Hepatocellular Carcinoma: Practical Implications of Emerging Data - Episode 3

Hepatocellular Carcinoma: Diagnostic Work-Up

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Richard S. Finn, MD: Reena, could you walk us through your patient who has an ultrasound in the background of chronic liver disease and has a nodule? How do we work that up?

Reena Salgia, MD: Typically, for the majority of patients, the mainstay of diagnosis is going to be with dynamic multiphasic CT or MRI, preferably MR for purposes of sensitivity and specificity characteristics. We try to reserve doing a biopsy in, generally, under 10% of cases, if we see atypical features on the multiphasic imaging. That’s most commonly what we do. There are still areas, both from the imaging standpoint, as well as tissue diagnosis, where we have some limitations in diagnosis. One of the things that we certainly hear about as a diagnostic tool for a lot of other oncologic diagnoses is PET [positron emission tomography] scan and we tend to order this less frequently or rely on this less commonly for a diagnosis of HCC [hepatocellular carcinoma]. Much of that has been based on the lower sensitivity for detecting HCC generally felt to be inadequate to consistently rely on that for purposes of sensitivity of diagnosis. Some of the data that have come out have suggested that the level of differentiation of the tumor can be associated with characteristics of FDG [fluorodeoxyglucose] uptake. A more poorly differentiated HCC, for example, would be more likely to be PET-avid, and that may help in diagnosis of metastases in the future. There are also some data emerging looking at other tracers, radiotracers, that could expand on our utilization of PET scan in the future.

Richard S. Finn, MD: You bring up a great point that I think a lot of us in the cancer medicine research area are very sensitive to, certainly because of how it’s impacted other cancers we treat, and that is tissue. Here is a disease where you just said we only get tissue on less than 10% of patients historically because we can make the diagnosis noninvasively with CT or MRI, and that PET/CT doesn’t necessarily add much or actually might miss some tumors. So, if we don’t have tissue, how are we going to move to personalized medicine in liver cancer? Is there a role for these molecular testing modalities?

Reena Salgia, MD: Certainly there’s a need for it, especially in this condition. One of the historic challenges of the molecular markers in testing in HCC has been the varied genetic profile. I think as more and more clinical-trial-based data have emerged, the hope is that we’ll be able to more reliably apply molecular targets, with the aim of precision medicine in mind for HCC as well. Historically, we’ve relied on AFP [alpha-fetoprotein]. I know Amit touched on AFP for screening purposes, and later on, we’ll talk about it more in terms of what we know in terms of AFP correlating with response to treatment. I think the goal is to expand the molecular targets and apply that to the individual patient and their treatment. There are more emerging data, though. I’m looking at some of these targets in HCC and circulating tumor DNA or doing liquid biopsies, all oncologic diagnoses, but applying that to HCC as well, and through that developing hopefully some reliable assays in the very near future that we can use both for screening and diagnostic purposes.

Richard S. Finn, MD: Anthony, how often do you end up sending NGS [next-generation sequencing] on your patients with liver cancer? Is that something you do at the get-go, like you might do in cholangiocarcinoma versus this disease?

Anthony El-Khoueiry, MD: Certainly not. I think most of the NGS work that we do or others do is related to research. At this point, when we look at HCC, most of the targets that are altered in this disease appear to be not druggable, at the moment, at least. The more frequent alterations are not easily targetable with specific drugs. Now, this is changing gradually, as Reena mentioned. We do see targets such as FGFR4 or FGF19, MET, and others that are evolving. Many clinical trials are coming that are more tailored to specific alterations. So I think at this time, the clinical utility is limited, unless the patient has refractory disease and still has conserved liver function, where you may find an alteration that could be targeted, mostly in a clinical trial.

Richard S. Finn, MD: Katie, how about at UCSF [Helen Diller Family Comprehensive Cancer Center]? Do you biopsy everybody and send it for molecular testing?

R. Kate Kelley, MD: That’s a great question. I think particularly with the advent of more treatment options for both HCC as well as cholangiocarcinoma, our tolerance of a misdiagnosis or missing the most common alternate diagnosis of a biliary tract cancer is much lower. Even putting molecular profiling aside, we are tending to do biopsies for patients with advanced disease prior to systemic therapy much more frequently than before in patients who are fit for systemic therapy. Again, I agree with Anthony’s point that we don’t have a great established clinical target yet for NGS profiling in HCC, and I hope that will change with FGFR or FGF19 and other targets. I think it’s more that now that we do have multiple therapies, both for HCC and cholangiocarcinoma, we really don’t want to miss the alternate diagnosis.

Richard S. Finn, MD: Sure. There are a lot of exciting things in that diagnosis evolving over time.

Transcript Edited for Clarity