Hello,
Has anyone had good results after a recurrence of a high grade glioma using Temodar on a daily low dose in combination with another agent? I'm looking for an approach that might increase it's effect for my wife who had a recurrence (AA3). Her NS has made the suggestion (just the TMZ alone) and I would assume her oncologist will be advising the same. Given that it appears her tumor didn't respond to TMZ in the first place I'm questioning that it will be the same outcome as before. Perhaps CCNU might be the better choice, or combining them if she tolerates it.
Ray
Hi Ray,
ReplyDeleteWas the MGMT status of the tumor determined (methylated vs unmethylated)? This information would help predict response to both TMZ and CCNU.
Also is a second resection an option? How large is the recurrence? A second resection followed by genetic analysis for hypermutation would be one option, esp. if the tumor is IDH1 mutant. Further TMZ for a hypermutated tumor could just make the situation worse. Hypermutation analysis is not routinely done though. Extensive genetic sequencing such as FoundationOne could determine that, but that particular testing is not covered by insurance agencies outside the US.
Hi Stephen, is the hypermutation analysis part of the foundation one genetic sequencing? I mean does it come as part of the report? We had that test done for my husband few times and I didn't see something called hyper mutation analysis as part of the report. Is it something that his doctor needs to ask for? Thanks so much
ReplyDeleteHi Noha,
DeleteThere is no hypermutation analysis specifically included within the Foundation report, but if you know what to look for you can tell a hypermutated tumor from a non-hypermutated one. Hypermutated tumors are usually found at recurrence rather than at first diagnosis.
1) Hypermutated tumors typically have mutations in one of the mismatch repair genes, most commonly MSH6, but other ones tested by Foundation are MSH2, MLH1 and PMS2.
2) A much higher than expected number of mutations. For a non-hypermutated tumor, the total number of mutations (both mutations of known significance at the top of the report, plus Variations of unknown significance in the appendix section) in a Foundation report is typically 1-20 (average 10-15). A hypermutated tumor on the other hand would typically have anywhere from 35 to over 100 mutations total on the report.
If a see a tumor with one of the known mismatch repair mutations (usually MSH6) and many mutations as described above, I would call it hypermutated.
Thanks so much Stephen. Appreciate the elaborate explanation.. Very helpful.. Never knew that. Many thanks
DeleteI have a phone friend , thriving, who was recently found to fail with optune after 6 mos of over 70 per cent compliance for daily use.She had a follow-up mri two weeks ago and con out her GBM had not only progressed but had a new tumor as well. During this time she had been on low dose TMZ and part of the CUSP9 protocol as tolerated our drugs could be found.So now she is set up to try neuroblate.I have SEx and am keeping in mind the neuroblate as well as polio virus.this friend husband has been a wealth of knowledge for me and his read of the medical literature had not shown the polio virus intervention to be all that great.hope this helps.you could do your wife a huge favor and begin reading some of the literature on interventions for her.being the medical person in our family,I am having to take on all the yuckystuff myself.
DeletePaul
Hi Stephen,
ReplyDeleteShe had the resection last week, total resection according to the surgeon. We had the sample flash frozen for further testing later, and the current pathology report revealed it be the same- AA3, idh1 no information about methylation. It showed a loss of atrx which the surgeon said wasn't as good but I understood it meant to be more favourable, so I'm unsure as to whether he misread it or had just forgotten. Their was a lot of scar tissue from radiation in the area resected but also active cells unfortunately. The cystic area had grown again from her previous MRI with a bit more thickening of the wall which was enhanced so her oncologist called it a recurrence, even though the enhanced area was present in every MRI since post radiation, but the oncologist disagreed with the radiologist and said it wasn't anything until it grew a bit thicker and the cyst stopped shrinking and enlarged. We will speak with the oncologist next week to discuss the next steps, but I would like to get the sample tested further in order to guide the treatment in the right direction.
Hi Ray,
DeleteI'm glad the surgery was a success and that it was still considered a grade 3. Another thing about hypermutated lower grade gliomas is that they always present as an evolution to grade 4 ("secondary GBM").
IDHmutant astrocytomas typically have ATRX mutations which manifests as loss of ATRX expression. Whether this is a good thing or not is relative. It's less favorable than having an IDH1 mutant, 1p/19q codeleted tumor, but for IDH1 mutant astrocytomas current evidence suggests it confers positive prognostic significance.
http://www.ncbi.nlm.nih.gov/pubmed/23904111
I would ask if they can test MGMT status for sure. I don't expect you're dealing with a hypermutated tumor based on what you've said, but this is always a risk factor with further TMZ alone for this type of tumor.
Thanks Stephen
DeleteThe MGMT status is what we will be trying to get it tested for next. As for the hypermutation, I checked Foundation One's website and they had the cost of the test- very expensive. It might very well be worth it but for us that is a significant amount of money. Should we have it tested for 1p/19q codeletion? I was under the assumption that oligodendrogliomas had that and not so much AA3s.
We are still surprised and disappointed at this recurrence despite all of the promising signs in regards to her initial resection, treatments and histopathology. At least she had another complete resection and it hasn't progressed to a grade 4.
Ray
The Foundation testing probably isn't worth it for you at this stage in the game. I would save that as an option for the future, if the tumor progresses to a grade IV (which hopefully it won't of course).
DeleteIf the tumor has loss of ATRX and overexpressed p53 then it almost certainly won't have 1p/19q codeletion, so I wouldn't worry about getting a test for that.
Thanks for clarifying that. Have you seen this study involving combining ginsenoside Rg3 with metronomic TMZ? Sounds interesting http://connection.ebscohost.com/c/articles/113035042/additive-antiangiogenesis-effect-ginsenoside-rg3-low-dose-metronomic-temozolomide-rat-glioma-cells-both-vivo-vitro
DeleteInteresting, although Gensenoside Rg3 is not for sale for human consumption that I'm aware of (perhaps it is in China?)
DeleteIt comes from China I believe and is available through supplement distributors in Europe and probably elsewhere. On another topic, do you know if Photo Dynamic Therapy is offered anywhere other than clinical trials? I know they have it in Ontario for other cancers but no mention of brain tumors. Thanks
DeleteThere is/was a location in Scotland that does photodynamic therapy for brain tumors (I learned about this as Anders Ferry had PDT therapy done there years ago). I don't have much information on it though. I contacted someone from the Ontario clinic a couple years ago and was told they're no longer doing PDT (at least for brain tumors).
DeleteHi Ray, a phone friend of mine has GBM and used Optune with over 70% compliance on daily use. Use has been for 6 months. During this time she also tried the low dose TMZ with the Cusp9* protocol(as she could tolerate or find the drugs in the protocol). MRI 2 weeks ago shows tumor growth and met to new area of brain. Neuroblate in the works now to deal with these findings. Low dose TMZ is in the CUSP9* protocol. Have to say it failed her. Her husband had been a wealth of information to me and reads a lot of the medical literature for GBM. His take on one of the newer interventions modified polio virus infusion into the tumor has not been that great. Duke U is doing this study.
ReplyDeleteStephen--does this site work with Android? I sent a message and had some odd inserts that I could not modify with Edit. So I am re sending on my PC.
Paul S
I'm not sure about Android, but your first version of this message appears above, in the responses to Noha's comment ^
Delete