• Hepatocellular carcinoma
• Overall survival
• Radiotherapy
• Staging system
• Stereotactic body radiotherapy

• Hepatocellular carcinoma
• Hypofractionated radiotherapy
• Propensity score
• Stereotactic body radiotherapy
• Surgery
• Transarterial chemoembolization

• MR-guided radiation therapy
• MRI
• adaptive radiotherapy
• hepatocellular carcinoma
• liver
• proton beam therapy
• radiotherapy
• stereotactic ablative radiotherapy
• stereotactic body radiation therapy
• targeted

• Humans
• Carcinoma, Hepatocellular/diagnostic imaging
• Carcinoma, Hepatocellular/radiotherapy
• Radiotherapy, Image-Guided/methods
• Proton Therapy
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/radiotherapy
• Radiotherapy Planning, Computer-Assisted/methods
• Magnetic Resonance Spectroscopy

• Barcelona Clinic Liver Cancer Stage A
• SBRT
• TACE
• hepatocellular carcinoma
• overall survival

• hepatocellular carcinoma
• radiation therapy
• systemic therapy
• transarterial embolization
• transcatheter arterial chemoembolization

• Child-Pugh B and C
• Hepatocellular carcinoma
• Non-transplant candidates
• SBRT

Hepatocellular carcinoma is the fourth leading cause of cancer-related death worldwide. Depending on the extent of disease and competing comorbidities for mortality, multiple liver-directed therapy options exist for the treatment of hepatocellular carcinoma. Advancements in radiation oncology have led to the emergence of stereotactic body radiation therapy as a promising liver-directed therapy, which delivers high doses of radiation with a steep dose gradient to maximize local tumor control and minimize radiation-induced treatment toxicity. In this study, we review the current clinical data as well as the unresolved issues and controversies regarding stereotactic body radiation therapy for hepatocellular carcinoma: (1) Is there a radiation dose–response relationship with hepatocellular carcinoma? (2) What are the optimal dosimetric predictors of radiation-induced liver disease, and do they differ for patients with varying liver function? (3) How do we assess treatment response on imaging? (4) How does stereotactic body radiation therapy compare to other liver-directed therapy modalities, including proton beam therapy? Based on the current literature discussed, this review highlights future possible research and clinical directions.

• HCC
• SABR
• SBRT
• hepatocellular carcinoma
• proton therapy
• stereotactic ablative radiation therapy
• stereotactic body radiation therapy

To evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) in patients with small hepatocellular carcinoma(sHCC) who were ineligible for surgery or ablation therapies.

From March 2011 to December 2012, 28 cases with sHCC which were ineligible or refused surgical resection, transplantation or local ablation were treated with CyberKnife SBRT. Median size of tumors was 2.1 cm (range:1.1–3.0 cm), a dose of 10-15Gy per faction was given over 3–6 consecutive days, resulting in a total dose of 35-60Gy.

The median follow-up period was 36 months, with the response rate of complete response (CR) in 17 cases, partial response (PR) in 8 cases, stable disease (SD) in 2 cases and progressive disease (PD) in one case. Overall response rate was 89.28%. Overall survival rates in 1, 2 and 3 years were 92.86, 85.71 and 78.57%, respectively. Local control rates in 1, 2 and 3 years were 96.43, 92.86 and 89.28%, respectively. No grade ≥ 3 hepatic toxicity was observed.

CyberKnife treatment was a safe and effective option for sHCC, which had shown good local control, high overall survival rates and low toxicity. CyberKnife SBRT could be served as an alternative treatment for patients with sHCC which is unsuitable for surgical treatment or local ablation.

• CyberKnife
• Efficacy
• Hepatocellular carcinoma
• Safety
• Stereotactic body radiation therapy

• charged particle therapy
• external beam radiotherapy
• hepatocellular carcinoma
• intrahepatic cholangiocarcinoma

• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/radiotherapy
• Humans
• Liver Neoplasms/pathology
• Liver Neoplasms/radiotherapy
• Radiosurgery/methods
• Treatment Outcome

Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity. Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis. However, the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment, management of motion and appropriate selection of dose regimen. This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines. Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation. Indeed, certain sub-populations, such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization, have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration. Implementing a liver radiation program requires three primary challenges to be addressed: (1) immobilization and motion management; (2) localization; and (3) dose regimen and constraint selection. Strategies to deal with motion include simple internal target volume (ITV) expansions, non-gated ITV reduction strategies, breath hold methods, and surrogate marker methods to enable gating or tracking. Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy, imaging modalities, and margin management. Finally, a dose response has been demonstrated and dose regimens appear to be converging. A more uniform approach to treatment in terms of technique, dose selection and patient selection will allow us to study liver radiation in larger and, hopefully, multicenter randomized studies.

• Hepatocellular carcinoma
• Liver metastases
• 4DCT
• Image-guided radiotherapy
• Stereotactic body radiation therapy

• Hepatocellular carcinoma
• Liver-directed radiotherapy
• Stereotactic body radiotherapy

To evaluate the safety and efficacy of stereotactic radiotherapy (SRT, both stereotactic body RT [SBRT] and fractionated stereotactic RT [FSRT]) in the treatment of patients with recurrent or second primary mediastinal lymph node metastases (R/SP-MLNMs) originating from non-small cell lung cancer (NSCLC).

Between 10/2006 and 7/2013, patients with R/SP-MLNMsoriginating from NSCLC were enrolled and treated with SRT at our hospital; their data was stored in prospectively-collected database. The enrolled patients were divided into Group A (without prior RT) and Group B (with prior RT). The primary end-point was overall survival (OS). The secondary end-points were the MLNM local control (LC), the time to symptom alleviation, and toxicity using the Common Terminology Criteria for Adverse Events (CTCAE v4.0).

Thirty-three patients were treated (16 in Group A with 19 R/SP-MLNMs and 17 in Group B with 17 R/SP-MLNMs). For the entire cohort, the median OS was 25.5 months with a median follow-up of 20.9 months (range, 3.2-82). The 1-year and 3-year actuarial LC rates were 100% and 86%, respectively. Symptom alleviation was observed in 52% of patients, after a median of 6 days (range, 3-18). CTCAE v4.0 ≥ Grade 3 toxicities occurred in 5 patients (15%; all in Group B); among them, Grade 5 in 2 patients.

We recommend exercising extreme caution in using SRT for R/SP-MLNMs in patients who received prior RT (particularly to LN station 7). For patients without previous RT, SRT appears to be safe and efficacious treatment modality; prospective studies are warranted.

• fractionated stereotactic radiation therapy
• local control
• mediastinum
• non-small cell lung cancer
• stereotactic body radiation therapy

• cyberknife
• hcc
• liver cancer
• radiosurgery

AIM: To compare therapeutic outcomes and adverse events in initial solitary hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) and CyberKnife^®.

METHODS: Seventy three consecutive patients with initial solitary HCC treated with RFA (38 patients; RFA group) and CyberKnife^® (35 patients; CK group) were enrolled in this study. Background factors were compared between the two groups. Local and intrahepatic distant recurrence control, and cumulative survival rates were compared between the two groups. These were determined using the Kaplan-Meier method, and the significance of differences was analyzed by log-rank test. The presence of more grade 3 on CTCAE ver. 4.0 early and late adverse events was investigated.

RESULTS: In background factors, age was significantly higher (P = 0.005) and the tumor diameter was significantly larger (P = 0.001) in the CK group. The 1-year local recurrence control rates were 97.4% and 97.1% in the RFA and CK groups, respectively (P = 0.71); the 1-year intrahepatic distant recurrence control rates were 85.6% and 86.1%, respectively (P = 0.91); and the 1-year cumulative survival rates were 100% and 95.2%, respectively (P = 0.075), showing no significant difference in any rate between the two groups. There were no late adverse event in the RFA group, but 11.4% in the CK group had late adverse events. In the CK group, the Child-Pugh score at 12 mo after treatment was significantly higher than that in the RFA group (P = 0.003) and significantly higher than the score before treatment (P = 0.034).

CONCLUSION: The occurrence of adverse events is a concern, but CyberKnife^® treatment is likely to become an important option for local treatment of early HCC.

• Hepatocellular carcinoma
• Radiofrequency ablation
• Stereotactic body radiotherapy
• CyberKnife^®
• Adverse event

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/secondary
• Carcinoma, Hepatocellular/surgery
• Catheter Ablation/adverse effects
• Catheter Ablation/mortality
• Disease-Free Survival
• Equipment Design
• Female
• Humans
• Kaplan-Meier Estimate
• Liver Neoplasms/mortality
• Liver Neoplasms/pathology
• Liver Neoplasms/surgery
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Pilot Projects
• Radiosurgery/adverse effects
• Radiosurgery/instrumentation
• Radiosurgery/mortality
• Retrospective Studies
• Risk Factors
• Surgical Instruments
• Time Factors
• Tomography, X-Ray Computed
• Treatment Outcome

The CyberKnife® is expected to be a novel local treatment for hepatocellular carcinoma (HCC), however, a long-term follow-up using dynamic computed tomography and magnetic resonance imaging is required to determine the effect of treatment in a number of the affected patients. Therefore, there is a requirement to evaluate procedures for early determination of the effect of CyberKnife treatment. The present study aimed to evaluate the changes in the hemodynamics of the tumors and the hepatic parenchyma surrounding the tumor prior to and following CyberKnife treatment for HCC. A total of 4 HCC patients were enrolled in this study. These patients underwent CyberKnife treatment and were evaluated by image analysis prior to and following treatment using contrast-enhanced ultrasonography (CEUS) with Sonazoid. CEUS was performed prior to treatment, at 2 and 4 weeks post-treatment, and every 4 weeks thereafter for as long as possible. The dynamics of the enhancement of the tumor and the hepatic parenchyma surrounding the tumor in the vascular phase, and the presence or absence of a hypoechoic area in the hepatic parenchyma surrounding the tumor in the post-vascular phase were assessed. Results showed that: i) In the patient with earlier changes, hemodynamic changes were evident in the tumor at 4 weeks and in the hepatic parenchyma surrounding the tumor at 2 weeks post-treatment, respectively; ii) the tumor showed hypoenhancement in all patients; and iii) with regard to findings in the hepatic parenchyma surrounding the tumor, strong hyperenhancement appeared in the vascular phase initially, followed by a hypoechoic area in the post-vascular phase. Evaluation of the hemodynamics of tumors and hepatic parenchyma surrounding the tumor using CEUS with Sonazoid may be therapeutically applicable, as it is less invasive than dynamic computed tomography (CT) and provides an early evaluation of the effectiveness of CyberKnife treatment.

• CyberKnife®
• Sonazoid
• contrast-enhanced ultrasonography
• hepatocellular carcinoma
• stereotactic body radiotherapy

• hepatocellular carcinoma
• proton therapy
• radiation therapy
• radiofrequency ablation
• stereotactic body radiotherapy
• transarterial chemoembolization
• tumor venous thrombosis
• unresectable hepatocellular carcinoma

• Cholangiocarcinoma
• Hepatobiliary cancer
• Hepatocellular carcinoma
• Radiation therapy
• Stereotactic body radiation therapy

• Bile Duct Neoplasms/pathology
• Bile Duct Neoplasms/radiotherapy
• Bile Ducts, Intrahepatic/pathology
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/radiotherapy
• Cholangiocarcinoma/pathology
• Cholangiocarcinoma/radiotherapy
• Combined Modality Therapy
• Humans
• Liver Neoplasms/pathology
• Liver Neoplasms/radiotherapy
• Radiosurgery
• Treatment Outcome

• liver metastasis
• local control
• stereotactic body radiotherapy