article supporting primary resection in metastatic setting

Surgery to remove the primary tumor.
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Olga
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article supporting primary resection in metastatic setting

Post by Olga »

We still have cases when our ASPS patient's diagnosed with metastatic state of ASPS are denied resection of their primary tumor on the basis that their disease is incurable anyways.
There is a new article from Massachusetts General Hospital strongly advocating resection of the primary tumor in the presence of the distant metastases:
Prognostic factors in alveolar soft part sarcoma: A SEER analysis.
http://www.ncbi.nlm.nih.gov/pubmed/26804150

"For DM (metastatic disease) patients, primary site surgery significantly improved survival...
surgery is indicated in patients presenting with DM."
Olga
Bonni Hess
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Re: article supporting [rimary resection in metastatic setting

Post by Bonni Hess »

Dear Olga,
Thank you for sharing this very important article which supports and confirms what you and I have always advocated regarding the critical importance of resecting the primary tumor in spite of the disease having already metastasized, in order to prevent the continued dissemination of tumor cells into the blood stream from the primary tumor and to reduce the body's tumor burden to strengthen the immune system to better fight the disease. There are several patients on this Board who could benefit from the confirmation of this approach to fighting this insidious disease, and Hopefully they will pursue sharing and discussing it with their uncooperative doctors. I am personally familiar with several ASPS Community patients who tragically lost their battles and who for various reasons refused to have their primary tumors resected, and/or who were not encouraged to do so by their doctors who took a palliative approach rather than a curative approach to managing and treating their ASPS.
With deepest gratitude for your thoughtful special sharing, and with continued Hope,
Bonni
D.ap
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Re: article supporting [rimary resection in metastatic setting

Post by D.ap »

Case Series: Abscopal Benefit of Surgery in 3 Immunotherapy-Treated Patients With Unresectable Cancer


Great write up, making 3 supportive cases, of usage of immunotherapy along with surgery ( and debulking ) to create a possible systemic immune response on metastatic tumors . Immunosupportive verses immunosuppressive .

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069027/
Debbie
Olga
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Re: article supporting primary resection in metastatic setting

Post by Olga »

Deb, its a great read, thanks for posting this article. I general I would suggest the debulking of the massive tumors are going to be supportive to immunotherapy having reduced the immune suppressive effects of it (for example as it is known already ASPS bulky tumors are releasing TGF-beta - a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation and the response to ICI drugs depends on the active lymphocyte population).
But on the other side, I've read their examples with great interest and IMHO they are very inconclusive to the proposed abscopal effect. First, the response to anti-PD-1 inhibitors can happen at any time without any obvious reason - i.e. it might just happen after the surgery. The medium time to response for ICI drugs is 6 months and there are cases known when it happened 2 years after the start.
On a side note, it is very interesting that in the last case they actually did not find any viable tumor tissue although all the radiological signs were for the massive progression. This article is also needed to be posted in the treatment response evaluation problems of the ICI drugs topic -
new sub-forum is opened for that here:
viewforum.php?f=92
Olga
Olga
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Re: article supporting primary resection in metastatic setting

Post by Olga »

This is how having unresected bulky primary or metastatic tumor can cause the resistance to immunotherapy:
Altered Cancer Metabolism in Mechanisms of Immunotherapy Resistance
https://pubmed.ncbi.nlm.nih.gov/30439456/
The altered metabolic landscape of the tumor microenvironment can suppress the infiltration of immune cells and other functions of antitumor immunity through the production of immune-suppressive metabolites. Metabolic dysregulation in cancer cells further affects the expression of cell surface markers, which interferes with immune surveillance. Immune checkpoint therapies have revolutionized the standard of care for some patients with cancer, but disease in many others is resistant to immunotherapy. Specific metabolic pathways involved in immunotherapy resistance include PI3K-Akt-mTOR, hypoxia-inducible factor (HIF), adenosine, JAK/STAT, and Wnt/Beta-catenin. Depletion of essential amino acids such as glutamine and tryptophan and production of metabolites like kynurenine in the tumor microenvironment also blunt immune cell function.
Olga
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