Hi folks/Stephen,
We had my mom's MRI just a week back, and her last MRI showed no growth of the disease, had no choline elevation(in the spectroscopy report) and didn't show perfusion either. :)
She has completed her radiotherapy, 3 cycles of temozolomide and 3 cycles of lomustine+temozolomide. We moved to the Lomustine + Temozolomide protocol because her disease was methylated.
This group, especially Stephan have been extremely supportive so far in this tough journey. I wish to run through you all my mom's cocktail, and wanted to ask specific questions on her cocktail. Would really appreciate your help! My questions on my mom's cocktail are as follows:
1. Should I consider adding anything, or updating anything in the current cocktail?
2. Because my mom's choline elevation has constantly been coming down in the past three MRIs, my oncologist suggests we do three more cycles of lomustine + temozolomide. However, my mom's WBCs never come up beyond 1500 after the chemotherapy. The oncologist supplements with Iron and Folic Acid for WBC support, post which the count reaches 4000, both of which from what I've aware are negative prognostic factors for GBM. He says the effect of the chemo overpowers the negative prognostic factor of Iron/Folic Acid. Do you think that it is the right approach to go about things, or should I consider stopping the chemo and not supplement with Iron/Folic Acid?
Is there anything specific that you have tried and has worked well for your patient for WBC support?
3. Are there any clinical trials/additional treatments that you would suggest doing beyond the current line of treatment that we currently are on? For now, we plan to do three more cycles of chemo along with the supplements mentioned below.
Following are the details from her biopsy
IDH1 and IDH2: Not detected
CHR 1p and CHR 19q: Negative for CHR 1p and CHR 19q codeletion
Methylation: Detected
Ki67 labelling index is 15-20%
Following is her FoundationOne report:
Genomic Alterations Identified
EGFR A289V – subclonal, amplification, EGFRvIII
PTEN I67T
CDKN2A/B loss
TERT promoter -124C>T
Additional Findings
Microsatellite status MS-Stable
Tumor Mutational Burden TMB-Low; 3 Muts/Mb
Additional Disease-relevant Genes with No Reportable Alterations Identified†
IDH1
PDGFRA
Following is the diet and supplements that my mom is taking:
Diet: Ketogenic Diet/Low Carb high fat diet
Supplements
I look forward to hear from you all!
We had my mom's MRI just a week back, and her last MRI showed no growth of the disease, had no choline elevation(in the spectroscopy report) and didn't show perfusion either. :)
She has completed her radiotherapy, 3 cycles of temozolomide and 3 cycles of lomustine+temozolomide. We moved to the Lomustine + Temozolomide protocol because her disease was methylated.
This group, especially Stephan have been extremely supportive so far in this tough journey. I wish to run through you all my mom's cocktail, and wanted to ask specific questions on her cocktail. Would really appreciate your help! My questions on my mom's cocktail are as follows:
1. Should I consider adding anything, or updating anything in the current cocktail?
2. Because my mom's choline elevation has constantly been coming down in the past three MRIs, my oncologist suggests we do three more cycles of lomustine + temozolomide. However, my mom's WBCs never come up beyond 1500 after the chemotherapy. The oncologist supplements with Iron and Folic Acid for WBC support, post which the count reaches 4000, both of which from what I've aware are negative prognostic factors for GBM. He says the effect of the chemo overpowers the negative prognostic factor of Iron/Folic Acid. Do you think that it is the right approach to go about things, or should I consider stopping the chemo and not supplement with Iron/Folic Acid?
Is there anything specific that you have tried and has worked well for your patient for WBC support?
3. Are there any clinical trials/additional treatments that you would suggest doing beyond the current line of treatment that we currently are on? For now, we plan to do three more cycles of chemo along with the supplements mentioned below.
Following are the details from her biopsy
IDH1 and IDH2: Not detected
CHR 1p and CHR 19q: Negative for CHR 1p and CHR 19q codeletion
Methylation: Detected
Ki67 labelling index is 15-20%
Following is her FoundationOne report:
Genomic Alterations Identified
EGFR A289V – subclonal, amplification, EGFRvIII
PTEN I67T
CDKN2A/B loss
TERT promoter -124C>T
Additional Findings
Microsatellite status MS-Stable
Tumor Mutational Burden TMB-Low; 3 Muts/Mb
Additional Disease-relevant Genes with No Reportable Alterations Identified†
IDH1
PDGFRA
Following is the diet and supplements that my mom is taking:
Diet: Ketogenic Diet/Low Carb high fat diet
Supplements
I look forward to hear from you all!
I'm not so sure it's correct to say folic acid is associated with worse outcomes for GBM. There was one study showing that GBM patients with reduced activity of the MTHFR enzyme (due to mutations in that gene) had worse survival. MTHFR is a key enzyme in the pathway that converts folic acid to 5-MTHF, a critical co-factor for remethylation of homocysteine to methionine. This study suggested that in some cases, folate supplementation could actually be a therapeutic strategy.
ReplyDeleteAlso,
https://www.ncbi.nlm.nih.gov/pubmed/19451595
Folate supplementation limits the aggressiveness of glioma via the remethylation of DNA repeats element and genes governing apoptosis and proliferation.
"Finally, we show that the folate-induced DNA methylation limits proliferation and increases the sensitivity to temozolomide-induced apoptosis in glioma cells through methylation of the genes implicated in these processes (PDGF-B, MGMT, survivin, and bcl-w)."
Rather than looking at overall WBC counts, it's more informative to look at specific populations, such as lymphocytes and neutrophils. What you want generally is a higher lymphocyte count and a lower neutrophil count (but not dangerously low), and a neutrophil to lymphocyte ratio under 4:1. This is because lymphocyte populations such as CD4+ and CD8+ T-cells can help fight the tumor, while neutrophils are often tumor-promoting.
ReplyDeleteIron supplementation is not the most ideal way to increase white cell counts, given that iron can be a tumor promoter, but if it's a choice between iron supplementation or stopping chemo I'd agree with your oncologist. However there might be other ways to support white cell counts, and I'd refer to you to a nutritionist specializing in helping cancer patients (see Links and Friends section at the bottom of the blog).
I hadn't seen these FoundationOne results before. Given the EGFRvIII mutation I would certainly consider chloroquine.
ReplyDeletehttps://www.ncbi.nlm.nih.gov/pubmed/29377763
EGFRvIII expression triggers a metabolic dependency and therapeutic vulnerability sensitive to autophagy inhibition.
"In line with these findings, retrospective analysis of glioblastoma patients indicated that chloroquine treatment improves survival of all glioblastoma patients, but patients with EGFRvIII+ glioblastoma benefited most."
Keep in mind chloroquine can contribute to low blood counts (thrombocytopenia, neutropenia, aplastic anemia), but these reactions to the drug are considered to be rare.