Sam from Florida - Dx 2007

[arojussi]

Thanks for sharing great news.

[D.ap]

Cindy
Here’s an excellent response to your quandary of why there is percieved metastatic progression ,while Sam is on pembro and axitinib while on the Miami trial


Jussi suggested the idea
From what you presented on Joshua’s post

Thanks for the update on Josh treatment.I forget to look here for his info. Sam is still on axi/ pembro but we are checking on a new possible met in femur so I'll post our news later. ASPS is challenging but glad there are more treatment options now.
PS. Glad he's keeping weight on!

,

Melanoma can mutate and become resistant to immunotherapy, but asps grows and therefore mutates extremely slowly. In 10 years my asps had zero new mutations. There was just one aspl-tfe3 fusion gene, that they use to diagnose asps. Nothing else. And sutent trial proved,that this is typical for asps. So if there is proven significant response to immunotherapy asps is relatively unlikely to grow again. Of course all is unfortunately possible.

[D.ap]

I’ve read serval places while reading about TKIs and their side effects / and or downside to the ingested Med , that they effect osteoclast recruitment ? So the very vascular bone when addressed by a TKI , isn’t able to complete its repair of itself when chemically that aspect of repair renewing of the bone , has been stopped by the TKI? An anti VEGF(R)? Causing low calcium levels —hypocalcemia

http://www.cureasps.org/forum/viewtopic ... mia#p10956

Cindy Sam’s been on the trial for a year correct ?
And was dx’d at the age of 12 years old?

[D.ap]

This is an article on EGFR


“In addition, these compounds have an anti-angiogenic activity, either direct by affecting the proliferation and survival of endothelial cells, or indirect by blocking the production of vascular endothelial growth factor (VEGF) in bone marrow stromal cells and in tumour cells. Finally, EGFR-TKIs can inhibit recruitment of osteoclasts in bone lesions, by affecting the ability of bone marrow stromal cells to induce osteoclast differentiation and activation. Taken together, these findings strongly support prospective clinical trials of anti-EGFR agents in cancer patients with bone metastases in order to define their role in the management of bone disease.”

https://www.ncbi.nlm.nih.gov/pubmed/16601275/

[jcs2007]

Thanks for your imput. Deb, Sam was diagnosed 2007 at 12yrs old and removed primary tumor in left quad. He just completed 1 yr on axi/ pembro trial in Miami but just kicked off due to new met in femur. We are waiting to meet with orthopedic oncologist to see what treatment is needed. Then may explore other trials like anlotinib. This disease is exhausting!

[Bonni Hess]

Dear Cindy, I am so sorry and heartbroken that Sam has been diagnosed with a new femur met, and has consequently now been taken off of the Universiry of Miami Pembrolizumab/Axitinib Clinical Trial which he seemed to be having a very successful response to for the past year. It seems that sometimes there are non responding mets with some systemic treatments as happened with Brittany a couple of months after she started her Cediranib Trial when she developed a subcutaneous abdominal met that was then successfully surgically removed so she could resume taking the Cediranib. Once the subcutaneous abdominal met was removed and Brittany resumed her Cediranib treatment, she had significant shrinkage and disappearance of all of her remaining innumerous and widely disseminated mets. Perhaps the nonresponding met is the case with dear Sam"s new femur met, rather than that the Pembro/Axitinib is no longer working?!? My heart and my most caring thoughts are with dear Sam, you, and your family, and I will be anxiously awaiting your next update. Sharing your heartbreak and anguish with deepest caring, healing wishes, love, and continued Hope, Bonni

[arojussi]

If most recent scan showed continued success in everywhere, but in the femor something is weird here. In asps immunotherapy responses are sometimes weid. Pseudoprogression can last up to 6 moths and it can appear even later at least in theory. There is a case, where asps-patient developed huge brain tumor while on immunetherapy trial and when resected lesion turned out to be completely dead. Of course doctors considered these possibilities, before kicking you out of the trial. So lesion is obviously highly vascular. Immunotherapy responses are often long lasting, but unfortunately tki`s responses are not. So if there was response only to tki then it is natural that asps shrinks first, then grows as resistange develops. Now you can try to turn Sam from immunotherapy nonresponder to responder. There are several ways, that can do this. All relatively experimental. First is to use radiation to one or few tumors. Approach I chose for my subcutaneous met, when I started immunotherapy for the second time. Unfortunately radiation doses for abscopal effect to increase effectivity to immunotherapy and radiation doses to kill the tumor are very different. For abscopal effect 8gyx3 is most studied. To kill tumor you need all radiation in single fraction. Ablation can also achieve abscopal effect. Also fecal transplant from responding patient can turn non-responder to responder.

So if possible I would have ablation for femoral tumor. 2 have fecal transplant. 3 Then continue keytruda off label with propranolol. Antibiotics kill gut microbes, so having surgeries while on immunotherapy is risky. Having ablation or radiation soon before or after infusion increases success. also Yervoy can be added to Keytruda, but this increases the risks of immunotherapy related side-effects.

[Olga]

Cindy - I found this very new article reporting of newly found Immune-related adverse events with immune checkpoint inhibitors affecting the skeleton -
resorptive bone lesions.
Immune-related adverse events with immune checkpoint inhibitors affecting the skeleton: a seminal case series.
https://www.ncbi.nlm.nih.gov/pubmed/30305172

[jcs2007]

Thanks for the information. Sam has appointment on Monday with the same orthopedic oncologist who performed his first surgery in 2007, so I’ll post after this appointment. After we deal with this met, we have to decide on staying with keytruda off label or doing a new trial so I appreciate the info!

[Olga]

Did they take a biopsy, was an MRI already done to figure out the nature of the bone lesion?

[jcs2007]

Well, initial open biopsy of the femur shows no sign of ASPS. The Dr. called it fibrous in nature but I will have the exact nature of the lesion next week with the final report. At this point, unsure if he would be eligible to resume axi/Pembro trail or should he look into another trial like anlotinib. Olga, they did the MRI of the femur after a new lesion showed on the abdomen CT and. It was inconclusive to what it was, so Ortho oncologist recommended biopsy verses watch it, so we could move forward with systemic treatment.
thanks everyone for the input!

[Olga]

Cindy - I am very glad to hear this is not the met although other conditions might be also very concerning as the bone might be damaged by a treatment now?
Also I do not remember that you informed us re. new lesion showed on the abdomen CT - was it during the trial, recently? Is it confirmed to be a met or?

[arojussi]

You should be allowed to continue trial and if not continuing axitinib and pembrolizumab off label should be possible. Very happy to hear these news. Of course you need to wait final biopsy report, but I am very optimistic. Fibrous lesion might not be treatment related, but just benign lesion, that sometimes happen, this would be big coincidence, but coincidences sometimes happen.

[D.ap]

Cindy
Good point from Jussi and Olga
Case and point , Sam to continue on trial ..
Love

[jcs2007]

Just got the final biopsy report on the lesion in the femur which is not ASPS. It is fibrous tissue with CD3+T cell rich Lymphohistioctic. We go to Miami this week to do the 3 month lung/ abdomen ct and pet scan. Sam is recovering from the biopsy pretty good but he Cannot run, jump or return to the gym anytime soon. Wishing everyone well this Holiday season!