This last couple of weeks has been pretty intense - going from total resignation, to meticulously crafting my preferred treatment plan. I've spent countless hours on this now, and it is kind of reaching its final form. For context, I have a recurring O2, unknown if progressed to O3, growth rate is kinda in ambiguous territory (~6mm/year along a narrow WM tract, very misty). I have no symptoms and am not on any medication.
I'll start by presenting my (current) final plan, followed by the reasoning.
Now: STR/Debulking, RT, Vora (when available/after RT recovery)
Next Recurrence: Olaparib (start prior to RT), RT, (Third surgery might fit in somwhere, depends)
Quite a bit of my recurrence is in unsafe territory, and will likely be leftover - but currently I am leaning on the debulk being worth it in the long run. Also just better for peace of mind. Might also delay new symptom onset.
Radiation is pretty much the single-most effective treatment anyone can do, second only to maximal resection (depending on context). I had long worried about the side effects of radiation, but after developing a better understanding of the structures most-associated with worse side effects, I feel more comfortable. The side effects are also amplified if you do TMZ at the same time, and necrosis risk is ~5x higher. I'm going to strongly urge my radio to bathe a good margin of my putamen+anterior limb+caudate, and further down my insular, so it doesn't recur in an even worse spot next time. If I'm gonna go this route, better not make it all for nothing. My only regret is not convincing myself to do RT sooner, but at least it gave me a few carefree years.
The next step in the plan is to get onto Vorasidenib, as soon as I've sufficiently recovered from RT. Although evidence of conjuctive IDH Inhibitors + RT is still in the early trial phases, it makes logical sense that Vora would have a much easier time suppressing the tiny residual cell population following RT - compared to the much larger residual following surgery alone. After a STR + RT, my residual burden is likely even smaller than my earlier GTR with no additional treatment. As for side effects, there is almost a 1:1 overlap across the placebo arm. The only "real" side effects (excluding liver issues) are rare and mild - being mild loss of appetite, and mild diarrhea. Although not PBS-listed yet, if the process continues smoothly then it may be available to me mid 2026. Regardless, I'll talk with my onc about other possible routes to getting it for reasonable prices early.
Now to explain my continued shunning of chemo, starting with TMZ. I see TMZ as a poison which ravages your quality of life, and sacrifices tail-end survivors in the name of nudging median PFS and OS forward by a year or two. In nearly two thirds (that we know of) of recurrences that happen after TMZ, the tumor carries a hypermutation caused by the TMZ, which causes progression even faster than prior. The time TMZ buys is likely within the PFS "incubation" period before it turns your tumor into a whole new beast. That's not to say I see no value in TMZ at all - just that I would absolutely not recommend it unless you are projecting to live <5 years without it. By comparison, the ~3% radiation-induced-glioma risk looks like a dream come true. As for PCV, there is less I can criticize - it is undoubtedly very effective. But it is still poison, and sacrificing my QOL to such an extent just for a possible few extra years bump is not worth it to me. That's if you even tolerate it, and the whole thing doesn't just turn out to be a big stressful exercise. And again, chemo is bad for your fertility.
It took quite a while to find the perfect non-chemo, readily-available systemic treatment that would be likely to work even after Vora has failed (due to different mechanism). Early trials show some pretty promising PFS boosts, especially in oligo. Though PFS benefit is typically measured in the way of a few months, the patients in these trials are mostly heavily pre-treated contrast-enhancing tumors, so the benefit likely stacks higher in a less-dire setting. Add that to the radiosensitisation effect of PARP inhibitors, and speculatively at least, we might see a much greater effect. Trials for RT+PARP are ongoing, but even if it has to be done off-label, Olaparib is much cheaper than off-label Vora - I can probably save the money for at least a few months worth of treatment. As long as I can convince my onc or another onc to cooperate, should be fine. As for side effects, it seems to just be a somewhat harsher version of Vora.
Some honorable mentions -
IDH vaccines: These look very promising, but are virtually unobtainable for me at this point in time. The mechanism *likely* works even after a depleted round of Vora, less likely after a IDH1-only inhibitor (eg. Ivosidenib). Definitely keep an eye on progress in this field, it is well worth the trouble if you can get treated somehow. Ideally synergize with post-RT. Also keep an eye on personalized vaccines.
MRgFUS: Opens up the blood brain barrier for easier drug entry. Might synergize well with Olaparib. Difficult to obtain this treatment.
Olutasidenib: Another IDH inhibitor - this one *might* work after Vora, since it targets some second-site mutations which Vora misses. Again, not easily obtainable right now.
There are probably going to be certain aspects of my plan which don't go quite right, but that's fine. I've got quite a lot stacked up here. Overall, if I can make it another 10 years with this no-chemo plan, I'll be happy. And whether its still grade 2 or now grade 3, this at least keeps me in the running.
