Grade II Astrocytoma (IDH1 Mutant) treatment plan

Hi Stephen and all,

Thank you for allowing me to create this thread. I am a 31 years old male from Australia.

I recently got diagnosed with a Grade II Astrocytoma with histopathology report as follow;

Clinical Notes: Incidentally found left Insular region glioma

Mitoses: 0/HPF

Immunohistochemical Stains: Block 1

Ki67: 1%

How estimated: Visually and IDH1, Ki67 dual stain

IDH1 R132H: Positive

ATRX:  Lost

P53:  10%(moderate/strong staining)

EGFR:  Negative

Other Positive:  GFAP, PHH3 highlights 2 mitotic figures, however, it remains possible that these cells are not tumor cells hence it shouldn't be used in grading

MGMT promoter Methylation: If clinically indicated. Block 1 Tumor 60%. Patient Agreement required.

I had Gross Total Resection and according to my neurosurgeon, there is no residual tumor left. Size upon diagnosis was around (14mm x 13mm x 10mm).

I had a few questions regarding Histopathology, wondering if you all can help, please?

1) Should I push for a more thorough genetic study on this tumor? Is it worth it at this point in time to get PTEN, MGMT (as it looks like they haven't performed this test) & Ip/19q codeletions? I know it is unlikely for it to be 1p/19q codeleted since it has p53 staining & ATRX loss.

  

2) Why does it mention mitotic figure: 0/10HPF, then goes on to mention PHH3 highlights 2 mitotic figures but 'possibly' nontumor cells? How do they know that they were nontumor cells?

3) Does Ki67 index & P53 values mean much?

My neurosurgeon has advised holding off any chemo/radiation for the time being and adopt a 'watch and wait' approach. I am happy to hold off chemo/radiation too but I do want to start taking supplements and other medication to possibly delay the recurrence. I plan on taking the following supplements and medication (Please tell if I am mental for doing it).

Supplements:

Curcumin (Longvida)

Vit D (4000IU)

Fish Oil

Vit C (4g)

Magnesium

Resveratrol

Green Tea Extract

Selenium

Milk Thistle

Sulforaphane (From broccoli sprouts)

ZINC: Should I add this? I read on this forum somewhere that it is not really beneficial for people who have enough Zinc levels in their blood. 

Medication:

Aspirin daily 100mg daily (COX 2 Inhibitor) or should I consider Celebrex?

Melatonin (10g - 15g daily)

Metformin 1000mg daily (Keeping the blood sugar level down)

I am thinking of using;

Metformin 1000mg daily (Keeping the blood sugar level down)

Betablocker (Propanolol)

Low dose Mebendazole (Cycle off every after a month use)

Angiogenesis Receptor blocker

DCA

Clomipramine

Thank you for pointing out Isosidenib and Vorasidenib Steph!

- I am really worried about my glioma acquiring hypermutation, is it possible that Agios inhibitors can turn IDH1 into Wildtype by how they operate? 

- I know no one knows for sure, but is it normal to adopt watch and wait approach for Grade II astrocytoma? 

- Are there any clinical trials I should consider? I can't seem to find any trials on LGGs at the moment.

Thank you so much for taking out the time to read this.

Regards

Ruki

Do statins, ACE inhibitors or sartans improve outcome in primary glioblastoma?

Hello all,
I spotted this paper and thought it was best to share: “Do statins, ACE inhibitors or sartans improve outcome in primary glioblastoma?” Although I’ve not read the full paper, it’s worth noting that they concluded:

This secondary analysis of two large glioblastoma trials thus was unable to detect evidence for an association of the use of statins, ACEI or sartans with outcome in patients with newly diagnosed glioblastoma

Should we abandon ACE inhibitors, etc?

Bioavailability of WokVel Boswellia Serrata vs "ordinary" Boswellia Serrata?

Hi all,

I've read here that WokVel boswellia serrata has greater bioavailability than the "usual" boswellia formulation.  But I've not been able to find anything in the medical literature or on the WokVel website confirming this.  If I could replace the canonical dose of 4200 mg H15 BS/day with a smaller number of WokVel pills (what's listed on the supplements spreadsheet as three 333 mg WokVel capsules/day), that would make my husband really happy.  Anyone have any insight or citations to offer?

I did contact the WokVel company but they're oriented towards the business end, not end consumers, and my inquiry just resulted in an email asking about my business plans.

Salt Tablets

Hi Everyone
Given that my daughters normal blood pressure has always been on the lower end of the scale, i have been giving her some OTC salt tablets (600mg Sodium Chloride) 4-5 times a day to counteract the Trandolapril and the higher dose of Verapamil over the week surrounding chemo treatments.
In reading an article from the library (Thank you Stephen for giving me access to the library) titled;
Losartan versus Enalapril on celebral edema, it states that lab rats were given a high salt intake to accelerate the appearance of celebral edema.
It concludes that chronic treatment with the AT receptor blocker Losartan prevents the development of celebral edema, and causes manifest cerebral edema to disappear in salt loaded rats?
I am totally new to all of this, and i struggle to understand the medical and scientific interpretations, so i guess my question is;
By giving my daughter a salt supplement to counteract her angiotensin medications, could i in fact be escalating the risk of additional edema.
Any feedback greatly appreciated.
Regards
Martin

Do statins, ACE inhibitors or sartans improve outcome in primary glioblastoma?

This is a new paper (click here for abstract) brought to us by some of the same authors who earlier produced:

Does Valproic Acid or Levetiracetam Improve Survival in Glioblastoma? A Pooled Analysis of Prospective Clinical Trials in Newly Diagnosed Glioblastoma

The group concluded:

"This secondary analysis of two large glioblastoma trials thus was unable to detect evidence for an association of the use of statins, ACEI or sartans with outcome in patients with newly diagnosed glioblastoma."

As with the previous study, there are some important caveats.  Some of the most intriguing data supporting the potential for angiotensin system blockers was in combination with bevacizumab:

Effect of angiotensin system inhibitors on survival in newly diagnosed glioma patients and recurrent glioblastoma patients receiving chemotherapy and/or bevacizumab

It would have been interesting to look at outcomes in those using/not using ACE inhibitors or sartans in combination with bevacizumab, for example in the Avaglio and RTOG-0825 trials.

Angiotensin-II has been shown to increase tumor-promoting macrophages in preclinical models:

https://www.ncbi.nlm.nih.gov/pubmed/23333075

and these tumor-infiltrating myeloid cells may play a significant role in resistance to anti-VEGF therapies such as bevacizumab.

https://www.ncbi.nlm.nih.gov/pubmed/26404753

Angiotensin system inhibitors + low dose Avastin

This June a study was published by Victor Levin et al. of Kaiser Permanente Hospital, Redwood City, which follows up on a previous study on the use of Avastin doses lower than the standard dose.

https://www.ncbi.nlm.nih.gov/pubmed/28631191  (I've uploaded the full study to the Brain Tumor Library -> Folder 1. Therapies - Human Studies -> Angiotensin System Inhibitors)

The current study looked at the use of angiotensin system inhibitors, including both ACE inhibitors (benzapril, captopril, etc.) and angiotensin II receptor blockers (losartan, telmisartan, etc.) used for hypertension simultaneously with chemotherapy and/or Avastin in newly diagnosed and recurrent glioma patients.

In a very large cohort of 1186 infiltrative glioma cases (grades 2-4), use of an angiotensin system inhibitor (ASI) was significantly associated with better survival (hazard ratio 0.82), in a multivariate analysis adjusted for other variables such as age, extent of resection, GBM versus other grade, use of Avastin, etc.  This advantage of ASI treatment was even more significant in patients who were also treated with Avastin (HR 0.75).

A previously published cohort of 181 recurrent GBM patients treated with various doses of Avastin was examined with regard to their use of ASI drugs (for hypertension).  The previous study had shown trend toward longer survival in the group treated with lower-dose Avastin, and this study has been summarized elsewhere.
http://virtualtrials.com/pdf2016/benwilliamsTreatmentOptionsUpdate2016.pdf   (Page 90)

Remarkably, of the 89 patients treated with doses of Avastin lower than 3.6 mg/kg/week (the standard dose amounts to 5 mg/kg/week),  the 47 patients also using an ASI drug had a very impressive median survival of 99 weeks (22.8 months) versus 55.6 months (12.8 months) for the 42 patients receiving low dose Avastin without ASI drugs.

99 week (nearly 23 month) median survival (from treatment for recurrence) for a sizeable (n=47) group of recurrent glioblastoma patients in virtually unheard of.  Although all the usual caveats apply because of the retrospective, non-randomized nature of this study,  the outcomes are too impressive to ignore.

As Levin et al. conclude "Prospective clinical trials combining ASIs with low-dose BEV in GBM patients are now needed to confirm whether ASIs can enhance the efficacy of VEGF-targeted therapies and thereby improve clinical outcome."

As a side note, Victor Levin is the founder of the Society for Neuro-Oncology (SNO) and often described as the "father of neuro-oncology", at least in America.

Celebrex control edema? also question about boswilla

Hi all,

I come from China,this blog is wonderful to help my GBM wife.I want to start with a quick question. Stephen,i saw in the library excel that celebrex can help reduce edema,but i can not find related study in the library, do you have it?

I read the study on boswilla serrata control edema pretty well, just want to confirm is that still the best way?

Regards
Roy

Dexamethasone vs. confusion

My wife is very confused lately - more so than usual. It's been about two weeks after the SoC of radiation and chemotherapy.

We have been trying to wean her of Dexamethasone so she's currently on 4mg in the morning and 2mg at night. But we're worried that her state of confusion is dampening her already dampened spirits.

I'm very wary of dexa - at our first hospital, the surgeon gave her a whopping 64mg a day, or 16 tabs. Her tumor wasn't considered "a time bomb" at the time but two weeks later, we rushed her to the hosptial as the tumor became very, very aggressive. I don't have anything to support this but I'm certain that the dexa had a hand in this as I feel it increased the glucose in her blood resulting in the growth. Our NO says there's little support for this.

Now, our new issue is that she was fine on 4/4 so we dropped her (per the NO) to 4/2 but her confusion has increased dramatically.

I'm trying to counter this is 2400mg of Boswellia (specifically http://www.amazon.com/Boswellia-Serrata-1200-Mg-Capsules/dp/B00C6B17VM) as well as turmeric and celebrex but it doesn't seem to be cutting it.

Questions

1. Are my fears of dexa over-blown?
2. If they are not, what alternatives do I have to the dexa?

Thanks in advance!