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Title: Influence of Tumor Thrombus Location on the Outcome of External-beam Radiation Therapy in Advanced Hepatocellular Carcinoma With Macrovascular Invasion

Abstract

Purpose: The present study evaluates the influence of portal vein (PV) vs. inferior vena cava (IVC) tumor thrombosis sites on the effectiveness of external-beam radiation therapy (EBRT) in advanced hepatocellular carcinoma (HCC) with macrovascular invasion. Methods and Materials: We retrospectively reviewed 181 HCC patients with PV and/or IVC tumor thrombi who were referred for EBRT at our institution between 2000 and 2009. EBRT was designed to focus on the tumor thrombi with or without primary intrahepatic tumors to deliver a median total conventional dose of 50 Gy (range, 30-60 Gy). Predictors of survival were identified using univariate and multivariate analyses. Results: The median survival was 10.2, 7.4, 17.4, and 8.5 months for patients with PV branch, PV trunk, IVC, and PV plus IVC tumor thrombosis, respectively. Unfavorable pretreatment predictors were associated by multivariate analysis with lower albumin and higher {alpha}-fetoprotein levels, poorer Child-Pugh liver function classification, multiple intrahepatic foci, lymph node metastases, thrombus location, less chance to receive post-EBRT transarterial chemoembolization (TACE) and the two-dimensional EBRT technique. In comparison to patients with PV tumor thrombosis, patients with IVC thrombi had a higher occurrence of solitary intrahepatic lesions (p = 0.027), well-controlled intrahepatic tumors (p < 0.001), and a better responsemore » to EBRT (p < 0.001), and they were more likely to receive post-EBRT TACE (p = 0.033). Conclusions: In HCC, patients with IVC thrombus treated with EBRT had a better response rate and longer survival than those with PV thrombus.« less

Authors:
 [1];  [1];  [1]; ;  [2];  [3]
  1. Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China)
  2. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032 (China)
  3. Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China)
Publication Date:
OSTI Identifier:
22149507
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 84; Journal Issue: 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ALBUMINS; CHILDREN; COMPARATIVE EVALUATIONS; GY RANGE 10-100; HEPATOMAS; LIVER; LYMPH NODES; METASTASES; MULTIVARIATE ANALYSIS; PATIENTS; RADIATION DOSES; RADIOTHERAPY; THROMBOSIS; VEINS

Citation Formats

Hou Jiazhou, Zeng Zhaochong, E-mail: zeng.zhaochong@zs-hospital.sh.cn, Zhang Jianying, Fan Jia, Zhou Jian, and Zeng Mengsu. Influence of Tumor Thrombus Location on the Outcome of External-beam Radiation Therapy in Advanced Hepatocellular Carcinoma With Macrovascular Invasion. United States: N. p., 2012. Web. doi:10.1016/J.IJROBP.2011.12.024.
Hou Jiazhou, Zeng Zhaochong, E-mail: zeng.zhaochong@zs-hospital.sh.cn, Zhang Jianying, Fan Jia, Zhou Jian, & Zeng Mengsu. Influence of Tumor Thrombus Location on the Outcome of External-beam Radiation Therapy in Advanced Hepatocellular Carcinoma With Macrovascular Invasion. United States. doi:10.1016/J.IJROBP.2011.12.024.
Hou Jiazhou, Zeng Zhaochong, E-mail: zeng.zhaochong@zs-hospital.sh.cn, Zhang Jianying, Fan Jia, Zhou Jian, and Zeng Mengsu. Mon . "Influence of Tumor Thrombus Location on the Outcome of External-beam Radiation Therapy in Advanced Hepatocellular Carcinoma With Macrovascular Invasion". United States. doi:10.1016/J.IJROBP.2011.12.024.
@article{osti_22149507,
title = {Influence of Tumor Thrombus Location on the Outcome of External-beam Radiation Therapy in Advanced Hepatocellular Carcinoma With Macrovascular Invasion},
author = {Hou Jiazhou and Zeng Zhaochong, E-mail: zeng.zhaochong@zs-hospital.sh.cn and Zhang Jianying and Fan Jia and Zhou Jian and Zeng Mengsu},
abstractNote = {Purpose: The present study evaluates the influence of portal vein (PV) vs. inferior vena cava (IVC) tumor thrombosis sites on the effectiveness of external-beam radiation therapy (EBRT) in advanced hepatocellular carcinoma (HCC) with macrovascular invasion. Methods and Materials: We retrospectively reviewed 181 HCC patients with PV and/or IVC tumor thrombi who were referred for EBRT at our institution between 2000 and 2009. EBRT was designed to focus on the tumor thrombi with or without primary intrahepatic tumors to deliver a median total conventional dose of 50 Gy (range, 30-60 Gy). Predictors of survival were identified using univariate and multivariate analyses. Results: The median survival was 10.2, 7.4, 17.4, and 8.5 months for patients with PV branch, PV trunk, IVC, and PV plus IVC tumor thrombosis, respectively. Unfavorable pretreatment predictors were associated by multivariate analysis with lower albumin and higher {alpha}-fetoprotein levels, poorer Child-Pugh liver function classification, multiple intrahepatic foci, lymph node metastases, thrombus location, less chance to receive post-EBRT transarterial chemoembolization (TACE) and the two-dimensional EBRT technique. In comparison to patients with PV tumor thrombosis, patients with IVC thrombi had a higher occurrence of solitary intrahepatic lesions (p = 0.027), well-controlled intrahepatic tumors (p < 0.001), and a better response to EBRT (p < 0.001), and they were more likely to receive post-EBRT TACE (p = 0.033). Conclusions: In HCC, patients with IVC thrombus treated with EBRT had a better response rate and longer survival than those with PV thrombus.},
doi = {10.1016/J.IJROBP.2011.12.024},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 84,
place = {United States},
year = {Mon Oct 01 00:00:00 EDT 2012},
month = {Mon Oct 01 00:00:00 EDT 2012}
}
  • Purpose: Defining hepatocellular carcinoma (HCC) gross tumor volume (GTV) requires multimodal imaging, acquired in different perfusion phases. The purposes of this study were to evaluate the variability in contouring and to establish guidelines and educational recommendations for reproducible HCC contouring for treatment planning. Methods and Materials: Anonymous, multiphasic planning computed tomography scans obtained from 3 patients with HCC were identified and distributed to a panel of 11 gastrointestinal radiation oncologists. Panelists were asked the number of HCC cases they treated in the past year. Case 1 had no vascular involvement, case 2 had extensive portal vein involvement, and case 3more » had minor branched portal vein involvement. The agreement between the contoured total GTVs (primary + vascular GTV) was assessed using the generalized kappa statistic. Agreement interpretation was evaluated using Landis and Koch's interpretation of strength of agreement. The S95 contour, defined using the simultaneous truth and performance level estimation (STAPLE) algorithm consensus at the 95% confidence level, was created for each case. Results: Of the 11 panelists, 3 had treated >25 cases in the past year, 2 had treated 10 to 25 cases, 2 had treated 5 to 10 cases, 2 had treated 1 to 5 cases, 1 had treated 0 cases, and 1 did not respond. Near perfect agreement was seen for case 1, and substantial agreement was seen for cases 2 and 3. For case 2, there was significant heterogeneity in the volume identified as tumor thrombus (range 0.58-40.45 cc). For case 3, 2 panelists did not include the branched portal vein thrombus, and 7 panelists contoured thrombus separately from the primary tumor, also showing significant heterogeneity in volume of tumor thrombus (range 4.52-34.27 cc). Conclusions: In a group of experts, excellent agreement was seen in contouring total GTV. Heterogeneity exists in the definition of portal vein thrombus that may impact treatment planning, especially if differential dosing is contemplated. Guidelines for HCC GTV contouring are recommended.« less
  • Purpose: We sought to determine efficacy, safety, and outcome of stereotactic hypofractionated radiation therapy (SHORT) as a suitable bridging therapy for patients awaiting liver transplantation (LT) for hepatocellular carcinoma (HCC). We also examined histological response to radiation in the resected or explanted livers. Methods and Materials: Between August 2007 and January 2009, 18 patients with 21 lesions received SHORT. A median total dose of 50 Gy was delivered in 10 fractions. Three patients underwent either chemoembolization (n = 1) or radiofrequency ablation (n = 2) prior to SHORT. Radiographic response was based on computed tomography evaluation at 3 months aftermore » SHORT. Histological response as a percentage of tumor necrosis was assessed by a quantitative morphometric method. Results: Six of 18 patients were delisted because of progression (n = 3) or other causes (n = 3). Twelve patients successfully underwent major hepatic resection (n = 1) or LT (n = 11) at a median follow-up of 6.3 months (range, 0.6-11.6 months) after completion of SHORT. No patient developed gastrointestinal toxicity Grade {>=}3 or radiation-induced liver disease. Ten patients with 11 lesions were evaluable for pathological response. Two lesions had 100% necrosis, three lesions had {>=}50% necrosis, four lesions had {<=}50% necrosis, and two lesions had no necrosis. All patients were alive after LT and/or major hepatic resection at a median follow-up of 19.6 months. Conclusions: SHORT is an effective bridging therapy for patients awaiting LT for HCC. It provides excellent in-field control with minimal side effects, helps to downsize or stabilize tumors prior to LT, and achieves good pathological response.« less
  • Purpose: To evaluate the potential role of external beam radiation therapy (EBRT) in the treatment of patients with hepatocellular carcinoma (HCC) who have portal vein (PV) and/or inferior vena cava (IVC) tumor thrombi. Methods and materials: One hundred fifty-eight patients with HCC who had PV and/or IVC tumor thrombus were reviewed and analyzed by Kaplan-Meier and Cox regression analysis. Forty-four patients with HCC who received local limited EBRT (in addition to other treatment modalities) were classified as the EBRT group. The total radiation dose was 36-60 Gy (median, 50 Gy) and was focused on the tumor thrombi. One hundred fourteenmore » patients with HCC who did not receive EBRT were selected from hospitalized patients with HCC who had PV and/or IVC thrombi during the same period; these were classified as the non-EBRT group, and their intrahepatic tumors were treated with transarterial chemoembolization or resection, on the basis of the patients' status. Parameters observed included survival rates and the tumor thrombus response to EBRT as seen on CT scan or MRI. Results: Of the 44 patients who received EBRT, 15 (34.1%) showed complete disappearance of tumor thrombi, 5 (11.4%) were in partial remission, 23 (52.3%) were stable in their tumor thrombi, and 1 (2.3%) showed disease progression at the end of the study period. The median survival was 8 months, and the 1-year survival rate was 34.8% in the EBRT group. In the non-EBRT group, the median survival and 1-year survival rates were 4 months and 11.4%, respectively. In stepwise multivariate analysis, EBRT showed a strongly protective value (relative risk = 0.324, p < 0.001). Survival was not related to intrahepatic tumor status in the non-EBRT patients. However, in the EBRT group, poorer prognosis was significantly related to intrahepatic multifocal or diffusion lesions, and the most common reason for death was liver failure caused by uncontrolled intrahepatic disease. Conclusion: Although EBRT is palliative in intent, it is preferred for prolonging survival in the treatment of tumor thrombi.« less
  • Purpose: To evaluate the safety and efficacy of three-dimensional conformal radiotherapy (3D-CRT) using single photon emission computed tomography (SPECT) in unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Methods and Materials: Patients with HCC with PVTT in the first branch and/or main trunk were selected for this study. The optimal beam directions for 3D-CRT were explored using a Tc-99m-galactosyl human serum albumin SPECT image for guidance. The SPECT image was classified as either wedge type or localized type. The clinical target volume to a total dose of 45 or 50 Gy per 18-20 fractions included the main tumormore » and PVTT in the wedge type and PVTT alone in the localized type. Results: Twenty-six patients were enrolled: 18 with wedge type and 8 with localized type. Mean tumor size was 7.1 cm (range, 4.4-12.3 cm). Clinical target volumes of wedge type vs. localized type were 111.2 cm{sup 3} vs. 48.4 cm{sup 3} (p = 0.010), respectively. Mean dose to normal liver and mean dose to functional liver were 1185 cGy and 988 cGy (p = 0.001) in wedge type and 1046 cGy and 1043 cGy (p = 0.658) in localized type, respectively. Despite an incidence of Child-Pugh B and C of 57.7%, no patients experienced radiation-induced liver disease. The progression of PVTT was inhibited, with an incidence of 92.2%; survival rates at 1 and 2 years were 44% and 30%, respectively. Conclusion: Single photon emission computed tomography-based 3D-CRT enables irradiation of both the main tumor and PVTT with low toxicity and promising survival.« less
  • Purpose: To assess the feasibility and efficacy of single photon emission computed tomography-based three-dimensional conformal radiotherapy (SPECT-B 3D-CRT) for large hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Methods and Materials: HCC patients with PVTT in the first branch or main trunk, 8 cm or greater in size, were admitted to the study. SPECT, using Tc-99m-galactosyl human serum albumin, was used in radiation treatment planning to explore the optimal irradiation beam angle. SPECT enabled the minimum possible irradiation of functional liver (FL). Clinical target volume (CTV) included the main tumor and PVTT. SPECT-B 3D-CRT targeted the CTV to amore » total dose of 45 Gy/18 fractions. HCC outside the CTV was treated by transcatheter arterial chemoembolization (TACE). Results: Nineteen cases were enrolled in this study. The mean maximum dimension, mean CTV, and mean dose to FL were 11.0 cm (range, 8.0-20.0), 435 cm{sup 3} (range, 60-2,535), and 1,102 cGy (range, 691-1,695), respectively. Follow-up SPECT demonstrated radiation-induced dysfunctional liver. Despite the inclusion of 6 cases of Child-Pugh B or C, no patients experienced Grade 3 or worse radiation-induced liver disease. The cumulative non-progression rates of PVTT and PVTT plus main tumor were 78.0 and 43.2%, respectively. Survival rates at 1 and 2 years were 47.4 and 23.7%, respectively. Conclusions: SPECT-B 3D-CRT with TACE appears to be tolerable to cirrhotic liver and to provide promising prognosis for patients with HCC sized 8 cm or more, in comparison with previous treatment methods. A longer follow-up period is required to evaluate these findings.« less