# Radiation Oncology/Bile duct/Unresectable Disease/EBRT

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External Beam RT for unresectable disease
* Kyoto Japan PMID 15966192 -- Unresectable hilar cholangiocarcinoma completely reduced by external radiation therapy. (2005 Kaido T, Hepatogastroenterology. 2005 May-Jun;52(63):725-7.)
** Case report - 1 patient, 4 years out, with complete resolution after RT (EBRT 60 Gy in 30 sessions)
* Yamagata Japan PMID 12828045 -- Management of unresectable hilar bile duct cancer--preoperative diagnosis, treatment selection, and clinical outcome. (2003 Hirai I, Hepatogastroenterology. 2003 May-Jun;50(51):614-20.)
** Retrospective. 40 nonsurgical patients.
** Reasons for no resection: extensive vessel invasion, broad biliary extension
** RT better prognosis than no RT (p=0.01)
** Conclusion: "Portal and arterial invasion were the principal reasons for unresectability. Use of an expandable metallic stent or radiation therapy, and a total bilirubin level of less than 2 mg/dL on discharge, were factors that enhanced survival in unresectable cases, but distant metastasis, dissemination, and poor general condition or liver function were negative factors for survival."
* Miami 1985-97 PMID 11677948 -- Management of hilar bile duct carcinoma. (2001 Bathe OF, Hepatogastroenterology. 2001 Sep-Oct;48(41):1289-94.)
** Retrospective. 55 patients, 19 curative resection.
** 2-year survival longer in resection 47% vs. 18% (p=0.03)
** No benefit to RT (either postoperative RT or in unresectable disease)
** Conclusion: "Locoregional extent of disease is the greatest problem in cases of proximal bile duct cancers. Resection provides the best hope for long-term survival, but new adjuvant strategies are needed."
* Ajou Korea 1990-93 PMID 11677950 -- The experiences of hilar skeletonization for the treatment of locally advanced proximal bile duct cancer. (2001 Kim MW, Hepatogastroenterology. 2001 Sep-Oct;48(41):1298-301.)
** Prospective. 45 patients (16 curative resection, 15 noncurative resection, 14 nonresection)
** Survival same for curative resection and noncurative resection + RT (p=NS)
** Conclusion: "he resection is the treatment of choice for locally advanced proximal bile duct cancer, if resectable and the noncurative resection followed by postoperative external radiotherapy may be beneficial to the patients with locally advanced proximal bile duct cancer."
* Amsterdam Netherlands 1992-99 PMID 11354319 -- Palliative treatment in patients with unresectable hilar cholangiocarcinoma: results of endoscopic drainage in patients with type III and IV hilar cholangiocarcinoma. (2001 Gerhards MF, Eur J Surg. 2001 Apr;167(4):274-80.)
** Retrospective. 41 patients treated with biliary drainage, 12 also PTBD
** Radiotherapy had no influence on survival (unclear from abstract if EBRT or BT)
** Conclusion: "The patients in this series had relatively long survival times, during which they had a substantial number of complications predominantly related to biliary drainage. Because biliary-enteric bypass operations result in effective relief of symptoms and excellent palliation, we suggest that when an exploration is done for patients with type III and IV tumours, a bypass should be made."
* Kagoshima Japan PMID 11064386 -- Length and quality of survival following external beam radiotherapy combined with expandable metallic stent for unresectable hilar cholangiocarcinoma. (2000 Shinchi H, J Surg Oncol. 2000 Oct;75(2):89-94.)
** Retrospective. 51 patients, 30 stent + EBRT vs. 10 stent alone vs. 11 PTBD alone
** Mean survival: PTBD 4.4 months vs. stent alone 6.4 months vs. stent + EBRT 10.6 months (p<0.05)
** Quality of survival: PTBD 57.7 KPS vs. stent alone 68.1 KPS vs. stent + EBRT 74.9 KPS (p<0.01)
** Conclusion: "These results indicate that external radiotherapy combined with metallic biliary endoprosthesis can increase the length and quality of survival and consequently provide a definite palliative benefit for patients with unresectable hilar cholangiocarcinoma."
* NHS Trust UK PMID 9038668 -- A retrospective comparison of endoscopic stenting alone with stenting and radiotherapy in non-resectable cholangiocarcinoma. (1996 Bowling TE, Gut. 1996 Dec;39(96):852-5.)
** Case-control. 56 patients treated with stenting alone (28 pts) or stenting + ILRT/EBRT (28 pts)
** Median survival: stenting 7 months vs. stenting + RT 10 months (p=0.06), but survival advantage for RT during first 9 months
** More RT patients required stent changes and had longer hospital stays
** Conclusion: "The survival advantage of radiotherapy in those with a type II/III stricture is seen only in the first 10 months after diagnosis. The costs of radiotherapy and significantly increased time spent in hospital, however, raise doubts over its routine use in the management of non-resectable cholangiocarcinoma."
* Jefferson 1983-1992 PMID 7480704 -- Cholangiocarcinoma: clinical significance of tumor location along the extrahepatic bile duct. (1995 Alden ME, Radiology. 1995 Nov;197(2):511-6.)
** Retrospective. 81 pts, 56 proximal, 25 distal. Median follow-up 28 months
** 5-year OS: proximal 13% vs. distal 53% (p<0.01)
** Proximal CA (RT or resection + RT or palliation): median survival no RT 6 mo vs. RT 17 mo (p=0.01). No benefit for resection in presence of RT
** Distal CA (resection +/- RT): no benefit for RT after resection
** Conclusion: "Patients with proximal cancer should undergo primary RT, and expectations should be limited. Patients with distal cancer should undergo resection, and RT may not be needed."
* Mayo 1980-84 PMID 7537346 -- "Natural history" of unresected cholangiocarcinoma: patient outcome after noncurative intervention. (1995 Farley DR, Mayo Clin Proc 1995; 70:425-9)
** Retrospective. 103 patients without curative surgery. 68% biopsy-proven mets (18% LN+)
** 1-year and 5-year OS: 53% and 4%
** Survival advantage if palliative surgery or other palliative intervention
** Conclusion: "Unresected cholangiocarcinoma is a rapidly fatal process, but early intervention affects the course of the disease and likely prolongs patient survival."
* Cleveland Clinic 1977-85 PMID 1709795 -- Role of radiation after operative palliation in cancer of the proximal bile ducts. (1991 Grove MK, Am J Surg 1991; 161:454-8.)
** 51 patients with proximal bile duct CA, 60% local, 40% extensive hepatic infiltration or distant mets. 44 patients dilated/intubated and analyzed
** Palliative RT (mean 37.7 Gy) in 30 (59%) patients. 3 received <10 Gy for intolerance or early death. 1 received BT
*** Metastatic disease: median survival 2.6 months -RT vs. 1.8 months +RT (p=NS)
*** Local disease: median survival -RT 2.2 months vs. 12.2 months EBRT (p=0.005)
** Conclusion: "These findings suggest that the addition of external beam radiation improves survival in patients undergoing palliative treatment of hilar tumors."
* Leiden Netherlands 1968-83 PMID 1687249 -- External radiotherapy and extrahepatic bile duct cancer. (1991 Tollenaar RA, Eur J Surg 1991; 157:587-9.)
** Retrospective. 55 patients treated with surgery, 29% received adjuvant RT (40-60 Gy)
** Median survival: overall 4 months, surgery only 3 months vs. adjuvant RT 16 months
** Conclusion: " 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."
* International PMID 1705417 -- Surgical management of 552 carcinomas of the extrahepatic bile ducts (gallbladder and periampullary tumors excluded). Results of the French Surgical Association Survey. (1991 Reding R, Ann Surg. 1991 Mar;213(3):236-41.)
** Retrospective. 552 cases treated at 55 centers. Extrahepatic BD only
** Please see Radiation Oncology/Bile duct/Surgery for surgical details
** Additional palliative RT 12 months (11-35) vs. surgical palliation only 8 months (3-14) P<0.1
** However, total number of patients treated with RT in both adjuvant and palliative setting was 27
* Hopkins PMID 1688486 -- Management of proximal cholangiocarcinomas by surgical resection and radiotherapy. (1990 Cameron JL, Am J Surg 1990; 159:91-7; discussion 97–8.)
** Retrospective. 96 patients, 55% resected (41% curative resection), 45% palliative stenting.
** 5-year OS: resected 8% vs. stented 0%
** RT given as EBRT 50-60Gy + some patients BT 2Gy boost: Adjuvant RT 72% (38/53), 51% BT boost;, palliative RT 58% (25/43), 10% BT boost
*** Adjuvant RT: 3-year OS 31% both groups (p=NS), but all long term survivors received RT
*** Palliative RT: 1-year OS 38% RT vs 9% no RT (p<0.05)
*** RT significantly extended survival in patients undergoing palliative stenting, but not in those undergoing resection.
** Conclusion: "We conclude that surgical resection of proximal cholangiocarcinomas can be performed safely and that it significantly prolongs survival."
* Amsterdam PMID 2162565 -- Results of radiation therapy in carcinoma of the proximal bile duct (Klatskin tumor). (1990 Gonzales Gonzales D, Semin Liver Dis 1990; 10:131-41.)
** Retrospective. 40 patients.
** Median survival: 12.3 months
** Median survival of patients receiving >40 Gy (EBRT only) was nearly twice that of those receiving <40 Gy (as reported by PMID 12095564)
* PMID 3980281 -- Primary cancers of extrahepatic biliary passages. (1985 Mittal B, Int J Radiat Oncol Biol Phys. 1985 Apr;11(4):849-54.)
** Retrospective. 22 patients.
** Failure or persistence: liver 67%, tumor bed 56%, peritoneou 22%, LN 17%
** Median survival 6.8 months
** RT >70 TDF 11 months vs. <70 TDF 4.4 months. All long term survivors >70 TDF
* Louisiana PMID 2983445 -- Malignant stricture at the confluence of the biliary tree: diagnosis and management. (1985 Beazley RM, Surg Annu. 1985;17:125-41.)
* Yale 1967-82 PMID 6439702 -- The role of radiation therapy in carcinoma of the extrahepatic bile ducts. (1984 Fogel TD, Int J Radiat Oncol Biol Phys. 1984 Dec;10(12):2251-8.)
** Retrospective. 34 patients.
** Median 11 months, 5-year OS 6%
* Japan 1974-81 PMID 6402803 -- Radiation therapy of carcinoma of the extrahepatic bile ducts. (1983 Hishikawa Y, Radiology. 1983 Mar;146(3):787-9.)
** Retrospective. 25 patients. EBRT (10-60Gy, 21 pts >40 Gy). 22 surgical stent placement
** Side effects: loss of appetite, nausea, vomiting, general fatigue, and duodenal ulcer
** Mean survival: 9.2 months, longest 6.5+ years
** Conclusion: "Radiation therapy proved effective in treatment of carcinoma of the extrahepatic bile ducts in terms of palliation and prognosis."
* PMID 7404288 -- Carcinoma of the bile ducts. (1980 Lees CD, Surg Gynecol Obstet. 1980 Aug;151(2):193-8.)
* Wash U PMID 78508 -- Radiotherapy of carcinomas of the extrahepatic biliary system. (1978 Pilepich MV, Radiology. 1978 Jun;127(3):767-70.)
** 11 patients. 4 adjuvant RT, 2 curative RT, 5 palliative RT
** Long-term DFS observed in some radically treated patients
** Conclusion: "The results suggest that radiotherapy may contribute to cure not only when used as a surgical adjuvant but also as the sole treatment modality in unresectable but still localized carcinomas of the bile ducts."
* PMID 74280 -- Carcinoma of the gallbladder or extrahepatic bile ducts: the role of radiotherapy. (1978 Hanna SS, Can Med Assoc J. 1978 Jan 7;118(1):59-61.)
* PMID 71193 -- Radiation therapy of carcinoma of gallbladder and biliary tract. (1977 Smoron GL, Cancer. 1977 Oct;40(4):1422-4.)
** 14 patients. Several long term survivors
** Conclusion: "A plea is made for utilizing planned radiotherapy and chemotherapy for tumors arising in the biliary tract.
* Van Nuys CA PMID 4129581 -- Cancer of the common hepatic bile ducts--palliative radiotherapy. (1973 Green N, Radiology. 1973 Dec;109(3):687-9.)
** Case report. 4 patients treated with cobalt.
** Mean survival 17 months