Saskia from Germany - Dx 2019 at 23 years old_RIP Aug 2020

[Olga]

Tanja, do you know the PET SUV values before and after the immune-checkpoint inhibitor treatment initiation - have they changed, increased, decreased? And also how the neutrophils to lymphocytes ratio changed under the treatment? Can you find the pre-and after blood work results and compare - is there any change? They fluctuate by natural reason so it is better if you take a few results if available.

[D.ap]

Hello Tanja
If your team can make the PET values comparison happen , begin that process.


You will need a prior PET , best taking preferably before Saskia’s treatment of Keytruda and during the treatment .

Is Saskia still on Keytruda ?

Thinking of you all .
Love ,

[Saskia]

Hello Olga and Debbie

It's really a mass.
We're pretty sure to only had regular CTs for lungs and never had a PETscan. So can't compare anything here despite all facts of the CT.
These 2 CT scans also had different conditions as it was first with contrast medium and second without.
The bloodtests we have every third week do also differ as they don't test same values every time. E.g. We had the differentiated bloodtest only once when I asked for it:
Neutrophils were at 62
Lymphocytes were at 22.
2,8 NLR. Right?
(this was during Keytruda)

How should the value of NLR develop during ICIs/Keytruda?

Saskia's 6th Keytruda was on 4th Dec and no more are yet planned because oncologist analysed progression because of growth of primary and one bone met.
We will ask to continue Keytruda for one more cycle because this seems to us the only option to find a surgeon for resection of primary and biopsy of one of the supposedly "skin Mets".

Big hugs
Tanja

[Saskia]

Sorry, two more things:
What do you suggest if surgeon
- can not do R0 (which we definetly think because it is close to the bone)?
- can not do R1?
- can do R1?
- can only operate and may leave some tumor rests?

BTW referring to your hint of the immense growth of the tumor and it could also be infectious material:
Saskia's primary tumor is completely hot all the time. We have to cool it most of the day.
I did nowhere read anything about tumors being so hot. So this might speak for an infection?!?!

[Olga]

The PET of primary before and during the K would help, it it works, it decreases but it seems that it was not done at all, correct? it is not rare but now recommended when the immune checkpoint inhibitors are used - before and during the treatment compare.
And you can not find any NLR from the times before of the K treatment too? It should decrease or stay the same if K works.
Then insist on skin mets biopsy if there is nothing else to review. If it is going to be a proven skin asps met< you might have an option to take her to Spain drs that make an intratumoral K injection.
Is the primary more hot than before of the K treatment? Might be local inflammation from the immune cells attack tumor, the visible size would increase as well then. Then it has to go down as the time goes, ask them to rescan in a month or two.
With the sarcoma updated guidelines they now consider the close margins acceptable if the tumor is contained in the same compartment as it does not cross the intra-facial planes. It is reasonable to go for the sub-optimal resection - i.e. clean resection with the very minimal margins - R1, just scrap the underlying bone if there is no bone penetration. Because the main danger for the life comes from the distant mets, not from the local recurrence, and you can position the surgery as the supportive, palliative treatment to improve her quality of life and to open the road to may be better systemic treatment efficiency. Tell them that it is very painful and hot all the time.

[Olga]

see this viewtopic.php?f=92&t=1816
also read re. treatment beyond progression (TBP) here:
The Evaluation of Response to Immunotherapy in Metastatic Renal Cell Carcinoma: Open Challenges in the Clinical Practice
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747319/
we are using data from RCC trials as this is the closest cancer by typical clinical history and by the morphology to ASPS
also a good write up on the subject to better understand the problems with the scanning:
viewtopic.php?f=3&t=1819

[Saskia]

Hello and quick info from today,
Lung CT was not so good, there is progress of Mets and one bigger met which was around 3,6cm grew as well. I don't have exact figures here as we didn't count the Mets before as well. Over 100 small ones all over. Saskia does not have any problems breathing and the big met is at the bronchial. That's for sure the reason why she's caughing. We are happy no big met is at the trachea.

Anyway, we convinced Saskia's oncologist and she supports us completely in our ideas - thanks to you! And all the info you provided - I forwarded all copies and links.
We will continue with Keytruda and hopefully not only one more infusion on 27th Dec.
She supports the idea to go this way and try to have a surgery of the primary to have the chance of abscopal effect and decrease the tumor burden for efficiency for treatment.

So our appointment with the surgeon tomorrow is crucial. I will stress the point you mentioned according updated guidelines of sarcoma resection also with R1 results, scrapping the bone etc.

We'll be back in 2 days latest with news. Hold your thumbs.

Thanks so much for all the important facts.
Tanja

[Saskia]

P. S. : forgot to answer one question: the tumor is very hot since 5 weeks, so under Keytruda. Let's say it was around the 5th infusion then.

[Olga]

There is also an article that it is safe to have the major resection while on the ICI drugs treatment. I'll try to find it later. Also try not to have any additional traumatic procedures for now like alkaline infusions etc to reduce the systemic inflammation, no damages aside of necessary ones - what about the skin mets biopsy?

[Saskia]

Thanks Olga.
We are not doing anything additionally at the moment.
We see the surgeon this afternoon and will also ask for the skin biopsy.
Can you send me the link or homepage of the doc in Spain for intratumkral injections?
In case there can be no surgery to have this at hand to attack the primary.
Should a biopsy be sent directly to Spain then?
I'm pretty sure there is a lot of inflammable or infectious going on in Saskia s body right now which hopefully means ICI tries to do its job but tumor burden is too high.

Tanja
I'll be back tonight with news

[Saskia]

Hello
The surgeon is willing to do the surgery on the primary which seems to be not too complicated to him except doubts on wound healing complications. Serom, sepsis etc.
We on the other hand think that saskias wound healing would develop much better without the tumor being inside and underneath.

He is also struggling with the fact of treatment during phase of surgery and healing because he thinks Keytruda is not compatible in this phase.
We heard of another asps patient that she was on Keytruda all the time during surgery.
Do you pls have a link to prove there are no complications seen by surgery+Keytruda?
He asked for that.

Tumorboard for saskias case will be tomorrow. 2nd opinion from Essen will be on 30th Dec and we hope they will support this way.
I canceled radiation now because if so, surgery will be done after 10th of January without radiation in advance.

We're pretty much exhausted after all those appointments now but hope to got it all right?!

Thanks again for all facts and support.prayers and hugs
Tanja

I will again ask for biopsy of those skin irregularly on 23rd when Saskia will have next K

[D.ap]

Hello Tanja
I posted an article back in 2018, about a small study of patients who were followed , after surgery while staying on ICIs

Here’s the short discussion Olga and I had -

viewtopic.php?f=3&t=1598&p=12163&hilit= ... ing#p12162
Certainly surgery is taxing on a patients body .
Maybe raising the neutrophils too high while on Keytruda ?

However the true immune suppressive mechanisms I see would be the anesthesia and the antibiotics that would be used before and after the surgery ?
TKIs like axitinib slow down healing for sure.
However I’d like to see your surgeons thoughts , of what he or she knows.😊
Certainly enjoy your evening after an exhaustive day!

[Olga]

1. What is the proposed planned extend of the surgery on the primary - is he going to remove the tumor only, the muscle only or few of them?
2. Re. surgery and immune-checkpoint inhibitors at the same time:
Perioperative Outcomes of Melanoma Patients Undergoing Surgery After Receiving Immunotherapy or Targeted Therapy.
https://www.ncbi.nlm.nih.gov/pubmed/31811340
looks safe to me but I would not have the surgery close to K, it is done once in 21 day so it is a good idea to have the space it out. The max PD-1 blockade is reached at 72 hours post K. May be in the middle of the cycle? If we assume the overall inflammation burden suppresses K effect, then after the surgery there might be no point to have it right away? I do not know, it is a complicated subject, some good immunologist input would be needed, if you know where to get one. Also agree with Deb that K might simply not work that well due to immune suppressive effects of the anesthesia and the antibiotics.

[Saskia]

Hello
1. One muscle needs to be removed. That's what we know for sure. Pre surgery talk will take place later with details
2. ICI and surgery: thx, but surgeon wants a break of ICI. So we'll have K on 23rd, mid of Jan surgery and maybe 2 weeks after that K again. Let's see

Tumorboard decided against surgery because of medical treatment guidelines and judicative reasons. As all other treatments failed they see chemo as next upcoming med.
They don't see it as a new situation with less tumor burden to have better efficiency on Mets. All my documents provided are either no good / reliable sources or not enough patient cases. (that was the argument).
I think It is ridiculous because for trabectedin for asps the clinical study is only with 7 patients.

Anyway we want to stick to our plan and oncologist sees the reasons. We will fix the date on Monday for Jan then with surgeon. We have to sign for taking over risks and that it is our wish to do so. Especially referred to surgery while having lung Mets.

We received feedback from Heidelberg from Master study for gen molecular analysis: they confirmed asps and TP53with deletion 17p.
I tried to understand anything I found here on the forum and with combination of Doxorubicin but unfortunately didn't really get it yet.
I understood this molecular outcome seems to be comen with asps?!
Does it still mean K could help or does it mean we should better switch to chemo? Shall we refer to treatment combination of CLL patients?!
Another analysis additionally confirmed FGFR4 mutation.

Do you see any problems or benefits out of those analysis?
I remember once to have read that it is not too important to know any Subtypes for asps?!

Thx
What would we do without you
Tanja

[Olga]

Thanks for the update. Add Q - skin mets biopsy?
About their arguments re. small number of the ppl on the study - that was my argument with our drs here in Vancouver, when they offered Sutent and would not cover Keytruda initially, I presented all the cases I found and told them that if they consider it reasonable to offer Sutent based on small sample statistic data, they can not say that Keytruda data is not statistically significant - they both relatively equally statistically insignificant.