Predictors of pretransplant dropout and posttransplant... : Hepatology (original) (raw)

Hepatobiliary Malignancies

Predictors of pretransplant dropout and posttransplant recurrence in patients with perihilar cholangiocarcinoma

Murad, Sarwa Darwish1; Kim, Ray W.1; Therneau, Terry3; Gores, Gregory J.1; Rosen, Charles B.2; Martenson, James A.4; Alberts, Steven R.5; Heimbach, Julie K.2,*

1_Divisions of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN_

2_Divisions of Transplantation Surgery, Mayo Clinic, Rochester, MN_

3_Divisions of Biostatistics, Mayo Clinic, Rochester, MN_

4_Department of Radiation Oncology, Mayo Clinic, Rochester, MN_

5_Divisions of Medical Oncology, Mayo Clinic, Rochester, MN_

*Address reprint requests to: Surgical Director of the Liver Transplant Program, Transplantation Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905

Email:[email protected]

Received 23 September 2011; Accepted 20 January 2012

Grant sponsor: 2010/2011 American Association for the Study of Liver Diseases (AASLD)/LIFER Clinical; Grant sponsor: Translational Research Fellowship in Liver Diseases Award.

Potential conflict of interest: Nothing to report.

See Editorial on Page 800

fax: 507–266–2810

Abstract

We have previously reported excellent outcomes with liver transplantation for selected patients with early-stage perihilar cholangiocarcinoma (CCA) following neoadjuvant chemoradiotherapy. Our aim was to identify predictors of dropout before transplantation and predictors of cancer recurrence after transplantation. We reviewed all patients with unresectable perihilar CCA treated with neoadjuvant chemoradiation in anticipation for transplantation between 1993 and 2010. Predictors were identified by univariate and multivariate Cox regression analysis of clinical variables. In total, 199 patients were enrolled, of whom 62 dropped out and 131 underwent transplantation at our institution, with six undergoing transplantation elsewhere. Predictors of dropout were carbohydrate antigen 19–9 (CA 19–9) ≥ 500 U/mL (hazard ratio [HR] 2.3; P = 0.04), mass ≥ 3 cm (HR 2.1; P = 0.05), malignant brushing or biopsy (HR 3.6; P = 0.001), and Model for End-Stage Liver Disease (MELD) score ≥ 20 (HR 3.5; P = 0.02). Posttransplant, recurrence-free 5-year survival was 68%. Predictors of recurrence were elevated CA 19–9 (HR 1.8; P = 0.01), portal vein encasement (HR 3.3; P = 0.007), and residual tumor on explant (HR 9.8; P < 0.001). Primary sclerosing cholangitis (PSC), age, history of cholecystectomy, and waiting time were not independent predictors. Conclusion: Outcome following neoadjuvant chemoradiation and liver transplantation for perihilar CCA is excellent. Risk of dropout is related to patient and tumor characteristics and this can be used to guide patient counseling before enrollment. Recurrence risk is mostly associated with presence of residual cancer on explant. Patients with PSC do not have an independent survival advantage over de novo patients, but present with more favorable tumor characteristics.