March 29, 2018 at 6:43 am #96784
Thank you so much. I have compiled a list of the ROS1 trials and will call and ask to speak to a member of the research team (I wouldn’t have known to ask for that, so grateful for your suggestion!)
I will call MSK and try to get them to let me talk to the doctor so I can ask about a 2nd opinion, IR consult, and the rest… I realize I am overflowing with questions without a sense that I can just ask the doctor, because our contact with him is so rare (we only see him when my dad travels to MSK to get his scans.) When I call, the nurse is the one relaying info. I can write online messages to their office, but it’s still the nurse or admin who will answer. In between scans, my dad gets his chemo every other week locally, where he gets seen by a PA. Even the local oncologist only sees him every couple months, and isn’t great with questions.
I am deeply grateful for this discussion board, and hope I can help others the way I have been helped here.
Thank you so much and all my warmest wishes!
LiliMarch 22, 2018 at 10:32 pm #96760
Thank you for the update.
Your questions about ROS1 targeted treatment might best be directed to the researchers. If you search on clinicaltrials.gov for trials using ROS1 and cholangiocarcinoma (also try ROS1 with biliary and with solid tumor), you will find listings for active and “not yet recruiting” trials. Near the bottom of each trial listing will be the name of the principal researcher and contact info. I would suggest calling some of the contact researchers, let them know about your dad, and see if they can discuss with you what his test means and how this might relate to trial participation.
If I were doing this, I might ask if I could speak to a member of the research team, so if the principal is busy, perhaps another team member could take time with you. I also would not worry too much if the trial is nearby geographically since at this point you are gathering information, not signing up for anything.
You had also mentioned your dad was concerned about offending his doctor by asking for a second opinion. In fact, second opinions are common in complex cases, and the doctor will not be surprised or offended. He may even have suggestions on how to arrange the second opinion. He may also be able to assist with a recommendation on an IR.
Best wishes that everything goes smoothly as you navigate the medical system on behalf of your dad. He is so lucky to have you helping him.
Regards, MaryMarch 22, 2018 at 4:05 pm #96759
Thank you so much, Positivity.
Here’s an update about the liquid biopsy – my dad’s local Miami oncologist just emailed: “The results of the Guardant 360 were remarkable for a single mutation detected in the ROS1 gene (R1948H) which is of uncertain significance and for which specific treatment is not available.”
I found that they use Crizotinib to target ROS1 in lung cancer, and found a few trials for multiple cancer types that refer to fusions, chromosomal translocations, or activating mutations involving the ROS1 gene – would my dad’s ROS1 mutation count as any of those?
I looked up ROS1 on these discussion boards and saw that some cholangiocarcinoma patients might have experience with it – can anyone tell me if my dad’s kind of ROS1 mutation is targetable?
Thank you!March 19, 2018 at 12:02 pm #96746positivityParticipant
The most important is you are proactive and not hesitating to ask questions. Tumor board is usually suggested by an oncologist which is a collaboration of oncologist, radiologist and GI doctor or anyone else who will be part of the treatment plan. They usually determine if surgery is possible. I am sure others will give more input. Usually an IR doctor is referred from the main doctor, mention that you want to speak to one. It should be the family members choice if there are sensitive topics and you would like to discuss in person privately. There should be a comfort level with the doctor to address all the issues you mentioned. Sorry, I could not be more detailed, but keep us informed.March 17, 2018 at 2:16 pm #96743
Dear Mary and Positivity,
Thank you so much. Your caring and insightful responses are deeply appreciated.
I went ahead and ordered a liquid biopsy from Guardant360 because it was non-invasive and had to try in case it yields anything helpful (although my hopes are not high for it – and it doesn’t test for immunotherapy indicators.)
Nobody has ever mentioned a tumor board to us. Is this something you have to ask for?
I have found a number of biliary trials on the clinicaltrials.gov site but it’s hard to tell if any are promising unless you have FGFR 2 (which I’m not even sure gallbladder patients can have?) or high MSI/TMB/etc… am I missing something?
I have been reading about liver-directed therapies, ablations, and percutaneous IRE, and I’m wondering how to talk to an interventional radiologist about the possibilities there. Do we need to ask permission from the MSK oncologist to refer us to an MSK interventional radiologist? Or do we just ask MSK for that consult separately?
I’ve been thinking maybe I should just call MSK and ask if our oncologist will speak to me by phone and be direct with me (so my dad doesn’t have to hear and get discouraged) and answer my questions like:
– What is the plan if Folfiri isn’t working?
– Is the liver met encasing the portal vein posing an urgent threat? If so, how can we address it? (percutaneous IRE?)
– Is there a strategically smart time to try checkpoint inhibitors in case they might work? Maybe with cyroablation?
– Is there a promising trial out there?
– Is there anything we can adopt from a similar cancer’s treatment to apply here?
And the impossible questions…
– Do you have a time period you imagine we have left?
– When is it better to stop treatment and get about the same amount of time but with better quality of life?
Not sure if we can rely on any answers for those… these questions keep me up at night.
As for getting another opinion – I think my dad would be afraid of upsetting his MSK oncologist to ask for a 2nd opinion. Could we just go to MD Anderson for a 2nd opinion without asking first? Do you think Dr. Javle can offer us anything else? Or is there a different expert we should see, someone who thinks more out of the box?
Thank you so much for your wishes for my dad.
My gratitude, wishes, and love to you and everyone on here,
LiliMarch 5, 2018 at 4:09 pm #96700
I wanted to add some thoughts on the question of why a doctor might discourage that a patient pursue a biopsy for the purpose of genomic/molecular profiling. These are observations in general, not related to any specific case.
1. The needed biopsy has a few downsides. Having a biopsy is not recommended if you are a surgical candidate because the doctors can take the sample tissue in conjunction with the surgery. A biopsy can disqualify patients from consideration for a liver transplant. The concern here is that there is a small risk of seeding cancer cells along the needle track. Patients in these cases can consult with their surgeons and other medical team members about the possible benefits of using tissue obtained through resection or transplant for genomic profiling.
2. Biopsies can be painful to the patient. Moreover, the doctor will look at the location of the tumor or met, its size and accessibility, in considering the merits and potential for success (or not) of a potential biopsy in yielding a sufficient sample for the testing.
3. At this point for our cancer, targeted treatments are mainly available through clinical trials. If a patient is in very poor health, a doctor may feel that he or she is unlikely to qualify for trials and may question the wisdom of putting that patient through a biopsy procedure.
4. As Lili noted, doctors may feel that the time it takes to receive the test results is too slow if a patient needs urgent treatment.
Nothwithstanding the above, if as a patient or caregiver, you wish to open the door towards finding and potentially benefiting from the emerging targeted treatments, it is important to have informed conversations with your medical team about the benefits you see from pursuing genomic/molecular testing, to see if objections to the testing can be overcome. Some of the concerns I listed may be less relevant in the future as liquid biopsy techniques (through blood testing) evolve and become more mainstream.
A substantial proportion of cholangiocarcinoma patients may have some type of treatable mutation or defect found in testing. About 2.5 percent may test positive for MSI-H (micro satellite instability-high)/dMMR (mismatch repair deficiency), which is treated with pembrolizumab (Keytruda), the first precision drug approved by FDA across cancers for a specific genomic defect, rather than for a specific cancer.
(Please note there is a wide range of estimates regarding how many patients have “actionable” targets. I have seen numbers as low as one-third and as high as five-sixths of all cholangiocarcinoma patients, which seems to reflect different patient samples and different views on what is “actionable.” Regardless, it is clear that precision medicine is gaining ground, which will push patients and their doctors to incorporate genomic testing up front in defining treatment plans.)
Regards, MaryMarch 5, 2018 at 9:07 am #96698positivityParticipant
Sorry for this tough time, and good that you are keeping on top of everything and asking questions.
Just to make a couple of points:
1. Surgery is usually anatomically impossible due to the location and being close to portal vein which could make it very risky (one reason from my experience)
2. I did not understand why the doctor is reluctant to get genetic testing on the tissue sample to see if there is a mutation which there may be a possibility for an effective treatment. It is important you are proactive and asking these questions. It seems the doctor should be open to a test you would like. I am going according to experience as sometimes I had to make a suggestion where the doctor did not. Even if I got a ‘No” response or “That won’t work” etc… Our oncologist did not even suggest genetic testing and I had to mention it later on, even though we discovered there was not enough tissue left to be tested.
3. Definitely get a second opinion. We went to three oncologists to determine each one’s viewpoint and differing treatment plan. Make sure you are comfortable with them and can easily communicate. Negativity can be an issue with some doctors, so determine if you need a more positive doctor or something you can work around.
The most important thing you are doing is being on top of his condition, asking questions, researching, and being aware. Never be in the dark and be proactive. It is tough, I know, but keep going and do what is best for your father.March 3, 2018 at 5:15 pm #96696
Thank you for the update, but I am sorry to hear your father has progressed. Your oncologist seemed to move him quickly into a second-line chemo, but you are right in thinking “what next?”
Targeted therapy is very new, and my impression is that some of the mechanics questions are not fully settled. One topic I listened hard for at the recent Cholangiocarcinoma Foundation conference was whether genomic testing should ever be repeated and if so, how often. My laymen’s understanding of what I have heard on this is that (1) some patients’ mutations might change over time, and (2) over time the testing itself is evolving because the number of mutations being tested for has been increasing. That said, there seems to be no specific guidance yet as to the responsible timing for repeat testing. Opinions such as your MSK oncologist gave are common when patients ask to be retested within months of a prior test.
There is not a lot of experience yet with blood testing (“liquid biopsy”) for genomic defects for our cancer. A few folks posting on the board have discussed having or trying to have liquid biopsies, and Gavin has posted some articles.
Targeted therapy options are generally offered through clinical trials, so one path may be to enlist the help of your father’s doctors to start investigating possible trials, and this exercise may help inform and clarify decisions about additional genomic testing. In this way, groundwork will be laid for when the day comes to find a new treatment option. Gavin posts info on clinical trials on this board, plus there is info on the Foundation website. Additionally, you can look at clinicaltrials.gov to search around and see what is out there.
Your questions are reasonable ones, but seem to demand experienced medical provider input. It may be a good time to consider a second opinion. Second opinions are very usual in complex cases, and your current oncologist should not mind in the least if you want to go this route and may even have suggestions on someone to consult. Also, do you know if your father’s case is being discussed by a tumor board? If so, the views your father’s oncologist is presenting may already have multi-expert input.
Fingers crossed the Folfiri gives your dad another good run of stable scans. He is so blessed to have you in his court seeking out info on his best treatment options. His 15-mile bike ride is impressive — hopefully there will be many more to come.
Regards, MaryMarch 3, 2018 at 1:58 pm #96695
We just got my dad’s latest scan result – after 11 months on Gem/Cis, there is progression. The scan report lists:
1. Unchanged soft tissue infiltration at the porta hepatis (this was the same unchanged met since diagnosis, encasing the portal vein)
2. New probable subcapsular low-attenuation implant: 2.1 x .9 cm, in segment 6
3. increased perihepatic soft tissue nodules
4. mildly increased peritoneal carcinomatosis
At our last scan in November, there had been slight shrinkage of the peritoneal mets and I had asked the MSK oncologist if we could do any localized treatment (surgery, radiation?) but he said no. I was never clear whether it was medically unjustified, or whether it’s just protocol not to operate. Now with the new liver lesion and nodules, it seems even less possible.
The oncologist said he thinks it’s resistance to Gem/Cis due to the scan, the timing (11 months), and that my dad has had some more intermittent abdominal pain. (Besides that, 11 months on chemo have fatigued him and he has neuropathy. But he is still athletic and even did a 15 mile bike ride the week before the scan.)
His CA 19-9 also went up (it started at 250 before chemo, then 60’s during chemo, then doubled and tripled in January – it’s now 317.)
When I had called MSK about my dad’s CA 19-9 suddenly shooting up in January, they said it was not reliable and asked if he had lost a lot of weight or anything. He hadn’t, but I wish I had pushed them to do the scan earlier – it was nearly 4 months after our last November scan because my dad was approved to take a 3 week chemo break in January. He also had sporadic chemo in February because he had low platelets once and low counts once when he didn’t take a booster shot. I wonder if the sporadic chemo schedule the past 2 months allowed the cancer to grow, or whether it was just bound to become resistant to Gem/Cis at this point.
Even though they don’t think so, it seems like CA 19-9 is a relevant marker for my dad too.
After we heard the latest scan results, the MSK oncologist immediately started my dad on a new chemo regimen this week, Folfiri.
I asked about getting a needle biopsy of my dad’s mets to see if he might have a targetable mutation? (His original gallbladder biopsy only showed KRAS (Q61H) and SMAD4, and unknown MSI or TMB status so no sign of being a good immunotherapy candidate… but we never biopsied the mets!)
The oncologist said he doesn’t expect to see new mutations and that he’d rather start my dad on Folfiri than wait for results of a biopsy, and that it’s not fair to my dad to go through that now.. but what if it would determine a better treatment?
I asked about a liquid biopsy but he said it’s experimental. Should I push for it?
Now I feel like we’re just waiting for 8 weeks until the next scan to see if Folfiri works at all. If it doesn’t, the cancer will be growing all that time. And then what? I have no idea of any promising trials out there… what next? Or even if it does work for now, it will stop working at some point.. what’s the plan??
I’m just expressing my desperation in the hopes that someone here will somehow have insight into what I should do… in the hopes that there is something I’m missing or something I should push for, advocate harder for my dad, anything…
My warmest wishes to you and yours, with all my gratitude,
LiliAugust 28, 2017 at 4:20 pm #95532
Dear Mary, Melinda, and Gavin,
Thank you so much for the kindness and deep understanding about my dad, the warm welcome, and the helpful information. I’m so sorry that you all are here as well, and I hope I can be of support to you too.
I will search the board for Avastin, metformin, and more trial info. Also thank you for the clinical trial links and for pointing me towards the NCI study on Kras mutations. I’m never sure what I should be doing now to plan ahead, but it sounds like calling trials is a good step.
About immunotherapy markers – unfortunately the MSK test did not show MSI/high or DNA mmr, but since his report came back with a note about low tumor tissue sensitivity, the MSI score could not be confirmed. They did not test for PD-1/PD-L1 (when I asked if they could, MSK told me that they put patients on checkpoint inhibitors regardless of PD-1 status). I asked if they can retest the MSK-Impact if the pathologist sends more samples, and they said it’s not likely to yield anything unless it was an entirely new biopsy. I’m not sure if we could do a new biopsy since his mets are currently inoperable – but perhaps there is a safe way. Or perhaps liquid biopsy would pick up enough ctDNA shed… I will ask the oncologist when we see him tomorrow and get the scan results.
Thank you for all your wishes. My best wishes go out to you and your loved ones too,
LiliAugust 27, 2017 at 5:53 pm #95531gavinModerator
Welcome to the site. Sorry that you had to find us all here and I am sorry also to hear about your dad. But I am glad that you have joined us all here as you will get a load of help and support from all of us so thanks for sharing as well. In addition to what the others have posted to you please take a look at this link as that may be of use to you as well –
We so know what you are going through right now and I went through all of this as well with my dad. Please keep on coming back and know that we are here for you.
My best wishes to you and your dad,
PS – I forgot to mention that we have a clinical trials board here on the site also so have a look at that too.August 27, 2017 at 2:09 pm #95530mbachiniModerator
When your dad’s tissue was tested did they check for MSI-High, Mismatch repair deficiency, or the presence of pd-1/pdl-1? These would be indicators of good response to immunotherapy drugs like Keytruda.
The NCI is doing a new study with KRAS mutations….not sure of the particulars, but might be worth a call.
Please keep us posted and welcome to the discussion board!
MelindaAugust 26, 2017 at 12:51 am #95529
Welcome to the discussion board. It is positive to hear your dad seems to be doing well so far with his current chemo regimen.
As you mention, with this type of cancer, it is advisable to be plotting next steps since treatments can run their course. I have copied the page on the Foundation’s website that lists clinical trials below for you, in case you did not see it. You would have to look and see if they include gall bladder cancer. The clinical trial section of the discussion board has similar information, plus some patient postings on their experiences with the various trials.
A few CCA patients who have been treated with Avastin have posted on the board – there is a search engine that can be used to find information.
Fingers crossed for good scan results!
Regards, MaryAugust 25, 2017 at 3:18 pm #13622
Hi everyone. I’m grateful for this discussion board where I can learn how to better advocate for my beloved dad, and share with all of you.
He got an out-of-the-blue stage 4 diagnosis in March – my mom, younger brother, and I were all in shock, and completely heartbroken. He just turned 61 and was the healthiest person we knew, cycling and jogging and eating a mediterranean diet. They removed his gallbladder and saw adenocarcinoma with spread encasing the porta hepatis and peritoneal carcinomatosis. They think it originated in the gallbladder (so officially his diagnosis would be gallbladder cancer, not cholangiocarcinoma), but since there is so much overlap in trials and treatments with our rare biliary tract cancers, I hope it’s ok that I’m joining this group.
He began chemotherapy at the end of March after traveling to Memorial Sloan Kettering for a consult: Gemcitabine/Cisplatin. He has been tolerating it relatively well, still exercising on the less tired days. His first scan 2 months later was stable, his next scan is this week. His CA 19-9 has dropped from 297 at diagnosis to around 52 now. I am hoping that means the chemo is having a reductive effect. If not, I’m not sure what next steps would be.
We sent the original tumor tissue for molecular testing, but they couldn’t confirm any actionable results due to issues with tissue percentage. They only confirmed K-Ras Q61H and SMAD4. I have read that mutations can change over time/chemo so perhaps we can test again through a liquid biopsy, or biopsy one of his currently inoperable mets…
If anyone has any information on promising clinical trials or immunotherapy, I would love to know. As of now it sounds like a checkpoint inhibitor trial for Keytruda or Opvido would be a shot in the dark for biliary cancers?
I have heard asking about Avastin might be helpful? Also metformin? Would love to know if anyone has experience with those. Or if anyone has any advice for what to ask the oncologist about when we get the results of the scan after the weekend?
Thank you so much.
My heart goes to all of you, with my deepest wishes.
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