Wednesday, 8 February 2017

Conversation with NO

Dear all,
I need some advice as to how much to share/not to share with our NO regarding my son's vaccine treatment. We just started vaccine with Van Gool  ( three weeks after the end of chemoradiation)who thinks my son should definitely not do any  chemo while on immunotherapy (except for, if we have PD1 , maybe Keytruda). He has low MGMT expression, which justifies the use of TMD, but his blood counts dropped really low the last few weeks of chemo and he generally tolerated it very poorly.  Our NO previously was talking about either doing avastin or/and maintenance or CCNU based on the post radiation MRI ( which we will have for the first time since surgery in October).
While I tend to go with Van Gool's idea, I am not sure how much I should tell our NO. I am afraid if we put it on record that my son is doing DC vaccine, that would preclude him from further clinical trials. Conversely , if we don't follow the standard procedure, maybe we could be excluded from trials as well. Our NO is a good guy ( not a brilliant professional, though), but I am not sure how much I should/should not share with him.


  1. How was his MGMT status tested? By immunohistochemistry (IHC)? or was there any methylation testing (by methylation specific PCR)? Some studies have concluded that simply testing for MGMT protein by immunohistochemistry is not as valuable or predictive as methylation status of the MGMT promoter.

    It seems to me that something like doing a dendritic cell vaccine is something your NO ought to know about, but yes it would likely disqualify him for immunotherapy trials, especially vaccine trials. Also not following the standard TMZ schedule or taking Avastin now could also disqualify from some trials. However, doing a vaccine at IOZK (combined with NDV and possibly a PD-1 inhibitor) probably has a better chance of helping him than most of the clinical trials out there. I think you need to go with what has the best chance of helping him now and preventing recurrence.

    CCNU is also hard on blood counts, so I'm not sure what the reason is for substituting that in place of TMZ if the problem is myelosuppression.

    17 years of age is quite young for a GBM. What part of the brain was the tumor located in? Was there any genetic testing done on it (for IDH1 mutation, H3F3A (histone H3) mutation? EGFR mutation/amplification)? This could also help inform the likelihood of chemo being helpful.

    1. Also, very important, what was the extent of his resection? Was it a complete resection, or was there residual tumor left after surgery. The vaccine approach is more likely to be effective with minimal residual tumor.

    2. Stephe, thank you so much for your response! He had a near total resection in October from left cerebellum. Frozen section pathology was pillocytic astrocytoma, but the final came back as malignant - high mytosis, no palisading necrosis or vasular proliferation. It was grade III, but then the H3K27 mutation puts it in IV.
      Other results are:
      INI1 retained
      BRG1 retained
      GFAP positive
      IHD1 negative
      P53 negative

      a more in-depth analysis later showed
      H3K27 mutation confirmed

      No EGFR or other typical GBM markers since his is a "pediatric version", I guess.
      Just checked that the NO - still a bit confused, but he said it was tested for MGMT promoter methylation (not IHC) .

    3. Thanks Olga, this puts things into much better perspective. What was the result of the MGMT methylation testing (methylated or unmethylated?).

    4. it said " low methylation"

    5. "Low methylation" or unmethylated status of the MGMT promoter implies a lesser chance that TMZ or CCNU chemotherapy will benefit. This is one more argument in favor of not doing chemo during vaccine treatment.

      Also I recall you were looking into Sativex for your son. While the new trial results for Sativex (see my recent comment) show that it looks to be beneficial in combination with TMZ, I'd be hesitant to use cannabis products in combination with a vaccine, due to the potential for cannabis limiting the vaccine-induced immune response.

    6. Yes, we were looking into that! This makes sense, Stephen, thank you!

  2. Unless I missed it ....what vaccine are we speaking about and is it available in the US?

    1. We're speaking about vaccines prepared at IOZK clinic in Koln (Cologne) Germany.

  3. Tell him. He would be disqualified anyways when they see his full medical report, unless you planned on hiding that from the trials.

    1. I tend to think the same. I don't think we will qualify for any trials here before recurrence anyway. My concern is for after recurrence - would it be back to square one in terms of qualification?

  4. My dear Olga - I've been without wifi for a month, so I'm happy to reunite with my blog family! I think it's terribly important that the NO knows what the patient is taking. You don't have to ask permission. When we implemented my son's cocktail (he was 38), I made a list of the items and wrote an explanation of why we were using each item. I never asked for permission - I just said here is what we are doing and here is why. I gave links to this blog, and to research for each item (including the Surviving Terminal Cancer movie). It puts the NO at a disadvantage to not know what the patient is taking and the last thing you want to do is put your son at a disadvantage! If the NO puts up resistance that you can't resolve, you may need to find another NO.