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Monday, 15 July 2019

IDH1+ GBM recurrence--any help appreciated!

Hi,  I have found Stephen and many of you to be great sources of information over the years and would really appreciate any help.  (Unfortunately, I can post but not comment thru some weird glitch.)  I have given my son's background before, but briefly he is a 26 y/o with secondary GBM (IDH1+) which was found to have recurred on a scan today.  He was diagnosed with AO2 (or perhaps AA3) in 2011 and had not quite total resection, "left-over" resected in 2012 and then had proton therapy as part of a clinical trial.  He did well for over 5 years--graduated from college and started med school.  He had a very small recurrence found 1/18 that had mutated to GBM (hypomutated with no actionable mutations other than IDH1 per Foundation One) with a very total resection.  He had never had any chemo and we opted to use a PARP inhibitor (BGB-290) with temozolamide--started 4/18.  He returned to medical school on chemo--tolerated both pretty well.  Today found out that 3 mm area of "uncertain significance" found 7 weeks ago is now 2.6x2x2.7 cm and near a ventricle (though some of size likely incorporates scar).  So, trying to figure out the next step. 

He was offered TMZ and radiation as options.  He wants to have the tumor "debulked", which seems supported in the medical literature.  (His tumor is left frontal lobe.) 

Options we have considered:  TOCA (thru IST program maybe?) with proton
                                                 LITT  with pembro
                                                 AZD-1390 trial --since ATM/ATR inhibitors useful if IDH1?
                                                 Duke Poliovirus--only works 21% and no better if mutant
  (Of course, I don't know if he will qualify for any of these.)

Would very much appreciate any suggestions!     Marcia

4 comments:

  1. Multimodal immunotherapy with NDV + hyperthermia + DC vaccines + immunomodulatory strategies can be of help.

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  2. Hi Marcia - I'm very sorry to hear your son is going through a recurrence. Another option would be vaccines (e.g. DC vaccines or for example an IDH1 peptide vaccine if you can somehow access in trial or otherwise).

    I'm also personally becoming very interested in PDT (photodynamic therapy). There are several different techniques / photosensitizers used, but the idea is to kill remaining tumor cells around the resection cavity during / following the operation via use of a photosenzitizer and lightsource to generate ROS which selectively kill remaining malignant cells. Some data suggests this may work particularly well for IDH1 mutant tumors (which are more sensitive to ROS). I am not sure where you are based, but there are various different methods being tested globally, with Japan being probably the most advanced. My hospital in Japan has an average OS of 31 months with PDT for GBM, which is an impressive statistic. They use a Talaporfin Sodium / laser based approach, and the treatment is basically risk free except you have to avoid bright light for a couple of weeks after.

    Might be another angle to consider...

    All the best wishes
    John

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  3. if a patient is planning for surgery, I am a major supporter of saving tumor tissue frozen. this gives a patient the opportunity to pursue a tumor Lysander vaccine if it becomes available in a few months. while the vaccine is being evaluated potentially this summer, (FDA, Health Canada, Europe), there is no guarantee hospitals will parafinize or freeze the tissue. a patient can still in the meantime take chemo or radiation or optune, etc...

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  4. I am an advocate for saving tumour tissue frozen after resection this gives the patient the opportunity to decide if they want to pursue a tumour lysate vaccine if one becomes available in the next few months. There's no guarantee that the hospital will paraffinze or freeze tumour tissue...but if a patient explicitly requests the process, in the meantime the tumour lysis vaccine is being evaluated by the FDA health Canada and European agencies perceivably this summer. in the meantime patients can decide if they want to do chemo, radiation or Optune, etc

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