Understanding the Abscopal Effect and its Potential Role in Developing a Cure for Cancer-Part 1

[NPfisherman]

Greetings FPC members,

One of the more intensely studied phenomenon in cancer research has been the abscopal effect. As a true believer in SBRT and the abscopal effect, I have faced posters questioning the existence and benefits of the effect via SBRT in treating PCa. But what is the abscopal effect??

From Wikipedia, "The abscopal effect is a hypothesis in the treatment of metastatic cancer whereby shrinkage of untreated tumors occurs concurrently with shrinkage of tumors within the scope of the localized treatment. R.H. Mole proposed the term “abscopal” (‘ab’ - away from, ‘scopus’ - target) in 1953 to refer to effects of ionizing radiation “at a distance from the irradiated volume but within the same organism.”

In a nutshell, localized treatment of tumors results in shrinkage of other tumors that are some distance away from the area of treatment as a result of activation of the immune response. This treatment can be a combination of a check point inhibitor like Keytruda, Yervoy, etc. with or w/o radiation or cryotherapy as well as possibly an infusion of an immune stimulator like GM-CSF or radiation therapy alone.

"Well gee, Fish--with that much going on, then why are we not seeing more cures in PCa??" The answer is that tumors have a way to block some of the immune response through regulatory T cells, avoid detection, and certain genetic factors may also play a role in blocking the response. Consequently, the studies have shown mixed response rates for the abscopal effect--see the article below:

futuremedicine.com/doi/full...

Part of the problem is determining: 1) who will be a responder, 2) ways to ensure a response will occur, and then....3) prolonging that response for a potential cure.

Research is ongoing on determining genetic predisposition to a response. At this point, response rates vary from studies-(refer back to article). In The ORIOLE trial, about 9% of the individuals receiving SBRT showed increased T cell clonality continued at 90 days. So, if the abscopal effect exists in treated patients somewhere between 10-30%, then how do we increase that number and prolong the effect??

That is indeed the issue. Increasing the response percentage and prolonging the immune response generated. Part of it will be sequencing I believe. Determining the proper treatment order that ensures that response and prolongs it... The other is discovering ways (treatments or drugs) to promote and prolong the immune response related to the abscopal effect.

I hope you enjoyed this introduction on the abscopal effect and I look forward to discussion.

Don Pescado

[cesces]

How widely accepted is the and abscopal effect?

[tom67inMA in reply to cesces]

I can say my MO isn't a big fan of it, and so far I've been unable to produce any anecdotal evidence that it's working in me. My personal view/fear is that with a high and aggressive tumor burden, the cancer simply has my immune system outnumbered and outgunned.

[tom67inMA in reply to cesces]

ps, I was on atezolizumab during radiation to my bladder, and my cancer redeveloped during this time. Very disappointing to me.

[NPfisherman in reply to tom67inMA]

You had intraductal from the beginning...not sure what type of radiation you had.... you have had it tough... My MO was not a fan of SBRT and discouraged me, until after the ORIOLE trial and then he said what I did in getting SBRT was "smart"... No treatment works for everyone... Hang in there....

Fish

[tom67inMA in reply to NPfisherman]

I asked and best I can remember I had image guided radiation, where they take a small CT scan to line everything up, and then zap a beam of radiation. It did a nice job of cleaning up what chemo left behind in my bladder. I was almost NED for my neuroendocrine cancer, but by the time the bladder cleared up it was already back in my liver. My bladder was still clear on last scan, and I've recovered most of my urine capacity. My prostate also looks normal on a scan apparently as they never comment on it. It started all this, and now it's playing innocent. Stupid useless organ. 😝

[6357axbz]

Out of the park fish! Nice primer on abscopal. TY

[NPfisherman in reply to 6357axbz]

Glad you liked it... As a believer in combo therapies, I think utilizing various strategies will increase abscopal responses. A drug like Veyonda with SBRT and a vaccine offers real hope for a cure, especially for nmHSPC or oligometastatic HSPC. Let the Science play !!!

Fish