Chul Ju Han

High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma

BackgroundRecent studies using stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) have reported high tumor response and local control. However, the optimal SBRT dose remains unknown, and it is still not clear whether a dose response relationship for local control (LC) and overall survival (OS) exist or not. We performed this study to determine whether a dose response relationship for LC and OS is observed in SBRT for inoperable HCC.MethodsBetween 2003 and 2011, 108 patients with HCC were treated with SBRT. All patients were unsuitable for surgery or local ablation and had incomplete response to transarterial chemoembolization. Eighty-two patients with a longest tumor diameter (LD) less than or equal to 7.0 cm who were treated with 3-fraction SBRT and were analyzed. This cohort comprised 74 Child-Turcotte-Pugh (CTP) class A patients and 8 CTP class B7 patients. The median LD was 3.0 cm (range, 1.0–7.0 cm), and the median dose was 51 Gy (range, 33–60 Gy).ResultsLC and OS rates at 2 years after SBRT were 87% and 63%, respectively, with a median follow-up duration of 30 months for all patients. The 2-year LC/OS rates for patients treated with doses of > 54, 45–54, and < 45 Gy were 100/71, 78/64, and 64%/30%, respectively (p = .009/p < .001). Multivariate analysis revealed that the SBRT dose (p = .005) and Barcelona Clinic Liver Cancer stage (p = .015) were significant prognostic factors for OS. Correlation analysis revealed a positive linear relationship between the SBRT dose and LC (p = .006, R = .899)/OS (p = .002, R = .940) at 2 years. Based on the tumor-control probability model, a dose of 54.8 Gy provides 2-year LC with a 90% probability. Five patients experienced grade 3 or higher gastrointestinal toxicity, and 6 had deteriorating of CTP score by greater than or equal to 2 within 3 months of SBRT.ConclusionsThis study demonstrated a dose response relationship for LC and OS with SBRT for HCC. Higher LC rates resulting from an increased dose may translate into survival benefits for patients with HCC.

Outcomes of stereotactic body radiotherapy for unresectable primary or recurrent cholangiocarcinoma

Purpose To report the results of stereotactic body radiotherapy (SBRT) for unresectable primary or recurrent cholangiocarcinoma. Materials and Methods From January 2005 through August 2013, 58 patients with unresectable primary (n = 28) or recurrent (n = 30) cholangiocarcinoma treated by SBRT were retrospectively analyzed. The median prescribed dose was 45 Gy in 3 fractions (range, 15 to 60 Gy in 1-5 fractions). Patients were treated by SBRT only (n = 53) or EBRT + SBRT boost (n = 5). The median tumor volume was 40 mL (range, 5 to 1,287 mL). Results The median follow-up duration was 10 months (range, 1 to 97 months). The 1-year, 2-year overall survival rates, and median survival were 45%, 20%, and 10 months, respectively. The median survival for primary group and recurrent group were 5 and 13 months, respectively. Local control rate at 1-year and 2-year were 85% and 72%, respectively. Disease progression-free survival rates at 1-year and 2-year were 26% and 23%, respectively. In univariate analysis, ECOG performance score (0-1 vs. 2-3), treatment volume (<50 vs. ≥50 mL), and pre-SBRT CEA level (<5 vs. ≥5 ng/mL) were significant in overall survival rate. In multivariate analysis, ECOG score (p = 0.037) and tumor volume (p = 0.030) were statistically significant. In the recurrent tumor group, patients with >12 months interval from surgery to recurrence showed statistically significant higher overall survival rate than those with ≤12 months (p = 0.026). Six patients (10%) experienced ≥grade 3 complications. Conclusion SBRT can be considered as an effective local modality for unresectable primary or recurrent cholangiocarcinoma.

Feasibility and Efficacy of Stereotactic Ablative Radiotherapy for Barcelona Clinic Liver Cancer-C Stage Hepatocellular Carcinoma

The purpose of this study was to assess the feasibility and efficacy of stereotactic ablative radiotherapy (SABR) for liver tumor in patients with Barcelona Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma (HCC). We retrospectively reviewed the medical records of 35 patients between 2003 and 2011. Vascular invasion was diagnosed in 32 patients, extrahepatic metastases in 11 and both in 8. Thirty-two patients were categorized under Child-Pugh (CP) class A and 3 patients with CP class B. The median SABR dose was 45 Gy (range, 30-60 Gy) in 3-5 fractions. The median survival time was 14 months. The 1- and 3-yr overall survival (OS) rate was 52% and 21%, respectively. On univariate analysis, CP class A and biologically equivalent dose ≥ 80 Gy10 were significant determinants of better OS. Severe toxicity above grade 3, requiring prompt therapeutic intervention, was observed in 5 patients. In conclusion, SABR for BCLC-C stage HCC showed 1-yr OS rate of 52% but treatment related toxicity was moderate. We suggest that patients with CP class A are the best candidate and at least SABR dose of 80 Gy10 is required for BCLC-C stage.

Outcome and current status of therapeutic hypothermia after out-of-hospital cardiac arrest in Korea using data from the Korea Hypothermia Network registry

Objective Therapeutic hypothermia (TH) has become the standard strategy for reducing brain damage in the postresuscitation period. The aim of this study was to investigate current TH performance and outcomes in out-of-hospital cardiac arrest (OHCA) survivors using data from the Korean Hypothermia Network (KORHN) registry. Methods We used the KORHN registry, a web-based multicenter registry that includes 24 participating hospitals throughout the Republic of Korea. Adult comatose OHCA survivors treated with TH between 2007 and 2012 were included. The primary outcomes were neurological outcome at hospital discharge and in-hospital mortality. The secondary outcomes were TH performance and adverse events during TH. Results A total of 930 patients were included, of whom 556 (59.8%) survived to discharge and 249 (26.8%) were discharged with good neurologic outcomes. The median time from return of spontaneous circulation (ROSC) to the start of TH was 101 minutes (interquartile range [IQR], 46 to 200 minutes). The induction, maintenance, and rewarming durations were 150 minutes (IQR, 80 to 267 minutes), 1,440 minutes (IQR, 1,290 to 1,440 minutes), and 708 minutes (IQR, 420 to 900 minutes), respectively. The time from the ROSC to coronary angiography was 1,045 hours (IQR, 121 to 12,051 hours). Hyperglycemia (46.3%) was the most frequent adverse event. Conclusion More than one-quarter of the OHCA survivors (26.8%) were discharged with good neurologic outcomes. TH performance was appropriately managed in terms of the factors related to its timing, including cooling start time and rewarming duration.

Predicting Outcome With Diffusion-Weighted Imaging in Cardiac Arrest Patients Receiving Hypothermia Therapy: Multicenter Retrospective Cohort Study.

Objectives: Many comatose patients following cardiac arrest have ischemic brain injury. Diffusion-weighted imaging is a sensitive tool to identify hypoxic-ischemic brain injury. The accurate prediction of the prognosis for comatose cardiac arrest survivors has been challenging, and thus, a multimodal approach, combining diffusion-weighted image findings, could be feasible. The aim of this study was to assess regional brain injury on diffusion-weighted imaging and to test the potential association with its neurologic outcome in patients treated with target temperature management after out-of-hospital cardiac arrest. Design and Setting: A multicenter, registry-based, retrospective cohort study was conducted using cases from 24 hospitals across South Korea. Of the 930 adult (≥ 18 yr) nontraumatic out-of-hospital cardiac arrest patients treated with target temperature management between January 2007 and December 2012 at these hospitals, we included the patients who underwent brain diffusion-weighted imaging in the first week after cardiac arrest. The brain regions examined included the four cerebral lobes, basal ganglia-thalamus, brain stem, and cerebellum. Imaging results were compared between a good neurologic outcome, defined as a cerebral performance category score of 1 or 2, and a poor neurologic outcome (cerebral performance category score ≥ 3). Measurement and Main Results: Poor neurologic outcome occurred in 118 of the 172 patients analyzed (68.6%). Positive diffusion-weighted image findings, defined as any regional brain injury lesion in diffusion-weighted imaging, were present in 106 patients. Positive diffusion-weighted image findings had 93% sensitivity, 86% specificity, 76% positive predictive value, and 96% negative predictive value for a poor neurologic outcome. The poor outcome group had higher numbers of affected brain lesions than the good outcome group (3.8 ± 1.9 vs 0.1 ± 0.6; p < 0.01). By multivariate analysis, positive diffusion-weighted image findings (odds ratio, 58.2; 95% CI, 13.29–254.91) and lack of a shockable rhythm (odds ratio, 0.13; 95% CI, 0.03–0.57) were associated with a poor neurologic outcome. Conclusions: Diffusion-weighted imaging allows reliable prediction of poor neurologic outcome in comatose patients treated with target temperature management after out-of-hospital cardiac arrest. Further prospective validation study will be required to generalize this result.

Low Hepatic Toxicity in Primary and Metastatic Liver Cancers after Stereotactic Ablative Radiotherapy Using 3 Fractions.

This study evaluated the incidence of hepatic toxicity after stereotactic ablative radiotherapy (SABR) using 3 fractions to the liver, and identified the predictors for hepatic toxicity. We retrospectively reviewed 78 patients with primary and metastatic liver cancers, who underwent SABR using 3 fractions between 2003 and 2011. To examine the incidence of hepatic toxicity, we defined newly developed hepatic toxicity≥grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 within 3 months after the end of SABR as a significant adverse event. To identify the predictors for hepatic toxicity, we analyzed several clinical and dosimetric parameters (rV5Gy-rV35Gy: normal liver volume receiving <X Gy, reverse VXGy). Hepatic toxicity≥grade 2 occurred in 10 patients (13%): grade 2 in 9 patients and grade 3 in 1 patient. On univariate analysis, baseline Child-Pugh (CP) score (5 vs. 6-8), normal liver volume, and planning target volume were the significant clinical predictors. All dosimetric parameters were significant: rV20Gy was the most significant predictor. On multivariate analysis, baseline CP score (hazard ratio, 0.026; P=0.001) was the only significant predictor. In conclusion, SABR using 3 fractions in primary and metastatic liver cancers produces low hepatic toxicity, especially in patients with a baseline CP score of 5. However, further studies are needed to minimize hepatic toxicity in patients with baseline CP scores≥6. Graphical Abstract

Outcomes of hanging-induced cardiac arrest patients who underwent therapeutic hypothermia: a multicenter retrospective cohort study.

OBJECTIVES The aim of this study was to analyze the outcomes of patients with hanging-induced cardiac arrest who underwent therapeutic hypothermia (TH). METHOD In this multicenter, retrospective registry-based study, discharged patients after out-of-hospital cardiac arrest and treatment with TH were enrolled between June 2007 and March 2013. Several prehospital and hospital variables were examined for an outcome analysis with multivariable logistic regression. RESULTS A total of 964 patients who had cardiac arrest were enrolled in this study. All patients underwent TH during post-cardiac arrest care after return of spontaneous circulation (ROSC). Of all patients, 105 were assigned to the hanging group and 859 to the non-hanging group. Six patients (6%) with good neurologic outcomes (Cerebral Performance Category 1 or 2) in the hanging group at the time of discharge were found. A shorter time interval between witnessed arrest and ROSC and a Glasgow Coma Scale over 4 after ROSC are statistically significant variables of good neurologic outcomes after hanging-induced cardiac arrest treated with TH. CONCLUSION A small number of patients who underwent TH after a hanging-induced cardiac arrest provided good neurologic outcomes, and some variables influenced these outcomes.

Radiofrequency ablation versus stereotactic body radiotherapy for small hepatocellular carcinoma: a Markov model‐based analysis

The aim of this study is to compare radiofrequency ablation (RFA) with stereotactic body radiotherapy (SBRT) for hepatocellular carcinomas (HCC) smaller than 3 cm. A Markov cohort model was developed to simulate a cohort of patients aged 60–65 years with small HCCs who had undergone either RFA or SBRT and were followed up over their remaining life expectancy. The inclusion criteria were: (1) HCC ≤3 cm in diameter with ≤ 3 nodules; (2) absence of extrahepatic metastasis or portal/hepatic vein invasion; (3) Child‐Pugh Class A or B. Twenty thousand virtual patients were randomly assigned to undergo RFA or SBRT. Predicted life expectancy was 6.452 and 6.371 years in the RFA and SBRT groups, respectively. The probability distributions of the expected overall survival were nearly identical. The 95% confidence intervals were 6.25–6.66 and 6.17–6.58 years for RFA and SBRT, respectively. The difference between RFA and SBRT was insignificant (P = 0.2884). Two‐way sensitivity analysis demonstrated that if the tumor is 2–3 cm, SBRT is the preferred treatment option. Our Markov model has shown that expected overall survival of SBRT is nearly identical to RFA in HCCs smaller than 3 cm, but SBRT may have an advantage for tumors 2 cm and larger. A randomized trial is required to confirm these findings.

Allopurinol-induced DRESS syndrome mimicking biliary obstruction

An 84-year-old man was admitted to our hospital with fever, jaundice, and itching. He had been diagnosed previously with chronic renal failure and diabetes, and had been taking allopurinol medication for 2 months. A physical examination revealed that he had a fever (38.8℃), jaundice, and a generalized maculopapular rash. Azotemia, eosinophilia, atypical lymphocytosis, elevation of liver enzymes, and hyperbilirubinemia were detected by blood analysis. Magnetic resonance cholangiography revealed multiple cysts similar to choledochal cysts in the liver along the biliary tree. Obstructive jaundice was suspected clinically, and so an endoscopic ultrasound examination was performed, which ruled out a diagnosis of obstructive jaundice. The patient was diagnosed with DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome due to allopurinol. Allopurinol treatment was stopped and steroid treatment was started. The patient died from cardiac arrest on day 15 following admission.

Relating factors to severe injury from outdoor falls in older people

The aim of the present study was to evaluate the clinical characteristics, including floor characteristics and factors, related to severe injury from outdoor falls in older adults.