jscott

Dorien,

In my experience, the most capable people at reading the CT scans are the radiologists (makes sense I guess!). The amount of information we got from the interventional radiologists (IR) was much more detailed compared to our discussion with the various oncologists. These are the guys who do the RE procedure, and I am pretty sure they do the procedure guided by CT scans.

Anyway, we asked the IR how he could tell the cells were dead. He said that looking at the scans before and after the contrast was injected as well as closely looking at the scans taken while the contrast was spreading was how he came to his conclusion (that is my memory anyway).

The doctors at UCSF, UCLA and Stanford all concurred that if you were having a strong response to Gem/Cis, the time was not right for RE. The IR doctors went further and said they thought identifiable active cancer was a needed before they would suggest RE. By this, I think they mean wait until there is a liver flare up of new cancer before thinking about RE.

If you are having a strong positive response to chemo I would definitely get another opinion or consultation to understand why RE is good now as opposed to later. 66% reduction…wow! Docs have estimated Andrea’s reduction at 50%+, but they are not certain if the remaining tissue is active or scar tissue.

Anyway, I am not meaning to upset the apple cart, but I don’t understand an RE recommendation given the strong response.

Jason

thebompie4:

That is what it sounds like to me, but there are two major caveats:

#1 – I am neither a doctor nor an expert in this field, so please keep that in mind.

#2 – I have only seen the abstract not the full paper.

The abstract talks about a “modified protocol” that greatly mitigated the risks, so understanding that protocol better is, in my opinion, critical.

Jason

Quick update

Dr. Kato regarding resection:
Dr. Kato reviewed Andrea’s images and reports, but was unwilling to resect. The main issue was the number of sattelite leasions. He didn’t think he could remove all the cancer and leave a viable liver behind. He also thought it would not be helpful to the prognosis to have surgery, but leave behind a number of cancer cells.

Dr. Chapman regarding a transplant:
Dr. Chapman actually reviewed Andrea for resection and transplant. Andrea however is not a candidate for either. Similar concerns as Dr. Kato for the resection. For the transplant, I found out the Dr. Chapman is following the Mayo protocol. As such, he does not consider a transplant for ICC. I asked his assistant if they had ever done an ICC transplant. Her answer was “We have never knowingly done an ICC transplant, however, we have done some transplants that we found out was ICC after the transplant occured.”

For now Andrea is getting Gem/Cis and is reponding well (shrinkage the last two scans!) We are still hoping surgery becomes an option at some point in the future.

Jason

hmm. I think it is one of those things that you can have access to if you go through google first.

Do a google search on the title and then click on the top link and I bet that will work.

If you are google impaired, not to worry! it is just a Q&A. Here is a copy / paste. Please delete if it is against site policy to post this.

Jason

EDIT – Upon further review, you may have to sign up for a medscape acct. It is free at least.

Early Diagnosis Is Critical

Medscape: What are the main challenges in cholangiocarcinoma?

Dr. Kerr: Diagnosis comes too late. The majority of cases are too far advanced for complete removal. Often, all we have is limited palliative treatment. Unless we can diagnose cholangiocarcinoma early and recommend complete surgical resection, there is no curative therapy. Chemotherapy and radiation therapy have important but limited roles in palliation, with slight prolongation of life and slight improvement in symptoms, but we have a serious lack of therapeutic options when the disease presents at an advanced stage.

The epidemiology of cholangiocarcinoma is still somewhat opaque, but we know that such diseases as primary biliary sclerosis, a relatively rare inflammatory condition, cause a narrowing of the bile duct system that is associated with increased risk. More attention is being paid to screening and watching carefully over patients with primary biliary sclerosis for early signs of cancer so that we can offer surgical intervention.

The incidence of cholangiocarcinoma is only 1-2 per 100,000 persons, so no population screening program would be even remotely cost-effective.

Medscape: Are there any early warning signs of cholangiocarcinoma?

Dr. Kerr: Many cases are relatively silent clinically until they are quite advanced. The presentation at that point is typically jaundice, often accompanied by pain. Usually, the primary care physician would quickly refer a patient presenting with jaundice for a thorough work-up with ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP), or whatever is required, but the patient who presents with vague upper abdominal pain is more likely to spend some time in primary or community care with painkillers, antacids, or a whole host of other reasonable over-the-counter therapeutic options. Often by the time the patient presents with jaundice, the disease may be too advanced for complete resection.

Specialist Multidisciplinary Teams Improve Care

Medscape: What is the standard of care for operable cholangiocarcinoma?

Dr. Kerr: Ideally, best care would include rapid referral of patients who have undergone the appropriate diagnostic and staging procedures, such as ERCP. There is an emerging trend for using endoscopic magnetic resonance pancreatography, but relatively few units have that technology. The main thing is that the patient be referred to a specialist center with good liver surgery facilities that are well supported by good imaging and radiology departments. I have no doubt that we have benefited in Oxford from having a multidisciplinary specialist hepatobiliary cancer team with leading surgeons, plus support from committed radiologists, pathologists, medical and radiation oncologists, and specialist nurses, all of whom want to drive the research agenda forward.

I don’t think that there is yet a proven role for either adjuvant chemotherapy or adjuvant radiation therapy in cholangiocarcinoma. In the absence of sufficiently compelling trials, this would be a non-evidence-based intervention and therefore not something one would recommend.

We urgently need more trials in the adjuvant setting following successful or presumed successful surgical resection.

Management of Unresectable Disease

Medscape: What is the standard of care for unresectable cholangiocarcinoma?

Dr. Kerr: The most compelling study was the one by Valle and colleagues[1] comparing cisplatin/gemcitabine vs gemcitabine alone for biliary tract cancer. This well-designed, 400-patient randomized trial showed a significant survival benefit of about 3.5 months for the cisplatin/gemcitabine combination. That is the best evidence we have for combination chemotherapy in advanced cholangiocarcinoma, so at the present moment I think that cisplatin/gemcitabine should be the gold standard for treatment.

There continue to be many phase 2 trials with various chemotherapy couplets,[2,3] sometimes with epidermal growth factor receptor kinase inhibitors,[4,5] with some interesting results. The problem is that for any phase 2 trial, there is a risk for selection bias, so we must not overinterpret those results.

Medscape: What is on the horizon for cholangiocarcinoma?

Dr. Kerr: Because of the drive toward personalized medicine and interest in use of biomarkers to select patients for particular types of drugs, Big Pharma is now paying more attention even to relatively rare tumor types, such as cholangiocarcinoma. For example, MET is a receptor tyrosine kinase triggered by hepatocyte growth factor, and the MET signaling pathway is associated with invasive growth. MET inhibitors are being investigated in several cancers, and it has been estimated that up to 58%% of cholangiocarcinomas have elevated levels of MET expression,[6] so MET inhibitors could be interesting to look at. Over 9% of cholangiocarcinomas also carry the ROS mutation[7] and might be candidates for treatment with ROS inhibitors, such as Pfizer’s lung cancer drug Xalkori® (crizotinib), which is also a MET inhibitor and might provide a double-whammy.

Medscape: What about new techniques, such as hepatic transarterial chemoembolization (TACE)?

Dr. Kerr: TACE has seen more rapid development in the Far East, where some studies have suggested interesting response rates in small numbers of patients treated with combinations of cytotoxic drugs and TACE. There are still no randomized trials, and most of the work with TACE has been in primary hepatocellular carcinoma, not cholangiocarcinoma. There are interesting case reports and early studies, but no compelling data that would cause us to take that up more widely.

The Search for Effective Targeted Therapies

Medscape: Have there been any recent surprises in cholangiocarcinoma research?

Dr. Kerr: The biomarker work is becoming very interesting. Looking at the molecular genotype, we are seeing quite a number of mutations. This should allow us to more accurately identify patients with cholangiocarcinoma who might benefit from the new drugs.[8,9] Although cholangiocarcinoma has always been an orphan tumor type, we are seeing much better genomic research that is already starting to throw out some interesting new targets.

Take the ROS mutation as an example. Crizotinib, which has been approved in the United States for treatment of certain types of late-stage, non-small cell lung cancer, appears to be a pretty effective drug. If the same mutation occurs in a different context, such as cholangiocarcinoma or colorectal cancer, are we likely to see the same level of effectiveness?[7] That’s at the cutting edge of translational cancer research.

Medscape: So you expect to see advances despite the rarity of the tumor?

Dr. Kerr: Exactly. We have also developed interesting collaborations, such as the INDOX trial network, which sees 100,000 new cases of cholangiocarcinoma each year. This is a beautiful model for bringing together East and West, combining the technology and genomic power in the West and the tumor types that are a more serious disease burden in emerging and developing countries.

Medscape: What is the most important unanswered question in cholangiocarcinoma?

Dr. Kerr: The most urgent is whether the cisplatin/gemcitabine couplet will be useful as adjuvant therapy, because it seems to be the most active treatment that we’ve got for advanced disease. I’d also like to see greater international collaboration to link the phenotype of the cancers with their genetics so that we can see whether there are subgroups likely to benefit from targeted therapies.