Tom from Pennsylvania - Dx 2002, RIP 2021

[Kathy]

It has been too long since we have posted but we are always reading updates and keeping you all in our prayers. We learned that while most of TJ's tumors are responding to the trial(we are so excited and thankful for this), there is a tumor at the S2 vertebrae that is not. Every other tumor has either gone down considerably in size or cannot be seen on scans any longer. The S2 has grown a little and is causing some increased and very intense pain. TJ's oncologist is consulting with his radiation oncologist to see if the spot can be treated with radiosurgery. This type of treatment should be allowed on the trial protocol, but the fact that he had growth could mean they take him off the trial. We are waiting for answers and the waiting is so hard. His oncologist did suggest that even if he is taken off the trial we can try to get the immunotherapy off label. We could use some prayers that this gets resolved ASAP, not only so we have a plan but so we can get TJ feeling better. Of course he never complains or slows down. He is currently on the road with Ellie, his Dad, and brother in law Matt. They are heading out to Cleveland to watch the NCAA wrestling tournament and to cheer on Penn State! Praying they have a fun and safe trip and they come home to a plan!

[D.ap]

Hello Kathy,

How much growth was seen ?
Is this spinal tumor from Toms primary tumor?
Hope you get news soon.
Love
Debbie

[Olga]

Kathy - sorry to hear that. Is it the same spinal tumor that was already treated by the radiation before? I hope the radiation oncologist already knows that there are successful stories and studies in treating by the irradiation while under the PD-1/PD-L1 treatments - they can even use the less optimal coverage if the optimal is to risky as the radiation treatment remains attract the immune system cells actively and then they find and eat the remaining tumour. The treatment should be done close to the radiation treatment - the same day or a day before/after.
The other (less probable) scenario is the treatment caused inflammation related increase in the spinal tumor size and increased pressure caused by the temporary increased size, it can come down as the times goes and the cells are taken away. I am pretty sure the people on a trial are already aware of it, but there are different now described treatment response patterns: I posted the article here and you can discuss it with them
http://www.cureasps.org/forum/viewtopic.php?f=90&t=1526
Evaluation of the pharmacokinetics and metabolism of pembrolizumab in the treatment of melanoma
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613934/


- Responses may be immediate or delayed;
- In total, 4 distinct patterns of response to immune checkpoint inhibitors have emerged: 1) timely regression of index lesions; 2) a slow but steady decline in tumor burden after stabilization of disease; 3) an initial increase in existing tumor burden followed by a delayed response; and 4) the appearance of new lesions followed by a delayed response. The latter 3 patterns of response are not seen with traditional cytotoxic therapies and may be associated with improved immunooncologic outcomes.
Another interesting option is to biopsy the non-responsive metastasis, there are cases (even with ASPS - I found it on the Brittany Sullivan blog) when the biopsy alone was enough to attract the immune system attention to that spot and to eat it away. Can you ask the team if they want to find out what is different in a make up of this tumor from the rest of them?

[D.ap]

Kathy ,

Olga’s suggestions are all excellent ideas .
With your spine tumor having been treated with radio surgery , inflammation sure could be the issue verses progression ?
Regardless , either of those above 2 sure can cause a painful situation .

[D.ap]

Kathy

Found the topic on scan reading to possibly distinguish inflamation from progression.
Thru imaging . Granted it’s in reference to cytotoxic treatments( written in 2005. : ) ) pre immune therapy.


http://www.cureasps.org/forum/viewtopic ... ion#p10848

Also Mario’s trial folks , gave him a 6 week break after reported progression , only to have his scan show reduction .
http://www.cureasps.org/forum/viewtopic ... ion#p10749

[Bonni Hess]

Dear Kathy, I Hope that you and Tom have found some good answers and resolutions to his non responding spinal met and heartbreaking increasing pain. ASPS continues to pose some perplexing questions and difficult problems when individual mets don't respond to treatments and the majority of the other mets do, as happened with Brittany's superficial abdominal met within a couple of months of her beginning her Cediranib treatment almost 9 years ago. In Brittany's case we were fortunately able to have the met successfully resected and then she continued the Cediranib with VERY thankfully thus far very successful, long term, sustained results. I understand that resection of Tom's non responding spinal met is not an option, but perhaps some of Olga's knowledgeable suggestions can be pursued. There have been some studies that indicate that there is more than one type of ASPS, and non responding mets like Brittany's and Tom's seem to support that theory. Perhaps, another type of systemic treatment to specifically target the ASPS of Tom's non responding met could be explored and pursued to be used in combination with his current treatment. I will be anxiously awaiting your next update, and holding you and dear Tom very close in my heart and most caring thoughts as always. Reaching out to embrace you with special hugs, deepest caring, healing wishes, warm friendship, and continued Hope, Bonni

[Olga]

I am reposting from Kathy FB page - Tom's update from Dec.6, 2018 re. his atezolizumab (TECENTRIQ) clinical trial at UPMC in Pittsburg:

After being on an immunotherapy trial for 18 months, he continues to have success. Tumors have disappeared, others have stayed the same and nothing new has grown. God has blessed us every step of the way. We are so thankful for our friends and family for helping us through. Our family would also like to thank Dr. Burgess at UPMC for making Alveolar Soft Part Sarcoma, as well as other rare cancers, her priority.

[D.ap]

Thank you Olga

Kathy and Tom ,
So incredibly happy to hear of continued success !
How big is the largest tumor being seen at this time?

Happy happy holidays!
Love
The Pearson’s

[Kathy]

Hi Everyone,
Tom has had 5 bowel obstructions in the past year. 3 since November and 2 in the past month. His surgical oncologist decided it was time for exploratory surgery to see what was going on. They thought they would find scar tissue, tumor, a kink...but they found nothing. They said they went through the entire colon 4 times and everything was clear and there was no sign of anything that would be causing his issues. Can anyone give us advice or ideas as to what could be going on. He has treatment Monday and will hopefully see his oncologist, but the surgical oncologist was stumped. He was left to question if it could be the treatment he is on.

[Bonni Hess]

Dear Kathy, I am so sorry for Tom's painful bowel obstruction problems, but so deeply grateful that surgical examination did not find any tumors or other concerning visible cause of Tom's 5 bowel obstructions. I Hope that an easily resolvable and treatable cause can be found, but I also Hope that it is unrelated to Tom's Atezolizumab treatment which has VERY thankfully thus far been so successful in shrinking/destroying his tumors and stabilizing his disease. Hopefully Dr. Burgess will be able to provide information regarding the possibility of the bowel obstructions being related to the Atezolizumab treatment, but as with all of the new Immune Checkpoint Inhibitor (ICI) treatments like Atezolizumab, there is very limited information available about the long term side effects of the ICI drugs as is the case with Brittany's now nine and a half years of Cediranib TKI treatment. Hopefully other Atezolizumab patients on this Forum or the Facebook ASPS site will share their anecdotal information with you regarding any gastrointestinal issues that they have experienced with Atezolizumab. In the meantime, take care, give yourself and Tom warm hugs from me, know how deeply grateful I am for your updates, and keep in touch as you are able. Heart to heart with special caring thoughts, healing wishes, warm friendship, and continued Hope, Bonni

[Olga]

Kathy - intestinal obstruction (partial or complete blockage of the bowel) is a registered side effect of atezolizumab.
Former owner of this drug Roshe in 2016 listed it as one of the most common Grade 3–4 adverse reactions (≥ 2%) - intestinal obstruction (partial or complete blockage of the bowel (4%). So it has to be shown in the leaflets that had to give you. By some reason in Tecentriq description after it was bought by Genetech there is no direct mentioning of intestinal obstruction? or I do not see it. This drug is mostly in the clinical trials and some immune related side effects are rare.
read the https://www.accessdata.fda.gov/drugsatf ... 000lbl.pdf closely see what you find there
also the latest review
Safety and efficacy of atezolizumab in the treatment of cancers: a systematic review and pooled-analysis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366347/

In my reading it looks like this is a rare complication for immune check point inhibitors overall, they even call it pseudo-obstruction as there is no obstruction but with the clinical symptoms of ileus.
I started to read on the possible causes of the intestinal pseudo-obstruction looking for some that could be immune system related:

1. Immune-related intestinal pseudo-obstruction associated with nivolumab treatment in a lung cancer patient.
https://www.ncbi.nlm.nih.gov/pubmed/29067858

2. A Report of Chronic Intestinal Pseudo-obstruction Related to Systemic Lupus Erythematosus.
https://www.ncbi.nlm.nih.gov/pubmed/30519633
so lupus is an autoimmune disease it should be suspected in case of the ICI use and rules out, lupus as an autoimmune side effects was described in Keytruda and Opdivo already . The severe dryness of the mouth Ivan had, as we figured, was a part of the rare autoimmune condition Sjogren's syndrome when the immune system attacks salivary glands.

Another possible cause associated with inflammatory cell infiltration
3. Histological characteristics of eosinophilic myenteric ganglionitis: an under-recognised cause of chronic intestinal pseudo-obstruction.
https://www.ncbi.nlm.nih.gov/pubmed/30607555
Did they sample the intestines for Lymphocytes infiltration? microscopic colitis?
it needs to be investigated by the gastro-enterologist

[Bonni Hess]

Hello again dear Kathy, As always, our extremely knowledgeable and always well researched Olga has graciously shared some excellent and invaluable information and insights which will Hopefully be very helpful to you,Tom, and his oncologist in determining the cause of Tom's perplexing bowel blockage symptoms, and also Hopefully help you find an easy resolution for them. It seems that even though the new meds thankfully apoear to be showing some very promising treatment success with providing tumor shrinkage and disappearance along with disease stabilization,, there are also unfortunately potential long term negative side efffects which are not yet fully known due to the drugs being so new and documented data not yet available, which is one of the reasons that shared current anecdotal treatment information is so critically important. With more special caring thoughts, healing wishes, and continued Hope, Bonni

[ntran727]

Hi Kathy and Tom,

I am glad to read about Tom’s response to Tecentriq. My oncologist is conducting a trial with that medication at Columbia currently and because of my new L4/L5, manubrium and right iliac bone Mets, I will likely be starting on that medication soon. Can you recap how long Tom has had the bone Mets and what was done for the treatment? I looked back on your posts and it seems like he’s has the brain met and L4 met since 2008? What were the sizes of them and how did they respond to the treatments you’ve had so far? I apologize because there are so many pages to read through and would be great if you could summarize for me. How is Tom tolerating the medication so far? I am sorry to hear about the bowel obstruction and that there is a nonresponding met, and I hope you get some answers soon in regards to treatment if the S2 met.

[D.ap]

Hi Kathy
I’ve spent the weekend with my young grand kids and have been following your post .
Has your doctors talked of IBS being a possible culprit ?
It’s a general diagnosis when the other possiblities of diverticulitus etc have been eliminated . It can and will in bloodwork show high white blood cell activity as the pain from the constipation raises the white blood cells counts.

Also Olga’s and Ivan’s thoughts on fiber and probiotics are excellent thoughts to discuss with your team as they can and will facilitate the bowel functions .
Also here’s a clinical study that talks of probiotics mitagating , specifics to CTLA-4 ici’s blockage.

“Bifidobacterium can mitigate intestinal immunopathology in the context of CTLA-4 blockade | PNAS“

https://www.pnas.org/content/115/1/157


We had to conjole our Josh by presenting the book
“Every body poops” to him to rib him into laughing on the subject of regulating bms . :)

[Kathy]

Hi Everyone,
I am writing with the news that Tom is no longer on the Atezolizumab trail. His recent scans showed a new tumor in the sacrum. He had another tumor in his ribs that was treated with radiosurgery and they feel that one did not respond. I don't have a lot of details as he took the call and learned the news as he was leading a board meeting, and I was with our girls at volleyball. Needless to say we have a ton of questions but I wanted to get the ball rolling on here. We would not have made it this far without this group and we are in need of guidance now. We have asked that they send us via email what they found and what they are proposing the next steps will be. I will post once we learn more. Even though I don't post a lot, there is not a day that goes by that we don't think of you all.
Kathy