jscott

Duke,

Andrea and I had some issues with the process as well. First, let me say I completely agree with your point…Don’t over think it! This is where many of our problems came up as well. Anyway, I talked with Nasra (the RN at Mayo that is supporting this process) and I think I have the correct answers to my questions. I thought I would pass along the things that I learned that were not obvious to me at least:

Where should I get the procedure done?

We tried to get the blood drawn at Andrea’s cancer center (UCSF), but we could not get them to do it. They didn’t know how to bill the procedure for insurance purposes (more on that later), and the fact that the request came from a different institution (Mayo) did not help. With effort, we probably could have gotten this to work, but we found it easier to just use a third party lab to do the blood draw. We used Quest Diagnostics.

Does this cost me anything?

No, but…

The easiest way to get this procedure done is to pay for it yourself, and then send the receipt to Mayo (Nasra) for reimbursement. I think this is the way most people end up doing it. If this is a problem, your best bet is to get the lab in contact with Nasra. Nasra can send over an invoice that should allow the lab to bill Mayo directly.

The problem here was really one of communication. Andrea and I didn’t realize we needed to pay and then get reimbursed. We were thus stumped when the cancer center asked us “Who is paying for this procedure?” Our answer should have been “it is patient paid,” but we didn’t know that…

When should I get the procedure done?

If you live in the U.S. or Canada, you need to plan on making an appointment between Monday and Thursday. Mayo sends you a prepaid overnight Fed Ex box to send the sample back to them. However, because the sample needs to arrive at Mayo on a business day (Mon-Fri), it needs to be given to Fed Ex on Mon-Thurs. If you are not in the U.S. or Canada, be sure to talk with Nasra about when you should schedule your appointment.

Do I need to do anything before I go?

Yes. You need to find the freezer pack that is in the package. The freezer pack is under the sample collection box (both of which are inside the return Fed Ex box) You should bring a frozen freezer pack to your appointment (at least 4 hours in the freezer is required)

What other issues can come up?

The clinic asked us if we had an “order” for the blood draw. It turns out there is the equivalent of an order in the sample collection box. If you are asked, say “yes, we do have an order!”

Let the clinic know that they need to give the materials to Fed Ex. If you try to give the box to Fed Ex yourself, Fed Ex may not take it since it contains blood. If Fed Ex doesn’t normally pick up at your clinic, you or the clinic can call them and they will make a special stop.

Those are the things that tripped us up.

If you tried participating in the Mayo study (successfully or unsuccessfully), please please please add any other things that you found confusing or challenging to this thread. As I understand it, the plan is to take all of this feedback and use it to improve the Mayo process. Part of that improvement will be a guide or FAQ on this website to help patients navigate potential problems.

Thanks!

Jason

Andrea and I are also planning on attending. We are not going to be able to stay overnight though.

Should be fun. See you there Marion!

Jason

The whole pd-1/pd-l1 was very confusing to me, but I found this article helpful in understanding the pd1 / pd-L1 interaction:

http://www.medscape.com/viewarticle/810688_3

If I read this right, MK-3475 is a pd-1 inhibitor. There are also trials looking at pd-L1 inhibitors. The Merck drug for anti pd-L1 is MSB0010718C. A trial with this drug is described here:

http://clinicaltrials.gov/ct2/show/NCT01772004

Both approaches are trying to stop the pd-1/pd-L1 interaction (which turns off the immune response). All very very exciting.

I hope your sister has a fantastic response.

Best,

Jason

Googled cholangiocarcinoma as well.

Carl,

In lieu of a biopsy, you could look for the IDH mutation via a blood test. I have seen a number of papers linking the IDH1/2 mutation to 2-hydroxyglutarate (2HG) levels in the blood. Here is one for example:

http://www.ncbi.nlm.nih.gov/pubmed/23641016

I do not know how difficult it is to get a blood test that looks for 2HG, but it might be something to track down if a sequencing is not possible. The level of 2HG does seem to correlate with tumor burden, so that would be a consideration as well.

Jason

Carl,
I am so sorry to hear Lynn is not responding well to treatment. I often worry about the day when Andrea’s treatment no longer works. I can’t imagine how difficult this is for you.

I keep a collection of thoughts and ideas for that time, and hopefully they help you. There might be some more localized treatments you can consider, but if it needs a systemic approach, here are things I am thinking about that you might research and talk to the oncologist about:

Losartan:
Losartan is a drug that lowers blood pressure. I mention it first because it is something you could consider right now. It has been prescribed to millions of people, and has a good tolerance profile.
Here is an overview of the research:

http://www.cancerresearchuk.org/about-us/cancer-news/news-report/blood-pressure-drug-improves-effect-of-chemotherapy-in-mice

Here is the main research article:

http://www.nature.com/ncomms/2013/131001/ncomms3516/full/ncomms3516.html

Why am I interested in this? During the stakeholders meeting, Christine Ferrone from MGH gave a lecture that claimed cholangiocarcinoma defends itself from the immune system by creating a barrier at the cell level. The research paper indicates that Losartan seems to work by lowering cell collagen, increasing the ability of blood to penetrate, and ultimately allowing more chemo to be delivered. They looked at pancreatic (which many have argued is similar to cholangio) and breast cancer cell lines in mice and noticed that the combination of losartan and chemo held the cancer in check much longer. The results are mostly summarized in Figure 7 panel c and panel f for the pancreatic cell line. For the pancreatic cell line, the chemotherapy they used in conjunction with Losartan was 5-FU (a component of FOLFOX). I believe the article argues that Losartan can help chemo work again after the cancer stops reacting. In any event, it has been shown to work in conjunction with a chemotherapy that Lynn is using, and has a reasonable tolerance profile, so based on that I think it is worth bringing up to your oncologist.

Immunotherapy

While you are waiting to see how FOLFOX does, I would definitely start looking into clinical trials. Immunotherapy seems like a good place to look, especially if cholangio really does have an existing good immune response. You already have identified the NIH trial (NCT01174121). The other hot thing in immunotherapy right now seems to be PD-1 based trials. There have been great results with other cancers for this type of drug, and reason to suspect it could work with cholangiocarcinoma given the immune response. Merck is the furthest along with this drug, and the Merck drug got designated a “breakthrough” drug in March. People seem to expect approval for the Merck drug (pembrolizumab aka lambrolizumab aka mk3475) later this year. If it gets approved soon, you could try to use it off label. If not, you could see if Lynn qualifies for a trial (e.g. NCT02054806). Other companies are coming out with their own anti pd-1 and anti pd-L1 drugs, so I would search for other trials. My rudimentary understanding is the tumors use PD-L1 to “turn off” nearby white blood cells and evade detection/destruction. By suppressing PD-L1 in the body, your immune system is better able to find and kill the cancer.

Targeted therapy:

Since she was on the MET trial, I assume Lynn has gotten a genetic sequencing done on her tumor? If not, I would definitely recommend getting it done. There are a number of trials open based on having a particular genetic mutation (e.g. IDH, KRAS, MET, NOTCH, + lots more). One I am focusing on is the IDH1/IDH2 mutation. A trial was opened up in March for intrahepatic cholangiocarcinoma patients that have the IDH1 mutation:

http://www.clinicaltrials.gov/ct2/show/NCT02073994

The odds seem pretty decent for having this mutation. If I recall correctly, the company running the trial (Agios), estimates that 20% of ICC patients carry the IDH1 mutation. An earlier paper by Foundation Medicine indicated that IDH1/IDH2 was found in ~35% of cholangiocarcinoma patients (If you have survived a while with ICC, the odds may even be a little better of having IDH1 since this mutation seems to be associated with above average survival in other cancers). The company had very good results with its initial trial of an IDH2 blocker and blood cancers. The scientists seem to be pretty excited about IDH1/IDH2 blockers and cholangiocarcinoma, so that seems like one to look at. For IDH1, my rudimentary understanding here is that cells with this mutation create IDH1 concentrations which causes immature cells to stop maturing and instead replicate (thus becoming cancerous). By suppressing IDH1, the immature cells stop prematurely multiplying, and continue to develop into normal cells.

One thing I truly believe is that if you want a different result, you are going to have to do something different. That is why I am a big fan of doing as many clinical trials as needed/possible to find something that works. Hopefully, some of these ideas help.

My heart goes out to you and Lynn,

Jason

PS – I think irinotecan is a common second line chemotherapy for cholangio. Since Lynn is using FOLFOX rather than FOLFIRINOX, I assume she is not taking irinotecan? Is there a reason for that?

Hi Olga,

I have fairly strong opinions about chemo, but please understand, these are only my opinions and I am not a medical professional. Here goes:

The sad fact about chemo is that the costs (how bad will the side affects be?) and the benefits (How much will it help me?) are very uncertain. Some people find the side effects very manageable, and some are debilitated by chemo. Moreover, chemo doesn’t really work very well for many, but some experience dramatic improvement.

Benefits:

I am convinced though that the wrong way to look at chemo for cholangiocarcinoma is that it will “buy me a month or two.” This puts far too much weight on what happens for the “median patient” and far too little weight on the minority of patients who really respond well. An alternative way of viewing chemo that reverses this emphasis is to say that you are at least four times more likely to be a multi-year survivor with chemo compared to without chemo.*

I think of it more like this: Imagine you have five cards face down and one of the five cards is an ace. You pick one of the five at random, and if it is the ace, you are one of the lucky ones that respond really well to chemo.

Compare that to a set up where none of the five cards is an ace. If we just look at the median (i.e. the third best card), we would say that both games are the same since the median in both cases is not an ace (this is analogous to the statement that chemo only “buys me a month.”) However, which game would you rather play? Unfortunately, chemo doesn’t insert 3 or 4 aces into the deck, but inserting one ace is still valuable.

Costs:

For some, chemo is very manageable, for others, it significantly degrades their quality of life. Should you do chemo if hammers your quality of life? probably not. My main advice here is don’t forget you can stop chemo! Nothing says if you start chemo and find out that you have a bad reaction that you have to keep doing it. At least you know you gave it a shot.

Overall, I would say you really want to take a peek at the card and see if it is an ace, but you want to have an acceptable quality of life in the process. For me, I would start chemo and see the effect on my quality of life. If things were manageable, I would do chemo at least long enough to get some feedback on whether it was working (I would really like to see if my card was an ace).

Again, just my opinions.

Jason

*I say at least because this number comes from the famous gem/cis vs. gem study and not a study of gem/cis vs. no chemo (e.g. best supportive care).