In a couple weeks I'll be beginning proton radiation therapy. I have a basic cocktail and diet strategy for the 6 week treatment and I wanted to run it by this blog community while also asking a few questions.
My story so far:
Focal seizure in Oct 2018.
4.5cm mass, frontal/parietal, no contrast enhancement, everything else typical for an oligo.
Surgery late Dec. GTR, no visible tumor remains.
Pathology: Grade III oligo, with 10/10 HPF mitosis, dense cellularity, moderate atypia, no vascular proliferation, no necro.
TMB 6.8
IDH1 mut
TERT mut
CIC mut
1p19q codel
P53 retained
ATRX retained
MGMT methylated
Current plan is proton+TMZ then up to 12 cycles of TMZ.
Did 1 cycle of TMZ in between surgery and radiation start.
Cocktail
Keppra, 1g x 2
Longvida, 1.6g x 2
GTE 1g (450mg egcg) x 2
PSK 1.5g x 2
Maitake, 50mg x 2
CBD (don't have it yet, still considering dosage)
Omega-3 3g (total EPA+DHA)
Pterstilbene 150mg x2
Resveratrol 250mg x2
D3 5000 IU x2
Berberine, 600mg x3
Silymarin, 450mg x3
Probiotics via yogurt or pills (occasional, can reduce gut diversity?)
Selenium 200mcg
Melatonin, 10-20mg
Magnesium, ~200-300mg
Still trying to get
Celebrex
Chloroquine
Ketogenic diet rough plan
72h fast 3 days prior
Protein under 65g, carbs under 20g and GKI as close to 1 as possible.
1000cal per day, possible 20:4 intermittent fasts 3 days per week, alternating
Lots of walking and probably very light but consistent exercise throughout.
Questions
1) Will any of these supplements (antioxidants specifically) potentially interfere with oxidative stress on the tumor cells?
2)The majority of this cocktail and diet plan is ripped from GBM research and GBM/AA3 posts on here. Are there IDHmt/oligo specific supplements/drugs etc that I may be missing?
3) I've heard GTE can be toxic. I have Nusapure GTE and Swanson's Teavigo caps as well. What are people on here buying for EGCG?
4) Is chloroquine as promising to an oligo as it is to a GBM?
5) Is cal restriction necessary if I were regularly fasting, and vice versa? This is a bit of a grey area that I don't quite have figured out yet.
Also, as of now, I intend to save PC chemo for future recurrences. TMZ is a much less damaging chemo. My main concern with TMZ, however, is hypermutation. I'm not sure how to possibly mitigate that.
Thanks in advance.
1) It's difficult to say, this question is understudied. The only thing I've seen experimental evidence for interfering with radiation effect in experimental glioma models is ascorbate (vitamin C).
ReplyDeletehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266032/
But even vitamin C can become a pro-oxidant if the dose is high enough.
This is still a really controversial topic. See Ben Williams essay
https://virtualtrials.com/pdf/williamssupplements2014.pdf
2) There is way less clinical and preclinical evidence on IDH1-mutant gliomas (including oligos). There's very little we can say is specific for IDH1-mut astros or oligos. PARP inhibitors and inhibitors of mutant IDH1, such as AG-120/ivosidenib/Tibsovo are among the few things that come to mind, but these might be difficult to access outside of clinical trials.
If you're under the age of 26, and in the USA or Canada there is a trial for BGB-290 (brain penetrant PARP inhibitor) + TMZ, soon to be recruiting
https://clinicaltrials.gov/ct2/show/study/NCT03749187
Ivosidenib was recently approved for IDH1-mutant leukaemia, so it's on the market now, but you might have a hard time getting insurance to cover it, as it's not yet approved for brain tumors. This is something I wouldn't combine with radiation or chemo necessarily because the IDH1 mutation may actually sensitize to those therapies.
Similarly you might consider Accutane (isotretinoin) after conventional therapies are complete, as a maintenance therapy.
3) I've never heard of green tea extract referred to as being toxic. Are you referring to actual clinical research or lab research?
4) We don't know, chloroquine has never been examined specifically in oligos.
5) I wouldn't use the word "necessary", but intermittent fasting on top of baseline caloric restriction is probably going to add additional metabolic stress on the system, which is bad for the tumor, but may also impact on quality of life. Each person has to find their balance between metabolic stress on the tumor versus impacts on quality of life. However if I were going to attempt extreme dietary restriction (such as restricted ketogenic diet or caloric restriction) the most effective time to do it in terms of impact on the tumor may be during the six weeks of radiation. I would want to monitor blood sugar though, as you don't want to weaken yourself too much or get into hypoglycaemic territory.
6) There is actually some long-term data from the German NOA-04 trial showing that PCV is more effective than TMZ for 1p/19q codeleted oligodendrogliomas. TMZ is also effective, and generally more tolerable, but most likely carries higher risk for future hypermutation. According to preliminary research coming out of UCSF, the rate of transition to a hypermutated tumor at the time of recurrence for grade 2, IDH-mutant gliomas treated with TMZ alone, is somewhere around 50%.
https://btcocktails.blogspot.com/2017/01/hypermutation-risks-of-temodar.html
I hypothesize that this risk is less when lomustine/CCNU is used because lab research shows that mismatch repair defective cells (which will hypermutate when exposed to TMZ) are more sensitive to chemo like CCNU and BCNU while being resistant to TMZ and procarbazine.
In the case of oligos, even hypermutated oligos usually do not occur as grade IV tumors, but stay at grade 3. It's not entirely clear whether a non-hypermutated recurrent grade 3 oligodendroglioma has a better prognosis than a hypermutated recurrent grade 3 oligodendroglioma. A hypermutated tumor has a better chance of responding to immunotherapy, such as checkpoint inhibitors.
Thank you for the very quick and detailed response Stephen.
Delete1) The PDF looks like a great resource, thank you.
2) Targeted therapies will be the most likely treatment in any future recurrences, at least that's what my NO seems to suggest. The others are currently not practical. It makes me wonder if perhaps if it would be possible/sensible to request targeted treatment as soon as it is approved, even in the absence of a recurrence..
I am seriously considering some form of oral retinoic acid post-treatment. I remember reading a study about ATRA's effect on IDHmt glioma somewhere on this blog.
3) Something I had read online and didn't followup on. The claim was that it caused liver damage. I couldn't find anything convincing as far as studies go, but I'm not very adept at combing through PubMed etc.
4) Kinda knew the answer to this before I asked it unfortunately.
5) Luckily I will be having weekly blood tests in addition to a blood test device at home for ketones and glucose. And I agree now is the time to pull all the stops metabolically. I don't believe in keto as a long term diet but it does look like it can very effective short-term. To that end, I'm trying to maximize my the effect.
6) I recently asked my NO about this, and his percentage was 18 as opposed to 50. It was a brief email response so I don't know his source, but I think if there is someone in the region who would know, it'd be him. He also thinks the idea of lessened risk of hypermutation in a case with no residual visible tumor, due to there being less cells overall (a concept I read on here somewhere) is a theory that holds water.
Perhaps at some point in the chemo I should attempt to switch to CCNU..
2) Has your NO suggested any specific targeted therapies? Ivosidenib would be in that category. In fact, I don't believe there are any other approved targeted therapies that would target any of the other mutations in your tumor besides IDH1.
Delete6) The 18% figure he quoted might have come from GBM studies, where the rate of hypermutation is much lower, probably due to the fact that the majority of GBMs are MGMT unmethylated, and therefore TMZ is already fairly ineffective, so there's not a huge need for the tumor to develop additional resistance mechanisms. We see higher rates of hypermutation in lower grade gliomas which are usually MGMT methylated, and sensitive to TMZ. These tumors can then become resistant to TMZ via mismatch repair defects, which leads to hypermutation after exposure to TMZ.
I do hold the theory that a maximally resected tumor with no residual tumor visible will have less risk for hypermutation, just on the basis of statistics. Fewer cells = less chance that one of the cells will undergo mismatch repair defects. This is just a hypothesis though.
2) Nothing specfic, though I will ask.
Delete6) This makes sense.
Thanks again.
Also, there’s data to support HBOT in combination with those therapies. Good luck - I’m so impressed with your plan!!
ReplyDeleteI had considered this, however it seems like there needs to be a short window between the HBOT and radiation therapy (15 minutes for a significant effect?). I will still explore the option with my radiation oncologist but it seems unlikely.
DeleteI had considered some kind of portable oxygen tank or asking for some o2 pre-treatment, but that seems insufficient next to a long session of actual HBOT.
At the very least I will be doing some deep breathing during the procedures. No reason not to and I'd imagine it would increase my oxygen saturation.
It makes sense that you were already familiar! :)
DeleteA few years ago, one of my buddies talked to the center where he was set up to do radiation and asked if they had a spare room or space for a personal HBOT pod, and they accommodated him. Maybe go in and ask? (He rented his pod and brought it in and set it up for the duration of treatment.)
Another good friend was diagnosed with a III olio, maybe 4 years ago, and she did similar things that you’re planning, if you want to know specifics I can ask her. She doesn’t follow Cocktails. I know for sure she did the HBOT, restricted keto - vegan, IV DCA, proton radiation, chemo and honestly I cant remember the other details. She hit it all at once, together and has had NED ever since (she started with a complete resection).
I had no idea that was even possible.
DeleteAnd any details from your friend would be great. Hopefully it will be useful not only for me but anyone with an oligo that searches this blog.
Sounds great, I’ll reach out now!
DeleteHere’s my friend’s protocol:
DeleteOkay - as for my protocol...
Therapeutic doses (I forget, but I think you know them) for the following:
Melatonin
Curcumin
Berberine
Vit D
Maitake mushrooms
Magnesium
IV Therapy 2x/week
Poly MVA
DCA
Hyperbaric Chamber 2x/week
I basically ate out of a blender - strictly green juice and blended greens, a piece of sprouted bread with sunflower seed butter was my "treat" once in awhile
raw garlic - you know the drill with this one - daily
Meditation
This Louise Hay audio nightly
Lots of walking Buttercup (her dog)
Deep breathing
And from my other buddy:
DeleteMine was a really weird situation. Someone I knew bought the unit but their office lease collapsed in they did not have any place for it. She let me use it and then I sold it for her. I sold it to Atlanta hyperbarics. You did not have an oxygen concentrator and so I needed to buy that but it just happened to fall into place perfectly. I got proton radiation from a private radiation center in Jacksonville Florida it is called Ackerman cancer center. At the time they were the only one in my area doing proton radiation and because it was a private clinic they were very kind and willing to help. They let me put it in a room and use it there while I was getting treatment.
Thank you Jessica, not so different from what I was planning (though I won't be doing the IV therapies). I'm looking forward to exploring my options with HBOT.. might have to get creative.
DeleteThis comment has been removed by the author.
ReplyDeleteI think from the studies I read PC(V) was far more superior regarding OS and PFS for 1p/19q co-deleted oligos. I also have it and I think I'd go with PC chemo and proton therapy when the time comes...maybe achieve long enough PFS that there are other options available at next recurrence (high hopes for Toca 511 and other immunotherapy treatments). As you have written, I would also probably drop V, since there is a suggestion that it doesn't cross BBB - especially in low grade gliomas with intact BBB. Also PC is probably better tolerated with younger age.
ReplyDeleteAll the best!
I was aware of this, and it's been a tough decision. PC is clearly superior treatment for oligo's, and I would probably tolerate it better now than years down the line. However, I am concerned about long term, permanent damage. Especially to my bone marrow/immune system.
DeleteI do have some time to figure out my chemo plan, and I'm not 100% committed to only TMZ for the entire 8-12mo. Maybe a bit of both? Start with PC and then move into TMZ? I'm not familiar with PC's long term side effects, and it would be even harder to know because virtually all studies are PCV, not PC...
There is no right or wrong decision when choosing which chemo. I would / will probably choose PC, because hypermutation risk of TMZ. I think I read few studies regarding Toca-511 & PVS-Ripo and they both concluded that responders have lower tumor mutational burden. So I figured that trying to keep it low would be a good idea - in hopes that these treatments get approved *soon*.
DeleteAre you familiar with CeTeg study (TMZ+CCNU combination)? They also included few GBM-O patients (I guess reclasified as anaplastic oligodendroglioma with new classification), but the authors didn't mention outcome of this subgroup specifically. I just wrote to study author, if he could give any data on these patients...I'll paste the answer here, if I get any.
Best regards,
Matjaz
Just received an answer:
Delete"We cannot say anything reliable regarding the oligodendroglioma grade III patients in the Ceteg trial. They are just too few for any reasonable scientific analysis. In this situation I would not apply the Ceteg/CCNU-TMZ protocol but stick to the PC(V) protocol which has ample evidence for efficacy in oligodendroglioma. That is what we are also offering our patients with oligodendroglioma. Of note, in patients who previously had only resection and no radio- or chemotherapy, I think PC(V) should always be combined with radiotherapy (in our center first RT, immediately after starting PC; we omit Vincristine since it does not penetrate into the CNS). All trials with combined treatment showed superiority to single modality therapy."
Interesting. There are a couple articles on the subject on CancerNetwork, though they are a bit outdated (2015):
Deletehttps://www.cancernetwork.com/oncology-journal/treating-anaplastic-oligodendrogliomas-and-who-grade-2-gliomas-pcv-or-temozolomide-case-pcv
https://www.cancernetwork.com/oncology-journal/treating-anaplastic-oligodendrogliomas-and-who-grade-2-gliomas-pcv-or-temozolomide-case-temozolomide
In any case, thank you for the feedback Matjaz. Very much appreciated.