New strategies against bone metastases from prostate cancer - Science Daily

[cujoe]

From the paper:

There are two types of bone disease from metastases: lytic metastases, which destroy bone tissue, and blastic metastases, which build new bone-like tissue with cancer cells. Currently, it doesn't matter if a bone metastasis is lytic or blastic -- they are both treated the same way. But the current study shows that the genetic and cellular landscapes of these two types of metastases are different, providing different drug targets and suggesting different treatments . . .

Importantly, both types of bone metastases also had characteristics that predict response to immunotherapy. Doctors and researchers call primary prostate cancers "cold," meaning they tend not to provoke an immune response. However, both blastic and lytic bone metastases had high levels of the protein PD-L1, which could mean they are more likely to respond to the class of anti-cancer immunotherapy known as checkpoint inhibitors.

"The other interesting point of our studies is that we developed a test that can directly measure immunotherapy and pathway targets in bone metastases," Owens says. "This is significant because we could potentially use this as a test to determine which of the many immunotherapies could be best for an individual patient, one at time, and truly provide a personalized therapy. If I had metastatic disease in bones, I would like a pathology department to know that the immunotherapy they wish to treat me with has a good level of target in the tissue they are hoping to treat." (emphasis added)

Science Daily article is here:

sciencedaily.com/releases/2...

Full research paper is available as PDF download using paper doi here:

sci-hub.se/

Dr. Don The-Wizard Pescado's Science keeps on coming. 2020 should be a banner year for PCa developments.

Happy 2020 to All & Be Well - Captian K9

[6357axbz]

Good post

[dougnola]

Thanks, Cujoe! My next face to face with Sartor is in February. I will be asking which type I have. They may have told me in my original diagnosis but the only words that penetrated my brain back then were ones like “terminal”, “castration” and stuff like that. Happy New Year from NOLA! DougNOLA.

[cujoe in reply to dougnola]

Doug,

Not having spent much time exploring the mechanisms of bone metastasis, the fact that there are two types was completely new info for me. Being able to know which type is at work would seem a major advance in making targeted treatment decisions. Good stuff.

Go Saints - Who Dat? Future 2020 Super Bowl Champs. Dat's Who. Happy New Year &

Be well - cujoe

[NPfisherman]

K9 Compadre,

Thanks for posting the Science to start the New Year...I read through the Science Daily as well as the "meatier" paper... When my voyage on this hell ship started, my MO told me I had a "lytic" lesion....of the two, the "blastic" lesions have a better prognosis for OS...

Consequently, he started me on Lupron and Zytiga right away and 6 weeks later, I had SBRT--3 sessions to the lesion on my clavicle... I have remained "undetectable" on my PSA since and hope my MO will send me to Dr. Tran who did the ORIOLE trial for Oligometastatic patients...the data continues from the ORIOLE trial... I had a cell free DNA test which barely had enough material to do the test and a very small amount of one mutation of unknown significance...I want to see if Tran has any other ideas to improve my OS...

From the article: A hallmark of lytic bone destruction is the increased activation of osteoclast resorption. Osteoclasts stain positively for CD68 because of their myeloid-derived nature that also stains a diverse macrophage population in the bone [9]. Lytic prostate cancers in bone possess CD68-positive osteoclasts and a large collection of macrophage cell types, which are more abundant than in blastic lesions ...Lytic type metastatic prostate cancer had increased cytotoxic cells, macrophages, exhausted CD8 cells, CD45 immune cells, neutrophils, and mast cells (Fig. 2e, f). The increase in immune cells in lytic disease are associated with fewer bone cells by gross histological analysis due to their destruction and replacement by tumor and stromal infiltrates.

I have posted two articles on getting macrophages into the fight :

healthunlocked.com/advanced...

healthunlocked.com/advanced...

and one article on "reawakening" T cells to fight cancer...

healthunlocked.com/fight-pr...

The Science is Coming !!! I need to figure out which Science to pursue for me...

Don Pescado

[cujoe in reply to NPfisherman]

Mr. PCa Wizard, You are way ahead of me with your PCa + general medical knowledge, but i'm trying hard to catch up. Thanks for the links and added insights. Good luck on stress-test Friday & Be Well - K9

[NPfisherman in reply to cujoe]

Thanks my K9 Amigo... Keep Sharnoosh in prayer for tomorrow....We are back to back stress testing...her tomorrow and me on Friday.....Holy Crap!!! Hope things settle down soon...

Fish

[cujoe in reply to NPfisherman]

Way TWO much stress for me. Give us some good results and please don't break the machine. Will be waiting for results from both of you with Fish-baited breath. Be Well . . . Captain's orders. K9 out

[marnieg46 in reply to NPfisherman]

Question to the expert on all things scientific....

Where will I find the words I'm supposed to be looking for - Lytic/Blastic? On the initial pathology report? Or wouldn't we have that information because it needs to be a sample taken from one of the actual bone metastasis?

As I'm struggling to get Zytiga into this picture maybe trying to sort this out as well is one step too far at this point in time🤷‍♀️

[NPfisherman in reply to marnieg46]

Hi Marnie,

Thanks for the compliment... I am not the expert on all things scientific but I have some knowledge...may God preserve my brain power

When Ron had a bone scan, or PET/CT, they should have looked at it where the bone lesions are and stated that information ...Lytic lesions do not show up well on a bone scan because they are erosions of the bone. The Blastic lesions are deposited in the bone and show up as sclerotic or hyperdense areas/ lesions...The lytic lesions get into bone marrow and cause major anemia issues...some info from ACS on bone metastases:

cancer.org/content/dam/CRC/...

Interestingly, about 15% of prostate cancers with bone involvement are a mixture of lytic and blastic lesions ....

As for Zytiga, it will work on either one. My MO chose it because of the recent STAMPEDE, LATTITUDE, etc studies for MHSPC patients...The earlier intervention is better as proven by those trials...

Keep things running in Oz.... Hope there is some coming rain for the bushfires ...

Be well, mate...

Fish

[marnieg46 in reply to NPfisherman]

Thank you Dave. Very clear now. You're a genius at changing the science into everyday language. I'm grateful.

I've checked and those words aren't on the bone scan. However, on the F18 PSR-PSMA + CT chest/abdomen/Pelvis with IV Contrast (25/1/19).... (can't believe that was nearly a year ago!!!).... the report notes that the avid bone metastases including target lesions on ribs right 3rd laterally 5.21, multifocal areas on 6th rib 5.84, lateral aspect of left 8th rib 10.45 and T3 8.31, and T5 5.28 as 'sclerotic' lesions. Is this relevant or do the descriptors actually need to be noted on bone scan and the PSMA can't pick up the differentiation referred to in cuJoe's article?

I know you'll make some sense of the above.

🤞and prayers for Friday coming your way. Marnie

[NPfisherman in reply to marnieg46]

Thanks for the prayers...Indeed, the sclerotic lesions indicate that it is blastic... a better prognosis....the PSMA scan is sufficient...my lesion could not be found on bone scan and small lesions may not be noted...mine was the size of a thumbnail on Axumin scan...not as good as PSMA scan but better than bone scan... the SUV readings listed indicate that Ron would likely be a good candidate for the Lu-177 or AC-225 or the combo...but I am not an RO...

I'll keep you posted on my test...

Fish

[marnieg46 in reply to NPfisherman]

Well then that's great ... that they aren't blastic. From the recent conference sessions I've watched/read it would seem that Lu 177 done earlier, rather than later as has been the trend, is preferable for some men. I think the AC 225 or combo were mentioned in one of the videos I watched recently so I'll go back and check them out.

Another hot one predicted here for tomorrow 43 degrees (109.4F).

Yes do keep me posted on how you go. m

[NPfisherman in reply to marnieg46]

They are blastic but not lytic....lytic is the worst....just my luck...hoping it cools down soon....looked like there was a chance of rain for NSW... Indeed, earlier, more aggressive treatment seems to be the new standard for MHSPC... The mixed Lu-177/AC-225 has a lower incidence of salivary gland and parotid gland toxicity

I'll keep you posted...

Fish

[marnieg46 in reply to NPfisherman]

Great. Most appreciated ☺️

[tom67inMA in reply to NPfisherman]

Oh great, I'm one of those 15% Anyhow, just wanted to clarify that my understanding is that most lytic lesions still have increased blastic activity, just not enough to compensate for the increased activity of the osteoclasts. As such, they will show up on bone scans, just not as well as a blastic lesion.

And of course, when you have as many bone lesions as I have, it doesn't matter whether they all show up on a bone scan or not as treatment will be systemic. In cases like mine, scans only need to show the ones that might get zapped with radiation to relieve pain.

[NPfisherman in reply to tom67inMA]

Sorry to hear this, but you are on Zytiga with Lupron and the lack of testosterone is like putting these lesions in an androgen desert... they do not thrive and some have reported resolving of lesions over time...I have read your profile and you are doing all the right things... Germline and somatic testing for other clues on where to attack....Some great new drugs are coming that will be "add-ons" for the current regimens... a 3 drug cocktail is about 3 years or so away...Keep "in motion" Tom...

Best of luck for the New Year....

Fish

[tom67inMA in reply to NPfisherman]

Yeah I'm one of those interesting cases of bad prognosis but great response to aggressive treatment. Holding off on generic testing for now, as they'll be testing for more genes and have more options in the coming years. With a bit of luck there will be new options when zytiga quits on me. Keep the science coming!

My next PSA test is tomorrow, hope I didn't just jinx myself.

[NPfisherman in reply to tom67inMA]

I'll put you in prayer this evening ...your track record on Zytiga is solid... Good luck...

Fish

[NPfisherman in reply to tom67inMA]

Any results yet? Hoping for the best for you ....stay in motion....

Fish

[tom67inMA in reply to NPfisherman]

Results just came online. PSA <0.01, ALP 43, Hgb 13.7, etc., etc. Only fly in my ointment is now I have blood in my urine. Yep, went to the can before leaving for my appointment and out came pink lemonade. Ugh. Should results of urine culture by Monday, and if it's not an infection it will be back to the urologist for a bonus check of the bladder cancer I'm sure. Let's hope it's all just scarring from the TURBT.

[NPfisherman in reply to tom67inMA]

Great results ....sorry to hear about the pink lemonade....bet is the TURBT or an infection....When they give you pink lemons, make pink lemonade....I will pass on your Lemonade Stand... <grin>...even if free... Have a great weekend...celebrate the solid results....

Fish

[tom67inMA in reply to NPfisherman]

I got a laugh out of the visual of setting up a lemonade stand, thanks for that! The wife and I are in celebration mode.

[TFBUNDY in reply to NPfisherman]

Great stuff Don. Keep it coming. Happy New Year. Hope it's GREAT for you. Cheers

[NPfisherman in reply to TFBUNDY]

I hope it is a great year for you as well and for all of us... Watching the Science for the breakthroughs... Cujoe gave us some interesting information with this article... I will be seeing about getting some posting done this week... Happy New Year and Cheers to you... Keep things going in the UK....

Fish

[GeorgeGlass in reply to NPfisherman]

NP, What are your thoughts on Dr. Tran? Is he primarily focused on the immunotherapy and radiation side of treatments, or do you go to him as your primary cancer doctor/advisor? Does he do lots of blood tests and thoroughly analyze your situation from a wide-lens perspective. I just stopped going to a semi-famous urologist because his appointments were like 7 minutes long and he would only do blood tests for psa and nothing else. I also have another oncologist I've seen. The local/semi-famouns urologist was pawned off on me by the oncologist at Duke. Thus, I'm still looking for a great cancer doctor with a wide range of expertise, so they aren't just pushing one or two SOC treatments or meds on everyone that comes through the door.

George

[NPfisherman in reply to GeorgeGlass]

I have never seen Dr Tran... I see Dr Ornstein at Cleveland Clinic for MO, and Dr Burton at UPMC for RO. I think Tran is focused more on the immunotherapy and radiation side of things. He did prove the abscopal effect by showing increased clonicity of white blood cells as a result of SBRT in the ORIOLE trial. I think he knows his stuff... For me, my MO is my primary information/ discussion course. I trust him. He lets me order my own labs, and have say in what happens with treatment. I am not sure there is a perfect doctor-patient relationship, but we come close...

Fish

[Snoger]

No

[Papillon2]

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