Anastasia Zherlitsyna — timeline

(0:51 - 1:00)

Hello, hello. This is Igor from Manor. This is Egor, right? Yes.

(1:01 - 1:20)

Nice to meet you. Is Anastasia with you? You've already spoken, right? Yes. I see.

(1:20 - 1:34)

Well, I might need... Yes, of course. I can help you. In general, you speak English, right? Yes.

(1:36 - 1:40)

Excellent. Good. I see that the doctor has received all the documents.

(1:44 - 1:59)

Here's the PET-site, the color, and the biopsy. Now I'll try to dial her in. I'll ask her to come in.

(1:59 - 2:44)

Okay? Okay, thank you very much. I'll call her back. If it's possible, I can dial Anastasia on the phone.

Me: Yes. But we can call her by phone if you have any specific questions. If she wants.

(05:58) Doctor: Whatever she wants.

Me: No, right now she gave me the opportunity to manage things and to talk with doctors.

(06:09) Doctor: Okay. So she knows we're speaking.

Me: Well, she doesn't speak English freely, but if we...

Doctor: Okay. So we speak and then.....and then you can tell her.

(06:21) Doctor: So I'm going over to remind myself of what she spoke about last time.

So she was diagnosed in September 2022.

She was diagnosed with cancer.

She was diagnosed with liver metastasis and abdominal lesions.

And a pathology from the liver showed leiyomyosarcoma.

She began Taxotere, Pazopanib with significant nerolgical side effects.

(06:43) They changed it to GIST, and also in Israel.

And we seek its standing as SDH deficiency. And she began Imatinib.

And we said Matinib is a available drug for GIST, she should repeat PET, consider ???,

(7:09 - 7:25)

consider for the SDH deficiency and CKIT mutation, which are mutually exclusive, and genetic testing, consider Tempus, and follow up for the uterine findings. So let's see what you sent. So we have the revision of the PET, which they did here.

(7:26 - 7:59)

So in the PET, they wrote that the liver lesions and the gastric lesion are a bit smaller, but don't have any uptake, which is good. In the uterus, it's smaller. In the lungs, it's the same as before.

(7:59 - 8:28)

Let's see what is in the second document.

Me: Yeah, she's a long-time smoker, and also she was a very strong cyclist and hiker. So it's an interesting combination, and maybe her anomalies in lungs, they might be not cancer, maybe just some sort of-

Doctor: It doesn't have any uptake, so we don't really know.

(8:29 - 8:47)

I'm looking at the summary.

Me: Yes, I can briefly also repeat the story for you starting from, so very shortly before and starting from me. So at first, she was diagnosed with leiomyosarcoma.

(8:47 - 9:00)

That was the diagnosis of pathologist in state-owned National Cancer Institute in Kyiv.

Doctor: I remember you made such a clear summary. Yes.

(9:00 - 9:13)

Continue, yes, you can continue, right.

Me: Yes, and-

Doctor: And then the case was diagnosed, and- Yes. She began-

Me: Yeah, she received a couple of courses of chemotherapy treatment.

(9:14 - 9:35)

The last one was Trabectedin, I believe, yes. And yeah, and during that, she made oncomine genetic test, which found a CKIT mutation. But they didn't take action, they just thought that this is a very rare sarcoma with CKIT.

(9:36 - 10:13)

And we tried pazopanib, and it was very efficient. She had like a 10% reduction of her metastasis in a week, but unfortunately, she had PRES syndrome, which my doctor thinks it was sort of tumor lesion, or PRES, or she thinks it's sort of close things. And we needed to stop that, because she was hospitalized with hemorrhagic syndrome in brain, and she recovered from that during some time.

(10:13 - 10:45)

And we made, in April, we made another biopsy, already took biopsy from everywhere, from gist, from stomach, from liver, but we didn't touch uterus, because gynecologists found that it's very complicated, and it would be invasive to go there. And you asked me why they didn't take the sample of gist from the stomach, why they use it externally.

Doctor: Right.

(10:45 - 11:11)

Me: There were two reasons. At first, this equipment is present in only one clinic in Kyiv, and at that moment, it was offline. The second reason was that when in LISOD, they studied her stomach using cameras, they found, they told that there is no traces of that gist inside stomach, so it's sort of outside.

(11:12 - 11:47)

So it's not, so their opinion was that it's not in the stomach wall, it's not visible from the inside. And they used an external needle to take biopsy from this thing near stomach, so that was their answer. And biopsy, which you also reviewed in Israel, it showed that this is a gist, but you found that, you studied genetic files in front of me, on me, and you found this mutation.

(11:48 - 12:14)

And we suppose that we continue treatment with imatinib. Just, there was a question about SDH deficiency. I asked many people about SDH deficiency later, and all of them told me that genetics and SDH is secreted, SDH are mutually exclusive, and in this case-

Doctor: Right, I also told you that-

Me: More trust is being given to genetic sequencer.

(12:15 - 12:42)

And so SDH is much simpler test, and maybe something is wrong there, because genetic sequencer is a king of things. And she started receiving Glivec, which is original imatinib supplier, and on summer, she felt herself bad. Maybe that was after the chemotherapy.

(12:43 - 12:57)

She visited Germany, and German doctor told that this is, her feeling is from imatinib. So she felt like poisoning. She thought that this is intoxication, which was given by cancer.

(12:57 - 13:17)

So she also had problems with head, she couldn't concentrate. So she was like in dizzy state, she couldn't think, she couldn't read, and she felt constant poisoning, and bad feeling like from poisoning, vomiting, sort of that. Consciousness, yes.

(13:17 - 13:44)

But the PET-CT on August showed good progress, and also the good things were visual examination. The doctor said that visually it's not present, so they like touch the stomach, they palpate, but there is no, so at first, they were very condensed, and they could feel those things. Right now, those things cannot be seen from the outside.

(13:46 - 14:02)

So she started taking treatment. There was an incident during autumn, which she thinks might be because of the fake drug. So she took imatinib from another vendor, because that vendor wasn't available at that moment.

(14:03 - 14:16)

And she felt like-

Doctor: But she's been continuing imatinib all the time, right?

Me: Yes, yes. Even though she didn't feel well, but she continued it all the time? Yes, all the time, without any skips. And she felt immediately very weak.

(14:17 - 14:36)

Again, the head is clouded, she felt that it always goes into head, the head becomes clouded. And she felt like very strong depression and panic attacks, and like fear without any cause. When we took the drug from original vendors, those symptoms disappeared.

(14:37 - 15:00)

Right now, she says that she feels generally better than at summer, she can read, her head is not clouded. But she started feeling strange things, which she as hiker and biker explains as similar to muscular inflammation. So like her right side, where the liver is, it becomes stiff.

(15:00 - 15:11)

She feels pain in joints. And even it's appearance, it's rise of the temperature. And she feels like being cold, being like there is inflammation.

(15:12 - 15:35)

And she treats that exactly like inflammation, she just keeps herself warm, and drinking warm tea, et cetera, and it passes away. But she has such things reoccurring starting from autumn. Also, she has a big amount of like stomach effects.

(15:36 - 15:57)

So she says that she feels pressure in the right side. So she feels not very well after eating protein food or cola-goggle food. So she feels bloating, clotting on the tongue.

(15:57 - 16:15)

Tongue becomes black, stool becomes sticky. And she again feels it like poisoning. And she feels pain in the place where the pancreas is, behind the ribs, where usually the pancreas.

(16:16 - 16:27)

Again, so that's a reaction. She drank a lot of mineral water. Maybe she a little bit overdid that, it's hard to say.

(16:30 - 17:08)

And overall, she complains that she needs a lot to keep her from being anemic and being weak. So she does a lot of things like yoga, stretching, et cetera, and she spends like half a day in those exercises, because if she stops them, she becomes very quickly weak, the mind becomes clouded, and she becomes to feel worse and worse. And usually she has good activity starting from morning, but later in the day, she becomes weak, and she feels herself not well.

(17:08 - 17:40)

And she is actually very concerned about her state, but the oncologist doesn't see anything from her side, because she says that PET-CT doesn't contain any things which could be suspicious in this case. And right now we did PET-CT, next regular CT scan, and did some blood tests, which you can also see. And on those PET-CT, we have very small decrease compared to August.

(17:40 - 18:12)

So it's like decrease only one centimeter for the mass in the uterus, in the liver, excuse me, some decrease of the mass near the stomach, and some decrease in the uterus, which also raises questions, what is it then? So, and generally, the question is, so we can take more imatinib, like double the dose, but it would be double her intoxication.

(18:12) Doctor: No, no, we don't want to double the dose. We only double the dose if there is progression.

(18:13 - 18:24)

The disease right now is stable. It's, you said that in the PET in August, there was a good response, and now it's stable, which is good in oncology. We don't want to double the dose at this point.

(18:24 - 18:38)

We want to continue the same, because the quality of life is important for us, and it is working. It's considered a good response. I don't think if we double the dose, we will specifically get a better response.

(18:38 - 18:57)

Me: So we want to continue with the same response, the same dose. But we already have not much decrease in masses, so-

Doctor: Right, I don't think you can expect more than that at this point. I don't think increasing the dose will help.

(18:58 - 19:20)

I think it will only make the quality of life worse. Right now, she's feeling well, and the tumor doesn't have any uptake, so it's like sleeping, and that's the best we can usually aim for with metastatic gists.

Me: Well, but we had such a big decrease at the moment.

(19:20 - 19:27)

Maybe we can just take another drug at this moment.

Doctor: No, only if there is progression. When there will be progression, we'll switch to second line.

(19:28 - 19:47)

But right now, it's not according to the recommendations. The recommendations are, as long as she is responding, we want to continue with the same drug.

Me: Okay, so it means that if it doesn't decrease that much as we expected, then it is, and we cannot do anything here.

(19:48 - 20:00)

Doctor: Then what?

Me: We can't do anything to speed up the decrease.

Doctor: I don't know. No, but we also, like we are happy with the response that she has, and she has a good quality of life.

(20:00 - 20:08)

The tumor doesn't have any uptake. It's a good response for gists. As long as it doesn't grow, we are okay with it.

(20:09 - 20:36)

Me: Well, maybe we can somehow improve her feeling, her quality of life, because right now, she needs to work a lot just to stay, to feel good. Otherwise, she feels worse. And she has those strange symptoms, starting from autumn, with her right side being like inflammated, like that's her feeling.

(20:37 - 20:52)

Doctor: So... Again, her right side, what?

Me: Well, she calls that like inflammation. So it's like her right side becomes stiff, and she feels like symptoms of inflammation. She has pain in joints.

(20:52 - 21:02)

She has a rise of temperature sometimes. And the mind becomes clouded again. And yes, and she feels cold.

(21:03 - 21:26)

She feels dizziness. So like you're becoming sick, but... So again, as a cyclist, as a biker, experienced biker, she compares that to inflammation of muscles when you, for example, have a lot of them. And she tells that those symptoms started from autumn, and they repeat periodically.

(21:27 - 21:46)

Doctor: So... Okay, and they say she saw the neurologist and the neurosurgeon. And at least according to June and July last year, so the MRI showed a very small PRES that was left there. And they were okay with it.

(21:51 - 22:09)

So the oncologist agrees with me to continue the imatinib. The uterus, we don't know in the meantime. And then you wrote here... That she feels better than the summer.

(22:10 - 22:22)

She can read and take walks and small bicycle rides. And this is what you said, the muscle inflammation. It can be because of the imatinib or other things that she's feeling.

(22:26 - 22:41)

She needs to do a lot of exercise, which is a good sign in oncology if she can do a lot of exercise. She was taking counterfeit Glivec. Wow, that's what... And you switch to the old dealer.

(22:44 - 22:50)

It's different than what she had before the disease. Okay, that's what we have. And then you sent everything.

(22:51 - 23:09)

So I think I agree with your oncologist there to continue the imatinib in the same dose and repeat the patient another three months, every three months. And as long as it's working, as long as it doesn't grow, we don't want to change anything.

Me: Okay, I see your point.

(23:10 - 23:29)

I have probably then the question about SDH deficiencies. So it's believed to be mutually exclusive, but may it happens that the tumor has, for example, two cell cultures inside of it. And maybe it's a second cell culture has SDH.

(23:30 - 23:51)

So maybe it's a poly...

Doctor: Again, I didn't understand.

Me: So can there be that there are two types of cancer cells in tumor and the second type of cells has SDH and the first type has C-Kit? So can it consist of two types?

Doctor: Anything can happen. It's one explanation.

(23:51 - 24:29)

I think the most logic thing to do would be to re-biopsy and send it again to genomic testing and see if again, they see the KIT mutation and the SDH deficiency. It's interesting because usually these two mutations, usually both of them, the deficiency and the mutation are in all the cells of the tumor. So it can always be that, like you said, it's two kinds of tumors that are mixed, but it's not something we usually see.

(24:30 - 24:49)

So I would just check it again right now and see if it still is the same.

Me: Okay, so you think that state may change. So if we had CKit mutation a year ago, when we took...

Doctor: Right.

(24:49 - 25:17)

Me: So if we take the new biopsy, we might see a different picture.

Doctor: And another option is to wait until there is progression, as long as there isn't any progression and the tumor doesn't have any uptake. So probably there isn't a new mutation, but when there will be growth of the tumor, then to take a re-biopsy and check it again, because then we know there can be a new mutation that causes resistance to the imatinib.

(25:18 - 25:39)

Maybe not, we don't have to do a biopsy, but it will be interesting to see, to check the re-biopsy when there is growth.

Me: Well, it would be quite uncomfortable to wait until it starts to grow. So probably you think that we can take a biopsy right now and check for new mutations.

(25:40 - 26:06)

Doctor: We can, but it will be the same cells. We would just like re-check the technical test, the technical side of the test. We don't think the tumor in the meantime has new mutations because if the tumor had new mutations, it would maybe stop responding to imatinib.

(26:06 - 26:31)

So we can do it now just to validate the previous tests, but it also makes sense to do it after there is progression and check what changed since then. So both of them have logic.

Me: So there's no need to do that until there is progression, but it can be done to re-check the results.

(26:33 - 26:42)

But what? But it can be done to re-check the results.

Doctor: Right.

Me: Yes, I see your point.

(26:43 - 27:04)

Well, maybe you have some comments about the uterus. So it reacted, but can it be that it's still not malignant? Can it be that-

Doctor: I didn't understand.

Me: Can it be that it is still not a cancer? So like as a matter of fact-

Doctor: It's cancer, but it's dormant.

(27:04 - 27:32)

It's sleeping, which is what the imatinib does to gist. It can... We see it a lot of times that imatinib causes the gist to be a bit smaller, but much less uptake. So it's different in chemotherapy or different in other cancers where we don't have to see it decrease in size, but if we see decrease in uptake, it's also a good sign because it means it's working well.

(27:32 - 27:39)

That's what the imatinib can do sometimes.

Me: Okay. I asked about the mass in uterus.

(27:40 - 28:03)

So everyone thought that it's not a cancer because it was not active on PET-CT in three. So, and it didn't change much during the year, but right now it's changed. So actually they made some research on it using ultrasound and they found that it has a blood supply.

(28:03 - 28:15)

So it has active blood supply, but it doesn't conclude anything. Just it can be still not non-malignant.

Doctor: We don't know until we do a biopsy.

(28:15 - 28:22)

It is all just theories. And I know you said it's hard to take a biopsy from there. Okay.

(28:22 - 28:28)

We can only guess until we do a biopsy.

Me: Okay. I see.

(28:28 - 28:43)

So, okay. So I want to thank you just to wrap up. So your recommendation is not to increase dose and not to switch to another drug until there is no growth.

(28:44 - 28:56)

Doctor: Yes.

Me: We can take new biopsy and to check the results, but there is no strong need to do that until there is no growth again. Yes.

(28:57 - 29:14)

Doctor: Okay, say it again.

Me: We can take the biopsy and to recheck the results of genetic testing, but until there is no growth, there is no need to do it again.

Doctor: Right.

(29:14 - 29:24)

Okay. And about her general condition, can it be related to the drugs she takes?

Doctor: Of course. Yes, yes.

(29:25 - 29:34)

Imatinib can cause a large, a very, very side effects. So muscle pain, of course. And weakness, yes.

(29:34 - 29:45)

But if she has strength to do so much exercise during the day, it's really a good sign. And she should continue whatever she's doing.

Me: Well, yes.

(29:45 - 29:55)

But she wonders whether her state will become better because she wants to start working, you know.

Doctor: I don't know. She has very extensive disease.

(29:55 - 29:59)

I'm not sure. But I think right now, the quality of life is good, considering.

Me: Yes.

Doctor: And we only hope it doesn't get worse.

Me: Okay.

But can we do something with those symptoms?

So maybe there are drugs which can be taken together with imatinib,

which are not to need to make conditions, I think.

(30:17) Doctor: And say if she has a bit of fever,

the muscle pain, so she can try and say it's like ibuprofen.

Sometimes it fails because, like you're saying, it's like sign of inflammation.

So, and say she can try and see if it causes the muscle to be better.

Of course, she should eat healthy food,

like proteins and everything,

which I'm sure she's doing.

Exercise is really great,

and meditation and everything.

There isn't anything specific.

It's, it's, it's, the side effects of the imatinib.

But it's a good, it's really a good drug.

Me: Can it be because the liver doesn't function properly

because of the cancer?

Can it be the result of that?

So because she has a lot of gastric issues.

So maybe...

Doctor: The gastric issues can also be from the imatinib,

because it's cause gastric issues in a lot of people.

It can also be from the cancer,

but right now the cancer is under control.

It's more probable that it's from the immatinib.

(31:30) Does she take a, um,

a proton pump(?) inhibitors? Like, um, a Omeprazole?

Me: No, she takes only imatinib.

Doctor: So she can try starting also,

and say to see if it helps with the muscle pain.

And also, PPI's, like, um, a Omeprazole.

To see if it helps with the abdominal pain.

If she has nausea, also,

for me, and the final good option,

I like it down.

Me: Okay, I see.

So it's just to remove the symptoms.

Doctor: Right.

Because we don't have another option.

Just, what do we do,

and to continue the immatinib, even the same dose.

So we have to treat the symptoms that it causes.

I don't think we have another option.

Me: Okay, so there is no option for rehabilitations of such patients,

so maybe there is some...

Doctor: For having what?

Me: rehabilitations.

So, for example,

making some doing something

or maybe eating some foods,

but specific foods,

to make it...

Doctor: Just eating healthy,

just eating healthy,

and keeping healthy,

nothing more specific than this.

Me: Okay. Okay, I see your point. So just to ask you, imatinib works differently for different patients

and different cancers, of course.

Doctor: Right

But can you conclude

something from this year?

She was taking immatinib.

So, how is it in your opinion?

Does it mean that immatinib

will be not efficient

in the short run?

(33:12)

Doctor: It means that one day, immatinib will stop working, and the tumor will grow sometime. I don't know when in the next period,

or another two or three PETs, but sometime, immatinib will stop working, and we will switch to a second line,

which is sunitinib? we will speak about, if and when it happens.

When we have also third and fourth line, it's not how though.

It's a bit different. Each one of them is tyrisine kinase inhibitor against the C-KIT, you know that.

But each one of them also inhibits other proteins inside, say, besides the C-KIT.

So, they have all kinds of side effects, like the sick, the immatinib can cause,

like, you know, high blood pressure, and edema around the eyes.

Other drugs don't do this, but they other TKIs (?) do other things.

(34:05)

But all of the TKIs(?), cause the abdominal discomfort or nausea or diarrhea, and can cause high blood pressure.

So, it's something very common for all the TKI's.

So, I think that, considering the side effects, she's doing quite well, because I have other patients

who could (?), it's continuing with the 400 milligram,

sorry,

it said it in Hebrew, but it could continue with the 400 milligram.

It has to go down, so if she can continue with the 400 milligram,

more or less, I know it's not a lot of pan (?), but it's keeping

the tumor really, really under control.

So, as long as she can continue it, and she has manageable side effects, and as long as the tumor is expanding, we don't want to change anything.

Does she have, does she check her blood pressure still sometimes?

(35:01)

Me: No, I don't have,

since, well,

I will, I will,

I may ask her,

I may call her

an ask her,

about...

Doctor: Okay, and also,

you can ask me later,

and also,

the thyroid function

tests, also,

she has to check

from time to time.

Me: What, what

check is, excuse me,

Doctor: the thyroid

function test,

because sometimes,

it can cause the thyroid

function test to be

abnormal.

(36:00)

Me: So those blood tests have a couple of parameters which Dr. told that might

mean that she has sort of anemia but so maybe that may tell you something. So

she has...

Doctor: It does so very very common that's why we do the blood test because

it's also very common. I'm opening them up in the file that you sent. How much was

her last time I grew up in until I opened it?

Me: Let me open them as well. I need to remember which...

Doctor: I see a complete blood count so I'm a multiple team. Let's see. I found this

okay. 120 which is not bad. It's okay. So she doesn't really have anemia or blood

count is not bad at all considering it's like almost normal which is good. I'm

looking at a biochemistry from March or so fulteens(?). So I see a biochemistry is also

okay. Your LVH is just a bit high and that's all. Okay. That's really good.

Me: So she doesn't have any sort of anemia. Maybe an iron deficit or something like that.

Doctor: According to the blood test she did two weeks ago? No. She doesn't.

Me: Okay. I see. Okay.

Well, I may try to call her if you have some questions for her as a patient. Maybe I can

ask her about blood pressure for example. Okay. Let me call her. If she's not sleeping at first.