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      Effectiveness of Stereotactic Body Radiotherapy for Hepatocellular Carcinoma with Portal Vein and/or Inferior Vena Cava Tumor Thrombosis

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          Abstract

          Background

          To report the feasibility, efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for the treatment of portal vein tumor thrombosis (PVTT) and/or inferior vena cava tumor thrombosis (IVCTT) in patients with advanced hepatocellular carcinoma (HCC).

          Materials and methods

          Forty-one patients treated with SBRT using volumetric modulated arc therapy (VMAT) for HCC with PVTT/IVCTT between July 2010 and May 2012 were analyzed. Of these, 33 had PVTT and 8 had IVCTT. SBRT was designed to target the tumor thrombosis and deliver a median total dose of 36 Gy (range, 30–48 Gy) in six fractions during two weeks.

          Results

          The median follow-up was 10.0 months. At the time of analysis, 15 (36.6%) achieved complete response, 16 (39.0%) achieved partial response, 7 (17.1%) patients were stable, and three (7.3%) patients showed progressive disease. No treatment-related Grade 4/5 toxicity was seen within three months after SBRT. One patient had Grade 3 elevation of bilirubin. The one-year overall survival rate was 50.3%, with a median survival of 13.0 months. The only independent predictive factor associated with better survival was response to radiotherapy.

          Conclusions

          VMAT-based SBRT is a safe and effective treatment option for PVTT/IVCTT in HCC. Prospective randomized controlled trials are warranted to validate the role of SBRT in these patients.

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          Most cited references 23

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          Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials.

          This study analyzed the natural history and prognostic factors of patients with nonsurgical hepatocellular carcinoma (HCC). Twenty variables from 102 cirrhotic patients with HCC who were not treated within prospective randomized controlled trials (RCT) were investigated through uni- and multivariate analyses. None of them was suitable for radical therapies (surgical resection, liver transplantation, or ethanol injection) or presented end-stage disease as reflected by an Okuda stage 3 or a Performance Status >/=3. Sixty-five patients were Child-Pugh A, 34 were B, and 3 were C. Most of them exhibited a preserved Performance Status Test (PST) (0 = 56; 1 = 38; 2 = 8). Tumor was solitary in 26 (
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            Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

            To report outcomes of a phase I study of individualized stereotactic body radiotherapy treatment (SBRT) for unresectable hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC). Patients with unresectable HCC or IHC, and who are not suitable for standard therapies, were eligible for six-fraction SBRT during 2 weeks. Radiation dose was dependent on the volume of liver irradiated and the estimated risk of liver toxicity based on a normal tissue complication model. Toxicity risk was escalated from 5% to 10% and 20%, within three liver volume-irradiated strata, provided at least three patients were without toxicity at 3 months after SBRT. Forty-one patients with unresectable Child-Pugh A HCC (n = 31) or IHC (n = 10) completed six-fraction SBRT. Five patients (12%) had grade 3 liver enzymes at baseline. The median tumor size was 173 mL (9 to 1,913 mL). The median dose was 36.0 Gy (24.0 to 54.0 Gy). No radiation-induced liver disease or treatment-related grade 4/5 toxicity was seen within 3 months after SBRT. Grade 3 liver enzymes were seen in five patients (12%). Two patients (5%) with IHC developed transient biliary obstruction after the first few fractions. Seven patients (five HCC, two IHC) had decline in liver function from Child-Pugh class A to B within 3 months after SBRT. Median survival of HCC and IHC patients was 11.7 months (95% CI, 9.2 to 21.6 months) and 15.0 months (95% CI, 6.5 to 29.0 months), respectively. Individualized six-fraction SBRT is a safe treatment for unresectable HCC and IHC.
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              Phase I study of individualized stereotactic body radiotherapy of liver metastases.

              To report on the outcomes of a phase I study of stereotactic body radiotherapy (SBRT) for treatment of liver metastases. Patients with liver metastases that were inoperable or medically unsuitable for resection, and who were not candidates for standard therapies, were eligible for this phase I study of individualized SBRT. Individualized radiation doses were chosen to maintain the same nominal risk of radiation-induced liver disease (RILD) for three estimated risk levels (5%, 10%, and 20%). Additional patients were treated at the maximal study dose (MSD) in an expanded cohort. Median SBRT dose was 41.8 Gy (range, 27.7 to 60 Gy) in six fractions over 2 weeks. Sixty-eight patients with inoperable colorectal (n = 40), breast (n = 12), or other (n = 16) liver metastases were treated. Median tumor volume was 75.2 mL (range, 1.19 to 3,090 mL). The highest RILD risk level investigated was safe, with no dose-limiting toxicity. Two grade 3 liver enzyme changes occurred, but no RILD or other grade 3 to 5 liver toxicity was seen, for a low estimated risk of serious liver toxicity (95% CI, 0 to 5.3%). Six (9%) acute grade 3 toxicities (two gastritis, two nausea, lethargy, and thrombocytopenia) and one (1%) grade 4 toxicity (thrombocytopenia) were seen. The 1-year local control rate was 71% (95 CI, 58% to 85%). The median overall survival was 17.6 months (95% CI, 10.4 to 38.1 months). Individualized six-fraction liver metastases SBRT is safe, with sustained local control observed in the majority of patients.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                30 May 2013
                : 8
                : 5
                Affiliations
                State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China
                Yonsei University College of Medicine, Korea
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MX L. Zhang L. Zhao QQL ZZF MZL. Performed the experiments: MX L. Zhang L. Zhao QQL SPG XWD XYH. Analyzed the data: MX L. Zhang XWD XYH ZZF MZL. Contributed reagents/materials/analysis tools: QQL XWD XYH. Wrote the paper: MZ L. Zhang MZL.

                Article
                PONE-D-13-04621
                10.1371/journal.pone.0063864
                3667854
                23737955

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Pages: 7
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Mathematics
                Statistics
                Biostatistics
                Medicine
                Clinical Research Design
                Retrospective Studies
                Oncology
                Cancer Treatment
                Radiation Therapy
                Cancers and Neoplasms
                Gastrointestinal Tumors
                Hepatocellular Carcinoma
                Radiotherapy
                Physics
                Medical Physics

                Uncategorized

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