Serious diagnosis (G9, IDC+, cribiform, PNI, lymph and bone metastasis). ARAT better than Dtx for IDC+ (OS m +50%), thereby Enza + 66 GY radiation to primary tumor. PSA drop to 0.03,
No sign of tumor activity on MR after treatment, all lesions (soft and bone) gone. NGS shows TMB-H (5), Pten Loss and ATM, signature 3.
I think of Pembro as 2line defense, then Ipatasertib/Abi - ThoriumPSMA 617 +BayerATR+Olaparib. Deficiency in ATM means hard to fix DSB, cancer cell must use NHEJ which is error prone. In my case will all kind of DSB be good, that’s why radiation workshop very well, especially alpha emitters.
Will have liquid biopsy everything 3 month - following the PTEN Loss amount as ctDNA.
Hope that’s all good but I have no clue what most of it means. If there’s some good info for the rest of us in there, I’d sure appreciate a Laymans summary
I was waiting for someone to broach the subject. With, hopefully(?), up to 10,000 tuning in regularly, one or two are going to be bewildered. lol
I have seen ARAT recently: Androgen Receptor Axis-Targeted, I believe. But even that might confuse some. It refers to agents that either inhibit androgen production or androgen receptor {AR] functionality. As such, it includes classic ADT drugs that inhibit gonad production, e.g. Lupron, as well as drugs such as Zytiga that also target adrenal production; and finally, AR antagonists such as Xtandi - either alone or in combination.
While ARAT is a new term, Charles Huggins was the father of ARAT (before I was born) & received a Nobel for it in 1966. ARAT isn't curative, but we are stuck with it, it seems.
Thx. That’s helpful. I’ll bet the overs on only “one or two” being bewildered lol. I’d guess more than half of us lol. How about the following terms that are also new to me and I’ve been on this site now for a few years:
How about this - those who feel comfortable with something in the list, please grab one - don't be greedy! Respond quickly to stake your claim, & post at leisure.
Docetaxel (chemo) - if you have the cancer cell subtype IDC (5% of the prostate cancer population initially rising when you reach CRPC) it is much better to use either Abiraterone og Enzalutamide, the MDs refer to them as ARAT, Androgen Receptor Axis-Targeted instead of expressing the long words - Apalutamide is also belonging to this group. Others are using the term CAB - Complete Androgen Blockade - meaning bringing the testerone to a very low level, all the cancer cells depending on AR will die. OK?
2. IDC
Lession 2 for me:
IDC - Intraductal carcinoma, subtypes dense, solid or loose. The prognosis is worse, that's why it is important - very important - to start off not using chemo (low ORR meaning Objective Response Rate for chemo) . OS median is typically 50% longer!
3, NGS
Lession 3 - very important!
Next Generation (DNA) Sequencing - meaning screening the cancer for which mutations that is causing your cancer, in my case PTEN (20% initially of all) and ATM (5% )which is the gene repairing breaks/faults/errors in the cancer cell DNA. ATM belongs to a group called HRR - homologous recombination repair.
When you know your gene mutations you will know what kind of treatments that probably would work for you - otherwise not.
4. TMB
Lession 4:
Tumor Mutational Burden: The amount of mutations. In general prostate cancer is regarded as cold - few mutations, thereby few terapeutic targets. Average is 0,9 pr megabase- then Checkpoint inhibitor (Pembrolizimumab) and Immune Checkpoint inhibitor Nivolumab almost never have an effect. BUT, if your value is more like 4 and upwards chances are much better.
5. ATM
Lession 5:
This is really interesting because all kind of radiation induces DSB - Double Stranding Breaks of the DNA. ATM is repairing DSB errors - no wonder having much better effects than average using radiation (SBRT, EBRT, Brachy) - the electrons cause DSB - they cut off the strands- OK? Again - with Radium 233 50% better results - OS median from 18 to 36 months.
Further- Radium 233 (alpha emitter), Thorium 617 PSMA (alpha emitter)- actinum PSMA (aplha emitter) - lutetium PSMA (beta emitter) induces DSB, kind of explosion from within the cancer cells. Nonfunctional ATM - no repair that way - killing rate very high obviously.
6. NHEJ
Lession 6:
When I started to study my own disease (normally working with IT virtual infrastructure as a profession) I had to understand all the abbreviations before I could move on - cancer on a molecular level is pretty complex. ATM variants alone are 2000!
I thought initially - ATM Loss -no repair, 100% kill! But the cells are wise - they have a backup solution called NHEJ - Non Homologuos End Joining
which is error prone - it's like fixing something thats broken in your car by tape instead of a proper job replacing the part with the original from the manufacturer - ATM.
Without NGS - I would never know I had a PTEN Loss and no possibility of including this treatment in my future plan!
Lession 8:
I have performed an extensive selfstudy in my disease - read everything in Pubmed from 2016 until know regarding my specific situation - and it turns out that the possibilities are pretty good! No cure - but I can extend my life by along time. It's also much easier to talk to my MD - I use his abbreviations - thereby the conversation is a lot more speedy and meaningful.
That’s awesome. Now I can follow a bit. Thanks so much for taking the time to educate me (and others here). You e really become quite the expert. Impressive!
Yes, whole body. No bone scan, had a few almost invisible bone lesions. Had two pet-scans, important regarding later PSMA treatments. A German professor noticed that using Enza in the CRPC phase before treatment upregulated PSMA density by 50%, thereby increasing the efficacy accordingly
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