My husband is considering starting Radiation/Chemotherapy combination to treat the Anaplastic Astrocytoma Grade 3 (located in right hemisphere) and I would like some feedback on your experience and suggestions for additional cocktails.
Here is a timeline and the current diagnosis:
- May 2001 - First craniotomy and at that time it was diagnosed as Astrocytoma Grade 2
- September 2013 - Second craniotomy and diagnosis as Anaplastic Oligoastrocytoma Grade 3
- August 2018 - Third craniotomy and diagnosis Anaplastic Astrocytoma Grade 3, IDH1 mutated, ATRX mutated, MGMT methylated, 1 P19Q no LOH detectable, proliferation index mib-1 to 10%
He never wanted to do Radiation/Chemo due to concerns of long term effects, so after the second surgery, he had declined further treatment. During this time he did not take any constant supplements but did do Ketogenic diet for about 2 years. The concern was always not to have some side effects.
He recently had another MRI check and it shows a further progression of the remaining tumor. The biggest part of the tumor is located in an area where they cannot operate without causing handicap. His left arm is already damaged and is showing signs of difficulty with walking (left leg) as the tumor is pressing on those fibers.
With all of your experience, I would like your feedback on where should we start. I am reading other posts to come up with a list of possible supplements.
He is almost 40 and we live in Switzerland.
Thank you for your feedback.
N
Hi N,
ReplyDeleteIn terms of conventional therapy, the long-term follow up from the NOA-04 trial (chemotherapy versus radiation for anaplastic gliomas) showed that radiation is the more effective therapy for IDH-mutant astrocytomas.
You can download one version of the paper here:
https://www.zora.uzh.ch/id/eprint/79916/
The relevant part is under the section "ATRX loss is a favorable prognostic marker" where it states
"we observed a trend toward a longer PFS in “molecular astrocytomas” who initially received radiotherapy compared to chemotherapy (median PFS 50.6 vs. 25.1 months, p = 0.0944; Supplementary Fig. 2a)." That is, in this patient group, median progression-free survival was about twice as long with radiation alone versus chemo alone (about 4 years versus 2 years).
But the CATNON trial also shows radiation plus adjuvant temozolomide chemotherapy monthly cycles is superior to radiation alone.
https://academic.oup.com/neuro-oncology/article/18/suppl_6/vi1/2541795
The benefit of concurrent temozolomide (simultaneous with radiation) isn't as significant in this patient subgroup, but may lead to better survival outcomes.
https://abstracts.asco.org/239/AbstView_239_248345.html
So for anaplastic astrocytomas with IDH1 mutation, in terms of PFS and survival benefit, radiation + follow-up chemotherapy is most effective, and radiation alone is better than chemo alone.
Proton radiation could be an alternative to standard photon radiation.
https://academic.oup.com/neuro-oncology/article-abstract/20/suppl_6/vi173/5154265
In the USA, the drug AG-120 (ivosidenib, Tibsovo) was approved for IDH1-mutant leukemia, and people with IDH1-mutant gliomas have been trying to get access to this drug off-label (though the applications are usually rejected). It would be something to ask about, though maybe not too likely. Also this class of drug is more likely to be effective in the early stages of the disease (eg. grade 2). As tumors evolve to higher grades of malignancy, they are generally less dependent on mutant IDH1 and more dependent on secondary and tertiary mutations.
There are also some notable clinical trials, but trials for recurrent glioma usually require the patient has already had standard radiation and chemo, so most of these would not be an option. An example of this would be:
https://clinicaltrials.gov/ct2/show/NCT03893903
In terms of off-label and repurposed drugs, I would look into Accutane (isotretinoin). In one of the early trials, 15 recurrent anaplastic astrocytoma patients were treated with this alone. 3/15 had a partial response and another 3/15 had stable disease, so 6/15 (40%) seemed to benefit to some degree.
https://www.ncbi.nlm.nih.gov/pubmed/9816151
I wouldn't consider this a replacement for standard treatments however. I also wouldn't combine it with chemotherapy as it may actually interfere. It is probably best used as a maintenance therapy after standard treatments are completed.
Ben Williams (IDH1-mutant grade 4 astrocytoma/glioblastoma, diagnosis in 1995) used verapamil as a chemosensitizer. This drug does have some lab evidence as sensitizing to the chemotherapy drug BCNU (similar to CCNU), but I haven't seen comparable evidence for combining with temozolomide.
ReplyDeletehttps://www.ncbi.nlm.nih.gov/pubmed/2366081
Dear Stephen, Thank you so much for taking the time to write. Really grateful for you!
ReplyDeleteWill review the studies and come back with updates and questions.
All the best,
N
I have heard Celebrex is a great chemo adjuvant
ReplyDeleteI have pretty much the same diagnosis.
ReplyDeleteI did Awake brain surgery 22nd of marcy, 2019. It was done with electrodes on the brain, I think people here know the drill.
22 May -> 9 July Proton beam + TMZ. The area of removal was also beamed.
About to finish my first of 12 cycles of 5 days of TMZ
You feel exausted from the proton+chemo, similar to two weeks -> 1 month post surgery. Long term hearth effects I have no idea. I aim to let you know in the future though.