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  • Analysis of Failure After Curative Irradiationof Extrahepatic Bile Duct Carcinoma

    STEVEN J. BUSKIRK, M.D.,* LEONARD L. GUNDERSON, M.D.,t STEVEN E. SCHILD, M.D.,* CLAIRE E. BENDER, M.D.,4HUGH J. WILLIAMS, JR., M.D., DONALD C. McILRATH, M.D., || JAY S. ROBINOW, M.D.,*

    WILLIAM J. TREMAINE, M.D., and J. KIRK MARTIN, JR., M.D.#

    Thirty-four patients with subtotally resected or unresectablecarcinoma of the extrahepatic bile ducts received radiation ther-apy; a minimum of 45 Gy (external beam) to the tumor andregional lymph nodes 5-fluorouracil (5-FU). Seventeen patientsreceived an external beam boost of 5 to 15 Gy to the tumor, anda specialized boost was used in the remaining 17 patients (iridium-192 transcatheter seeds in 10 and intraoperative radiation therapyIIORTI with electrons in seven). The median time to death in all34 patients was 12 months (range, 4 to 98 months). The onlypatients who survived longer than 18 months were those eitherwith gross total or subtotal resection before external irradiation(2 of 6) or who received specialized boosts ('92Ir, 3 of 10; IORT,3 of 7). Local failure was documented in 9 of 17 patients whoreceived external beam irradiation alone 5-FU, 3 of 10 patientswho received an '92Ir boost, and 2 of 6 patients who received anIORT boost with curative intent.

    C ARCINOMA OF THE extrahepatic bile ducts is anuncommon malignancy associated with a highmortality rate."2 Of all bile duct neoplasms, 15%

    to 20% occur proximally in the porta hepatis, 30% arefound in the proximal common bile duct, and 50% de-velop in the distal common bile duct.3

    These tumors are usually well-differentiated adenocar-cinomas and are associated with fibrosis (scirrhous car-cinomas) in one third ofpatients.3 The predominant routeof dissemination is by direct extension within a rich lym-phatic network in the submucosa, with extraductal in-volvement of surrounding organs, or to lymph nodes inthe porta hepatis and celiac axis. 1'4 Intra-abdominal spreadinvolving the peritoneal surface or ovaries was noted inonly 7 of 77 patients (9%) initially explored at the LaheyClinic.5

    Because of the anatomic location of these tumors andthe operative limitations, most of these carcinomas are

    From the Section of Radiation Oncology, * the Department ofDiagnostic Radiology, and the Section of General and

    Vascular Surgery,# Mayo Clinic Jacksonville, Jacksonville,Florida; and the Division of Radiation Oncology,t theDepartment of Diagnostic Radiology,* the Section of

    Gastroenterologic and General Surgery, || and the Division ofGastroenterology and Internal Medicine, Mayo Clinic and

    Mayo Foundation, Rochester, Minnesota

    either unresectable or there is gross or microscopic diseasepresent after attempted resection.6 Of the 15% to 30%of patients who are able to undergo potentially curativeresection, a local recurrence develops in approxi-mately 50%.2

    Because local progression oftumor is the most commoncause of treatment failure and death in these patients,4'7we began a program of aggressive local irradiation aloneor in combination with 5-fluorouracil (5-FU) or with spe-cialized radiation boost techniques. When lesions wereunresectable, percutaneous transhepatic biliary drainagewas used for decompression8 followed by irradiation de-livered with curative intent. External beam irradiationwas used to treat the tumor or tumor bed and regionallymph nodes. When technically feasible, a supplementalboost dose was given to unresected or residual diseasewith either transcatheter iridium- 192 or an intraoperativeelectron source.

    Materials and Methods

    From January 1980 through December 1984, 34 pa-tients with a diagnosis of carcinoma of the extrahepaticbile ducts received irradiation delivered with curative in-tent in the Division of Radiation Oncology of the MayoClinic in Rochester, Minnesota.

    125

    Address reprint requests to Steven J. Buskirk, M.D., Mayo ClinicJacksonville, 4500 San Pablo Rd, Jacksonville, FL 32224.

    Accepted for publication May 17, 1991.

  • BUSKIRK AND OTHERS

    The median age ofthe patients was 66 years (range, 35to 86 years). Twenty of the patients were men, and 14were women. Symptoms at presentation included pruritusin 18 patients, anorexia and weight loss in 16, right upperquadrant pain in 13, nausea in 9, fever in 4, and vomitingin 2. Two patients had a history of chronic ulcerativecolitis. The duration ofthe symptoms ranged from 4 daysto 3 years (median, 5 weeks). Physical findings includedjaundice in 30 patients, right upper quadrant tendernessin 9, fever in 3, hepatomegaly in 1, and palpable gall-bladder in 1.

    Investigations

    Thirty-three of the thirty-four patients had increasedvalues on liver function tests. Serum alkaline phosphataselevels ranged from 235 to 2259 U/L (normal, 90 to 240U/L). Serum aspartate aminotransferase values rangedfrom 33 to 366 U/L (normal, 12 to 31 U/L). Direct andtotal bilirubin values ranged from 0.4 to 22.5 mg/dL(normal, 0 mg/dL) and 0.9 to 31.3 mg/dL (normal, < 1.1mg/dL), respectively.

    Chest radiographs were negative for metastasis in all34 patients. Twenty-seven of the thirty-four were evalu-ated by percutaneous transhepatic cholangiograms(PTHC). All the PTHC studies were abnormal and showedan intraluminal component oftumor. Right upper quad-rant ultrasonograms showed dilated ducts in 17 of 20 pa-tients evaluated. Dilated bile ducts were noted also in 18of 19 patients evaluated by computed tomography (CT)of the abdomen. Endoscopic retrograde cholangiopan-creatography (ERCP) showed tumor obstruction of bileducts in four patients. Neither ultrasonography nor CTstudies were useful in determining the extraductal com-ponent of disease for the purpose of planning radiationtherapy.

    Pathology

    A tissue diagnosis could not be secured before irradia-tion in three of the 34 patients; however, the findings onPTHC were diagnostic in each. One of these patients wassurgically explored, and several biopsy specimens werenegative for tumor. At autopsy, a histologic diagnosis ofsquamous cell carcinoma was obtained. The other twopatients were not surgically explored. Needle biopsies andbile cytology were negative for tumor in these two patients(both died of tumor progression). A review of the tissueof the remaining 31 patients disclosed grade 1 adenocar-cinoma in 5 patients, grade 2 in 19, grade 3 in 4, andgrade 4 in 1. Two tumors were diagnosed as adenocar-cinoma but were not assigned a specific Broders' grade.

    Ann. Surg. * February 1992

    Tumor Location and Surgical Treatment

    Tumor extent was variable. Eighteen ofthe thirty-fourpatients had contiguous tumor in the right hepatic duct,left hepatic duct, and common hepatic duct. Tumor waslocated in the common hepatic duct in five patients, thecommon bile duct in four, the right hepatic duct andcommon hepatic duct in three, the common hepatic andcommon bile duct in two, and the right hepatic duct inone. One additional patient had contiguous involvementof the right hepatic, left hepatic, common hepatic, andcommon bile ducts.

    Surgical exploration was performed in 31 of the 34 pa-tients. Biopsy only was performed in 24 patients. Subtotalresection and formation of a hepaticojejunostomy orcholedochojejunostomy was performed in six patients. Aright hepatic lobectomy was performed in one patient withtumor confined to the right hepatic lobe and duct. Lymphnode sampling was performed in eight patients, and alymphadenectomy was performed in one patient. Six ofthese nine patients had lymph node involvement withtumor. Percutaneous transhepatic biliary tube de-compression alone was performed in the three patientswho were not surgically explored.

    Treatment With Radiation Therapy

    The volume of the radiation field and the total dosevaried within the patient population (Table 1). Since Jan-uary 1981, all patients received external beam irradiationwith 10-MV photons by using a four-field technique de-signed to deliver 45 Gy in 1.8-Gy fractions to the tumorand regional lymph nodes. Treatment fields included amargin of 3 to 5 cm beyond ductal involvement as dem-onstrated on PTHC. The porta hepatis, pancreaticoduo-denal, and celiac lymph nodes were routinely included inthe initial volume to receive 45 Gy. Thirty patients alsoreceived an external beam boost of 5 to 15 Gy to thetumor volume plus a 2- to 3-cm margin. In most patients,the external beam boost doses were limited to 55 Gy whena portion ofthe small intestine or stomach was within theboost field. The total dose to the volume receiving externalbeam boost was usually limited to 50.4 Gy ifa specializedradiation boost was planned.The method of achieving a boost to the residual or

    unresected tumor was dependent on tumor location, op-erative procedure, and the presence of dose-limiting or-gans. The options for accomplishing the boost to the tu-mor included: (1) intraoperative irradiation, (2) '92Ir im-plant, and (3) additional external beam irradiation.Starting in July 1981, an attempt was made to supplementthe external beam irradiation with intraoperative electronbeam irradiation (IORT) or transcatheter 192ir wheneverfeasible. If the patient had a choledochoenterostomy or

    126Clinical Features

  • EXTRAHEPATIC BILE DUCT CARCINOMA

    TABLE 1. Radiation Therapy Volume and Dose Data

    External 5-fluorouracil External + Specialized Boostt

    External Beam Dose Subtotal Resection Unresected Tumor '92Ir Boost IORT(Gy)* of Tumor (no.) (no.) (no.) (no.)

    Tumor and lymph nodes45 6/6 11/11 10/10 7/7

    Boost to tumor5 1 8 310 2 515 4 3

    Before operation5 4

    * Majority treated with 1.8-Gy fractions 5 days/week.t Transcatheter '92Ir dose of 20 to 25 Gy at 0.5- to 1.0-cm radius;

    IORT dose of 15 to 20 Gy in one fraction.

    hepaticoenterostomy, the boost was given with externalbeam irradiation, w