for the nurses in order to pre-position your patient accurately and get rid of those rotations.

    So, in order to see whether or not it was working, we did a little study on 10 patients, and we started our study after 5 fractions once the patients were familiar with the treatment. And we pre-positioned them three times with the ExacTrac Dynamic, and then afterwards three fractions with the laser alignment, and the residual positioning error was measured with the cone-beam CT. It's a small population group, so it's not statistically relevant, but you see for sure that the ExacTrac Dynamic pre-positioning is within alignment with the laser alignment. And when we were speaking with our nurses about that kind of pre-positioning, they were feeling that it was more efficient. As they can see and visualize the rotations, they were feeling that they could more easily reposition the patient prior to perform the cone-beam CT.

    When we speak about efficiency, I took some data from the group of Reims where they had one month experience with the system. And what we did there is that we randomly selected a day of treatment and we were recording the time of pre-positioning for all the patients on that particular day. So there are cranial and extracranial indications, and we see that on average, we can pre-position with the ExacTrac Dynamic a patient within three minutes, which is, I think, very acceptable, and it shows also the efficiency of using the ExacTrac Dynamic for repositioning purposes. So that's a bit the concept.

    One drawback about the pre-positioning is the robustness. So, up to now, we only use a structured light to perform the pre-positioning. The thermal information is switched off at that time, and we believe that adding the thermal information will increase the registration accuracy. The reason that we are thinking that is that in the patient that we were pre-positioning using the structured light, sometimes the camera get lost and we couldn't perform the pre-positioning in a decent way. So, adding the information of the thermal camera is, I think, of major importance for the pre-positioning robustness. When we look into literature, it was also already confirmed by some groups that are showing that the use of a three-camera system compared to a single-camera system will give a better surface coverage and, of course, also a more accurate patient setup.

    The other reason why we think that the structured light together with the thermal information will increase the registration accuracy is also because once we start the workflow of the two-camera system, we didn't have any issues anymore about getting lost of the positioning of the patient. So, again, the surface scanning using structural light and thermal information was very stable, and so adding that in the pre-positioning phase is, I think, also a good solution in order to be able to have the robustness that we are looking for in the pre-positioning case.

    When we move on, so we can align our patient quite decent and past before performing the cone-beam, but what about the intrafraction motion monitoring? So, as in our department we are treating our patient with simultaneous integrated boost, a cone-beam CT is still the way to go for the moment as we want to see whether or not the boost region is positioned correctly. But intrafraction motion monitoring, for the moment, we are not performing that, and so we were looking into the solution of the ExacTrac Dynamic. So, first of all, before that you can perform intrafraction motion monitoring with the ExacTrac Dynamic, you have to look and to choose your region of interest in a correct way.

    So, as you can see on those images, so depending on the situation, they are contouring the breast in a different way, and we were also seeing that this will affect the accuracy of being able to follow the intrafraction motion monitoring. So, first of all, choose the region of interest correctly in order to be able to have the surface scanning working well. So that's the idea. Once you have contoured the region of interest, you see directly that, again, it will give you the three shifts and the three rotations in order that you can follow during the old treatment course, whether or not your patient is moving. So that's a bit on the SGRT monitoring. It's like a lot of system already showing so you get the 6D information of your patient positioning.

    So I speak already a little bit about intrafraction motion monitoring. Is it really necessary? So when you look into literature, you see that whether or not the deviations are large, like in that publication, you see that sometimes patient can move more than one millimeter. So, again, it's not that it's for every patient, but some outliers can cause that you will misalign your patient during treatment because of the motion of the patient. So, again, if you can monitor it, it can be interesting in order to cope for those outliers and in order to be sure that all the patients will be treated in a decent way.

    So that's a bit the idea, but these studies that you can find for the moment in the literature are basically based on SGRT positioning and monitoring. And whether or not they have a feeling that the SGRT is showing that there is a misalignment, they redo an [inaudible 00:58:58] positioning or they do a CBCT. So, basically, nothing can be performed directly together with the SGRT at the moment, and so we believe that coupling the surface imaging together with the [inaudible 00:59:14] with the stereoscopic X-ray images can be an advantage because you directly get confirmation of the anatomical information. And as your threshold for repositioning will become smaller because you can directly take images, we also believe that maybe you can more easily reposition your patient with the surface information that you will get during the treatment.

    So how does it work? So, basically, during the old treatment goes you have the surface and the thermal camera that gives you the information about the motion of the patients. So these are the numbers over here. And depending on the way that you want to trigger, do you want to trigger MU-based, on a gantry angle-based, or when the surface is out of a certain action level, you can directly also trigger the X-rays like you see over here. The positioning is performed automatically, so it's an automatic fusion, and then you get directly also the results of your X-rays. And so basically also there, you can directly feel confident whether or not what the surface is mentioning as errors. Is it also completely correct with the anatomical matching of your stereoscopic X-ray images? So we believe that SGRT together even IGRT workflow can make things more easy in order to be able to see whether or not you have to reposition your patient.

    So, of course, these indications that I was showing, it's just for intrafraction motion monitoring. But, of course, for left-sided breast, as Professor De Ridder was already mentioning, we also performed deep inspiration breath hold. So we have a breathing monitoring, so what about that stability, and can it affect also the intrafraction motion as we will ask the patient to perform a deep inspiration? So, again, there, we will see whether or not we can use the information of the SGRT and IGRT in order to do your positioning. So we are performing in our clinic a gating window of 4 millimeter because it proved to be adequate for clinical routine. And when you choose that kind of gating window too small, you will see that some patients have problems to keep their inspiration within that level and the treatment will become very long, which means the patient can start to move, and, of course, also, you will lose also the benefits of your deep inspiration breath holds. So, again, here, you see that on the thermal camera, you can see also the patient breathing and performing the deep inspiration breath hold.

    So then when we move to clinical situations, so, again, we take a deep inspiration breath hold of our patient. At the time of the DBH, we perform X-ray positioning. So, we block out the spinal cord, the clavicula in order that those kind of anatomical information will not be used for the registration. We then get rid of the table, of the couch, in order that this error will not affect the registration. And then you restart the X-ray positioning, you see whether or not it's acceptable. And if the X-ray's fusion is acceptable, you start and you go to the treatment. And once you go to treatment, you have directly the surface scanning that will be switched on in order to monitor your patient. And here in this situation when the gantry will be up 90 degrees, we will take automatically stereoscopic X-ray images to see if you can see it's also anatomical. So you see if SGRT is correct, and you see that the numbers are matching together, so it means that SGRT is well in place and the anatomical matching is just showing you that...it's giving you the confidence that the patient is not moving during the complete treatment course. So this is a bit the idea about how the workflow is working now, how we tried to implement it with the first version in order to cope for intrafraction motion during the treatment.

    So then we have a second case where the nurses were telling me upfront that that patient was moving time to time. So, again, we take X-ray images in a deep inspiration breath hold prior to treatment. We tried to get rid of the moving parts like the spinal cord, the clavicula, and so on. You perform your registration, so you saw that there was a small part of the spinal cord over here, so we blocked it out in order to make sure that the registration is really performed on the rib cage. You'd check the registration if it's acceptable, you acquired it, and you perform the treatment. So, again, we start the surface-guided monitoring, and, again, at a certain gantry angle, we will take some stereoscopic X-ray images.

    And here, in that case, we see that the X-rays is seeing a motion. Of course, it's a preliminary data. We didn't correct for it as we want first to get familiar with the software. We're just starting to monitor the patient. So you see that for the moment, we are out of tolerance with the X-rays and with the surface guidance, and then, suddenly, due to the couple of deep inspiration breath hold the patient is performing after each time, you see that suddenly she's repositioning herself and that we are, again, within the tolerance. Of course, also, what I have to mention is that we took a tolerance of three millimeters, so when we were outside of those three millimeters, it will give us a red zone. So that's also something that we have to get familiar with, what kind of threshold will we accept for performing and repositioning based on the surface guidance and the X-ray imaging. But it's also to show you...so the nurses were telling me from that typical patient was not relaxing on the couch and was time to time moving. We see also directly that the surface guidance together with the stereoscopic X-ray images is also showing that there was a movement detected.

    And so what we performed also, so on DIBH patients, so we took five patients, which were the five first patients that we treated together with the surface guidance and the X-ray images with the ExacTrac Dynamic. And so we took those five DIBH patients, we took two fractions and we were looking into the greatest deviations from the 6D displacement. So, basically, each monitor unit, this graph is showing the greatest deviation of all 6D information. And you see that that curve over here is the patient that I was just explaining, and you see for the other four patients that you are within that 3-millimeter tolerance except for that patient where you see that it's slightly getting out of tolerance.

    So, again, for the moment, we don't do anything with those kind of information. We are just monitoring it because for us also it's a new tool. We have to understand how it works. It's a first version, so we want just to have a proof of principle for the moment and then to write down a protocol in order to merge together with a solution where we will also cope for motion and correct for the motion that we will see with the ExacTrac Dynamic. So when we think back about the presentation of Professor De Ridder about the NTCP modeling, so that modeling, if we want to perform that in a clinical way for all patients, we have to rely on the assumption that we have a correct dose delivery. So, dose gradients towards the heart and the lungs remain sensitive to positioning variation. So we have to have a kind of robustness evaluation of the positioning variation of our patients in order to be sure that all the patients that will be treated will be within a kind of tolerance that we will have to decide. And we believe that monitoring it and repositioning it with the ExacTrac Dynamic based on surface guidance and image guidance, we believe that this is the best option in order to be able to correct in a very accurate way the motion that we will see with our patients during treatment.

    So, to conclude, again, it's more a proof of principle. So we believe that ExacTrac Dynamic provides guidance for correcting patient posture. We can go to a tattoo-free workflow. It's a combined workflow of surface guidance and image guidance. So, basically, you have the surveillance of the intrafraction motion based on surface and thermal information. And you can, at the same time, perform automatic triggering, which I think it's an addition to the surface in order that you get internal anatomy and you can perform registration based on internal anatomy to see whether or not your patient was moving. And, of course, also, it will offer you the possibility to evaluate whether or not you have a deep inspiration breath hold stability.

    So these verification images during treatment, so during the surface scanning, I believe that it will also change the philosophy of the action levels for typical SGRT devices. Up to now, the SGRT is just giving us information about how the patient is moving during treatment, but we don't get any information of the internal anatomy. So adding that information will give us more confidence to more easily also reposition our patient during the treatment. I thank you for your attention.

    Bogdan: Thank you for your talk, Thierry. And for those of you interested in seeing a more integrated solution for DIBH setups, please go to the virtual Brainlab booth and request a demo for our ExacTrac Dynamic product. With all four lectures completed, I would like now to start our live question and answer session.

    Excellent. Well, thank you all for your presentations, and let's see if we can go into a live question and answer session. And, Professor Niyazi, perhaps I will start with you. Thank you for reviewing the benefits of a radiosurgery or SBRT spine program. A question I have, what, in your opinion, do you think are the challenges for the radiation-oncology field in establishing spine radiosurgery programs? What would be your guidance to other radiation-oncologists that wanna start one? And also, based on the polls today, it feels like even though some responded that improvement in collaboration with the referral patterns, medical oncology or neurosurgery would help, almost 50% attributed the success of a radiosurgery spine program to having dedicated technology. So what do you think?

    Prof. Niyazi: OKay. So, thank you so much, Bogdan, for this question. Can you hear me, actually? Is that fine?

    Bogdan: I can, yes. Thank you.

    Prof. Niyazi: Okay. So connection works, so, perfect. So, actually, it's entirely correct that you need, like, a referral pattern, and according to NOMS criteria, you need the collaboration within the center and the referral pattern should be in a way that you have, like, neurosurgeons or orthopedic surgeons that could, for example, reduce epidural disease if it's necessary. If the Bilsky score is high, that's the one part, but the technique itself is important as well. And as you've seen on the ASTRO right now, there have been these very nice data from Arjun Saghal in this CCTG and C24 trial. It was really highly positive if you look at the complete remission rates. So, spine SBRT from an evidence level is very high, so you should at least try to proceed in that way.

    And we're now facing, let's say, the situation that we have the technique, we have the machine there, and we'd like to force our program and now moving from 10 to 5 to now, 1, 2, 3, or 5 fractions And I think the first step will be you have the collaboration with the neurosurgeon, but they're actually very motivated to proceed with SRS spine radiosurgery normally. And you need, like, the technique, of course, and you need some local guidelines, and there's plenty of data out there from ISRC. And I think it's only, let's say, you should just start with the program as soon as possible as evidence is there, it's fine. Some people argue with reimbursements, but if you, like, try to start with stereotactic therapy, normally, the high precision is at least reimbursed in another way compared to moderate hyperfractionation, so I think there will be ways to force this technique.

    Bogdan: Excellent. And, Phil, maybe I'll ask you a related question. Last time, we also had a lot of technical questions regarding spine radiosurgery. So, first of all, maybe we start with what kind of energies do you select for treatment, and maybe then we'll go into IGRT. So do you use both 6X and 10X for spine [inaudible 01:13:24] beams? And do you go to the highest dose rates possible given your energy? And in link to that, what do you do on the IGRT side for checking for any intrafraction changes?

    Dr. Freislederer: So, first of all, we are in the fortunate situation that we cannot choose between the energy because on our linac, we only have 6 MB, so 10 MB is not entirely an option, but I don't see any specific reason why you would use higher energies for the spine. It's still possible. We could go flattening filter-free, but we do not at the moment. It doesn't really for those mostly stereotactic cases, we haven't seen quite a benefit also when it comes to time. Just an example, we just had a spine SRS case plan with dynamic conformal arc and three different couch rotations. So it's always one arc per couch rotation, so I don't think there's really a necessity at the moment to go to flattening free, but it is still possible.

    Bogdan: And, Professor Niyazi, it seems that there's still no real consensus in terms of what kind of margins to assign for the PTV definition for SRS's SBRT spine treatments. What do you do in your practice? What is your opinion on what you should be doing for these kinda treatments? And in link to this, what IGRT solutions would you recommend in order to be in sync with the margin definition that you would embrace?

    Dr. Freislederer: Okay. Thank you so much. Very good question. Actually, if you have a look at the study protocols, for example, for different, like, SBRT regimens comparing with moderate hyperfractionation, you normally will find something with around one to three millimeters added to the CDV according to the ISRS recommendations, for example, not include the entire vertebral body but spare out the spinal cord, spare out the spine process if it's not involved, for example, or if the posterior elements on both sides are [inaudible 01:15:39] you have to include it. So you have, like, a donut structure, then you can spare out the cord.

    And the cord in the thecal sac volume, so the PRV is depending on the technique you are using. So I would advise at least to have the best possible technique to track the situation. ExacTrac Dynamic at least enables to have the highest possible tolerance here on the [inaudible 01:16:01] gradient. So it's important to know which movement is there intrafractionally, and then you choose your constraints. And, after that, you can add to your CTV, like, let's say, definite margin. If you have, like, extraspinal disease and some soft tissue, you should probably go beyond, like, five millimeters and then you add up this PTV margin in the end. And that's your CTV and PTV, and then you exclude the spinal canal as you cannot achieve these high-dose gradients to the cord.

    But, of course, you have the confidence to treat, let's say, the lytic disease if you keep the constraints, if you have, like, a small PRV with 1 to 1.5 millimeters and PTV margins of, let's say, 1 to 3 millimeters according to situation and literature, and that would be my advice. Audit your own results, look at the technique you're using. And if you have, like, something, the ExacTrac Dynamic really enables to check for these margins throughout the treatment, then you can reduce your margins in the end, and that should at least allow you to achieve the highest local control rates and the best gradients to the cord and other organs at risk around. Thanks.

    Bogdan: So, Dr. Freislederer, a linked question to this would be what do you recommend for IGRT utilization and how frequently to image patients based on how you create treatment plans. And also, you were mentioning that you're considering completely switching to ExacTrac Dynamic while most users are probably still going to have some sort of cone-beam utilization, so what is your rationale when doing that?

    Dr. Freislederer: So, in general, for all our patients where we apply the couch shift according to ExacTrac Dynamic, we're not using any cone-beam CT positioning at all. We're solely pre-positioning the patient on the surface. We still have two skin marks drawn up on the patient, but most of it is done
    Info
    Title:
    ASTRO 2020: First Clinical Applications of ExacTrac Dynamic
    Topic:
    Cranial neoplasia (benign)
    Intracranial metastasis
    SBRT
    Spine radiosurgery
    Year:
    2020
    Speaker:
    Thierry Gevaert
    Niyazi Maximilian
    Freislederer Phillip
    De Ridder Mark
    Language:
    English
    Category:
    Duration:
    01:09:39
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