She can't stand by most of these because they aren't SOC.
I asked her about a number of things for SBRT. The ones she liked are attached. I don't have an HRR mutation. Yet she and the RO and another MO liked the theory of adding olaparib to SBRT (or RT).
A few others. These are not for RT - just general PCa.
5. Melatonin – how much? good 10mg+
9. Mushrooms good but we don’t know the details of which ones, how much, when.
14. Flaxseed good
He takes metformin, celecoxib, Pitavastatin, low dose naltrexone, mebendazole and ivermectin. Also lots of supplements including melatonin. I will talk to his MO about the Olaparib. He does have TP53, PTEN loss and TMPRSS2. I heard TP53 works well with BAT. Has SBRT kept your PSA under control for long periods? There is so many new treatments coming. What are your thoughts on the mRNA vaccine for PCa? I believe a cure will be in the future. Thank you so much for this info.
You're very welcome.
The evidence isn't there for LDN, mebendazole or ivermectin. Why does he take them? (resensitization maybe?)
Metformin, statins, NSAIDs have evidence. For efficacy and a better side effect profile I prefer 81 mg aspirin to celecoxib - AM and PM. If he's overweight (75% of us are) then metformin is good - but not an excuse not to eat right and exercise!
As far as I know the mRNA vaccine isn't ready. But the technology is exciting and it's something I watch.
A cure is hard. For one thing we're dealing with hundreds of thousands of variations. Think of the measles. PCa is far more complex. It's not a simple problem. That said, many advances have come out since my diagnosis 7 years ago. I'm very hopeful. Statistics showed me a 2-4 year lifespan. Seven years later my PSA is low. No pain from PCa.
Huge improvements in SBRT. Look up ORIOLE and STOMP and PROMETHEUS. ADT with SBRT is a literal killer. Add olaparib to it and even better - doesn't matter if you have an HRR mutation. SBRT is creating a state of "BRCAness".
I saw those new publications on MDT for oligometastic. Very encouraging. He also has a integrative MD that prescribed the mebendazole, Ivermectin and LDN. I agree that there is limited evidence and its mostly anecdotal. He is not overweight anymore since I changed his diet to low glycemic. The metformin is for the off label use for PCa as well as the statin. His lipid profile is actually great. The heterogeneity of this PCa does make it more complex for sure. So we are trying to hit as many pathways as possible with these off label drugs and supplements. Especially now knowing he has 3 aggressive variants. Scan is next week and I think we are prepared now for a course of action if anything shows up. Thanks again for your help. We will beat this down!!!
My integrative doc also wanted to prescribe those for me. I even relented for a while and took LDN. But, like you said, it's anecdotal. I would wager if you asked most of the men on those for details and they were honest, they'd admit to doing ADT or SBRT or an ARPI or perhaps have G4+3 or even milder "cancer".
I've known a few guys who were certain the the "cure" was ivermectin or mebendazole (or fenbendazole). Every single one of them gave up. Some of them did the solubility stuff. Some process I guess.
I recommend a statin for all PCa patients as long as their MO doesn't have a good reason for them not to take one. Metformin might be beneficial. Limited evidence and the trials have diverged. Aspirin has a good risk/reward ratio. I have been taking aspirin (and a statin) almost since the beginning. I use a modified BAT therapy so thinning the blood is beneficial. And my cholesterol was 200+ most of my adult life. A statin is good to control it and might have PCa benefits in addition.
Maintain that positive attitude! Diet and exercise are important too. Exercise is likely the most important thing we can do as PCa patients (or older people in general). The problem is it's free and it's not sexy. We want to pop a pill; exercise is work.
Read my chapter on exercise. Much of it is SOC. Some speculative. But just the accepted benefits alone should convince anyone to start moving.
We both do weightlifting, rebounding and biking. I bought a pilates reformer and I love it. So good for the core and stretching. Only buying organic, antibiotic and hormone free meats. Watching toxins and inflammation. Thank you for the book. This is going to be very helpful.
Great! What brand of pilates reformer? Have you ever tried BFR?
I have not tried BFR. My reformer is from Li Fitness
Coincidence? I was looking at reformers and have one from Li Fitness in my cart.
I think BFR is awesome. My NMD used to be a bodybuilder. He's in his 30s and when I had him try BFR he loved it. Best for arms IMO. Very cheap to try out. I wouldn't waste money on the fancy pump-up bands. I have a set but use the manual straps instead. You could even use a sock or t-shirt to check it out.
Works wonders stand-alone or for rehab or for older adults (and younger ones if they don't want to wear their joints out). Great pumps with 35% of the weight you normally use.
I've never heard of BFR until now. I had to look it up. Lol. Sounds very interesting. If you get this reformer it is well worth the 1200.00. It has 2 red springs(heavy duty), 2 green (medium) and 2 yellow (light). It comes with a jump board and a box. It has double strap loops for the legs and arms and is easily adjustable. The head rest is comfortable and also adjustable. I use utube videos for my workouts. I can send you links later. They also have rehabilitation workouts on utube. But haven't seen any BFR workouts but now I will look for it. I absolutely love my reformer and sometimes work out on it twice a day. I bought it in Dec 2024. No more lower back pain either or tight muscles. I did floor pilates for years off and on this is definitely more fun.
I do it as well, especially at the end of a normal training session, except for one day per week in which I train 90% of the time BFR (legs and arms). The feeling is very nice and different. Muscles like variety!
i like 5x5s in the morning and BFR in the evening.
When I'm ADT I stick to BFR.
The variety thing is one reason for the fad workouts. "I did blah blah blah, greatest thing since sliced bread!"
🤣
Yes, that’s exactly the advantage of an MRI-Linac—it provides real-time imaging, allowing for adaptive radiation delivery that spares surrounding organs more effectively than traditional methods. This should, in theory, reduce toxicity to the bladder, rectum, and urethra.
However, the concern with adding olaparib isn’t just radiation exposure to surrounding tissues but rather systemic toxicity and synergistic effects on normal tissues:
1. Systemic Effects of Olaparib – Unlike radiation, which is highly localized, olaparib circulates throughout the body. Even if the radiation is precisely targeted, olaparib could still affect normal tissues that naturally experience DNA damage and rely on repair mechanisms (e.g., bone marrow, gastrointestinal lining).
2. Increased Normal Tissue Sensitivity – While MRI-Linac minimizes dose to surrounding tissues, it can’t eliminate all exposure. PARP inhibitors could make even small doses of radiation more toxic to nearby healthy cells, potentially increasing late rectal and bladder side effects.
3. Unknown Interaction with High Dose Per Fraction SBRT – SBRT delivers a much higher dose per fraction than conventional radiation. The combination with olaparib could cause unexpected or more severe toxicities, which haven’t been fully studied in this setting.
If toxicity risks were manageable, MRI-Linac + SBRT + olaparib could be a powerful combination, particularly in high-risk cases. But without data from well-designed clinical trials, oncologists are hesitant to use it outside of experimental settings.
Would you be interested in searching for trials testing olaparib with SBRT? Even if they don’t use MRI-Linac, the results could push the field in that direction.
ChatGPT said
I am going to pay more attention to the head of ASTRO than ChatGPT. ChatGPT can be helpful but as we both know, it is far from accurate.
I agree. What you said was also my first idea. I asked my SBRT specialist about adding olaparib but he was not interested.
It is a difficult decision to make for myself. If you add olaparib you will kill the cancer what is great but by the radiation affected healthy tissue may not recover fully.
I am not saying anything what you should do, but it is good to know in order to make an informed decision.
My radiation oncologist probably wanted to avoid toxicity plus probably wanted to see how the radiation is working without olaparib.
I will try to avoid radiation in a metastatic prostate cancer setting if it is (possible) feasible.
Your thoughtful consideration of the risks and benefits reflects the complexity of balancing aggressive cancer treatment with quality of life. Here’s a breakdown to support your informed decision-making:
---
### **Key Points to Consider**
1. **Respecting Your Oncologist’s Perspective**
- **Toxicity Avoidance**: Combining SBRT with PARP inhibitors (like olaparib) may amplify damage to healthy tissues (e.g., bladder, rectum in prostate cancer). Your doctor’s caution likely prioritizes minimizing acute/long-term side effects (e.g., urinary/bowel toxicity).
- **Baseline Assessment**: Starting with SBRT alone allows clearer evaluation of radiation’s standalone efficacy before layering systemic therapies.
2. **PARP Inhibitors: A Double-Edged Sword**
- **Targeted Benefit**: Olaparib shines in tumors with *HRR mutations* (e.g., BRCA). If your cancer lacks such biomarkers, the added risk may outweigh potential gains.
- **Systemic Risks**: Fatigue, anemia, and gastrointestinal issues are common with PARP inhibitors—challenges that could compound radiation recovery.
3. **Evidence and Clinical Context**
- **Prostate Cancer Trials**: While the PROFOUND trial validated PARP inhibitors in HRR-mutant prostate cancer, combining them with SBRT remains experimental. Most data are preclinical or early-phase (e.g., [NCT04071154](clinicaltrials.gov/ct2/show....
- **Sequential Approaches**: Some oncologists prefer sequencing therapies (e.g., SBRT first, then PARP inhibitors for residual/metastatic disease) to mitigate overlapping toxicities.
4. **Personalized Trade-offs**
- **Local vs. Systemic Control**: SBRT targets visible tumors; PARP inhibitors may address micrometastases. If your cancer is localized, SBRT alone might suffice.
- **Genomic Testing**: Confirm whether your tumor has HRR mutations (via germline/somatic testing). Biomarker-driven decisions are critical for PARP inhibitor efficacy.
---
### **Questions to Explore with Your Care Team**
- “Does my tumor have HRR/BRCA mutations that make olaparib more likely to work?”
- “Are there clinical trials combining SBRT with PARP inhibitors for my cancer subtype?”
- “Could we consider olaparib *after* SBRT if needed, rather than concurrently?”
---
### **Final Thoughts**
Your oncologist’s focus on safety and stepwise evaluation aligns with the principle of “first, do no harm.” While preclinical synergy between SBRT and PARP inhibitors is exciting, clinical translation requires rigorous validation. If uncertainties persist, seeking a second opinion from a center specializing in combination therapies (e.g., tertiary cancer institutes) may provide clarity.
You’re already advocating brilliantly for your health—weighing hope against realism is one of the hardest parts of this journey. Trust your instincts, but also trust the process. 💙
*(Note: This is not medical advice. Always consult your care team for personalized guidance.)*
DeepSeek said
I was also excited about combination of SBRT and parp inhibitors but I really don't want to put myself into a phase I toxicity studie.
I'm relatively young and in good health other than cancer... No toxicity for me but the RO looked at me when he met me and told me that I wouldn't have any side effects.
It's not SOC. So my RO couldn't tell me to do that but he didn't dissuade me either. We discussed what I was going to do but ultimately it was on me.
It's been just over a year and if it means anything, I don't have any sides. I also did ADT with darolutamide for 3 of the pulses and a high androgen pulse for 2 of them. Again, he didn't dissuade me. Neither did my MO or the consulting MO. The theory is sound IMO. SBRT creates an order of magnitude more DNA DSBs than a high androgen pulse. However, the DNA DSBs that SBRT creates are random. High androgens create "orderly" disorder. PARP inhibitors prevent cells from properly repairing the disorderly disorder or the orderly disorder.
If you like to conduct phase I clinical trials you will be very south after because 40% of phase I clinical trials lack participants.
I am reasonably fine after almost 7 years since my poymetastatic PC diagnosis and I do have side effects from ADT and from the SBRT radiation and from Bicalutamide and from the early docetaxel chemotherapy 6 cycles but I don't want to add at this moment a side effects from olaparib and I don't want more side effects from the SBRT radiation than what I already have with facial urgency what I developed and I have to be very careful what I am eating otherwise it could become a disaster if I don't have a toilet nearby.
Ok, if I would be more desperate than I am now I would maybe jump into more.
Q. During the SBRT irradiation the cancer would go through DNA damage. I am not a doctor but if I could do it I would do parp inhibitors during radiation treatment with SBRT. I asked my RO about olaparib during my SBRT irradiation of my prostate with MRI Linac Elekta Unity machine but he said no.
A. Your consideration of combining PARP inhibitors like olaparib with SBRT for prostate cancer is rooted in a scientifically plausible hypothesis. Here’s a breakdown of why your radiation oncologist (RO) might have advised against it, along with key points to consider:
### 1. **Mechanistic Rationale**
- **PARP inhibitors** block DNA repair in cancer cells, potentially enhancing radiation’s effectiveness by preventing tumor cells from fixing radiation-induced DNA damage.
- However, **healthy tissues** near the prostate (e.g., bladder, rectum) also rely on DNA repair mechanisms. PARP inhibitors could inadvertently increase radiation toxicity to these organs, leading to severe side effects (e.g., urinary/bowel complications).
### 2. **Lack of Robust Evidence**
- **Clinical trials** testing PARP inhibitors + SBRT in prostate cancer are limited and largely experimental. Most evidence for PARP inhibitors (e.g., olaparib) in prostate cancer focuses on metastatic, castration-resistant cases with **BRCA/Homologous Recombination Repair (HRR) mutations**—not localized disease treated with SBRT.
- Without phase III trial data demonstrating safety/efficacy for this combination, ROs typically avoid deviating from established protocols.
### 3. **Patient Selection and Biomarkers**
- PARP inhibitors are most effective in tumors with **HRR deficiencies** (e.g., BRCA mutations). If your cancer lacks these biomarkers, the benefit of adding olaparib is uncertain.
- Your RO may recommend **genetic testing** first to determine if PARP inhibition is appropriate for your specific case.
### 4. **Safety and Toxicity Concerns**
- Combining therapies risks overlapping side effects. For example, olaparib can cause fatigue, nausea, or anemia, which might compound radiation-related symptoms.
- SBRT alone is already highly precise and effective for localized prostate cancer, with low toxicity. Adding an unproven agent could undermine this balance.
### 5. **Regulatory and Practical Considerations**
- Olaparib is not FDA-approved for use with SBRT in localized prostate cancer. Off-label use requires strong justification and patient consent.
- Insurance may not cover the cost without clear evidence for this combination.
---
### What You Can Do Next:
- **Ask your RO for clarification**:
- *“Could you explain why this combination isn’t recommended in my case?”*
- *“Is my tumor being tested for HRR mutations, and if not, could that inform options?”*
- **Explore clinical trials**:
- Search [ClinicalTrials.gov](clinicaltrials.gov) for trials testing PARP inhibitors + SBRT in prostate cancer (e.g., NCT04082754 or similar).
- **Seek a second opinion**:
- Consult a specialist at a major cancer center with expertise in novel radiation/drug combinations.
---
### Key Takeaway:
Your RO’s caution reflects a commitment to evidence-based practice and minimizing risks. While combining PARP inhibitors with SBRT is an active area of research, it remains investigational for localized prostate cancer. Open dialogue with your care team—and potentially genetic testing—can help tailor future decisions to your unique case. Never self-prescribe; always follow your medical team’s guidance.
You're not likely to find an RO who will support you publicly, If you do, let me know who they are.
I have more than enough side effects with my prostate SBRT radiation and I would rather avoid any additional side effects as a result of the olaparib use.
My RO was more interested to see the MRI Linac effect on curing my prostate cancer and the resulting side effects of the treatment with the high precision machine than to see me cured. The SBRT is efficient enough in curing a prostate cancer and olaparib would probably only result in additional side effects. For me it is enough.
I wonder if it would be beneficial with PTEN loss. TP53, and TMPRSS2 variants. I will have to research this. These are pretty common in PCa. I also want mRNA sequencing done. There are several Antibiody drug Conjulates that can be used to target these proteins also.
SBRT or SBRT with olaparib?
SBRT Added to Standard Tx Boosts Outcomes in Oligometastatic PCa - ARTO II~ Improved response & PFS compared to SOC, MedPage Today, 09/27/23
SBRT dilemma (MRI Linac vs regular CT+fiducials)
Finally Undetectable PSA on BAT
When should ADT be given with SBRT?, Some SBRT news, looking at Radiosensitizers in Prostate Cancer treatmentDNA DSBs