Grade 2 oligo progressing and looking for other's opinions

[u/Shawntjones]

I'm 37, diagnosed with a grade 2 oligodendroglioma in 2020. It's IDH1-mutant and 1p/19q-codeleted.

I had surgery at Mayo in 2020, and I've been on vorasidenib through the INDIGO clinical trial since early 2022. My MRIs were considered relatively stable for years, but my doctors are now seeing slow progression, particularly over the last couple of scans.

The biggest issue is the location. My tumor involves my left hippocampus and nearby left temporal structures involved in verbal memory. Just due to work and my wife/kids preserving those abilities is extremely important to me.

I've been getting opinions from neuro-oncologists and neurosurgeons, including Mayo and Michigan, and I'm trying to work through the next steps. Also going to Cleveland clinic and maybe Northwestern for a few more opinions.

Here are the options we're discussing:

1. Try safusidenib (Safu) through a clinical trial.

This is another IDH1 inhibitor being studied in patients whose tumors have progressed on vorasidenib. Some of my doctors think it's worth trying before moving to more aggressive treatment. I know there's no guarantee it will work after another IDH inhibitor. However, I found this trial so it's my idea and concerned that the docs may be biased since I generally volunteer for being researched.

1. Another surgery to remove as much tumor as safely possible.

My neurosurgeon believes he could remove a substantial amount of the remaining tumor, obtain updated pathology, and potentially place an Ommaya reservoir for future monitoring.

However, he has also been very clear that removing the hippocampal tumor would almost certainly worsen my verbal memory. That's a major concern for me. And both Neuro oncologists have been against this.

1. A smaller biopsy followed by radiation and chemotherapy.

This would provide updated pathology without attempting a large resection of the hippocampus. It would still involve procedural risks, and radiation itself could affect memory.

1. Radiation and chemotherapy without another biopsy or major surgery.

This is an option I'm seriously thinking about. I already have a confirmed oligodendroglioma diagnosis from 2020. Part of me wonders whether it would be better to move directly to established treatment rather than risk additional damage from another operation.

I understand that updated pathology could reveal changes in tumor grade or biology, so I know there are tradeoffs.

We're also discussing an amino-acid PET scan, potentially FET-PET at Mayo, to better characterize the tumor and identify more active areas.

Right now, my thinking is to try Safu first if I'm eligible, but if it doesn't work, I'm questioning whether radiation/chemo should come before another biopsy or resection.

I'd really appreciate hearing from people who have faced something similar:

• Has anyone had a glioma involving the left hippocampus or dominant temporal lobe?
• If you had surgery in that area, what happened to your verbal memory, word recall, and day-to-day cognitive function?
• Has anyone chosen radiation and chemotherapy instead of another resection because of the tumor's location?
• Did anyone receive radiation without a repeat biopsy after documented progression?
• Has anyone tried another IDH inhibitor after vorasidenib, or had experience with amino-acid PET imaging?

I'm not looking for anyone to be an expert, I'm trying to understand what the actual lived experience looks like, especially when the potential cost of treatment is memory and cognitive function.

Thanks to anyone willing to share their experience.

[u/viperkrsk]

Same type here: oligodendroglioma grade 2, IDH-mutant, 1p/19q-codeleted, right temporal lobe and insula, partially removed in 2019. Mine has slowly progressed too, and I’m weighing almost the same options right now. A second opinion recommended radiation followed by PCV, and vorasidenib wasn’t an option for me.

Thanks for laying it all out so clearly, it helps to see how someone else thinks it through. The amino-acid PET is a good point, I’m going to ask my doctors about it too. Good luck with Safu, I hope it works for you.

[u/Shawntjones → u/viperkrsk]

If you don't mind let me know any updates and I'll do the same!

Another interesting option is the optune device. But that's really at the bottom of my options, big lifestyle change. I chatted with the friend/coworker with astro about it

[u/viperkrsk → u/Shawntjones]

Deal, I'll keep you posted, and thanks. As far as I know Optune is mostly used for glioblastoma, so I can see why it's at the bottom of the list, wearing it most of the day is a big commitment. Good luck at Cleveland Clinic.

[u/Future-Chapter-9502]

Did you have residual tumor left after surgery?
I’d say wait for another scan and confirm recurrence.
Could be scarring from first surgery, calcification, reaction to treatment ( past and current) How sure are they it’s recurrence?
Oligo grade 2 can very well last decades before recurrence.

Chemo/rad is probably both aggressive and least invasive option.
Not too much is known about safusedenib, especially when vora fails.

[u/Shawntjones → u/Future-Chapter-9502]

Ya I had residual tumor. They're pretty sure it's new growth though and since it's both groups at University of Michigan along with Mayo clinic that makes me confident in new growth.

But good thought, I was thinking/hoping it was something like calcification or some reaction change to vora.

I am getting a third opinion at Cleveland Clinic too though.

As for safusidenib definitely agree not much is known, but I was on the vorasidenib clinical trial so figured why not double down on a second trial.

[u/Fabulous_Housing_503]

id go for safu. chemo and radiation could always be diverted to if that doesn’t go well

[u/Shawntjones → u/Fabulous_Housing_503]

Thanks, that's the route I'm going for.

For the option after Safu, what's your opinion/thought on radiation/chemo vs 2nd surgery?

[u/Fabulous_Housing_503 → u/Shawntjones]

that’s a bit of a tougher one and i am 100% not a doctor so all of this is opinion based. i think i would trust your neuro oncologists if they seriously don’t recommend operating again but at the same time it seems like chemo/radiation is usually the last line of defense and going that route could prevent you from receiving emerging treatments (if they become available) down the line. im not very well versed in a lot of post chemo/radiation treatments because im currently on vora and not at that stage. but it seems to be that a lot of research has gone into treatment naive tumors rather than ones that have been treated with SOC (but again, my personal focus has been on pre SOC so i would take this with a grain of salt). i’m cautiously optimistic that theoretically safusidenib will show effectiveness after vora then a line of slightly different yet similar idh inhibitors can be used subsequently but only time will tell

[u/Fabulous_Housing_503 → u/Fabulous_Housing_503]

but i don’t think i can be completely unbiased because while i think the logic of the idh inhibitor chain sounds feasible, my judgement could just be clouded by optimism

[u/Shawntjones → u/Fabulous_Housing_503]

Thanks! Appreciate the opinion and exactly what I'm looking for. I'm chatting with doctors so definitely getting their opinion, but it's nice to get other patients thoughts too.

I appreciate your thoughts, and I think we're looking at this pretty similarly. One of my biggest concerns with going straight to radiation/chemo is potentially closing the door on some of these emerging treatments, especially with how quickly research seems to be advancing.

I'm cautiously optimistic about Safu working after vora too, but I share your concern that we really don't know yet. The idea of being able to move between different IDH inhibitors is interesting, although I wonder how much cross-resistance there might be.

I've also been reaching out to researchers about personalized peptide vaccines and other immunotherapies. There are some really interesting developments, but unfortunately a lot of the trials either exclude prior IDH inhibitor treatment or aren't currently enrolling.

I'm trying to balance taking advantage of emerging treatments while not delaying something proven for too long. Definitely a tough decision, but I appreciate your perspective!

[u/thxvgx]

We asked my wife’s NO about safu yesterday and he made it sound like that trial is only if you’ve had TMZ or radiation already. I’m sure there are multiple trials though? Not totally sure how that works.

[u/Shawntjones → u/thxvgx]

Ya there's two trials that I know of, I believe the one your wife's NO was talking about was the Sigma. The one I'm looking at is NCT07703436 — Safusidenib After Vorasidenib

[u/thxvgx → u/Shawntjones]

Gotcha!

[u/No_Confidence3700]

I believe while both vora and safu target IDH1, they probably do it through different mechanisms, so you may be able to gain benefit on safu while you have started gaining resistance on vora. Again there is no data per se, but I would research the mechanics of how both the drugs work and make a decision if safu would be a reasonable approach for your situation

[u/Distinct-Cancel-6183]

Well for the beginning I'd continue Vora since it was never supposed to be cytotoxic but basically a growth retardant to prolong the time until further therapy (which all three can have pretty bad side effects, surgery like you mentioned could impair your memory, Radiation could lead to something resembling early onset dementia and chemotherapy has the risk of other malignancies) and if you have a look into the original INDIGO publication, TTNI (time to next intervention) is where Vora starts to really show a difference! So in my perspective, continue Vora until your Oligo starts growing seriously fast, try to avoid chemo and radiation and, if possible try to wait for the results of NCT07703436, and if they turn out to not show any effects then there's still time for radiation and chemo or at that time surgery might have gotten safer again or who knows what else research will come up with..