High Intensity Focused Ultrasound

So the whole situation started a few months ago when we were talking with Dr. Sze following Laurie's chemo embolization.  It went something like this:

Dr. Sze:	If Laurie's continuing to have some pain from the bone radiation you might need to consider something that we do here at Stanford and may help her. It's called HIFU.
David:	Gesundheit
Dr. Sze:	No, I said HIFU
Laurie:	Gesundheit
Dr. Sze:	[sigh] I'm talking about High Intensity Focused Ultrasound. Some of my colleagues are using it and it may really help if you need it.

OK, so maybe it wasn't quite like that, but Dr. Sze was the one who told us about it and it may be just the ticket to deal with the discomfort that Laurie has had since about a week after her radiation. It's been steadily growing so we are looking at this procedure as a possible palliative treatment.

We met with Dr. Pejman Ghanouni, MD at Stanford on July 10th to talk about this and to see if Laurie was a candidate.  He had really good things to say.  He spent a lot of time with us and briefed us on how HIFU works.


So what is HIFU.  High Intensity Focused Ultrasound is based on the same concept that many of you have used to fry ants with a magnifying glass.  Normally ultrasound is used with a very wide beam and all the energy gets dissipated over a large area, so there's no heat generated.  The concept of ultrasound for therapy has been around since the 1930's and focused ultrasound has been used clinically since the 1950's.  Over the last 10-15 years they've really been accelerating investigation for treatment.


The goal of the treatment is to provide relief from painful bone metastases.  It can also be used to do some degree of tumor treatment, although this is not the current intention and is more of a future possibility for HIFU.  HIFU uses converged energy to heat tissue or bones.  This has been coupled with MR guidance since the 1990's.  They can do immediate post procedure validation to verify that the treatment has been successful. There's a very small risk that heating a bone could cause a fracture, but that would be rare.  He indicated there were only 2 instances that he knew of that happening and one was because the treated person went out dancing sometime after the treatment.  When used on bones and tissue HIFU will heat the bone to the point where the nerve endings inside the bone die.  So, it doesn't correct any weakness, but it will make things more comfortable. In Laurie's case it probably won't matter too much as it's not a weight bearing bone.  Although she probably should avoid roller coaster rides.  This is an out patient procedure and it's expected that there will be some discomfort for a few days afterward.  They say it's no more than can be handled with ibuprofen.



There are actually 2 versions of the HIFU machine.  One is a standard MRI machine, but has some modifications on what you lie on.  The other is more portable, but is experimental and due to the location of Laurie's bone, it isn't possible to use it.  Dr. Ghanouni's presentation even showed us an example where this was used on the exact same bone Laurie's had discomfort on (that's the picture to the left).

So, where does this leave us?

We are currently in the process of requesting approval from Cigna (oh joy). It's expected that Cigna will reject the initial request, but they have had good success when appealing and doing the peer to peer reviews for this procedure.  If all goes well, it's hoped that the procedure can be done in 4 weeks.  We'll see how the appeals and approval process go.

PET scan June 27, 2014

Good morning all,

For those of you who like to read such things, here is the report of my recent hard-fought-for PET scan.

If you click on them they will become a bit larger and easier to read. Happy reading!

An Intriguing Visit to Stanford (aka the Trial Summary)

As many of you already know from FaceCrook, we went to Stanford this week and learned about some interesting and exciting possibilities for drug trials that may help Laurie out.  Oh, by the way, Laurie's alter ego David is writing this one.  Something about my writing looking worse than a doctor's prescription pad....

There are 5 new trials that may be opening in the near future at Stanford.  When asked which one was best for Laurie, Dr. Fisher said that he’s excited about all of them for different reasons and any of them would be a good opportunity.  Of the trials, 2 are new drugs, 2 are ways of stimulating the immune system and 1 utilizes a drug that causes an existing drug that was specific to the lack of a gene mutation. Before Dr. Fisher even saw us he had added Laurie to the list of patients interested in the first trial and he was going to seek to have her on the list for the rest of the trails.  With the exception of the immunotherapy trials, none of the trials are exclusionary.  In other words, as long other trials have openings, there is no reason that if Laurie needs to drop one (if it’s not effective or if it’s too painful) that she couldn’t join another trial.

One thing that we didn’t understand initially is the way immunotherapy works.  When they use immunotherapy drugs, the goal is to stimulate the immune system to attack the cancer in a systemic way.  This can be done by treating the largest tumor in the body.  By treating the largest tumor it is easier to administer the immunotherapy drug.  The body then creates an immune response that is systemic.  For example, they might find the largest tumor in Laurie’s liver that is active.  They apply the immunotherapy treatment to it.  As a result of the systemic immune response, her lung spots would then be treated.  So the immunotherapy drugs don’t just treat the one tumor, they are a systemic treatment.

Here they are the trials as we understand them (from my notes that read like they were written in the same hand as a doctor on a prescription pad)

1.      Radio RX

This trial is a randomized phase 3 trial that is a 50% randomization.  They have skipped phase 2 as they had such good results with phase 1.  The drug was initially developed by a Stanford student that had a degree in a different area and was studying to become a doctor.  It’s based on TNT, so initially there was hesitation to work with it as it was not known if it could be explosive.  The drug has been proven safe and they are now entering a phase 3 trial to seek FDA approval.  The way the drug works is that it looks for tissue that is lacking in oxygen (i.e. tumors) and caused intense oxidation of the tissue.  This effectively blows up the tumor.  The infusion must be given very slowly (6 hours) and is done 2 times a week initially and then is tapered off to 1 time a week.  Originally the trial was done with chemotherapy, but now they don’t believe it’s needed.  They will add irinotecan after the trial.

Patients who are not selected for the drug in the trial will be given Regorafenib (Stivarga^®).  This is because Regorafenib is the one drug that is specifically approved for the treatment of colon cancer. In order to qualify for this trial you cannot have been treated with Regorafenib.  This is the case with Laurie.

2.      Antibody InterlucanAlpha (IL1α)

This is a molecule that is released by “angry” tumors.  From google:

Interleukin-1 alpha is a protein of the interleukin-1 family that in humans is encoded by the IL1A gene. In general, Interleukin 1 is responsible for the production of inflammation

This trial is done with an antibody for IL1α.  The idea is to shrink the tumor.  This trial is also in phase 3 and like the RadioRX, it skipped phase 2 and has moved directly to the approval phase.  This trial is a randomized 2-1 placebo trial.  That means that there is a 33% chance that one could receive the placebo.

3.      IPI with PDL1 CTLA4 Target

PDL1 is an immunotherapy drug.  It has already closed for colon cancer, but they are seeking to test the drug along with IPI to enable a bigger response from PDL1.  The trial is seeking grants/funding at this time.  The drugs will be given by Genentech, but there is no funding for administration and delivery at this time.

4.      Radiation & PDL1

The idea of this trial is that the use CyberKnife to disrupt tumor cells and then give PDL1 to attack those damaged cells.  So they apply radiation along with interlumen antibodies.

5.      Bristol CD137 antibody with cetuximab (Erbitux®)

This is a really intriguing treatment.  Cetuximab is a treatment that is used for those colon cancer patients that do not have the KRAS gene mutation.  The way that Cetuximab works is to bind to the cells without the gene mutation (which are cancerous by nature) and kill those cells.  Cetuximab will bind to cancer cells that do have this mutation, but doesn’t activate.  The antibody from Bristol gets the Cetuximab to activate against the cells it’s bound to even though they have the gene mutation.  This is not a randomized study and is being done at multiple sites (I believe he said UCSF is one site).

The recommendation from Dr. Fisher at this time is to complete Laurie’s radiation, but to hold off therapy as long as possible.  The reason for this is that all of the trials require patients to be off chemotherapy and free of radiation therapy for 4 weeks.