"Tratamiento de Tumores Neuroendocrinos Avanzados" con Jaydira Del Rivero (LACNETS)

Hello everyone, I am doctor Yadira del Rivero, I am an oncologist and I am also an endocrinologist who is working at the National Institute of Health and today we are going to talk about the treatment of advanced neuroendocrine tumors. First we are going to discuss what the anatomical distribution of neuroendocrine tumors, as you see here, the tumors, not seeing that they cannot occur anywhere in the body, among the most common neuroendocrine tumors, as you see here, the small intestine is one of the most frequent neuroendocrine tumors in the body, and the neuroendocrine tumor is also found. of the pancreas and the neuroendocrine tumor of the lung, as you see here, these are the most common neuroendocrine tumors, but there are also other neuroendocrine tumors that are less common but are also seen, one of them is the neuroendocrine tumor of the colon and also the rectum and there are other neuroendocrine tumors as you see here that they are less than 3% of neuroendocrine tumors among them are thyroid cancer or medullary thyroid cancer the cold as it is taken and the para ganglion ma and there can also be neuroendocrine tumors In other parts of the body, such as the ovaries and the cervix, the incidence of neuroendocrine tumors has increased in recent decades.

As you see here, there is a very marked increase in recent decades in terms of the incidence of neuroendocrine tumors. You see here. For example, in the blue line this has increased the incidence of neuroendocrine tumors of the lung as well as of the small intestine of the rectum. There are also neuroendocrine tumors that have also increased the incidence of the pancreas of the stomach and thus many neuroendocrine tumors. That means that during the last decades We are seeing more and more neuroendocrine tumors and why is that one of the things that we think that the incidence of new neuroendocrine tumors has increased is because we do more diagnostic procedures for example colonic spit endoscopy there is also a diagnostic image to detect the neuroendocrine tumors and that is cali 68 that has also helped us diagnose the different neuroendocrine tumors that are found throughout the system.

There is also one of the causes that we think is why there is a higher incidence so they took neuroendocrine tumors, it is because there may be some changes epigenetic changes due to these epigenetic changes plus diagnostic procedures it may be that for that same reason the incidence has increased but at the same time we have to also treat these neuroendocrine tumors because as we are going to discuss later these autocross tumors also tend to metastasise. caesar and we will talk more in detail about that now as to the classification and grade of endocrine tumors are found or divided into two groups the first group is the well differentiated neuroendocrine tumors which can be either grade 1 grade 2 3 and we are going to talk about that in a moment and the other group of neuroendocrine tumors is neuroendocrine carcinoma, which are more aggressive in terms of well-differentiated neuroendocrine tumors, grade 1 is when it is 15 xxi, less than 3% is sold and that this is the xx that you see, the 15 that you see reflects the tumor activity and that also helps us determine the proliferation of the tumor and is a marker of tumor proliferation, as you see here, grade 1 of the neuroendocrine tumor. differentiated the quiz exists they see is less than 3% the grade 2 the 15 that they know is 3 to 20 percent and the grade 3 the 15 that they know is more than 20% but normally it is less than 55 percent now in the neuroendocrine carcinoma, which is much more aggressive, normally the tumor cultural activity is much higher and in these types of tumors the treatment for the most advanced tumors is chemotherapy and we are going to talk more about that now in terms of the classification of these neuroendocrine tumors.

We already discussed that there are two groups, the well-differentiated one and those that are neuroendocrine carcinomas that are more aggressive. It also helps us to differentiate what the tumor activity is depending on the xx and they know, but at the same time the images are also important for the diagnosis. of these neuroendocrine tumors, well-differentiated neuroendocrine tumors, pp gallium 68 is an imaging study that is very important to determine and also diagnose neuroendocrine tumors. Now, when these neuroendocrine tumors are more advanced, they are more aggressive, these neuroendocrine tumors no longer have the possibility of stage 68 because they begin to lose the somatostatin receptors and we are going to talk more about that but those more aggressive tumors are more positive in the glucose receptor which is the pp so we are going to talk more about that also in terms of systemic treatments of neuroendocrine tumors we are going to discuss each of them but it is important that every patient who has a neuroendocrine tumor, especially one that is advanced or already has metastasis, is important to discuss the possible treatments with a team that is specialized in neuroendocrine tumors and here they are The different systemic treatments The first systemic treatment that I am going to talk to you about is the somatostatin analogues, we have two of them, which is obstructive or rapid lan.

We are also going to discuss a little about what radionuclides are, which is the last radioactive one and We are going to also talk about when this radioactive news is used other systemic treatments to targeted therapies that those are pills that are given and we are going to discuss more about that but targeted therapies are those that are based on the knowledge of the molecular biology of neuroendocrine tumors we have two treatments that have been given in different types of neuroendocrine tumors, which is this and we also have chemotherapy chemotherapy there is a chemotherapy treatment normally it is two medications that are given together and we will talk in more detail when gives the chemotherapy and in what type of tumors different types of chemotherapies are given.

We are not going to discuss now the analogues of soma christina. The majority of well-differentiated neuroendocrine tumors express somatostatin receptors, approximately 80 percent, so in those patients who express statin statin receptors, these somatostatin analogues can be given, which have a double role, one that controls tumor growth and the other role that somatostatin analogues have is that they control hormonal production. We already discussed that there are two types of analogues that maximize that either objectivity and creative lnd these medications can be given every 28 days also if there is excess tumor production it may be that instead of every four weeks it can be given every three weeks to also control the symptoms of hormonal production but if these They are resistant to the control of hormonal production.

There are also analogues to this morning that have an immediate action. These ones of operability that can also be given as injections and have an immediate action. Now we are going to talk about what it is in the lipid rays and let's to discuss what gallium 68 is, as to those who see the test with gallium 68, it is the most sensitive for the functional evaluation of well-differentiated neuroendocrine tumors, as you see here in the left drawing, you have a scintigraphy of another kilo, this means Previously, to diagnose neuroendocrine tumors, there was a camera of the object, but this is no longer used as much because we have cardio 68, which is an image that can more than diagnose all the lesions of the neuroendocrine tumor.

You see here that in the face as a graphic from another life, the tumors are more blurry, but you see here in French 68 the tumors in a dogma look more defined, so in this image that helps us diagnose neuroendocrine tumors, it has been very useful not only for diagnosis but also for treatment and we are going to discuss that now what are the fundamentals of applications diagnostic prognosis means that it is a combination of the terms of therapy and diagnosis we discuss that to diagnose well-differentiated neuroendocrine tumors we are Using calcium 68, that means, as you see here in this drawing, that the neuroendocrine tumor cells on the surface of the cell have a receptor, those somatostatin receptor receptors, so you have to find a link to work to register that receptor.

So that is what we also call what is the Teran Gnostic application because to make this application we can not only diagnose the neuroendocrine tumor but it can also be treated with the radioactive office and the therapy with radioactive peptide receptor nuclei or the radioactive office is a gnostic track radiation that can be administered systemically to treat metastatic disease and the effectiveness is also determined due to the proximity and retention of you see here to the tumor that is a study that was done that was published in 2017 this was the study that the rda approved for the treatment of neuroendocrine tumors diesel ute ctera you see here that these patients who were included in this study were neuroendocrine tumors of the small intestine but something that I want to teach you here is that in this study there was beneficence of what What is the progression-free survival?

The patients who received radioactive information are in blue and the patients who received optra time are red because this was a study that divided the patients into whether they received radioactive information or who received the Austrian injections. time and you see here that the patients who received radioactive lutetium have a tremendous benefit in terms of procreation-free survival. This means that the patients who received this type of treatment could see the tumors and the tumors were more than they did not progress, which is what which refers to progression-free survival. They prescribe every two months, it is very important that the patients who receive this treatment, as I told you before, have to understand positivity in Carlos 68, as you see here in this drawing, here is a patient who had a PET Cali 68 who has many tumors. neuroendocrine and after you see how it improves after four cycles of radioactive justice as you see here that is a diagram of how radioactive news infection occurs again age there are four doses in total of four doses that are given every two months We are going to talk about targeted therapies, they are two types of targeted therapies that occur in neuroendocrine tumors, one of them is tyrosine kinase inhibitors or multi-kinase inhibitors.

These targeted therapies are based on the molecular biology of the neuroendocrine tumors that have given rise. led to the development of multiple studies that have evaluated the effectiveness and also how readable these medications are due to the molecular receptors that these neuroendocrine tumors have, as I already told you, one of them is tyrosine kinase inhibitors such as zenit nor persona inem has been given in patients who have neuroendocrine tumors of the pancreas. This has an angiogenic extract, which means that it blocks the tumor blood vessels. This has been approved due to its effectiveness in a phase 3 trial and we will discuss later what They are clinical trials in neuroendocrine tumor of pancreatic origin.

Another targeted therapy is the protein inhibitors in the name of this medicine. I hope that the efficacy has also been demonstrated in several trials. It is easy 3 in neuroendocrine tumors, whether pancreatic, intestinal or lungs we are now going to talk about chemotherapy in terms of chemotherapy who are those who receive chemotherapy and we also have to discuss as we discussed previously which are the well-differentiated neuroendocrine tumors and which are the tumors to the newell carcinomas 2 grains that are more poorly differentiated, as I told you before, remember that neuroendocrine tumors are divided into two groups, well differentiated people and those that are poorly differentiated, it is important to know that because due to which group this neuroendocrine tumor is found, they have to have certain specific treatment here, for example chemotherapy for well-differentiated neuroendocrine tumors there are two types of chemotherapy that give each other an important thing that I want to mention that neuroendocrine tumors of the pancreas are more sensitive to chemotherapy, not necessarily those of the small intestine and two types of chemotherapy have been used in doublets one of them is streptokinase with 5 flower has been now that treatment is given more in Europe than here but here we use a lot what we have or the measure in combination with capecitabine and that has also been found to be effective In patients who have neuroendocrine tumors of the pancreas, now the tumors of the neuroendocrine carcinomas that are more poorly differentiated, these demonstrate a high response rate to chemotherapy and we have combinations of chemotherapy, either cisplatin elkar bocatín or in combination with topo been this You have to talk in more detail with your oncologist to decide what treatment should be given depending on what type of neuroendocrine tumor you have and you also have to discuss what the effects are.side effects of each of these drugs, now we discuss where neuroendocrine tumors are found, we also discuss what the two groups of neuroendocrine tumors are and the grades of neuroendocrine tumors, and we also discuss what treatments are available for those neuroendocrine tumors that are more common. advanced but also in terms of the treatment of neuroendocrine tumor, we as a specialist have certain obstacles because there are few therapies approved by the fcya but the questions we have is when and what combined therapeutic approach should be used, another question we also have is how long should it be used?

You should continue the treatment if you respond well we continue for a long time what is the time that should be given and in which group of patients should a particular treatment option be used because as we know certain treatments are more effective on the tumor neuroendocrine tumor of the pancreas other treatments may be more effective in the small intestine and so we have to know what option should be given in order to treat the patient and that is many answers that we have as an expert in this neuroendocrine tumor is also one of The questions we have is what is the role of immunotherapy in our mood, in the most aggressive way, so in terms of treatment, El Orondo believes there are still several questions that must be answered, so we also work, one of the jobs that What I do here at the National Institute of Health is study these neuroendocrine tumors because there is a comprehensive classification system that incorporates the clinical stage of the tumor, genomic and epigenetic alterations, and genetic expression profiles.

This could serve to better define what biology is. of these neuroendocrine tumors that could also help us establish correlations with clinical results and also to understand these neuroendocrine tumors it can also help us develop more effective therapies but something that I want to mention is that patients who live with non-endocrine tumors that made families also face obstacles The only one of them is because a lot of time passes by the time they are diagnosed or the patients are diagnosed with neuroendocrine tumors. This means that many times the cancer is identified in advanced stages. There are many medical centers that have limited experiences with these tumors because the Patients sometimes have to look for experts and sometimes those patients have to travel outside the region where they live to see a doctor who is a specialist in neuroendocrine tumor.

As we discussed previously, there is no standardized treatment guide that tells us these are the treatments that It must be given in terms of phase 1 to phase 2, so sometimes we have to look for what to see in the guide so that we can decide what is the best treatment for a neuroendocrine tumor patient, which is why we have a very disciplined team to also decide what is the best treatment but sometimes this creates some uncertainty and patients want to seek more answers about this and sometimes patients can feel isolated because this neuroendocrine tumor is considered a rare neuroendocrine tumor but at the same time we talk previously that the incidence has increased but patients still feel isolated so what we are working on is that we want to develop a network of participation of national and international patients with easy access for research into neuroendocrine tumors and it is also important that we We have in collaboration with patients with support groups, for example English is a support group that has been focused on educating patients who have neuroendocrine tumors and just like acne, there are also other support groups that also look for someone to communicate with experts. also to answer one of the questions that we discussed earlier that will also address the needs with neuroendocrine tumors and also increase patient access to also have clinical trials and treatments that are more effective for neuroendocrine tumors neuroendocrine tumor researchers as well They face certain obstacles to develop more treatments or to develop cures, one of them is because there is a lot of time, it is necessary to accumulate patients in clinical trials, sometimes you have to have multiple care and nar since it is necessary for patients. who have these neuroendocrine tumors because as we described previously, these neuroendocrine tumors can present clinically in different ways and they can, as I explained before, also be found anywhere in the body, so it is necessary to have a multiplier team to treat these patients with neuroendocrine tumors and also treat these patients who have rare cancer syndrome associated with the neuroendocrine tumor but that can also be an obstacle if you are not in one center in all specialties to see these neuroendocrine tumors this can also be a lack of coordination between teams and this can create cities that limit the efficiency of clinical trials.

One very important thing I want to mention is that in terms of neuroendocrine tumor research, there is limited diversity of cell lines and there are no preclinical models that are validated and for that reason many of the preclinical studies in which certain drugs can be treated we see this q2 every day there is another important thing that sometimes fundraising for research is difficult and there are fewer sources of grant funding but we think that having a collaborative research network for neuroendocrine tumors would promote the development of new therapies and standard care for patient care, one of the things I always say regarding the care of neuroendocrine tumors is that we must have collaboration between patients, doctors, researchers, researchers who are in laboratories, clinical researchers, and also with companies. drugs, all of them have to work as a team for us to be able to reach and have new therapies and more effective therapies for neuroendocrine tumors.

We here in the work that I do for us to be able to answer is one of those questions that we discussed previously, we and here in the National Institute of Health we have a study of this natural history of children and adults with neuroendocrine tumors or with neuroendocrine spaces. This is a protocol that is part of a protocol for rare tumors also in children and adults because we want to do this because we want to characterize The natural history of neuroendocrine neoplasms These data include all patient demographics Clinical characteristics Patterns of disease progression We also want to understand the response or lack of response to certain therapeutic interventions when there is a recurrence of the disease and We also want to understand the general survival of all neuroendocrine tumors because we believe that by having all this clinical information we could understand more the biology of these neuroendocrine tumors to be able to develop more effective therapies in this study that we have here in the institution in the institution where I am. working is a study that is long term this is we want to study all patients with neuroendocrine tumors in a way from our perspective it means that everything that happened in terms of the treatment in terms of the clinical aspects but also in a prospective way we want To say that the patients that we are going to study in the longer term can be done remotely or the patients can also come here to our clinical center of the National Institute of Health.

We are also studying patients and biological relatives or certain carriers of mutations. of predisposition to germline cancer, in one of the talks I gave previously I mentioned that the majority of neuroendocrine tumors are sporadic and there is a group of neuroendocrine tumors that are associated with a cancer predisposition syndrome, one of them, for example, is The one we had discussed about von Hippel' is not one of them. We had also discussed what multi-endocrine tumor syndrome is. We had also talked about that and we had also talked about others like neurofibromatosis type 1. These are certain conditions that are caused by cancer. germline that are also predisposed to neuroendocrine tumors in this part of the study we also want to be doing clinical and laboratory evaluations we also have to obtain information from the patient about the psychological and social functioning because we also understand that having this diagnosis this can also cause a lot of stress As for the family, as for ourselves, we also want to understand what the deficiencies are in terms of social psychological functioning so that we can also help.

What we do in this study is that we obtain the tumor to also make certain molecular profiles in the tumor. in the blood and also in the saliva because we also want to extract the DNA to do many studies later and also this study is not helping us to have a repository of these tissues to make biological samples to do future studies because we want to do this because as we discussed earlier we want to have more therapies for neuroendocrine tumors that are more effective and we want to develop new therapies we also want to develop certain endpoints for certain clinical trials and also for us to have screening guidelines and if these 1,121 because it can also be a hereditary way so we want to understand all this in a clinical way so we can develop new therapies in the not too distant future how this study works either the participant himself or his doctor who is treating him refers him to us so we with we put the patient to the rare tumor protocol and that can be done externally the patient does not have to come here with us to see us we collect all the clinical information, the pathology, the image reports and we have a multidisciplinary discussion in which we come together as a team and we provide an opinion to the patient and the doctor at the same time to obtain the tumor we do molecular and genetic analyzes once the patient is participating in that study whether it matures or we follow this patient in the rare tumor protocol it can be If a certain medical intervention is needed, we can refer this patient to the treatment protocols at the National Institute of Health or you can also participate in what is your protocol for this protocol for rare tumors.

You see here my clinical interest in me. experience is in neuroendocrine tumors and so that's why we have a protocol to study neuroendocrine moles patients deeper than dating we connect first the two participants can do it from home they don't necessarily have to come here here at the national institute of health but we have a medical and family history because we want to understand what genetic, physiological and environmental factors can contribute to the development of these neuroendocrine tumors. We also want to understand what certain symptoms or certain clinical characteristics are that are interfered with or that can interfere with what the state is. physique of patients with neuroendocrine tumors one of the things we want to understand is if a patient does not have depressive symptoms fatigue if sometimes they can have cognitive functioning we also want to understand those social and psychological aspects related to the neuroendocrine tumor We believe in the characteristics of cancer due to the image of that pathology and we also do a complete sequence of the tumor because we want to understand in a more molecular way the biology of these neuroendocrine tumors.

Now the patients who come here to the clinical center we have apart of the clinical data that had been mentioned we also have the blood to study whether the success of blood cells or immune cells as the immune system responds to the presence of that neuroendocrine tumor and also with this information and when we have tumor in us we also want to establish new cell lines and preclinical models to then be able to treat different drugs and see that all of them can be effective for these tumors. We also have genetic counseling and all the results that are obtained from this information are also results that are available to the patient.

This has been made due to an initiative that is a rare tumor initiative, I have to mention that Dr. Reilly and Dr. Widemann are the directors of this initiative, which is an initiative for adult and pediatric patients with rare tumors and then once we obtain this information We also want to determine the happiness for current clinical treatment trials. What is the objective of this protocol for neuroendocrine tumors? We want to establish a mechanism for the referral of patients. Have a systematic compilation of allEpidemiological and clinical data 30,000 tumor samples We also want to establish a classification system integrated by the clinical stage of the tumor, the genetic and epigenetic facilities and gene expression profiles aswad that can help us better define the biology of neuroendocrine tumors We are going to follow these patients long-term during the course of the disease to better understand the natural history and what the causes or biological and clinical characteristics are and also that allows us to also identify certain symptoms of hereditary cancer as we mentioned, most of them are sporadic, we do not know which one. the cause but a small percentage of these neuroendocrine tumors may be associated with a hereditary cancer syndrome as a friend we have discussed before and other terms that we have studied these patients but we can understand if we can do something preventively to not now what are the clinical trials we had discussed about what neuroendocrine tumors are about the treatment we discussed what our this approach in terms of helping patients who have neuroendocrine tumors and what our goals are for doing this study but also in terms of that I want I want to discuss with you and define what clinical trials are.

Clinical trials are research studies that prove that new medical approaches also work. Each study tries to improve ways to prevent, detect, diagnose or treat a disease. Clinical trials can also compare a new treatment with a treatment that is already available and the objectives of those clinical trials is because we must want to know if these clinical trials are safe and effective, we are going to discuss the different phases of clinical trials because I imagine that this when a patient enrolls in a clinical trial there are different phases of clinical trials that I want to discuss with you for example the phase 1 clinical trial is when researchers test a drug or treatment on a small group and the purpose is to study the drug or treatment to find out if those treatments are safe and also identify what the side effects are Phase 2 is when this drug or treatment is administered in a larger group to determine its effectiveness and study more deeply what these side effects are Phase 3 is when the drug is administered in a larger group of people to confirm its effectiveness because in phase 1 it is already said that it is effective but in phase 3 we want to confirm the effectiveness with a larger group of people and also to know what the side effects are and compare them. with the treatments that I did, they have been given that they are approved by the fd, which are the ones that we give initially and we also want to know if the drug can also be used in a safer way. phase 4 is when after the fd approves the medication and it is Available to the public the researchers are following these patients in a long-term way to learn more about the drug and what its most optimal use is now we are going to discuss certain clinical trials that are at the national institute of health where they are currently working for tumors neuroendocrine we are going to discuss what is the phase 1 and phase 2 clinical trial we heard that the phase 1 trial is what are the side effects and if it is safe to give it and the phase 2 clinical trial are that we are going to determine what it is the effectiveness of these drugs so we have a study that is for neuroendocrine carcinoma it is a study that is lulac terine in combination with another drug called verso usher tiff that means that the combination of these two can be synergistic that it could be that the Two together can be more effective than if they were seen alone.

The primary investigator of that study is Dr. Thomas. He is my colleague. Here we are working on neuroendocrine tumors. His specialty is neuroendocrine tumors of the lung, but they are those that are the most aggressive and in In his study he wants to determine what is the maximum tolerated dose with the combination and after that once that is determined then he is going to evaluate what the efficacy is and in terms of the clinical response rate and we want to determine what the disease-free survival is. Progression and overall survival means how long the tumor is without growing and how long you can live with the amount of tumor you have in the long term.

Those are the questions we want to investigate regarding this study. This study is open. We are in the process of rolling out. patients here we heard before what the fundamentals of the diagnosis are we explain that the trans gnostic what does diagnosis and treatment or treatment and diagnosis mean we also talk about what the radioactive beginning is and what the effectiveness of these tumors is and it is a A study that has been published and that has been approved by the SDA has tested this drug for neuroendocrine tumors, including the small intestine and also the pancreas, and we know that this type of drug also causes neuroendocrine tumors to establish themselves for a certain period of time, but one thing What I want to mention is that we know that this type of treatment is effective but we want to make it more effective.

We want to make that tumor help neuroendocrine tumors become much, much smaller, so we are doing a clinical study of a combination of drugs. with the multi closure of active but before that I want to explain to you what is the reaction mechanism of the radioactive trade the 'radioactive news is a type of radiation that can already be a direct effect, it means that it can be damage to the DNA or it can be An indirect effect means that it is accumulating reactive species of superoxide but when this happens it puts the cell under stress and this can also damage what is the DNA as you see here further down in this figure once there is an injury in The DNA that does not pass in the cell wants to repair itself and enzymes that are the enzymes of the park, as you see here, once it is above, they do what they want the DNA to repair and sometimes when those pass, it may be that the tumor no longer Either the treatments that are given are no longer as effective, then there are medications that are on top of it because they do not continue to prepare the DNA, so we think that a potential synergy with DNA repair inhibitors with Lola for the Labrit is a drug that is already It has been tested for what is breast cancer, also prostate cancer, ovarian cancer, these are medications that have been tested precisely by this mechanism and that this help must prevent the cell from not repairing itself, so with that idea we We have a clinical trial of the uterus in combination with the wall because we know that the kettle is a type of radiation that this type of relationship causes damage to the DNA by causing DNA damage so the cell wants to repair itself products we want to prevent that repair to make the lottery more powerful more effective so that is a study as I had previously explained that it was the phase 1 phase 2 study but the primary objective is to determine the safety and tolerability of the combination of the labrit with the noticion and that is a phase 1 phase 2 and also determine what the response is in terms of and whether the tumors can shrink after four cycles we also want to obtain what the overall response rate is and we also want to understand what is present in the free progression of those tumors that is a study that is active not now and we are going to start enrolling patients in the next 12 months now we are going to discuss about another neuroendocrine tumor that neuroendocrine tumor is the chromosome and in order to breed older people I previously discussed that those are tumors less common than the other neuroendocrine tumors that I explained to you that they are from the small intestine that they are from the pancreas these neuroendocrine tumors that these are called fi or formosa and take and for ganglion ma they are tumors that produce catecholamines so what are the catecholamines are produced by the gland adrenal and are what make you feel that the pressure has to rise the heart beats faster than what we call when it is the feeling of fright the feeling that something is going to happen that feeling you have is due to the realistic catecholamines but sometimes these tumors can produce much more catecholamines so those symptoms are more pronounced they are rare and there are no treatment options they are limited when there are metastases but one thing I want to mention here is important is fibroids there are shots the for quantity they maintain receptors of somatostatin more than 90%, also as I had mentioned with our neuroendocrine tumors of the small intestine and pancreas, this is to mention Dr.

Pasaia, who is the researcher of this study of neuroendocrine tumors, it is the natural history of the bio chromosomes, here we have For example, a functional study, an imaging study that is implemented in patients who trust cards and also for what they have created. For example, here we have an image between what is the mv, which is a diagnostic study of the foot as it is taken here in the second we have a study of what glucose or df is, here it is a glucose study that also helps to diagnose, he saw how they were taken for gandia more but as you see here gallium is a study that is very very good for diagnosing the patients in a contest for can cream because like that classic day previously, these patients have sistine semac receptors, which is why this diagnostic study is an important study based on that, I had already mentioned that reactive exercise is given and approved for neuroendocrine tumors but here at our institution we have this radioactive nutrition study for patients who have skin like oil mail for cancri omar and the objectives of this study is that we also want to improve the progression-free survival of these tumors in patients who have positive somatostatin receptors it is important that one must know that to participate in this study you have to be positive in the petal the other secondary objectives are to evaluate the tolerability we also want to know what the objective response rate in terms of tumors The treatments can also reduce the fact that we want to understand what the progression of the tumor is.

We also want to determine what the biochemical markers of these hormones are. Also, as I explained before, this forms symptoms. They produce a hormone that is catecholamines, which are metals. fine then we want to know if giving this drug can also decrease these plasma biochemicals that can also help reduce the symptoms associated with the cold how to take it how to reduce blood pressure how to reduce heart rate sweat so those are the symptoms that are related to the excess of catecholamines, they are killed fine to mention doctor franklin is the nuclear medicine doctor that with the rascal I am working on with this study for the foot how to eat here in cream we also have a phase 2 clinical trial for it what is the fie with exactly for cangri ama what is the single measure theme or the themes or the measuren combination or the wall this as I had already explained to you before in combination with the themes or life may be that they are more powerful more effective for these neuroendocrine tumor, which is to say how it is taken.

I am the main researcher along with Dr. Pérez who is in Lana Fárber. We have this study that is open and we are enrolled patients with neuroendocrine tumors with neuroendocrine tumors like the river, as if it takes one thing that What I want to mention is that we want to determine if the effectiveness of an agent alone or a drug only with the subject or the measure or the combination, which is going to be more effective, then something that we have to mention because the subjects or the measure are already It is occurring in patients who have forms, there is a take, but we want to know what the difference is and which is more effective.

Now I want to talk to you about the song Manuel Do, which I did not mention before, which was neuroendocrine carcinoma, what are some of the treatments that can be used? try normally are that respond to chemotherapy but I also want to tell you that there are clinical trials of neuroendocrine carcinoma and you can find this if you go on the internet and if you put what is the clinical trials dotcom you can find information about all the studies available for neuroendocrine tumor but here today to mention some of the clinical studies that are for the casino major el domino advanced she wanted in various therapies and this information is going to be available to you and so that you can come back and have access to this information one thing that I want to inform you here is that as one searches for clinical wisdom or research studies especially when it refers to treatment for a specific cancer then as I had already mentioned before you have to go to the internet and on the internet you put what the clinical trailers dotcom is and this window will appear and here you can put what the condition is or what type of tumor you have, for example I put neuroendocrine tumor and here in the second it can be put the name of the researcher what is the drug you want to see or you can also see what is a number sometimes those clinical studiesThey can have a number as I had shown you in the previous slide and also because those studios can also be in various parts of the world, you can also have here what country you are in so you can put here if there are studios near you now when you have already decided who wants to participate in the clinical study what are the questions you should ask your doctor one of them is what is the purpose of the study or another question is why the researchers believe the approach may be effective what are the risks and The possible benefits are something that must be discussed in very detail with the doctor who is treating you or the doctor who is helping you to participate in clinical trials, as well, since they may also ask you what type of therapies and procedures or tests you will have during the course. clinical trial and how participating in this study could affect your daily life.

These are questions that are general questions, but they are questions that can give you a lot of information about the stage of the clinical trial and they are questions that can also help you understand what the purpose of the study in which you want to participate and what are the tips for asking your doctor about clinical trials do you consider the possibility of always bringing your family or friend I know that during the pandemic that was restricted but now that Now the cases are lower, more people are vaccinated. I think that now there are more people who can go with a family member to help them and so that they can also help them with these questions or record the answers when you ask your doctor too.

You can plan what question to ask and never hesitate to ask new questions. It is very important that all the concepts of the clinical trial are clear to you and you write the questions in advance so that you always remember them all, even if you do not remember them now or you can put them in your mind. your notebook and then ask him another time when you see your doctor and also write down the answer for when you want to go back and see the answers are available sometimes when you go to the doctor there is a lot of information that one acquires and sometimes it is difficult to understand because That's the same thing, I think it's important that when you see your doctor you have this available for you so that you can always come back and if you have any questions you can always ask us again remember that we are available for you and we want you to understand everything about the treatments they laid down in the doctrines and what are possible clinical trials in which you can participate and this is my last law of this presentation and one very important thing is that for the treatment of neuroendocrine tumors They need different medical specialists to participate in a tumor committee created to guide the management of the patient.

You see here that there are several specialists. The oncologist is the one who is going to give you the systemic therapy that we had discussed or the one who is also going to to decide if this match can be or can participate or if you are eligible for a clinical trial the endocrinologist is the one who always helps or for everything that is excess hormones the endocrinologist always has knowledge and can also help with excess hormones the Surgeon If you see a previous presentation in which I talk about how neuroendocrine tumors are treated, the surgeon can also have an important role in terms of the management and treatment of neuroendocrine tumors, as well as the nuclear doctor because they are the ones who They give the radioactive lutetium the crazy digest or the gastroenterologist because many of these tumors are found in the digestive tract the pathologist also helps us, as I mentioned before, we understand neuroendocrine tumors how they are classified what the grade is important because depending on the grade they are different therapies also the biochemist so that he can help with all the hormones that are being made in the neuroendocrine tumor and also the radiologist as well as this time a team that has to discuss all their cases so that we can also give the best information and we can also discuss what can be the best treatment for neuroendocrine tumor and by that I mean I want to finish my presentation first of all I always dedicate my presentation to Giovanna Idiot who is the founder of the class she she has been a person who has helped us to Let's continue fighting for the treatment of neuroendocrine tumors.

Her presence will always be with you. I also want to thank her and sallent. She is the coordinator of all the neuroendocrine tumor education courses. She works day and night to educate all patients taking neuroendocrine also lynch and who always helps us to get everything ready for you this information is spread to all of you anywhere in the world and also marí marí donleavy and dona gavin and cavia who are are very involved in what it is this acne organization if you have any questions please here is my email my phone number and any I am always available to answer some of your questions and with all this I thank you very much for your attention