lilitm

I wish I knew for sure how to help you ~ I think the reason they are saying it is unlikely immunotherapy will work is because there is low Tumor Mutational Burden and Microsatellite Stability. Did they check for PD-1 or PD-L1 expression? Or any DNA mismatch repair genes? Those are also potential indicators that immunotherapy might work…

What kind of K-ras is it? Ours is K-ras (Q61H) but the NIH has a trial for K-ras G12V I believe… contact Ellen (Dr. Steve Rosenberg’s nurse) at ellen.bodurian@nih.gov and show her your K-ras result and ask if the trial might be a possibility? (I know you would have to travel but maybe she can advise you further?)

I don’t have experience with the other mutations but I would search each of them on clinicaltrials.org. Maybe there is a targeted treatment…

Just found out our immunotherapy trial did not work : ( I am  devastated and hoping somehow it will be ok. No idea what is next.

my best  wishes to you and your loved family

dear Priscilla, I’m so sorry for what your father is going through, and you and your sister with him. My dad also has metastases (peritoneal carcinomatosis and perihepatic nodes, and a tumor around the portal vein/bile ducts, which required him to get a plastic stent.)

He does not have any genomic markers for immunotherapy either, but we are on an immunotherapy plus ablation trial at the NIH. It uses anti PD-L1 (durvalumab) and anti CTLA4 (tremelimumab) with one ablation procedure to one tumor (we did it to a perihepatic lesion, in the beginning of August, after 2 months/infusions of the immunotherapy.) The first scan at the end of Aug was stable. I hope that’s a good sign. Our next scan is next week – scared but hoping for good.

The idea behind using ablation with immunotherapy is that the ablation (radiofrequency ablation in our case) releases neoantigens, and the primed immune system would hopefully then recognize the cancer and create an abscopal effect (go after metastases all over.)

Apparently combination immunotherapy (like nivolumab and ipilimumab, or our combo) showed some efficacy for lung or liver cancer patients who did not express PD-1/PD-L1… as far as I know, they don’t have the data yet for biliary cancer.

Sending my hopes and wishes with love, Lili

Dear Barish, I am so sorry for all that your mother is going through, and you with her.

You sound like an excellent advocate for her from the start. I am relieved to hear she does not have mets and that you have already sent her tissue samples to Foundation One. You may want to call them asap and ask for the separate PD-1/PD-L1 testing (they do not include it with everything else – although they do include other immunotherapy indicators like MSI, TMB, and DNA MMR genes.) I hope she will be a candidate for targeted therapy or immunotherapy – hopefully also she will respond well to the chemo.

Some things we did during chemo that helped my dad tolerate it were: as much exercise as possible, lots of water, healthy plant-based diet with good protein and calories (lots of avocado, nuts, tahini, hemp seeds… vegetable juice or soup, lentils and chickpeas and beans, eggs, some fish…) Also ginger for nausea, I’ve read that Wisconsin Ginseng can help with fatigue, and we did probiotics with bifido, coriolus supplements, and vitamin D. when on folfiri chemo, we did turmeric also. Acupuncture helped him feel better, as did marijuana (vaping the pure plant only, and taking CBD oil orally. Also some people take THC oil orally too.) We are now on an immunotherapy plus ablation trial at the NIH so no more marijuana or supplements in case it might interact with the trial drugs. At any time, I feel de-stressing helps them – laughter, rest, being in nature, being with loved ones… whatever you can do to help her enjoy herself. And it’s so hard but you must take care of yourself too. Sending my hopes and wishes with love, Lili

Hi B,

You are being an incredible advocate for your dad from afar, learning so much in such a short time.

I do not know from the information you provide here whether or not he has enough tumor tissue slides from his biopsy to be sent for genomic testing. You mention he had to get a 2nd one – do you know how they obtained it? A needle biopsy shouldn’t be too difficult a procedure for him to undergo if needed…

I highly recommend you contact a trial at the NIH that you would be interested in for your dad, and ask them whether his biopsy can be sent to them for genomic testing. We did this for my dad when he was being evaluated for a trial upon diagnosis – we called this trial – even though he did not end up entering it at the time because he was advised to do chemo first, they did the testing – and this is the same trial we are now on: https://clinicaltrials.gov/ct2/show/NCT02821754

Regarding liquid biopsy testing – you might as well do it just in case, but I am not sure it will find as many mutations as tissue testing. Ours did not. We did the liquid biopsy testing with Guardant360, but they only found 1 non-targetable ROS1 mutation, and they did not find the same mutations that appeared on all our other tissue genomic testing with Foundation One, MSKCC, and the NIH: K-ras (q61h) and Smad4. This makes me wary that the liquid biopsy may not find obvious mutations someone has. Also as far as I know, they do not test for the immunotherapy indicators.

I have read that there are simpler ways to test for PD-1/PD-L1 and MSI, perhaps those can be tested separately from any liquid biopsy you do. I would contact your dad’s pathologist in Greece and ask if they can test for these at the hospital lab? Also ask them about sending his blood to the drug sensitivity testing in Greece because might as well?

I’m sorry I don’t know anything about Medicare yet – my dad is still too young for it and even when he has to take social security disability due to his diagnosis, they won’t give you medicare until 2.5 years after diagnosis : (

This is so beyond impossible to cope with but you are making a huge difference to your dad by taking care of all this and looking into cutting edge options for him. Sending you much love, Lili

Dear Dancer41, I am so sorry about what your husband is going through, and you with him.

His results sound potentially promising!

I would ask the cholangiocarcinoma specialists and any immunotherapy specialists (maybe you can contact immunotherapy clinical trial contacts through the numbers listed on their clinicaltrials.gov page and ask whether the trial investigator doctor can weigh in) whether his findings mean he should pivot to immunotherapy NOW (and if so, which one? Is a combination trial a better bet for him – like those pairing radiation or ablation with immunotherapy, or 2 checkpoint inhibitor drugs, etc?) Chemo will always be there to go back to if he doesn’t see results from immunotherapy, but my understanding is that it’s better to look into immunotherapy if it could be a promising option asap.

All my hopes and wishes, with love
Lili

Hi Betti, I’m so sorry about what your dad is going through, and you with him. I am also on this board for my dad, who was diagnosed in March 2017, also stage 4 from the start.

I appreciate the Greek way of not devastating the patient – the first oncologist my dad saw in the US was so negative and bleak… I would not listen to their time periods, because they truly don’t know how anyone will respond and the median time of a year means that people also outlive that amount. My dad is here 18 months post diagnosis, still fighting. If you saw him on the street, you would not guess what he is going through.

I hear you completely on how hard it is to see him unrecognizably frail. I’m guessing this is his reaction to the chemo. Is there any chance they can lower the doses? They did this for my dad when he was on Gem/Cis, and he stayed on it for 11 months with stability/slight shrinkage before a scan showed progression and he had to switch to Folfiri.

He was on Folfiri for about 3 months but it didn’t work and then he needed a biliary stent. At the end of June 2018, he began a clinical trial at the NIH in Bethesda, Maryland – using immunotherapy (2 checkpoint inhibitors: durvalumab and tremelimumab) and ablation, in the hopes that the ablation will release neoantigens that can be recognized by the primed immune system. The first scan in Aug was stable and we are hoping for even better in the October scan.

The most important thing I would say is to ask them to please send him tumor tissue for genomic testing ASAP (like at Foundation One). If he has targetable mutations or immunotherapy indicators (ask to test for PD-1/PD-L1, MSI, TMB, DNA MMR…) – then maybe he will respond to targeted treatment or an immunotherapy trial.

Unless he is having a major shrinkage response to the chemo, I would question whether it is the right choice for him since when surgery is not the goal, then the goal of chemo here is supposed to be extending his quality of life time – “more good days”, an oncologist told me. But if the side effects of the chemo are taking all the quality of life, then I would reassess the balance… perhaps look into metronomic/low-dose chemo?

Can he also get a CT and not just an MRI? (They always do CT at the major institutions here in the US.) Did they say there is a chance for surgery after chemo? I think you need clear answers on this to better assess the goals of the chemo.

There is absolutely hope – I also read the book Radical Remission and try to apply the 9 factors to my dad in some way. Sending you my hopes and all my compassion and love

Thanks so much Mary ~

Exactly – you put it so well.

I tried reading everything I could find on biliary stents, plastic vs metal, uncovered vs covered metal… and even endoscopic biliary bypass, which I thought might be a way to solve the problem with a little harder recovery up front but less problems down the line…

But I could not find out how long SEMS (either the covered or uncovered metal stents) are supposed to work for, or whether there is any way to remove them if the patient becomes NED.

All I could find was similar to the example you shared, which states: “2. If expected survival is >4 months, SEMS is more cost-effective.”

Like you said, that doesn’t capture the details of a specific patient’s situation, nor does it address our real concerns. It only tells us which is more cost-effective for the medical industry!

Re: the comment from the article that says: “if there is no definitive management decision, plastic stenting is indicated.”

This is basically the reason we would consider a plastic one again – maybe hold off a few months and give the immunotherapy trial a chance to work?

It’s just so hard to know whether making decisions from a hopeful place like that is ok… on the other hand, it seems the doctors will take the opposite approach and make decisions from an assuming-the-worst place…

Since the realities of stage 4 can be so harsh (and the doctors so dismissive), I don’t really know how to effectively communicate any concerns related to optimistic outcomes.

For example:

My dad had the same tumor around the bile ducts upon diagnosis March 2017. For over a year, he did not require a stent. However, when there was a little growth in May 2018, he started getting elevated bilirubin and itching – so he needed a stent for the first time.

Once the stent was placed, it worked perfectly and the symptoms cleared up. Then he began the immunotherapy trial. The first scan shows stable disease.

If he were to see any shrinkage in the coming months, even if the tumor around the bile ducts just shrank a little, to where it used to be, then he could conceivably go back to not needing a stent?

About asking the doctors – my dad has an appointment this week with the local GI who performed the last ERCP (he seems kind but is not a biliary oncologist – he just knows how to place stents very well.) I will prepare questions for him. I will reach out to an interventional radiologist for their input as well.

When I called the research nurse for the TIL trial, she said any stent would make him ineligible because of infection risk – and it takes a couple months to prepare the TILs from the tumor sample. So things would have to be ok for a while without a stent for this trial to be an option – perhaps a stretch, although perhaps possible. Then again, it would be so hard to close the doors on this trial by taking a permanent stent.

Hopefully our current trial works and whatever stent choice is made is for the best…