Wednesday, 11 July 2018

Gliosarcoma early recurrence?

I am mostly reader of this blog,  and I found many useful information and hope. Simultaneously, I tried to be as anonymous, as it is possible. Sometimes I afraid to even name the beast we face.

But now our situation looks dramatic and I seek help and additional information.

The short story: a young adult, diagnosed almost one year ago with a front lobe tumor (gliosarcoma). There were no prior symptoms, only sleepiness prior to a major seizure.

After double surgery at the end of July 2017, we spent a month recovering from complications. Next, our doctor administered irinotecan+carboplatinum. After 2 cycles of the chemo, we passed through 6-weeks radioteraphy with maximal possible doeses and TMZ administered daily. Next, from December: once cycle of TMZ and 3 cycles of TMZ+CCNU. MRI's at the early January and at the middle of April indicated stabilization.

Unfortunately, MRI at the end of June reveals contrast enhancement and a new diffused area outside the primary site.  Our doctors say its most likely non-resectable recurrence and or progression, and they changed the chemo to a new combo (topotecan and dacarbozine). I have asked, whether it could be a pseudo-progression, due to radiotherapy, but they exclude that.

Since December, when I discovered this blog and the Ben's book, we introduced some supplementation, including PSK/grifolan, bee-honey products, curcumin, berberine, fish oil, boswellia, 5-10 mg of melatonin, syllimarin. I was very afraid of including any of ``the regular drugs'' in coctails mentioned here.

The current neurological status of the patient is essentially stable and reasonably good, and we did not notice any particular symptomps indicating the progression.

I seek for any information, whether the new drugs could be supported by the coctail approach, and perhaps there are persons who have undergone a similar treatment. I am thinking on a few most frequent drugs (CQ, metformin, celebrex, melatonin in high doses), as well as POH.  Unfortunately, we have no information on the genetic status of the disease.

I would be also very grateful for your advice and/or information on clinical trails in Europe, we live in Poland and US/Canada are likely non-available for us.


  1. If your patient meets all the inclusion/exclusion criteria, the MDNA55 trial which is apparently recruiting in Poland might be a good option.

    Mazovian Brodnowski Hospital Recruiting
    Warsaw, Poland, 03-242
    Contact: Karolina Karas +48 600 953 994

    1. Thank you Stephen, I am going to call them, although the criteria sounds tight, and I am afraid that we do not qualify, particularly due to the prior, new chemo treatment.

    2. Unfortunately, the trail is actually closed and/or a decision on a new recruitment is pending at the moment...

    3. Dear Stephen,

      could you please comment on, regarding our situation? The cohort is rather small, and I believe that the drug is experimental. I am also not sure whether there is a chance of TMZ working with the new drug, given that the TMZ+CCNU apparently failed at relatively early stage of treatment.

    4. I don't have a whole lot to say about this because there's not a whole lot of evidence. There was a study in mice, and it was tried in 3 dogs with spontaneous glioma. In the dogs, PAC-1 by itself had no dramatic effect (5% and 6% tumor reduction in 2 of the dogs and 19% tumor increase (progressive disease) in the remaining one. Combined with temzolomide and radiation, responses were much larger (100%, 60% and 43% tumor reduction), but it's impossible to say how much of that was due to the conventional treatments alone.

      "Fan said a much larger study in dogs would be needed to determine whether the therapeutic effects were consistent and reproducible, and to quantify how much PAC-1 contributed to the positive results."

      I'm not sure if the PAC-1 would have any chemosensitizing effects in a tumor that was already chemoresistant. I haven't seen any data from the phase 1 trial you mentioned. It is also a phase 1 trial whose primary endpoint is maximum tolerated dose (rather than efficacy). These kinds of trials aren't ideal from a patient perspective because the optimal dose hasn't been worked out yet.

    5. Thank you so much, Stephen. I have been mostly attracted by the reported 100% response of one of the dogs. I found also only limited information on the drug and tests on humans. Btw. we would not qualify for the earlier phase 1 trial.

  2. I would always get a second opinion. I went for second opinion and surgery to Montpellier, France (dr. Duffau) and would do the same again. I think he is one of the leading neurosurgeons in Europe / in the world.

    Genetic testing was done and you just didn't get the information or it wasn't done in the first place? Although after radiation and chemotherapy, genetic makeup of the tumor could be different from the one at diagnosis.

    1. Thank you, Matjaz. Unfortunately, no genetic testing was peformed in the first place, and I checked that before asking on screening of particular mutations. I am also afraid that testing after the past therapy may be "obsolete" and non-representative but I have no better option nor idea at the moment.

      I am trying to get an appointment with am independent neurosurgeon.

  3. One can combine multimodal immunotherapy together with POH and the metabolic cocktail and the CBD/melatonin.

    1. Thank you, SVG. As the multimodal immunotherapy, do you mean an approach such as conducted in IOZK?

  4. I have one more question regarding chloroquine. In a description of the drug I have, there is a warning that it may provoke serious seizures. The person suffers of a kind of ``hacks'' a few times per day, in spite of taking 2x1000mg of Keppra (levetiracetam). Do you think (I mean people taking both drugs) that the risk is then really serious, when taking chloroquine? I found some papers reporting the unwanted effects (even the grand mal attacks).

    I must say that after reading the blog and everything I found, I feel as a complete ignorant. Being aware on possible benefits of the coctail approach, I am paralyzed with by the fear of making things worse, particularly since a few months of the standard treatment seemed worked well. Our oncologist and doctors I spoke with are against any supplementation. They are against even in this situation.

  5. Depending on the situation......I think it is always good to get a second and/or third opinion regarding recurrence/progression. They thought my husband had recurrence. We got a second opinion who concurred with the first opinion but I did not feel second opinion NO in our city had enough experience. I went to UCSF for third opinion. They did not feel it was recurrence/progression. My husband went 4 more yrs w/o surgery or treatment since it was not recurrence. Moral of the story...... additional opinions are a worthy consideration!

    1. Thank you very much for the encouraging comment. In fact I seek an independent opinion from two world-class neurosurgeons, but they are terribly occupied, and we must wait a week or so for a visit.

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  7. I am back to my story, and with an update.

    After MRI in the end of July, which showed changes identified by our NO as progression, I have got opinions from three neurosurgeons from different hospitals who said that they would not change the TMZ+CCNU treatment due to uncertain images, essentially contradicting the original diagnosis. However, a second, independent radiologist confirmed the original opinion of our NOs and radiologists.

    After two rounds of Topotecan and DICT (dicarbazine), the next MRI mid-August was better, with some missing contrast areas detected approx 1.5 month before. We are shortly scheduled for the fourth round of the chemotherapy (after the third round at the beginning of September). The issue is a low WBC (neutrophiles fall down below 1000).

    Meanwhile, I received the results of gene screening made with Ilumina HiSeq1500. The tumor samples after surgery (early August 2017) were confronted with a blood sample. The following gene mutations are identified

    H3F3A (G34)

    TERT promoter (sequencing made with the Sanger method) - no changes in the most common hotspot areas (C228 and C250) characteristic for GBMs

    There are also described deletions in regions 4q, 13q, 16q and 17q which I cannot understand, and a translation could be biased by my ignorance.

    As far as I understood, these results mean one of pediatric GBM (K3 G34) types, with the last there mutations interpreted in the report as rare and non-well documented. Also, if I understand correctly, the tumor is non IDH1/2 mutated (since the K3 G34), and non-MGMT methylated. (I do not forgot on the gliosarcoma diagnosis).

    I would be very grateful if you could comment on this report and suggest, if possible, drugs or supplements that could be useful in the treatment. The patient is now on keppra and still suffers from ``hacks'' a few times per day; I found that depakote could be beneficial with the G43 mutation.

    Many thanks,

  8. Apologies, the first bad MRI indicating progression was in the end of June, not July as written in my post above.