When should ADT be given with SBRT?, Some SBRT news, looking at Radiosensitizers in Prostate Cancer treatment

[NPfisherman]

Greetings FPC folk,

It has been months since my last post, and I thought I would post something near to my situation and pick your brains on the issues... I am nearing the end of my 20 month vacation as my PSA has risen to about 0.7 now, and I had a Pylarify scan showing one lesion so I remain oligometastatic. I will try and go back to see Dr Steve Burton at UPMC, who did one of the Phase 2 SBRT trials with Dr Herron proving the value of SBRT in cancer treatment and treated my clavicle lesion--fully resolved per my scan...

The question is..."When should ADT be given with SBRT??" and the last time I waited until 6 weeks after starting ADT to do treatment... However, a recent article that I received from Cujoe, the K9 Terror says I should do it at the start. I am leaning towards this after the article-see below:

ncbi.nlm.nih.gov/pmc/articl...

Anyone have other input or thoughts??

Next, a recent article from Practice Update on the benefit of getting dual tracer studies in non metastatic PCa patients to find lesions and undergo SBRT versus ADT. While a small study, a survival benefit for SBRT was shown.-- see below:

practiceupdate.com/c/134094...

Lastly, I am looking at radiosensitizers for radiation treatment and my big disappointment is that Veyonda is not available, and the cost of Idronoxil is prohibitive to make my own Idronoxil suppositories... Nalakrats --get back in the lab please....LOL... I read an article from 2013 on radiosensitizers for radiation in PCa and that article is below:

ncbi.nlm.nih.gov/pmc/articl...

Any thoughts on radiosensitizers....I have just started looking at this issue and welcome thoughts...

Enjoy the weekend, folks....Off to DSW in South Hills and then getting some Thati food in Pittsburgh...

Don Pescado

[cujoe]

Don Pescado,

Welcome Back to the world of shared patient information and that of "The Science Is Coming". Since we have both had to relinquish our much-valued treatment vacations - due to rising PSA/BCRs, and have had confirmation of disease state via PSMA PET scans, we are once again paddling in similar waters and in the same direction.

I'll check my files on radiosensitizers, as I did quite a bit of research back when I did IMRT. (Hindsight Note: It wouldn't have hurt to have boosted them for the PSMA scans - as every little bit of effect on cancer cells is good and protection for healthy cells warranted even with routine scans where RT tracers/scan tech is involved.)

Good to have you back on-line. Enjoy the outing and esp. the Thai Food.

Keep It Safe and Well,

Ciao K9 Terror

[NPfisherman in reply to cujoe]

K9 Wonder,

Thanks for the kind comments...I have some more posting to do...either later today or tomorrow... Yes, it is back into the PCa ocean for both of us.... swimming well requires knowledge of the currents... staying informed is the key... Hope all is well in NC....had some great pad thai...

Life is Good !!!

Fish

[marnieg46 in reply to NPfisherman]

My thanks too Dave. Some great references to this topic...always one of some contention for me.

Long before this post you were a great source of information for me and provided support and helpful advice to ponder on this topic when we had contrary advice from his two MO's on whether Ron should have SBRT to that one last met with exponential growth from SUV of 8 to 57 in a month...before he added Xtandi to Lupron.

Obviously the right decision and made adding in the various relevant articles you provided at the time and your patience to try to answer my inane questions before taking the plunge.

Your keen knowledge of the science and new developments are always greatly appreciated as is your willingness to readily search out relevant articles...and change into plain English at least for m.... when a topic is raised.

Your help is never taken for granted. Marnie

[NPfisherman in reply to marnieg46]

Thanks Marnie,

I have done some more research and found the following article as well on natural radiosensitizers, so am looking into having suppositories made for upcoming procedure-see below:

ncbi.nlm.nih.gov/pmc/articl...

Some more research is needed before I start this project...

Hope things are well in Oz....

Dave

[MateoBeach in reply to marnieg46]

Hi Marnie. See my reply below to NPfisherman. Flying your way this evening. That book, Emperor of All Maladies, is amazing. Have you read it?

[marnieg46 in reply to MateoBeach]

G'day Paul, you will be flight bound as I write. We're all hoping you are having a very smooth flight and it's the start of a new chapter of your journey on the road to continued excellent health...a choice you'll look back on later as one of the best you've ever made.

I haven't read The Emperor of All Maladies but cujoe always knows the best books and has recently 'strongly recommend' I read it. I always try to follow up what he suggests because he has a good idea of the 'gaps' in my knowledge on this topic. I might add, he knows the best music too. I see a link to the book in Dave's post so I'll download it today.

With fish, they both try their best, given my limited scientific knowledge, to send references my way that will better help me to help Ron and then they are always willing to clarify what might be outside my 'comfort zone'.

I'll just add... the family are all very excited about your time with us in Sydney...and hoping the stars are aligned so you have a wonderful time. We'll talk soon...Marnie.

[MateoBeach in reply to marnieg46]

Yes they are both valuable contributors to the APC forum that I too greatly appreciate. I am happy to note you are connected to them for exploring and clarifying PC related topics. Given your role with Peter Mac cancer center and your advocacy role you will find the “Emperor of All Maladies” book to provide insight into the history of modern science based treatments in the fight to find cures for cancer. And why that is so difficult. I would bring you my hard bound copy, but am maxed out in my carry on only luggage. Not a quick read but a carefully crafted and accessible history.

Counting down to departure time. Happy the wait is over.

Paul

[marnieg46 in reply to MateoBeach]

Yes they are my 'go to' people and have been so generous in providing me with advice, helpful suggestions and also unwavering emotional support as Ron has travelled a complex and complicated journey especially over the last three years. Now, hopefully, you can be added to the mix which would be fabulous.

Great you are on your way. All of the family are actually quite excited for you. I've added you to my WhatsApp contacts and I'm sure we'll speak very soon..when you're settled perhaps you might text when you arrive safely. Be reassuring to know you are on Oz territory.

[MateoBeach]

Big Fish - Great post. My comments:In 2019 I planned a trip to GenesisCare Australia for Lu-PSMA-I&T treatments by Nat Lenzo. I asked if I could adjuvant Veyonda outside of trial. He was able to arrange it if I would pay for the drug under his supervision. However I did not do that as my PSMA scan with pelvic only oligo LN disease favored pelvic RT. So I did that in Oregon.

Fast forward 3 years. My PSA remains detectable but low (<0.2) but f/u PSMA scan shows 2 new LNs. Consulted DR Lenzo and my RO again and decided on two phase treatment. 1) SBRT to the 2 LNs (done). Then 4 weeks later two treatments with Lu-PSMA-J591, a highly binding monoclonal antibody ligand. I fly to Perth this very evening and get the first dose this Friday. Second follows in two weeks.

I asked him about the Veyonda again but he does not favor it with this protocol for clean-up of any unseen micromets. I told him I have been on high dose cyclic testosterone for my modified BAT program. Expecting he would want me to stop that. He said no, rather he wanted me to stay on high Testosterone regimen through the SBRT and on through the Lu treatments. My T level is currently >1500.

This fits with your referenced study showing the benefit of ADT with SBRT appears limited to the LHRH flare, which is tantamount to a testosterone surge. So interesting.

Finally, looking over the radiosensitizers article again, and noting they include well known natural agents that are in my usual regimen, including genius to , resveratrol, curcumin and others. While they are also known as antioxidants and normally would be avoided during any kind of RT. It seems that their radiosensitizing activities may be predominant. I did ask Dr Lenzo if I should stop them and he said that was not necessary. He also favors continuing Metformin. So interesting. And thusly I will proceed.

The Little Dog, Mateo

[NPfisherman in reply to MateoBeach]

Best of luck with your treatment....Have fun with Ron and Marnie... I hope to make it that way at some point...Safe travels....

Fish

[MateoBeach]

Rapamycin (Sirolimus) also has many references as radiosensitizer. Will continue my low dose regimen, 3 mg once weekly.

[NPfisherman in reply to MateoBeach]

Good to know....Thanks...

Fish

[MateoBeach]

Don Pescadero (the fisherman, not the fish!)

I came across this post from some months ago. Fascinating (for me) discussion of radiation sensitizers. I read it in may for my SBRT. Under the category of "natural radiosensitizers" I remember being surprised that certain natural supplements that I am already using regularly in my cancer-fighting health and longevity-promoting regimen.

These include some of the "usual suspects" including genistein, resveratrol, curcumin and quercetin which, except for genestein, I have been using daily. I asked my RO if I should discontinue these for my SBRT since conventional thought is their anti-oxidant effects might impair results of RT. He said "No need. You can continue them." (!)

Looking at the other proposed sensitizers I noted the COX2 inhibitor celecoxib, which I also take daily (400mg). Of the other natural plant-derived possibilities, 3 are interesting: Gossypol (from cottonseed) notably has strong 5-Alpha reductase activity. Parthenolide, an anti-inflammatory available in Feverfew herbal supplements is widely available. And finally, of most interest is Embelin.

Embelin is the main component in the fruit-seeds of Embelia ribes, "False Black pepper" long used and widely available in Ayurvedic medicine suppliers (powder and fruit berries). It is sold under the Auyurvedic name "Vidanga". It has multiple actions, but most important to radiation effects is inhibition of the X-Linked Inhibitor of Apoptosis, XIAP.

ncbi.nlm.nih.gov/pmc/articl...

"The mechanisms of the action of embelin are numerous, and most of them induce apoptotic cell death that may be intrinsic or extrinsic, and modulate the NF-κB, p53, PI3K/AKT, and STAT3 signaling pathways. Embelin also induces autophagy in cancer cells; however, these autophagic cell-death mechanisms of embelin have been less reported than the apoptotic ones."

I would consider adding this should I ever need radiation again. BTW, on the implication of the "Androgen Flare" as providing much of the benefit of ADT with RT. Many are not able to precisely manage starting ADT without bicalutamide when scheduling RT. Or the RO may not be in agreement with deviating their usual practice. For me, being an outside-the-box fellow, I would consider the alternative of using testosterone gel for a week or two at the start of RT even if on ADT already. Of course that is not SOC, and I cannot advocate it for others. Just exploring a possible idea. Trolling in deep waters. Pablo

[NPfisherman in reply to MateoBeach]

Pablo,

Trolling in deep waters reduces your risk of snagging your lure for sure...lol... Yes, Lulu700 called me Don Pescado years ago, and so....the name is... Thanks for the reply on the radio sensitizers and Embelin is new to me... I do like the thought of boosting T with Androgel prior to SBRT which I might try if there is a next round...

Tonight, the Lady M has returned from a 10 day Locum tenens assignment and I am enjoying having my best friend and true love back home...gotta get back to the one and only...

DD

[MateoBeach in reply to NPfisherman]

👍💕🌹. Regards to you and Lady M together again.that is indeed the best. P