Thank you Stephen for the invite, and thank you to this community for all information gathered here, and Astrocytoma Options, regarding my sons recent diagnosis of a Grade 2 Astrocytoma.
This is all very overwhelming, in processing a lot of information, in a short period of time, while making decisions regarding treatments and such.
My son Brett, had a bad seizure on Christmas eve morning while playing football with his friends. Fast forward, he had surgery the following Friday, December 30th. His tumor was located on his right frontal lobe(cerebral), apparently just over 4 centimeters.
Post-op MRI report stated a full resection, however the Neurologist who preformed surgery said that he feels as though a piece, possible the rim of the tumor remained. When discussed with the tumor board, the over all consensus of the group, agree with him. Being that is it a slower grower tumor, that are allowing his body to heal, and have scheduled his next MRI next week, to further review.
We met with his Neuro Oncologist yesterday to go over his pathology report. Which is where I am seeking advice. Trying to stay positive through all of this, I felt like a UFC fighter kicked my in my stomach when I learned that his tumor is IDH1 negative, 1p/19q not co-deleted(none detected), his TP53 mutation: Present, 60 percent of nuclei stain positively by immunohistochemistry.
We have an appointment at UPenn Thursday afternoon for a second opinion. Do you have any recommended questions, regarding anything? I am starting to feel lost. From what I have read(very carefully), prognosis is quite favorable with IDH1 mutated, co-deletion in tact.
She offered us a treatment of radiation w/ Tremodar, or radiation 5x's a week followed by a restrictive diet chemotherapy, Matulane, Lomustine, Oncovin. She does not lean one way or the other. The choice is ours, however, she stated that statistics back up the second suggestion. I read that combination chemo and radio are best.
Please forgive me for throwing this all out there, I'm writing in my car while picking up my 12 and 14 year old from school. Absolutely and advice would be much appreciated!!
Sincerely,
Marlena
I apologize, what I meant to say is that from what I understand, prognosis is unfavorable with IDH1 negative, no co-deletion.
ReplyDeleteI am sorry to hear of your son's seizure and diagnosis.
ReplyDeleteWith regard to the IDH mutation, it is essential to have a genetic test and not rely solely on the usual first level test by immunochemistry, which can only detect the most common IDH132H mutation. There are other much less common varieties of the IDH mutation. My daughter, as a case in point, was initially told she did not have an idh mutation, but when we insisted on genetic testing two years later, it turned out that she had a relatively rare (about 2% of idh mutations) 132S mutation. I believe that as far as anyone knows, the different varieties of IDH mutation all behave the same (although there are so few of these that I don't think there are any statistics). IDH mutated tumors are a quite different disease than GBM tumors and it is very important to be sure by genetic tests about IDH status, especially when the patient's age is young and the tumor is low grade.
One other thought about surgery is that many trials of vaccines and other treatments (e.g. a low grade glioma vaccine trial at UCSF, a tocagen trial) require that the treatment be given in connection with surgery. If there is time, it might be a good idea to consider the possibility of such trials before doing a second surgery.
Stephen W is a great source of information. If you like I would also be happy to share some of my experiences with you as the parent of a child with this disease.
I completely agree with Dave. Given your son's age and the strong staining for p53 in the tumor cells, I would certainly ask to have the IDH1 gene sequenced for less common mutational variants. About 7 out of 100 IDH1 mutant gliomas do not have the common IDH1 R132H variant, but some other variant (R132C, R132S, R132G etc.). Also about 1% of IDH mutant astrocytomas are IDH2, not IDH1 mutant. So definitely ask to have IDH1 (and perhaps IDH2) genetically sequenced to make sure he doesn't have one of these less common mutations.
ReplyDeleteThe Matulane/Lomustine/Oncovin chemotherapy being offered is more commonly known as "PCV" for procarbazine, CCNU, and vincristine (which are the other names for these 3 drugs).
The choice of chemotherapy for lower grade gliomas, temozolomide versus the PCV regimen is still being debated. One issue is that large trials for grade 2 gliomas take so long to carry out, it's only in the past few years we've gotten final results for trials that were initiated in the 1990s. Very few randomized trials for lower grade gliomas have compared TMZ and PCV head to head. One of the ones that did, the German NOA-04 trial, resulted in an interesting finding in the latest trial update, published in October 2016.
"When comparing TMZ and PCV in the sub-groups, patients with CIMPcodel tumors had better PFS and a trend toward better TTF with PCV versus TMZ, whereas OS was
not different but did show a limited number of events. This difference was not visible in CIMPnon-codel or CIMPneg tumor patients"
I will try to translate this statement. IDH mutant tumors almost invariably belong to a tumor subtype called CIMP (CpG Island Methylator Phenotype). The overlap between CIMP and IDHmutant might not be 100%, but is fairly close to it.
In the lingo of this trial "CIMP-codel" can be interpreted as molecular oligodendroglioma with 1p/19q codeletion, "CIMP non-codel" can be interpreted as (for the most part) IDH1 mutant astrocytomas, and the "non CIMP" can be interpreted as mainly IDH non-mutant gliomas. The statement in quotes is saying that while PCV led to better average progression-free survival for the oligodendroglioma cases, the superiority of PCV was not evident in the other two subgroups (IDH mutant astrocytomas, and IDH non-mutant gliomas).
This information is found in the study "Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide"
http://neuro-oncology.oxfordjournals.org/content/early/2016/06/30/neuonc.now133.abstract
I'll upload this study to the Brain Tumor Library if it isn't there already.
Another issue is the potential for use of temozolomide leading to hypermutated recurrences, but this has been documented mostly in cases where TMZ was used as a single therapy (as opposed to being combined with radiation).
Trials for newly diagnosed grade 2 astrocytomas are few, but I try to keep this page updated:
http://astrocytomaoptions.com/currently-recruiting-trials-low-grade-glioma/
My best to you and your family
Thank you very much for the feedback! We are moving ahead with further tumor testing, at UPenn. Now, the big choice here is treatment. Radiation simultaneous with Temodar vs. PCV. We are leaning toward Temodar, which was also recommended by the Neuro Oncologist at Penn. I am praying that is the right choice in our situation.
ReplyDeleteDave, I would really appreciate your experiences with your daughter, and your her journey through this, if you would so kindly share. The support means a whole lot, as you are painfully aware, the emotional component can be overwhelming.
Be blessed!
Marlena
Hi Marlena,
ReplyDeleteI also have a grade 2 astrocytoma, IDH1 mutated. But beware the first test I had came back negative for the mutation, a later test in 2016 came back positive. When the original sample was retested it also came back positive for the mutation. So sometimes the test results are just wrong.
I was diagnosed in 2005, 80% debulked followed by radiation without chemo, 2011 recurrence 100% resection, 2016 recurrence 100% resection, Plus 3 additional craniotomies for a subdural hematoma, infection and reconstructive surgery. To date I haven't had chemo but testing suggested PCV as a good option.
None of my doctors have ever mentioned a restrictive diet. Do you know what kind of diet your son's doctor had in mind?
Correct me if I'm wrong Marlena, but I was assuming the "restricted diet" was the low tyramine diet recommended while doing the PCV regimen. This is because procarbazine is thought to be a MAO inhibitor. However, warnings about these dietary precautions while on procarbazine are probably overstated. Procarbazine is only a weak MAO inhibitor, and there are probably only very few foods that would have to be avoided.
DeleteThere was an enlightening article on this subject published back in 1980 called "Reexamining the dietary restrictions with procarbazine." I have a copy of this study and can upload it to the Library if anyone is interested.
Hi Julio,
DeleteI really appreciate your response, it is helpful to me. We are having his tumor sent to UPenn for futher testing to include MGMT.
Stephen is correct, the restrictive diet is the Low Tyramine Diet if choosing the PCV regimen.
Thank you Stephen for that information. We were basically told by our Oncologist that there are foods that can kill him.
We are still undecided which route to take, it's a difficult call. Both Neuro Oncologists we have met with differ on treatments.
Thanks again, I appreciate the feedback!
There has been some debate whether the vincristine is at all helpful. Vincristine has never been shown to be effective in GBM as a single agent, and has poor ability to cross the blood-brain barrier. There's the possibility that it only adds to overall toxicity without improving the efficacy of the regimen. Some retrospective studies have shown the PC regimen (without the vincristine) has comparable efficacy.
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