Chapters Transcript Management of Gastrointestinal Stromal Tumors Dr. Natasha Leigh, MD shares an overview of GIST tumors including symptoms, staging and treatments. Now for our first presenter, we have Doctor Natasha Lee who earned her medical degree at the University of Birmingham School of Medicine in Birmingham, England. She then obtained her residency in general surgery at Khan. Is it, is that how you pronounce it? Icon, icon School of Medicine at Mount Sinai. Saint Luke's Roosevelt Hospital in New York. Doctor Lee did her fellowship in Pary Pancreatic and G I Surgery at Wash U University School of Medicine and is currently an assistant professor of the H PB surgery division with was U physicians at Barnes Jewish Hospital. So, thank you so much for your time today. Doctor Lee and educating us on H PB management of gift tumors. So it, what does G stand for? Oh, I'll get that. It sounds good. I'll let you, I'll let you do the other words that I can't pronounce. Perfect. Well, thank you and thank you to everyone who is attending this conference today and thank you for inviting me to speak. Um You already did my intro for me. So that's great. Um Today I'm gonna be talking about the management of gastrointestinal stromal tumors, which is probably, you know, something that I see a decent amount of um in my practice. So just an overview um about these tumors, they are the most common soft tissue tumors in the gastrointestinal tract with an annual incidence of around just under one in 100,000 in the United States. As you can see in this picture here, they are submucosal masses that are typically composed of smooth muscle cells and spindle cells. The mo the distribution throughout the gastrointestinal tract is varied, but the vast majority of these occur in the stomach around 60%. Next up is the small bowel Jen and ilium. About 30% occur here. And the other sites in the G I tract are fairly rare, namely the esophagus, duodenum, colon, appendix and rectum. So, not a whole lot is known about the gist tumors that occur in these other rare sites as we'll get to a little later, about 20 to 30% of the minority of these present incidentally and are picked up on some scan that's done for some other reason. But the vast majority of these about 70% are actually symptomatic whether they present with early satiety or vague symptoms of abdominal discomfort or fullness. But they can also be complicated by g uh bleeding, either intraluminal causing symptoms of A G I bleed or anemia or extra Luminal meaning outside of the intestine and can present with bleeding into the abdomen itself. Intraperitoneal. Very rarely do they cause tumor rupture but they can cause tumor, uh obstruction of the G I tract, especially when they are either much, much larger in the stomach or they're located somewhere else in the intestinal tract. And typically the development of symptoms is driven largely by the size of these tumors. So with increasing size comes increasing, symptomatology work up. I will go through each of these individually, but typically consist of abdominal imaging, either a CT MRI or pet scan. And I'll go through indications for each of these chest imaging for completion staging. And in certain cases is uh a biopsy of the tumor. Most importantly because these are complex tumors and involve sort of multidisciplinary uh treatment modalities. It's important that these tumors are evaluated and managed by a multidisciplinary team. So, ac T scan of the abdomen and pelvis with IV contrast is the best imaging modality. The staging of uh tumors in all patients. Oral contrast is not typically necessary and can actually obscure the lumen of the bowel making it sometimes more challenge to evaluate these lesions. So, intravenous contrast is better. It can also be used to evaluate response to neoadjuvant therapy, which we'll get to later and is the standard scan that we get for surveillance post operatively to evaluate for any tumor recurrence. As you can see on this scan here up by the spleen uh uh on the greater curvature of the stomach. There's a well circumscribed solid mass that enhances homogeneously and like I said before, it can either be extra Luminal like this one or intraluminal like that picture I showed you before. Um high risk features that could be more concerning for more malignant degeneration would be irregular borders, heterogeneity, cystic spaces, ulceration, central necrosis or evidence of hemorrhage and uh pertaining to the chest imaging. It's important mostly we get ac t of the chest um to get this for all tumors except very low risk tumors which will address in a little bit, which are those that are less than two centimeters in the stomach. An MRI can be useful in cases where there is suspicion for a liver metastasis on CT or in patients who have a contraindication to uh iodinated contrast and can therefore safely get gin based contrast for an MRI. This is uh some pictures of what liver metastases typically look like in just tumors. So on the T one phase you can see in the left picture, there's some arterial enhancement with that white rim around it. And in the uh venous phase, it washes out meaning it does not enhance. And on T two, these are typically very hyperintense lesions. A pet scan is typically not indicated. It really is useful as an additional scan to CTO MRI if a patient has receptible disease but would require a very morbid operation. And therefore, we should consider neoadjuvant chemo. And this is really only used if uh to rule out metastatic disease. If the other scans are suboptimal. Um It can also be used to assess response to neoadjuvant therapy if a pet scan was done free neoadjuvant therapy to help differentiate viable tumor um from necrosis or scar. And by the same token, it can also be used to evaluate for disease recurrence in somebody who's already had some scarring there. And it might not be obvious if it's just scar or if it's true recurrence. Most of these tumors are pet added on imaging, but especially large tumors that outgrow their blood supply, they can have central necrosis and therefore, maybe just the rim appears pet abi and the center of the tumor does not preoperative biopsy is really not indicated in most cases because these are fairly friable tumors. And so, in order to minimize the risk of tumor seeding, we try and avoid preoperative biopsies in most patients. However, there are specific indications which are uh the following here. So any time we're thinking about neoadjuvant therapy, which we'll get to indications in, in a minute. But it's important to have a biopsy because we want to be able to see if they have certain genetic mutations and therefore tailor their neoadjuvant therapy towards those. Um if there is an unclear diagnosis on imaging. Um and we need to figure out what this is and rule out an adenocarcinoma, for example, then a biopsy might be indicated or in patients who have unreceptable disease. And again, to confirm a, the diagnosis and B genetic profiling prior to initiating any systemic therapy. In this very select group of patients that I alluded to before very low risk patients for aggressive or metastatic disease. So those are gastric tumors less than two centimeters. It's important to consider a biopsy in order to make sure there's no aggressive features if you're considering putting these patients on a non operative non therapy surveillance strategy. So there's two types of biopsies that we can do. An endoscopic biopsy is usually preferable for multiple reasons. It can be used with uh ultrasound to help us evaluate the extent or depth of the tumor. As you can see here on this picture on the right hand side, uh this is the scope, the black circle is the endoscope and you can appreciate this mass seen at three o'clock. But you can also appreciate that there's some tissue in between the black scope and the mass, which is the mucosa demonstrating this is a submucosal tumor. An E US biopsy definitely has less risk of tumor hemorrhage or tumor dissemination. And so it's usually the preferred route, especially in uh if it's accessible this way. So typically, that would be gastric and upper G I and maybe even potentially lower a colonoscopy for those rarer tumors. However, um percutaneous biopsy may be warranted in patients who do not have a tumor that is accessible endoscopically, but that have locally advanced or metastatic disease and are not going to undergo surgical resection. So genetic mutations are pretty common in these tumors and it really important to recognize because they enable the potential use of and predict response to certain targeted therapies. The most common mutation that we see is a kit mutation to receptor tyrosine kinase. This occurs in about 80% of patients with disc tumors. There are different mutations on different exons as shown here which I'll allude to later because they have some prognostication value. PGGFR A mutations and also for receptor th in K is slightly different, but this occurs in about 5 to 10% of patients. And the vast minority of patients, about 5 to 10% have no discernible mutation in either of these mutations. And in those patients, we usually recommend further genetic analysis with next generation sequencing to see if they have any other target mutations. The most common of which is an S DH deficient mutation occurring in about 10 to 15% A B raf mutation, an NTKR mutation or rarely uh NF one or an FGFR mutation. Not all of these mutations unfortunately have targeted therapy and we'll get to sort of targeted therapy in a little bit. But that's why it's important to send these analyses on patients who are being considered for neo A therapy. So in terms of the receptor tyrosine kinase mutations as alluded to before there are two types. The most common type is the kit mutation, which I'm sure you've all heard of. It's the most responsive to a mat nib, which is the most common, the systemic therapy that we have itself. The mutation is not useful in determining malignant potential. But mutations in Exxon nine and 11 are associated with worse disease free survival. And the PD FTP DGFR A mutation is also very responsive to a map. NIB with the exception of this rare mutation, which is D 842 V and certain mutations. In other words, Exxon 18 are actually associated with better disease free survival. So these can be somewhat helpful in counseling patients. The S DH mutations are actually unfortunately more aggressive. They're usually seen in gastric tumors and younger patients and are associated with more aggressive disease or metastases even though the tumors are typically slower growing. And this uh genetic counseling is recommended for all patients who have an sch deficient G tumor. Unfortunately, they're typically I ma nib resistant, but there is some efficacy seen from other uh uh therapies such as SNT nib or regain, they actually have a risk of paraganglioma which is extra adrenal pheochromocytoma. So, preoperatively, they need to be screened for this. Typically with either serum or urine catecholamines or metanephrines. About 10 to 30% of gist are actually clinically malignant. And I'll show you a nice table in on the next slide to help us determine the patient's individual risk. The small bowel is much more malignant behaving than gastric. And as mentioned before, the other G I sites are fairly rare. And so there's not a whole lot of data available to determine how they behave. But from what we have, it does appear that these sites are also more malignant behaving and more akin to small bowel tumors. An increased size increases the risk of a just potential malignant potential. As does the number of increased mitoses with less than or greater than five per 50 high powered field being a cut off. So this is the knife table to show the influence of not only size and mitosis but also sight on the prediction of uh metastatic potential. Note that uh within the gastric uh tumors as circled here that my toes really is what's driving the malignant potential. Even those tumors that are greater than 10 centimeters or 5 to 10 centimeters with low mitoses have a pretty low malignant potential. The ones that are highlighted in red are those which are intermediate or high risk patients that should be considered for some sort of uh TK I therapy, whether that be uh adjuvant or neoadjuvant. Um All the other tumors are lumped into this non gastric category. And as you can appreciate here, they have a significantly higher malignant potential and the mitotic rate really plays a lot less of a role. So as such, the new NCCN guidelines have actually incorporated tumor site as well as size and mitosis into the wrist stratification guidelines. Of note, these two these are, this wrist ratification applies more to CK I and PDGFR A positive gist. Uh We have a lot more data on them as they're a lot more common. And the S DH deficient GIFS, we have a lot less information and they behave more unpredictably. So it's not as reliable to use this. So let's get on to management of these tumors do or GS need treatment. Well, as demonstrated on this slide previously, and I'll go back to this. So you can appreciate it once more is the ga really small gastric tumors. So if you look size less than two mitosis, less than or equal to five al, essentially a 0% chance of malignant degeneration. So with that in mind, it's pretty safe to consider surveillance for these tumors. Uh irrespective of their mitosis. It's important as stated before to fully stage these patients with imaging. So they need at least AC TM and Pelvis and they should undergo an E US FN A to rule out any high risk features which would therefore take them off the surveillance strategy and put them more onto the treatment strategy. All other gist tumors have a much uh more considerable risk of malignancy um and therefore should be considered for active treatment. So, surgery really is the first line curative treatment for patients with localized receptible primary gist tumors without significant surgical morbidity. So all receptible disease should be considered for surgery as an upfront therapy with the exception as mentioned before are very small gastric tumors who've undergone a biopsy and staging with low risk features. Any patients who have receptible that advanced disease after maximal neoadjuvant therapy with a good either stable disease or a good disease response can also be considered for surgical intervention. And I'll show you some data as to that in a little bit. It can also be considered in disease recurrence. But this really is for very, very select patients with stable or improved disease response after a trial of neoadjuvant therapy for the most part. And these patients need to be carefully evaluated in a multidisciplinary approach. The principles of surgical resection are are important because as mentioned earlier, these are very friable tumors. And so it's important for our surgeons to think about how we do the surgery and what surgery we're going to perform for these patients. So, it's important for us to avoid tumor rupture and to remove them with an intact pseudo capsule. Typically, especially since gastric are the most common ones that we see. We don't need to perform a formal gastrectomy with lymph node dissection or anything like that. Usually a non an atomic segmental resection or a wedge resection is sufficient. There's not usually a need for a formal lymphadenectomy because these tumors typically see hematogenous. And so, unless there's a pathologically enlarged lymph nodes or the um GIS tumor is an S DH deficient gist, which has a higher risk of lymph lymphadenopathy and involvement. Then we wouldn't typically perform a lymphadenectomy. So we would typically just perform a wedge resection of whichever part of the stomach. This gist was in the only real need for a formal resection would be if it's very close to either the pylorus or the ge junction. Sometimes if they're very large but receptible, they may need a multi visceral resection. So sometimes a piece of small bowel, some bladder, some colon, um et cetera that might be attached to it even sometimes on pancreas or liver. Um But there's really no role for in nucleating these tumors. Um We typically take them out, we aim for an R zero resection. However, sometimes based on an atomic ro location, it is not possible to get a totally rze resection, meaning no microscopic tumor cells on ink and we, and we can get an R one resection which means no grossly uh no gross evidence of disease. If you a the surgeon is aiming for an R zero resection and somehow they get an R one resection, it's OK. They don't need to re resect since the data shows they actually have fairly similar outcomes in terms of survival. And the other thing is we always remove it in a bag to make sure that the tumor is not touching other tissue, increasing the risk of spread. Uh There's been some data recently about uh given some concerns, especially from the community about. Well, is it really safe to perform this minimally invasively? Are we getting the same outcomes? And you know, fairly similar discussions have been had in the past about pancreas surgery and colon surgery for, for cancers. So this is a nice systematic review from 2015 and meta analysis of lab versus open gastric gestal section of 19 studies with about what just over 1000 patients, their lab group was associated with uh much improved short term outcomes such as lower estimated blood loss, earlier time to bowel function, shorter length of stay and lower morbidity without any difference in long term recurrence rates. So, in my practice, I unless it's a huge g with a multi VSC resection, I will consider either a laparoscopic or a robotic surgery for almost all patients, especially if there, it's in a favorable anatomical location such as stomach or small bowel postoperatively. An R zero resection can be obtained in about 85% of primary gist tumors. Although about 50% of them have recurrence or metastasis depending on the site and aggression, uh aggressive behavior with a median of about two years in high risk patients. The five year overall survival if there's recurrence or metastasis is still about 50%. Though we're gonna move on now to systemic therapy, which mostly consists of tyrosine kinase inhibitors. Again, it's really important to know if the patient has genotype sensitive disease on pathology. Whether that be on a neoadjuvant bio on a biopsy if we're considering neoadjuvant or on a surgical pathology. If they've been resected, there's lots of different agents that we have and I've just listed some of them here so that, um you, you know, you probably know the most common ones which is a matin E um which is a selective uh kit inhibitor also known as Gleevec or Cetin, which is a multi targeted in a kit inhibitor typically used in a ma of resistant patients. There are also other agents that target some of the other mutations such as pggfras DH and NTRK. So again, again, highlighting the importance of pathology prior to initiation of therapy a little bit about an amount nib since it's the most common one that we use, it's an inhibitor of transmembrane receptor Tracy kinas CK IP GGFR ABC R A, about 85 to 90% of GIST are responsive to this. As stated prior, the exon 11 mutation typically exhibit a best response and an Exxon nine is uh least responsive. It's nice because it's a really well tolerated drug with pretty minimal G I side effects. And so patients can stay on it for a really long time. So what's the data to show this is pertaining to the patient that I showed you before with uh a resectable gist tumor, talking about the utility of adjuvant imma for those that are resected. So this is the Z 9001 randomized control trial from 2014, which took patients with a primary localized gist who then underwent surgery and were randomized adjuvant to either 400 mg a day of a matin li for one year versus placebo. And what they saw was that if you look at the one year time point here, you could notice a big difference in s in uh survival, but as you sort of go out and those patients have been taking off mat nib um the survival kind of levels out. So we do see that there's an inquiry, a significantly longer recurrence free survival in the Amat Nibba, especially in those patients who have the kit exon 11 deletion not seen as much in those with different deletions or the PGGFR A mutation. This was another randomized control trial from 2015, which selected out only intermediate and high risk just who underwent surgery. And as I I sort of told you before, the A Z zero and R one group had pretty similar survival who then underwent two years of adjuvant imma versus placebo. And again, you can appreciate similar looking curve. The recurrence free survival is significantly longer in the in that nib arm with a three year survival of 84 versus 66%. But as those patients come off in that nib uh the you can see the survival curves kind of come back together. Again, this is a much more recent trial um really what the medical oncologists are basing their adjuvant therapy on now is again, it took intermediate, this is a persist trial, sorry from 2018 that took intermediate and high risk just again who underwent surgery and gave them five years of IAT nev, this was not randomized. So all patients got IAT nev. And what you can see here is that they significantly different survival to what you saw for when the patients had dropped off because imatinib was, you know, was terminated, but they have a five year recurrence, free survival of 90% with an overall survival of 95% and zero patients had recurrence whilst on imatinib as gave before, it is extremely well tolerated drug and pretty minimal side effects. And so what we really think is that three years is the standard five years based on the persist trial is really safe. Uh especially given the minimal side effect profile and very um encouraging survival curve that you see here. So when do we consider adjuvant therapy for resected gist tumors? Well, really in those that are intermediate or high risk tumors? I've highlighted and read on that table I showed you before or those with tumor rupture. Um The duration really is based on the data I just showed you. So if they have not received any neoadjuvant therapy, they typically are a candidate for adjuvant it for three years, but should consider five years based on the most recent persist trial. If they receive neoadjuvant, then at least a minimum of two years, I would say most patients who are on neoadjuvant therapy get at least six months of neoadjuvant. Um or uh you know, can also be considered adjuvant. For as long as there's a clinical response or stable disease, you can resume these uh treatments when the patient is taking oral medications after the surgery, it's very safe. This is a really nice nomogram for Memorial Sloan capturing which demonstrates uh it's like a prognostic nomogram demonstrating the importance again, of size mitotic index and sight. So I just plugged in a patient. Um but as you can see here, it's really easy to use. So this patient had a size of five centimeters which you sort of correlate that up to the points at the top and then add the points. So that would give you 30 points, a mitotic index of 10 per high powered field. So that's greater than five. And that would give you a score of 80 then the site was the stomach. So that's right at the left hand side and that would give you a score of zero. So that would translate into a total of 110 points, which then if you if calculate that and look at the recurrence free survival probabilities below that gives you a two year recurrence free survival of 55 and a five year recurrence free survival of 30. So this patient should be considered for adjuvant therapy, but it's a really nice way to help decide which patients are higher risk for recurrence or metastatic disease. So, what about those patients who are not upfront receptible? Well, as mentioned before, these typically spread Hema hematogenous and lymph node involvement is rare with the exception of the sch deficient tumors. Um The prognosis of local regionally advanced disease is actually fairly similar to distant metastatic disease, which then brings into question. Well, what's the role of TKIS in this these patients? And is there ever any role for surgery in them? So I'm gonna take you through some of the data for neoadjuvant use of tyrosine kinase inhibitors. And this is specifically targeted to the patient population I just mentioned. So the RT OG uh 0132 trial from 2011 took patients with receptible gist tumors, meaning that they were either primarily unreceptable or have recurrence or metastatic disease but could potentially get downstage were given a higher dose of a ma ne 600 mg instead of 400 who then underwent surgery and then were given adjuvant also a mat, what they saw was there was a partial response or stable disease in 90 to 96% of the patients. And these are patients who then underwent uh surgery and had a two year overall survival of 91 to 93% with a progression free survival of 83% to these. Numbers are very impressive in that these patients were initially ruled out as having any potential cure or long term survival. But here, what you see is really the numbers suggest otherwise. And I and I, and I believe it's really the combination of uh tkis and surgery. This is another trial from 2013 where they looked at the same group of patients and gave them a ma nib lower dose, uh and then who underwent surgery and again, adjuvant and that amat nib, they saw a partial response in 60% and 36% of those initially unresectable, untreatable patients were able to undergo surgery. And a million of seven months, as I said before, we treated most pe most people with about six months plus of neoadjuvant. They saw that these patients who got to surgery underwent a had a significantly longer progression free survival. In fact, it wasn't even reached versus 24 months of those who did not get to surgery. And again, significantly longer overall survival. This wasn't reached versus 42 months in the res uh in the uh non resected group, they had a three progression free survival of 67% and a three year overall survival of 89% if they also had adjuvant in that name. So clearly, it's a combination, I think of a ma both TKIS and surgery in these patients. And impressively, you know, almost 40% of these unresectable patients were managed to get to surgery. So these are really the indications for neoadjuvant therapy, patients who have initially unreceptable metastatic or recurrent disease if they are initially receptible, but the or would require significant morbidity and that can be minimized potentially by downs staging such as those involving the ge junction or rectal sphincter or those that are being considered for a multi visceral resection. Again, I underscore the importance of needing genetic profiling and a biopsy to ensure that it is a genotype sensitive gis tumor. And then really, this is treated, you know, patients are treated until they get a maximum treatment response on imaging. Typically, we reimage about every 2 to 3 months and then see the sort of size of the tumor, how it's responding. And once you sort of reach the point where it's not responding anymore or getting bigger, then that's the point to say, all right, if we can resect it, that's the point we'll go in. And if they have a response or stable disease, we would then consider that patient for surgical resection, including resection of metastatic disease. If we can reach an R zero or R one resection, if it's an R two resection, meaning we're leaving gross disease behind, there's really no role for debulking these patients. Um We would typically recommend stopping neoadjuvant TKIS about a week before surgery. And then, as mentioned before, we would resume these when the patient's taking oral medications after surgery. So if patients however, go on neoadjuvant therapy and are seen to have disease progression. Then the option really are to either increase the dose or switch the medication. But it's important to consider those patients also for a clinical trial. If any exist at that institution, in terms of surveillance and follow up, we would typically recommend uh an H and P and AC T scan with IV contrast every uh few months and I'll get to that in a second. An MRI like I said before, if the CT is contraindicated for some reason, uh these are the really the frequencies. So in patients who are small low risk gastric tumors, as we talked about before undergoing surveillance strategy, we would usually recommend every 6 to 12 months for about five years. And then it's a decision after that of spacing it out postoperatively, the lower risk patients are usually on a 6 to 12 month screening uh surveillance strategy and those with higher risk for recurrence are on A Q 6 to 3 to 6 month uh surveillance strategy. And as mentioned previously, those on neoadjuvant therapy about every 2 to 3 months to assess treatment response. So now I'm gonna go through a few case presentations with you of real patients uh who I've had and sort of go through the thought process of working them up and management plan with you. So this is an 86 year old female with no significant medical history, very healthy, very active with an equal score of zero who had this ct scan done for some other reason and have incidentally found 2.4 centimeter mass on the greater curvature of the stomach. Completely asymptomatic as you can appreciate here. Although the arrow seems to be a little off. Um it's exophytic and pedunculated. It's homogeneous and enhancing. This looks pretty classic for a GS tumor on imaging. So the question I posed to you is any further work up. And I don't think we can and, and you can guys can feel free to uh chat your answers if you want to. But I'm gonna go through my thought process for this patient. So given everything we've just sort of said before, what I would would recommend is ac T chest, a complete staging work up going through the other answers. I would not recommend a biopsy because on CT, it looks pretty classic for a gastric gist tumor. And given that it's greater than two centimeters, there's really no role for observation in a patient who's a good operative candidate, which this patient is uh therefore A and B would be wrong. It's uh important to complete the staging imaging with a chest CT since this is greater than two centimeters. Hence, YC is the correct answer. And there's no real role for pet CT in this patient because there's no evidence of metastatic disease. Uh and this is clearly a receptible tumor and obviously, we don't wanna do no further work up. We do need to complete staging. So the ct chest was negative, what would be the best treatment plan? So I'll give you a second to look at these. So this is a patient who, to me is a very good operative candidate and has a operable tumor without much morbidity and is receptible. So that's why surgical resection upfront is the best curative treatment. So, because it's a gastric tumor that's greater than two centimeters, there's really no role for surveillance in this candidate. And there's no real role for neoadjuvant because this would be a minimally morbid surgery. And uh it wouldn't really neoadjuvant wouldn't really change anything surgically. So she went to the operating room for a uh partial gastrectomy and a wedge of that gist tumor which was closed primarily, we did it uh robotically and she went home the next day. So the pathology demonstrated a 2.5 centimeter gastric gist negative margins, no lymph nodes in the specimen, less than five mitoses per 50 high powered field and it was a kit positive. So now the question is, what's the next step? Should we do? Just surveillance? Should she be considered for adjuvant, imatinib or should we go back and get some lymph nodes? I'll give you a second to think about that. So, really surveillance is the best strategy for this patient as a. Um So I showed you this table before the risk of malignant degeneration. Um As you can see here, it's pretty low. It's only 1.9%. So there's really no role for adjuvant therapy. Only surveillance imaging is needed. And as mentioned before, the gist, they've spread hematogenous, not usually via lymphatics, especially in those that are not s DH deficient. And so there's really no need for a lymphadenectomy. So what if this patient's tumor was, this was the same patient? But what if they had 20 mitosis per 50 high powered field, same everything house. Would you do anything differently? I'll give you a second to think about this. So as we plug the, the numbers into this uh to this table, you can see that really the risk is a lot higher now, because of the high number of mitosis. So I think this patient should be considered for adjuvant therapy and again, no role for lymphadenectomy in this patient. So now I'm gonna give you another case. What if we have this same exact patient as the first time around uh healthy 86 year old uh with the same exact mass that it was 1.5 centimeters instead of 2.4 centimeters. Would you do anything differently on initial work up? So I'll give you a second to look at these. So yes, I think importantly, this patient can be considered for a surveillance strategy. So you want to make sure that we exclude any high risk features. So we should get a biopsy uh as mentioned before, an E US biopsy gives significantly less risk of bleeding and seeing. So that will be preferred over percutaneous. And in this very early stage low risk disease, there's not really a role for any further staging imaging. Ok. Very different patient. So this is a 58 year old female with vague pelvic pain who came in with a complex 10 centimeter mass in the pelvis. Uh As you can appreciate partially here from this cut, it communicates with multiple loops of small bowel with the bladder with the rectum. So I'll give you a second to look at these. But w should we consider any further work up in this patient? And if so what so clearly, this patient has a much more locally advanced tumor. It looks like it's also small bowel in origin rather than gastric. Although it's not a totally clear diagnosis that it suggests it also appears very complex involving the small bowel bladder rectum. So we need a biopsy here to confirm a diagnosis. There's probably no good way to access this endoscopically. I'll show you the image again. As you can see it's way away from the stomach and the s and the duodenum. And so percutaneous biopsy is likely our best bet here. We also need to complete the staging imaging with AC T chest. So the CP test was negative and she underwent a perp biopsy which shows a small bow, just tumor, five mitoses per high powered field and kit positive. And I'll give you a second to think about what should we do next? Should we survey, should we do Neo Avent or should we do upfront resection? Mm. So, clearly, totally different patient to the first public I showed you this is a very, very complex mass involving multi organs which would require a very morbid multis resection, especially if it's involving bladder and rectum. So and it's seek positive. So it should respond to a matin which could hopefully make the resection much less more. But if it shrinks, maybe we wouldn't have to do uh an L A, maybe we wouldn't have to do a total cystectomy. Um So I think neoadjuvant would be the way to go. She's actually on neoadjuvant therapy currently with uh demonstrating some pretty significant shrinkage in her disease. So, with that in mind, we're continuing um neoadjuvant therapy to see what we can get as a maximal tumor response. There's really no uh maximum length that you can do neoadjuvant. So, provided that the patient is responding and it's going to benefit them surgically, meaning they're gonna get a much less, more, potentially, much less morbid resection and more guarantee of a negative margin, then we would continue with neoadjuvant therapy. So that's what she's on right now. So this is sort of a nice um algorithm to think of uh gist tumors and try and triage them into different treatment. Arms, you know, starting with primary disease. Is this localized and receptible or is this either metastatic or unreceptable or would require a very morbid operation, you know, and again, localized receptible disease really should be considered for upfront surgery, especially if it's not going to be morbid small bowel gas for it. Even if it's, you know, got a bit of liver involved or whatever like that would really be, you know, a much less morbid, uh, thing than something that's involving the sphincters or multis. And then the question of, should we give adjuvant therapy based on pathology? And those sort of with recurrent disease really fall into the same category as I mentioned before as those with Mets or unreceptable or a morbid operation. And those patients should really be considered for upfront neoadjuvant um TKS based upon biopsy and genetic profiling. And then either they respond or have stable disease in which case is surgery feasible? What's the morbidity of surgery? What's the benefit to that patient or do they progress? Should we change? Uh Should we change TK I or should those patients go on a clinical trial? So, uh I know that's been a lot of information to absorb. And I thank you very much for inviting me to speak today. Uh I hope it's been helpful and useful um to you. And I would be absolutely happy to take any questions that you have. Looks like we do have one. If the patient does not want surgery, any reason not to just keep them on, on the mat. So I think if the patient doesn't want surgery or you think they're not a good surgical candidate, even if it's resectable, I think it's really a discussion with the patient. I personally would say if you risk ratify the patient and the patient, um, meets criteria for one for, you know, a higher risk, then I would put them on a mat nib. If they reached criteria for a lower risk. Then I it's really a discussion with the patient of, we can keep you on a MAT nib for X number of years or we can do surveillance of a MAT nib if they're lower risk, even if they don't meet that small gastric tumor criteria. Um And then you could do surveillance imaging every 3 to 6 months. And if the tumor were to grow or demonstrate features that made you concerned that it was not so benign appearing and then I would start uh in that nib at that time. Thanks so much for your time. We really appreciate it. Absolutely. And um like she said, if there's any other questions um after the session, I'm happy to answer them. She can give you my details for you to reach out to me. Sounds good. Thanks so much. Created by Presenters Natasha Leigh, MD Assistant Professor of Surgery, Gastroenterology View full profile
