The Lynx Group
Cholangiocarcinoma News

Next-Generation Sequencing and Interventional Oncology in Cholangiocarcinoma

December 2021, Vol 2, No 4

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 M.D. 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 are 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 M.D. 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.

Related Items

A Global Perspective on CCA
By Virote Sriuranpong, MD, PhD
Videos
Dr Virote Sriuranpong provides a perspective on key issues facing Thailand and other Asian countries in the prevention, screening, and early diagnosis of CCA.
Molecular Targets in iCCA Surgical Candidates
By Keri Lunsford, MD, PhD, FACS; Alice Wei, MD, MSc, FRCSC, FACS
Videos
Drs Keri Lunsford and Alice Wei provide their perspectives on how the molecular profile of iCCA patients can help direct surgery and locoregional therapy.
Periadjuvant Therapy in iCCA
By Cristina Ferrone, MD; Shishir Kumar Maithel, MD, FACS
Videos
Dr Cristina Ferrone discusses the use of adjuvant therapy, and Dr Shishir Kumar Maithel speaks to the role of neoadjuvant therapy in patients with iCCA.
New Frontiers in Surgery for CCA
By Skye Mayo, MD, MPH, FACS; Alice Wei, MD, MSc, FRCSC, FACS
Videos
Drs Alice Wei and Skye Mayo discuss options for induction therapy prior to surgery in iCCA.
Transplantation in iCCA
By Keri Lunsford, MD, PhD, FACS; Maria B. Majella Doyle, MD, MBA, FRCSI, FACS
Videos
Drs Keri Lunsford and Maria Majella Doyle explore clinical data on neoadjuvant treatment before transplantation in patients with iCCA.
New Pathways and Molecular Targets in Cholangiocarcinoma
By Erin Burns, PhD
December 2021, Vol 2, No 4
Potential therapeutic targets for cholangiocarcinoma (CCA) include oncogenic pathways and other options, such as epigenetics, posttranslational modifications, and metabolism, according to presentations delivered during Session I, “Advances in Translational/Molecular Targets in CCA: New Molecular Targets/Pathways in CCA,” at the 3rd Annual CCA Summit.
Molecular Epidemiology of Cholangiocarcinoma: Identifying New Inherited Variants
By Erin Burns, PhD
December 2021, Vol 2, No 4
Cholangiocarcinoma (CCA) involves genetic heterogeneity, highlighting the need to identify new inherited variants, as discussed at the 3rd Annual CCA Summit in Session II, “Molecular Epidemiology of CCA.”
The Future of Chemotherapy in Cholangiocarcinoma
By Erin Burns, PhD
December 2021, Vol 2, No 4
Personalization of therapy and novel regimens are needed to improve options for patients with cholangiocarcinoma (CCA).
Understanding Predictive Biomarkers and Resistance to Immunotherapy in Biliary Tract Cancers
By Erin Burns, PhD
December 2021, Vol 2, No 4
Improved understanding of predictive biomarkers is needed in immuno-oncology, and various immunotherapy combinations using different mechanisms of action are being investigated in cholangiocarcinoma (CCA) and other biliary tract cancers, according to presentations delivered at Session IV, “What’s New in Immuno-­oncology in BTC? Monotherapy and Combo Therapies,” at the 3rd Annual CCA Summit.
Biomarker Testing and Imaging in Cholangiocarcinoma
By Erin Burns, PhD
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.

Subscribe to CCA News

Stay up to date with personalized medicine by subscribing to receive the free CCA News print publication or weekly e‑Newsletter.

I'd like to receive: