Next-Generation Sequencing and Interventional Oncology in Cholangiocarcinoma

TOP - March 2022 Vol 15, No 2 - Cholangiocarcinoma

The benefits of next-generation sequencing, liquid biopsy, the need for integration of local and systemic therapies, advanced intraductal interventions, and advanced radiotherapy technologies in biliary tract cancers were addressed in Session VII, “Interventional Oncology and Locoregional Therapy,” at the 3rd Annual CCA Summit.

Ignacio I. Wistuba, MD, University of Texas MD Anderson Cancer Center, Houston, highlighted challenges in tissue procurement and next-generation sequencing testing in patients with cholangiocarcinoma (CCA).

“Getting tissue before treatment, after treatment, and hopefully during treatment is very important to assess the changes associated with the immune response,” said Dr Wistuba.

The presence and location of certain cell types are important for the immunogenomic landscape of resected intrahepatic CCA. The expression of immune checkpoint markers B7H4 and B7H3 is associated with BAP1 mutations.

Liquid biopsies are easily done after surgical resection; however, they are more difficult to perform with small biopsy samples. Next-generation sequencing has a high level of detection and high level of sensitivity, using small routine tissue samples and liquid biopsy. Next-generation sequencing provides information on multiple targetable gene aberrations in intrahepatic, distal, and perihilar CCA subtypes.

Liquid biopsy in cancer is currently used as an option for molecular testing to help the use of targeted therapy. Liquid biopsy can also be repeated to detect treatment efficiency or genomic changes resulting from resistance to therapy. It is an alternative approach in patients with solid tumors if biopsies are not accessible, or after earlier tissue yields were unsatisfactory.

Sarah B. White, MD, MS, Medical College of Wisconsin, Milwaukee, discussed the integration of local and systemic therapies. The phase 2 MISPHEC clinical trial included 32 patients in the per-protocol population, and evaluated the combination of Yttrium-90 plus systemic therapy. The primary end point was the response rate at 3 months.

The disease control rate at 3 months was 98%, and the overall response rate was 39%, with the best response of 41%. The median progression-free survival was 14 months. Grade 3 or 4 adverse events were reported in 71% of patients. Overall, 22% of the patients were downstaged to surgery. The combination was also cost-effective.

Combination therapy is safe and effective, Dr White said, and is not worsening patients’ adverse event profiles. The addition of locoregional therapy prolongs overall and progression-free survival. Further clinical trials are needed to understand the optimal timing of combination therapies and the immune environment after therapy.

Andrew Wang, MD, University of Virginia Medical Center, Charlottesville, VA, discussed advanced intraductal interventions in hilar CCA. Controversies remain regarding best practices, he said, especially about percutaneous versus endoscopic transhepatic biliary drainage. A study investigating these modalities was not completed, because of limited patient enrollment.

Photodynamic therapy and stenting led to improved survival at more than 10 months compared with stenting alone. The side effects of this approach include photosensitivity, pain, nausea, cholangitis, and a cost of approximately $40,000 for a single dose.

Endoscopic radiofrequency ablation, in combination with stenting, has been shown to improve the median overall survival compared with stenting alone in patients with unresectable hilar or distal CCA. Endobiliary ablation and endobiliary radiofrequency ablation have led to improved survival in patients with unresectable perihilar CCA, Dr Wang said.

Finally, Ethan B. Ludmir, MD, University of Texas MD Anderson Cancer Center, Houston, discussed radiation oncology in CCA.

“Advanced technologies have really changed the paradigm and the face of radiotherapy for cholangiocarcinoma over the last 10 years, as we have used increasingly sophisticated technologies to safely deliver highly conformal radiation therapy,” said Dr Ludmir.

On-board imaging and respiratory management have allowed for real-time monitoring and minimization of risks. Integration of ablative doses with safety, using simultaneous integrated boost, has allowed for sparing of unaffected organs.

A study of supermassive tumors (volume >800 cc) managed with definitive radiation therapy to the primary tumor resulted in a doubling of median overall survival; however, the retrospective and single-institution nature of the study may limit the impact of these results, Dr Ludmir said.

Tumor resecting after high-dose radiotherapy has led to major issues with wound healing. According to Dr Ludmir, proton beam therapy delivers a much higher dose to the skin than photon beam therapy, but may be better for patients being bridged to transplantation.

According to Dr Wistuba, liquid biopsy will not replace tissue biopsy, in part because of the immune landscape, in which the location of cells is meaningful.

According to Dr Wang, patients whose tumor is amenable to resection should undergo resection. Photodynamic therapy and radiofrequency ablation are offered as part of a neoadjuvant strategy for locoregional therapy.

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Last modified: March 30, 2022