Registry Study of Neoadjuvant Chemoradiation & Transplant for Cholangiocarcinoma Patients

• Primary (Phase I): Proportion of patients with grade 3 or 4 DLT. [ Time Frame: Approximately 5 years. ] [ Designated as safety issue: Yes ]
• Primary (Phase II): Rate of excess toxicity, proportion of patients with stable disease, or better, response at completion of chemoradiation, and the proportion of patients who are alive at 2 years after transplant. [ Time Frame: Approximatly 5 years. ] [ Designated as safety issue: Yes ]

This is an observational study intended to validate results of a previous study done at the Mayo Clinic. Patients are treated with combination chemotherapy and radiation and maintained on oral Xeloda until they can receive liver transplant. A staging laparotomy is performed before chemoradiation in order to identify patients who will most benefit from the treatment and to improve outcomes.

Primary care clinic.

• Heimbach JK, Haddock MG, Alberts SR, Nyberg SL, Ishitani MB, Rosen CB, Gores GJ. Transplantation for hilar cholangiocarcinoma. Liver Transpl. 2004 Oct;10(10 Suppl 2):S65-8. Review.
• Jarnagin WR, Fong Y, DeMatteo RP, Gonen M, Burke EC, Bodniewicz BS J, Youssef BA M, Klimstra D, Blumgart LH. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg. 2001 Oct;234(4):507-17; discussion 517-9.
• Casavilla FA, Marsh JW, Iwatsuki S, Todo S, Lee RG, Madariaga JR, Pinna A, Dvorchik I, Fung JJ, Starzl TE. Hepatic resection and transplantation for peripheral cholangiocarcinoma. J Am Coll Surg. 1997 Nov;185(5):429-36.
• De Vreede I, Steers JL, Burch PA, Rosen CB, Gunderson LL, Haddock MG, Burgart L, Gores GJ. Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma. Liver Transpl. 2000 May;6(3):309-16.
• Brandsaeter B, Isoniemi H, Broomé U, Olausson M, Bäckman L, Hansen B, Schrumpf E, Oksanen A, Ericzon BG, Höckerstedt K, Mäkisalo H, Kirkegaard P, Friman S, Bjøro K. Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliary malignancy. J Hepatol. 2004 May;40(5):815-22.
• Madariaga JR, Iwatsuki S, Todo S, Lee RG, Irish W, Starzl TE. Liver resection for hilar and peripheral cholangiocarcinomas: a study of 62 cases. Ann Surg. 1998 Jan;227(1):70-9.
• Shimoda M, Farmer DG, Colquhoun SD, Rosove M, Ghobrial RM, Yersiz H, Chen P, Busuttil RW. Liver transplantation for cholangiocellular carcinoma: analysis of a single-center experience and review of the literature. Liver Transpl. 2001 Dec;7(12):1023-33. Review.
• Goldstein RM, Stone M, Tillery GW, Senzer N, Levy M, Husberg BS, Gonwa T, Klintmalm G. Is liver transplantation indicated for cholangiocarcinoma? Am J Surg. 1993 Dec;166(6):768-71; discussion 771-2.
• Hassoun Z, Gores GJ, Rosen CB. Preliminary experience with liver transplantation in selected patients with unresectable hilar cholangiocarcinoma. Surg Oncol Clin N Am. 2002 Oct;11(4):909-21.
• Sudan D, DeRoover A, Chinnakotla S, Fox I, Shaw B Jr, McCashland T, Sorrell M, Tempero M, Langnas A. Radiochemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma. Am J Transplant. 2002 Sep;2(8):774-9.
• Broomé U, Olsson R, Lööf L, Bodemar G, Hultcrantz R, Danielsson A, Prytz H, Sandberg-Gertzén H, Wallerstedt S, Lindberg G. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut. 1996 Apr;38(4):610-5.
• De Santis M, Bellmunt J, Mead G, Kerst JM, Leahy M, Maroto P, Skoneczna I, Marreaud S, de Wit R, Sylvester R. Randomized Phase II/III Trial Assessing Gemcitabine/Carboplatin and Methotrexate/Carboplatin/Vinblastine in Patients With Advanced Urothelial Cancer "Unfit" for Cisplatin-Based Chemotherapy: Phase II--Results of EORTC Study 30986. J Clin Oncol. 2009 Sep 28; [Epub ahead of print]
• Williams KJ, Picus J, Trinkhaus K, Fournier CC, Suresh R, James JS, Tan BR. Gemcitabine with carboplatin for advanced biliary tract cancers: a phase II single institution study. HPB (Oxford). 2010 Aug;12(6):418-26.
• Harder J, Riecken B, Kummer O, Lohrmann C, Otto F, Usadel H, Geissler M, Opitz O, Henss H. Outpatient chemotherapy with gemcitabine and oxaliplatin in patients with biliary tract cancer. Br J Cancer. 2006 Oct 9;95(7):848-52. Epub 2006 Sep 12.

Inclusion Criteria:

1. The diagnosis of cholangiocarcinoma will be established preoperatively by at least one of the following criteria:

   1. A positive brush cytology or biopsy result obtained at the time of cholangiography;
   2. Fluorescence in situ hybridization demonstrating aneuploidy;
   3. A serum CA 19-9 value greater than 100 U/mL in the presence of a radiographically characteristic malignant stricture in the absence of cholangitis.
2. Tumor is above the cystic duct and is unresectable.
3. Patient is a suitable candidate for OLT and judged a good candidate for the study by a radiation oncologist, a medical oncologist, and the liver transplant team.
4. Maximum Eastern Cooperative Oncology Group performance status of 2 and a minimum daily caloric intake of 1200kcal.
5. No evidence of metastatic disease.
6. Between ages 18 - 70.
7. Patient must provide written informed consent.

Exclusion Criteria:

1. Patients with intrahepatic metastasis
2. Patients with uncontrolled infections (sepsis)
3. Patients undergoing prior attempts at resection
4. Prior treatment with either irradiation or chemotherapy for this disease
5. Evidence of extrahepatic disease, including local lymph node metastasis (except peri-hilar nodes).
6. History of another malignancy diagnosed within 5 years, excluding superficial skin and cervical cancers