Second Opinion Confirms Things - It Is Back & Inoperable - Not Happy :(

Mikenh said:

Do you have KRAS G12D or G12V

Do you have KRAS G12D or G12V?

If you have KRAS G12D and one of two HLA (helper Alleles), then there's a Clinical Trial at NIH in Maryland using something called TIL Therapy. The first patient that they tried it on (7 lung mets) had an amazing recovery.

KRAS (NM_033360) exon2 p.G13D (c.38G>A) is the one I have.  One of the things i asked on the second was should I do further genetic testing (this second from Mass General), was told no and that MSK test was enough. May still ask.  Not sure about the helper Alleles.  NIH is about 3 blocks from my brother.  I was scanning this site today - http://www.clinicaltrials.gov

I know you mentioned you were tested by Mass General (Dana- Farber?) in MA.  I looked to find a testing center in NYC area or would travel to Boston.  Which test did you do?  (I have never gotten search down on this site )   I can ask my PCP to arrange it.  Anything that can possibly help, I would do.

Trubrit said:

Drat!

Not good news, New, I am sorry to hear it. 

I know you will feel better to have gotten the second opinion.

You know that you will now take over the batton from our friend, John; and report on how the TCM is working for you. He would be so chuffed to know that his words influenced you. 

You are a positive spirit, New, and that will help you as you face the future. We will face it with you. 

Tru

 

And you know it. Still sounds risque.  LOL 

The second opinion was worth it and I would highly recommend going to get one.  The report was nicely done and having an 8 page document and the ability to ask any questions and get answers was worth it.  One of the big ones was confirming it really is inoperable due to location and that it probably is running around everywhere at this point.  I do appreciate that they are not sending me into a h--lish surgery that would have limited benefits and would really dink me on the quality of life side.

I wish John was around, would have a couple of questions to bounce off him.  Some guidance on TCM side of things would help.  Like Western Medicine, I have run into divergent opinions from a couple of TCM pracitioners.  The one I am working with is studied in both Eastern and Western medicine and someone from Asia.  (Not sure if you recall one of the things John and I discussed about selecting someone, he believed in someone who had an inherent belief as part of traditon, the pracitoners I have met with meet that criteria.)  The person I selected has me dosing on Vitamin D and C in high amounts (nothing crazy).  Some other supplements, Selenium and Artichoke Pills, plus also herb mixtures.  It is funny, as I stir the mixture in the pot, I think of John's instructions.  It seems to be a different mixture and different rules (about 12 tablespoons a day, not drinking cups, the first TCM had me drinking a glass of mixture tea twice a day.

Will definately let everyone know how the next scan goes.  Fingers crossed that satys the same or shrinks.  That would be awesome.

Mikenh said:

Immunotherapy works by

Immunotherapy works by targeting structures on the cell surface and telling the Immune system to go after cells with a particular structure. KRAS mutations are inside the cell so normally the immune system would be unaware of a cell that's bad. There are helper alleles. I've read that there are hundreds but that we typically have six of these. These Helper Alleles will signal bad cells to the cell surface if they find a problem. But the Helper Alleles need to be able to detect problems. The Allele HLA-C*08:02 will signal KRAS G12D to the cell surface. The Allele HLA-A-A*11:01 is thought to present G12D and G12V to the cell surface.

So far, the trials are only for G12D and maybe G12V. It may be because G12D is the most common of the KRAS mutants. Or that it was the first match between HLAs and mutations that they ran into. I chatted with my son's manager and he told me that this area holds a lot of excitement but it would mean analyzing all of the mutations and the helper alleles to see which are useful for flagging tumor cells and then coming up with the immunotherapy for targeting the cell surface structures and that doing this would take a fair amount of time.

The story of the first person (a lady on another board) that got this treatment is at:

https://cancerriot.blogspot.ca/search?updated-max=2016-08-10T10:37:00-04:00&max-results=7

And there's a more english version of what happened.

So that's why I asked about G12D and G12V. I am not aware of anything in this space for G13D but so far they're only working on two out of a large number of mutations.

One thing on terminology: genetic testing refers to testing your genes. Genomic tumor testing refers to testing the tumor. MGH requested what remained of my biopsy from my local hospital (the first part was sent to Mayo to confirm cancer) and had it transported to MGH. They performed two assays using their Next-Gen Sequencing Platform. An RNA assay looking for fusion transcripts as a result of translocations. They looked at 50+ target genes. The second assay looks at DNA variants for 91+ genes. BTW, this is the technology that you want as it finds your mutation instead of telling you what you don't have - in the old days, you tested for things one or two at a time.

I believe that they do the complete sequence of the tumor and store it so I think that I could ask if they could tell me which HLAs are in the tumor to see if I have one of the two known HLAs that signal KRAS G12D to the cell surface. I've already had chemo, radiation and surgery so a lot of damage has already been done but it would be nice to know if I had the helpers in case I get a recurrence. It would also be nice if we could map out all of this stuff for all of the KRAS mutations to the HLAs. That way, future tests could just tell you if immunotherapy was an option. It seems to be luck of the draw right now. I've seen some of the statistics but they're on relatively small samples.

Papers that I'm looking at: Adoptive T cell therapy for cancer in the clinic; Identification of T-cell Receptors Targeting KRAS-Mutated Human Tumors; T-Cell Transfer Therapy Targeting Mutant KRAS.

If MSK uses the same tech as MGH, then they should have your entire tumor sequenced. But this other stuff wouldn't be helpful at this time because the research isn't there for G13* yet. When you said that your mutation was common - I assumed G12D which is why I asked.

There's a long discussion on the therapy, called TIL, at http://coloncancersupport.colonclub.com/viewtopic.php?f=1&t=49736

I thought I had replied (I did and I hit post) to your post Mike.  I am not sure why it did not take.  Quick takeaway - you are seriously smart and I appreciate all you wrote ...  Not sure what happened.  The title of my reply was You Are Seriously Smart Mike.  And then went from there.  Urgh.  But thank you.