Biomarker Testing and Imaging in Cholangiocarcinoma

December 2021, Vol 2, No 4

New biomarker technologies may be combined with cholangiocarcinoma (CCA) characteristics to predict patient response to treatment, according to presenters at Session V, “Biomarker Testing in CCA: New Technologies/Imaging as a Biomarker,” during the 3rd Annual CCA Summit.

James Costello, MD, PhD, Moffitt Cancer Center, Tampa, FL, discussed enhancement patterns of computed tomography (CT) and magnetic resonance imaging (MRI). Intrahepatic CCA with a hypovascular enhancement pattern shows worse disease-free survival than hypervascular or rim-enhancing intrahepatic CCA.

Patients with scirrhous-type intrahepatic CCA also have lower overall survival. In contrast, patients with hypervascular patterns of intrahepatic CCA have prolonged overall survival.

“With MRI, we have the ability to administer extracellular contrast agents and also hepatocyte-specific contrast agents, which are excreted into the biliary system,” said Dr Costello. “These hepatocyte-specific contrast agents allow us to generate 20-minute delayed hepatobiliary phase images, where we can assess the tumors for how they enhance at that 20-minute delayed time point.”

Dual-energy CT uses dual acquisition at different kilovoltage levels, providing image reconstruction techniques. Dual-energy CT may also be useful for assessing response to treatment, because it demonstrates intratumor heterogeneity. Positron-emission tomography and CT scans have been used for detection of distant metastases, lymph node staging, and to investigate the genetic makeup of tumors noninvasively.

Diffusion-weighted imaging evaluates random Brownian motion of water molecules between intracellular and extracellular compartments. The apparent diffusion coefficient (ADC) map can provide insight into a tumor viability and structure: viable tumors have low ADC values and cellular necrosis results in higher ADC values, according to Dr Costello. Diffusion-weighted imaging can also be used for diagnosis and tumor grade: lower ADC values are associated with a diagnosis of a higher tumor grade. Response to treatment can also be reflected by a continuous increase in ADC values.

Magnetic resonance relaxometry can be used to quantify imaging biomarkers that reflect tissue biophysical properties. T1 mapping characterizes longitudinal relaxation and can be used to evaluate response to therapy and tissue fibrosis or extracellular changes. T2 mapping reflects the rate that the transverse magnetization decays to zero. Malignant masses have lower T2 values than benign masses.

“What becomes incumbent upon us is trying to figure out a pattern among all of the data,” said Dr Costello.

Laurent Dercle, MD, PhD, Columbia University Irving Medical Center, New York City, discussed how new imaging technologies, such as AI and radiomics, offer an objective approach that may guide clinical decision-making and the potential role of imaging as a biomarker.

Elevated tumor burden shortens overall survival. The location of metastatic involvement has been linked to survival and to response to treatment. Patient anthropomorphic characteristics, including skeletal muscle index, are associated with patient survival. AI has been used to develop a radiomics signature that is associated with patient survival. Bone marrow metabolism can also be used to predict bone marrow and spleen metabolism, overall survival, and transcriptomics.

“We are demonstrating that [imaging biomarkers] can also be combined with clinical and biological characteristics,” said Dr Dercle.

“From a broader perspective, we think that there is a need to develop advanced imaging technology, and there is a need to develop comprehensive programs of radiomics, to develop probabilistic and predictive tools that could improve the diagnosis and assessment of response in cancer patients,” he concluded.

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