Nino from Berlin - Dx 2015

[D.ap]

Hello again Nino

Good advice to wait until your cold is better .

I’d sure hope that a brain scan would be performed before you start axitinib as if the healing isn’t complete then there is more of a chance for bleeding from the tki ,as well as inflammation later from prembro.
Certainly I’m not a doctor but run it by your team.

As I understand it Asps operates on VEGF to grow ,and the sarcoma causes tryosine kinases factor to cause growth and become dis-regulated . This is why our tumors are a quagmire of vessels that are seen with in our resected tumors . This as an end result of the tumor VEGF/TK gone rogue .😬

The radiation of the brain tumors can exasperate the tissue to attract the tryosine kinase (TK) cellar activity..the repairing of the damaged tumor. You would be on a tyrosine kinases inhibitor(TKI) which would throttle back the activity of the TKs ,but what would be the cost /benefit factor is my question. Especially within the skulls limited area where inflammation should not be happening if can be avoided .

[Ninko]

Hey, just wanted to give a quick update. Last scans revealed two lesions, one in the right lung and one in the brain. The one in the lung was a pre-existing node that showed a growth of about 2mm (so now ~4mm) and the one in the brain was a bit bigger, 8x7x5mm in the left frontal lobe. Unfortunately the brain scan was done later than planned, so more than 4 months passed since the last MRI, so it probably could have been found at an even smaller size. Also in February I already noticed a small ~1mm lesion on the scans in that part of the brain, but my oncologist said it did not really look suspicious for metastasis. The other two lesions that have been treated with radiation are showing good response.
The new lesion was treated with stereotactic radiosurgery and I tolerated the treatment really well and didn't have to take any steroids. Also three days after radiosurgery I received another dose of pembro, so hoping for some synergy here 😅 But given that new lesions, though just a few, were appearing, I now think it was definitely the right decision to start systemic treatment.

Otherwise I am tolerating the combination treatment quite well. In the beginning I had some rash and pruritus, but only for the first few weeks. Also I am currently slowly escalating axitinib dosage, being at 6mg bi-daily right now. The only adverse event that I am experiencing from axitinib is slight oral mucosits, but as PMID 31101577 described I am adding some folic acid supplement now and then, which does not make that AE really noticable at all.

In September I am going to have my next scans, including lower extremities to check on that weird lesion again. My oncologist also decided to switch to MRI for abdomen scan to reduce radiation exposure in the long term :)

[Ninko]

Hey everyone, it has been a while since my last update. I have been on Pembro and Axi for over one year now and the response has been mixed.

The 3- and 6- month update scans showed one new brain met each (~5mm) and both have been treated with SRS. Also the nodule in the lung increased by about 1mm and they decided to also give SBRT to that (3x20Gy). In the meantime I had been on and off Axitinib since I had problems with oral mucositis and it was difficult to eat, I even lost my taste for a while. After around 5 months I also developed dermatits, covering my trunk, upper legs and arms but luckily it was quickly managed with topical steroids.

At my 9 months scan for the first time I did not have any new lesions, but the irradiated one from 2 months before had increased in size. Also the lung tissue was showing signs of inflammation/scarring at the site of radiation. However the radiation therapists said that it would be just changes due to the SRS/SBRT and we should just wait for the next scan. In my 12-months-scan the brain lesion reduced in size again (the scarring in the lung kept increasing, but I did not experience any symptoms), so that was a good decision. Also there were no new lesions again, but two previously irradiated lesions from before the start of the therapy had increased in size. On my 15 months scan - one month ago - I had a FET-PET MRI instead of a normal MRI for my brain to check for possible radiation necrosis of the previously increasing lesions. After the scan I was sent to the ER to talk to a neurosurgeon. Turned out the frontal lesion increased to about 31mm, with a huge perilesional edema and an almost 1cm midline shift. I was experiencing only a slight headache, for which I did not put too much thought into since it is kind of normal for me to have a headache around the time of scans 😅 I was put on dexamethasone iv and they told me that I would require surgery for the lesion since it is putting lots of pressure on the brain and its structures.

Also this spring I had been off Axitinib for almost 3 months because I developed a bleeding duodenal ulcer. That is also why I am on PPIs as long as I am being treated with Axitinib.

So about 4 and a half weeks ago I received surgery to remove the lesion. Everything worked well and the lesion could be completely removed. Also the pathology report noted about 98% of the resected specimen was “regressively changed CNS tissue” and the rest was a small accumulation of ASPS cells with very slow growth (KI-67 of 1-2%), also T- and B-cells were present in the tissue. My case was discussed on the tumor board and in their perception the quick lesion growth was legitimate and the Axitinib somehow started working on that lesion and this lead to the necrosis. But regarding the CNS involvement in the pathology and also the unusual growth dynamics (I was on Axitinib for the whole 3 month when it would have grown from about 8mm to 31mm and again “destroyed” the met) in my case I was still convinced on radiation necrosis. So I contacted my radiation therapist again and he agreed with me that radiation necrosis would also be a highly likely possibility and if the other lesion (which was irradiated at the same time and also grew at the 12-months-scan but was stable in size at 15-months-scan) grew again they would - given it does not show explosive growth like the last one, which would make surgery inevitable - they would treat it like radiation necrosis instead of recurrence.

However I am happy that given the missing response to the treatment in the beginning, for the last three scans I did not have any macroscopic recurrence.

Right now I am waiting to fully recover as my cardiovascular system is not fully up and running yet, slowly starting with some small runs again. I even fell unconscious about two and a half weeks ago after standing for too long. Afterwards I was at the ER because of my surgery and they wanted to check that everything was fine with it and that it was not a direct cause for the syncope and they did a quick CT of the brain and there was just a slight bleeding into the resection cavity, but they said it was nothing of danger and consistent with the post-surgery MRI.

[D.ap]

Hello Nino,

It’s good to hear from you.☺️
Your recent happenings with the inflammation from the treated brain lesion , sounds quite scary . However it sounds like your team addressed it quite quickly and successfully.

Our son had to undergo LITT for a frontal lobe treated lesion , after it was SRS treated back in 2015.
His inflammation was the result of the breakdown on the tumor after the SRS treatment,and not from a medication treatment.

This procedure successfully allowed the necrotic material to dissipate without any further inflammation.

Thank you for letting us know how you are doing.
In the meantime , take care of yourself .

Edited 11/01/24

Nino writes

Sat Jul 22, 2023 10:51

The new lesion was treated with stereotactic radiosurgery and I tolerated the treatment really well and didn't have to take any steroids. Also three days after radiosurgery I received another dose of pembro, so hoping for some synergy here 😅 But given that new lesions, though just a few, were appearing, I now think it was definitely the right decision to start systemic treatment.

Otherwise I am tolerating the combination treatment quite well. In the beginning I had some rash and pruritus, but only for the first few weeks. Also I am currently slowly escalating axitinib dosage, being at 6mg bi-daily right now. The only adverse event that I am experiencing from axitinib is slight oral mucosits, but as PMID 31101577 described I am adding some folic acid supplement now and then, which does not make that AE really noticable at all.

Nino
Are you still on folic acid supplements by any chance?
And are you by any chance following a ketogenic lifestyle, diet ?

Also was there a reason the doctors felt the tumor was AVM ? Was there history of yours that suggested it may of been the case?

My questions are because it appears you have a tendency to have brain tumors when the rest of your body seems to be keeping the body in check for any pop up disseminated disease.

Our son experienced a rapid increase in disseminated disease ie 1st set of brain tumors ,after embarking on a ketogenic diet, in hopes of reducing sugar in his diet . Ketogenic diets not only decrease sugar but they increase lactate. Ie ASPS utilizes lactate

Ketone bodies, together with lactate, are the main alternative fuels for the brain and both are able to cross the blood–brain barrier through monocarboxylate transporters (MCTs) in endothelial cells and astroglia

Blood brain barriers are also opened up with this change in diet and if the immune system isn’t functioning at its premium , then certainly micro-mets can grow.

Ketogenic diets are used with epileptic patients to aid in brain seizures where med deliveries haven’t been successful. It calms down the brain .

Granted I feel we weren’t managing the diet in its strictest form, ie checking ketone levels , eating in an 8 hour time frame and making sure the meals were calculated in the correct proportion of proteins etc

Folic acid deficiencies/ gene mutation can contribute to primary brain tumors . AVM is ,in my limited understanding possible connected to a gene mutation which can be attributed to folic acid deficiencies, as a result of gene mutations.

[Ninko]

Hey Debbie,

yes it was pretty weird to be sent to the ER without any specific reason 😅 I was also researching about the possibility of LITT, but iirc it can cause an increase of the lesion of up to ~300%? which would have definitely been too much for my 3cm lesion, but maybe it will be an option for the smaller occipital one.

Are you still on folic acid supplements by any chance?
And are you by any chance following a ketogenic lifestyle, diet ?

Back when I wrote about the folic acid supplementation I did not have any high dose supplements at hand, so it was just a combination of b12+folic acid. I just started recently to add folic acid regularily with about 400µg/d. I might increase that dosage as soon as the mucositis flares up again. And I was following a mostly vegetarian diet, so rather high in carbs. Just recently I started incorporating more animal products again to help me gain some weight and increase my iron levels, so I will see how that works. I was also prescribed iron supplements because I developed iron deficiency anemia after my peptic ulcer.

Also was there a reason the doctors felt the tumor was AVM ? Was there history of yours that suggested it may of been the case?

I think their primary reason for that was that there was no rapid growth of the tumor and the dense vascular structure mimicked that of an AVM. Unfortunately I do not have the pathology report from back then, so I can only guess. As for gene mutations, they did an analysis on my first resected brain tumor and there <50% of analysed cells each contained a p53 or UGT1A1 mutation.

[D.ap]

Hello again Nino ,

Does your blood work report bilirubin values?
Did you by chance have jaundice as a baby?

[Ninko]

Hey Debbie,

my bilirubin values are in the norm, usually around 0.2-0.4 mg/dl. And no, not that I would know.