Chul Koo Cho

Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization

The objective of this study was to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) as a local salvage treatment after incomplete transarterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC).

Preliminary result of stereotactic body radiotherapy as a local salvage treatment for inoperable hepatocellular carcinoma.

To evaluate the toxicity and efficacy of stereotactic body radiotherapy (SBRT) for the treatment of localized hepatocellular carcinoma (HCC) in the absence of another standard treatment option.

Image-Guided Stereotactic Body Radiation Therapy in Patients With Isolated Para-Aortic Lymph Node Metastases From Uterine Cervical and Corpus Cancer

PURPOSEnThe aims of this study were to evaluate the role of stereotactic body radiation therapy (SBRT) as a local treatment for isolated para-aortic lymph node (PALN) metastases originating from uterine cervical and corpus cancer.nnnMETHODS AND MATERIALSnWe retrospectively enrolled 30 patients with isolated PALN metastases originating from uterine cervical and corpus cancer who had received SBRT using the CyberKnife (CK). All patients were shown to have isolated PALN metastases by computed tomography (CT) and/or positron emission tomography (PET)-CT. The overall survival (OS), local control (LC) rate, and disease progression-free survival (DPFS) rate were calculated according to the Kaplan-Meier method. Comparison between prognosis groups was performed using log-rank analysis. Toxicities were also evaluated.nnnRESULTSnThe 4-year OS rate was 50.1%, and the median survival time was not reached. The OS rate among symptomatic patients was significantly lower than that among asymptomatic patients (p = 0.002). The 4-year actuarial LC rate was 67.4%. Patients with a planning target volume of </=17 ml had significantly higher LC rates (p = 0.009). The 4-year DPFS rate was 45.0%, and the median time to disease progression was 32 months. Small planning target volume was a favorable prognostic factor (p = 0.043). Grade 3 or 4 complications requiring hospitalization were reported in 1 patient at 20 months after SBRT.nnnCONCLUSIONnThe OS and LS rates were promising, and the incidence of toxicities was low. Use of SBRT with the CyberKnife is an effective modality for treating isolated PALN metastases in patients with uterine cervical and corpus cancer.

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.

Stereotactic Body Radiation Therapy Using Three Fractions for Isolated Lung Recurrence from Colorectal Cancer

Objective: To determine the feasibility of stereotactic body radiotherapy (SBRT) using 3 fractions for isolated colorectal lung metastases. Methods: From June 2003 to December 2006, 13 cases of isolated pulmonary metastasis from colorectal cancer were treated by SBRT due to an inoperable state (7 patients), or the patient’s refusal to undergo surgical excision (6 patients). All patients underwent chemotherapy for salvage treatment. SBRT doses ranged from 39 to 51 Gy in 3 fractions. Nine patients had a solitary lesion, 3 patients had 2 lesions, and 1 patient had 3 lesions. Median tumor volume for the 18 lesions was 5.9 ml (range 1.6–45 ml). Results: Follow-up duration was 15–57 months. Three-year overall survival, local control and progression-free survival rates were 64.7, 52.7 and 11.5%, respectively.Univariate analysis showed that total internal target volume was a significant prognostic factor for local control. During the follow-up, 11 of the 13 patients experienced local recurrence, distant metastasis or both. The most frequent site of failure was in a nontargeted lung region. No severe complication was attributed to SBRT. Conclusion: Our study suggests the potential feasibility of SBRT for selected patients with 1–3 small metastatic nodules. A further larger-scale study is required to define the indications for SBRT in cases with isolated pulmonary metastasis from colorectal cancer.

Involvement of p38 mitogen‐activated protein kinase in the cell growth inhibition by sodium arsenite*

It is well‐known that p38 mitogen‐activated protein kinase (p38MAPK) participates in cellular responses to mitogenic stimuli, environmental and genotoxic stresses, and apoptotic agents. Although there are several reports on p38MAPK in relation to cell growth and apoptosis, the exact mechanism of p38MAPK‐mediated cell growth regulation remains obscure. Here, we examined possible roles of p38MAPK in the sodium arsenite‐induced cell growth inhibition in NIH3T3 cells. Sodium arsenite induced transient cell growth delay with marked activation of p38MAPK. In addition, arsenite induced CDK inhibitor p21CIP1/WAF1 and enhanced its binding to the CDK2, which resulted in inhibition of CDK2 activity. The levels of cyclin D1 expression and the CDK4 kinase activity were also significantly reduced. pRB was hypophosphorylated by sodium arsenite. SB203580, a specific inhibitor of p38MAPK, blocked arsenite‐induced growth inhibition as well as the arsenite‐induced p21CIP1/WAF1 expression. Expression of dominant negative p38MAPK also blocked arsenite‐induced p21CIP1/WAF1 expression. Inhibited‐CDK2 activity was also completely reversed by SB203580 or expression of dominant negative p38MAPK, while the decreased‐cyclin D1 protein by the compound was not restored. These data demonstrate a possible link between the activation of p38MAPK and induction of p21CIP1/WAF1, suggesting that the activation of p38MAPK is, at least in part, related to the cell growth inhibition by sodium arsenite. J. Cell. Physiol. 190: 29–37, 2002.

Oligometastases confined one organ from colorectal cancer treated by SBRT.

To determine the feasibility and efficacy of stereotactic body radiotherapy (SBRT) for oligometastases from colorectal cancer (CRC). Total of 59 patients with 78 lesions confined to one organ and treated from 2001 to 2006 were involved in this retrospective review. These patients presented with 1–4 metastatic lesions of largest diameter of <7xa0cm, progressed after chemotherapy, and were amenable to local treatment. The median radiation dose administered was 42xa0Gy, which was delivered in 3 fractions. Lymph node lesions were most frequent, followed in order by the lung and liver. Five-year overall survival and local control rates were 29 and 19%, respectively. Cumulative gross tumor volume, site of metastasis, and SBRT dose were found to be significantly associated with overall survival. In terms of local control, a cumulative GTV below 23xa0ml was found to be a significantly favorable prognostic factor. Acute grade 1–2 toxicities occurred in 24 of the 59 patients, and a late grade 4 complication occurred in 2 (3%), and these were relieved by bypass surgery. CRC patients with oligometastases generally fare well after SBRT. In particular, the survival rates of patients with a pelvic LN or a small tumor are promising.

Image-guided stereotactic body radiation therapy for localized prostate cancer.

PURPOSEnWe report the results of a retrospective study of stereotactic body radiation therapy (SBRT) using CyberKnife for localized prostate cancer. The study focused on the safety and feasibility of this treatment modality.nnnMATERIALS AND METHODSnBetween October 2002 and December 2007, 44 patients suffering from localized adenocarcinoma of the prostate were treated with SBRT using CyberKnife at the Korea Cancer Center Hospital. The patients were divided into 3 groups: a low-risk group (5 patients), an intermediate-risk group (10 patients), and a high-risk group (29 patients). Five patients received 32 Gy in 4 fractions, 28 patients received 34 Gy in 4 fractions, and 11 patients received 36 Gy in 4 fractions.nnnRESULTSnThe median age of the patients was 69 years (range, 53-79 years) and the median duration of follow-up 40 months (range, 12-78 months). There were 6 acute and 3 late grade 2 urinary toxicities, and 4 acute and 5 late grade 2 rectal toxicities, but there were no grade 3 or higher treatment-related toxicities. The 5-year cause-specific survival rate and progression-free survival rate were both 100%. At last follow-up, the biochemical failure-free rate of the low-risk, intermediate-risk and high-risk patients was 100%, 100% and 90.8%, respectively.nnnCONCLUSIONnSBRT using CyberKnife for localized prostate cancer is safe and well tolerated. We obtained promising results with 34 Gy in a 4-fraction regimen especially for the high-risk patients.

Inhibition of heat shock protein 27-mediated resistance to DNA damaging agents by a novel PKCδ-V5 heptapeptide

Heat shock protein 27 (HSP27), which is highly expressed in human lung and breast cancer tissues, induced resistance to cell death against various stimuli. Treatment of NCI-H1299 cells, which express a high level of HSP27, with small interference RNA specifically targeting HSP27 resulted in inhibition of their resistance to radiation or cisplatin, suggesting that HSP27 contributed to cellular resistance in these lung cancer cells. Furthermore, because HSP27 interacts directly with the COOH terminus of the protein kinase C delta (PKC delta)-V5 region with ensuing inhibition of PKC delta activity and PKC delta-mediated cell death, we wished to determine amino acid residues in the V5 region that mediate its interaction with HSP27. Investigation with various deletion mutants of the region revealed that amino acid residues 668 to 674 of the V5 region mediate its interaction with HSP27. When NCI-H1299 cells were treated with biotin or with FITC-tagged heptapeptide of the residues 668 to 674 (E-F-Q-F-L-D-I), the cells exhibited dramatically increased cisplatin or radiation-induced cell death with the heptapeptide having efficient interaction with HSP27, which in turn restored the PKC delta activity that had been inhibited by HSP27. In vivo nude mice grafting data also suggested that NCI-H1299 cells were sensitized by this heptapeptide. The above data strongly show that the heptapeptide of the PKC delta-V5 region sensitized human cancer cells through its interaction with HSP27, thereby sequestering HSP27. The heptapeptide may provide a novel strategy for selective neutralization of HSP27.

Local tumor control after retreatment of spinal metastasis using stereotactic body radiotherapy; comparison with initial treatment group

Abstract Background. The aim of this study is to evaluate local control rates after stereotactic body radiotherapy (SBRT) in recurrent spinal metastasis after external beam radiotherapy (EBRT) and new spinal metastatic lesions. Material and methods. Retrospective review of medical records and radiological data was performed on 54 retreatment and 131 initial SBRT patients. To compare various fractionation schedules, the biologically effective dose (BED) was applied. SBRT dose was calculated with linear-quadratic model and normalized to a 2-Gy equivalent dose (nBED, α/β =2 Gy for spinal cord, α/β =10 Gy for tumor). Doses to a point within the spinal cord that received the maximum dose (Pmax) were checked. Local control failure was defined as progression by imaging study. Overall survival, progression free survival, delivered radiation dose to tumor and spinal cord, and spinal cord Pmax nBED were compared in two groups. Results. The mean delivered radiation doses to tumor margin during SBRT were 51.1 Gy2/10 (retreatment) and 50.7 Gy2/10 (initial treatment). Mean survival was 29.6 months (overall)/20.7 months (retreatment)/ 32.4 months (initial treatment). Mean progression free period was 23.9 months (overall)/18.0 months (retreatment)/ 26.0 months (initial treatment). Radiological control rates of retreatment and initial treatment group were 96%/95% at six months, 81%/89% at 12 months and 79%/90% at 24 months. Among 54 retreatment lesions, 13 lesions showed local control failure during follow-up. With regard to spinal cord radiation dose during SBRT, Spinal cord Pmax nBED was 46.2 Gy2/2 (retreatment) and 48.7 Gy2/2 (initial treatment). In retreatment group, total nBED to spinal cord was a mean of 83.4 Gy2/2. There was no case of radiation myelopathy detected. Conclusions. Retreatment of spinal metastases using SBRT provided effective local control without neurological complications.