Three surgical oncologists offer exciting news on hepatobiliary, thyroid and breast cancers. First up is a look at benefits of minimally invasive robotic surgery for rectal cancers; regional therapy for metastatic GI cancer; 3D virtual surgical planning; and biomarkers for pancreatic cysts. Next, learn why the U.S. thyroid cancer epidemic isn’t just a case of overdiagnosis and which factors should drive thyroidectomy decisions. Finally, hear about breast cancer technique alternatives that boost patient – and staff – satisfaction, such as intraoperative radiation therapy, instead of traditional radiation, and the Magseed, instead of wire, to localize lesions.
Well, good evening everyone. I'm dr laura crecido, the CMO and VP of Cancer services at UCSF. And I'd like to welcome you to the UCSF Cancer Center. Grand rounds, current advances and controversies in surgical oncology. Best of the year, Part two. And tonight I'm very excited to have three great speakers focusing on surgical oncology. Each speaker will have 30 minutes. Will take a few questions immediately following each presentation. Please put any questions that you might have in the chat and we will make every effort to answer all the questions time permitting. Uh we do have a tight schedule so we'll begin first. I'd like to welcome dr RJ Maker, our new chief of the Division of surgical oncology at UCSF. DR Maker recently joined us from the University of Illinois at Chicago where he was the director of surgical oncology for the cancer center there. He's an expert in the surgical management of complex gastro intestinal and hepatic pancreatic, oh biliary diseases, melanoma and sarcoma. And he built a high volume programme that included laparoscopic and robotic approaches to pancreatic me and hepatic to me, what I found interesting was that as an undergraduate, he actually had a double concentration in fine arts, drawing and painting as well as biology. So perhaps we have the new netter on our hands. But he'll be speaking on current advances in the surgical management of gi tumors. So now I'd like to turn it over to DR maker. Great! Thank you so much. Doctor Chris Cheeto, Let me see if I can share my screen here. Wonderfully those slides portraying. Yes. Fantastic. Well, I really appreciate that introduction. It's an absolute pleasure to be here um in san Francisco and specifically, obviously at UCSF, it's really uh the dream come true. This is a fantastic opportunity to be part of just an amazing team and this is a really nice opportunity to be able to talk to many of you whom I look forward to meeting in person as the pandemic lines down and having the opportunity to talk about some of the great work that's happening in surgical oncology and specifically in gi surgical oncology here in our division of surgical oncology at UCSF. I have no C. O. I. This is our division and this is just a group of outstanding outstanding scientists and surgeons that I'm fortunate to be part of this team. And I'll mention where many of them are involved in the components of the highlights we'll talk about today. So the division of surgical oncology is made out of multiple pieces. The section of endocrine surgery of H. P. B. And upper Gi surgical oncology, Colorectal surgery, breast care, sarcoma, melanoma. And I'll talk today about the program in regional therapeutics. And really one of the advantages of being part of this outstanding faculty is that it's a multidisciplinary approach to these cancers. And all of these programs have dozens of clinical trials from Phase one to phase three that make the care of the patient holistic and forward looking and so when patients come to see us, they're getting cared, not only by experts in the technical components of the surgery, but they also have the opportunity to participate in the clinical trials program mm Within G. I. And HPV surgical oncology, the tertiary and quaternary care is quite complex on a routine basis. So gastric and HPV surgeries are performed for primary medicine cancers routinely almost on a weekly basis, whipple procedures with vascular involvement are performed liver receptions to more regulations. And a lot of these receptions will include bile duct cancers that often have incidental findings of gallbladder cancer found during routine laproscopic, holy suspect Amis in our community partners within the section of colorectal surgery. All of the gamut of receptions necessary for colon, rectal and anal cancers are performed. And one of the advantages is participation in a cruel from our section into NIH clinical trials that involved the timing of chemotherapy and more recently in cutting edge the potential non operative management, a rectal cancer after receiving neo adjuvant chemo radiation when uh complete responses are encountered. Another advantage of being part of the multidisciplinary team that the G. I. Section and colorectal section has taken advantage of is working with some of the partners, for example, the Oceans Center for Integrative Medicine where the patients can have a holistic and integrative approach to their care. And finally, we'll talk a little bit about a burgeoning program involving regional therapies that can provide surgical options for patients with metastatic disease that otherwise would not be surgical candidates. And these have been shown to improve quality of life and patient survival. So here's the section of colorectal surgery dr verma. At the top is the section head and these are members of the section of colorectal surgery and will focus just on to highlight its today of minimally invasive and multi organ resection for rectal cancer. And then a very unique program that's not offered in many places, which is trans anal minimally invasive surgery to remove low rectal cancers. Now, many of you, the audience know what minimally invasive surgery is. Um Some do not. I will just briefly show you some of the differences and highlights as it pertains to colorectal surgery. This is a traditional indecision for a colon resection for a colon cancer right after surgery. And this is still what happens in close to the majority of centers around the country. Um This is what an incision after a minimally invasive surgery looks like. And in this case just large enough to remove what was a six centimeter tumor around the umbilicus. And this is immediately after surgery. And this is three weeks after surgery. Now, actually, as I was putting these slides together, I I noticed that the patient is actually wearing the same underwear here immediately after surgery and the three week follow. So I'm assuming that that underwear was changed in between. But nonetheless, you can see how well this heels and in patients with smaller tumors. Um the incisions can be barely discernible. The advantage are not merely cosmetic. This involves postoperative pain. This involves rates of hernia, both after the surgery and decades down the line, and inter operative blood loss, to name a few, as well as activity recovery and post operative care. And so the experience here is considerable. Almost 500 cases have already been performed and remarkably, 100 just in the last year during the pandemic. So the pace of the program is continuing to increase and uh the technology is starting to increase in the sense that a single port robotic trials planned once the FDA approves this just in a few months and what that means instead of having having multiple different ports to do the minimally invasive surgery on the robotic platform, it's just one port, one small incision. And this program is being driven by a doctor in Katzrin and dr Hugh return. Right Now, a low rectal cancer can be a very problematic thing for our patients. This is looking inside the rectum. This cauliflower lesion is a rectal cancer approximately eight cm from the Anus. Now, traditionally these surgeries would require a low anterior resection which is a large colon resection. Sometimes potentially even with the diverting Ostuni. And if it's lower down in the rectum, sometimes these surgeries even need a permanent colostomy or an abdominal perennial reception for selected patients. Where these tumors can uncle logically be managed with local reception. You can actually do robotic surgery through the anus and that's put thomas stands for trans anal minimally invasive surgery. And these tumors can be completely resected through the rectum with a wide margin sparing the patient not only an incision but from a colon or anal reception. And this is a great program that dr sarin is really taking off the ground and which is an option for our patients and around the country. This is not something that's easy do we able to being able to find moving now to the section of H. P. B. Or hipAA dope anchor at oh biliary surgery and upper Gi surgery which is the section run by DR core vera. And the members on the right. There are some highlights I thought it would be interesting to talk about today. one is 3 d. virtual planning, neuroendocrine tumor program, pancreatic cyst program. The approach to minimally invasive HP be surgical oncology. Similar to what we talked about with colorectal and finally novel immuno therapies. I'll just show this video so that you can picture what I mean by virtual surgical planning. So this is a CT scan that's been loaded just onto a desktop computer here in my office. And you can see we're looking for a liver metastases which is here in blue. And before you go into the operating room you can virtually plan this surgery. Move the liver around on your screen in your mind and see how much liver we're going to remove. Where is the um are located. What are the landmarks here in the operating room? That's the segment of liver involved. This is a little venus branch. Here's that same venus branch and you can really start to line up the anatomy to make sure that you have planned your surgery safely and correctly. And it's not a guessing game in the operating room. And the technology of this software has increased significantly to improve the safety of these receptions. So here's a patient that has over a dozen liver metastasis. And after Neo a german treatment, we are planning the reception as to where we're going to divide the liver. And we want to make sure that enough liver is left behind for the patient to safely recover and using virtual surgery and artificial intelligence software, which is an interest of Dr al Sadi, who I'm putting his picture here is in the corner. Doctor Core vera myself as well as other members of the section. We are using these technologies to determine how to do this surgery with the most accurate quantitative planning. So in this case 35 of the liver is left behind, which is just enough for that patient to not have a higher risk of liver failure. Uh And these are programs that go far beyond just presenting these percentages and are an interest of the members of our section for the patients that are referred to us. Now moving shifting gears a little bit to the pancreas. Many of you in the audience will see a cat scan like this. You've ordered a cat scan for another reason and assist becomes identified in the pancreas. Well you're not alone. Over 6.5 million people are walking around with pancreatic cysts. So 15 to 20% of all cat scans and mris ordered what show pancreatic cysts. And now the question is how to manage them. And the problem is that really there are no mechanisms that exist to accurately characterize the chance of that cyst being cancerous or even a potentially a problem for our patients. And so we are left to make decisions based on radiographic criteria and patient demographics as to what that cyst is and whether we should operate on it. And this is a a study done by a group of surgeons out of Wisconsin. And it turns out that even we though we have all these guidelines were only about as good as the flip of a coin in making the correct preoperative diagnosis at the current time. And so If we looked at this, is this a problem? So we looked at all the pancreas checked. Um he's done in one year in the United States, over 5000 pancreas technologies, over 100 institutions done specifically for a subtype of these pancreatic cyst called I. p. m. n. And it turns out that 77 of the surgeries around the country that are done for pancreatic cystic disease were low risk on final pathology, meaning those patients potentially could have been surveyed instead of undergoing a reception. And how we can do better about choosing those patients is something that UCSF surgery. We take seriously and try and figure this out for the future. And this is a research interest of dr Kimberly kirkwood here in our division as well as myself. And so what we're trying to do is to push this field forward. Now we looked at markers in the cyst and if we look at us, cystic fluid cytology, tumor markers in the fluid musicians which are markers of malignancy and the fluid cytokines, DNA sequencing. RNA sequencing. In including micro RNA sequencing, we can now create potentially a multifaceted panel and so we've created a single platform biosignature on a micro fluid X plate. Here it is. I'm just holding in front of the PcR machine, you see 386 samples can actually be run simultaneously and And some selected samples, accuracy up to 94 of determining which cysts will progress to cancer versus which will stay benign can potentially be accomplished. And this is compared to an accuracy of current best guidelines that we use in surgery of about 50%. These are the local guidelines or up to 76 for the American Gastroenterological Association guidelines. So the point of me showing you that was that it's not just about doing the technical aspects of the surgery. We're really trying to figure out who should we be operating on and what's the future going to look like. And that's a segue into robotic pancreatic to me. So this is not the robot that's doing the surgery, thankfully. Nor is this the robot that's doing the surgery. These are the robots doing the surgery. So these are the members of our HPV section and the robot itself looks like this. This is the intuitive davinci robot. Of course we have multiple X. I. Robots to help perform these surgeries and what's the advantage of this over an open surgery. So again, I'll just show you an example. This is a patient that has an IP men, which is one of those pancreatic cysts. And there you can see the cystic tumor here above the instrument and well ultrasound, the pancreas to try and find this tumor. And now through these delicate instrumentation available on the robot with stability, three D. Visualization and degrees of freedom start to isolate and basically perform microsurgery on all the tiny branches that are feeding the tumor in the pancreas so that we can save the spleen and remove the pancreas. Here is the splenic vein and the splenic artery being exposed and being divided away from the tumor. You can literally hang the pancreas up from the rest of the abdomen here so that the tumor can now be divided with the pancreas and now using the fine instrumentation of these instruments, be able to save the splenic vessels and remove the pancreas with the tumor. They are completely divided. And here you can see the vasculature is still intact to the screen. Now these surgeries are challenging even to be done open and challenging to be done in a minimally invasive fashion. But this robotic platform is really a program that we are interested in developing even further in this coming year at U. C. S. F. And the next frontier is doing these surgeries including whipple procedure fully robotically. And our teams that include Dr LCD and Dr Mohamed adam are working on getting this program up and running this year which will be very unique not only for the Bay Area but one of the few centers in the country that can provide some of this care. Now I did want to speak a little bit about rare tumors and one of the advantages of being in U. C. S. F. Is a referral of rare tumors from around not only the area but from surrounding states and gi neuroendocrine tumors is one of the areas of expertise. The multi distant mary team around G. I, never consumers is tremendous and multiple clinical trials are in place and in fact we have a tumor board that meets to discuss only gi neuroendocrine tumors. Dr eric Naqoura, this is his passion and this is a paper that he published just last year with colleagues, Dr Heros E. And core vera showing some of the outstanding outcomes of liver surgery for metastatic neuroendocrine tumors with up to 75% long term survival after surgical resection for widely metastatic neuroendocrine tumor. That's absolutely tremendous. And our our expert medical oncologists, including Dr Berglund and Dr Warren, who's been a member of our division of surgical oncology for decades are have really helped grow this into one of the expert centers in the country and it's not just again about performing the technical aspects of the surgery, it's also about what's coming next. And so in the lab, Dr Warren and Dr Nakako have identified tack to 28 which is a uh tyrosine kinase inhibitor that has activity against neuroendocrine tumor and based on their pre clinical findings that was done in um urine model. That agent is now in a. N. C. I. A. Phase one trial at over 189 study locations? Excuse me, A phase two trial. Mm. Cool. Now I've been talking a lot about the technical aspects of surgery but of course many of you that are medical in the oncologists in the audience realized that surgery is often not enough. And at the end of the day, biology is king. And all of these technical details that I've been talking about are quote the princes of the veil who try to overthrow the queen often to no avail. And so what do we do for these patients where we can't offer the knife? Well we have to do better. This is a patient with widely metastatic liver disease from colorectal primary and maybe there's some new therapies. And so in the lab within our division we are interested in finding those new therapies. This is a preclinical model of a metastatic colorectal cancer where it reaches the point of palpable growth. And if we turn on an immuno stimulatory cytokine in this tumor, these tumors now shrink away and have complete responses with T. Cells infiltrating the U. S. And if we combine that T cell infiltration of that stimulatory cytokine. Now with checkpoint blockade which many of you in the audience are giving to your patients and have for up to a decade for melanoma and now other indications from micro satellite and staple gi cancers. If we can combine it to we can now say there is a stimulatory component and then we are inhibiting the suppressive factors of the immune system with no treatment. The liver of this pre clinical model is completely replaced by um er with treatment with checkpoint blockade alone with people in a mob there is a mild response which is as expected for a microsatellites stable colorectal cancer Which is what's 95 of our patients have. If we increase that immuno stimulatory cytokine which is called light. Here we see a partial response. But now if we combine that immuno stimulatory cytokine with checkpoint blockade, complete responses can be identified in colorectal liver metastases. This is extremely exciting and this is the type of work that we hope to now try and get into our patients uh and potentially put ourselves out of business, which would be the greatest day for all of us. But there are ways that this may even need to be administered in a surgically relevant way. But are there surgical options now for these patients, either this patient with widely metastatic liver tumor from colorectal primary or these patients that have peritoneal carcinoma, ketosis or uh pseudo make some appear to neon, which is metastatic disease throughout the abdomen. And the answer is there are some options. And that consists of our regional therapies for medicine, Gi Cancer Programmatic Development. So, I'll talk for a moment about what we do for the liver metastases. Now, the idea of regional therapies are to be able to deliver these agents directly to us in high concentrations to enhance the efficacy and decreased systemic side effects. And this is well established in regional profusion is for the limb from melanoma and sarcoma. And this has been now put into the liver. So this is a pump that's placed under the skin with a catheter that goes directly into the hepatic artery, where high dose chemotherapy can be delivered directly to the liver with low systemic side effects. And this has been shown now in multiple multiple reports well over, well over a decade to improve survival and select patients with widely metastatic by low bar colorectal liver metastases and even select patients with intra hepatic Colangelo carcinoma and Dr warren and Dr core vera had been putting these pumps in along with colleagues like Dr Van Aken Medical Oncology here. And so this program is well established at UCSF. And we're looking forward to only increasing uh the efforts in this program as it's reaching more and more popularity. This is a program that's not available in much of the bay Area or even the state. And so we hope this is a program where our patients can benefit. And for the second patient that I showed, the example of which is this widespread metastatic disease to the abdomen. There are options for cider reductive surgery, which means surgery to remove all visible tumor and sometimes combine it with a profusion, much like we should in the liver, but this time a profusion to the abdomen. And again, this is not a program that is widely available throughout the country. Um And there's a few options available in California. But with the recent recruitment of DR adam, this program will be launching within the next month. And we are very excited for the s the enhanced programmatic development that we can offer our patients. So in this case this is a patient that has this tumor that you can see actually dissed ending the abdomen and there's a large amount of tumor. But surgically as much of this can be removed as possible, as much close to zero visibility as possible and then profusion will occur into the abdomen of heated chemotherapy for about an hour and then the patient is closed and the indications for this are not for every type of cancer, but in select patients and select cancers, this can improve survival and progression free survival and sometimes even enhance quality of life in the setting of large societies that are specifically mutinous nia plasm, the pedestal and colorectal add no carcinomas and even from malignant peritoneal mesothelioma as well. I really appreciate the opportunity to talk to everyone today about some of the highlights that are offered within the division of surgical oncology here at UCSF. Thank you so much. Thank you dr Maker. That was excellent. Um if anybody has any questions, please feel free to put them in the chat. And I think I'm going to start with a question on, I was really excited to hear about the pancreatic biomarker and I did have a question is that a blood test that you're thinking of or would it actually have to be from a cyst fluid that you aspirated? That's exactly right. Thanks for the question. Dr chris Cheeto. The data we showed was from Um pancreatic cyst fluid that's aspirate at the time of the US. uh now what makes that exciting is often you don't get much fluid from some of those cysts and this asset can be run on 50 micro leaders. Um So that that's how the biomarkers are currently set up from the blood. It's been complicated to have an essay that is as accurate as it is from the cis fluid. Yeah. Great. Okay. And then I did have a question about one is exciting to see that you're going to be doing robotic. Pancreas attacked me. You know when I went through training many, many years ago we were told to stay as far away from the pancreas as possible. So I've always admired anybody that was willing to operate on the pancreas. But it seems to me that robotic surgery would really be helpful. I mean besides all the other reasons lower blood loss may be better visibility but also because your hands aren't in there and because maybe you can be a lot more gentle or with the tissue but I don't know what's your sense of that? Well to your point, you know it's a it's a tool that can be beneficial in certain circumstances. All these surgeries are already being done here extensively laparoscopically and so the robotic platform it just adds uh degrees of motion to the arms as you all know some stability three D. Imaging. And this is a program that those these cases are being done but we want to develop this and launch this in a much greater fashion in the in this coming year. Yeah. No that's great. And then I have one last question which is do you do any liver receptions robotically? Sure it's similar. I just didn't show that in today's presentation similar to the robotic pancreas program that will be taking on a new life this year. Hopefully the liver program is part and parcel with that. But the laparoscopic liver re sections have been performed. Some some of the Largest numbers in the country have been performed here over the last five to even 10 years and so yes it's being done minimally invasively on multiple platforms. So I was thinking about likening it to the prostate. I know it's not similar at all but the fact that you were doing the three D. Rendering pre op and then um if you are doing something on a robotic platform in trop I would imagine you would be able to at some point use intra ultrasound, emerged the images. So maybe we'll be looking forward to some technology like that so that it's not just like a visual pre op rendering. So Dr Al Saeedi I believe has a grant that he's putting together or maybe has just submitted on exactly that topic. So it's a very exciting um present and future for the field and it's something that we're very excited to have in the division. So one last thing and maybe you can help just I know that we've seen a decrease in patients coming in for care and getting screening. And so for gi cancers in general um I'm a little concerned that we've seen people not coming in. What's your sense and what would your recommendation be going forward? And actually I'm just really glad that you're thinking of some treatments for patients who are later stage disease. Because I fear that that might be one of the outcomes of covid. Sure. You know, it's like you said, it's been an issue. I think the the numbers have really been staggering for the impact on breast and colorectal cancer as a result decreased Ma'am. A graphic screening and um colonoscopy screening. We'll see the impact of that in 5 to 10 years I think for these other diseases. Uh there's really no reason I believe to um to inhibit care if you're if a patient is not feeling well or needs to see their doctor showing. There's no limitations on our end to be able to see those patients and and they do not need to wait to be seen. Right, Thank you very much. Okay. I think now we're going to switch to our second speaker, so I would like to introduce dr Julianne Sosa. These are current chair of the Department of Surgery at UCSF and an endocrine surgeon who specializes in thyroid cancer. Her research focus is on developing treatments for advanced thyroid cancer and understanding the environmental factors that can raise a person's risk for the disease. She's actually been at UCSF for three years, joining about the same time as I did. She came from Duke University where she was the chair of endocrine surgery there. Additionally, what I thought was really interesting about Julianne and probably a little known fact is that she actually was going to get a PhD in Economics and I love it because I love economics and even considered a PhD at one point, but she wrote a book or um and at that point was looking at the market for phds in the future and realized it didn't look very good. So she changed course and ended up in medicine. Or at least that's the story I'm told. So lucky for us. Um And so now I'd like to think I'd like to welcome dr Sosa for her talk on controversies and thyroid cancer. And when is less, more and more or less. All right, well thank you very much for that very kind introduction doctor chris ito. It's a privilege to be able to speak to everyone today. And I guess you've proven that I'm an opportunity opportunist at the very least. Um I am gonna shift gears and shift our conversation uh and move uh trail uh to uh the area above the clavicles, focusing on the thyroid gland, which is a passion of mine. And I'm also gonna shift the focus away from the technical aspects of surgery, all of which we do in endocrine surgery at UCSF, but I'd like to focus on the cognitive aspects of surgery. Um increasingly, I would say our focus at UCSF and endocrine surgery is on the innovation and the discovery that assures that we stay not at the leading edge but that we are the leading edge. And in so much of endocrine surgery and in the treatment of thyroid cancer, there is frankly a lot of evidential equal poise, there's a lot of ambiguity about what is the best strategy and I think increasingly, a recognition that the patients and patient preference values and attitudes should be at the epicenter of decision making and what we do in endocrine surgery is take a thoughtful approach, giving patients many different options Through Italians disciplinary management team. And I think increasingly that is what patients are looking for and what patients need in 2021. These are my disclosures. They do not pertain to the substance of today's conversation, which will be on differentiated thyroid cancer. So this is a slide I've shown maybe for about a year and a half and all joking aside, I used to introduce this slide by saying that there was a pandemic. I'm not kidding of thyroid cancer. I have now amended what I say to say there's just an epidemic of thyroid cancer, but this isn't a very this is a very important point. Uh, and this is that more and more we are seeing the diagnosis of thyroid cancer and it's being seen in every demographic subgroup in women in men in young and old, in all racial and ethnic subgroups. Indeed, the incidence of thyroid cancer has increased more than 300 in the last three decades. We now know that at least one in every two Americans will have a thyroid nodule, and somewhere between five and 50 of those modules ultimately will merit interrogation. So what is going on? Why is there this epidemic of thyroid cancer? So, it's amazing how threadbare the evidence is to explain this epidemiologic phenomenon. Until very recently, there was basically one seminal pivotal study looking at this question, published by Welsh and Davies in Jannah Back in 2006. And let me just quickly walk you through it. Starting in the left, upper left hand column, you see the rising incidents, and then what appears to be the engine for this? It is a single histological subtype believed to be papillary thyroid cancer. When I graduated medical school, it represented 80 of incident cases. Now that is above 90% of incident cases. Then the second figure to the right hand side, it appears to be the smallest tumors, those tumor less than one centimeter in size, which we call papillary thyroid micro carcinomas that appear to be driving this epidemic. And finally, perhaps the most controversial figures shown in the bottom in the center. You see this exploding incidents and then level mortality. Leading the authors to conclude quote, we believe increased diagnostic scrutiny is the most likely explanation for the apparent increase in incidents. That is, it's all over diagnosis and I suspect we have many medical oncologists on this grand rounds. You do multiple imaging studies to stated your patients to surveil your patients and almost certainly you have identified incidental thyroid modules that could be the genesis of this epidemic. But I got to tell you that last figure Bothered me. It bothered me a lot. And I probably read that Welsh in Davies study more than 50 times. And what bothers me is this is you see this increasing incidents now more than 55,000 Americans will be diagnosed with thyroid cancer each year. So this arithmetic scale is scaled to accommodate a very large number, Fortunately very few patients die of their disease. Indeed, survival of thyroid cancer overall is somewhere between 95 and 98 at a decade. So the number is small and I wondered is it not possible that the arithmetic wise scale, maybe new ding changes in mortality? Well I'm not an epidemiologist but fortunately I've got good friends who are epidemiologists. So I called carry Kitahara an epidemiologist at the National Cancer Institute. I said can you take these data and throw them on a log arrhythmic Y Axis, took her 30 minutes. She sent this figure back to me. And what you see is something very interesting in something important in the field of oncology. You see this continuing increase incidents for thyroid cancer. But in the mortality portion of the figure, you now see movement and in fact, we see what appears to be increasing mortality. And this should really stand out to you because overall in the United States were winning the war on cancer except for four cancer diagnosis, number one, apatow cellular carcinoma and number two we know now thyroid cancer. And by unmasking this very interesting phenomenon, we redid the welsh in Davies study and this is our study that was recently published in the war in the journal Jama in 2000 and 17. But let me show you what we found very interesting on the incident side, we see this increasing incidents in localized disease that is disease confined to the thyroid that could be compatible with over diagnosis, being the explanation. But look at what we also see. For the first time, we see increasing incidents of regional disease metastatic to cervical lymph nodes and increasing incidents of distant metastatic disease. No one would say that this is over diagnosis. Indeed, this our diagnoses that people succumb to and on the mortality side, where the explanation of over diagnosis should show stable or declining mortality. We see something very different and that is increasing incidents based mortality for regional, distant and localized disease, including localized disease that is diseased confined to the thyroid. This does not fit an explanation of overdiagnosed diagnosis, but rather suggest the biologic profile of thyroid cancer may be evolving in the United States. So what is the conclusion and the takeaway for everyone on this grand rounds While over diagnosis and those of us on this call may be a large part of the explanation and to blame for the epidemic. It is clearly not the only explanation, and I suspect there is evolving by logic underpinnings of the disease and I believe that we are doing ourselves a disservice. If we say to the NIH NIH distract funding from the arena of thyroid cancer, I would argue we should be investing in thyroid cancer in order to facilitate treatment, particularly for patients with advanced diagnosis. Now in the field of oncology, we are spending more and more money trying to save patients near the end of their lives in the last months. Weeks, days, maybe even hours and minutes of life. So we typically, when we seek costs, we see money spent here in the black area that is immediately proximal to death. But with thyroid cancer, we see something very different and that is money spent in the green area. That is in the surveillance phase of care. Why? Because patients are diagnosed in youth and middle age, they don't succumb to their disease. They live with their disease. And in so doing accumulate the costs of imaging and remedial treatment with surgery and radioactive iodine treatment. We're all thinking about financial toxicity now in oncology and thyroid cancer is an important diagnosis to understand. In the arena of financial toxicity, any cancer diagnosis Will double the risk of bankruptcy of a patient compared to an American who does not have cancer. But thyroid cancer is that cancer most associated with bankruptcy 3.5 times the risk of bankruptcy. Much more so than other, much more mortal diagnosis. So a lot of people say julie and that makes no sense. That is, that is unbelievable. But of course it does make sense for the reasons I showed you diagnoses are made when patients are young. Unfortunately, today in America it is the young who are most likely to be underinsured or frankly uninsured. And because they live with their disease, they accumulate the costs of care over time, leading to bankruptcy. So how should we as a community combat this? And that's where it is. So important to understand the evidence that is the underpinning of the guidelines. And it is so important to follow guidelines to standardize practice and in so doing standardized and improve the quality of care. And these are the current guidelines in the United States. They're publicly available and I'll tell you they're publicly available and the public patients bring them in each and every week to our clinics asking us to benchmark our care to the care recommended in the guidelines. And I had the good fortune of helping to write these guidelines. Well what do we need to understand about how we care for the thyroid cancer patients? Will the guidelines share many tenants and principal with other cancer guidelines? We want to facilitate survival. We want to minimize recurrence. We want to facilitate surveillance and we want to permit accurate staging. But I think more and more. This principle of less is more and the understanding that we need to minimize treatment related morbidity if in the end survival from this diagnosis is superlative. Well how do we do this? And I'm gonna show you some of the unique ways that U. C. S. F. We tackle this idea of reducing treatment related morbidity. So let's start with those tiny tumors. The papillary thyroid micro carcinomas that I mentioned to you before. So this was a very thoughtful, very provocative editorial written back in 2014 by two endocrinologists asking the question of whether we really should surgically eradicate all of these tumors or whether indeed we could leave them in C. Two and actively surveil them. I always say if we're going to surveil something, we better do it better than the editors of the journal thyroid who obviously misspelled the word microbe Papillary. Well are there any data now to support active surveillance for cancer is less than one cm in size Only starting to emerge from the United States but a huge body of evidence that exists in Japan. Um this is one of my favorite studies published again in 2014, looking at more than 1230 patients Followed over a mean of 75 months, divided into three age groups and these patients did not undergo surgery for their cancers. They rather were followed for demonstrated evidence of enlargement, the development of nodal metastases or progression to an absolute size of 1.2, 7 years or greater and look at what we see. It's fascinating. At one decade, just eight of these patients experienced any enlargement of their tombs. And also at a decade, just 3.8 of patients experienced the development of metastatic disease. And if you divide the patients into age group, you will see that it is the youngest patients shown in a dotted line who had the most progression of disease, and the oldest patients shown in a solid line who had the least progression of disease and indeed age was an independent predictor of survival. So what did the authors conclude? The authors concluded that if we're going to actively surveil patients with micro carcinomas, do it in older patients. But even if we actively surveil patients who are younger, there is almost certainly time to salvage or rescue the patient by deferring surgery until we see evidence of progression. There is still time to rescue those patients. So what is now recommended in the United States? Well, the principal surgical strategy is still thyroid lumpectomy, sadly in the United States today, still three quarters of patients are undergoing total thyroidectomy, so they are being not only potentially overdiagnosed but over treated for this disease for the first time, however, and this is a word that is so frequently overlooked in the guidelines. We added the word if if surgery was chosen, surgery. If it is not chosen, and active surveillance is pursued. Risk and risks and benefits of active surveillance need to be discussed with patients. And we must assure we have exquisitely compliant patients. So there is risk to the strategy. But obviously a great deal of benefit for those patients who would like to avoid surgery. At UCSF. We have a trans disciplinary team and a very careful, very fastidious program in place to assure that we do not lose patients to follow up. And so this is a treatment option. Offered images. In addition to surgery. Well, let's switch gears and moved to the bread and butter of thyroid cancers. The low risk differentiated tumors, that is tumors 1 to 4 centimeters in size confined to the thyroid without evidence of nodal metastases. This is the age old debate. Should we take the whole thyroid out or should we take half the thyroid out? And there are data to support both camps, those who say take the whole thyroid out, say up to 75 of the time it is multifocal or even bilateral. Sometimes we want to use radioactive iodine. And isn't it better to do total thyroidectomy and zero out the thyroid globulin level, thereby facilitating thyroid globulin surveillance? Well, those who argue from Quebec to me say who wants supplementation, let alone replacement? It's an indolent disease with an excellent prognosis. And when you do bigger surgery, are there not more often complications? Well, until just a couple of years ago, the recommendation in the United States was to do total thyroidectomy and it's amazing how thin the evidence was supporting that surgical strategy. It boiled down to a single study. These are the data from that study by Billy Moriah at Al, and what you see is something extraordinary. and that is the suggestion that if a patient has half their thyroid out, they are 31% more likely to die than if their whole thyroid was taken out. Certainly compelling. But at the very least surprising some of us said shocking. So what does U. C. S. F. Do when we see something that doesn't make sense? Well sometimes we ask a new question in a new way but sometimes we ask an old question and we answer in a new and perhaps more innovative way. So we took that villa Maria study and we enriched the data set that had been deployed but asked the same question should have to be taken out or should home Thyroid be taken out. And these are our data just recently published looking at nearly 62,000 patients across the United States comparing lumpectomy and total thyroidectomy. You'll see statistically significant values here. But I would argue based on these demographic variables, they are not clinically significant, but these variables which were missing in the villa Maria study are definitely clinically significant and you see statistically significant differences. Nothing surprising. When we do total thyroidectomy, there is more often multifocal disease, extra girodo extension and metastatic disease. But when we adjust for this enriched data set, we came to a very different conclusion That is survival from Lubeck to me is equivalent to survival following total thyroidectomy. And at U. C. S. F. We try to do science that it is impactful not only locally but nationally and internationally. And the study transformed how we practice thyroid surgery in the United States. So in 2009, the guidelines based on the laborious study had been take the whole thyroid out and today in the United States we should be offering patients choice to either have total thyroidectomy or thyroid lumpectomy. In the end, their preferences and values should drive the decision making. I will tell you sadly many times this recommendation has been misinterpreted to say that low beck to me is the preferred strategy. It is not. They are equivalent. And in the end the patient should be at the epicenter of decision making, informed by a trans disciplinary team and I will tell you endocrine surgery at UCSF is focused on patient centered care such that we are able to personalize that care. Well, I don't want you leaving thinking that less is always more when it comes to thyroid cancer care. There is one dramatic area where more is definitely more and that is the question of surgeon experience and patient outcomes. So in many different specialties for many different diagnoses and procedures, there has been a lot of energy over the last 10-20 years showing that practice makes perfect. The more you do, the better you are, The interesting and important thing to know is that surgeon volume is a continuous variable. But for some reason in the literature it is rarely treated as a continuous variable. Rather, it's almost always treated as a categorical variable with a variety of different cut points used. And quite frankly, none of us have never have ever understood why different cut points have been selected. Well, you could say who cares? Doctor says, so what cut points are used? Well, the important thing to know about categorical variables is they tell you a lot about outliers, the low volume outliers and the high volume outliers. But what is missing is all the folks in the middle? Well, you could say who cares about surgeons who are in the middle? Well, all of us should care about these surgeons. Why? Because increasingly, in this era of value based care, we are deploying volume thresholds to determine what surgeons should be allowed to do an operation based on their experience. So, May 18th 2000 and 15 was a very famous day in american surgery because on that day, three different academic institutions, Dartmouth, johns, Hopkins and Mission michigan asked their surgeons to take a volume pledge on that day. If they did not perform enough operations based on cut points from the literature, they had to stop doing those operations even if they had trained all of their lives to do them. Well, let's look at the case of thyroidectomy in America. So this is all the thyroid surgeons in the United States at a population level. And we're focusing here on total thyroidectomy. And you see the range Is from 1 to 157 total thyroidectomy in a year, highly skewed to the left. But the question for forever has been is there a volume threshold after which we can afford patients superior outcomes and I am happy to relay. And these are pretty new data that there is such a threshold. And what we now know is that each incremental total thyroidectomy a surgeon does on an annual basis, Up to the number 25 on average affords their patient a benefit with regard to reduce complications. After the number 25, there is no longer a demonstrated association. So for the first time we now have a definition for a high volume thyroid surgeon, 25 cases a year. So when we then look at outcomes based on the number 25 which had never been deployed before. What we see is that on average, a patient who has surgery by a low volume thyroid surgeon will have a 55% increase in the risk of a complication and concordant lee an increased likelihood of protracted length of stay and increased costs. And here is the most discouraging statistic. I'm going to show you more than half of the surgeons today who performed total thyroidectomy in the United States do just one per year. I'm not trying to prove causation, but this is a dose response association that it is extremely profound And I would argue quite compelling. So what can we conclude? Well, surgeon volume is associated with outcome for thyroidectomy. But now we have for the first time a definition 25 per year. And sadly in the United States, the overwhelming majority of patients are being exposed to undue risk by having surgery with low volume surgeons. Does anyone care about this? They sure do. And that's because thyroidectomy is one of the five most commonly performed operations in America. Within a week of these data being published, the new york times and the Washington post called me and asked me what what is going on here and perhaps more worrisome blue cross blue shield and anthem cold to say should we stop paying to refer patients out of network um or in network to low volume surgeons but rather pay for the referral of all patients to high volume surgeons. I don't think we're ready to do that. There are not enough high volume surgeons and they're not geographically well located in America. But this is something to think about. If you have patients with thyroid cancer who require surgery fortunately at U. C. S. F. We have high volume surgeons. So where do I want to leave you? A very dynamic area, thyroid cancer research and thyroid cancer care? I think all of us need to be open minded to evolving evidence and open to changing our practice. I have the good fortune of chairing going forward the next thyroid cancer guidelines committee, along with Matt Ringel at the Ohio State University and I expect these to go online later this year or in early 2022. These are our endocrine surgeons at U. C. S. F. We are the largest endocrine surgery center in North America with six full time endocrine surgeons to full time thyroid ologists. You see an extraordinarily diverse and experienced group. All of us are full professors and high volume surgeons and thyroid ologists. This is our department of surgery 800 people, extremely talented and also a very happy group of folks. And our endocrine surgery clinical platform crosses all of our platforms centered at Parnassus. But now for the first time extending to Zuckerberg san Francisco General Hospital, which we now staff with a dedicated endocrine surgeon because of our belief in health equity and resolving disparities in access to high quality care. Our Children are done at mission. They and several of our endocrine insurgents continue to be based at Mount Zion. With that. Thank you for the privilege of speaking today. Thank you Julianne. That was great. I am one I found this fascinating because I found it very similar to what has been happening over the past many years in prostate cancer. We moved from you know prostate total prostatectomy to now focal therapy and active surveillance. So kind of a similar shift and weighing the pros and cons and the risks of putting someone on active surveillance. Um one thing I don't know though is how do you diagnose, how are most people diagnosed with thyroid cancer? And is it something that, you know I looked at the numbers and you know it's primarily in women and younger women. So you know if I'm at risk, what is it I need to know um is it something I can do myself or is it some other screening that happens? Yeah. So thanks for that and an increasingly judgment is needed around this. I think first of all your observation that a lot of the trends I've shown could be discussed around breast cancer care and prostate cancer care where small tumors, even things like D. C. I. S. Were discussing should be surveillance. Should we remove it? So a lot of these discussions are shared across many diagnoses. I think what we're doing more and more is lifting the threshold to perform a biopsy. And the current guidelines say don't put a needle into the smallest tumors less than a centimeter in size because of this. Less is more movement. Having said that if you don't know how to wisely and efficiently actively surveil patients, too much could result in elevated costs that will be turned down by insurers and pears. Too little. You could miss a clinically significant cancer and the patient returns with either locally advanced or metastatic disease. So it's a lot of judgment evolving evidence and I would say increasingly the adjunct of molecular testing. So profiling tumors to understand their likely prognosis at U. C. S. F. We have a portfolio of molecular profiling tests that really inform our approach to the indeterminate thyroid nodule and for all tumors to guide the extent of surgery in the aggressiveness of adjuvant treatment. Great. And then you mentioned briefly about environmental factors that may be responsible for some of this increase. What are some of those environmental factors or do you know? Yeah it's evolving and it's a focus of energy at U. C. S. Number one obesity Which is a shared observation with other cancers. We now believe about 25 of incident thyroid cancers are associated with obesity and overweight and obesity and overweight are associated with increased aggressiveness of the tumor. And a second area of research at UCSF is exposures in our biosphere and an evolving area of interest is flame retardants, anything that is black. I hate to tell it. Tell you your cell phone, your big screen, tv, your computer screen. All of these contain chemicals called P. B. D. E. S. And they are now evolving evidence that are worrisome that this too might be associated with papillary thyroid cancer. More to come. Great, That's great. Okay, well thank you. And I think now we're gonna go on to our final speaker this evening and I'd like to introduce dr Michael Alvarado. He's a cancer surgeon at UCSF caring for patients with both breast cancer and melanoma. His research is focused on radiation therapy for breast cancer and molecular markers for breast cancer screening. Uh Dr Alvarado is also a former semi pro cyclists and food and wine enthusiasts. So maybe afterwards we'll make sure to get our wine recommendations from Dr Alvarado and I like reds, but now I'll turn it over to dr Alvarado who will be speaking on technology and breast surgery, efficiency outcomes and patient preference. Great, thank you so much. It's a pleasure to be here and such incredible company. So it's quite an honor. So, thank you so much. Get this set up for you um and I think there we go. So yeah, so, um it's great to be here. My name is Michael. I'm when I'm over in the in the breast surgery department as well as in melanoma and now under the tutelage of DR Ajay maker. So that's wonderful to have him as well. So I thought tonight I just kind of touch on some of the things that we've done here in the breast group um kind of around technology, which is great but technology that's improved patient outcomes as well as patient satisfaction, um efficiency, which also helps not us, but also our patients are very happy about it as well. And I'd just like to share some of that stuff that we're doing here um with regard to disclosures, some of the things I'll be talking about have to do with a company called endo Magnetics. Um We have no I have no financial relationship, however they were the sponsor or they supported a clinical trial that we were the lead institution for something called MAC Trace that I'll mention during the talk as well. So technology um equals efficiency. Right? Well, that's not always the case, which we see a lot here in Mission Bay. Um, this is very technological. I'm not sure how efficient it is, but it is kind of funny to see this. Uh Tootling around Mission Bay. Um, so efficiency around breast cancer surgery. So I'd like to focus on a couple areas of breast surgery for breast cancer, the partial mastectomy or the lumpectomy with sentinel lymph node biopsy for proper staging. And I'm going to comment on something called I. O. RT or intra operative radiation therapy and you may or may not know. But when a woman has a lumpectomy typically she undergoes whole breast radiation which will take around three weeks with daily treatments. And that's done at a radiation facility. And it's not all that efficient for the patient. And it's actually kind of a pain to have to go to a radiation facility. So um the I. R. T. Has become not only efficient for us but extremely efficient for our patients. Now when a patient has a lumpectomy or partial mastectomy, what we used to do is coordinate with radiology for the localization where they would place a wire through the skin into the breast to identify the breast lesion that you couldn't feel. So you needed to find a way to get to that spot. So there was a lot of working with radiology and that needle localization or the placing of the wire could only take place on the day of surgery. We also needed to coordinate with nuclear medicine to do an injection with the technetium a small amount of fluid so we could find the sentinel node at the time of surgery. And then of course there's coordination of with radiation oncology. So a lot of things going in to the mix just to get the patient in the operating room for her surgery. So what about inter operative radiation therapy or? I. O. R. T. Well we were very fortunate to be part of a clinical trial called the target, a trial that started over 15 years ago. Um Back at that time when this first started. Um dr Esterman who leads up the breast oncology program. Um and also one of my colleagues in the breast surgery. She identified that this was potentially going to be something very very good for patients. And she actually was able to get the machine the intra beam radiation device that we have here in the operating room to deliver the inter operative radiation therapy. And so we were one of two U. S. Sites for the target a international trial which was a randomization of the target group which was risk adapted therapy with intra operative radiation therapy. And that was randomized against the standard whole breast radiation where patients would go on to get whole breast For 3- five weeks after surgery. Now in the risk adapted arm, it was great because this was the new the newest form of radiation therapy where you would give the one time dose of radiation. However, if the final pathology report showed any kind of high risk features then the patient would go on to whole breast radiation and the I. O. R. T. Would count as the boost to the lumpectomy bed. So it truly was risk adapted based on the final pathology report. And so we were part of that trial we were the highest accruing center in the U. S. And that trial went on for a fair amount of time because it was kind of an exponential in terms of patient cruel. Now the first data was published in the Lancet looking at five year outcomes and this was a median follow up of five years and it showed very good outcomes at that time. This was a trial that was done uh not as a superiority but as a non inferior trial. And the the the amount of difference for non inferiority was 2.5% between the two Arms. So here you can see that there was a difference of about one in local recurrence after lumpectomy with I. R. T. Vs. Standard radiation. So at this point it was meeting the non inferiority criteria of a margin of 2.5%. But this was early data, it was median follow up and a lot of people wanted longer follow up. So although the trial had concluded we were having to now to wait for longer term outcomes so that people would accept this as a way to treat patients. And the two at five years was much better than for example, no radiation at all, which would hover around 5-6%. So what we did at that time was that we wanted to continue to use the I. R. T. For patients. And so here at UCSF we started the Target US registry trial and there were about 23 institutions across the country. And you can see the eligibility for those patients. And so we continue to enroll patients on a single arm registry trial for patients that met criteria for the I. R. T. And that data looked very very well. We enrolled about 750 patients over the time. Um and this is just a little bit of information showing that for example the complication rates were very very low compared to standard treatment and that was very good. And we are continuing to follow these patients for their median follow up and outcomes as well. But what this did was allow us to continue to use the therapy because we felt that the data look very very good. But we wanted to do it in a very controlled and fashion on this registry trial. Finally just this last fall um last year uh the full five year outcomes for the target a trial came out the data that we have been waiting for for the I. R. T. And this showed basically what we saw earlier. So an absolute difference of 1% and it met the non inferiority. And so this is great. So we've been treating patients with I. R. T. And it really has become not just efficient for patients. Um but also uh a proof of Preferred treatment for patients. And again this is even longer follow up showing that 12 year outcomes. There was really no difference in the two arms in terms of living without local recurrence and survival was the same as well as breast cancer specific mortality. So patient preference. Women were choosing this even before this data came out to go on the registry trial. So it was a preferable treatment just as dr Sosa was saying we're listening to patient preference and what they what they feel is important to them. And we continue to use the I. R. T. With the intra beam source here at Mission Bay for patients that fit the criteria for these low risk patients. So Technology that was started almost 15 years ago the outcomes look great. They continue to look great. The patient preference was such that women would Choose this type of therapy even though it had a very low slightly one high difference with regards to local recurrence but no difference in long term outcomes with regards to survival. So really technology moving in the right direction and even more importantly it's very uncommon for technology to be cost saving. But we've also published data here from our group showing that with regards to cost effectiveness that this is actually better for societal cost actually drives the cost of medicine down. So now I'd like to move on to targeting the breast lesion itself and utilizing lesion localization technique that gets rid of the wire localization. We've also started targeting the lymph nodes in the armpit, the sentinel node biopsy for patients that have positive lymph nodes, the so called targeted axillary dissection. And we've been using one platform and this is called the mag seed. Um and the mag seed has really uh revolutionized what we do here. Um not not just on the technology front but also in efficiency and patient satisfaction. So we used to use wires to localize the breast lesion, but this was very fraught with difficulties with scheduling. Oh, our efficiency. We'd have late starts in the operating room, longer surgical times. There was issues with, with placement of the wire. It really relies heavily on communication between radiology and the operating room. There was limited surgical approach when the wire came in one side and you wanted the lesion on the other side. And where were you going to place the incision? And then patient satisfaction with the high anxiety. After they had the wire and the wire sticking out of the breast. And then they had to go on uh two preoperative area and such. So here are just some examples of what the wire looks like at the time of mammography. You can see the wire coming in um and it comes out of the skin. And then you can see there's a clip there that localizes the lesion. And really trying to use the wire for generating a lumpectomy. Where what you want is that clip right in the middle of your lumpectomy. And you can see with a wire sometimes it can be very challenging. So why did we choose the mag seed? Well, it's a small seed. It doesn't migrate. It's easily detectable in the operating room. Um It utilizes para magnetic a portion of it. It can be placed any time before the surgery, a day before, a week before the morning of a month before. Um It can be placed anywhere in the soft tissue for for this case. It can be helpful for Anka plastic surgery to get better outcomes and cosmetic outcomes. It's efficient. It's accurate that it helps with improved hospital workflow. And then another product that utilized the same technology called Mag Trace means that we can stop utilizing nuclear medicine. Use one type of technology and really eliminate a lot of problems with scheduling these cases. And so now we can start these cases at 7 30 in the morning because they've had the seed placed the day before the week before and the sentinel node biopsy. Instead of utilizing technician with nuclear medicine, we can actually put in the mag trace for localization after the patient goes to sleep. The magazine placement can be done with ultrasound or mammogram. Um As I said, it really improved the efficiency and radiology patients are much happier with it. Our breast imagers love utilizing the mag seed. Um and it's much better for them as well. So here you can see this is just for ultrasound placement. You can see here's the mask. Here comes the needle, here's the previous clip and then once the introducer is placed under ultrasound, then they dropped the magazine right into place. And so that's great for these patients here, you can say. Even with some cases where the patient might have breast augmentation. Previously having a wire place, there was always a chance of rupturing the implant. But now you can see with the magazine that's placed very nicely right next to the clip and there's no issue with the wire causing a problem with the implant. You can use multiple seeds for bracketing of the lesion. So you can see that here utilizing multiple magazines to bracket a large area for lumpectomy and that works exceptionally well for these cases. So just to give you an idea of once the patient is in the operating room and instead of using the wires and the mammograms and trying to look at three dimensions, trying to come in here and try to get down to the wire. Now we utilize the technology in the operating room. Mhm. And you can see this, identifying the seed and knowing exactly where it is, the depth of it, based on the sound and the numbers and now we know where exactly it is as opposed to utilizing the wire. So this is a great way for localization of our breast lesions at the time of surgery here, you can see a very nice lumpectomy specimen after that surgery showing the seed and the clip and the tumor right in the middle. So the mag seed a great way to utilize this kind of what we might refer to as GPS clip technology. So how did we approach it? We really used a multidisciplinary approach, having everybody all together with breast imaging and surgery. We had a dedicated wire free period where we did the Maxine cases. We had prospering observing cases for those who had more experience with it and weekly meetings with both the breast surgeons and breast imaging to go over some of the, the areas where we felt we could improve and what and how we felt about those cases. We looked at the 1st 73 patients on our initial experience dr price and breast imaging published this data uh and showing basically that it was very successful. As you can see placement of the seed very close to the clip. Um 70% of the time it was in with within one millimeter, which is great. And then actually within 2-5 mm, almost all the rest of the cases. Um so this showed some great outcomes with with regards to positive margin outcomes. And then when we looked at the next 254 patients, we found that the positive margin rate of needing to go back for a second surgery was very low, about half of what Is quoted in the literature across the country, with about a 15 risk of re excision or second surgery where our data shows with the magazine that's about half that so very good outcomes with regards to not having to go back for a second surgery. And then here you can see again, just kind of showing um utilizing mag seed versus wires across the country and as well in the UK. So really low risk of having to take women back for a second procedure. Now. What about the lymph nodes? So you can also utilize the mag seed for identifying positive lymph nodes in the armpit or the ax illa when you do a targeted actually no dissection and in breast as well as in melanoma, we've really transitioned from doing Axillary dissections that are aggressive with removing 15-30 lymph nodes to really targeting the positive lymph nodes in the sentinel node era. Um and really decreasing the morbidity associated with actually no dissections. And so we needed a way to identify those positive nodes and it's really difficult to place a wire into the axle a because of the nerves and the arteries and veins. So now what we do is we are able to place the mag seed into the lymph node to target that lymph nodes. So for example if a woman had a positive lymph node up front with her breast cancer, she might get neo adjuvant chemotherapy to try to downstage the axillary. So before the neo adjuvant chemotherapy she would have an ultrasound identifiable clip placed on that node after the neo adjuvant chemotherapy. If she appeared to have a complete response, we then place the mag seed right next to that ultrasound identifiable clip in the axillary. And then we do the sentinel node procedure, making sure we remove that previously positive node to make sure that we know if she had a complete pathologic response. So you can see here in our first experience with the 38 of these lymph nodes, we had excellent retrieval of those um upwards of 37 of them and on the 38th won the seat actually fell out of the lymph node when it was on the back table, the seed was recovered and it was the right notes. So a great way of targeting these um for these patients and eliminating the need for a complete axillary lymph node dissection. And we're not only using utilizing it in neo adjuvant cases but women that present with node positive lymph node that don't need potentially chemotherapy. Now we can take them straight to surgery and again they typically would be patients that need a complete axillary lymph node dissection. But we can place that mag seed and do the targeted sentinel node or targeted actually no dissection for those patients as well. So a great way to eliminate um the morbidity of the axillary node dissection. Um So just to move forward again, um As I was saying, we were utilizing technetium 99 for sentinel node identifiable uh Olympus integra fee that required nuclear medicine to eject inject the patient before the surgery. But now we're utilizing something called MAG trace. It's a nanoparticle that has para magnetic properties and utilizes the same uh machine in the operating room for identifying the sentinel notes. It's easy to use. You can place it at the time of surgery after the patient goes to sleep. There's no radio activity, it's clinically accurate. And again it's the platform that eliminates all of these other uh inefficiencies of scheduling patients and they don't need to have the injection in pre op, which actually can sting and hurt at that time as well. So once the mag traces injected, um you do uh massaging of the lymphatic and then you can start the case about 20 minutes in. And again utilizing that same detector here. You can see how we utilize to identify the central node. Yeah. So here's a way of identifying that sentinel node. And then the great thing about the mag trace is that not only can you hear it, but you can see it as well because the mag trace because it's made with the iron oxide nanoparticles, it also gives a discoloration to the lymph node for visual visualization as well. So number of clinical trials showing the efficacy. Um We utilized uh as I said we were the lead institution for the U. S. Multi center trial and that showed excellent outcomes as well. And then finally now we've moved into utilizing the targeted actually no dissection with non radioactive tracer, the mag seed for the positive lymph node. Um and it's a great way to use these for patients um that don't need actually no dissections. And again, it's all one type of technology. And here at UCSF, we were the first in the world, not only to use mag seed for localization, but also for non radioactive target. Actually no dissection. Um and it was a great to have them here and to to film us for this first ever targeted actually no dissection in a non radioactive sense. And so I'm very, you know, honored to be part of such an incredible institution um and take part in things like this. That happened not only in our department, in our group, but also across the entire gambit of U. C. S. F. And especially in surgical oncology as well and in the cancer center. Um, so with that, I'd like to say thank you again. It's an incredible honor to be part of this group and I just appreciate your time. Thank you. That was a great talk. I have a question just because I don't know too much about this. But what's the difference between the clip and the mag seat And why would you have bowls? Yeah sorry about that. That's a great question. So the clip is a titanium clip that's um Uh you know about two in size and it has there's no way to detect it. So it has no it has no para magnetic qualities it has. It's not radioactive. You can't feel it you can't see it. So that is a clip that is placed at the time of biopsy. To prove that they biopsy the location that they were looking at on mammogram or ultrasound. So the clip is left as a way to identify the area on mammogram or ultrasound at a later time. I see that makes sense. And then I did have another question about why using the sound versus like ultrasound are not all lesions visible on ultrasound. And so is that the reason that you need another modality? Exactly. So a couple of things. So you're absolutely right. So there are a lot of lesions that you can't see on ultrasound. So that's one reason. The second is that you for lesions that you might be able to see on ultrasound. But you can't feel, you can ultrasound on the skin and you can kind of see where it is. But then when you make your incision, all those tissues start to move all over the place and utilizing the ultrasound. You can't really see it once you're inside the breast tissue or from the skin. So um now there are people that utilize ultrasound once the patient goes to sleep, to place the wire at the time that the patients asleep and then use the wire localization. But we still think that the wires is suboptimal compared to the magazine. Yeah, no. That's great. That's very exciting. And maybe my last question is just again, I want to go back to screening and and um let you talk a little bit about what's been happening with breast cancer screening with Covid and any recommendations you might have going forward for people. Yeah, sure. So just as dr maker said, um you know, there was kind of uh lower numbers leading up into the middle of last year and even into the fall that obviously women were not getting their mammograms. I think today they definitely should be getting them. We've really all of the groups across the state of California especially have gotten great pathways for getting breast imaging done in a very, very safe way. Um Now that so many people have been vaccinated, I think risks are going down farther and farther and then in these institutions where you're getting mammography and especially here at UCSF, the amount of precautions that that have gone into place have been absolutely incredible in terms of lowering the any possible risk of someone contracting covid at the time of their breast imaging. Now, having said that, I think what's interesting um and uh now go into what Dr Sosa said is that what she said about papillary carcinomas is really very similar to the whole breast world as well as prostate as you know with regards to over diagnosis and over treatment. So I think what will be really interesting um is to look at some outcomes with regards to screening over this past year and how it may or may not have actually probably not affected um survival detection in terms of uh stage at presentation and etcetera. Which will be really interesting to see. Um and identify the fact that we may be over screening women for breast as well, just like Dr Sosa was saying with regards to over detection or you know uh over diagnosis with pathway carcinoma and also you know dr gill. Well she has done so much in screening in general. Uh Well he's one of my former professors at Dartmouth is an exceptional person. That's shown a lot of data with screening and how maybe there's a much better way to do it. And as the group knows, Doctor S Truman's Trial, the wisdom trial for breast cancer screening is really looking at a way to do precision medicine for screening and not just treatment. That's great. So maybe we're going to have just kind of a natural experiment, observation or experiment which is going to be way better than what happened with prostate cancer and screening and active surveillance. So okay, well thank you very much to everybody all the panelists tonight who gave great excellent talks, very informative presentations. Um I want to let everybody know that we will have a video recording of this available on our website shortly. And also we plan to resume this series in the fall. So uh we do have an exciting lineup of speakers. So look for more information on that in the future. So thank you everybody and good night.
