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Cholangiocarcinoma News

Genomic Testing in Cholangiocarcinoma: Look for Actionable Molecular Alterations

December 2020, Vol 1, No 3

At the 2020 Cholangiocarcinoma Summit, Nabeel El-Bardeesy, PhD, Associate Professor, Medicine, Harvard Medical School, and Associate Geneticist, Center for Cancer Research, Massachusetts General Hospital Cancer Center, Boston, MA, moderated a session titled “Molecular Biomarkers in CCA: Focus on Current and Emerging Technologies.” The session focused on how best to integrate the array of genomic testing platforms into clinical practice. The session included 2 presenters who discussed this topic.

Kenna R. Mills Shaw, PhD, Executive Director, Khalifa Institute for Personalized Cancer Therapy, M.D. Anderson Cancer Center, Houston, pointed out the difficulties in operationalizing precision medicine.

“We see over 100,000 patients a year and we perform over 20,000 molecular tests across our leukemia and solid tumor patient populations. When we started to look very discreetly at the number of molecular results that were utilized for treatment decisions in our patient population a few years ago, we found that it was a very small number of patients,” Dr Mills Shaw said.

“On a 46- and 50-gene hotspot panel, when we looked at 2000 patients that were not getting tested for standard of care but were looking for clinical trial opportunities, we found that only about 4% of our patient population overall—4% of the 2000—or just about 11% of the patients with a mutation and an actionable gene, were ultimately matched to a therapeutic target. This is, of course, concerning to us, as we wanted to try to inform or push forward precision medicine,” Dr Mills Shaw added.

She cautioned that regardless of how much of the genomic landscape is being sequenced, oncologists are still working with only a very small amount of an actionable genome. Her advice for oncologists is to make sure that they understand what’s being tested, what’s on the panel, what’s not on the panel, and what’s not included in the assay so the data can be properly interpreted.

Next-Generation Sequencing in Cholangiocarcinoma

Afsaneh Barzi, MD, PhD, Clinical Medical Director, Access Hope, and Associate Professor, Clinical Medicine-Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, focused her discussion on next-generation sequencing in cholangiocarcinoma (CCA) and the challenges in interpreting these data.

“My own sense is that it’s just not enough to say what we see on these reports. It’s also important to know what we’re not seeing on these reports, and whether that requires additional testing, or whether we should pay attention to what is unknown. It’s important to familiarize yourself with the report you’re commonly using,” Dr Barzi said.

She highlighted the importance of fusions and translocations as drivers in CCA. Maximizing the detection of such fusions enhances the benefit of precision medicine for various solid tumors. However, Dr Barzi noted that DNA-based next-generation sequencing can miss some fusions.

“The majority of these missed fusions were actionable. This only tells us that by looking at the DNA only, you may be actually missing some of these fusions. As clinicians, we have to be aware of it and look at alternatives to answer a clinical question,” Dr Barzi advised.

She emphasized that maximizing the rate of variant diagnosis for targeted therapy relies on precise identification of common and rare fusions. RNA sequencing yields information beyond what conventional DNA next-generation sequencing alone can provide. The addition of RNA sequencing will enhance the detection of targetable fusions and translocations in patients with intrahepatic CCA, she said.

“Don’t be satisfied with the results if you think there is something that can change the outcome. Always reach out to the labs who are doing the tests. They have resources that can help with interpretation of the results,” Dr Barzi concluded.

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