External radiation therapy and transcatheter iridium in the treatment of extrahepatic bile duct carcinoma.

Foo ML, Gunderson LL, Bender CE, Buskirk SJ. Int J Radiat Oncol Biol Phys 1997 Nov 1;39(4):929-35

Radiation Oncology, Mayo Clinic Jacksonville, FL 32224, USA.

PURPOSE/OBJECTIVE: Review survival, prognostic factors, and patterns of failure in patients with extrahepatic bile duct (EHBD) carcinoma treated with external beam irradiation (EBRT) and transcatheter iridium. METHODS AND MATERIALS: The charts of 24 patients with EHBD cancer treated with EBRT and transcatheter boost were reviewed. All patients had transhepatic biliary tubes or endoprostheses placed. Two patients underwent hemihepatectomy with hepaticojejunostomy formation but had residual disease. Two patients had biopsy proven adenopathy. Five patients had Grade 1 adenocarcinoma, nine Grade 2, six Grade 3, and one Grade 4 disease. Median EBRT dose was 50.4 Gy delivered in 1.8 Gy/day fractions. Median transcatheter boost at 1 cm radius was 20 Gy. Nine patients received concomitant 5-Fluorouracil (5-FU) during EBRT. RESULTS: Median survival was 12.8 months (range 7.5 months to 9 years). Overall 2- and 5-year survival rates were 18.8 and 14.1%, respectively (three disease-free survivors > or =5 years). One patient is still alive without relapse 10 years from diagnosis and 5 years after liver transplantation for liver failure (no cancer in specimen, underlying sclerosing cholangitis). Two additional long-term survivors had no evidence of relapse 6.9 and 8.2 years after diagnosis. Histologic grade, lymph node status, cystic, hepatic, common hepatic or common bile duct involvement, surgical resection, radiation therapy dose, and chemotherapy did not significantly effect survival due to the number of patients analyzed. There was a trend towards improved survival with the addition of 5-FU chemotherapy (5-year survival in two of nine patients, or 22%). Eight of 24 patients (33%) demonstrated radiographic evidence of local recurrence. Distant metastases developed in 6 of 24 (25%) patients. The most common complications were tube related cholangitis (50%) and gastric/duodenal ulceration or bleeding (42%). CONCLUSION: External beam irradiation combined with a transcatheter boost can result in long-term survival of patients with EHBD cancer. Both distant metastases and local recurrence develop in 25-30% of patients despite irradiation. Survival may be improved by using chemotherapy in combination with EBRT to impact disease relapse (local and distant). Because there may be a dose response with irradiation, survival may also be improved by increasing the dose of radiation delivered by transcatheter boost. A Phase II trial is being developed using a combination of 45-50 Gy EBRT with concomitant 5-FU delivered by protracted venous infusion followed by a 25-30 Gy transcatheter boost.

Combined external beam radiotherapy and intraluminal high dose rate brachytherapy on bile duct carcinomas.

Fritz P, Brambs HJ, Schraube P, Freund U, Berns C, Wannenmacher M.  Int J Radiat Oncol Biol Phys 1994 Jul 1;29(4):855-6

Department of Clinical Radiology, University of Heidelberg, Germany.

PURPOSE: The aim of this study was to investigate the effectiveness and complications of combined external beam and intraluminal high dose rate irradiation and various adjuvant biliary drainage techniques on patients with bile duct carcinomas. METHODS AND MATERIALS: Eighteen patients with carcinomas of the hepatic duct bifurcation and 12 patients with carcinomas of the choledochus duct or the common hepatic duct were treated with combined external beam radiotherapy and intraluminal high-dose rate brachytherapy. Nine patients received radiotherapy after palliative tumor resection and 21 patients were primarily irradiated. Twenty-five patients completed the full course of radiotherapy. On these patients, the reference doses for the external beam varied from 30 to 45 Gy and for brachytherapy from 20 to 45 Gy. Biliary drainage after radiotherapy was achieved either with percutaneous catheters, endoprosthesis, or stents. RESULTS: The median survival for the entire group was 10 months. The actuarial survival was 34% after 1 year, 18% after 2 and 3 years, and 8% after 5 years. The subgroup with palliative tumor resection exhibit a significantly better survival (median: 12.1 months vs. 7.9 months). Three patients are still living without evidence of disease since 35 to 69 months. Major complications like bacterial cholangitis could be lowered from 37% to 28% through exchange of percutaneous transhepatic catheters to endoprosthesis or stents. The longest lasting drainages were achieved through stents. The frequency of radiogenic ulcera were lowered from 23% to presently 7.6% after the total dose of the high dose rate afterloading boost was reduced to 20 Gy. CONCLUSIONS: The present standard treatment schedule 40 Gy for the external beam and 20 Gy (fourfold 5 Gy) for the afterloading boost seems to be appropriate and well tolerated. After radiotherapy, a permanent supply of drainage should be made with a stent.

Role of radiotherapy, in particular intraluminal brachytherapy, in the treatment of proximal bile duct carcinoma.

Gonzalez Gonzalez D, Gouma DJ, Rauws EA, van Gulik TM, Bosma A, Koedooder C.   Ann Oncol 1999;10 Suppl 4:215-20

Department of Radiation Oncology, University of Amsterdam, Academic Medical Centre, The Netherlands. D.Gonzalez@amc.uva.nl

PURPOSE: To perform an analysis of the results obtained with radiotherapy in patients with either resectable or unresectable cholangiocarcinoma of the proximal bile ducts. Emphasis will be paid to analyse the role of radiotherapy, particularly brachytherapy. PATIENTS AND METHODS: Between 1985 and 1997, 109 patients received radiotherapy. In 71 patients (group I) tumor resection was combined with postoperative irradiation in 52 patients and pre- plus post-operative irradiation in 19 patients. Among this group, 41 patients had a boost of 10 Gy to the biliodigestive anastomosis using intraluminal brachytherapy. Median total dose was between 50-55 Gy. The other 38 patients (group II) had an unresectable tumor at laparotomy (16 patients) or were considered primary unresectable because locoregional tumor extension (22 patients). Brachytherapy boost through a nasobiliary approach was given to 19 patients (22-25 Gy). The median total dose varied between 60 to 68 Gy. Mean follow-up was 25 +/- 23 months. RESULTS: In group I, the survival rates at 1, 3, and 5 year were 84%, 37%, and 24%, respectively. Median survival was 24 months. Sixteen patients did live longer than 4 years. Analysis of prognostic factors among resected patients showed the tumor differentiation grade, microscopically involved margins other than the upper (hepatic) and lower (choledocus) resection parameters analysed, only the total dose had influence on margins, and elevated alkaline phosphatase as factors which significantly influence survival. From the different radiotherapy prognosis, patients receiving a total dose above 55 Gy had a shorter survival. It is important to note that patients receiving brachytherapy boost did not have a better survival than patients treated with external beam irradiation alone. Preoperative radiotherapy did not have impact on survival but recurrences in the surgical scars were not observed as compared to 15% recurrences if preoperative radiotherapy was not given. In group II the median survival was 10.4 months. Survival rates at 1 and 2 year were 43% and 10%, respectively. The only significant prognostic factor found was if unresectability was defined primarily or during laparotomy. As it was the case in group I, brachytherapy boost did not have influence on prognosis as compared to external beam irradiation alone. Observed late complications consisted of duodenal stenosis, upper digestive tract bleeding and cholangitis. Probably these complications were not only attributable to radiotherapy, as tumor relapse was also present in the majority of the cases. CONCLUSIONS: The role of radiotherapy either as adjuvant or as primary treatment remains to be demonstrated in prospective randomised studies. From our results, it seems that high radiation doses could be dangerous and could detriment prognosis. Brachytherapy boost was not superior to treatment with external beam irradiation alone.

The role of radiotherapy in the management of extrahepatic bile duct cancer: an analysis of 145 consecutive patients treated with intraluminal and/or external beam radiotherapy.

Kamada T, Saitou H, Takamura A, Nojima T, Okushiba SI.  Int J Radiat Oncol Biol Phys 1996 Mar 1;34(4):767-74

Division of Radiation Medicine, Research Center of Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.

PURPOSE: To determine the feasibility of high dose radiotherapy and to evaluate its role in the management of extrahepatic bile duct (EHBD) cancer. METHODS AND MATERIALS: Between 1983 and 1991, 145 consecutive patients with EHBD cancer were treated by low dose rate intraluminal 192Ir irradiation (ILRT) either alone or in combination with external beam radiotherapy (EBRT). Among the primarily irradiated, 77 patients unsuitable for surgical resection, 54 were enrolled in radical radiotherapy, and 23 received palliative radiotherapy. Fifty-nine received postoperative radiotherapy, and the remaining 9 preoperative radiotherapy. The mean radiation dose was 67.8 Gy, ranging from 10 to 135 Gy. Intraluminal 192Ir irradiation was indicated in 103 patients, and 85 of them were combined with EBRT. Expandable metallic biliary endoprosthesis (EMBE) was used in 32 primarily irradiated patients (31 radical and 1 palliative radiotherapy) after the completion of radiotherapy. RESULTS: The 1-, 3-, and 5-year actuarial survival rates for all 145 patients were 55%, 18%, and 10%, for the 54 patients treated by radical radiotherapy (mean 83.1 Gy), 56%, 13%, and 6% [median survival time (MST) 12.4 months], and for the 59 patients receiving postoperative radiotherapy (mean 61.6 Gy), 73%, 31%, and 18% (MST 21.5 months), respectively. Expandable metallic biliary endoprosthesis was useful for the early establishment of an internal bile passage in radically irradiated patients and MST of 14.9 months in these 31 patients was significantly longer than that of 9.3 months in the remaining 23 patients without EMBE placement (p < 0.05). Eighteen patients whose surgical margins were positive in the hepatic side bile duct(s) showed significantly better survival compared with 15 patients whose surgical margins were positive in the adjacent structure(s) (44% vs. 0% survival at 3 years, p < 0.001). No survival benefit was obtained in patients given palliative or preoperative radiotherapy. Gastroduodenal complications increased in those receiving doses of 90 Gy or more, and serious biliary bleeding was experienced in three preoperatively irradiated patients. Complications in other patients was tolerable. CONCLUSIONS: High-dose radiotherapy, consisting of ILRT and EBRT, appears to be feasible in the management of EHBD cancer, and it offers a survival advantage for patients not suited for surgical resection and patients with positive margins in the resected end of the hepatic side bile duct. Expandable metallic biliary endoprosthesis assists the internal bile flow and may lengthen survival after high dose radiotherapy.

Radiation therapy in extrahepatic bile duct carcinoma.

Mahe M, Romestaing P, Talon B, Ardiet JM, Salerno N, Sentenac I, Gerard JP.   Radiother Oncol 1991 Jun;21(2):121-7

Department of Radiation Therapy, Hopital Lyon Sud, Pierre Benite, France.

Fifty-one patients with carcinoma of the extrahepatic bile ducts (EHBD) received radiation therapy between January 1980 and December 1988. The location of the tumors was: proximal third, 20 patients; middle third, 23 patients; distal third, 3; diffuse, 5 patients. Thirty-six patients underwent surgery with complete gross resection in 14 (10/14 with positive margins), incomplete gross resection in 12 and only biopsy in 10. Fifteen patients had only biliary drainage without laparotomy after cytologic diagnosis of malignancy in 11/15. Radiation therapy was done with curative intent after complete or incomplete resection (n = 26) and it was palliative in patients who had no resection or only biliary drainage (n = 25). Twenty-five patients received external radiation-therapy (ERT) alone to the tumor and lymph nodes (mean dose 45 Gy/2 Gy per fraction for cure, 35 Gy/10 fractions for palliation), 8 patients had only iridium-192 (192Ir) implant (50-60 Gy at a 1 cm radius for cure, 30 Gy for palliation), 17 patients had both ERT + 192Ir (ERT 42.5 Gy + 192Ir 10-15 Gy for cure; ERT 20 Gy/5 fractions + 192Ir 20-30 Gy for palliation) and one intra-operative irradiation + ERT. The overall survival for the entire group was 55, 28.5 and 15% at 12, 24, 36 months and median survival 12 months. Median survival was 22 months in patients treated with curative intent and only 10 months after palliative treatment (p 0.03). Among patients who had curative treatment, median survival was 27.5 months after complete gross resection and 13 months after incomplete gross resection

Interventional radiology and radiotherapy for inoperable cholangiocarcinoma of the extrahepatic bile ducts.

Milella M, Salvetti M, Cerrotta A, Cozzi G, Uslenghi E, Tavola A, Gardani G, Severini A. Tumori 1998 Jul-Aug;84(4):467-71

Division of Radiology C, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.

AIMS AND BACKGROUND: To evaluate the effectiveness of external radiation therapy (ERT), alone or combined with endoluminal brachytherapy (BRT), following percutaneous transhepatic biliary drainage (PTBD) in the treatment of patients affected by inoperable cholangiocarcinoma. METHODS & STUDY DESIGN: From September 1980 to June 1996, 130 jaundiced patients affected by inoperable cholangiocarcinoma were submitted to PTBD at the Division of Radiology C of the National Cancer Institute of Milan. Nineteen were excluded from the present analysis due to the short survival after PTBD (< 30 days). The other 111 patients were divided into three groups according to the following therapy: no further treatment after palliative PTBD in 89 patients (80%, group 1); ERT in 10 patients (9%, group 2); ERT plus BRT in 12 patients (11%, group 3). All the ERT + BRT patients were enrolled after 1990 and were treated with high-energy photon beams followed by endobiliary insertion of one or two iridium-192 wires. RESULTS: Median overall survival among the 111 assessable patients was 126 days; for groups 1, 2 and 3 it was 108, 345 and 428 days, respectively. The patients submitted to radiotherapy (ERT alone or ERT + BRT) were evaluated by radiologic examinations after the end of radiation. In group 2, a partial remission in 3 cases, a progression of disease in 1 case, and no change in 6 cases were observed. Among the patients of group 3, complete remission in 5 and partial remission in 7 patients were achieved. In all the patients achieving complete remission, the PTBD could be removed. CONCLUSIONS: The combination of ERT plus BRT improves survival and quality of life of the patients submitted to PTBD for cholangiocarcinoma. Under the technical point of view, radiation treatment is easy to perform, but much caution is required in defining clinical and planning target volumes. Moreover, drainage during the radiation treatment has to be submitted to a very meticulous surveillance.

Combined modality treatment in unresectable extrahepatic biliary carcinoma.

Morganti AG, Trodella L, Valentini V, Montemaggi P, Costamagna G, Smaniotto D, Luzi S, Ziccarelli P, Macchia G, Perri V, Mutignani M, Cellini N.  Int J Radiat Oncol Biol Phys 2000 Mar 1;46(4):913-9

Cattedra di Radioterapia, Universita' Cattolica del Sacro Cuore, Roma, Italy.

PURPOSE: Cancers of the extrahepatic biliary tract are rare. Surgical resection is considered the standard treatment, but is rarely feasible. Several reports of combined modality therapy, including external beam radiation, often combined with chemotherapy and intraluminal brachytherapy, have been published. The purpose of this study was to evaluate the effect of chemoradiation plus intraluminal brachytherapy on response, local control, survival, and symptom relief in patients with unresectable or residual extrahepatic biliary carcinoma. METHODS AND MATERIALS: From February 1991 to December 1997, 20 patients (14 male, 6 female; mean age 61 +/- 12 years; median follow-up 71 months) with unresectable (16 patients) or residual (4 patients), nonmetastatic extrahepatic bile tumors (common bile duct, 8; gallbladder, 1; Klatskin, 11) received external beam radiation (39.6-50.4 Gy); in 19 patients, 5-fluorouracil (96-h continuous infusion, days 1-4 at 1,000 mg/m(2)/day) was also administered. Twelve patients received a boost by intraluminal brachytherapy using (192)Ir wires of 30-50 Gy, prescribed 1 cm from the source axis. RESULTS: During external beam radiotherapy, 8 patients (40%) developed grade 1-2 gastrointestinal toxicity. Four patients treated with external-beam plus intraluminal brachytherapy had a clinical response (2 partial, 2 complete) after treatment. For the total patient group, the median survival and time to local progression was 21.2 and 33.1 months, respectively. Distant metastasis occurred in 10 (50%) patients. Two patients who received external beam radiation plus intraluminal brachytherapy developed late duodenal ulceration. Two patients with unresectable disease survived more than 5 years. CONCLUSION: Our data suggest that chemoradiation plus intraluminal brachytherapy was relatively well-tolerated, and resulted in reasonable local control and median survival. Further follow-up and additional research is needed to determine the ultimate efficacy of this regimen. New chemoradiation combinations and/or new treatment strategies (neoadjuvant chemoradiation) may contribute, in the future, to improve these results.

Clinical efficacy of brachytherapy combined with external-beam radiotherapy and repeated arterial infusion chemotherapy in patients with unresectable extrahepatic bile duct cancer.

Nomura M, Yamakado K, Nomoto Y, Nakatsuka A, Ii N, Shoji K, Takeda K. Int J Oncol 2002 Feb;20(2):325-31

Department of Radiology, Mie University School of Medicine, Mie 514-8507, Japan. goto-m@clin.medic.mie-u.ac.jp

The objective of this study was to evaluate the clinical efficacy of brachytherapy combined with external-beam radiotherapy and repeated arterial infusion chemotherapy in improving stent patency and prognosis in patients with unresectable bile duct cancer as compared with brachytherapy alone. Seventeen patients were treated. Five patients received brachytherapy alone before stent placement. Twelve patients received brachytherapy combined with external-beam radiotherapy (n=5), repeated hepatic arterial infusion chemotherapy using an implanted catheter and port (n=1), or both (n=6). Mean survival was significantly improved in the group that received combined therapy as compared with the group that received brachytherapy alone (16.2 months vs. 4.6 months, p<0.01). Although stent occlusion rates were similar in the two groups (42% vs. 40%), there was a trend towards longer stent patency in the combined therapy group than in the brachytherapy group (22 months vs. 3.6 months, p<0.2). Radiation gastritis necessitating gastrectomy developed in 1 patient who received external-beam radiotherapy at more than 50 Gy. Brachytherapy combined with external-beam radiotherapy and repeated hepatic arterial infusion chemotherapy increases survival compared with brachytherapy alone in patients with unresectable bile duct cancer.

Carcinoma of the extrahepatic bile ducts. The University of California at San Francisco experience.

Schoenthaler R, Phillips TL, Castro J, Efird JT, Better A, Way LW.  Ann Surg 1994 Mar;219(3):267-74

Department of Radiation Oncology, University of California at San Francisco.

OBJECTIVE: The authors investigated the combined experience of a single institution in treating bile duct carcinoma during the modern era. SUMMARY BACKGROUND DATA: Bile duct carcinomas are notoriously difficult to cure, with locoregional recurrence the rule, even after radical resection. Adjuvant efforts have included various radiation modalities, with limited success. Recently, charged-particle radiotherapy has also been used in these patients. METHODS: The authors performed a retrospective chart analysis of 129 patients with bile duct adenocarcinomas treated between 1977 and 1987 through the University of California at San Francisco, including 22 patients treated at Lawrence Berkeley Laboratory with the charged particles helium and neon. The minimum follow-up was 5 years. Survival, outcome, and complication results were analyzed. RESULTS: Sixty-two patients were treated with surgery alone (S), 45 patients received conventional adjuvant x-ray radiotherapy (S + X), and 22 were treated with charged particles (S + CP). The median survival times were 6.5, 11, and 14 months, respectively, for the entire group, and 16, 16, and 23 months in patients treated with curative intent. There was a survival difference in patients undergoing total resection compared with debulking (p = 0.05) and minor resections (p = 0.0001). Patients with microscopic residual disease had increased median survival times when they were treated with adjuvant irradiation, most markedly after CP (p = 0.0005) but also with conventional X (p = 0.0109). Patients with gross residual disease had a less marked but still statistically significant extended survival (p = 0.05 for S + X and p = 0.0423 for S + CP) after irradiatio CONCLUSIONS: The mainstay of bile duct carcinoma management was maximal surgical resection in these patients. Postoperative radiotherapy gave patients with positive microscopic margins a significant survival advantage and may be of value in selected patients with gross disease.

Location, not staging, of cholangiocarcinoma determines the role for adjuvant chemoradiation therapy.

Serafini FM, Sachs D, Bloomston M, Carey LC, Karl RC, Murr MM, Rosemurgy AS. Am Surg 2001 Sep;67(9):839-43

Department of Surgery, University of South Florida, Tampa 33601, USA.

The role of adjuvant chemoradiation therapy (CT/XRT) in the treatment of cholangiocarcinoma is controversial. We undertook this study to determine whether CT/XRT is appropriate after resection of cholangiocarcinomas. One hundred ninety-two patients with cholangiocarcinomas were treated from 1988 to 1999. After resection, patients were assigned a stage (TNM) and were stratified by location of the tumor as intrahepatic, perihilar, and distal tumors. Data are presented as mean +/- standard deviation. Of 192 patients 92 (48%) underwent resections of cholangiocarcinomas. Thirty-four patients had liver resections, 25 had bile duct resections, and 33 underwent pancreaticoduodenectomies. Thirty-four patients had adjuvant CT/XRT, three had adjuvant chemotherapy, four had neoadjuvant CT/XRT, and 50 had no radiation or chemotherapy. Mean survival of resected patients with adjuvant CT/XRT was 42 +/- 37.0 months and without CT/XRT it was 29 24.5 months (P = 0.07). Mean survival of patients with distal tumors receiving or not receiving CT/XRT was 41 +/- 21.8 versus 25 +/- 20.1 months, respectively, (P = 0.04). Adjuvant chemoradiation improves survival after resection for cholangiocarcinoma (P = 0.07) particularly in patients undergoing resection for distal tumors (P = 0.04). Benefits of adjuvant CT/XRT are apparent when stratified by location of cholangiocarcinomas rather than staging.

Benefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinoma.

Todoroki T, Ohara K, Kawamoto T, Koike N, Yoshida S, Kashiwagi H, Otsuka M, Fukao K. Int J Radiat Oncol Biol Phys 2000 Feb 1;46(3):581-7

Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-Shi, Japan. todorov@md.tsukuba.ac.jp

PURPOSE: The objective of this study was to determine the benefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinoma (Klatskin tumor). METHODS AND MATERIALS: We conducted a retrospective review of 63 patients who underwent surgical resection of Stage IVA Klatskin tumor. Of the 63 patients, 47 had microscopic tumor residue (RT1). Twenty-eight of the 47 patients with RT1 were treated by adjuvant radiotherapy and the remaining 19 patients were treated exclusively by surgical resection. Seventeen of the 28 patients with RT1 were treated by both intraoperative radiotherapy (IORT) and postoperative radiotherapy (PORT); of the remaining 11 patients with RT1, 6 underwent resection and IORT, and 5 underwent resection and PORT. RESULTS: The major complication and 30-day operative death rates were significantly lower in the radiation group (9.5% and 0.0%, respectively) than in the resection alone group (28.5% and 9.5%, respectively). Of the eight 5-year survivors with RT1, 6 had adjuvant radiotherapy and the remaining 2 had resection alone. Adjuvant radiotherapy for patients with RT1 yielded significantly (p = 0.0141) higher 5-year survival rates (33.9%) than in the resection alone group (13.5 %). The best 5-year survival rate (39.2 %) was found in patients who underwent a combination of IORT and PORT after resection. The local-regional control rate was significantly higher in the adjuvant radiation group than in the resection alone group (79.2% vs. 31.2%). CONCLUSION: Our data clearly suggest the improved prognosis of patients with locally advanced Klatskin tumor by integrated adjuvant radiotherapy with IORT and PORT to complete gross tumor resection with acceptable treatment mortality and morbidity.

External radiotherapy and extrahepatic bile duct cancer.

Tollenaar RA, van de Velde CJ, Taat CW, Gonzalez Gonzalez D, Leer JW, Hermans J.   Eur J Surg 1991 Oct;157(10):587-9

Department of Surgery, University Hospital Leiden, The Netherlands.

The hospital records of patients with extrahepatic bile duct cancer who where treated surgically between 1968 and 1983 were reviewed. Of 55 patients, 16 (29%) received radiotherapy after surgery. The total dose given ranged from 40 to 60 Gy. Median follow-up time for analysis was 4.0 months and lasted until January 1988. The overall median survival was 4 months (range 0-36), that of the irradiated patients was 16 months (range 2-36), and that of the 39 patients who were not irradiated was 3 months (range 0-32). When the 13 post operative deaths were excluded the median survival was 4 months. Radiotherapy did not cause any severe complications. No firm conclusion about the role of radiotherapy can be drawn from these data because the patients were not randomly chosen to receive radiotherapy and selection was therefore biased. We conclude that most patients with extrahepatic bile duct cancer still die of locoregional disease. Effective adjuvant treatments are needed and should be evaluated in prospective randomized trials.

Definitive radiation therapy for extrahepatic bile duct carcinoma.

Tsujino K, Landry JC, Smith RG, Keller JW, Williams WH, Davis LW.  Radiology 1995 Jul;196(1):275-80

Department of Radiation Oncology, Emory University College of Medicine, Atlanta, Ga, USA.

PURPOSE: To evaluate retrospectively the role of radiation therapy for extrahepatic bile duct (EHBD) carcinoma. MATERIALS AND METHODS: Twenty-seven patients with local-regional EHBD carcinomas were treated with definitive radiation therapy. Radiation therapy was delivered by means of external beam radiation therapy (EBRT) alone or combined with transcatheter iridium-192 brachytherapy. The median total dose was 54 Gy (range, 30-144 Gy). Survival rates were calculated and compared by using the log-rank test. Possible prognostic factors affecting survival were evaluated by means of univariate analysis. RESULTS: The median survival of all patients was 13 months, with 1- and 2-year actuarial survival rates of 52% and 10%, respectively. Univariate analysis revealed that men, patients with tumors limited to the bile duct, and patients receiving EBRT doses of at least 45 Gy had significantly better outcomes. Local-regional recurrence was the main cause of treatment failure (82%). Two patients developed gastric outlet obstruction. CONCLUSION: Patients with locally advanced EHBD carcinomas have a low survival rate. Certain factors, however, appear to have prognostic significance.

Radiotherapy and multimodality management of cholangiocarcinoma.

Urego M, Flickinger JC, Carr BI.   Int J Radiat Oncol Biol Phys 1999 Apr 1;44(1):121-6

Department of Radiation Oncology, The University of Pittsburgh School of Medicine, and the Pittsburgh Cancer Institute, PA 15213, USA.

PURPOSE: To evaluate the results of radiotherapy in cholangiocarcinoma patients managed with various combinations of chemotherapy and surgical resection with selective liver transplantation. METHODS AND MATERIALS: From January 1990 to December 1995, 61 patients with histologically confirmed biliary duct adenocarcinoma were seen in the Radiation Oncology Department of the University of Pittsburgh. Median follow-up was 22 months (1 to 91 months). The extent of surgery was complete resection in 23 patients (including 17 with orthotopic liver transplant), partial resection in 4, and biopsy in 34. All patients had radiotherapy; median dose was 49.5 Gy. Thirty patients received chemotherapy: 5-fluorouracil (5-FU)-leucovorin with interferon alpha (IFNalpha) in 27, and taxol in 3. RESULTS: The median survival was 20 months (95% CI 15-25 months). The 5-year actuarial survival was 23.8 +/- 6.8%. The only significant variable in multivariate analysis was achieving a complete resection with negative margins through conventional surgery or liver transplantation (p = 0.001, hazard rate ratio [HRR] = 0.25, 95% CI 0.12-0.54). Patients with complete resections had a 5-year actuarial survival of 53.5 +/- 10.9%. CONCLUSION: Combined modality therapy that includes complete surgical resection with or without transplantation can be curative in the majority of patients with biliary duct carcinoma. Further study is needed to better define the roles of chemotherapy and radiotherapy in cholangiocarcinoma.