Jeong Il Yu

Prognostic Index for Portal Vein Tumor Thrombosis in Patients with Hepatocellular Carcinoma Treated with Radiation Therapy

We performed a retrospective review of 281 hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) treated with radiation therapy (RT) between 1998 and 2008 to develop a prognostic model for those patients. Of the 281 patients, PVTT and intrahepatic main masses completely disappeared in 10 patients (3.6%), and shown a partial response in 141 patients (50.2%). The median survival was 11.6 months. Patients who had more than PR have shown significantly longer survival than the others (22.0 months vs 5.0 months, P < 0.001). On the multivariate analysis, pre-treatment poor prognosticators for overall survival were ECOG performance status, Child-Pugh class, multiple tumors, main PVTT, complete portal vein occlusion, lymph node metastasis, and primary tumor size. Prognostic index of RT for PVTT of HCC (PITH) scores were defined as the number of pre-treatment poor prognostic factors. PITH scores correlated well with overall survival. In the analysis of 1 and 2 yr overall survival rate, patients who had PITH scores of 3 or greater showed a significantly lower rate of overall survival than the others (33.0%, 17.3% vs 70.1%, 40.8%, respectively, P < 0.001). The PITH scoring model, proposed in the current study in HCC patients with PVTT, reliably predict overall survival.

Differences in prognostic factors and patterns of failure between invasive micropapillary carcinoma and invasive ductal carcinoma of the breast: Matched case–control study

PURPOSE We designed this study to identify differences in prognostic factors and patterns of failure between invasive micropapillary carcinoma (IMPC) and invasive ductal carcinoma (IDC) in patients with breast cancer. EXPERIMENTAL DESIGN We identified 72 cases of IMPC who were diagnosed between 1999 and 2007 at the Samsung Medical Center. These patients were matched with 144 controls who were diagnosed with IDC during the same period. Exact matches were made for age (+/-3 years), pathologic tumour and node stage, and treatment methods (surgery and radiation therapy). RESULTS The median follow-up period was 45 months (13-116) for IMPC and 50 months (16-122) for IDC. Lymphovascular invasion (LVI, p<0.0001), axillary lymph node extracapsular extension (ECE, p=0.001) and high nuclear grade (p=0.032) were more frequently detected in patients with IMPC. During the follow-up period, treatment failed in 15 IMPC patients (20.8%) and in 26 IDC patients (18.1%). Loco-regional recurrences developed in 11 IMPC patients (15.3%) and eight IDC patients (5.6%). Importantly, of 57 IMPC patients who had positive axillary nodes, seven patients (12.3%) had axilla and/or supraclavicular recurrence. Therefore, at 5 years, the loco-regional recurrence-free survival was 79.1% in the IMPC patients vs. 93.3% in the IDC patients (p=0.0024). CONCLUSION Our study showed that IMPC is associated with LVI, ECE, high nuclear grade, and a greater degree of loco-regional recurrence, especially in the axilla and supraclavicular areas. Therefore, axillary and supraclavicular radiation therapy should be considered in IMPC patients with axillary node metastasis.

The feasibility of combined transcatheter arterial chemoembolization and radiotherapy for advanced hepatocellular carcinoma

Sorafenib is regarded as the standard treatment of care in Barcelona Clinic Liver Cancer (BCLC) stage C patients. However, the modest overall survival (OS) and disease control rate warrants for a better treatment modality. This study aimed to investigate the feasibility of combined transarterial chemoembolization and radiotherapy (TACE+RT) in comparison with sorafenib for advanced hepatocellular carcinoma (HCC).

The first private-hospital based proton therapy center in Korea; status of the Proton Therapy Center at Samsung Medical Center

Purpose The purpose of this report is to describe the proton therapy system at Samsung Medical Center (SMC-PTS) including the proton beam generator, irradiation system, patient positioning system, patient position verification system, respiratory gating system, and operating and safety control system, and review the current status of the SMC-PTS. Materials and Methods The SMC-PTS has a cyclotron (230 MeV) and two treatment rooms: one treatment room is equipped with a multi-purpose nozzle and the other treatment room is equipped with a dedicated pencil beam scanning nozzle. The proton beam generator including the cyclotron and the energy selection system can lower the energy of protons down to 70 MeV from the maximum 230 MeV. Results The multi-purpose nozzle can deliver both wobbling proton beam and active scanning proton beam, and a multi-leaf collimator has been installed in the downstream of the nozzle. The dedicated scanning nozzle can deliver active scanning proton beam with a helium gas filled pipe minimizing unnecessary interactions with the air in the beam path. The equipment was provided by Sumitomo Heavy Industries Ltd., RayStation from RaySearch Laboratories AB is the selected treatment planning system, and data management will be handled by the MOSAIQ system from Elekta AB. Conclusion The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015.

Scheduled Interval Trans-Catheter Arterial Chemoembolization Followed by Radiation Therapy in Patients with Unresectable Hepatocellular Carcinoma

Combination treatment of trans-catheter arterial chemoembolization (TACE) and conformal radiation therapy (RT) reported promising results in patients with hepatocellular carcinoma (HCC), but, optimal interval was not determined. We hypothesized that a two-week interval between TACE and RT would be optimal. Therefore, we designed this study to evaluate the safety and efficacy of scheduled interval TACE followed by RT. HCC patients who were not eligible for standard therapies were enrolled for scheduled interval TACE followed by RT (START). Patients received TACE on the first day of treatment, and then RT was delivered after 14 days. The entire course of treatment took between four and five weeks. In 81 patients (96.4%), START was completed in the planned treatment period. RT was delayed in the remaining three patients because of decreased liver function or poor performance status after TACE. Of the 81 patients, objective response was observed in 57 patients (70.4%). One unexpected death occurred after START due to hepatic failure. Other toxicities were manageable. The median survival was 14.7 months. There was a significant difference in overall survival according to the response to START (P < 0.001). In conclusion, START is safe and feasible.

The Role of Diffusion-Weighted Magnetic Resonance Imaging in the Treatment Response Evaluation of Hepatocellular Carcinoma Patients Treated With Radiation Therapy

PURPOSE We investigated the role of diffusion-weighted magnetic resonance imaging (DW MRI) as a response evaluation indicator for hepatocellular carcinoma (HCC) treated with radiation therapy (RT). METHODS AND MATERIALS Inclusion criteria of this retrospective study were DW MRI acquisition within 1 month before and 3 to 5 months after RT. In total, 48 patients were enrolled. Two radiation oncologists measured the apparent diffusion coefficient (ADC). Possible predictive factors, including alteration of the ADC value before and 3 to 5 month after RT, in relation to local progression-free survival (LPFS) were analyzed and compared. RESULTS Three months after RT, 6 patients (12.5%) showed a complete response, and 27 patients (56.3%) showed a partial response when evaluated using the modified response evaluation criteria in solid tumors (mRECIST). The average ADC ± SD values were 1.21 ± 0.27 ( × 10(-3) mm(2)/s) before and 1.41 ± 0.36 ( × 10(-3) mm(2)/s) after RT (P<.001). The most significant prognostic factor related to LPFS was mRECIST (P<.001). The increment of ADC value (≥ 20%) was also a significant factor (P=.02), but RECIST (version 1.1; P=.11) was not. When RECIST was combined with the increment of ADC value (≥ 20%), the LPFS rates were significantly different between the groups (P=.004), and the area under the curve value (0.745) was comparable with that of mRECIST (0.765). CONCLUSIONS ADC value change before and after RT in HCC was closely related to LPFS. ADC value and RECIST may substitute for mRECIST in patients who cannot receive contrast agents.

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

PURPOSE To 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). MATERIALS AND METHODS The 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. RESULTS After 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. CONCLUSIONS Positive 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.

Effects of adjuvant radiotherapy on completely resected gastric cancer: A radiation oncologist's view of the ARTIST randomized phase III trial.

PURPOSE We investigated which subgroups might benefit from adjuvant radiotherapy (RT) and suggested optimal RT targets by analyzing the results of the Adjuvant Chemoradiation Therapy in Stomach Cancer (ARTIST) trial. METHODS We conducted randomized controlled trial in 458 gastric cancer patients. Patients were randomly assigned to XP (6 cycles of capecitabine and) or XPRT (2 cycles of XP+RT 45Gy/25 fraction with capecitabine+2 cycles of XP) groups after D2 resection. Minimum follow-up was 5years. RESULTS During follow-up, 77 patients (33.8%) in the XP arm and 60 (26.1%) in the XPRT arm experienced recurrence. Among these patients, locoregional recurrence (LRR) developed in 44 (9.6%; 29 in XP, 15 in XPRT; P=0.03). The local recurrence rate (4.8%) did not vary between arms. Regional recurrence was the most important difference between the two groups (23 in the XP arm, 5 in the XPRT arm, P<0.001). LRR-free survival (LRRFS) was significantly different between study arms (P=0.03), especially in patients with LN metastasis (P=0.009). CONCLUSIONS Adjuvant RT after D2 resection in gastric cancer reduced LRR, especially in group 3 LNs, and improved LRRFS. Patients with LN metastasis benefited more from the adjuvant RT treatment than the other subgroups.

Prognostic factors in breast cancer with extracranial oligometastases and the appropriate role of radiation therapy

Purpose To identify prognostic factors for disease progression and survival of patients with extracranial oligometastatic breast cancer (EOMBC), and to investigate the role of radiation therapy (RT) for metastatic lesions. Materials and Methods We retrospectively reviewed the medical records of 50 patients who had been diagnosed with EOMBC following standard treatment for primary breast cancer initially, and received RT for metastatic lesions, with or without other systemic therapy between January 2004 and December 2008. EOMBC was defined as breast cancer with five or less metastases involving any organs except the brain. All patients had bone metastasis (BM) and seven patients had pulmonary, hepatic, or lymph node metastasis. Median RT dose applied to metastatic lesions was 30 Gy (range, 20 to 60 Gy). Results The 5-year tumor local control (LC) and 3-year distant progression-free survival (DPFS) rate were 66.1% and 36.8%, respectively. High RT dose (≥50 Gy10) was significantly associated with improved LC. The 5-year overall survival (OS) rate was 49%. Positive hormone receptor status, pathologic nodal stage of primary cancer, solitary BM, and whole-lesion RT (WLRT), defined as RT whose field encompassed entire extent of disease, were associated with better survival. On analysis for subgroup of solitary BM, high RT dose was significantly associated with improved LC and DPFS, shorter metastasis-to-RT interval (≤1 month) with improved DPFS, and WLRT with improved DPFS and OS, respectively. Conclusion High-dose RT in solitary BM status and WLRT have the potential to improve the progression-free survival and OS of patients with EOMBC.

Clinical outcomes of stereotactic body radiotherapy for spinal metastases from hepatocellular carcinoma

Purpose To investigate the outcomes of patients with spinal metastases from hepatocellular carcinoma (HCC), who were treated by stereotactic body radiotherapy (SBRT). Materials and Methods This retrospective study evaluated 23 patients who underwent SBRT from October 2008 to August 2012 for 36 spinal metastases from HCC. SBRT consisted of approximately 2 fractionation schedules, which were 18 to 40 Gy in 1 to 4 fractions for group A lesions (n = 15) and 50 Gy in 10 fractions for group B lesions (n = 21). Results The median follow-up period was 7 months (range, 2 to 16 months). Seven patients developed grade 1 or 2 gastrointestinal toxicity, and one developed grade 2 leucopenia. Compression fractures occurred in association with 25% of the lesions, with a median time to fracture of 2 months. Pain relief occurred in 92.3% and 68.4% of group A and B lesions, respectively. Radiologic response (complete and partial response) occurred in 80.0% and 61.9% of group A and B lesions, respectively. The estimated 1-year spinal-tumor progression-free survival rate was 78.5%. The median overall survival period and 1-year overall survival rate were 9 months (range, 2 to 16 months) and 25.7%, respectively. Conclusion SBRT for spinal metastases from HCC is well tolerated and effective at providing pain relief and radiologic response. Because compression fractures develop at a high rate following SBRT for spinal metastases from primary HCC, careful follow up of the patient is required.