The Value of PET/CT Imaging for Gynecologic Malignancies

Good afternoon, my name is Amy Carr, on behalf of Siemens Healthineers Petnet solutions, I'd like to welcome you to today's webinar. The value of pet CT imaging for gynecological cancers. It is my pleasure to introduce today's speaker, Doctor Richard Black. Doctor Black is the clinical specialty director of nuclear Medicine and pet imaging, atratus fear, national radiology group. Welcome doctor black. Thank you Amy. OK, so will spend about an hour here and will try to get through all the slides and if you have any questions I guess you can jot them down and will try to address them at the conclusion. So. Go to the next slide here. We have some objectives and first of all I wanted to find the diagnostic capabilities of PET CT specific to gynecological malignancies and will review a little bit of the Epidemiology of cervical, endometrial and ovarian carcinoma and will describe the application of the pet technology in the staging and re staging of gynecological cancer and then what I'd like to do is spend the last part of the talk discussing a unique quantitative approach to the evaluation of malignancy treatment intervention. So first of all, we've got some disclaimers here. The statements by Siemens customers that are described within the context of this talk are based on results that were achieved in my unique setting. Since there is no typical hospital in many variables, for example, hospital size, case mix and the level of IT adoption, there can be no guarantee that other customers will achieve the same results. An as far as actually, geez concerned. It's indicated for positron emission tomography in the following settings. We're all familiar with oncology, which will be talking about today for the assessment of Admiral Glucose metabolism to assist in the valuation malignancy in patients with known or suspected abnormalities found by other testing modalities or in patients with existing diagnosis of cancer. The cardiology application is for the identification of the left ventricular Cardium with residual glucose metabolism. And reversible loss of systolic function in patients with coronary artery disease and known left ventricular dysfunction when used together with myocardial perfusion imaging to demonstrate the presence of viability and then finally neurology for identifications of regions of abnormal glucose metabolism associated with foci of epileptic seizures. There's some important safety information that I just have to briefly discuss. First of all, radiation risk creation, admitting products including FTG injection may increase the risk for cancer, especially in pediatric patients. Obviously, then, you want to use the smallest dose necessary for imaging. Ensure safe handling to protect the patient and health care worker, blood close blood glucose, abnormalities in the oncology and reliant neurology setting. Suboptimal imaging may occur in those patients with inadequately regulated blood glucose levels in those patients. You might want to consider medical therapy and laboratory testing to assure at least two days of normal glycemia prior to your FG injection. Finally, adverse reactions, hypersensitivity reactions with parictis demon rash had been reported an obviously, as in any imaging Department, you have to have imaging emergency resuscitation, equipment and personnel that are immediately available to interject if necessary. And then our FTG injection dosage forms and strengths is provided in a multiple dose 30 or 50CC glass file containing 0.7. Four is 7.4 giga becquerel's per MLFG, 4.5 milligrams of sodium chloride with 0.1 zero point, 5 with ethanol is stabilizer approximately 15 to 50 milliliters volume for intravenous administration. Only smoke OK so we got through all of that. I'm going to get started on the slides here and the first thing I want to show you is just to re familiarize you with the capabilities of FDG pet across the spectrum of ontological imaging. This is the data that was presented to Hickford beckoned the turn of the century. Sounds like a long time ago, bout 15 years ago by primarily the individuals at UCLA, which accumulated all the data and you can see that in those 419 articles we had an excellent sensitivity and specificity. What really caused the. Attention of Hector if you will at the time was the change percent management. If you look on the right hand side in about 13,000 patients in 80 three articles there was comparisons done between FTG Pet, standalone PET and conventional image modalities primarily. See T and you can see that there was a superior capability of PET versus CT in those analysis, and that's primarily why hit but decided to make the decision to start to approve after Jeep, an emerging in the realm of ontological disease. Now this is a meta analysis that I performed from December of 2014 through June of 2015. I looked at every article in Pub Med dating back to the early 1990s to assimilate and see if the characteristics of SG Pet were maintained compared to what's published 15 years ago, and you can see that there still remains a significant difference in the sensitivity and specificity for both staging and re staging of disease and over 60,000 patients of every paper published in every language. In the world. This next slide, just this is obvious for all of us that work in the imaging environment, particularly when we're working with individuals that may or may not have malignant disease, and basically what we're tasked with doing either as the physician of the technologist as the team that is involved in the evaluation of patients with perspective, or known malignancy is to first of all, diagnose the primary tumor which can then be used to localize the unknown primary tumor or direct biopsies, and then establish the stage of disease. And with FTG pen imaging, oftentimes we upstage or downstage disease compared to conventional imaging and then detecting recurrence re staging disease and then defining the response to treatment. If you look on the left hand side, this all basically then boils down to the capability of the procedure to differentiate malignant and non malignant disease, and then Secondly to assess the response to therapeutic intervention. Now this is all gynecological malignancies based on the meta analysis, initial staging of pet versus. Siti, if you hang on a second here, we have to make sure that the slide advances. Bear with me one moment. It seems like the slides are stuck here, just for a second there with this just for a moment. Are you guys good? Are we good OK? Alright, my apologies for the interruption. At any rate, we want to make sure that you're seeing the correct slide, so this should say all conic logic malignancy's an initial staging and left hand column is the sensitivity and specificity for PET and the right hand columns are sensitivity and specificity for CT conventional imaging this is all the papers. And here is the synopsis. If we go to the next slide and we've got the literature on the left hand side and then the difference between PET and CT, and this is PET CT primarily at this point compared to conventional imaging, both sensitive and specificity for initial staging of gynecological agencies. And this is re staging and recurrence. OK, and this is again a little bit more extensive meta analysis shown here. But again I think if you look on the left hand side the columns are demonstrating a sensitivity and specificity for pet of 91.5 and 85.3 compared to numbers of 70.1 and 85.2 for see T. If we go to the next slide. We can see that this is all the literature published regarding Re staging and detection of returns, and we can see that there's essentially similar specificity, but certainly a greater sensitivity for the evaluation of re staging of gynecological malignancy with PET. And this is the results of the NR NPR data National Logic pet registry that was published in the Journal of Nuclear Medicine in 2008. And we have several of the different malignancies shown here, and we have cervical carcinoma, an Dimitriou carcinoma, an ovarian carcinoma. You can see the number of patients above the bar graphs an compared to conventional imaging pet produce. Significant changes in patient management, whether it's changing in the type of treatment downstaging upstage in the disease, 32.7% for cervical carcinoma, 36.5% for endometrial carcinoma, and 41.4% for ovarian. Push to the next slide. So we're going to talk specifically about cervical carcinoma. Hey push to the next slide. We'll talk a little bit here, just quickly about the Epidemiology of circle carcinoma. Presently, it's the third most common gynecological cancer diagnosis and cause of death in the United States and countries without screening programs and prevention programs, it ranks second in diagnosis in cancer death in developed countries like the United States in Western countries that has fallen to the third place because of our cancer screening programs for individuals with potential cervical carcinoma, the main risk factor is the HPV virus. It's detected in almost 100%. Of cervical malignancies, and it's central to the development of the neoplasm itself. The global incidence is about 528 thousand new cases. In 2012 two 166 thousand deaths. In the United States, we have 13,000 new cases. 4100 cancer related deaths. The mean age of diagnosis is approximately 48 years old. Think around the correct slide now. The developed countries, the incidents it's the 11th most common malignancy in women. About 9.9 of 100,000 women versus developing countries where it's almost twice that amount. 15.7 per 100,000 women. The most common histologic types are squamous cell which account for approximately 70% of presentations and add no carcinoma which is approximately 25% of presentations. Let's push to the next slide. Great, we're on the same slide, so we've got surgical staging remains the gold standard for the lymph node metastasis. The mechanism of tumor dissemination starts at the junction of the squamocolumnar junction moves to the cervical stroma, then to the parametrium, then to the uterus, and finally the vagina. The local regional metastasis generally spreads through three different separate lymphatic pathways to have gastric root, the lateral root and the pre sacral root. You can see that they follow the internal and external iliac vessels and the ureteral sacral ligament, respectively. The presence of extra pelvic disease. That presentation is rare about 12% of patients at presentation haven't access beyond regional lymph nodes. Generally, this is attributed to Hematogenous spread. We end up with lung, liver or bone involvement. Distant metastasis are rare. In the absence of pelvic lymph node involvement, which makes sense about 10% of the patients have distant asses to the left. Superficial lymph node, of which 40% will have periaortic involvement as well. We push to the next slide. And this is the initial staging weighted amount. Weighted meta analysis of FG PET versus CT and conventional imaging and the main function of PET CT in this situation. Initial staging is to accurately portray lymph node and then those rare cases of distant metastatic disease which obviously will impact patient care and patient management. Push to the next slide. Here is a list of articles that were shown in the previous database and we have the significant increase in sensitivity versus of FG PET versus CT and then similar specificity's for the evaluation of initial staging. Push to the next slide will talk just briefly about detection of recurrent disease. The definition of recurrent cervical carcinoma tumor development that exists greater than six months following this flexible treatment of an index lesion, or metastatic foci recurrence may occur into up to 35% of patients. High risk patients are those that have initial parimutuel involvement or periaortic lymph node involvement. Local recurrence of circle carcinoma typically occurs in the vaginal vault. Very then, the pelvic sidewall and parametrium. Distant metastasis unfortunately or president about 70% of patients that present with recurrent disease. The instances and metastasis as you can see, we have both lymph node involvement on the left and sites of distant Minnesota disease, which is generally hematologist Lee born on the right failure Arctic lymph nodes. 11% abdominal cavity lymph nodes 8% super Victor lymph nodes 7% and then the lung parenchyma assessment, access and liver and adrenal glands. At 2120 at 15% respectively. Push to the next slide. And here's our re staging weighted meta analysis for several carcinoma our spreadsheet. Again, you can see superior sensitivity and specificity push to the next slide, which is easier. And we've got our articles on the left and our capability of FG pet versus conventional imaging for sensitivity and then a higher specificity as well. Who pushed in the next slide? This is the results of the an alarm NPR data for cervical carcinoma. The overall impact on patient management was approximately 33%. Impact on initial staging. 36% re staging about 27% in recurrent disease again 36%. Push to the next slide. Just a couple of case examples for you to show you the difference between petanque T in the evaluation of the individual, both presenting for initial staging of cervical carcinoma as well as re staging. We got a 48 year old female here presenting for initial staging. You can see that there's a synopsis of the metabolic findings in the lower left hand corner and if you look at the impression for the see T they certainly have findings consistent with cervical or under mutual carcinoma. But there is a great deal more abnormalities defined on the pet study to include the abnormalities within the abdominal retroperitoneum as well as the left lung field. There's another push to the next case. 48 year old female with history of cervical carcinoma presenting for initial state examination compared to MRI of the pelvis. The MRI of the pelvis. If you look in the upper right hand corner of the impression shows a large endo cavitary mass within the uterus consistent with neoplasm and also as well as that abnormality, are the pelvic mesenteric abnormalities. Defined with FG PET CT which are not mentioned an missed with MRI. Go to the next slide. This is a re staging case. A 68 year old female who is originally studied eight 3115 with cervical carcinoma. After treatment asymptomatic they then present the re staging examination roughly six months later and you can see that we have both the chest admin and pelvis. CT report enlarged mediastinal lymph nodes which doesn't mean that they have neoplasm just there mentioned and also in the impression in the see T we have no change in the left pelvic sidewall lymph node as well as retroperitoneal adenopathy and you can see that there is a great deal more going on. With the pet study as you look at the lower right hand corner, we have a number of abnormalities to find that definitively fulfill the criteria for neoplasm. So again our capability of FG PET versus conventional imaging supersedes that achieved with see T in this case example. Push to the next slide. I'm going to talk a little bit about endometrial uterine carcinoma specifically. Next slide. But I think we're all In Sync now. The most common gynaecologic cancer diagnosis and cause of death in the US and other developed countries is attributed to uterine carcinoma. It's the second most common cause of gynecological malignancy's and developing countries behind cervical carcinomas. We previously discussed the 2008 global instance. Roughly, almost 300,000 women were diagnosed with uterine cancer more than 50,000 cases per year, almost 9000 deaths per year. The average age of diagnosis a little bit older than that obtained with cervical carcinoma at 61 years. The main risk factor is exogenous and or. Excuse me. Excess endogenous during sagginess estrogen without opposition by progesterone. So that's estrogen therapy without progestin as well as obesity, tamoxifen therapy, and nulliparity. Main subtypes are and Dmitry Oid which is 80 to 90% cases and then non enemy troid which account for the remainder. Adenocarcinoma is the most frequent histologic type associated with uterine lining. Other histologic subtypes include uterine sarcoma and carcinosarcoma. About 25% of these cases occur in premenopausal patients. Early detection obviously leads to discovery of stage one disease and greater than 70% of patients with stand will obviously impact prognosis. Push to the next slide in terms of initial staging. Basically what you have is the Federation of Gynecologists and Obstetricians. Staging is typically performed surgically. With an exploratory laparotomy, the surgical intervention and peritoneal lavage and fat and ectopy is recommended in high stage one disease or in the presence of serious or clear cell carcinoma. Under the staging of endometrial carcinoma under staging of anamitra carcinoma may occur in up to 20% of patients with the clinical staging methods. It's so consequently, this leads the clinicians to rely somewhat on the imaging modalities. The initial spread of the tumor is the invasion of the Meiomi trim, which then extends to the cervix or fallopian tubes, onto the ovaries and then local invasion of other organs of the pelvis. Switch to the next slide. Our little weighted meta analysis here again of FG Pad versus eventual imaging. You can see we have an 85% sensitivity for pet versus 57% for. See T conventional imaging. Go to the next slide. Again, our bar graph analysis and the summary of the papers and see that there is superior performance of PET in this instance. Next slide. Re staging and detection of recurrent disease treatment failure in low risk patients is exceedingly rare. The majority of recurrences occur within three years of the original diagnosis. Recurrence is most common in advanced stage disease that's Faygo stage three through 4 and you can see them delineated there with them. One disease or N1N2T4 or T38 be serious or clear. Cell Histology. 50% of these recurrences are symptomatic. The individuals for will present with him. Aturia of rectal bleeding, vaginal bleeding. Some adjust per present with more generalized symptoms to include anorexia, unexplained weight loss in adima. The remaining treatment failures are defined with surveillance, which can be achieved with a clinical examination, imaging evaluation, an elevation of the tumor serum tumor markers. To improve the CA 125. The pattern of recurrence is directly related to the initial disease status, initial disease stage, and degree of involvement. Patients with advanced primary disease obviously will have snapping at levels of abdominal or systemic metastasis. About 1/3 of the patients with initial uterine disease will have local recurrence. The remaining 60% will have distant failure. Is our little men analysis again? We got the see T and tumor marker, follow-up of enemy trio uterine carcinomas associated with the Minish specificity for the adequate assessment of suspected recurrence. We have to rely on imaging to define what's happening. Again, if we're going to rely on conventional imaging, we're going to miss a significant number of patients. You can see the meta analysis results here. We go to the next slide. This is a list of the papers and we can see a significant difference. Almost 20%, roughly 20% difference in the sensitivity and similar specificity's. So the issue is is that with sensitivity we're looking for the abnormality, and if we've got 20% of the patients right off the bat with a diminished sensitivity, we're going to miss significant number of individuals with recurrent disease next slide. And this is again the NPR results, and about 36.5% overall impact on patient management. You can read the numbers for yourself. For initial staging, we stage again recurrent disease. There is a significant. Change in patient management. Again achieved with FG pet CT as opposed to conventional imaging modalities that push to the next slide. Some examples here. This is a 72 year old female with uterine carcinoma presenting for initial staging after their recent hysterectomy and you can see that there is disease within the abdominal cavity, the pelvic cavity within this context, as well as the bilateral lung fields and results of our CT of the other and pelvis obtained after the hysterectomy. We can see that there is evidence of entropy carcinoma without evidence of metastasis, so again a superior sensitivity for the. Capabilities of FDG pet. Another example shown here Re staging examination and we've got the initial study done. This is re staging that was accomplished in March of 2015. We have a negative examination. Patient returns with elevation of their serum tumor marker. They now have an abnormality within the left me pelvis and you can see that our examination of see T that was accomplished within three or four weeks of that pet study. In February of 2016 demonstrates no evidence of recurrent malignancy. Talk about. Ovarian carcinoma. Which to the next slide as far as Epidemiology is concerned, it's the second most common malignancy and leading cause of death in the United States and other developed countries. And a variant personnel is the third most common cancer that six most common latency and women worldwide in the United States. There is about 22,000 new cases of variant carcinoma per year, an 14,000 cancer related deaths. It is the 5th leading cause of cancer death of women in the United States. The global incidence to earn 25,000 new cases in 2012 and about 140,000 death. The majority of ovarian malignancy's will arise from the epithelial cell population. The remainder are germ cell and stromal. Tumor an origin serious carcinoma is the most common subtype of epithelial origin ovarian carcinoma an is related to the fallopian, tubal, and peritoneal carcinoma subtypes. Initial staging. The NCCN guidelines. Include physical and pelvic examinations. The CA 125 level measurement, and imaging to include CTM are as well as FG PET. 75% of these initial presentations of ovarian carcinoma associated unfortunately with advanced stage disease and this is due to the absence of effective screening programs and the number of individuals that present asymptomatically. The metastasis is directly into the peritoneal cavity, yet penetration of the ovarian capsule and you have invasion of the proximal viscera. The pelvic peritoneum then to the contralateral ovary. The peritoneum and uterus and abdominal cavity. And it seems to go in a clockwise fashion. If you look at the little diagram on the lower left hand corner and see how it tends to produce a clockwise distribution of metastatic disease and then we have just the discussion of lymph node involvement on the right hand side. Distant metastasis rare only two to 3% of those patients presenting with ovarian carcinoma have dismissed at disease to involve the lung liver an plural. Next one. This is again are not allowed lot going on the literature in terms of staging with ovarian carcinoma, but we can see that there is roughly similar sensitivities, but superior specificity for PET. If we go to the next slide. As I mentioned, there's very few papers for the initial stages of variant carcinoma. We have basically similar sensitivity. The only disease that demonstrates a similar sensitivity. Additional staging with bed far exceeding the conventional image values. Otherwise an A superior specificity. Next slide. So as far as re staging and detection of recurrence, the epithelial origin ovarian carcinoma is the most fatal gynecological malignancy. However, there about 200,000 ovarian cancer survivors in the United States at any one time, 80% of the patients enter remission following their primary intervention. Recurrence rates are as high as 25% of early stage patients and approaching 90% for advanced stage disease. The majority of women with advanced stage variant carcinoma will relapse despite surgical cytoreduction as well as chemotherapy. Chemotherapeutic side with toxic intervention. The overall overall likelihood of relapse is roughly 60%. The likelihood of this recurrence will be dependent upon the extent disease, obviously at initial presentation the results of the surgical cytoreduction and the rapidity of the CA-125 resolution and the treatment response that solicited following primary intervention. And the results of the medical research County 05 Council study demonstrated there was no clear impact. The results of CA. 125 levels on survival women treated with ovarian carcinoma are at high risk for recurrence and most survivors unfortunately will not have a permanent cure. Next slide. Time for our weighted men analysis. Again re staging can see that there is a significant difference again between the sensitivity and specificity of SG Pet versus conventional imaging based on this weighted now since in the spreadsheet go to the next slide. Here are the articles. Significant increase in the number of publications regarding the staging of a variant carcinoma utilizing FG PET as opposed to the initial staging. Go to next slide results of our NPR data again, significant changes in impact in patient management as well as initial staging, RE staging and recurrent disease. Show you a couple of examples. This is an example of a 69 year old female who has the FG PET study up, staging, ovarian carcinoma and see that are abnormalities are present within the minimum down retroperitoneum and there is no evidence that metastatic disease on the see T of the chest evident pelvis that was accomplished within several weeks of the FG PET study. Go to the next slide. The 72 year old female with history of variant carcinoma. This is pre surgical debulking. The CT describes probable liver metastasis which are not defined on the FT PET study and it misses the pleural neoplasm involvement that we discussed occurs in ovarian carcinoma. So again, a difference between the FG PET study with see T as opposed to eventual imaging. For the next slide. Here we have an example of recurrent disease that follow-up initial study performed may of 2015 and the following examination in March of 2016, and our study accomplished had baseline after therapy has been concluded, the patient has no evidence of disease. They now demonstrate malignancy in the left inguinal region and left me pelvis. Inguinal lymph node of the external iliac lymph node is discovered. It is not characterized. All we have is the size characteristics and will show a little bit more about that in just a second. At any rate, we see that we have the superior capability of FG pad versus conventional imaging, and both staging and re staging of linked disease. OK, so go to the next group of slides here. Got one more? It's another re staging exam example and if you look at your see T report again you can see they're describing hilar adenopathy. It's nonspecific, they're even providing a differential diagnosis, and on the lower hand side there you've got suspected progression of disease and the nice thing about FG PET imaging is that. If done properly, you're providing precise evaluation of count statistics and definitive information as to whether or not blood disease is present or absent, and that's what we're after. We're trying to provide as much objective data as possible to the referring position, so they can make an appropriate decision based on their future case management. Alright next slide. OK, so we're going to follow patients with malignant disease and follow their treatment. We're going to have to come up with some way to define what's happening in terms of the abnormality, whether it has malignancy or does not have malignancy. So I'm going to talk a little bit about how to approach this from a standardized corrected quantification approach. Next, slide. So when we look at and FDG PET study or any abnormality on an imaging study, we're going to try to identify the target or index lesions and we can do this from a pet study perspective subjectively and we could just look at it and say there's increased count statistics at Todd. It's not spot the dots however you want to describe this, so it's positive there's perceived perceived increased uptake or it's negative. There's no perceived increased uptake. We can take it a step further, which is still subjective, and we can compare the uptake visually or from a qualitative perspection. Perspective to the liberal mediastinal blood pool. So lot of people like to do this both in terms of defining the presence or absence of malignant disease as well as then defining the response to treatment, and it's interesting. We've gone from quantification, at least in lymphoma. Back to a purely qualitative method that shut some method that's been described within the last few years to try to define the response to treatment. So we have a positive study where the uptake is greater than liver. Mediastinal blood pool? Equivocal where it's equal to or? Deliver me discount bloodpool or negative. It's less than the mediastinal word liver parenchyma and then we can do it from an objective perspective. We have positive increased uptake. Uncorrected pet where we basically calculate the SUV and then we have the PERSIST criteria which defined our target lesions is 1.5 times the target lesion which was greater than the SQL reference value in the liver. Next, slide OK. Now this has nothing to do with endometrial, ovarian, or cervical carcinoma, but I want to show you why we have such a dilemma with SUV calculations, and these are two different reports. Two different patients with pulmonary nodules and you can see on the left hand side that there is a barely discernible abnormality within the left lung that correlate's with a parental density on the. See T an. The report describes the SUV as 10.4 and I think it's pretty easy to assimilate the fact that that uptake isn't even discernible on the map image. So you can't even see it registered basically against the mediastinal blood pool, and it's certainly equal to not greater than the liver. We look on the right hand side. We have a case where the SUV is 1.8 and that certainly doesn't correlate with what we're seeing visually. That uptake is significantly greater than the mediastinal blood pool. Significantly greater than liver, so we've got these situations where we've got issue vise quantification that don't make any sense with regard to what we're seeing from a qualitative perspective, so it's no wonder that there is confusion. When we interpret PET CT studies in terms of quantification and when you're looking at something from a molecular perspective, mean that's when things change earliest from the cellular biological perspective. From the molecular biochemical perspective. So if there's some way that we can harness that information from what's derived from the count statistics that are unique to nuclear medicine, then we've got the battle more than halfway fly. So the factors that are necessary for accurate quantification, first of all, it means you have to choose the correct reference tissue. You have to derive if you insist on to work, there's going to have to be something that's going to be a constant reference value. If you're going to use a variable reference value, then all bets are off and then we have to recognize and identify that there are site specific threshold values, basically meaning that different regions of the body may have different thresholds for differentiating malignant and non malignant disease based on the calculated standard uptake value. And then we have to utilize that proper quantifiable value in the determination of what's happening with the patient status. Go to the next slide. So this is work that I did and I looked at all the different literature since the early 1990s to define whether or not there were different thresholds for differentiating malignant and non malignant disease based on the location of the abnormality, and I think most people agree that most usually we use a value of 2.5 or greater to demonstrate the presence of a malignant presentation. But we can see from that example that I had a couple of slides ago that doesn't hold any water. So first of all we have to understand that there are different thresholds for different locations. And Secondly, somehow or another we're going to have to correct these values to get a number that makes sense. That's reproducible. That's consistent and can be used in any patient at anytime on any vendor hardware. So we go to the next slide. An look on the right hand side. There's a meta analysis of every paper written in the literature that demonstrated normal visceral SUV's, and in these eight publications, there is a constant that is capable of being derived if you use that constant, then you can make a definitive statement as to the count statistics from one study to the next, regardless of the patient situation. Regardless of the vendor specific hardware and the reason the liver is chosen is first of all. It's the only organ that demonstrates a plateau of uptake between 50 and 110 minutes after injection. Nothing else does that. The cerebellum bone mediastinal blood pool, spleen, soft tissue musculature, the great vasculature. None of that produces a plateau of uptake over the normal time frame of injection. When we do the imaging. So with that in mind, we have to realize that if we're going to use a visual comparison. That the liver is the only the only basically this role component that can be utilized for this and we have the radiation reader is reiteration of the stability of the liver parenchyma. Less UV has actually been described in the Perseus method. The issue with the PERSIS method is the fact that the liver reference value couldn't very by more than .3 units from one study to the next without a known constant, and that's why the PERSIST method did not achieve the degree of acceptance that we would have liked to have seen. Push to the next slide just a little bit about here about what SUB you should use should always use the SU VMAX. It should be drawn around the entire ADD malady just like this is all the same patient. You can see the SV is 10.67. That's the maximal issue be if you draw it in the region of interest of the abnormality. It's only 7.6. That's a 30% difference, and if you're going to look at from one study to the next and try to make these count statistics work for you from one example to the next, it's not going to happen if we've got a 30% difference, so we want that. Maximum SUV, and it's obvious that if we draw it in the abnormality, there is going to be very little variability between the mean issue be in them. Access should be if we draw it around the entire amount. With normal tissue, there's going to be a huge difference. So you want to use that Max SUV as shown in the middle on the top. Also, the paper that was published in the Journal of Nickel Medicine in 2004 just want to point that sound to you may not be able to see it. I know it's pretty small on your screens, but several things were pointed out by pack way an associate's. In this study, that was accomplished in Liege, Belgium. First of all, correcting for the blood glucose levels would increase the variability of the values and should be avoided, as well as normalizing for the body surface area or lean body mass did not improve the reproducibility of the measurements. Consequently, we could get by with the regular SUV. Go to our next slide. So our methodology of comparative quantification is we can use the two middle level ratio. And that means we just draw a region metric and that should be in our tumor compared to our liver reference value and then determine what that ratio is from one study to the next. We could use the persyst approach was 1.5 times are abnormality. To identify our target lesion and then define its relationship to the liver reference value and again the liver reference value without a constant cannot vary by more than .3 units and then we can also use what I have initiated which is a standardized correction. We called the liver uptake constant and we have a four part. Equation in this can be utilized. Then every study all the time from one exam to the next, regardless of the vendor piece of equipment. Next slide. Just to give you a little taste of what this means from a diagnosis or staging re staging perspective. Identifying malignant disease with a constant corrected S UV, we don't expect much difference. It's interesting. There's a little bit of a difference in sensitivity and corrected versus uncorrected and 143 patients with non mediastinal soft tissue lymph node involvement and a variety of malignancies which included ovarian, cervical and endometrial carcinoma. But the huge differences in the specificity and that's what you would expect if you look on the right hand side, there's the aroussi curve. And if we just flip a coin, first of all, if I read every single cases positive, regardless of whether it is positive or negative, I would never miss a single case of cancer, but I would tell 100 people that didn't have cancer, that they did, so that's not acceptable. So we're always doing is we're always pairing sensitivity versus specificity, and that's exactly what the receiver operator curve does. So if you look at the difference between the corrected data and the uncorrected data, that linear line would be for every study I got, right? I got one wrong. So if we're above that line, we're doing better, and basically that linear line is a guess, and anything under that line is not going to work. And why would it be that a guess actually, or uncorrected data is worse than the guest, because the data is wrong, and we know that there are millions of reasons why lymph nodes and everything else will demonstrate increased uptake. We could have obviously white blood cells, any type of inflammatory reaction, an infectious ideology with infiltration of the inflammatory response. All of that uses white blood cells. As its metabolite or utilizes, glucose says its metabolites, so we're going to have a huge reason for false positive examination. For the next slide. So let's take a look at the significance of PET CT and gynecological malignancies specifically. Alright, so we just got a couple of papers here. All of this data comes from the Mallinckrodt Institute and the University of Washington in Saint Louis or watching University excuse me in Saint Louis and got a couple of papers showing here. We have no residual left. The pet uptake versus residual FTG pad update in the paper in 2006, and we can see that there is a significant difference in the survivability of both and then 36 patients shown on the right by Julie Schwartz is paper that was published in the Red Journal and he got again a mean percent. Pretreatment change in the SUV demonstrates an increase in survivability and that is are a positive response to therapy. The next slide. Is 238 patients. This was published in the Journal of Medicine and Supplement in 2009. Again, we can divide these patients up into a complete response. Partial response. Progressive disease. It's interesting if you look at this and This is why it's so important in my opinion, to have the capability to adequately quantify what's happening from our count statistics that are readily available from nuclear medicine procedure. If you look at this, a complete metabolic response was absence of the pretreatment uptake, progressive disease, or new sites of involvement. Let's look at the middle. The partial metabolic responses. Persistent update on the post treatment examination. That's very subjective, so it's very difficult, I think, to take these categories and make. Now obviously it works, but we can take this a lot. Make it a lot more refined if we're able to accurately quantify the count statistics associated with the FG PET examination for the next slide. So 168 patients with ovarian carcinoma. You see there's a difference in survivability for the pet, negative versus pet positive studies, and obviously that's that's common sense. Go to the next slide. Alright, so how can we apply this corrected quantitative PET CT analysis of FG PET imaging? And I'm not going to get into this, but you know, there's a million ways to try to try to figure out what's happening with the response to therapy. We have the molecular markers somewhat sensitive, not specific. We have serum markers. We can use conventional imaging, but we all know that things do not change. From an anatomic perspective. I mean, they may not change at all, and they actually may get bigger, and we actually get smaller, and we have no idea what's happening from a molecular perspective. It just stands to reason if we know what's happening at the biochemical level and we're going to be able to predict the response. Treatment much more effectively. This is accomplished basically with FG PET. You look from the right right hand side there and we got these new now. Qualified quality qualitative assessments of the Five Point scale, again making a comparison between the liver and mediastinal blood pool as opposed to the actual target lesion abnormality. There are the quantitative pet interpretation starting out with the European organization. Retrieve research treatment of cancer in 1999 and then that persist data and we've got other molecular parameters of which those are not available. If we don't have a cyclotron following us around on the highway. Go to next slide. So I think this perfectly demonstrates why FTG pet should provide superior information to conventional imaging, and that's because first of all things that occur biochemically there going to be expressed way before the anatomic images occur. And that's almost the same thing as everything else we see in nuclear medicine. For example, perfusion, imaging and cardiac perfusion SPECT. We're going to see changes in the regional perfusion before we start to see changes in the functional response to stress, so our FO changes are going to follow the perfusion abnormalities. So the same principle applies here. And not only does it mean that a decrease in cellular proliferation and an increase in cell death decrease in viable cell number, we can also determine the presence of increased cell proliferation, decreased cell death, and an increase of viable cell number in something that has not changed one iota from a size perspective. And when we accomplish this with count statistics that are corrected with a constant value, we have precise, not guesswork but precise quantification. It's not operator dependent. So we're not looking in an abnormality that might be 16.8 millimeters, 18.5 millimeters, and 15.2 millimeters. We're looking at a corrected. There should be at 4.5, regardless of how you look at it. Next slide. So obviously our intent is to provide the referring position with the information they need to know what to do. So if we have a complete metabolic response, let's easy they continue therapy. A partial metabolic response. They're going to continue therapy and generally under the terms of metabolic stability, they continue therapy. If we have progressive disease that only makes sense, you stop therapy and try to figure out what the next echelon of therapy will be. And this is all going to be contingent upon our capability to differentiate malignant and nonmalignant disease. Next slide, so here's what we're faced with every day we've got the patient on the left orange number one, we've got significant disease after treatment. You can see there's six cycles that took place. It's all gone, so that's easy. Look on the bottom, #2 in red. We have an abnormality, and then after five cycles of treatment we have more abnormalities. Well, that's easy, but what about #3? And isn't that where most of our patients end up? How do we know what to do with this? I mean can we look at this and say, alright it's the same? I guarantee you. If you look at this and try to say based on the qualitative criteria, comparing it to the liver or comparing it to the media sound blood pool, it's going to be tough. Next slide. So if we have corrected data, we can apply either of the parameters, not the approach, but the parameters of the RTC or PERSIST criteria. So E RTC would be a 25% change and our purchase criteria would be 30% change. So we can apply these correct numbers and get our data. Next slide. Our target, the index lesion detection assignment right we could go subjective. We can be objective with the SUV, but it's uncorrected or the purchase criteria which generally doesn't work or objective criteria utilizing our four port four part. Component equation next slide. I don't know if you can see this and I'm going to have to make it bigger for myself, but let's just take a look at these two examples. These are not patients with endometrial, ovarian, or cervical carcinoma, but look at our issue V in the left lung. Excuse me, the right long on the top patient six 514. We got an extra be of 7.06. Let's check it out. After therapy we have an SUV of 0.07. So you send that information to are referring position, then maybe like what and if you look at this I know it doesn't show up well enough, but between these two reference values of the liver on the initial study we have a reference value of 2.6 that we made the second study a reference value of 0.0, three that is a 258 unit difference in liver reference value under recipes don't make any sense if they're not corrected. We've got the flip of this on the bottom. We've got a 23 unit difference or 833% difference and look at our issue. Be in or abnormality. At baseline 4.5, four are corrected or liver value is 0.49. Now let's check out. After therapy, you can see looking at it qualitatively, it's nearly gone, but we have an issue be at 3.68. That's basically the same as 4.5. Four and our livers 2.8 one you can see what a dilemma this produces for the interpreting position and then our position that's trying to make sense out of what's happening. But limitations of basing this on uncorrected data are both for the target deliver. Ratio as well as the purchase method. I looked at 50 patients on the GE Discovery 600 at Phillips JXL and 30 patients on the Siemens Biograf 16 and you can see the number of patients that demonstrated a more than three unit difference from one study to the next in the liver reference value, which would disqualify them for persist analysis. So let's take a look at what's happening here with regard to adequately seeing what's happening from the metabolic perspective. We've got the tumor cell population in relation to the PET scan abnormality. It was shown by Castleman Associates and Doctor Wallen and Yvette Castleman in several different publications that a 1 centimeter abnormality will have about 10 to the 11th cancer cells present within it. A 5 millimeter lesion, roughly 10 to the 8th, 9th, and then anything 3 millimeters or less less than 10 to the 7th. We won't be able to see those with PET. What does that mean? So we go to our next slide. That means that after two cycles, we can pretty much predict, and this is what they discussed what's happening from the metabolic biochemical perspective. So we've got our initial analysis at 10:50 cells, and if we drop below the detection rate, we know that we're below 10 to the 7th, and we're going to achieve at log killed for each one of these cycles, roughly along kill. So if after 8 to 9 cycles we after two cycles, we see no evidence of uptake, that means we're less than. 10 to the 10. To the 7th we know that a denying cycles we're going to achieve a complete metabolic response, and we're going to have the patient in remission. On the other hand, we can finitely define what's happening with these individuals if they don't demonstrate complete resolution of the update. We can define stable disease. We can define a partial metabolic response, and we can actually define quantitative progression at two cycles based on the corrected SV without the corrected issue, it's impossible. And why is the issue be capable of performing this task? Because it's a 3 dimensional measurement. It's not a 2 dimensional measurement, so when you look at your anatomic abnormality, you're doing transversal napy. We're also developing the thickness of the slice, those count statistics that are being contributed from the slice thickness, so it should be is actually a 3 dimensional measurement. Once corrected, it's going to give us accurate information. Our next slide then shows where are we with all of this so we gotta couple of capabilities here that actually circumstances that were presented with when the individual is being treated for blood disease. First of all, we can continue treatment that's not working. We don't want to do that. We can discontinue treatment that is working. We don't want to do that. Obviously, we want to continue. Treatment is working and discontinue the treatment that does not working with conventional imaging. It's impossible to generally to tell exactly what's happening at the biochemical level as well as uncorrected FG pet. If we don't have corrected count statistics. We have no clue where we are, so only with corrected count statistics. Can we adequately say at two cycles, three cycles, 6 cycles exactly what's happening at the biochemical level. And we can use the differential biochemistry that is inherent to malignant and non malignant cells. Obviously this is very important, particularly in patients with cervical carcinoma undergoing radiation therapy intervention. We know that the normal or inflammatory cell generally has glucose 6 phosphatase and about 9% of cases that breaks down the sugar phosphate or FTG phosphate bond. If that happens, FTG equilibrates between the intra and extracellular space, and we don't have continued accumulation of FG's or S UV. It's corrected. Will not change, it will go down. On the other hand, the believe itself because it wants to hold on to glucose because it prefers anaerobic metabolism to arrow event catabolism, which is another story altogether. 90% of those cells don't have glucose 6 phosphatase, so in those circumstances we can use biochemistry to our advantage, but all of this is obviously is contingent upon adequate count statistic measurement. Let's take a look at a couple of examples and then we'll be done. So here's a case. 68 year old female initial staging into cervical carcinoma in July of 2015 they undergo two cycles of cytotoxic therapy. They have a complete resolution of their previously defined abnormalities. All of them. You can see that patient has some Brown adipose tissue and thoracic paravertebral muscle tension artifact, but we have a complete metabolic response so we can make the determination at this point that after two cycles, if we continue the therapy in the patient tolerates the therapy, they should go into clinical remission. At about 8:00 cycles. Next slide. Here's an interesting case. You got an FDG pet study that was tamed, obtained in October of 2015, after four cycles of cyto toxic therapy. That's our baseline and that is just you can't do that if you're going to follow these patients from a black perspective, they have to have a pet study at baseline. If they don't have no clue where you are once you start therapy. If you look on the right hand side, these are lymphoma patients, but look at this example in the lower right hand corner, you have the baseline exam, cytotoxic therapy begun. 24 hours later they do a PET scan. This is published in the J&M. Back in 2004, it's all gone, so this shows you that up in the upper left hand corner we've got problems. We're going to do this, and unfortunately so they're cooking along and thinking the patient's doing well, and after the therapy is completed, they actually have residual or recurrent disease. Alright, here's three cycles of Avastin in the cervical carcinoma, patient, 71 year old female. An obviously, let's just look at this from a qualitative perspective. Yep, looks worse. Can we actually make this make sense? Well, first of all, we know that after several cycles, if we have progressive disease, things are working well. Alright, that's fine. We can make that assumption qualitatively, but let's take it to the next level. If we have corrected quantified count statistics, we now have a new baseline, so the new echelon of therapy will be able to be functionally. Followed accurately as you initiate your new treatment protocol. Next slide. Alright, this is after two cycles so we have a partial metabolic response and a complete metabolic response depending upon the abnormalities. Again, so we see that part of this is all gone, but part of it remains so now what do we have right? We can look at this from a positive perspective until the Commission. Yep, it's working continue, but what is most advantageous about this methodology is the fact that we have now established a new baseline that's accurate that can be used from the next evaluation of the patient. From the metabolic perspective. And here is a baseline. We stage examination demonstrates recurrence. We undergo two cycles of therapy, and here's one of those cases like I showed you just a few minutes ago where it kind of looks about the same. Obviously it's a little bit more intense, so we can play with the intensity of the machine, but I would say from a qualitative perspective it looks worse. Is that all you're going to say? I mean, is that the response we're going to have to the Commission looks a little bit worse, thanks? Or are we going to provide the clinician with a definitive, objective piece of information, and that is achievable? With corrected count statistics. So we've now defined a new baseline for all our abnormalities as we follow this patient with a new echelon of therapy. And then here is a 54 year old female with history of several carcinoma and this is survival. If you look on the right hand side. This is one of the papers we referred to just a few moments ago. So we have our initial evaluation in September of 2015 and then at the conclusion of treatment in April of 2016, we have a complete metabolic response and if you notice, it's interesting. Slides, you know it's interesting on the see T report here. It just says continued decrease in the size of pelvic adenopathy and when we look at the pet study, we consider that definitely say hey, it's gone. It's completely gone. Then we can extrapolate it to our curves. There's another case, 76 year old female with primary uterine carcinoma. An initial staging. We have a partial metabolic response achieved in August. And then at that time, after therapy was discontinued in August, the patient comes back in January of 2016 and you can see they have dramatically increased progressive disease and we could have predicted this basically. First of all, have we looked at it at two cycles? Generally we would have seen persistent uptake, so we would know that the patient is going to be these individuals that don't demonstrate a complete mailbox response. They're going to be obligated to some sort of treatment, probably for the rest of their lives, because they have not achieved that magical decrease. And the uptake that occurs after two cycles that can be adequately quantified with count statistics that are corrected. And then we can see that there is another study accomplished just recently in April of 2016, with another partial metabolic response. And here is a late failure, and it's interesting we've got our initial presentation in November of 2010. We have a complete metabolic response after completion of the radiotherapy. We have completed follow-up continued follow up and April of 2013, and then unfortunately a late recurrence that manifests itself in distant metastasis in this person with cervical carcinoma. I like this case because this shows this paramit real involvement extending outside of the pelvis, and then we end up with the lymph node involvement. As you see in. April of 2015, and then after several cycles we have a response after six cycles in our. Initial uterine abnormality and we have progressive disease within the abdominal retroperitoneum. Again with, this allows us to do is to provide new baseline information as the clinician follows the case. And this just goes to show you can always trust what you see on CT. Let's take a look at that lymph node that's shown on the right hand side monitor and 11:25 fifteen demonstrating a significant amount of uptake. The maximal SUV is 8.6 and look what happens in April of 2016. We actually have an increase in the size of the lymph node in a decrease in the quantity degree of uptake. And basically this has been shown that you'll have cellular edema that occurs. With successful chemotherapy, you're going to change, not a decrease in the size of the abnormality anatomically, but an actual increase. I've got a paper on there for you from the Breast Journal in 2001 that showed this change in breast tissue that have been treated with chemotherapeutic intervention. So in conclusion. I think we made it. We got pet CT provides. Good sensitivity and specificity in the staging and re staging of gynecological malignancy's. Thank the previous slide spoke for themselves. The assessment of biochemical status of known disease sites with sequential PET CT allows for more precise evaluation of the response to treatment if we provide corrected pet quantitative data, we consistently and reliably and reproducibly evaluate the status of known or suspected disease and the use of this corrected pet affords the accurate appraisal of the treatment of milling disease and patients not only what kind of logic, malignancy, but all malignancies, and that is what allows us then to take this very, very powerful technology. And allow it to do what it was originally designed to do when it was introduced in the marketplace more than 15 years ago. So that concludes my talk and you have any questions. I will be happy to address them. I just got a little card here from the amazing Karnak that says there are no questions. While I think Doctor Blackford, today's webinar, that was quite a bit of information, we will have today's webinar archived on M iPad source. It will take about 30 days, so please do check back on our customer portal an my pet source so that concludes the web and R. Thank you for participating and thank you very much. Doctor black. My pleasure.

Weighted Meta-Analysis of FDG PET vs. CIM in Malignant Disease through mid 2015 Fludeoxyglucose F 18 injection (18F FDG) * Methodology Please note that the learning material is for training purposes only! Kinetics of tumor cell kill and relation to Target I Index lesion detection, assignment OBJECTIVES OF IMAGING Procedures In Malignant Disease Cervical Carcinoma: Initial staging Weighted meta-analysis. Weighted meta-analysis: Restaging - endometrial carcinoma Weighted meta-analysis: Initial staging Weighted meta-analysis: Initial staging-cervical carcinoma Weighted meta-analysis: Restaging-cervical carcinoma Cervical Carcinoma: Restaging weighted meta-analysis Ovarian Carcinoma: Initial staging Ovarian Carcinoma: Restaging weighted meta-analysis Endometrial Carcinoma: Restaging weighted meta-analysis Endometrial Carcinoma: Initial staging Weighted meta-analysis: Restaging-ovarian carcinoma Weighted meta-analysis: Initial staging-ovarian carcinoma •ymor cell population and-relation E'.Tymor cell population and-relation Tumor cell population and relation Ovarian carcinoma: PET Impact on patient management Assessment of therapeutic response to radiation therapy Assessment of therapeutic response: Ovarian ca Cervical carcinoma: PET Impact on patient management Endometrial PET Impact on patient management • Initial staging - endometrial carcinoma PET-CT Interpretation, Producing reliable consistent quantitative analysis EORTC Standardization and accurate-objective PET-CT reporting Summary of Oncological FDG PET Literature All gynecologic malignancies: Initial staging - Predicting Tumor Response to Therapy All gynecologic malignancies: Restaging, detection recurrence Cervical Carcinoma: epidemiology Cervical Carcinoma: Initial staging weighted meta-analysis Cervical Carcinoma: Restaging - detection of recurrent disease Ovarian Carcinoma: Initial staging weighted meta-analysis Ovarian Cancer: Restaging - detection of recurrent disease Ovarian Carcinoma: epidemiology Gynecologic malignancies: FDG PET Impact on patient mgt. Endometrial Carcinoma: Epidemiology Endometrial Carcinoma: Initial staging weighted meta-analysis Endometrial Cancer: Restaging - detection of recurrent disease The Value of PET/CT in Gynecologic Malignancies gynecologic malignancies: Initial staging EORTC and PERCIST Target / Index lesion detection, assignment Methodology of comparative quantification Survival based on response to therapy in cervical carcinoma FDG* Injection Conclusions: Sponsored by: PETNET Solutions, Results: Non-mediastinal lymph node involvement in various malignancies results of PET 104/17/15 103/20/15 Factors necessary for accurate quantification Conventional imaging, uncorrected FDG PET, corrected FDG PET: therapy assessment For the proper use of the software or hardware, please always use the Operator Manual or Instructions [or Use (herein- Determine threshOld assigned, livercorrected SUV change Determine threshOld assigned, livercorrected SW change Determine threshOld assigned, Ijvercorrected SUV change Injection for Intravenous Use Intracellular processing Correct Identification and Quantification -CIQ Individual patient dependent, site specific thresholds Clinical parameters, RECIST versus Metabolic data set in predicting response to FDG PET scan abnormality Rationale for hepatic parenchymal, liver calibration Assessing the response to therapeutic intervention: Is seeing believing? - Surgical staging remains the gold standard for LN metastasis - NCCN Guidelines for staging ovarian cancer: Physical and pelvic exams, o PET scan abnormal Cervical Cervical C.rcimma C.rcimma 32 patients with biopsy proven cervical - Obstetricians) Staging - (International FederationofGynecoIogistsand Obstetricians) Staging 238 patients with cervical carcinoma studied with FDG PET/PEVCT treated with external beam Results of NOPR Rationale for SUV max calculation - Ovarian carcinoma generally staged surgically - Most common gynecologic cancer diagnosis and cause of death Including-ovarian, cervical and endometrial carcinoma 36 pts with known cervical ca studied with •t Restaging Ovarian 49: O: - Definition of recurrent cervical carcinoma: tumor development 6 mo. - Treatment failure in low risk pts is exceedingly rare - Epithelial ovarian carcinoma is the most fatal gynecological malignancy - Third most common gynecologic cancer diagnosis and cause of Stop therapy Main function of FDG PET-CT is in the accurate portrayal of lymph node and distant metastatic disease - 168 patients with known ovarian carcinoma were studied with FDG PET at restaging following All Malignant Diseases: Staging FDG PET Arrival Into Mainstream Medicine and the Medical Marketplace of FOG of - Major role of FDG PET-CT for the initial treatment strategy is to exclude lymph Correct Identification and Quantification - CIQ - CT and tumor marker follow up of endometrial-uterine carcinoma is associated Division of Siemens Healthcare after collectively "Operator Manual") issued by Siemens Healthineers. This material is to be used as training material Uncorrected. non-standardized, no thresholds Continue therapy - Second most common malignancy and leading cause of death - Molecular markers: SENS FOG SENS Important Safety Information Dosage Forms and Strengths SPEC FOG SPEC •Pts SENS CIH SENS SPEC SPEC SPEC FOG SPEC •pts SENS CIH SENS SENS FOG SENS - Molecular/ Metabolic imaging: •pts SPEC SPEC SPEC SPEC Webinar Objectives: carcinoma studied with FDG PET-CT 1900% and intra-cavitary brachytherapy. Results Of post therapy FDG PET correlated with outcome One01S9: 221, i99S Oneo'S9: 221. i99S 9:221.1995 9:221. i99S 221, 221.199S 221, 199S 2010 221, i99S n. CA 125 level measurement, imaging to include-CT, MRI and FDG PET-CT CA 125 level measurement, imaging to include-CT, MRI and FOG PET-CT surgically: exploratory laparotomy, TAHBSO, peritoneal lavage r, • 209 n • 209 n. 209 2010 1300 10.3 Change therapy FDG PET early, mid and late treatment 1300% 103% - PET-CT provides good sensitivity and specificity in the staging and 1330 100 20100 100% at least 6 months following surgery and adjuvant chemotherapy/radiation therapy n.273 only and shall by no means substitute the Operator Manual. Any material used in this training will not be updated on 3960 572. 25920 4592 2013 756 7060 91.5% 93.4% n. 1436 in United States and other developed countries p. 0.01 p • 101 cm wghtd I wghtd I - Mechanism of tumor dissemination: Squamo-columnar junction cervical following successful treatment of index lesion, metastatic foci Tumor to liver ratio death in United States PERCIST Standardized correction FOG wghtd FOG wghtd wghtd cm wghtd node metastatic involvement and define distant metastatic disease 212.2011 o' PET PET However there are 200,000 ovarian ca survivors in the US with diminished specificity for adequate assessment of suspected recurrence Ithin.Patient Variability of "F.FDG: Ithin.Patient Variability Of "F•FDG: •thin-Patient Variability of "F•FDG: •thin-Patient Variability of "F.FDG: n. 813 1936, Indications and Usage Amitet al. tm: 65, n. 763 n.iS9 100 2100% 10086 0.8 98 90.4% 80.7% 94.4% at baseline and 3 months following Non-treatment to treatment, Treatment to non-treatment, Change in type of treatment, downstage, upstage Med 2013 Med 54: IS17, 2013 Smith 263, Chunget 103: 76 186 19 18 98 72 .e€D COSTRAST 9, 92 9, 2014 32 24080 Re-evaluaticm Re-evaluaticrt 72.5 OUBJECTIVE SUBJECTIVE 876% 1300% n.6S4 n. 1220 92.1% HER2in breastcarcinoma Patient response Complete metabolic Of pretreatment uptake Patient response categorization: Complete metabolic response-absence Of pretreatment uptake Patient response categorization: Complete metabolic Of pretreatment uptake UNCORRECTED n • a regular basis and does not necessarily reflect the latest version of the software and hardware available at the time of 85.4% -t -2 -Glucose FOG -t -2 -D -Glucose FOG - Majority of recurrences occur within three years of original diagnosis Stan&rdized Uptake Values in Normal Tissues Standardized Uptake Values in Normal Tissues 918% - In a series of 133 pts studied with FDG PET-CT prior to surgical staging, 16% of patients demonstrated n: J IS. J Med St: IS. st: is. IS. et ao 3440 85.0173) J Med* 1510, 2013 1 n. CA 2000 2016 2013 2011 20013 90.3 - Lymphadenectomy recommended in high risk Stage I disease or in the 12 96 32 11 75 72 52 J 2013 restaging of gynecologic malignancies restaging of gynecologic Malignancies Park et al. Ko«ean r: Grigsby et 457.1999 32 457.1999 Havriles.ky et al, 97:183. Havrilesky et al, 97:183.206 Havrilesky et al, 97:183. ZOOS Havrilesky et al, Gyn«oIOrxol 97:183. ZOOS 32 1300 3200 32 15 4559 46 4760 1440 Sott tissue lymph nodes Soft tissue lymph nodes Sott tissue non-Ndiasinal lymph nodes 2013 after 6 cycles cervu cervO 100 00 80 Anatomic stroma parametrium uterus vagina completion of therapy Partial metabolic response-persistent uptake on post treatment examination - Correct choice of reference tissue For currently approved codes: 83 articles, 13446 patients For currently approved codes: 83 articles. 13446 patients et 496, 1988 496, 496, 1988 9888 Commissioned presentation J Med SS: Clinical applications of oncological CT, MRI SS: On an 698% Avoids surgical staging in poor surgical risk patients-comorbidities 80.7% 89. s 191.1993 •9.48 641 M) EORTC - Second most common cause of gynecologic malignancy in developing - All subjects had a restaging FDG PET study if (l) elevation Of the serum CA 125 or (2) :yspicious findings with - All subjects had a restaging FDG PET study if (1) elevation Of the serum CA 125 or (2) :yspicious findings with - All subjects had a restaging FDC PET study if (l) elevation Of the serum CA 125 or (2) susoicious findings with the training. 44; 44; 44: 44; 461, - 75% of initial presentations of ovarian carcinoma are associated with - In countries without cervical cancer screening and prevention • 18F FDG is indicated for positron emission tomography (PET) imaging in the so 103 44:461.2014 Saühet al, 263, 198 • KRAS codon 12, 13 colorectalcarcinoma al, On l: 263.198 Lett 10.3892/01 10.3892/01 10.3092/01 SUBJECTIVE SUBJECTIVE OBJECTIVE • Radiation Risk: Radiation-emitting products, including Fludeoxyglucose F 18 Of therapy therapy Stop therapy 12 pent* 12 12 pents 17 pents 100 100% 1600 ROC OBJECTIVE 53 (n RoseetaLJCEnonc0117:41.1999 extra-abdominal lymph node metastasis that would have been missed with surgical staging procedure 9457 1900 : 00 too 'too 96.7 n 341 n -341 n = 341 5472, 1 cm 4845 3145 51 788 1375 n = 2160 4334 4732 Multiple-dose 30 mL and 50 mL glass vial containing 0.74 to 7.40 GBq/mL (20 %taboåc %tabolic parameters - 80% of the pts enter remission following primary intervention 1197 1998 SO disease-any new sites of disease involvement on post treatment study n •961 imaging Imaging presence of serous or clear cell cancer al, 60 Il 20 71 80 11 10 Restaging Endometrial -Uterine Car&ioma Restaging Endometrial -Uterine Carcioma Restaging Endometrial -Uterine Caroioma Resta•ng Endometrial -Uterine Car&ioma n. 232 232 et SS: 6120 272 8925 SS: 25920 FOG wohtd 0.6 63.6 62.2 82.6 61.6 SJ.6 1.5xA Wghtd wohtd cm wohtd FOG • Normal liver parenchyma! • Normal liver parenchymal CT/ Conventional 76S% IJncorrected Uncorrected n = 4509 n 4509 - Recurrence may occur in up to 35% of patients (high risk: initial parametrial 80 51 n -4509 m: 572. 272. 572. 272.5 Sewaraetal, J Nucl Mede 199 CT or MRI J Nucl Med 40: J Nud MedeO: Quatutive QuaEutive (+) positive: 82.9% 82.7% J 199 199 1993 140 Differentiate malignant and Mean volume Mean tun" volume Mean reduction in 100 25 9: 80 Partial response Injection, may increase the risk for cancer, especially in pediatric patients. Use following settings: et al, and PET-CT EGFR kinase in NSCLC al. tot: 50: 1702, 2009 SO: 1702, 2009 69 - In developing countries, ovarian carcinoma third most common cancer countries behind cervical carcinoma Initial Staging Cervical Carcinoma 84 1806 3720 96 13200 10088 21050 32100 20013 32400 20801 6500 57 51197 3260 83 32053 - Define the diagnostic capabilities of PET-CT advanced stage disease (Stage Ill or IV) programs, ranks second in diagnosis and cancer death •pts SENS •pts SENS FOG SENS SENS FOG SENS FOG SPEC SPEC FOG SPEC FOG SPEC •Pts SENS SENS FOG SPEC •Pts SENS cm SENS •Pts SENS cm SENS •Pts SENS SENS SENS SENS 1197 n.3S9 n.3% •Pts •pts SPEC cm SPEC Transverse x AP Normal or n: 1059 n -1059 44.5% SS. 3200 41.4% 43.1% IS. SS: 7100% 71.0% 41.4% 82.7% 89.5% 36.7% 79.7% too 119 so 950 100 100% 1004 Quanbtaåve SUV Ouanütaåve SUV Quantitaåve SUV Torre •t •l, C' 6S: 201S 82-6 82.9 to 200 mCi/mL) of Fludeoxyglucose F 18 injection and 4.5 mg of sodium by volume With volume With radiate' volume With extern radiate' With extern al radiate' With extern SS9 80 81 Med Disclaimer** FDG PET FOG PET Constant is calculable Imaging Differentiate malignant and Biochnzal Molecular Biochemzal Molecular Bbchnzal Molecular Posiåve increased Positve increased Positive increased et 2040, 69, 2011 J 69, 2011 The Operator's Manual shall be used as your main reference, in particular for relevant safety information like warnings 100 20 32 83 2011 20107 3200 1400% 41.0% 1300% 100% 2100% 50 12008 1 00 et 2556 29010 PET 46 32376.2 41 2556 2016 2550 Recurrence rates are 25% for early stage and 80 - 85% for advanced stage disease non-malignant disease malignant disease 1803 46 83.3 80 4233 42332 5112 24080 45080 14080 4080 5112 8925 • Intemational Working Group (IWG) 5112 01 51 7050 n 341 41.6% Standardized correction - Recurrence most common in advanced stage disease (FIGO Stage Ill-IV: et Nud Med40: 1999 Nud Med40: 1999 + = Positive + = positive Bipatet 91: 59, Bipatet al, 91:59. 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J Gynecologic Carver n -2869 65.6% - Assessment of the biochemical status of known disease sites with sequential the smallest dose necessary for imaging and ensure safe handling to protect to and HD to pelvis and HD Wghtd cru wghtd 41.4% 41.0% Wghtd to FOG inflammatory Nodalities/ n -1971 n -1064 'too 89 2790 53000 - Under staging of endometrial carcinoma may occur in up to 22% of benign disease based on and verifiable based on 13 Initial Sta•ng Endometrial Sta•ng Endometrial 34646 34200 21900 32400 31 3772 294.4 2944 sixth most common malignancy in women worldwide Initial Staong Ovarian CarOinoma Initial Staong Ovarian Carcinoma Initial Staong Ovarian CarOnoma Consistent ACCURATE Definition Sl: St: n: 2869 984 103 27935.6 7935.2 7931.2 90 10088 Irruging by ET Imaging by Irruging by SO 61 by ET n *tents - Serum markers: et al, Wong et Wong 6: SS, Wong et SS, Mole 19,100 10,100 Wong 90903 and cautions. et WHAT IS THE CLINICIAN ASKING AND WHAT DO THEY WANT TO Casey et al, 331.1994 0.4 00 463, 00 Acta 463, al, Acta 463, al, 463, tost 69, Out so 463, es.7 62.2 63.9 62. i 1799.7 Lai et al. 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Int Gyrpcol Cancer It: 263, Narayan et al. Gyrpcol Cancer It: 263, Positive 36:1952. 2650 7056 46 76 vana*ty Of Of 18606 32.7% 36.5% 72 4233 72.5 15 1714 12215 1215 122186.5 •150 100 60 140 18300 12304 6408 94.3 813 747 5472 74720 7935.2 t Char" al. Neoplavna 45: 7935.21 859.01% 59.1% -CEA Assessment of therapeutic response 40 51 80 peer reviewed literature wghtd wghtd no Wghtd 8486.4 8186.4 FOG Wghtd 10088 80.3 7935.2 97 970 FOG X? X? Modalities/ 570% 5707% mL volume) for intravenous administration. > 50,000 cases/year and 8600 deaths, average age at diagnosis: 61 years n.S61 61 93 25 72.5 747 n -353 16051 2013 2790 28 1140 3360 1215 9287.5 94287.5 75 57. t 57.1 32.7% 57.7% 36.5% LN, Chstart LN, - In the United States, approximately 22,000 new cases of ovarian et al, al, Yoshidaet al. Am J 182: Yoshida et al. Am J 182:227. 94.4 8925 15 205 19090 2325 205100 9590 24580 25,100 Note: Some [unctions shown in this material are optional and might not be part ot your system. Note: Some functions shown in this material are optional and might not be part ot your system. and of mediastinal Unger et al. Gynecol 94: evaluation of malignancy in patients with known or suspected abnormalities et Eur J Nud Med Md 60 4720 72 - Local recurrence of cervical carcinoma typically vaginal vault > pelvic - Diagnosis Of primary tumor - Diagnosis of primary tumor • - Diagnosis Of primary tumor • and or mediastinal • Deauville 5 Point Scale Deauville 5 Point Scale 80 80 100 et Am J 22'. et Am J 182: 22'. FOG •pts SENS •pts FOG SPEC •pts SPEC •pts 40 •pts SENS •pts SENS CIMSENS •pts central to development of neoplasia et Am et Am J 182: SENS FOG SENS •pts SPEC FOG SPEC •pts SENS cru SENS •pts SPEC cru SPEC -CEA -PSA Comments - Derivation of constant reference value Perceived Suzuki •t al, Int 17: PET and 12, Incorreased Increased PET - Majority of women with advanced stage ovarian carcinoma will relapse 9495.0 18511.5 72.5 14862.5 O LN. Otstart O LN. Ovstart "The statements by Siemens' customers described herein are based on results that were achieved in the 36 94 91 3185 al, Once Lett 10.3892/01 13500 57.7% Gynecologic Malignancies 35 97 - 50% of recurrences are symptomatic (vaginal bleeding, hematuria, rectal bleeding of the presence or absence of malignant disease - Metastasizes directly into the peritoneal cavity; penetration of the ovarian capsule 2000 83 : 460 Kitajimaet Ann Ann Chat" al, Cancer 6120 1824 68 6408 68 6664 63 15 found by other testing modalities, or in patients with an existing diagnosis of 3680 6958.0 88 blood pool 15080 13010 et blood pool -CA 27.29 .CA27.29 meg met' carcinoma per year and 14,000 cancer related deaths too Cervical Carcinoma O LN. C*sturt O LN. 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Since there is no "typical hospital" and many variables exist (e.g., hospital J n; - Initial spread of the tumor is the invasion of the myometrium cervix sidewall and parametrium - Review the basic epidemiology of cervical, endometrial and 53.1% 47 50 60 32 40 95 72 15 - Localization of unknown primary tumor 68 • Intra-vendor comparison • 258 unit in liver reference value 26.9% PET negative FOG PET negative Differential biochemistry 2056 355 18511.5 Risum et al, Int GynecdCarxer 19: Risum et al, Int 19: Risum et al, Int GynecolCarxer 19: Risurn et al, Int 19: 7024.5 47205 14862.5 uptake 85 83 4233 1233 A = SUV 4182 2550 25920 2 00 Significance of PET-CT u: IN, M despite surgical cytoreduction and platinum-taxane combination therapy Application of Corrected Quantitative PET-CT 3960 1680 81.6 80.3 55.5 1691.7 7935.7' 10 294.4 94.4 93.4% 8486.4 03/20/15 Certain products, product related claims or functionalities (hereinafter collectively "Functionality") may not (yet) be so 02/26/16 03/20/15 66 4160 1289, 7600 53700 1080% 1600% 16080 16001 1500% 4448.2 4619.2 49190.2 47 650 2016 6120 1440 276 83.3 85.7 81.6 1830 5285 Sironi et al. Eur J Nud Med Md : 00 26080 32000 6120 47230 4020 47320 O LN -CA 125 anorexia, unexplained weight loss, edema) Ceu Death Death A = SUV invasion of proximal viscera I pelvic peritoneum contralateral ovary, peritoneum, uterus 03/18/16 07/15/15 04/13/15 104/17/15 10/22/1 s 09 81 cancer. 15 80 FOG PET vs. A' FOG PET vs. size, case mix, level of IT adoption) there can be no guarantee that other customers will achieve the same suboptimal imaging may occur in patients with inadequately regulated blood Castenxi et al. Nud Med Commun 28: Cast&i et al. Nud Med Commun 28: • Tao separate scanner locations • Accurate definition of quantitative response 76.3 76.9 1691.8 1221 55.5 85.7 12.5 1221 - Main risk factor: excess endogenous or exogenous estrogen without al, 49: 1936. al, 49:1936. 46 Nud Med 46 47381 77 9888 01/04/16 03/204/15 24080 20920 76 1140 3680 . Metabolically stable disease O LN. mes O LN. mets 10/22/15 107/15/15 105/22/15 02/19/16 103/18/15 03/30/16 03/18/16 05/19/15 72 5820 49190.2 5820 92 - Global incidence: 528,000 new cases in 2012, 266,000 deaths 1221 J Med 29•, J 29•, 109112.0 169112.8 1221 42 9: EORTC PERCIST too 9003 9003 93 91.7 97 7912 3500 5704 1600 24080 42 O LN O LN,Chstart via standardized-corrected quantification Equivocal: Khan al. Cm NO Sakurai et al. or fallopian tubes ovaries local invasion of other organs of pelvis Lin 89: 13, Lin al, Cancer 89: Lin al, Cancel 89:73.2Ø3 Lin al. Cancel 89:73.2Ø3 1210912 -CA 19-9 commercially available in your country. Due to regulatory requirements, the future availability or said Functionalities 2016 76.3 7230 2451 ass9 - Directing biopsy procedures Park et Korean Park et Korean 51, Kitajima Am Roentgenol 190: 1652, Kitajima Am J Roentgenol 190: 1652, 24920 84.4 22434.7 76. t 18948.9 1080 1 abdominal cavity. Cells transported to abdominal cavity and flow in a clockwise manner 75 results. 63 3760 97 2 00 5216.4 5218.4 80 2056 4182 17140 78 75 72 51 1215 ovarian carcinoma Cervical Carcinoma 4730 4720 92 6552 47 4559 IN, •o_ - Provision of corrected PET quantitative data provides consistently reliable Overall likelihood of relapse is 62% glucose levels. In these patients, consider medical therapy and laboratory 2920 12720 85 51 20101 .E 0.6 O LN. CRst&t Ciscontinue Treatment 6.445 Chang al, 45: Chang et al, 45: al, 45: Gucia•Velknoet •l, Eur j Med Gucia•Velkhoet •l, Eur j Gucia•Velkh0et Eur j Gucia•Velknoet Eur j al, Eur j Mid Wd - Fifth leading cause of cancer death in women in the United States 589, so so, mmths - Remaining treatment failures are defined with surveillance (clinical exam, Sun Anticancer 80 20 100 60 Chu" et al, Gynecol Oncol Chu" et al, Gynecol Oncol 103:165.2m7 et J Nucl Med et J Nucl et J Med • Alpha feto•protein Alpha feto•protein Med opposition by progestin (estrogen therapy without progestin), obesity GEOiscoveryDS600 GEDiscoveryDS600 GEDiscoveryOS600 106914, Philips Philips Gemini GXL - Quantitative FDG PET interpretation - Qualtitative FDG PET interpretation SiernensBiograph 16 Siemens Biograph 16 uptake 73 73. 7311.2 6429.6 8429.6 814.3 7166.8 2016 20016 in any specific country is not guaranteed. Please contact your local Siemens Healthineers sales representative for the .RAEXCa«. . 32 4233 3765 3765 60 63313.1 63318.2 11400 100% 24080 97 10.3 3774.1 32 3900 103 51 83 2763.6 4738 3:60 756 75.6 Equal to the 9000 186050 1696 1196 IN, 'N, met* met' 91.7 11.7 4676.7 34 3:50 4080 O LN. Chstut O LN, Chstart 75 756 38925 6696 4080 - Distant metastasis are present in 70% of patients with recurrent disease Treatrrnt treatment treatrrnt 650 Evaluating the response to the Evaluatir•gthe response to the the response to the 03/30/16 al Sites demonstrate In"creased al Sites demonstrate increased al sites demonstrate ' "creased - Extent Of disease (staging) Upstaging, down-staging Extent Of disease (staging) Upstaging, down-staging - Local-regional metastasis: via three separate lymphatic pathways: Cardiology: For the identification of left ventricular myocardium with residual 34: 1396, 34:1396. Following initiatio Following initiation toxic therapy, no testing to assure at least two days of normoglycemia prior to Fludeoxyglucose CMR PMR -B HCG -B • HCG 22 Is working • HCG 50 29: xm 21 90 29: mm 20 28 83 40 27 650 2571 xm 7235 96.7 11424 511424 64080 75 355 92 32 54 year old female with ist Ovarian carcinoma restag Initial staging examinatio 98 m, 10374 as: d by restaging after 6 cycles •nation PET > CT, precise of cervical carcinoma nation PET > CT, precise O met* O 'N, met* O 'N, met' Initial FDG PET study ta ed after 4 cycles of Restaging examination 186800 18600 10088 All Malignant Diseases: Sestaging All Malignant Diseases: Restaging ET u Restaging examination ation demonstrates Baseline restaging PET > CT staging; Initial staging 47 340 103 56 100 42 460 45 32 tages ovarian liver and or 46 3264 3264 16: m 42 .2 Weresenaestordise•se %eresenaestordbease EORTC PERCiST EORTC PERCtST most current information. and reproducible evaluation of the status of known or suspected disease 1785 imaging evaluation, tumor marker — CA 125) of Cnstant 04/16/15 272. 572. 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Gynecol Cancer 1m: 65, XD6 F 18 Injection administration. 21 28 88 1806 1848 1 = PERCIST: 1785 1806 1626 Kitajima •l, Eur J Nue Med Mol Im•øng Kitajima •l, Eur J Nud Mol Im•øng mediastinal blood zone Irnagng. e.g,CT Irnagng. ag,CT Imagng. ag,CT Imnagng. ag,CT Irna". ag,CT ag,CT 03/15: Negative presenting for restagin FDG se. sea see 02/16: Positive EORTC of CT, T-CT and diagnostic CT 1900 2014 30 6120 et.L 19: 1999 94 19: 19: S103.1999 19: 1999 19:8 19 84 78 cytotoxic therapy (10 22/1 ), followed by examination cytotoxic therapy (10122/1 ), followed by examination Recurrence, metastatic d sease (01/08/16) induced edema induced carcinoma Endocervical ca - Detection of recurrence (restaging) 2920 80 40 21 82 saoo so 50 34720 3772 - Recognition and identification of site specific Hypogastric route: internal iliac vessels 32053 20013 90.3 94.4 169112.8 18511.5 18511.5. 892.5 55.5 47205 retroperitoneal lymph nodes to the 9630.5 30732 et Eur J Med Wong et SS, Upstages disease liver and or 2W7 PET-CT detects recurrent uterine malignancy in setting uptake IN, M SO eco 100 1472 14720 SO 2490 cow.wsos - Global incidence: 225,000 new cases in 2012, 140,000 deaths 4676.7 9495.0 29201 Pan et al, Arch 283: Pan et al, Arch 283: 335, Pan et al, Arch Gynecol 283: 81.3 cr cr w CT CT w 24001 2499 1999 of countstatistics Count statistics new baseline metabolic a 2010 1300 50 80 2011 5100 1200 coronary artery disease and left ventricular dysfunction, when used together 2236 4825 51900 2660 WiaUe Cell Number Wiawe Cell Number pool Cell Cell Number 36 100 80 100% 961 3772 37831 34831 Ur«et al. GynecolOxol% 212.2004 4738 ) 2451 45 Lott et al. 75 756 71 25 97 Lott et Mean age at diagnosis: 48 years Slice thickness 77 73 377431 96.7 3960 90 9888 4600 14738 94 - Describe the application of PET imaging in the staging progression n. at J 2010 2590 • Decay corrected SUV remains A tumor max SW A tumor max SUV The reproduction, transmission or distribution of this training or its contents is not permitted without express written 9362.7 93630.7 8355 58.8 63318.2 64868.2 7024.6 10.3 77 80 8961 3960 Lateral route: external iliac vessels diaphragm to the supraclavicular Increased No increase 1.5xA> 1.5 x A > - Pattern of recurrence is directly related to the initial disease status therapy at therapy Average sensWvi9• Average Percent change sensWvi9• Average Percent change -Conventional Imaging - Conventional Imaging 36: 362, 2009 36: WIV.antce• 28 98 08 77 2499 46 1140 4676.7 4676.3 9676.7 43860 2016 32000 20016 29001 O Ct O CT, distant O CT Extent of disease at initial presentation, results of surgical cytoreduction, rapidity of Ct "I distant A = tumor SUV max or mean A = 1.5 x tumor SUL FOGPET A = tumor max SUV of a negative diagnostic CT examination 13251 J S329, Nud S329, - Monitoring of treatment response = PERCIST: PERCIST - Main subtypes: endometriod (80-90%) and nonendometroid mediastinal blood 35300 1714 17197 2883 2538 2538 60 51 SO Med": 01 J Med 49; al, Ann Nud Med 197, Tranet al. al. with myocardial perfusion imaging. 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SW . 2-8 SW 2.5. 2-8 SW•8.S SW Liver Lymph node involvement 186 34 18600 18606 8186.4 1486045 34200 34720 340 970 29590 have been reported; have emergency resuscitation equipment and personnel 71 L hhe•ent 10 16 90 100 103 60 40 19 15 L = liver reference SUV max or 76.46831 86.47059 L = liver reference SUL L = reference value liver SUV 57.04545 i 57.04545 j 57.04545) umbilical lymph nodes reference 92 52 MRI therapeutic intervention Partial r esponse Piechio •t •l Nuclear Medicine 4482 4448.2 Malignant cell malignant disease X LV constant corrected t esponse response Metabolic stability All names and data or patients, parameters and configuration dependent designations are fictional and examples - Majority of ovarian malignancies arise from epithelial cells, remainder: uptake > liver Uptake < liver - Common and Para-aortic LN Common iliac and Para-aortic LN therapy — Neurology: For the identification of regions of abnormal glucose metabolism - Adenocarcinoma is most frequent histologic type associated with 15 1221 98 3362 FOG PET 1221 8925 2592 95 u. 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It has Spensitivity Spensitivity increases with Stage of disease: radiation •20 40 Osseous metastasis: 20% FOG PET FDG PET FOG PET - Utilization of PET-CT allows for determination of disease Abdominal cavity lymph nodes: 8% 15 .2 84 24 21 36 72 87 SUV and PET-CT FOG PET-CT CT describes probable liver metastasis 2400 Middle and inferior uterus LN drainage Ciscontinue Treatment Restaging Gf gynecologic Malignancies Restaging Gynecologic Malignancies 90.44859 80.75 60.751 80.751 80.75 L PET > CT staging; PET upstages cervical 69.81618 Recurrent disease malignant disease 79.618421 79.61842/ 79.61842, in uptake uptake liver parenchymal SUV in Restaging choUne — into cell membrane chonne — hnto cell membrane choüne — into cell membrane chonne — into cell membrane chonne — incorporates into cell membrane choUne — incorporates into cell membrane reference Overall impact Cervical Initial staging Endometrial Of cervical carcinoma presenting Quantification Of Quanffcation Of QuarM:atiOn Of QuanffcatiOn Of Of All rights, including rights created by patent grant or registration or a utility model or design, are reserved. Distant metastases rare in absence of pelvic LN involvement Cycles Of chemotherapy Ovarian 10.3 1221862.5 122086.5 1420862.5 1220862.5 61220 185112.5 528 28051.8 34053 reference value variation that S s in normal are X = LC constant corrected Initial Staging Gynecologic Malignancies Disease stabilization stage • 25%, stage Il and stage I • 25%, stage Il and stage • 25%, stage • and stage • 25%, stage Il • and Dual phase •Please see •Please see accornpanyirG •Please See prescribirg •Please see accornpanying •Please see accorroanyrng •Please see accorroanying prescribirg •Please see accorroenying Initial Staging Cervical Carcinoma Restaging Cervical Carcinoma 20 40 60 80 120 20 40 60 80 120 140 son issue LN son tissue LN tissue LN therapy - 25% of cases occur in premenopausal patients, early detection leads - Parametrial and Obturator LN - Parametrial and ObturatorLN - 1/3rd of pts with only with initial uterine disease will have local recurrence; the PERCIST method Cellular biology/biochemistry R CIST R CIST eria •Please see accomoanying prescribing •Please see accompanying prescriber.g 2 year survival 4 year survival 100% 08 50 •Please see accompanying prescribing - Utilization of the proper quantifiable value Liver and adrenal glands: 15% evaluation of malignancy treatment intervention 89.43607 53.12841 74.02826 - Serous carcinoma is most common subtype of epithelial origin ovarian 82.88289 Restaging Endometrial-uterine Carcinoma; Detection of recurrence Supraclavicular lymph nodes: 7% - Women with treated ovarian carcinoma are at a high risk for recurrence for initial staging examination, extent and defining the baseline pre-systemic treatment metabolic parameters (negative on PET), PET defined pleural 89010.9 72759.0 336 with (4), for the liver SUV, which is quite stable with (4). for the liver SUV. which is quite stable with (4), except for the liver SUV, which is quite stable with for the liver SUV, which is quite stable 29190.1 2236 2932.5 Time in months 18497.8 with (4), except for the liver SUV. which is quite stable Clinical 11 92 18 51 90 80 101 55 21 20 75 98 57 40 91 15 95 10 Impact on pt - Most common histopathologic types are: squamous cell (69%) and carcinoma to Stage IV disease Initial Sta•ing Ovarvican CarOinoma Initial Staging Ovarian Carcinoma Intra•veMr. samne same location Intra•veMr. sarne same location Intra•veMr. same same location information on slides 97-107 information on 97-107 information on *des 97-107 information on sues 97-107 "'formation on suides 97-107 inforrnat•on on slides 97-107 On patient Cyck two Cyck carcinoma Cyck four four two stage • stage IV stage SUV one 71.64167 | Precise quantitative measurement *'formation on sues 97-107 *'formation on sudes 97-107 "'formation on sues 97-107 hnformatlon on sbdes 97-107 "'formation on slides 97-107 *'formation on slides 97-107 74281.8 3590 67232.4 32376.2 359 32831 65.64": thymidine — marker of DNA synfresis thymidine —marker of DNA synfresis Conventional Imaging Modalities Sensitivity and or mediastinal and of mediastinal Tine in mmths post therapy Tine in mmths therapy in mmths in mmths therapy Continue therapy 91.85851, 89.49446/ 89.49446: 63.8733 n 63.87331 79.73190D 79.7319/ 79.73191 10% pts have distant metastasis to the left supraclavicular LN of which 40% will have over can with Mid value Added dimension of Restaging Ovarian Carcinoma over time Richard R. 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PET upstages MRI to discovery of Stage I disease in > 70% pts over over can 91.45125 j 77.296361 77.29636 i 77.29636: 77.29636! 77.29636, 9209918 i 92.09918 9209918J 91.45125 Copyright C Siemens Healthcare GmbH 2020 metastasis remaining > 60% distant failure O" 20 20 End FDO EDO et No variability, not operator depen±nt NO variability, not operator depene•nt - Distant metastasis rare 2-3% lung, liver and pleura management management ca and is related to fallopian-tubal and peritoneal ca and most survivors will not be cured Cumulative survival in ongoing study of 378 pts with cervical caner Turkingtonand Coleman, Semin 37: 102, 200Å9 Turkingtonand Coleman, Semin Roentgen0137: 102, 200Å9 Page 4 Page 6 Page 5 pts with SUV change 2 30 47 73 42 10 98 20 28 40 34 86 43 52 57 94 63 650 75 13 92 60 72 50 61 33 82 81 56 32 22 83 71 65 31 96 76 29 95 9, 55 756 90.3 51 41 199 91 100 23 25 35 78 88 80 90 45 58 24 15 97 21 1073 19 70 pts with units SUV PB with units SUV pts 20.3 units SUV change pts with SUV pts SUV 14 (such as CT) adenocarcinoma (25%) figure 3 this Figure 3 this 229: 2012 229: blood pool Turkingtonand Coleman, Semin Roentgen0137: 102, Count statistics para-aortic involvement Lymph node involvement FOG PET vs. 0M of FOG PET vs. 0M Restagi% of FOG PET vs. 0M Of FOG PET vs. 0M Restagirvf FOG PET vs. 0M Restagi%0of FOG PET vs. 0M Restagi%0f FOG PET vs. 0M Restagi" of An Ries et SEER Cucer Statistics Review. Cucer I.stitute Betbesda.MD 2007 Ries et SEER Cucer Statistics Review. Cucer I.stitute 2007 Ries et SEER Cucer Statistics Review. Cucer Imtitute Bethesda. MD Ries et SEER Cucer Statistics Review. Cucer Imtitute Bethesda. MD 2007 Ries et SEER Cucer Statistics Review. 197.8-2004. Cucer I.stitute 2007 Ries et SEER Cucer Statistics Review. Cucer I.stitute Bethesda. MD 2007 Can define status Of residual uptake Can define Status Of residual uptake Can define status of residual uptake Data accumulated through comprehensive analysis of PUBMED through mid 2015 See slide 11 for references slide 19 for references slide 22 for references slide 45 for references — measure Of synthesis 01122/13 06,'20113 01122113 06/20113 on examinations on sequential examinations On examinations on sequential examinations • 23 unit (833%) Progressive disease