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

[D.ap]

Thx Debbie for your quick reply.
The MRI was discussed on the local tumorboard and with other specified sarcoma clinics in Munich, Berlin and will be discussed with Essen as well. As the tumor grew 2cm in every direction plus new Mets developed they are of the opinion not to speak of pseudo progression. We hope for the lung results to prove better but it's not expected, we've been told.
But if so, I'd love to continue with ICI Keytruda plus radiation.
Do you agree or is it better to have a break of the DNA by chemo Trabectedin plus radiation?
Were kind of lost and so devastated by this quick growth in total.

Tanja

Hello Tanja and Saskia ,
So the 2cm(20mm) is the growth from April to December ?
What had the lung scan report showed as additional mets as compared to recent ? Were the lungs viewed with the same type of CT ?

You talk of seroma being currently reported on the primary?
Was that in the first report scan ( MRI) back in April ?

When our son first embarked on opdivo off label back in mid 2016 , we all agreed to not scan too soon , knowing of pseudo progression possibilities and how little was known to diagnose it’s happening by just a scan .

You’ve had 2 scans performed on the primary thus far ?
1 in April and the second 12 weeks ? into Keytruda axitinib treatment?

[D.ap]

Tanja
Path report ( ASPS) talking of melanoma similarities -

The rarity of and treatment of ASPS ,was so incredibly misunderstood just 7 years ago by doctors when we embarked on our current journey but to-date so so much more has been discovered by shared information from around the world .😊
100 cases or less being seen around the world !

BUT I can only imagine how the folks who’ve built this website , felt back 20 plus years ago ! These folks have been a great part of our success and I try and thank them every day .


https://www.archivesofpathology.org/doi ... 14-0385-RS

Noted on path report -

“Differential Diagnosis
The differential diagnosis includes other primary soft tissue neoplasms, such as rhabdomyoma, hibernoma, clear cell sarcoma of soft tissue, perivascular epithelioid cell neoplasm (PEComa), paraganglioma, and granular cell tumor. Metastatic tumors with similar cytologic features can mimic ASPS, such as clear cell RCC, hepatocellular carcinoma, adrenocortical carcinoma, and melanoma”

[Saskia]

Hi,

Thx for the link for comparison to Asps. This supports and stresses the point to have resection as well I guess to strengthen the outcome and effect of ICI or other treatment on Mets.

1st MRI of leg/primary: April 19
2nd MRI in August, no growth, stable
3rd MRI 4th Dec, growth 2cm since 1st Aug.

CT lung: may19 (over 100 small mets) and 1st Aug 19
They only told us there were more mets, not stable.

Treatment was:
May - aug: cabozantinib
2 weeks pazopanib
22nd Aug - 04th Dec. Keytruda + axitinib inlyta

[Olga]

We usually do not advise a biopsy as the precation to disseminate the tumor. But the skin mets would be easy to biopsy without dissemination and would give you the very important information that is needed now. As the matter of fact we have already suggested the biopsy to few patients on immune-checkpoint inhibitors in order to verify what is going on, it was not done as far as I am aware of, but when the need is strong, it makes sense.
What kind of radiation is suggested?

[Saskia]

Okay thx Olga.
Radiation appointment will be on Tuesday to be infformed. What is important to know exactly pls?
I will also ask for an appointment with the surgeon in person and will contact the clinic in Essen, Dr. Bauer, to have a second opinion.
I'd suggest or wish radiation plus Keytruda to hope for abscopal effect and resection of primary instead of trabectedin. Which we still could do later I guess.
Are those thoughts reasonable?

Thx
You are the best
Tanja

[Olga]

Any radiation to this tumor will most probably not be definite and can suppress the immune system further, especially if the skin is going to be burned as the immune system is very sensitive to the radiation damage to the skin. It looks to big for the irradiating it with the goal to create the abscopal effect as it is noted the target has to be smaller and safely located, so the there will be no significant inflammation in the body. Like something 10-20 mm.
Ask them what is the goal of irradiation, all the articles say ASPS is not treatable by the conventional irradiation.
There is a clinics in Frankfurt https://www.saphir-radiochirurgie.com/saphir/team/ we were in the contact with Dr.Oliver Blanck - he is not a medical dr but a scientist, he helped us to get one of Ivan's met irradiated for the abscopal effect, he works in the research and helped to explain to our drs in Canada what was the point. May be contact him and ask for the advise what met could be irradiated in your daughter case

[Saskia]

Hello
Radiology appointment was today and they want to radiate the whole primary tumor with 20 radiations and 60gy.
They say it is too late, it's an advanced disease and we cannot hope or have time for an abscopal effect.
Radiation will start next week Thursday.
On 16th we'll have the lung CT and on 17th we will see the surgeon to know if he sees any chance for resection. Maybe after radiation...

Tanja

[D.ap]

Hello Tanja,

How big of an area will they be radiating and what is the goal ? To reduce for surgery maybe with pre-op radiation to reduce size ? What kind of machine will be used for the radiation treatments? You will continue on Keytruda ?

So 2-6 weeks to recover after 20 treatments ( 5 months ).
Hugs and prayers .
Love ,

[Olga]

Tanja, what about the biopsy the skin mets and the latest lungs CT scan result - is it done yet? You should wait for biopsy result before starting the radiation. I am not sure if it even makes sense to have this radiation, it is a very big deal. Going to be easy in the beginning as the doses are small since it is broken down in small fractions, but later it5 is going to be bad. Get a second surgical opinion.

[Olga]

there is some new article for the drs to review:
Pathology of immune-mediated tissue lesions following treatment with immune checkpoint inhibitors.
https://www.ncbi.nlm.nih.gov/pubmed/31816081
Abstract
Immune check point inhibitor (CPI) therapy has revolutionized treatment paradigms for several cancers, but at the cost of triggering a diverse spectrum of immune-mediated injury to non-cancer tissues. The complex biology of these toxicities remains incompletely understood, partly because tissue acquisition from affected areas can be challenging to retrieve, thus hindering development of targeted therapy. Here, we review the literature describing pathology of immune-mediated tissue lesions including gastrointestinal, skin, rheumatic, pulmonary, cardiac, renal and hepatic lesions and highlight key immunological insights.

[Saskia]

Hello Debbie and Olga

The radiation was intended to stop the growth or reduce it. Radiation team doesn't see any chance for abscopal effect. But today we talked to another prof who supports the surgery of the primary to have this chance and wrote to the surgeon we will see on Tuesday! We are very happy to have found someone of this opinion.
He also said surgery first and radiation afterwards. Let's see what prof Dr. Schwarzach will tell us then.
He also said to start yondelis after surgery if at all. See if abscopal effect and DLMethadon might do its job on metastasis as well then.

Discussed radiation from yesterday would be with medical accelerator Varian true beam. 1500ml mass of radiation area 20 times with 60 gy.

What are the ranges of pseudo progression of asps primary tumor to prove ICI worked or not?
Up to 25%growth ok?
We had 2cm during Keytruda in 4 months.

We are proud now not to overreact like all the months and hurry to fast to the next ideas but trying to think straight to fight this disease.

Tanja
Will keep you posted on lung CT on Monday and surgeon appointment on Tuesday.
Open for any hints from your side to ask, suggest or prove by clinical studies

[D.ap]

Tanja
Great news of connecting with a surgeon !
Certainly make sure they are knowledgeable of ASPS and it’s vascular nature .

In reference to your pseudo progression question -
Without a biopsy it’s hard to
A) know if it’s pseudo progression
B) progression

There are some liquid biopsies being used . I’m not sure of their success.

At 5mm a month ,20mm increase , the question anyone should ask is if it’s reducing or endangering the organ and or limb( bone circulation )by it’s location and increasing in size.
Your primary increase doesn’t follow most ASPS progression that I recall reading ?I’ve read of 1-2mm a month .

I’ve read of 50% increases in the lungs during ICI usage ,being biopsied to know of inflammation etc to be the culprit of increase , not cancer progression .
The problem is not much followup was being documented with patients being discontinued from ICI meds from what was first being seen as “hyper progression “ back in the early infancy of ICI trials etc , which later was termed pseudo progression.

https://www.hindawi.com/journals/crionm/2019/8356148/

So happy for your news !
Love ,

[D.ap]

Tanja
Another good write up on pseudo progression .
This is from the 2017 American Society of Clinical Oncology meeting .

https://www.immunosym.org/daily-news/ev ... unotherapy

I’d visit with your team about the pros and cons of using yondelis after surgery and radiation as well . Especially if you all are able to obtain positive margins with the surgery.

[Olga]

I agree with Deb, it is hard to say but since the growth looks faster than before, it is reasonable to suspect some inflammation going on in that tumor and causing it to swell. If they resect the tumor, they will slice it, freeze it and review. You can also ask it to be tested for other possible treatment targets. You can also insist that the skin mets are biopsied.
When the prof said - surgery first and radiation afterwards - did he mean that the resection area needs to be irradiated? I would consider not to due to the big immune system suppression by it, but lets not to get ahead of ourselves and first wait what surgeon tells. People with ASPS leave for a long time with multiple metastases even if untreated and removing primary is considered to be beneficial in ASPS even in the multiple metastases setting. To open the road to other possible treatments. So I would be prepared to get the second or third surgical opinion. We usually get at least 5 from the best ones, what is impossible or not right from one surgeon point of view, can be ok from the other ones. Heidelberg have a lot of skilled surgeons as well. She is young and has a right to get the best possible options.

[D.ap]

Tanja ,

Another reason to stay on pembrolizumab prior to surgery ,

viewtopic.php?f=92&t=1733&p=13720&hilit=Abscopal#p13720

Night to you all