would comprise a group of trophoblastic tissues that either can invade locally or even metastasize. And the most common site of metastasis would usually be the lungs. But other sites would be, especially if the patient already has lung lesions, would be distant sites such as your brain and your liver. That's why the importance of having to look for other sites of metastasis in this patient. Now, despite the seemingly morbid course of these patients, the cure rate for low-risk GTN would still be very, very high. In fact, some literature would report almost 100% remission rates for low-risk GTN patients. And for high-risk patients, you can have a more than 95% cure rate. And this cure rate would be attributable because we have the beta HCG as a marker. And then we now have lots of diagnostic tests which can help us do treatment surveillance. And of course, we have also the use of combined treatment modalities that can help our patients. Now, in the Philippines, I have been listening to your discussion a while ago, and you were already going on with the prognostic scoring. This patient has already been scored as a high-risk patient. But in our country, we use the combined FIGO scoring with a stage of the disease, as well as the WHO prognostic scoring. So in this case, since there were no metastasis, we will still be putting this patient under stage one with a high-risk score of 10 in this case. So however, in our country, if you have a stage one disease regardless of the score, what we usually do is to start these patients with single agent chemotherapy. So that is probably the difference that I am trying to reconcile now with how this patient was managed. So if you have a stage one, regardless of the risk score with us, we usually just start with a single agent or depending on the variables or the risk factors which were present, we can opt to choose double or triple agent in this case. We can always individualize. But if for stage two or three diseases with low risk score, then we can also opt to choose using the single agent chemotherapy. And it has been our protocol to do two consolidation therapies. For metastatic diseases with high risk scores, then we usually proceed with multi-agent chemotherapy and our go-to combination has always been EMACO where it can be combined with the adjuvant therapy. And regardless of the risk, whether it's the regular high risk or ultra high risk, we follow the three consolidation therapies. And what we usually give as consolidation therapies would be the last group of drugs that was given to this patient to achieve remission. So for example, the last drug was single agent, methotrexate, then our consolidation therapy would still be methotrexate, but two other additional courses for low risk patients and for high risk, three additional EMACO or whatever salvage therapy has been given. Now, this is quite similar to this guidelines. And for this patient, of course, she's gravid before. I was just wondering because the HCG result was more than 15,000 and in the risk scoring, there was a score of a zero, one to four. But of course, if we're going to follow, it will always fall within the high risk for anyway. So no other, initially this patient, if we were going to, if I were going to manage this, we might have started her on a single agent or at least a triple agent chemotherapy and not EMACO. Now, because this is, but I followed your protocol and assumed that the rest of the findings were within normal. So if she was already showing signs of toxicity, then probably we could have already lowered the dose for the different drugs. Okay, so this is how we give the different chemotherapeutic agents. For methotrexate, we usually give it. Because of our limited resources in our country, what our way of giving methotrexate is usually via intramuscular dose for five days, repeated at seven to 10 days interval. You hardly give the combination of methotrexate with the folinic acid rescue. And unfortunately, because also of the limited resources that our patients have, we only give the filgrastate only if the patients are presenting with the severe toxicities. Okay, if they are showing resistance to methotrexate, then we proceed to the second line, first single agent, which is actinomycin. So we reserve etoposide for the multiple agent protocol. So the overall survival rate for EMACO for high-risk patients would still be quite high as seen in the different literature. In our country, it's usually more than 70% for our patients. So this would be the primary remission rate in the Philippines with a sustained remission rate using EMACO of 80%. And our patients would have a survival rate of 86%. So our five-year GTN census for the past five years would still be relatively in the... These are new cases of GTN cases. So we were averaging previously in the early parts of 2000 up to 2010, we were averaging around 100 new cases of GTN. But now it has gone down to around a half mainly because we have graduated more trophoblastic disease trainees. So we have more specialists in the different provinces who are training in the different provinces. That's why they don't need to go to the center that I am working in, which is the Philippine General Hospital. And it's the tertiary referral system for GTN in the whole country. So we're seeing less. And of course, during the COVID, it has now gone down to only around 20 plus new cases for last year. And most of our patients are stage two and three high-risk cases. Okay, so we have a lot of experience in terms of giving adjuvant therapy, usually in the form of hysterectomy and whole brain irradiation for CNS metastasis and even for liver metastasis. So this is just to show you some of the readings that I've had in terms of the remission rate with the use of EMACO as the primary treatment for high-risk GTN. And according to this article by Shen, still a good drug combination for curing high-risk cases. However, 25% of GTN tumors will be resistant or will relapse after an initial chemotherapy and may have to require salvage chemotherapy with or without surgery as seen in this case. So it's quite fast. The way the HCG of this patient fell was quite fast. However, the recurrence of the tumor or the increase again in the HCG was quite faster in this case. So again, what we follow would be EMAEP after the failed EMACO or if there's resistance to EMACO, what we usually give would be the EMAEP regimen in our institution. So this is how we define plateau. We have two plateauing values over three consecutive serum beta-HCG determination. So this would be around less than, a plateau is defined as less than 10% increase or decrease from the baseline, or if we see a more than 10% increase from the baseline. And this is quite evident. This was not actually plateau anymore in our patient's case, but already arise. So, and this one would be one log increase, for example, over a period of six weeks. There are several mechanisms by which the tumor can have resistance to the chemotherapy. So different modes of molecular mechanisms, such as the following, the ones that are presented here in front of you. And here, okay, this would be the more common mechanisms for the two drugs that are quite notorious. For having a resistance. Okay, so you have your etoposide and methotrexate, and this would be the different mechanisms for chemo resistance. So in the paper, in this paper by Kim and colleagues, they showed that the following factors that can be seen in the patients with resistance to the first-line chemotherapy would be a tumor age of more than 12 months, number and site of metastatic organs, so more than two metastatic sites, and incomplete previous treatment. So in our patient, the only evident risk factor is tumor age of more than 12 months from the initial of emaco shifting onto the next salvage drug. Okay, so this would be now our go-to for our salvage. We usually give a platinum etoposide-based component. Okay, so we do the EPMA, okay? Because again, this shows a high cure rate, around 82% of high-risk GTN, who failed the initial multi-agent chemotherapy, which is emaco, would also have a higher cure rate with the platinum-based. And this is responsible for survival in 53% of high-risk GTN. So other, this paper by Ananta Raju in 2019, in the International Journal of Gynecologic Cancer, looked at 82 high-risk GTN patients with emaco resistance. And they looked at the clinical response, survival, and factors affecting outcomes. And these were the different combination, salvage combination chemotherapy that were given with these patients. So the emaco followed by MIEP, or MIEP followed with VIP. So these are all the question that was raised a while ago at the end of the presentation, what other chemotherapeutic combinations can be given to our patients salvage, if she comes back again with recurrence or relapse or an increase in the HCG titer. So after giving your TETP, there are a gamut of combinations that you can give, but none would probably as effective, will be as effective as emaco. Once they fail emaco or MIEP, and then it's such, it will already be like a free-for-all for all these other salvage chemotherapy combinations. So now the question comes in whether an adjunctive procedure should be done in this patient. And I think this has already been, some of these were mentioned by my colleagues a while ago, such as the irradiation and even the hysterectomy. So in my institution, our usual route or our usual procedure would really be hysterectomy. And if possible, depending on the size, the location following the TOMODA criteria for the lung lesion, we can actually refer this patient for excision, but I'm not so sure regarding this patient. Okay, so the complete response to salvage therapy would still be around 80%. So relatively still a good survival for our patients with GTN. And the factors for remission and survival would still be the beta-HCG level at the start of the salvage therapy, and would actually be the beta-HCG levels, and probably the presence or absence of other metastatic lesions, especially distant metastatic lesions. So some words on TPTE, in the Philippines, we actually shy from using this, aside from the fact that it's quite expensive. I don't know if it's a genetic or it's a sort of a ethnicity, based on ethnicity, but most of our patients show very, very toxic reactions to this combination. So we would rather go with TPTE because they really have, they show severe adverse reactions to the paclitaxel component. So again, I'm just showing you the different choices that you can give for this patient. Probably if she again relapses, we would go the route of TPTE, but because she already has neuropathy, I might follow the route of Dr. Ray Osborne and just make sure that we give etoposide and see, or just decrease the doses of the different drugs that are given. So other additional agents that are out there now, but with potential ability to cure treatment-resistant TPTE and would be the following, but we don't really have, I personally don't have an experience with using these other combination agents. So for adjuvant treatment, we're quite, I'm quite aggressive with the surgery. I'm used to doing surgery for patients with GTN, and this would be the reasons, the justifications to do adjuvant surgical intervention. And here, if this patient comes back again with such a high level of HCG and still a large tumor, depending probably on the risk for this patient to undergo surgery, I have seen a lot, well, I don't know if Filipinos and Ugandans would have same characteristics in terms of constitutionality. So like we're hardly individuals, so I'm not so sure regarding the ability of this patient to tolerate the procedure. So other adjuvant surgery that can be utilized to be able to control the bleeding and thus cure the anemia in this patient would probably be embolization. But this is more for the symptomatic approach to the on and off bleeding for this patient if it does recur. Okay, so there. So I would just like to show you a patient that we have right now in my institution. This patient presented with us, initially she was thought to have cervical cancer from a private institution, and it turned out that she has a very high HCG. So this is, I think really GTN with a cervical metastasis. And after induction chemotherapy with EP and followed by going back to EMACO and embolization, this is now the picture of her current, the current picture of her cervix after four courses of EMACO and an HCG level of nine is seen here in this picture. So after the seventh EMACO course, of which that seventh course is the first cleanup, it's almost back to normal. Okay, so just to show you what we did in this, for this patient to control the bleeding initially, since we cannot, this patient is quite young, no? So we just did embolization to control the bleeding. Okay, so we actually have two patients currently with the same presentation. So this one, this is another patient. She's younger, but look, chemotherapy is really very, very good at eradicating and almost making the tumor disappear there. So a big improvement, okay, from a baseline of 1 million, 1.3 million here on the left most, now down to 1,464 after only two courses of EMACO. There. And now this one, just a month ago, is 30, level of 30 for the HCG. So the vaginal meds, vaginal cervical meds is almost gone. So these are the different adverse effects of chemotherapy and looking at the chemotherapy-induced peripheral neuropathy. Okay, so this can also be accompanied by motor and autonomic changes of varying intensity. So the most neurotoxic chemotherapeutic agents are usually the platinum-based agents, as well as the toxin. So it's really no wonder that this patient is complaining of so many urologic peripheral neuropathic complaints. So there. So the choice of what other drugs to give, I'm now thinking if we can still go back to EMACO in this case, given that she has already these types of side effects. Okay, so we might have to refer this patient also to the multidisciplinary unit to treat this adverse effects of chemotherapy. So my take for this patient would really be to convince her to undergo surgery, especially if she's already having so much adverse effects from the chemotherapeutic drugs, plus the fact that she is a poor follow-up. She has problems with compliance. So I'm not so sure with your protocol right now in Uganda regarding surgeries during COVID pandemic. And of course, always make sure that we treat the complications as well with the chemotherapeutic agents. So if you were to ask me what chemo agents to give, of course, I would really like to see and assess the patient, but I would like to think that I can still go back to EMACO in this case. But I would rather do the surgery first before going to the chemo. Thank you so much. Thank you, Doc. Thank you so much, Doc. Can I come in? Questions? Yes, go ahead. Okay, Doc. Thank you so much for the presentations. I guess-

gestational trophoblastic neoplasia

trophoblastic tissues

metastasis

cure rate

beta HCG

chemotherapy