Dexamethasone limits benefit of Immune checkpoint blockade

 New study published in clinical cancer research:

Concurrent Dexamethasone Limits the Clinical Benefit of Immune Checkpoint Blockade in Glioblastoma

https://pubmed.ncbi.nlm.nih.gov/33239433/

from the abstract:

Results: Despite the inherent responsiveness of GL261 to immune checkpoint blockade, concurrent dexamethasone administration with anti-PD-1 therapy reduced survival in a dose-dependent manner. Concurrent dexamethasone also abrogated survival following anti-PD-1 therapy with or without radiotherapy in immune-resistant CT-2A models. Dexamethasone decreased T-lymphocyte numbers by increasing apoptosis, in addition to decreasing lymphocyte functional capacity. Myeloid and natural killer cell populations were also generally reduced by dexamethasone. Thus, dexamethasone appears to negatively affect both adaptive and innate immune responses. As a clinical correlate, a retrospective analysis of 181 consecutive patients with IDH wild-type GBM treated with PD-(L)1 blockade revealed poorer survival among those on baseline dexamethasone. Upon multivariable adjustment with relevant prognostic factors, baseline dexamethasone administration was the strongest predictor of poor survival 

Conclusions: Our preclinical and clinical data indicate that concurrent dexamethasone therapy may be detrimental to immunotherapeutic approaches for patients with GBM.

The GL261 referred to is a mouse model of glioma.

Blockade Strategy Feedback

 Hello, everyone!

I was diagnosed in May 2019 with GBM and I have completed SOC in Apr. 2020 (Total resection, 42days Chemo/Radiation, and 6 months maintenance chemo). I have done a lot of research on supplements and medications as well as reviewing many promising techniques to stop GBM. One, in particular, had caught my eye which is the CUSP9 protocol. I like this protocol because it attempts to stop GBM in its tracks not just slow or delay things until a recurrence. In addition, I find the results from this study to be one of the best and I believe the strategy used to attack a recurrence is very logical by blocking all the known survival pathways of GBM. I feel that current strategies only partially attack GBM and because of its adaptive characteristics only delays or slows down the inevitable. Cutting off survival paths seems the best strategy until something more profound is developed for people with GBM.

I devised this because it is a helpless feeling treatment is over without much to prevent a recurrence, cocktails are either partially attempting to stop GBM or there is no rhyme or reason to them, dosing strategies do not follow the research, and posted research used in cocktails does not come from peer-reviewed information.

I do not have access to prescription drugs like some people to be able to copy the CUSP9 protocol if I ever have a recurrence or for the newly diagnosed protocol. So I tried researching supplements to see if I could find a supplement-based comparable solution. Unfortunately, when supplements are tested in studies, there is little information on the survival pathways impacted by supplements in the study. I had to reassess my strategy at this point.

I did notice supplements did have common terms in the studies such as proliferation, apoptosis, etc. So I went through many studies and found 9 common mechanisms referenced in the studies as shown.

So I went through studies (NCBI) on many popular supplements used in many "cocktails" and identified the mechanisms impacted by the supplements. I came up with this:

I chose a list of supplements which should provide a blockade to all the mechanisms. I also chose redundancies of each mechanism as I suspect there are many pathways behind these mechanisms. To give a validation to my blockage strategy, I researched Ben Williams protocol he uses to see what mechanisms his protocol covers. I was surprised to find this

His protocol impacts all the mechanisms I found and he also has redundancies in each mechanism of the blockade.

Another argument for this is my oncologist informed me in March of 2020 I had a tumor remnant leftover from surgery 2.5cm in size at the largest diameter with no metabolic activity(contrast and spectroscopy). He thought it was swelling but the MRI with spectroscopy verified as a tumor remnant. This was a shock because I was told by the surgeon I had a complete resection. I was told the only way to get rid of it was removal during any additional surgeries I may experience and since there was no metabolic activity, it would be monitored. In my July MRI, the remnant was 1.8cm in size with a "significant" reduction in blood flow to the original tumor area. In my last October MRI, it was at 1.0cm with more "significant" reduction in blood flow (no metabolic activity). 

So my questions are these:

1. My oncologist attributes the reductions to SOC. However, he admits never seeing such a positive result as this. Could this be the result of SOC, my blockade, or something else?

2. Does anyone see limitations in this or recommend improvements?

Thank you for your feedback.

Regards,

Eric

Questions for newly diagnosted (Melatonin, Chloroquine, Celebrex and NO)

 Hi everyone,

I'm so grateful to have found this blog to give me hope for my sister.  Thank you so much Stephen to have create this. 

She's been diagnosed recently with glioblastoma (Methyled). She's starting her treatment in a couple of days and I have some question:

Melatonin:

My sister is set to have 6 weeks of radio/chemo (TMZ). Melatonin needs to be taken at night but will there be enough in her system to have an effect during the day when She's receiving the radio/chemo? 

Open mind NO or doctor: 

Also, is there anyone who had good luck to find an open mind about supplements and medications that we want to add to her protocol? We are in Canada (Montreal).

Chloroquine: 

If I can't find any doctor willing to prescribe it, is Artemisinin a good plan B? If so, what dosage would be best?

Celebrex:

If for the same reason I'm not able to find a doctor, is Boswellia extract a good plan B?

thanks a lot for your help.

frederique

Lomustine hair loss (alopecia) experience

Hi all

Wondering if anyone who has taken lomustine or CCNU experienced hair loss or low-grade alopecia as a result. If so, could you share the experience, how much loss, how long did it take for hair to grow back, etc.

Thanks!