All right, so based on the time restrictions, I decided to focus on just high-risk GTN. And we at UT Houston, for some reason, have had quite a few of these patients lately. And we've had a few lessons that were hard-learned. So talk about how to manage this. So gestational trophoblastic disease has both benign and neoplastic components. The benign, as the fellows in Vietnam probably are aware, are complete mole and partial mole. And then you need to monitor these patients, as they will transition to neoplasia on occasion, with complete mole about 6% to 32%, partial mole less than 5% to transformation. The types that we're going to talk about today are invasive mole and poreocarcinoma. The placental site trophoblastic tumor and epithelioid trophoblastic tumor are unique in their treatment options. And I'm not going to try to address those tonight. The first thing to do is staging. And the FIGO staging is listed here. So stage one is disease confined to the uterus. Two extends outside the uterus, but limited to genital structures. Three is involving the lungs. And four is anything beyond lungs and genital tract. And then we use the WHO scoring system. This is the most current, with the different components. So the risk factors are graded one, two, three, and four. And you just sum these up to get the overall risk. So the age of the patient, antecedent pregnancy, the interval from the antecedent pregnancy to diagnosis, pretreatment beta HCG, the largest tumor volume, and site of metastases and number of metastases, and whether or not they've failed prior chemotherapy. Seven and above is considered high risk, which we'll talk about in just a minute. So definition of high risk is either invasive mole or choreocarcinoma. FIGO stage four, so metastasis beyond the pelvis and the lung. FIGO stage two to three, with a WHO score greater than six or seven or greater. And a WHO score of greater than 12 is considered ultra high risk. And these patients have a high risk of failing even multi-agent chemotherapy. So when you're documenting this, we usually do the FIGO stage with a colon and then the WHO score. What do we need to do to evaluate these patients? Well, first, good history and physical. The labs, CBC, CMP, liver enzymes and function, thyroid panel, and quantitative beta HCG. And I would welcome my colleagues' comments, but I've never seen abnormal thyroid with a beta HCG below 800,000. If you all have seen that, I'd like to know it. But generally, I don't do thyroid studies unless the beta is really high. So pelvic ultrasound can rule out a normal pregnancy. FIGO uses a chest X-ray, but we always use a CT, chest, abdomen, and pelvis to assess the disease. If there's lung disease or neurologic symptoms, CT or MRI of the brain. And then review any pathology that might be available, but you don't need pathology for this diagnosis or to initiate treatment. So if the new score is less than 6, they have an excellent cure rate with single-agent chemotherapy with about a 70% with the majority of the remaining patients being salvaged with multi-agent therapy. If it's 7 to 11, there's higher risk of resistance to single-agent chemotherapy, so multi-agent therapy should be used. And the ultra-high risk has an overall five-year survival of about 68% even with multi-agent chemotherapy. I'm just using the NCCM guidelines here to talk about the treatment regimens. And so if you confirm high risk, generally it's EMICO. If there's brain metastases, there's a recommendation to increase the methotrexate and mucoborin doses. And some people consider radiation therapy. We generally don't at our institution unless it's being recommended following a resection of a brain lesion, and in which case we would be doing stereotactic radiation. But using whole brain radiation is pretty rare for us. Neurosurgeons here are very aggressive, and actually several of the patients came to us because they presented with neurologic symptoms and ended up with a craniotomy before the diagnosis was made. And we've had good outcomes with surgical resection. If the patients have a very high Q-score, we generally start with three cycles of etoposide and cisplatinin as an induction, and then going to EMICO. And the reason for that is that we've had patients with significant toxicity from either tumor lysis syndrome or rapid involution of the tumor. And if we have time, I'll go over a little case presentation at the end that is an example of that. So if these patients aren't responding appropriately, we go on to EMA-EP or EP-EMA, which will be outlined in one of the subsequent slides, which is here. There's the EMICO regimen. Again, consider induction chemotherapy with etoposide and cisplatinin for those patients with very high risk scores or concern for a significant amount of disease with tumor lysis as a concern. And this is the EMA-EP and the EP-EMA regimens. I'm not going to go through these in great detail. I'm happy to share the slides, or you can go on to NCCN and get this information pretty easily. Again, consider induction for a very advanced disease. Then also in NCCN, they list several different options for patients that haven't responded to EMA-EP or EMA-CO or can't tolerate the platinum. So a variety of different options, including immunotherapy as a possibility. Any questions? Or I'll go on to a quick patient presentation. Yeah, I think you can go ahead. All right. So this is one of our relatively recent patients, probably about four years ago now. A 38-year-old woman who presented. She's a G3P3 who was three months postpartum who presented to the emergency room with new onset seizures and a positive pregnancy test. Because of the seizures, they got a CT scan of the brain and found a 5-centimeter mass in the left temporal area and called neurosurgery, who proceeded directly to resection of the mass. Pathology came back a couple of days later as choriocarcinoma, and then they consulted us. And so after they consulted us, we finished the evaluation. And so she was recovering from her neurosurgery with her neurologic deficits gradually improving. We got a CT chest, abdomen, and pelvis with lung mets that were too numerous to count and multiple large liver mets. The MRI of the brain only showed the one lesion that was resected with post-op changes. And so we started Emma on post-op day six, which completed late in the evening on post-op day seven. And she was discharged home on post-op day eight. I'd like to ask, would anybody have done anything differently in this patient? I was going to ask you that, Joe. If you saw her before the neurosurgeons saw her, what would you do? Because I probably would not have sent her to neurosurgery. Since I didn't see her then, but I understand that she had a significant mass effect with midline shift and increased intracranial pressures. So based on that, she probably did benefit from resection. And also, initially, she did have a fair amount of neurologic dysfunction. But over about a week, it really was quite minimal. So we've been doing more resections in these kinds of cases if there are significant neurologic symptoms. But you're right. If there weren't, then I would have just treated with chemotherapy. So unfortunately, this particular patient has a very tragic ending. I think there's another question somewhere. Hi, sorry, Joe. Thank you. That was a really awesome intro. And we recently had actually a patient just like this that we gave induction chemotherapy to who died of tumor lysis syndrome three days later. It was horrible, a very young woman. And so I was wondering about the EMMA, and if you could explain a little bit more about induction chemotherapy versus full-on chemo, or how do you navigate that? So I, too, have had problems using EMMOCO in large-volume disease with tumor lysis syndrome. I vividly remember a 19-year-old that we treated with EMMOCO for very advanced disease, had a huge tumor lysis, was on dialysis for months and in the ICU on a ventilator. And so I recognize that being very aggressive with chemotherapy up front can be very difficult on these patients, even if they're young and otherwise healthy. So the induction chemotherapy is something we've gone more to. And over the years, I've kind of gone back and forth, whether trying to use just high-dose methotrexate or using the EP regimen that's currently recommended for the NCCN guidelines. And if it is EP, we do dose-reduce initially, unless there's brain metastases, which the recommendation is to increase the dosing. This patient was actually seen and treated before the recommendation for EP prior to EMMOCO, and that's why she was treated with EMMOCO and was discharged. So the patient, after she got home, she was quite lethargic and just went to bed and slept for about four hours. When she woke up, she started with hemoptysis. And she was taken to the local ED by ambulance, but she died about eight hours after discharge due to uncontrollable pulmonary hemorrhage. So even if it's not tumor lysis syndrome per se in the traditional sense of the toxins in the blood, it's tumor lysis in that it eroded into the blood vessels in the lung with a rapid evolution and resulted in her demise. And so lessons learned from this, as I mentioned, we are doing more EP induction at lower doses for two or three cycles in these patients. Occasionally, we'll go to methotrexate high dose. And we definitely watch these patients for several days after the chemotherapy to make sure there is no tumor lysis syndrome that requires treatment. And I don't know if any of you use radiation on a regular basis prophylactically in the brain or liver to prevent hemorrhage, but we've kind of given that up at our institution. Does anybody still do that? Hearing no comments, I'll assume nobody does it. All right. So then if we start with EP, we follow up with them at EP. And now the recommendations on the NCCN are that you treat three to four cycles past the negative beta HCG. So we're extending our treatment cycles a little bit further than what we used to do. So any questions, any comments? I welcome anyone's suggestion. I didn't answer fast enough. John Soper still does radiation for brain mets. OK. Just FYI. All right. I would say we do. I'm sorry. I'm sorry. I would say we do radiation for brain mets as well. And the challenge that I have with the redox is the discussion about whole brain versus stereotactic. I know why they want to do stereotactic. And I, but the challenge is you can get some solitary mets, but you frequently get multiple mets. And stereotactic doesn't address that very well. Just complicates it. Dr. Lucci, may I ask you a question? Like, you know, like we usually use the V-CAP SOs prognostic scoring system for the primary GTN. But I would like to ask if the patient with the recurrent GTN, so do you use this prognostic scoring system to re-evaluate the patient? Yes, we do. And that's based on that last line that failed prior chemotherapy? Yeah. Very good. Well, I know that we've gone over 10 minutes or so, so I appreciate all the folks who have stuck it out.

gestational trophoblastic neoplasia

high-risk GTN

chemotherapy

FIGO staging

tumor lysis syndrome