Choice of adjuvant TMZ or PCV, leaning towards PCV

[Narwhal77]

I recently finished radiotherapy for my diffuse brain stem tumor. Things went pretty well and it looks like there has been a moderate response to treatment and some of my symptoms have improved. Overall I feel good and am happy with the results.

I am now moving on to chemotherapy, which has lead me to a tough decision needing to be made between TMZ and PCV. I feel that I am getting great care from my oncology team, but my doctor told me there is no clear choice in this matter and it is up to me based on pros/cons with each chemo choice. I am leaning towards PCV but wanted to get additional opinions/input.

Background:

I am a 31 year old male. My tumor is a diffuse IDH-Mutant p.R132G Anaplastic Astrocytoma grade III, no 1p/19q codeletion, no CDKN2A/B homozygous deletion and the array pattern is not considered complex. I have loss of ATRX expression and widespread overexpression of p53 in the glioma cells. Scattered mitotic figures are identified (including 2 mitoses in a single high-power field), the Ki67 labeling index is up to approximately 5-10%, and there is no unequivocal microvascular proliferation or tumor necrosis. My tumor is negative for H3K27M, IDH1-R132H, and BRAF V600E. The tumor does not enhance, including on my most recent MRI which was completed 1 month after finishing radiotherapy.

The tumor is primarily located in my left pons, the tumor has infiltrated the right pons as well but not quite as bad as the left. It has also infiltrated the left middle cerebellar peduncle and left cerebellar hemisphere.

Thoughts:

My main issue with TMZ is the risk of Temozolomide-induced hypermutation. I know there is no guarantee that PCV and/or radiotherapy will not cause hypermutation, but it seems like the risk is somewhat significant with TMZ. It also looks like, from limited data, that PCV may have more benefit than TMZ when combined with radiotherapy for my tumor type. This is based on the recent paper in The Oncologist, published February 1st 2021, titled:

"Radiotherapy Plus Procarbazine, Lomustine, and Vincristine Versus Radiotherapy Plus Temozolomide for IDH‐Mutant Anaplastic Astrocytoma: A Retrospective Multicenter Analysis of the French POLA Cohort"

Which seemed to find that radiotherapy + PCV had a longer progression free survival than radiotherapy + TMZ in Anaplastic Astrocytomas.

The only other concern I have is whether or not PCV has a higher risk of radiation necrosis when combined with radiotherapy, versus TMZ plus radiotherapy. I have not had a chance to do any significant research on this yet.

Overall, based on the information I have, it seems like if I am willing to tolerate the increased toxicity of PCV, it is the better choice long term in my case.

I am very appreciative of any thoughts anyone may have. I need to make this decision in the next couple of days.

Thanks

[musella]

You can use our patient navigation program and get the opinion of a few experts. We have 3 neuro-oncologists and a few PhD research scientists who look at this all of the time. Go to virtualtrials.org click on LEARN then Patient navigation.

My thougts: 1. The risk of radiation necrosis is only when you mix the drugs with radiation.. Radiation is over - correct? So neither drug you take now will have an impact on the radiation necrosis. Taking a drug after radiation shouldn't affect formation of radiation necrosis.
Some people think that the Vincristine does not really contribute to the benefit, but it does cause most of the side effects, so might be worth thinking about OC without the V.

There is a clinical trial for Analastic astrocytoma worth looking at https://www.stellarstudy.com/ it is for recurrent but can't hurt to try to get it on compassionate use and try it now.. That might be hard.. but worth looking at. (Orbus is a sponsor of our organization)

My own opinion is I would go for temodar and maybe optune.

[Narwhal77]

Unfortunately Optune is not available in my case due to the infratentorial location of my tumor. Unless something has changed and they now can use Optune in those situations.

Do you feel temodar is the best option primarily due to its lowered toxicity vs PCV?

Also, for adjuvant chemotherapy after radiation, is there a window of time where the chemotherapy needs to be started? It seems like waiting at least 4 weeks after radiation before starting chemo is normal. Is there a maximum amount of time you can wait before the synergistic effect of adjuvant chemo is reduced?

I do plan on signing up for the patient navigation program soon.

[musella]

The patient navigation program can answer those questions better. They are experimentaly using optune for infratentorial tumors but it is not generally available. They would hve to get a new style of transducer arrays approved by the FDA, and it is probably not as comfortable with the arrays having to be so low.