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Treatment endpoints for advanced cholangiocarcinoma

Nature Clinical Practice Gastroenterology & Hepatology volume 1, pages 4–5 (2004)Cite this article

Cholangiocarcinoma is a malignant solid epithelial-cell cancer arising from extrahepatic or intrahepatic ducts. Although cholangiocarcinomas can arise anywhere in the biliary tree, there is a predisposition for this cancer to occur in the perihilar region, involving the right and left hepatic ducts and their confluence. Perihilar cholangiocarcinomas frequently arise in patients with chronic biliary inflammation, especially primary sclerosing cholangitis.1 However, many patients have no identifiable risk factors for cholangiocarcinoma. Unfortunately, the incidence of cholangiocarcinoma is increasing in Western countries.2 The disease is frequently advanced at the time of clinical presentation, which precludes potentially curative surgical procedures—advanced disease is uniformly fatal. There is no proven effective medical treatment for this cancer and systemic therapies need to be evaluated. This evaluation is difficult because treatment endpoints are ill-defined.

Endpoints for clinical trials on solid tumors are undergoing a re-evaluation. Previously, the endpoints for the evaluation of cytotoxic drugs were often a decrease in tumor size and therapeutic objectives were to obtain a complete remission or sustained partial remission. However, with the current evaluation of many cytostatic drugs (e.g. epidermal-growth-factor inhibitors, anti-angiogenesis agents, etc.) durable periods of tumor stability have become accepted as legitimate endpoints for clinical trials.3,4 Progression-free survival is, therefore, an attractive endpoint. In the context of cholangiocarcinoma, these prior and more recent endpoints are problematic. We have assessed the problems of using the current criteria as endpoints for cholangiocarcinoma and propose a new objective and quantitative system for assessing disease progression.

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Authors and Affiliations

  1. Reuben R Eisenberg Professor of Medicine Mayo Clinic College of Medicine, Rochester, MN, USA

    Gregory J Gores

  2. Instructor of Surgery Mayo Clinic College of Medicine, Rochester, MN, USA

    Edwina S Baskin-Bey

  3. Professor of Medicine Mayo Clinic College of Medicine, Rochester, MN, USA

    Todd H Baron

  4. Associate Professor of Oncology, all at Mayo Clinic College of Medicine, Rochester, MN, USA

    Steven R Alberts

Authors
  1. Gregory J Gores
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  2. Edwina S Baskin-Bey
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  3. Todd H Baron
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  4. Steven R Alberts
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Corresponding author

Correspondence to Gregory J Gores.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Figure 1

Disease progression in the left lobe of a patient with cholangiocarcinoma. Top panel: Representative endoscopic retrograde cholangiograms of a patient with advanced hilar cholangiocarcinoma. Lower panel: Quantitation of brightness area product (BAP) for the cholangiograms shown in the top panel. The BAP, a quantitative measurement of the area represented by contrast-filled bile ducts, mathematically represents the average brightness of pixels or voxels above a threshold value in a region of interest. For each cholangiogram, the biliary region of choice is mapped (areas shaded in red) and the number of pixels or voxels are measured which correspond to a brightness threshold value. The marked decrease in BAP for the cholangiogram dated 10 September 2003 compared with the one dated 5 June 2003 should be noted. This loss in biliary surface area, depicting disease progression, was apparent even when biochemical studies had improved due to better stenting of the right lobe. On 5 June 2003, total serum bilirubin was 13.2 mg/dl and serum alkaline phosphatase was 870 U/L (normal <115 U/L). On 10 September 2003, total serum bilirubin was 5.2 mg/dl and serum alkaline phosphatase was 646 U/L.

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Gores, G., Baskin-Bey, E., Baron, T. et al. Treatment endpoints for advanced cholangiocarcinoma. Nat Rev Gastroenterol Hepatol 1, 4–5 (2004). https://doi.org/10.1038/ncpgasthep0008

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