Consideration of the role of radiotherapy for unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 75 patients.

UNLABELLED: The role of radiotherapy in the treatment of intrahepatic cholangiocarcinoma is controversial. We undertook this study to determine if radiotherapy is appropriate for patients with unresectable or lymph node metastatic intrahepatic cholangiocarcinoma. METHODS AND MATERIALS: The records of 75 patients with intrahepatic cholangiocarcinoma were reviewed and analyzed by Kaplan-Meier method and Cox proportional hazards analysis. Thirty-eight patients who received limited local external-beam radiotherapy were classified as the radiotherapy group. This group included nine patients with resected intrahepatic cholangiocarcinoma with macroscopic residual lymph nodes receiving postoperative external-beam radiotherapy, seven patients with postoperative recurrences in lymph nodes receiving external-beam radiotherapy for salvage failure after treatment with surgery alone, and 22 patients with unresectable intrahepatic cholangiocarcinoma. The median total dose was 50 Gy (range, 30-60 Gy) in daily doses of 2 Gy/fraction, five times a week. Thirty-seven patients with intrahepatic cholangiocarcinoma (including 14 with resectable disease and synchronous or asynchronous lymph node metastases, and 23 with unresectable disease) who did not receive external-beam radiotherapy were selected from hospitalized patients in the same period and were classified as the nonexternal-beam radiotherapy group. Parameters observed included survival rates and tumor response to external-beam radiotherapy demonstrated both by clinical symptoms and by computed tomography scan/magnetic resonance image. RESULTS: Objective responses to external-beam radiotherapy were 36.4% for intrahepatic tumors in 22 patients with unresectable intrahepatic cholangiocarcinoma, and 52% for lymph node metastases in 25 patients with resectable or unresectable intrahepatic cholangiocarcinoma. Pain was relieved in 90% of the patients who received external-beam radiotherapy. The survival rates at 1 and 2 years for patients with unresectable intrahepatic cholangiocarcinoma treated with external-beam radiotherapy (n = 22) compared with those who did not receive external-beam radiotherapy (n = 23) were 36.1% versus 19.0% and 5.2% versus 4.7%, respectively (log-rank P = 0.021). The survival experience of the 16 patients with lymph node metastases (synchronous or asynchronous) who underwent hepatectomy combined with external-beam radiotherapy was superior to that of the group (n = 14) who did not receive external-beam radiotherapy (median survival, 468 and 211 days, respectively; log-rank P = 0.075). These results show that external-beam radiotherapy influenced the survival in the patients with unresectable intrahepatic cholangiocarcinoma or lymph node metastases. The most common reason for death was liver failure caused by uncontrolled intrahepatic disease. Grade 3 toxicity in the external-beam radiotherapy group was infrequent. CONCLUSION: External-beam radiotherapy seems to improve the prognosis of patients with unresectable intrahepatic cholangiocarcinoma and deserves further study.

Consideration of role of radiotherapy for lymph node metastases in patients with HCC: retrospective analysis for prognostic factors from 125 patients.

OBJECTIVES: To evaluate the role of radiotherapy (RT) for hepatocellular carcinoma (HCC) patients with abdominal lymph node (LN) metastasis at our institution in the past 7 years. METHODS AND MATERIALS: We identified 125 patients with HCC metastasis to regional LNs treated with or without external beam RT (EBRT) between 1998 and 2004. Clinical characteristics collected included alpha-fetoprotein status, gamma-glutamyltransferase, status of intrahepatic tumors (size and number), previous therapy for intrahepatic tumors, metastatic LN status (location, number, and size), tumor thrombi, and Child-Pugh classification. Of the 125 patients, 62 received local limited EBRT and were classified as the EBRT group. They received locoregional LN irradiation. The tumor dose ranged from 40 to 60 Gy in daily 2.0-Gy fractions, 5 times weekly. Another 63 patients, who did not receive EBRT, were selected from hospitalized patients in the same period and were classified as the non-EBRT group. The parameters studied included survival rates and tumor response to EBRT both as demonstrated by clinical symptoms and as seen on CT. The Kaplan-Meier method was used to evaluate the survival rates, and the Cox regression model was used to identify predictors of outcome. RESULTS: After EBRT, partial responses and complete responses were observed in 37.1% and 59.7% of patients, respectively. The median survival was 9.4 months (95% confidence interval 5.8-13.0) for the EBRT group and 3.3 months (95% confidence interval, 2.7-3.9) for the non-EBRT group (p < 0.001). Multivariate analysis showed that multiple intrahepatic primary tumors, occurrence of tumor thrombi, no therapy for intrahepatic tumors, and greater Child-Pugh classification were related to a poorer prognosis in all patients. In the EBRT group, the survival periods decreased as the distance of LN involvement from the liver increased (following the natural flow of lymph) and was also associated with the intrahepatic primary tumor size. The incidence of death resulting from LN-related complications was lower in the EBRT group. CONCLUSION: Lymph node metastasis from HCC is sensitive to EBRT. EBRT with 25 fractions of 2 Gy is an effective palliative treatment for patients with LN metastases from HCC presenting with good performance status and may prolong overall survival.

Radiation therapy for adrenal gland metastases from hepatocellular carcinoma.

BACKGROUND: The adrenal gland is a common site of extrahepatic metastases from hepatocellular carcinoma. However, it has been the subject of few studies, and the optimal treatment remains unclear. Methods previously tried for the management of adrenal gland metastasis of hepatocellular carcinoma included surgical resection, transarterial chemoembolization or percutaneous ethanol injection, on the basis of case reports. External beam radiation therapy has seldom been applied for patients with adrenal gland metastases. METHODS: We retrospectively studied 22 patients with adrenal metastases from hepatocellular carcinoma who were treated with limited-field external beam radiation therapy. The radiation dose to the adrenal lesion ranged from 36 to 54 (median 50) Gy, while the intrahepatic lesions were treated with either surgical resection or transarterial chemoembolization. RESULTS: Among the 14 patients who had pain related to adrenal metastases, 11 (78.6%) had complete pain relief without medication that lasted until death. Two (14.3%) patients had marked pain relief, but still required analgesics. Partial responses were observed in 73% of the patients. The median survival period for all patients was 10 months. No patient died from complications related to adrenal metastasis. Adverse effects were mild. CONCLUSION: Adrenal metastases from hepatocellular carcinoma are sensitive to radiation treatment. Radiation therapy with 50 Gy for adrenal gland metastases is a good palliative therapy with reasonable safety.

A comparison of chemoembolization combination with and without radiotherapy for unresectable hepatocellular carcinoma.

PURPOSE: This study evaluated the effect of transcatheter arterial chem-oembolization combined with external beam radiotherapy on the response rates and sur vival of patients with unresectable hepato-cellular carcinoma. Transcatheter arterial chemoembolization is frequently used for the treatment of this cancer, but complete or massive necrosis is seldom observed. Historically, radiotherapy for hepatocellular carcinoma has yielded poor long-term survival. Multimodality therapy has been initiated in an effort to improve survival statistics. PATIENTS AND METHODS: We retrospectively studied 203 patients with unresectable hepa-tocellular carcinoma, who were free of tumor thrombus, lymph node involvement, or extrahepatic metastasis based on computed tomography scans of the chest and abdomen. Among the 203 patients who received transcatheter ar terial chemoembolization as initial therapy, 54 also received combination therapy with external beam radiotherapy. Tumor response rate, survival, and failure patterns were analyzed and compared between the two groups. RESULTS: Objective responses (complete and partial responses) on computed tomography study were obser ved in 31% and 76% of patients in the non-radiotherapy and radiotherapy groups, respectively. Overall survival rates in the patients in the radiotherapy group were 71.5%, 42.3%, and 24.0% at 1, 2, and 3 years, respectively, improved over the non-radiotherapy group rates of 59.6%, 26.5%, and 11.1% at 1, 2, and 3 years, respectively. Intrahepatic failure was lower in the radiotherapy group than in the non-radiotherapy group, but the difference was not significant. Side effects from radiotherapy were common, but rarely severe. CONCLUSIONS: This retrospective study suggests that the outcome of unresectable hepatocellular carcinoma can be influenced by radiation therapy, but a prospective randomized trial would be necessary to draw definitive conclusions.