Sang Min Yoon

Stereotactic body radiation therapy as an alternative treatment for small hepatocellular carcinoma.

Background Even with early stage hepatocellular carcinoma (HCC), patients are often ineligible for surgical resection, transplantation, or local ablation due to advanced cirrhosis, donor shortage, or difficult location. Stereotactic body radiation therapy (SBRT) has been established as a standard treatment option for patients with stage I lung cancer, who are not eligible for surgery, and may be a promising alternative treatment for patients with small HCC who are not eligible for curative treatment. Materials and Methods A registry database of 93 patients who were treated with SBRT for HCC between 2007 and 2009 was analyzed. A dose of 10-20 Gy per fraction was given over 3-4 consecutive days, resulting in a total dose of 30-60 Gy. The tumor response was determined using dynamic computed tomography or magnetic resonance imaging, which was performed 3 months after completion of SBRT. Results The median follow-up period was 25.6 months. Median size of tumors was 2 cm (range: 1-6 cm). Overall patients’ survival rates at 1 and 3 years were 86.0% and 53.8%, respectively. Complete and partial tumor response were achieved in 15.5% and 45.7% of patients, respectively. Local recurrence-free survival rate was 92.1% at 3 years. Most local failures were found in patients with HCCs > 3 cm, and local control rate at 3 years was 76.3% in patients with HCC > 3 cm, 93.3% in patients with tumors between 2.1-3 cm, and 100% in patients with tumors ≤ 2 cm, respectively. Out-of-field intrahepatic recurrence-free survival rates at 1 and 3 years were 51.9% and 32.4%, respectively. Grade ≥ 3 hepatic toxicity was observed in 6 (6.5%). Conclusions SBRT was effective in local control of small HCC. SBRT may be a promising alternative treatment for patients with small HCC which is unsuitable for other curative therapy.

Radiation-induced liver disease after stereotactic body radiotherapy for small hepatocellular carcinoma: clinical and dose-volumetric parameters

BackgroundTo investigate the clinical and dose–volumetric parameters that predict the risk of radiation-induced liver disease (RILD) for patients with small, unresectable hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT).MethodsBetween March 2007 and December 2009, 92 patients with HCC treated with SBRT were reviewed for RILD within 3xa0months of completing treatment. RILD was evaluated according to the Common Terminology Criteria for Adverse Events, version 3.0. A dose of 10–20xa0Gy (median, 15xa0Gy) per fraction was given over 3–4 consecutive days for a total dose of 30–60xa0Gy (median, 45xa0Gy). The following clinical and dose–volumetric parameters were examined: age, gender, Child-Pugh class, presence of hepatitis B virus, gross tumor volume, normal liver volume, radiation dose, fraction size, mean dose to the normal liver, and normal liver volumes receiving fromu2009<u20095xa0Gy tou2009<u200960xa0Gy (in increments of 5xa0Gy).ResultsSeventeen (18.5%) of the 92 patients developed grade 2 or worse RILD after SBRT (49 patients in grade 1, 11 in grade 2, and 6 inu2009≥u2009grade 3). On univariate analysis, Child-Pugh class was identified as a significant clinical parameter, while normal liver volume and normal liver volumes receiving fromu2009<u200915xa0Gy tou2009<u200960xa0Gy were the significant dose–volumetric parameters. Upon multivariate analysis, only Child-Pugh class was a significant parameter for predicting grade 2 or worse RILD.ConclusionsThe Child-Pugh B cirrhosis was found to have a significantly greater susceptibility to the development of grade 2 or worse RILD after SBRT in patients with small, unresectable HCC. Additional efforts aimed at testing other models to predict the risk of RILD in a large series of HCC patients treated with SBRT are needed.

Verification of Accuracy of CyberKnife Tumor-tracking Radiation Therapy Using Patient-specific Lung Phantoms

PURPOSEnTo investigate the accuracy of the CyberKnife Xsight Lung Tracking System (XLTS) compared with that of a fiducial-based target tracking system (FTTS) using patient-specific lung phantoms.nnnMETHODS AND MATERIALSnThree-dimensional printing technology was used to make individualized lung phantoms that closely mimicked the lung anatomy of actual patients. Based on planning computed tomographic data from 6 lung cancer patients who underwent stereotactic ablative radiation therapy using the CyberKnife, the volume above a certain Hounsfield unit (HU) was assigned as the structure to be filled uniformly with polylactic acid material by a 3-dimensional printer (3D Edison, Lokit, Korea). We evaluated the discrepancies between the measured and modeled target positions, representing the total tracking error, using 3 log files that were generated during each treatment for both the FTTS and the XLTS. We also analyzed the γ index between the film dose measured under the FTTS and XLTS.nnnRESULTSnThe overall mean values and standard deviations of total tracking errors for the FTTS were 0.36 ± 0.39 mm, 0.15 ± 0.64 mm, and 0.15 ± 0.62 mm for the craniocaudal (CC), left-right (LR), and anteroposterior (AP) components, respectively. Those for the XLTS were 0.38 ± 0.54 mm, 0.13 ± 0.18 mm, and 0.14 ± 0.37 mm for the CC, LR, and AP components, respectively. The average of γ passing rates was 100% for the criteria of 3%, 3 mm; 99.6% for the criteria of 2%, 2 mm; and 86.8% for the criteria of 1%, 1 mm.nnnCONCLUSIONSnThe XLTS has segmentation accuracy comparable with that of the FTTS and small total tracking errors.

Comparison of chemoembolization with and without radiation therapy and sorafenib for advanced hepatocellular carcinoma with portal vein tumor thrombosis: a propensity score analysis.

PURPOSEnTo compare efficacy of transarterial chemoembolization with and without radiation therapy (RT) versus sorafenib for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT).nnnMATERIALS AND METHODSnThis single-center retrospective study involved 557 patients with HCC with PVTT who initially received chemoembolization (1997-2002; n = 295), chemoembolization and RT (2003-2008; n = 196), or sorafenib (2009-2012; n = 66) according to eligibility criteria among an initial population of 617. The three groups were divided into three pairs (chemoembolization vs chemoembolization/RT, chemoembolization vs sorafenib, and chemoembolization/RT vs sorafenib), and time to progression (TTP) and overall survival (OS) were compared by propensity-score analyses.nnnRESULTSnThe chemoembolization/RT group had longer median TTP and OS than the chemoembolization-alone and sorafenib groups (P < .001). Multivariate Cox analysis revealed that chemoembolization/RT treatment was an independent predictor of favorable TTP and OS. In the matched cohort, median TTP and OS were significantly longer in the chemoembolization/RT group than the chemoembolization-alone group (102 pairs; TTP, 8.7 mo vs 3.6 mo [P < .001]; OS, 11.4 mo vs 7.4 mo [P = .023]) or the sorafenib group (30 pairs; TTP, 5.1 mo vs 1.6 mo [P < .001]; OS, 8.2 mo vs 3.2 mo [P < .001]), in agreement with the inverse probability of treatment weighted (IPTW) outcomes. In matching analyses, the chemoembolization-alone group had longer median TTP and OS than the sorafenib group (46 pairs; TTP, 3.4 mo vs 1.8 mo [P < .001]; OS, 5.9 mo vs 4.4 mo [P = .003]). There was no significant difference in terms of OS with the IPTW approach (P = .108), but there was one in terms of TTP (P < .001).nnnCONCLUSIONSnWithin the limitation of a retrospective study, the present data indicate that transarterial chemoembolization combined with RT could be considered as an alternative to the standard sorafenib in the treatment of patients with advanced-stage HCC with PVTT.

Use of serum squamous cell carcinoma antigen for follow-up monitoring of cervical cancer patients who were treated by concurrent chemoradiotherapy

BackgroundTo investigate the significance of monitoring the levels of the serum squamous cell carcinoma antigen (SCC-Ag) for the detection of recurrent disease in patients with cervical cancer treated by concurrent chemoradiotherapy.MethodsThe records of 112 patients with cervical cancer were reviewed. Serum SCC-Ag levels were measured at regular follow-up visits. A SCC-Ag level of 2 ng/mL was considered the upper limit of normal. Biochemical failure was defined as two consecutively increasing SCC-Ag values above normal. Recurrent disease was confirmed by histologic and radiographic studies.ResultsEighteen patients (16%) developed recurrent disease. Sixteen patients had initially elevated SCC-Ag, post-treatment normalization of SCC-Ag, and tumor recurrence. The SCC-Ag difference (ΔSCC-Ag), defined as the difference between the last value after two consecutively increases above normal and the value immediately before the elevation, had good clinical performance in predicting cancer recurrence. The cutoff value of ΔSCC-Ag was 0.95 ng/mL.ConclusionsSCC-Ag is a relatively good method for the detection of disease recurrence in patients with cervical cancer who were treated by concurrent chemoradiotherapy.

Two‐week schedule of hypofractionated radiotherapy as a local salvage treatment for small hepatocellular carcinoma

In cases of small hepatocellular carcinoma (HCC) where established curative treatment cannot be applied, stereotactic body radiotherapy (SBRT) has been used as a non‐invasive alternative treatment modality. However, short‐course SBRT may not be safe if the tumor is located around a critical normal organ. Therefore, we applied hypofractionated radiotherapy for these tumors and evaluated outcomes of this treatment.

Radiotherapeutic strategies for hepatocellular carcinoma with portal vein tumour thrombosis in a hepatitis B endemic area.

This nationwide, multicenter study investigated treatment outcomes as well as the optimal radiotherapeutic strategy in patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT).

A prospective phase 2 multicenter study for the efficacy of radiation therapy following incomplete transarterial chemoembolization in unresectable hepatocellular carcinoma

PURPOSEnThe purpose of this study was to investigate the efficacy and toxicity of radiation therapy (RT) following incomplete transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC).nnnMETHODS AND MATERIALSnThe study was designed as a prospective phase 2 multicenter trial. Patients with unresectable HCC, who had viable tumor after TACE of no more than 3 courses, were eligible. Three-dimensional conformal RT (3D-CRT) was added for HCC treatment with incomplete uptake of iodized oil, and the interval from TACE to RT was 4 to 6 weeks. The primary endpoint of this study was the tumor response after RT following incomplete TACE in unresectable HCC. Secondary endpoints were patterns of failure, progression-free survival (PFS), time to tumor progression (TTP), overall survival (OS) rates at 2 years, and treatment-associated toxicity. Survival was calculated from the start of RT.nnnRESULTSnBetween August 2008 and December 2010, 31 patients were enrolled. RT was delivered at a median dose of 54 Gy (range, 46-59.4 Gy) at 1.8 to 2 Gy per fraction. A best objective in-field response rate was achieved in 83.9% of patients, with complete response (CR) in 22.6% of patients and partial response in 61.3% of patients within 12 weeks post-RT. A best objective overall response rate was achieved in 64.5% of patients with CR in 19.4% of patients and PR in 45.1% of patients. The 2-year in-field PFS, PFS, TTP, and OS rates were 45.2%, 29.0%, 36.6%, and 61.3%, respectively. The Barcelona Clinic liver cancer stage was a significant independent prognostic factor for PFS (P=.023). Classic radiation-induced liver disease was not observed. There were no treatment-related deaths or hepatic failure.nnnCONCLUSIONSnEarly 3D-CRT following incomplete TACE is a safe and practical treatment option for patients with unresectable HCC.

Clinical impact of combined transarterial chemoembolization and radiotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: An external validation study

PURPOSEnTo evaluate the relationship between portal vein tumor thrombosis (PVTT) response and clinical outcomes in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization followed by radiotherapy (TACE-RT).nnnMATERIALS AND METHODSnThe study enrolled 329 patients in the training set and 179 patients in the validation set. All patients who were treated with TACE-RT from 2002 to 2008 and satisfied the inclusion criteria were enrolled in the study. The median follow-up period was 11.7 months (range, 1.6-108.6) in the training set and 11.9 months (range, 1.7-105.1) in the validation set.nnnRESULTSnAfter TACE-RT, PVTT response was complete or partial in 32 (9.7%) and 134 (40.7%) patients of the training set and in 18 (10.1%) and 96 (53.6%) patients in the validation set, respectively. Failure to obtain PVTT response was significantly related with elevated post-treatment Child-Pugh score (P<0.001). Furthermore, progression-free survival was significantly related with PVTT response (P<0.001, hazard ratio 0.33, 95% confidence interval 0.25-0.42) in multivariate analysis. In receiver-operating characteristics analysis of 1-year progression prediction, the PVTT response showed an area under the curve of 0.74. Most of the findings were successfully reproduced in the independent external validation set.nnnCONCLUSIONSnPositive PVTT response was closely associated with favorable clinical outcomes. The PVTT response to TACE-RT reduces metastasis and makes it possible to maintain normal liver function and achieve longer survival.

A dosimetric comparison of volumetric modulated arc therapy (VMAT) and non-coplanar intensity modulated radiotherapy (IMRT) for nasal cavity and paranasal sinus cancer.

BackgroundTo compare dosimetric parameters of volumetric modulated arc therapy (VMAT) and non-coplanar intensity modulated radiotherapy (IMRT) for nasal cavity and paranasal sinus cancer with regard to the coverage of planning target volume (PTV) and the sparing of organs at risk (OAR).MethodsTen patients with nasal cavity or paranasal sinus cancer were re-planned by VMAT (two-arc) plan and non-coplanar IMRT (7-, 11-, and 15-beam) plans. Planning objectives were to deliver 60xa0Gy in 30 fractions to 95% of PTV, with maximum doses (Dmax) of <50xa0Gy to the optic nerves, optic chiasm, and brainstem, <40xa0Gy to the eyes and <10xa0Gy to the lenses. The target mean dose (Dmean) to the parotid glands was <25xa0Gy, and no constraints were applied to the lacrimal glands. Planning was optimized to minimized doses to OAR without compromising coverage of the PTV. VMAT and three non-coplanar IMRT (7-, 11-, and 15-beam) plans were compared using the heterogeneity and conformity indices (HI and CI) of the PTV, Dmax and Dmean of the OAR, treatment delivery time, and monitor units (MUs).ResultsThe HI and CI of VMAT plan were superior to those of the 7-, 11-, and 15-beam non-coplanar IMRT. VMAT and non-coplanar IMRT (7-, 11-, and 15-beam) showed equivalent sparing effects for the optic nerves, optic chiasm, brainstem, and parotid glands. For the eyes and lenses, VMAT achieved equivalent or better sparing effects when compared with the non-coplanar IMRT plans. VMAT showed lower MUs and reduced treatment delivery time when compared with non-coplanar IMRT.ConclusionsIn 10 patients with nasal cavity or paranasal sinus cancer, a VMAT plan provided better homogeneity and conformity for PTV than non-coplanar IMRT plans, with a shorter treatment delivery time, while achieving equal or better OAR-sparing effects and using fewer MUs.