 Okay so really what I want to do today is do a little bit of a review so I'm going to basically try to tell a story okay and obviously no story is fully complete and so I will have to try to make it an overall review a global view rather than to go into a lot of very specific details because all the details hopefully will be at will be addressed by the rest of the speakers during the week is that okay? Okay so just to say it again I will try to go over basically a broad broad view of how do we move from very early radiotherapy to what we have now and perhaps I'm not even going to be able to touch the most advanced things but that leads to get us the framework for the rest of the week so let me start by asking a question how many of you are doing IMRT just raise your hand okay so it's about maybe 15-20% how many of you are you doing 3d conformal therapy using you know those volume histograms for evaluation and so on so it's about half okay that's great and how many of you are doing about basically 2d therapy in external beam there is quite a few okay not not as many but I mean quite a few and we're not doing radiotherapy at all there is a couple okay alright so hopefully I will be discussing things that may be of interest for those that are going to be moving from 2d to 3d to IMRT and hopefully I'm not going to bore all of you that are doing IMRT already okay if you are bored just leave and come back at the end okay so let me basically tell you how what did the process in radiotherapy looked very very early on we had a patient that was assessed the physician decided to treat decided what he wanted to treat so he did some target localization and we'll see you know the sophistication of that defined what the treatment was to be calculate some treatment parameters verify the patient position and deliver the treatment okay this is an early radiotherapy in 1d basically there is basically no team the physician decided to treat a breast tumor he has an apparatus a very early x-ray tube puts it on the tumor and he has a timer on his hand so that's the way he defines the treatment that's the dosimetry at the time of course I mean this is many years ago probably much before I was even born but what was the prescription in not necessarily those days but even later on I mean in the 40s 50s this is a typical chart on a patient the description of a patient in a chart so what did we have here there was some text and I know that you cannot read it because it's blurry but there's some text that says that this patient needs to be treated to the femoral red probably some you know complications some metastasis and so on and you have two drawings made by hand because the physician knows the anatomy and he draws what he knows about the anatomy there is no x-rays so he defines and in this case you have a anterior right anterior and right posterior I don't know if you can read that and it shows the extent of the fields and basically that's the simulation if you want to kind of translate it into your modern days so many of you have probably seen cobalt units cobalt units were introduced in around the 1950s there is a number of models that were available in the market this happens to be one that I just saw not even two years ago in Russia in Moscow it's a very interesting unit but it's a cobalt unit and it has some specific motions that basically were designed to do radio surgery if you believe it or not okay but most of you probably will be familiar with a unit like this with a cobalt unit like this more or less more modern with a beam stopper and the mechanism to generate the radiation is extremely simple we have a head of the unit with some aperture that will allow the radiation to come out collimators to restrict about the amount of the field size and a radioactive unit a pill if you want a radioactive source that with a mechanism just to move it in front of the aperture and you do the exposure and you move it back and that ends the exposure so many of you have seen is anybody here not seen a cobalt unit or not work with a cobalt unit so there is a few well interesting because I guess the majority of us particularly if you are my age I mean we definitely saw cobalt units but the principles about doing using cobalt and even later linear accelerators when they were just introduced it was basically a 1d or if you want and we'll see it in a moment a 2d treatment so what was the dose symmetric calculation what did you calculate those typically we had what we called a SSD beam on time table was a table that we generated based on some measurements but the but all of those were completely related to just one number and that number is this number here the output of the unit and this is from 1969 that was I found it in the records in my hospital when I became chair of chief of physics in 1985 and it was in the records and this is an interesting table and I kept it because it was signed by Lillian Jacobson Lillian Jacobson was a medical physicist in New York one of the pioneer women in radiation therapy and by the time I was there she was you know longer tired but if you see here this is a table for 80 centimeter SSD treatment with a single field just to calculate the beam on time how much time do we need to keep the beam on to give a specific amount of radiation and in this case the output was in rendients per minute not in rats rendients per minute at 80 centimeter SSD 104.8 Rengar Rengar's per minute and if you wanted to treat something which was and this is specific for a 10 by 10 field that the hundred SSD and if you wanted something else you just went through the table it say you had a field that was bigger and was equivalent field size of 220 by 20 and with a particular depth you calculated this is the time that you need to have the beam on and it give you another number and that's interesting that this is was another number was of importance because if you gave the dose that you wanted at depth you had a much higher dose somewhere else okay and that was at the entrance of the beam and these tables were used either for single fields or sometimes for two fields perhaps parallel opposed so I'm sorry I cannot understand no no this was in in water I mean it was calculated in Rengar's you know per minute for yeah so in radiotherapy 3d if we were to summarize or just to say an overview the planning is very simple beam arrangements and we'll see a little bit of an example of different primar renderance the prescription usually was to one point that was all and the calculations used either standard tables we would correct for SSD sometimes I mean if you had a patient who was too large or you wanted to treat at the next and the distance you call you adjust for the different SSDs and if there was a little bit of blocking which was not very typical at some point they will put some blocks on the corners they didn't they knew they didn't want to treat too much tissue that was not necessary and you will calculate what was the equivalent square okay so there were formulas to do that and you could have sometimes one other point of interest where you calculated the dose but that was about it okay so as we moved with time we came to an era of what I call the 2d treatment planning area or 2d radiotherapy process so we added a few blocks to this diagram to this flow diagram and in addition to the acquisition of sometimes we had an image and we'll see it in a moment you had different dose distribution calculations and typically the calculations at that time were done by hand how many of you have done I saw the scores calculated point by point by hand one two three good four wow so we are like a six okay so so and then we had something which we call the plan approval somebody looked at the plan and decided to check perhaps some of the numbers transfer the information to the unit basically it was just a number of beam on for the beam on time and verify the things and deliver the treatment so that the process didn't get too much complicated but in the 1980s there was a big output of radiation therapy textbooks and I don't know if all of you are familiar with Fletcher's book anybody that didn't see the book that was basically the the text books for radiation therapy physicians and physicists but Fletcher's book and this is the edition the I think it's the second edition from 1980 and I took a couple of pictures just to illustrate one thing if you look here there is a radiograph and you see this little marker here it's a physical object that was put in the patients into the patients up to the cervix okay it was for treatment and how is the field defined here you see the field definition it was a radiograph and the physician drew with a marker just they drew it on the film and that defined the field but if you notice there were some well you cannot notice it here if you read the book there were some rules how to the where to put the fields because you couldn't see inside except for that marker so if you went on the radiograph you put the fields according to some certain rules and the rules were related to the bony anatomy because you couldn't see soft tissue now when you take those took these radiographs in order to know where you were to the outside of the field because you couldn't put the patient no you can treat the patient when you took the radiograph you have to move it to the treatment machine they were all kind of very clever mechanical devices developed and this is just one where you had the x-ray tube was going to be connected to this plastic box and the plastic box was attached through this marker you see the marker is going into the into the patient and there were measurement devices and things that would allow you to relate the inside of the patient to the outside okay and this is another one so with all this and the other thing that you knew people started realizing the patients were not just made of a block of water and I know that some of you have seen this picture and I know that Santiago did see that but anybody knows what this is huh no okay well for those of you that think it's a torture device it's not the torture device had the points coming in the sharp points this is just to take a patient's contour and many of you have taken contours with other devices they were all kind of methods with plaster of Paris with lead wire and so on but the idea was that because the patients were not square we need to take into account the contour of the patient so here we have a two diagrams one of them which is a series of diagrams a we see the external contour of the patient and we see a block here in the middle this rectangle in the middle which basically is the dimension of the two fields from the laterals and the anterior and posterior that's our supposed target that's what we want to treat and there were fields which were calculated and there is three diagrams here the first one is an APPA treatment in which we try to treat this area and in order to treat this area with APPA we see that the isodosis and this was to treat this with about 5000 rats or centigrade nowadays it had 15 5500 which means 10% more here and up to 60 5600 at some point so basically what this demonstrates that with this type of treatments we couldn't really avoid over treating normal tissue and in order to compensate for that new developments came along one of them is to increase the energy of the beams with higher energy linear accelerators by then they were available or a betatron in this case a 25 mEV betatron and you can see that even with the APPA we improve the situation much better because now the 5000 it's covering basically the box that we want to treat but still there is quite a significant those outside with the advent of isocentric machines that can rotate around the patient which was much easier to keep the patient in place and irradiate from different directions typically it was from very conventional directions laterals APPA not nothing too sophisticated and with that we came and made a big step forward because now the 5000 not only enclose this but outside of the 5000 we went down to less than 40% in this case 2000 isodose line okay so we made some advances in that direction and then with the advent of some very primitive computerized treatment plans we were able to calculate lines of isodoses on a very complex anatomy like this one that's the that's a nasopharynx I believe and we were able to take into account wedges or other beam modifiers now one of the things that this allowed us to if we were to summarize what this step allowed us to do is that we started still keeping in mind that the target is defined in relation to the anatomic landmarks the bonnie bonnie anatomy essentially but the extent of the field was still knowledge by the anatomy and the disease pathways because you couldn't see every detail of the tissue and the physicians needed to rely on knowing how diseases progressed how did they know how the diseases progressed many times from postmortems of or surgery after the fact so there was no way to know so they had some rules and if you were to treat something you needed to treat the certain lymph node chains so the physicians were the ones that had that knowledge and basically here created the target that included all that stuff and still there was this extensive reliance on physical examination palpation physical measurements of the patients the dose distribution information was still limited to one plane of interest as we saw it before just one plane one usually a crossplane and the fields were set in order to cover the anatomy and the energy selection was extremely important as I just saw it show you in those three slides the energy and the able to come with from different directions and the protection of the critical organs was again set by experience so if a physician after doing probably dozens of cases saw that there were certain complications with rectal bleeding he knew that I mean he had to cut down on the field sizes okay so that's what the the 2d radiotherapy period so in the process basically we added a couple of more things I mean we just spoke about this and the measurements and contours and the beam arrangements and the dose calculations obviously all the rest and we started seeing much more use of blocking and the blocking sometimes was manual or was custom made and we have all the rest of the process many of you have seen pictures of patients with tattoos well what was the idea of a tattoo we wanted to know where to position the patient into the treatment beam usually we had a crosser projecting to the to the patient that was your reference to where your beam was going to be and you needed to know the outside to the inside the relation and that was the purpose of the tattoos the tattoos were sorry the tattoos were done on under floral usually or some other method that you could relay them with the introduction of simulators radiographic simulators fluoroscopic simulators we still had to rely on palpation the use of planar images but we still didn't have information of actual volumes because usually x-ray units didn't have the capacity to give you the contrast for soft tissues except in some cases for instance if the lung if you could see clearly a mass in the lung you could perhaps tell that and but we still were keeping the rules to this disease sites as the way to decide on what the field size should be and the blocking was not done in order to conform the dose distribution to the target it was mostly driven by avoiding complications so that was the main the main purpose of blocking and shaping fields now I hope I can keep a secret here I mean are you all promising not to divulge this okay all right can I have all your promise okay well basically we never treated 2d patients with radiation therapy I mean with all this stuff for many years but I can tell you all our patients were really three-dimensional all our patients were three-dimensional okay we just didn't know any better because we could only use radiographs that collapse everything into one plane like you know you collapse everything compress it and all we can only represent one pay one plane at the time sometimes perhaps two but our patients all of them were three-dimensional we didn't have two-dimensional patients okay so don't tell anybody because I mean otherwise we'll get in trouble all right so in the 1990s I mean about ten years after Fletcher's book there is another series of books with the advent of city simulation cities became more accessible and more available to radiation therapy and we see now the textbook is now all based on this type of images city images okay now I think this book by the way I don't want to get in trouble myself but I think if you Google it you can probably download it you know from the internet the old book okay so what is different here first of all we have cities but only on top of the cities we have all these lines which basically simulate fields or the width of fields on that particular plane we have this type of image where we see superpose into a cross-section of the patient a reconstruction and onto the reconstruction these little loops here which will go further later I mean are basically the representation of targets that were defined on each city slice but reconstructed in a way that we can superimpose it into the radiograph where the radiograph origin regular radiograph wouldn't allow us to see that and we can shape now beams or or apertures and we can do diagrams of different kinds so very powerful tools so what is basically if we wanted to get a definition of 3d conformal radiotherapy is basically this designing a delivery both the design and the delivery of treatment plans based on 3d image sets with the treatment fields individually shaped to treat just the target that we want to treat basically that would be your operational definition of 3d conformal therapy now obviously this required a lot of new tools that the new treatment planning systems started developing first of all being able to design beam orientations on a structure which is reconstructed for my from multiple planes we were able to display what's called the beams I viewer a simulator basically was a device that had a beam side view because the source as just explained the other day on Friday I mean the source is located geometrically in the same configuration as the radiation source for the radiation treatment unit but now we wanted to do it before with based on city so there were geometric projections that you could use you could design or plan when they beam weights to compensate for different amounts that you wanted to come into the target from different directions we could calculate the dose distribution throughout the volume and that was an important thing because before that we were doing it only one plane at the time now we can calculate into the volume which meant the computation of the 3d dose both for the target and for critical structures was required as much higher sophistication of the algorithms to calculate the dose because if we could before calculate just a ray trace on one on to each point on a plane now we had to calculate the contribution from a ray coming in this plane on to the plane behind it or before it so this required no algorithms for those computation and I don't remember if somebody is giving a talk about this or not but this is a very important part of it and the other thing that this allowed us is to use what's called with those volume histograms is I'm sure that everybody that's doing conformal and I am RT is being using those volume histograms is somebody that is not familiar with the concept of those volume histograms everybody knows that okay so that's great so but those volume histograms required that you define the volumes for calculating the dose to those volumes and that was only feasible with the advent of the heavy use of CT images and another thing that started to be developed is to be able to calculate predictively or to at least have some models and I'm sure that Colin Orton who is going to talk about this about two more control probabilities and normal tissue complications probabilities so all of that was made possible by this big advance the process got a little bit more complicated along the way so we had now 3d those matrices statistics on those matrices like the DVH is a statistic and so on I'm going to skip a little bit because I know my talk is long and some was very generous and allowed me to extend a little bit on a few things that will make you know in preparation for this talk so I'll ask you to bear with me so I apologize for that's a bad quality image is fuzzy but what I wanted to show you is that because we were trying to be tighter to the target now the issue of immobilization of making sure that the patient was in the same place all the time and every time became a little bit more important but not only that you see all this writing on this immobilization I don't like to call it immobilization because really if any of you has been inside of one of these you know that you are not immobile you can really move around that okay but it's basically to remind the patient don't you'll just walk out of the table okay so they but you see all these things well these are not get well wishes that somebody tattoos on somebody breaks a hand and you know just they do on the cast and so on they these were many times instructions okay well we did this alignment to this position when we did the CT but when we want to treat we want you to move three centimeters superior and maybe two centimeters to the left of the patient and all those are instructions and this became a very important place where errors could be made okay but we are not going to talk about errors today we'll talk about this I think on Thursday so how did we know the outside to the inside we couldn't know that unless we put something physically that showed on the CT but was physically on the patient so it this is like a central cut for one simulate simulation you see these little dots here basically our high Z BBs or some other material that could that you could relate any anatomy inside the patient to that point that was a tool on the patient outside because otherwise we cannot do the CTs every time we treat except that nowadays there are some new techniques where you do CT simulation every single fraction okay but that's you know much later so if we went to so we had those reference marks and basically the other thing that we needed to do is in order to define what the target is we needed to be a little bit more sophisticated and say well what what are these things that go into the thinking process of the physician in order to come up from what he sees to what he wants to treat and once he tells us what he wants to treat how do we assure that what he wants to treat is going to be treated every day and there we have all these new concepts of GTV the gross tumor volume that's what he can see you know I can see you can see anybody can perhaps see maybe not necessarily interpret very well but we can see it to the clinical target volume the clinical target volume is completely a clinical decision it's not up to physicists or anybody else other than the physician the radiation oncologist to the side he needs to decide this is what I see but I need to treat this because there is microscopic disease or there is certain things that I need to consider needs to be treated every single day to such and such those so and that's a clinical target volume then once we get that we have what's called the planning target volume because not the volume that the physician wants to treat we have to enlarge it or make accommodations because nothing is perfect in life okay except a few of you and myself that we all think that we are totally perfect everything else is not okay and treatment radiation therapy is not perfect either so we have to accommodate for all these things and then we come up with what's called the pTV the planning target volume which is what we want to cover every single day and we need to define also the volumes that are at risk that we want to protect otherwise we won't be able to calculate what if we don't define the volumes at risk what I cannot hear the dvh I mean we won't be able to calculate dvh on something that we don't define all right okay so this is still conformal therapy and just to get an idea about how this works in the process why did we need to go all through all these steps is because before we were setting up fields which were very simplistic like blocks or so on or squares rectangles but if we look at any anatomy and this is just a prostrate case and you can see the prostate the patient is prone so there is the bladder and the rectum the rectal wall but if we move a few centimeters superior to that that anatomy changed significantly here we are already beyond the process into the seminal vesicles the bladder is much bigger the rectum is different and the femoral heads are different and so on so this is where the three-dimensionality comes about and if we represent it into a beam side view with the dvh a digitally reconstructed radiograph we can project those volumes here now I want to tell you a little story because that's when we started doing 3d conformal therapy in our department our both the physicists and the physicians were all used to the old school so one of the first things that we did is we take we took this digitally reconstructed radiograph and we had very experienced radiation oncologist and some of them were even radiologists because at the time I don't know in many of your the countries that you work in many of the old school were trained in radiology and radiation oncology both so we took this digitally reconstructed radiograph this is the right view from that lateral and we say I didn't show these things okay we didn't show this and we didn't show the and with with all the physician well how would you treat this what can you just draw the fields okay for those of you that remember I mean for the prostate and the treatment was a press prescribed to 65 grade to the isocenter and this is a small prostate but we didn't show that so we just show the anatomy you didn't know really what the prostate was so how we did it go it takes a 10 by 10 for the lateral this is a 10 by 10 field takes two centimeters posterior to the synthesis pubis okay the center the isocenter is at the same level at that level and and this is you are one of the fields so you went through all these fields through the fields and say okay well let's now calculate the dose distribution from your fields we didn't show him this the actually the volumes okay he only saw the radiographs because that would what he would have done before that correct so we show the dose distribution we project it calculate it show it in three in in a isometric display and we show him well this is it here this is the prostate these are the lines that describe the process that he delineated and this is the cloud of the 65 grade that you prescribed okay what would you say he says my god we missed it we are missing the completely all right we are treating outside so I say okay don't worry okay because that's not the end of the complete story this is 65 gray if we just take that cloud but take it to 63 gray which is just 3 percent below the prescription okay it's not so bad look see nice you covered everything except that you treated all this that you didn't need to treat all right so and we did that for not just a small prostate but for a large prostate okay in the past before we had CT we wouldn't know the difference so for his large prostate the 63 gray well it was a little better but still we missed part of it and we still were treating all these of the rectum but this was what used to be the standard of practice in radiation therapy for prostate treatment there was no better way to do so virtual simulation was something that happened when the CT scanners made were made available and some companies in this case is picker developed software to work with the simulator to be able to project your beams onto the anatomy that software usually nowadays for all those that of you that have IMRT I'm almost sure they all have the equivalent software so there is no need of another so piece of software somewhere else but the basic thing that I want to show is this that what this allows us to do is to project beams in directions that in the past we couldn't use the bony landmarks to define our fields because this was totally not something was easy to interpret and in this case you have like a 45 degree beam and you can see the diagram of the beam coming here and we can we started being able to not only select the field size electronically but also select in this case is a multi lift collimator setting what does that allows us to do is the following not only we can shape the fields rotate collimator angles rotate gantry angles and so on but defining the fields we couldn't define them unless we had what we had to have the anatomy delineated without that we can't tell where to go okay so this was a big advancement with this we needed some new tools and that was the portal evaluation tools how did we know that what we simulated we are actually able to confirm when we go to the machine and obviously the DRRs the digital you reconstruct the trade graphs where the central element instead of your regular radiograph you have a digital radiograph and port verifications films were still being used at the time how many of you take port films with film very few that's it okay so it's about eight or ten how many of you take port films with onboard imagers of or or digital you know epits electronic portal imaging so that's more now okay so we still have people that are taking film and but when we started obviously that we were just taking films and now you can take them with epits that are integrated into the head of the machine both for diagnostic quality x-rays and high-energy beams and but you need to be able to compare you know one image from one system to another image the digitally reconstructed radiograph came from the city scanner so those tools are an important component of being able to verify that what you plan to do is what you are going to be doing when the patient is under going to be treated so we could get conformal plans in this case and I want to point to your this number 77.4 gray to the ptv the first one that I show when we just started conformal 65 to the isocenter 63 to the periphery now we are going to 77.4 and that was just when we started and I will show you why we were doing this this is now a conformal field now you can conform it with blocks or you can conform with mlc there is no need to have an mlc an absolute need to do 3d conformal therapy unless you have an mlc it makes it much simpler much much easier but it's not a must as a matter of fact we started doing conformal 3d with blocks okay so I want to mention that because some people may think unless you have an mlc you cannot start doing some conformal and with that we were able to do things which were much tighter distributed around the target okay and with those as much higher and that didn't make a difference whether we were treating a small volume or a larger volume what else came along when we started doing CT we got very nice images but better than radiographs but there was also a need to integrate other information and this is an example if this is a patient which we scanned and I'm not a radiation oncologist I'm not a radio diagnostic radiologist if somebody shows me what's wrong with this patient I would say probably something around this looks weird this much different than this yeah would you all agree but I wouldn't be able to tell I said meh maybe there is something here okay well with the advent of MRI okay we could do much much better okay this is the same set of cross sections taken from a set of MRIs where you have much much better contrast resolution so soft tissue can be really beautifully displayed the only thing is that usually MRIs are not in the radiation oncology department how many of you have access to MRI okay about ten eight and any of you who has MRI in their department in the radiation oncology department one great okay but the majority okay of cases you have to have the patient send somewhere else for an MRI MRI images are usually taken under different circumstances the patient is not immobilized the patient may be in totally different position so once you get that's in a set you need to do what's called image registration you have to register the sets and you have to generate artificially artificially reconstructed cross sections that match your CT if you want to compare the two and that's what we are doing here next to each other so this was not the original set but from the original set you could just resize it reconstruct it move it magnify it tilt it etc so once you have that tool though which is extremely useful you need to have some tools to check whether what you are doing is correct and new tools were developed this is just an example of it it's called the checkerboard the chest you know board if you want where you see alternating pieces of CT and MRI CT and MRI in a pattern and you can see that for instance this is the bone in the CT which is shown as a bright area because it has a lot of calcium and in the MRI hardly shows it's a black it doesn't have signal because there is no free three protons and but you can but what you need to do is this is your quality assurance that your reconstruction was correct and you go from one to another in a smooth transition and you can see this here as well okay this is black white this becomes black in the MR okay so we have those tools there is many new tools now available which is ability to project the beams onto the patient's skin or the external anatomy in this case the patient is also in an immobilization mask but you can project the fields for each one of those directions not only that you have to now have a new component because now you have immobilization devices and you have to know how to treat them dosimetrically so there is a reference at the bottom of the screen there that I encourage you to look at it's an APM task report on immobilization devices on their effect on beam dosimetry including what's that three minutes I borrowed a few minutes from Sam he agreed gently get gently to do that okay so and so I would encourage you to download all of these are free I'll just give you a reference okay what the other thing is we can do now is do non complainer beams before we were limited to the simulator you know we could sometimes steal the couch was very complex and difficult to tell what you were doing and the most important thing is like you can treat now with beams that come from here that what's the problem with that any problem with that the dose to the body good okay you need to keep in mind although this ends the body here because that's where they stop the last slice in the head but the patient continues so if we were to do something like that we must make sure that this beam doesn't go exit through the body and we may want to tilt the head so it exits in front of the body okay so all these things are no tools that we are aware but they are not perfect so you need to understand a little more than just what you see on the images okay so I'm going to skip all this but one important thing and this is what probably for me was one of the big things about 3d conformal any of you treat craniospinal irradiation of children quite a few of you what do we do we treat laterals we treat the posterior spine field or sometimes to if it's too long and so on well and the physicians know from past complications that they need to keep a proper gap in the junction correct well how do before we had CT we couldn't know exactly the dose distribution around that gap and here we have a case where I can project everything on the patient and I see this is the gap that we created but there is a serious under those there and we don't want that either because that is basically a source of a recurrence okay so by doing 3d conformal we are able to do all these improvements and go from here to this where we have a much it's still safe and we can take other steps to make it safe so there is no accidental overlap but we can basically treat in more reliable way so I'm not going to go through this because you'll have all you have all these presentations in your package I believe Renato when they are going to get all this okay all right so I'm not going to recite this you can read it yourself but basically this is essential use of city information for 3d and basically the dvh is one of the main tools that now we must use for plan evaluation I'm not going to go into that that would be a separate lecture but the main importance of this development of the dvh is that's now we started accumulating gradually information about the actual doses to sensitive organs and not only to the organs but also to parts of the organs now we are far from being able to have a complete prescription what an organ tolerance is in terms of partial dose in particular when the dose is fractionated in different ways but that will not have been possible without the development of 3d conformal with dvhs okay well we wouldn't even have the information available so this is just to illustrate I mean these are two dvhs for the dose escalation on that prostate case one was prescribed to 6500 65 gray but it was to the isocenter we went from prescribing to the isocenter to prescribing to the 97 95% isodose which meant that we have not only a sharper falloff but we went to doses which were significantly higher so that was great and why did we do that well this is a slide from 1998 so this is right the beginning of 3d conformal maybe and this is from Memorial Sloan Kettering it shows these statistics of relapse free survival of patients with treated for prostate cancer with two different regimes 64 to 70 and 75 to 80 81 and what this shows is that sure within a year or two years even up to a year and a half or two years didn't make any difference patients need almost the same but if you look five years down the line up to here basically we missed four out of five patients had relapses four out of five whereas when they went to higher doses okay it was perhaps every other patient had their relapse still not good but much better than before and that was confirmed with another study and so on the issue with that was and we all know that I mean that in theory at least we know about these curves okay about tumor control probabilities and we know that if we increase the dose we have a better probability of control and different aggressiveness of disease are different curves but we know this in theory now here we start having some actual dose points and this is from 1998 so it's already almost 20 years ago and we could see that there was an increased importance to treat with higher doses and we were people at that time were already starting to talk about treating to 81 gray the only problem with that was this can you tell what this is these are statistics on complications and morbidities at 65 gray everybody was safe no problem okay they were just not cured but there was no problem no complications and as we started increasing the doses this is a 76 that would be 81 look at this for instance a GI complications about 30 percent every third patient has a complication that's no physician wants to see that okay so because of that people knew that yes you wanted to go higher but you couldn't do it freely there was a price to pay and the way of that if I was you know starting my new career as a as a as a drama writer okay I would basically write the drama of radiotherapy okay we can give radiation doses as high as we want we can sterilize any tumor and cure supposedly any localized cancer except those tissues that get in the way and they ruin our wonderful technology and they create complications for us okay so basically I'm going back to one of those slides that you saw before with a 3d I mean if we come from a lateral I mean we it's not too difficult to see how we can shape the beam so we avoid the wreck the bladder we avoid the rectum but as soon as we start doing these other directions we start overlapping and no matter how we do this in order to cover this we will be covering quite a bit of rectum and quite a bit of bladder and there is no technology that can let us avoid just by shaping the beam that's doesn't matter blocks or MLC's and so on so we started the process of IMRT and IMRT I mean was modulating the intensity in order to overcome that problem and I'm going to just give a short example about the IMRT without inverse optimization okay we all knew about intensity modulation when we use wedges that was a one-dimensional modulation basically from left to right or right to left compensators anybody if you use compensators that was a two dimensional you know intensity modulation con beams people went to con beam we treated like 4500 and then went down for another 2000 to a smaller field that's intensity modulation it's just temporal intensity modulation two steps by level then there were dynamic ways instead of wedges multi dynamic wedges independent jaws we made with independent jaws the multi-leaf and the slit field I don't go into detail but I just want to show you what many tend to call this poor man's IMRT okay this is a case for a breast and that's a place where this is very easy to implement I'm just going to show an example typically if you just come with the tangents you have a hot spot here because there is much less tissue in this in the apex of the breast so what do we typically use to do is put wedges but the wedges are one dimensional so they only compensate in this direction from here to here but they cannot do anything else and they cannot compensate in the superior inferior direction so one way to do that is you start with two tangents without wedges at all and you look at your isodose distribution so from a cross section you will see these hot spots up to 15 or 20% hot spots that are not acceptable and if you look at that from the beam side view direction this is our medial border of the field that's the apex and you project the dose distribution on that but you just project the hot spot in this case the 115% hot spot you generate like a volume of dose and you block that sorry you block that with your MLC you see this is blocked now so we created the second field now which is just this part and you do it again now for the 110% you move the leaves again and you create another field which is much smaller much more posterior and the last one and you can do that and you can achieve a very nice distribution by just weighing how much beam you give on to each of these four segments of the same field so it's the same field geometrically except that it's blocked progressively and obviously the majority of the field will be given the majority of monitor units with the first one which was the open but you don't give it all of it and you see the relative weight of that was only 86% and you do it in three or four steps and you can get pretty nice dose distribution the advantage of that is that you can also compensate in this direction okay so that's what people call forward planning or poor men's IMRT so IMRT is really conformal therapy except that we have to add the modulation to the beam so that was just a very simple example but typically we need we will go to inverse optimization of inverse optimization is basically instead of us using the judgment after we do a dose calculation to say well this is acceptable let's move this let's change that we say this is what we want to achieve and we'll give all that information to a black box a computer and let them do the job for us we can go take coffee come back in an hour it's all done for us except that computers don't know radiotherapy they don't they just don't know they only understand numbers okay so there are some steps that we need to add to the process now and one of them is this one they find the treatment planning the planning the treatment and the volume at risk and we need to define all of them now all of you must have read ICRU 50 and ICRU 52 anybody didn't okay those that are lying just raise your hand okay all right so you if you didn't you should okay if you didn't you should it's free I don't know if it's freely available but information is available in many places so but basically this is a cartoon if I want to treat this the GTV which is what we see and this is next to something else which is the organ in blue or this other organ in blue the physician will tell me well I don't want to treat this I want the CTV this is what the clinical target should be and then by then we are the margin because we say well we are not perfect so we added this margin and we end up actually designing beams and we end up treating something that looks like this this pink area and obviously that is the area where hopefully we managed to cover everything and but there is there is a conflict there's a conflict we cannot do this if we want to not treat the other right and that conflict needs to be resolved so the first thing is to define what the volumes are well the beginning we were treating a little box you remember a block a brick now these are the volumes that we are defining and these are just the typical definitions of a volume for head and neck and I think we covered some of that in the exercise on Friday or we are covering it today today today I'm sorry but this is the list of volumes some of these volumes are real volumes some of them are theoretical volumes basically you say it's a imaginary volume that you want to treat and the important thing is that people need to train in how to define those volumes the physicians particularly the ones that we started with were not familiar with designing volumes in cross sections so there is a full thing of training that needs to take place for you to do that for you and your physicians basically not just you the one thing I want to warn you and this is typical from what happened at the beginning this is a volume and we expanded it and you look at this I've never seen an anatomic volume that looks like that a scallop thing typically in the anatomy things are much smoother so and the reason is that when you when you delineate in one cross section you have this so you see looks this pretty smooth everything is nice but you go to the next one you forgot what this was okay and you put it in the thing when you put it in the stack and you show it it's obvious that you need to be adjusted but these are just the volumes and you have to define not only the target the GTV in this case but all the rest of the things that you are interested in knowing those about and I'm not going to talk about this because you can read a little bit about the uncertainties but the you have two different categories of extractions or extrapolations of the volumes that you started from and I'm just going to say one thing that there is internal margins that are added to that volume some of those margins you have no control that's part of the way the body is built but some of the margins are due to uncertainties in the localization and then we'll go back to that later okay so the uncertainties in localization or this setup margins this is something that you must make a big effort to reduce because otherwise you keep expanding those volumes and there is a cost a physical medical cost to the patient by doing this so now you have to define what are the prescriptions gold what is your prescription and the prescription there is a new concept it's not now well I'm going to trade this to volume to that kind of dose and then if it doesn't work you go back and you make adjustments now you have to tell it all up front to the computer so you have to the desired dvh's basically you define your volume those constraints by the dvh of over that volume and you need to assign goals priorities and penalties I'll give a couple of words about that so this is the new fashion in prescriptions you know 5th Avenue New York City that's a fashion now okay these are the prescription in this is a prescription in I am RT I'm just going to talk about a couple of little things there is there is a number of points I mean you you can define what's the resolution and there is these numbers priorities 80 90 85 and these are arbitrary numbers but I'm going to refer to those because you need to understand what that black box is doing behind the scenes so we do it for critical structures as well as targets how do we know what the critical structures can tolerate there is first of all your facility has to develop those numbers you should not take those numbers from somebody else you can get help from other places but everybody needs to get their own set of tolerances because that's what you feel comfortable with doing and this is just an example I'm not telling you to take that I'm just telling you this exists you can look at that and it's free in the internet not on Childress I mean did that and they put it on the web so anybody can download it and it's a nice spreadsheet but what it has is for different structures you can see the different amount of volume some structures will tolerate different doses to different parts of the volume and there is some endpoints and there is some references from RTOG studies and so on so my take-home lesson here do not use that table just develop your own you can just take that one modify it and use it for your facility but the bottom line is you need to have those DVH limits in order to do IMRT okay so inverse optimization now we are going to give all this information to a computer tell me the tell me the result Sam you want me to go ahead all right okay so basically we are giving the computer a problem which is just a simple mathematical problem relatively simple it's not that complex what's the inverse it's an inverse problem basically let's say that we have some tissue there is some target this green area and there is a point I or the point I can be anywhere in this thing and we have in this case schematically we have three beams one here one here and each beam is in homogeneous of in homogeneous intensity and that's what these x j's are that the intensity for each one of those beam let's these portions of the beam so the dose to a point I basically is the contribution from each each one of these little intensities times a factor which is basically a matrix is for this beam this unit then unit fluence to this point there is such and such contribution that's the DI the DI DJI's okay so we calculate those so just the dose to the point I is the sum of all those contributions very simple and then we create an objective function that's a function that we create there is nothing anatomic or or or clinical about that it's a function because we need to tell the computer how is it going to judge if this is a good match or it's not my good match to what we wanted to achieve so a tip an example of an an objective function and that's just one example is we create an artificial function which is a function of these two vector of this vector x and vex it's a vector basically it's a number of numbers and that's the sum of the differences between what I prescribe for that point and what the calculation gives me to that point for that intensity x distribution of intensities x and I give it some weights w i's and these are the numbers that indirectly relate to those priorities that we solve for well if I create this function which is a quadratic difference it's it's useful because it tells me if DI what I calculate for that point is what I prescribed that function is zero I'm just right on on that those okay perfect and for each point of obviously I have to calculate it but if it's different either bigger or smaller that's why I take the square of it I say that's not good enough this function has a value which is different from zero positive you know above zero and what do I want I want to make this all perfect so I want this ideally I would like all these numbers to be zero so I would say well if they are not zero change the intensities the excess until you minimize that bring it as close to zero as possible that's inverse optimization that's all there is all right is this new for any of you you all know that okay great no so once we have that then the question of what are those W's the W's are related to those priorities so there is two types of the of W's for a target I want to give a penalty or calculate the numeric value which is different from zero which is bigger if it's if I go above the prescribed those and I probably can should give a range of doses a lower and upper border of the prescription if if I'm above that and this for the target I say that's not okay it's okay I mean because I will give more dose to the target and that's usually not too bad if I am below I want to give a bigger slope or a bigger quadratic function because I don't want to under those the target that's the goal of my treatment okay so I can have two different W's on the other end for an organ at risk I don't care if I give it zero dose okay so there is no penalty for giving in less dose but there should be a penalty if I give more dose and obviously each organ can have a different value of W and this curves will look different but all this is behind the scenes so when I go to the actual plan optimization the computer will do this I will get the beam side view for each beam and I can divide that field into mini beams or beamlets each beamlet I you know just for this example it could be a one one by one centimeter square beamlet or five by five depending or if you do it with a multi leaf what is the size and the computer will start iterating and giving me intensities that keep changing and after each calculation it will calculate those numbers is this better or worse it will go back and calculate and do this millions of times okay yeah this is what's inside the box in the plan in the program that runs the computer what typically the interface that you have is give me relative importance and that's why it was I put on that prescription the big prescription table the importance was related to those W's if something is really you want to give it a big importance value okay so at some point this finishes okay and we have this is a control I mean I know I'm not going to go that the process has to end at some point you either end it manually or you give it some preset parameters and this is what you wanted basically your dvh points you could select the number of points is from a variant system but other systems of similar things and this actual calculated dvh's will keep updating as the system progresses and you end up with a distribution the desired distribution of fluence that you want to use something like this for a prostate a prostate posterior field this is the shadow of the rectum in the middle and these are the two sides of the prostate probably going on the sides of the thing so this is a typical just an example of those distribution this is in two dimensions but how do we create that a how do we create that let's just take one slice so we want let's say a distribution which looks like this of intensity calculated by the optimization program how do we actually do that there are numerous ways of implementing this just this is just one example let's say that this is along the path of one pair of leaves left and right okay so we first of all divide this in ten segments let's say ten ten intensity levels for each intensity levels will have a point and we bring the left side leaf to this point the right one to this point the rates are when the intensity is going down the yellows intensity going up and we deliver a tent of the intensity or we calculate the intent of intensity and we move to the next one and another 10 and another 10 until we get to the last point of the going down at that point this will leave will jump to the other side and we continue doing it we just build this ten percent of the time and increase that and we are done okay this can be delivered with mlcs either sliding windows step and shoot I'm sure you'll hear about this plenty you need to review the plan because that was a theoretical intensity delivered now that we and because that has to be done in order to make the algorithm move fast this is not the actual fluence going to be delivered because the actual fluence has to take into account that there is leakage between the leaves there is there is a different intensity along the tip of the leaves the distribution and so on so all these calculations need to be repeated and most of the systems will incorporate that at the last step so the first thing is how do we know that what we deliver is right the first time that we are going to deliver so we need to associate this dmc or or files for the motion of the leaves and we need to verify that each the each say at the start of the beam when we were setting the patience what did we do in order to deliver to know that the patient was treated correctly let's say we had the shapes field I mean many times they tattooed or the marked the patient on the skin we went to put the field the field size with the light field looked at the patient we walked out of the room and turn the beam okay now it's a little more complicated because there is no one shape okay but there is like an an initial shape so we can have the drr this is the drr with the leaves the starting position of the leaves we can incorporate that into the treatment you the control area and we can take a port film with the leaves in that position before we treat and now we look at this we have this graphical which tells us where the cross the crosser would have been in an optical field and we see that this is the right position basically it's like a fingerprint of the field each one will be different and that's your start position so you confirm that and now you can I'm not going to go through that the question is how do we know next day the next day the next day that we are doing the same thing okay well there is a variety of methods I'm not going to again going to detail but first of all it's very important to do continuous quality assurance of the motion of the leaves and the machine you need to verify it very very close periods that you're that the key the mlc is performing according to the specifications or the quality control program that you had you need to you and you are able in most systems you are able to have a file a digital file that tells you for this field on this day the leaves moved correctly to this position this position is really so much time and so on so this is a digital file you have to have some way of looking at that that it's not you're not going to get dizzy after 20 seconds but this is it's a one way of checking and the electronic patient record this is one of our therapists when we started I am RT and these happy and smiling so I asking what are you smiling this is well with I am RT we started with an 80 leaf or 52 live mlc 52 lives and it says well with oh that was an 80 leaf I'm sorry it was on the other machine that had the 40 live mlcs I says well you know I would have to just check for every day about 2000 parameters 15,000 leaf positions and everything has to be right every day I say well what are you happy about and he says well you know the record and verify I mean without the record and verify forget it I mean this is not really possible okay so record and verify systems and IAA has a publication it's all in there you need don't need to write it down and you can download it about record and verification systems so okay let me skip this because otherwise son was going to be really mad at me okay I'm not going to talk about this so basically what's the challenge here everything looks so good but the challenge is that the better we can fix the target or know where the target is and deliver the dose a we will be able to spare the dose to critical structures however the tighter the dose distribution we make the better we must know where the target is at all times because otherwise we will just get the opposite result we will get the very tight distribution and miss the time means the tumor or heat the sensitive structure with it so there is a plenty of material the APM has published reports this is one of them you should be able to download it for free the IAA has published a very very nice document which is the transition from 2D to 3D and to IMRT I strongly encourage you to look at this table table one is to classify conformal therapy what you are doing in your department which level are you level one level two level three and this is conformal therapy and the other tool that is there also which is I really urge you when you go even before you go home just do it tonight okay look at the appendix a it's about 50 50 questions and and 12 more questions for IMRT 50 questions for 3D are you doing A B C D are you doing it if you're not doing it it's not a shame just this is something that you need to move along this is what you need to do that's your to-do list but unless you do that and you go through all this list you probably may be missing some things so if you are going to move along this chain 2D to 3D to IMRT do this exercise look at the table make it you know write it for your institution for your situation and then do the self-assessment questionnaire which is in the appendix a I'm going to give you this which is I call it the reference of references and this is a colleague Jake Van Dyke many of you probably heard him or know about him he put a series of books modern technology of radiation oncology compendium one of the chapters chapter 16 it's freely available you can download it and he updates it I think once or twice a year with new references and you can just go to medical physics this is the reference and you can download it and from there you'll have you know directions to access almost anything you can think of and if there's something it's not there let him know he will be happy to add it okay so IMRT is a powerful and sharp tool in the treatment of cancer with radiation but we must use it with great care okay very careful otherwise you may cut your finger okay thank you Sam thank you for