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1.  Clinical outcomes of radiation therapy for early-stage gastric mucosa-associated lymphoid tissue lymphoma 
AIM: To evaluate the clinical outcomes of radiation therapy (RT) for early-stage gastric mucosa-associated lymphoid tissue lymphoma (MALToma).
METHODS: The records of 64 patients treated between 1998 and 2011 were analyzed retrospectively. For Helicobacter pylori (H. pylori)-positive patients (n = 31), chemotherapy or H. pylori eradication therapy was the initial treatment. In patients with failure after H. pylori eradication, RT was performed. For H. pylori-negative patients (n = 33), chemotherapy or RT was the first-line treatment. The median RT dose was 36 Gy. The target volume included the entire stomach and the perigastric lymph node area.
RESULTS: All of the patients completed RT without interruption and showed complete remission on endoscopic biopsy after treatment. Over a median follow-up period of 39 mo, the 5-year local control rate was 89%. Salvage therapy was successful in all relapsed patients. Secondary malignancies developed in three patients. The 5-year overall survival rate was 94%. No patient presented symptoms of moderate-to-severe treatment-related toxicities during or after RT.
CONCLUSION: Radiotherapy results in favorable clinical outcomes in patients with early-stage gastric MALToma who experience failure of H. pylori eradication therapy and those who are H. pylori negative.
PMCID: PMC3785628  PMID: 24106407
Gastric mucosa-associated lymphoid tissue lymphoma; Radiation therapy; Treatment response
2.  Role of Radiotherapy in the Multimodal Treatment of Ewing Sarcoma Family Tumors 
The aim of this study was to evaluate the role of radiotherapy (RT) in the management of Ewing sarcoma family tumors (ESFT).
Materials and Methods
Retrospective analysiswas performed on 91 patientswith localized ESFT treated from 1988 to 2012. Primary tumor size was ≥ 8 cm in 33 patients. Surgery, RT, and combined surgery with RT were applied in 37, 15, and 33 patients, respectively.
Median follow-up was 43.8 months. Forty-three patients (47.3%) showed recurrence or progressive disease. Twelve patients (13.2%) showed local failure after initial treatment. Thirty-nine patients (42.9%) experienced distant metastases. The 5-year overall survival (OS), progression-free survival, and local control (LC) were 60.5%, 58.2%, and 85.1%, respectively. According to treatment, 5-year LCwas 64.8% with RT and 90.2% with combined surgery and RT (p=0.052). Prognostic factors for OS were tumor size (≥ 8 cm, p < 0.001) and surgical resection (p < 0.001). In large tumors (≥ 8 cm), combined surgery and RT produced better LC compared to RT (p=0.033). However, in smaller tumors (< 8 cm), RT without surgery resulted in a similar LC rate as RT with surgery (p=0.374).
RT used for patients with unfavorable risk factors resulted in worse outcome than for patientswho received surgery. Smallertumors could be controlled locallywith chemotherapy and RT. For large tumors, combined surgery and RT is needed. Proper selection of local treatment modality, RT, surgery, or both is crucial in the management of ESFT.
PMCID: PMC4614204  PMID: 25687849
Ewing sarcoma; Surgery; Radiotherapy; Tumor burden
3.  Reduced-dose craniospinal radiotherapy followed by tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk medulloblastoma 
Neuro-Oncology  2012;15(3):352-359.
We assessed the feasibility and effectiveness of reduced-dose craniospinal (CS) radiotherapy (RT) followed by tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) in reducing late adverse effects without jeopardizing survival among children with high-risk medulloblastoma (MB).
From October 2005 through September 2010, twenty consecutive children aged >3 years with high-risk MB (presence of metastasis and/or postoperative residual tumor >1.5 cm2) were assigned to receive 2 cycles of pre-RT chemotherapy, CSRT (23.4 or 30.6 Gy) combined with local RT to the primary site (total 54.0 Gy), and 4 cycles of post-RT chemotherapy followed by tandem HDCT/autoSCT. Carboplatin-thiotepa-etoposide and cyclophosphamide-melphalan regimens were used for the first and second HDCT, respectively.
Of 20 patients with high-risk MB, 17 had metastatic disease and 3 had a postoperative residual tumor >1.5 cm2 without metastasis. The tumor relapsed/progressed in 4 patients, and 2 patients died of toxicities during the second HDCT/autoSCT. Therefore, 14 patients remained event-free at a median follow-up of 46 months (range, 23−82) from diagnosis. The probability of 5-year event-free survival was 70.0% ± 10.3% for all patients and 70.6% ± 11.1% for patients with metastases. Late adverse effects evaluated at a median of 36 months (range, 12−68) after tandem HDCT/autoSCT were acceptable.
In children with high-risk MB, CSRT dose might be reduced when accompanied by tandem HDCT/autoSCT without jeopardizing survival. However, longer follow-up is needed to evaluate whether the benefits of reduced-dose CSRT outweigh the long-term risks of tandem HDCT/autoSCT.
PMCID: PMC3578484  PMID: 23258845
autologous stem cell transplantation; high-dose chemotherapy; late effect; medulloblastoma; radiotherapy
4.  Interfractional Variation of Radiation Target and Adaptive Radiotherapy for Totally Resected Glioblastoma 
Journal of Korean Medical Science  2013;28(8):1233-1237.
This study aimed to evaluate the effects of volume adapted re-planning for radiotherapy (RT) after gross total resection (GTR) for glioblastoma. Nineteen patients with glioblastoma who underwent GTR and postoperative RT were analyzed. The volumes of the surgical cavity on computed tomography (CT) obtained one day after GTR (CT0), the first RT simulation CT (sim-CT1), and the second simulation CT for the boost RT plan (sim-CT2) were compared. The boost RT plan was based on the surgical cavity observed on the sim-CT2 (boost RTP2) and was compared with that based on the surgical cavity observed on the sim-CT1 (boost RTP1). The volume reduction ratios were 14.4%-51.3% (median, 29.0%) between CT0 and sim-CT1 and -7.9%-71.9% (median, 34.9%) between sim-CT1 and sim-CT2 (P < 0.001). The normal brain volumes in boost RTP1 were significantly reduced in boost RTP2, especially at high dose levels. Target volume in sim-CT2 which was not covered with the boost RTP1, developed in five cases (26.3%). The surgical cavity volume was reduced following surgery in patients with glioblastoma who underwent GTR. The application of volume-adapted re-planning during RT could decrease the irradiated volume of normal brain and prevent a target miss for boost RT.
PMCID: PMC3744714  PMID: 23960453
Glioblastomas; Surgery; Brain; Radiotherapy, Image-Guided
5.  Postoperative Adjuvant Radiotherapy for Patients with Gastric Adenocarcinoma 
Journal of Gastric Cancer  2012;12(4):205-209.
In gastric adenocarcinoma, high rates of loco-regional recurrences have been reported even after complete resection, and various studies have been tried to find the role of postoperative adjuvant therapy. Among them, Intergroup 0116 trial was a landmark trial, and demonstrated the definite survival benefit in adjuvant chemoradiotherapy, compared with surgery alone. However, the INT 0116 trial had major limitation for global acceptance of the INT 0116 regimen as an adjuvant treatment modality because of the limited lymph node dissection. Lately, several randomized studies that were performed to patients with D2-dissected gastric cancer were published. This review summarizes the data about patterns of failure after surgical resection and the earlier prospective studies, including INT 0116 study. Author will introduce the latest studies, including ARTIST trial and discuss whether external beam radiotherapy should be applied to patients receiving extended lymph node dissection and adjuvant chemotherapy.
PMCID: PMC3543969  PMID: 23346491
Stomach neoplasms; Radiotherapy; Adjuvant
6.  Treatment outcome of hepatic re-irradiation in patients with hepatocellular carcinoma 
Radiation Oncology Journal  2015;33(4):276-283.
We evaluated the efficacy and toxicity of repeated high dose 3-dimensional conformal radiation therapy (3D-CRT) for patients with unresectable hepatocellular carcinoma.
Materials and Methods
Between 1998 and 2011, 45 patients received hepatic re-irradiation with high dose 3D-CRT in Samsung Medical Center. After excluding two ineligible patients, 43 patients were retrospectively reviewed. RT was delivered with palliative or salvage intent, and equivalent dose of 2 Gy fractions for α/β = 10 Gy ranged from 31.25 Gy10 to 93.75 Gy10 (median, 44 Gy10). Tumor response and toxicity were evaluated based on the modified Response Evaluation Criteria in Solid Tumors criteria and the Common Terminology Criteria for Adverse Events (CTCAE) ver. 4.0.
The median follow-up duration was 11.2 months (range, 4.1 to 58.3 months). An objective tumor response rate was 62.8%. The tumor response rates were 81.0% and 45.5% in patients receiving ≥45 Gy10 and <45 Gy10, respectively (p = 0.016). The median overall survival (OS) of all patients was 11.2 months. The OS was significantly affected by the Child-Pugh class as 14.2 months vs. 6.1 months (Child-Pugh A vs. B, p < 0.001), and modified Union for International Cancer Control (UICC) T stage as 15.6 months vs. 8.3 months (T1-3 vs. T4, p = 0.004), respectively. Grade III toxicities were developed in two patients, both of whom received ≥50 Gy10.
Hepatic re-irradiation may be an effective and tolerable treatment for patients who are not eligible for further local treatment modalities, especially in patients with Child-Pugh A and T1-3.
PMCID: PMC4707210  PMID: 26756027
Hepatocellular carcinoma; Radiotherapy; Toxicity; Re-irradiation
7.  The first private-hospital based proton therapy center in Korea; status of the Proton Therapy Center at Samsung Medical Center 
Radiation Oncology Journal  2015;33(4):337-343.
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.
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.
The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015.
PMCID: PMC4707217  PMID: 26756034
Proton therapy; Proton beam therapy; Particle accelerator; Radiation oncology
8.  Dosimetric and Clinical Influence of 3D Versus 2D Planning in Postoperative Radiation Therapy for Gastric Cancer 
The purpose of this study is to investigate the dosimetric and clinical influence of computed tomography–based (3-dimensional [3D]) simulation versus conventional 2-dimensional (2D)–based simulation in postoperative chemoradiotherapy (CRT) for patients with advanced gastric cancer in terms of parallel opposed anteroposterior-posteroanterior field arrangement.
Materials and Methods
A retrospective stage-matched cohort study was conducted in 158 patients treated with adjuvant CRT following curative surgery and D2 dissection from 2006 to 2008 at Samsung Medical Center: 98 patients in the 3D group; and 60 patients in the 2D group. For comparison of the dosimetric parameters between 3D plan and 2D plan, second sets of radiation treatment plans were generated according to the same target delineation method used in the 2D group for each patient in the 3D group (V2D). Acute toxicity, recurrence, and survival were analyzed. The median follow-up period was 28 months (range, 5 to 51 months).
The 3D group showed better dose-volume histogram (DVH) profiles than the V2D group for all dosimetric parameters, including the kidneys, liver, spinal cord, duodenum, pancreas, and bowel. However, no difference in acute gastrointestinal toxicity and survival outcomes was observed between the 3D group and the 2D group.
The 3D plan enabled precise delineation of the target volume and organs at risk by visualization of geometric changes in the internal organs after surgery. The DVH of normal tissues in the 3D plan was superior to that of the V2D plan, but similar clinical features were observed between the 3D group and the 2D group.
PMCID: PMC4614202  PMID: 25672580
Radiotherapy; Stomach neoplasms; Computer-assisted radiotherapy planning
9.  Clinical outcomes of stereotactic body radiotherapy for spinal metastases from hepatocellular carcinoma 
Radiation Oncology Journal  2015;33(3):217-225.
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).
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.
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.
PMCID: PMC4607575  PMID: 26484305
Stereotactic body radiotherapy; Spinal metastases; Hepatocellular carcinoma
10.  Evaluation of variability in target volume delineation for newly diagnosed glioblastoma: a multi-institutional study from the Korean Radiation Oncology Group 
This study aimed for a collaborative evaluation of variability in the target volumes for glioblastoma, determined and contoured by different radiotherapy (RT) facilities in Korea.
Fifteen panels of radiation oncologists from independent institutions contoured the gross target volumes (GTVs) and clinical target volumes (CTVs) for 3-dimensional conformal RT or intensity-modulated RT on each simulation CT images, after scrutinizing the enhanced T1-weighted and T2-weighted-fluid-attenuated inversion recovery MR images of 9 different cases of glioblastoma. Degrees of contouring agreement were analyzed by the kappa statistics. Using the algorithm of simultaneous truth and performance level estimation (STAPLE), GTVSTAPLE and CTVSTAPLE contours were derived.
Contour agreement was moderate (mean kappa 0.58) among the GTVs and was substantial (mean kappa 0.65) among the CTVs. However, each panels’ GTVs and modification of CTVs regarding anatomical structures varied. Three-fourth of contoured panels’ CTVs encompassed the peritumoral areas of T2-high signal intensity (T2-HSI). Nine of nine GTVSTAPLE encompased the surgical cavity and the T1-enhanced lesions. Eight of nine CTVSTAPLE encompassed the peritumoral T2-HSI area. The median MARGIN90 and the median MARGIN95 were 1.4 cm and 1.5 cm, respectively.
Moderate to substantial agreement existed in target volumes for 3-dimensional or intensity-modulated RT determined by radiation oncologists in Korea. According to the estimated consensus contours, the initial CTV encompassed the GTV with margin less than 2.0 cm and the whole peritumoral areas of T2-HSI. The findings of our study propose the need for further studies and modified guidelines.
Electronic supplementary material
The online version of this article (doi:10.1186/s13014-015-0439-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4489390  PMID: 26134973
Glioblastoma; Target volume; Peritumoral edema; STAPLE; Margin
11.  Changes in Arterioportal Shunts in Hepatocellular Carcinoma Patients with Portal Vein Thrombosis Who Were Treated with Chemoembolization Followed by Radiotherapy 
In this study, we retrospectively investigated the prevalence of arterioportal (AP) shunts in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and evaluated the changes in AP shunts after chemoembolization followed by external beam radiation therapy (EBRT).
Materials and Methods
We analyzed 54 HCC patients with PVTT who were treated with chemoembolization followed by EBRT. EBRT was uniformly delivered at a total dose of 30 to 45 Gy (median, 35 Gy), with a daily dose of 2 to 4.5 Gy. Angiographic images of chemoembolization before and after radiation therapy (RT) were reviewed to investigate the AP shunt.
During the initial session of chemoembolization, 33 of 54 patients (61%) had an AP shunt. After EBRT, 32 out of 33 patients had an additional session of chemoembolization and were evaluated for a change in the AP shunt. The AP shunt decreased in 20 of 32 patients (63%) after chemoembolization followed by EBRT. The 1-year calculated overall survival (OS) rate for all patients was 52.6% and the 2-year OS was 36.4%. The median OS in all patients was 13 months. Patients with AP shunt showed poorer median OS than those without AP shunt, but there was no statistically significant difference (median, 12 months vs. 17 months).
The AP shunt frequently occurs in HCC patients with PVTT. This study suggests that a poor prognosis is associated with an AP shunt. Chemoembolization followed by RT may produce a decrease in AP shunts.
PMCID: PMC4398114  PMID: 25578056
Hepatocellular carcinoma; Arterioportal shunt; Radiotherapy; Chemoembolization; Therapeutic
12.  Clinical Practice Guidelines for Gastric Cancer in Korea: An Evidence-Based Approach 
Journal of Gastric Cancer  2014;14(2):87-104.
Although gastric cancer is quite common in Korea, the treatment outcome is relatively favorable compared to those in western countries. However, there are currently no Korean multidisciplinary guidelines for gastric cancer. Experts from related societies developed guidelines de novo to meet Korean circumstances and requirements, including 23 recommendation statements for diagnosis (n=9) and treatment (n=14) based on relevant key questions. The quality of the evidence was rated according to the GRADE evidence evaluation framework: the evidence levels were based on a systematic review of the literature, and the recommendation grades were classified as either strong or weak. The applicability of the guidelines was considered to meet patients' view and preferences in the context of Korea. The topics of the guidelines cover diagnostic modalities (endoscopy, endoscopic ultrasound, and radiologic diagnosis), treatment modalities (surgery, therapeutic endoscopy, chemotherapy, and radiotherapy), and pathologic evaluation. An external review of the guidelines was conducted during the finalization phase.
PMCID: PMC4105383  PMID: 25061536
Stomach neoplasms; Multidisciplinary; Guidelines
13.  Nanostring-Based Multigene Assay to Predict Recurrence for Gastric Cancer Patients after Surgery 
PLoS ONE  2014;9(3):e90133.
Despite the benefits from adjuvant chemotherapy or chemoradiotherapy, approximately one-third of stage II gastric cancer (GC) patients developed recurrences. The aim of this study was to develop and validate a prognostic algorithm for gastric cancer (GCPS) that can robustly identify high-risk group for recurrence among stage II patients. A multi-step gene expression profiling study was conducted. First, a microarray gene expression profiling of archived paraffin-embedded tumor blocks was used to identify candidate prognostic genes (N = 432). Second, a focused gene expression assay including prognostic genes was used to develop a robust clinical assay (GCPS) in stage II patients from the same cohort (N = 186). Third, a predefined cut off for the GCPS was validated using an independent stage II cohort (N = 216). The GCPS was validated in another set with stage II GC who underwent surgery without adjuvant treatment (N = 300). GCPS was developed by summing the product of Cox regression coefficients and normalized expression levels of 8 genes (LAMP5, CDC25B, CDK1, CLIP4, LTB4R2, MATN3, NOX4, TFDP1). A prospectively defined cut-point for GCPS classified 22.7% of validation cohort treated with chemoradiotherapy (N = 216) as high-risk group with 5-year recurrence rate of 58.6% compared to 85.4% in the low risk group (hazard ratio for recurrence = 3.16, p = 0.00004). GCPS also identified high-risk group among stage II patients treated with surgery only (hazard ratio = 1.77, p = 0.0053).
PMCID: PMC3943911  PMID: 24598828
14.  Transcatheter arterial chemoembolization and radiation therapy for treatment-naïve patients with locally advanced hepatocellular carcinoma 
Radiation Oncology Journal  2014;32(1):14-22.
To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) followed by radiotherapy (RT) in treatment-naïve patients with locally advanced hepatocellular carcinoma (HCC).
Materials and Methods
Eligibility criteria were as follows: newly diagnosed with HCC, the Barcelona Clinic Liver Cancer stage C, Child-Pugh class A or B, and no prior treatment for HCC. Patients with extrahepatic spread were excluded. A total of 59 patients were retrospectively enrolled. All patients were treated with TACE followed by RT. The time interval between TACE and RT was 2 weeks as per protocol. A median RT dose was 47.25 Gy10 as the biologically effective dose using the α/β = 10 (range, 39 to 65.25 Gy10).
At 1 month, complete response was obtained in 3 patients (5%), partial response in 27 patients (46%), stable disease in 13 patients (22%), and progressive disease in 16 patients (27%). The actuarial one- and two-year OS rates were 60.1% and 47.2%, respectively. The median OS was 17 months (95% confidence interval, 5.6 to 28.4 months). The median time to progression was 4 months (range, 1 to 35 months). Grade 3 or greater liver enzyme elevation occurred in only two patients (3%) after RT. Grade 3 gastroduodenal toxicity developed in two patients (3%).
The combination treatment of TACE followed by RT with two-week interval was safe and it showed favorable outcomes in treatment-naïve patients with locally advanced HCC. A prospective randomized trial is needed to validate these results.
PMCID: PMC3977127  PMID: 24724047
Hepatocellular carcinoma; Transcatheter arterial chemoembolization; Radiotherapy
15.  Changes of the liver volume and the Child-Pugh score after high dose hypofractionated radiotherapy in patients with small hepatocellular carcinoma 
Radiation Oncology Journal  2012;30(4):189-196.
To investigate the safety of high dose hypofractionated radiotherapy (RT) in patients with small hepatocellular carcinoma (HCC) in terms of liver volumetric changes and clinical liver function.
Materials and Methods
We retrospectively reviewed 16 patients with small HCC who were treated with high dose hypofractionated RT between 2006 and 2009. The serial changes of the liver volumetric parameter were analyzed from pre-RT and follow-up (FU) computed tomography (CT) scans. We estimated linear time trends of whole liver volume using a linear mixed model. The serial changes of the Child-Pugh (CP) scores were also analyzed in relation to the volumetric changes.
Mean pre-RT volume of entire liver was 1,192.2 mL (range, 502.6 to 1,310.2 mL) and mean clinical target volume was 14.7 mL (range, 1.56 to 70.07 mL). Fourteen (87.5%) patients had 4 FU CT sets and 2 (12.5%) patients had 3 FU CT sets. Mean interval between FU CT acquisition was 2.5 months. After considering age, gender and the irradiated liver volume as a fixed effects, the mixed model analysis confirmed that the change in liver volume is not significant throughout the time course of FU periods. Majority of patients had a CP score change less than 2 except in 1 patient who had CP score change more than 3.
The high dose hypofractionated RT for small HCC is relatively safe and feasible in terms of liver volumetric changes and clinical liver function.
PMCID: PMC3546287  PMID: 23346538
Radiotherapy; Hepatocellular carcinoma
16.  Scheduled Interval Trans-Catheter Arterial Chemoembolization Followed by Radiation Therapy in Patients with Unresectable Hepatocellular Carcinoma 
Journal of Korean Medical Science  2012;27(7):736-743.
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.
PMCID: PMC3390720  PMID: 22787367
Carcinoma, Hepatocellular; Radiationtherapy; Trans-Catheter Arterial Chemoembolization; Combination Treatment
17.  Trans-Differentiation of Neural Stem Cells: A Therapeutic Mechanism Against the Radiation Induced Brain Damage 
PLoS ONE  2012;7(2):e25936.
Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases.
PMCID: PMC3277599  PMID: 22347993
18.  Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Young Children with Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System 
Journal of Korean Medical Science  2012;27(2):135-140.
The feasibility and effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) were evaluated in children younger than 3 yr of age with atypical teratoid/rhabdoid tumors (ATRT). Tandem HDCT/autoSCT was administered following six cycles of induction chemotherapy. Radiotherapy (RT) was administered if the tumor relapsed or progressed, otherwise, it was administered after 3 yr of age. Tumors relapsed or progressed during induction chemotherapy in 5 of 9 patients enrolled; 3 of these 5 received tandem HDCT/autoSCT as a salvage treatment. One patient died from sepsis during induction chemotherapy. The remaining 3 patients proceeded to tandem HDCT/autoSCT; however, 2 of these patients showed tumor relapse/progression after tandem HDCT/autoSCT. All 7 relapses/progressions occurred at primary sites even in patients with leptomeningeal seeding. Toxicities during tandem HDCT/autoSCT were manageable. A total of 5 patients were alive with a median follow-up of 20 (range 16-70) months from diagnosis. Four of 5 patients who received RT after relapse/progression are alive. The probability of overall survival at 3 yr from diagnosis was 53.3% ± 17.3%. Our tandem HDCT/autoSCT is feasible; however, early administration of RT prior to tandem HDCT/autoSCT should be considered to improve the outcome after tandem HDCT/autoSCT.
PMCID: PMC3271285  PMID: 22323859
Rhabdoid Tumor; Central Nervous System; Drug Therapy; Stem Cell Transplantation; Radiotherapy; Child
19.  Prognostic Index for Portal Vein Tumor Thrombosis in Patients with Hepatocellular Carcinoma Treated with Radiation Therapy 
Journal of Korean Medical Science  2011;26(8):1014-1022.
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.
PMCID: PMC3154336  PMID: 21860551
Carcinoma, Hepatocellular; Portal Vein Tumor Thrombosis; Radiotherapy; Prognostic Index
20.  The Role of Radiosurgery in Patients with Brain Metastasis from Small Cell Lung Carcinoma 
The purpose of this retrospective study was to evaluate the outcome of gamma knife radiosurgery (GKRS) and/or whole brain radiation therapy (WBRT) for the treatment of small cell lung carcinoma (SCLC) metastasis to the brain.
From 2000 to 2010, 50 patients underwent GKRS for metastatic brain lesions originating from SCLC. Among these patients, 11 received prophylactic cranial irradiation (PCI) before the development of metastatic lesions (PCI group), and GKRS was performed as an initial treatment for newly diagnosed lesions in 12 patients who had not received PCI (primary GKRS group). In addition, GKRS was performed as a salvage treatment for progressive lesions after WBRT in 27 patients (salvage GKRS group). The medical records and imaging data of all patients were retrospectively analyzed.
The overall survival of the 50 patients was 20.8 months (range 1-53) after the diagnosis of primary tumor and 12.0 months (range 1-47) after the development of cerebral metastasis. Median survival after GKRS was 4.8 months (range 1-15) in the PCI group, 4.6 months (range 0-18) in the primary GKRS group, and 7.6 months (range 0-33) in the salvage GKRS group. Further treatment for progressive lesions after GKRS was necessary in 15 patients, after a mean interval of 3.8 months. Causes of death were systemic organ failure in 15 patients, deterioration of neurological state in 13 patients, and unknown or combined causes in 16 patients. The local control rate of the lesions treated with GKRS was 76.4% (decreased in 13 patients and stable in 16 patients at the final imaging follow-up (mean 5.60 months).
GKRS is an effective local treatment for brain metastasis from SCLC both as an initial treatment for newly diagnosed lesions after PCI and as a salvage treatment for recurrent or progressive lesions. However, the survival benefit is not significant because most patients die of systemic multi-organ failure with a short life expectancy.
PMCID: PMC3206286  PMID: 22053227
Small cell lung carcinoma; Radiosurgery; Gamma knife; Metastasis
21.  Primary CNS lymphoma other than DLBCL: a descriptive analysis of clinical features and treatment outcomes 
Annals of Hematology  2011;90(12):1391-1398.
Diffuse large B-cell lymphoma (DLBCL) constitutes most primary central nervous system (CNS) lymphoma (PCNSL), whereas T-cell, low-grade and Burkitt’s lymphomas (BL) are rarely encountered. Due to the paucity of cases, little is known about the clinical features and treatment outcomes of PCNSL other than DLBCL. The objective of this study was to describe the clinical characteristics and outcomes for patients with PCNSL other than DLBCL. Fifteen patients, newly diagnosed with PCNSLs other than DLBCL between 2000 and 2010, were included. The male to female ratio was 0.67:1 with a median age of diagnosis of 31 years (range 18–59). Pathologic distributions were as follows: peripheral T-cell lymphoma (PTCL; n = 7), marginal zone B-cell lymphoma (MZBCL; n = 1), lymphoplasmacytic lymphoma (LPL; n = 2), Burkitt’s lymphoma (n = 1), other unspecified (T-cell lineage, n = 2; B-cell lineage, n = 2). Thirteen patients (87%) showed Eastern Cooperative Oncology Group performance score (ECOG PS) 1–2. The remaining two were one PTCL patient and one Burkitt’s lymphoma patient. Of the nine patients with T-cell lymphoma, five (56%) had multifocal lesions, and one (20%) with LPL of the five patients with B-cell lymphoma showed a single lesion. Leptomeningeal lymphomatosis was identified in two patients (one with Burkitt’s lymphoma and one with unspecified B-cell lymphoma). Two patients (22%) with T-cell lymphoma died 7.7 and 23.3 months later, respectively, due to disease progression, despite HD-MTX-based therapy. Six patients with T-cell lymphoma (6/9, 66.7%) and four patients with low-grade B-cell lymphoma (4/5, 80%) achieved complete response and have survived without relapse (Table 3). One patient with Burkitt’s lymphoma showed poor clinical features with ECOG PS 3, deep structure, multifocal, and leptomeningeal lymphomatosis, and died 7.6 months after the initiation of treatment. In comparison with previously reported DLBCLs (median OS 6.4 years, 95% CI 3.7–9.1 years), T-cell lymphoma showed equivocal or favorable clinical outcomes and low-grade B-cell lymphomas, such as MZBCL and LPL, had a good prognosis. However, primary CNS Burkitt’s lymphoma presented poor clinical outcomes and showed a comparatively aggressive clinical course. In conclusion, primary CNS lymphoma other than DLBCL occurred more in younger patients and showed a generally good prognosis, except for Burkitt’s lymphoma. Further research on treatment strategies for Burkitt’s lymphoma is needed.
PMCID: PMC3210363  PMID: 21479535
Primary CNS lymphoma; Diffuse large B-cell lymphoma
22.  Impact of adjuvant chemotherapy for gliomatosis cerebri 
BMC Cancer  2010;10:424.
Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of tumor cells throughout CNS, however, few details are available about the chemotherapeutic effect on GC. The aim of this study was to investigate its clinical course and to determine the efficacy of chemotherapy for GC.
Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy.
Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008).
Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC.
PMCID: PMC2933624  PMID: 20704759
23.  Efficacy of High-dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Relapsed Medulloblastoma: A Report on The Korean Society for Pediatric Neuro-Oncology (KSPNO)-S-053 Study 
Journal of Korean Medical Science  2010;25(8):1160-1166.
The efficacy and toxicity of high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) were investigated for improving the outcomes of patients with relapsed medulloblastoma. A total of 15 patients with relapsed medulloblastoma were enrolled in the KSPNO-S-053 study from May 2005 to May 2007. All patients received approximately 4 cycles of salvage chemotherapy after relapse. Thirteen underwent HDCT/ASCT; CTE and CM regimen were employed for the first HDCT (HDCT1) and second HDCT (HDCT2), respectively, and 7 underwent HDCT2. One transplant related mortality (TRM) due to veno-occlusive disease (VOD) occurred during HDCT1 but HDCT2 was tolerable with no further TRM. The 3-yr overall survival probability and event-free survival rates ±95% confidence intervals (CI) were 33.3±12.2% and 26.7% ±11.4%, respectively. When analysis was confined to only patients who had a complete response (CR) or partial response (PR) prior to HDCT, the probability of 3-yr overall survival rates ±95% CI was 40.0±15.5%. No patients with stable disease (SD) or progressive disease (PD) survived. Survival rates from protocol KSPNO-S-053 are encouraging and show that tumor status prior to HDCT/ASCT is an important factor to consider for improving survival rates of patients with relapsed medulloblastoma.
PMCID: PMC2908784  PMID: 20676326
Recurrence; Medulloblastoma; Transplantation, Autologous; Tandem; Hematopoietic Stem Cell Transplantation
24.  Reduced-dose craniospinal radiotherapy followed by high-dose chemotherapy and autologous stem cell rescue for children with newly diagnosed high-risk medulloblastoma or supratentorial primitive neuroectodermal tumor 
The Korean Journal of Hematology  2010;45(2):120-126.
In this study, we investigated the effects of reduced-dose craniospinal radiotherapy (CSRT) followed by tandem high-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) in children with a newly diagnosed high-risk medulloblastoma (MB) or supratentorial primitive neuroectodermal tumor (sPNET).
Between March 2005 and April 2007, patients older than 3 years with a newly diagnosed high-risk MB or sPNET were enrolled. The patients received two cycles of pre-RT chemotherapy consisting of cisplatin, etoposide, vincristine, and cyclophosphamide (cycle A), and carboplatin, etoposide, vincristine, and ifosphamide (cycle B), followed by CSRT with 23.4 Gy and local RT with 30.6 Gy. After four cycles of post-RT chemotherapy (cycles A, B, A, and B), tandem double HDCT with ASCR was performed.
A total of 13 patients (MB=11, sPNET=2) were enrolled. Of these, one patient progressed, one patient died of septic shock after the second cycle of B, and one patient relapsed after the third cycle of B. The 3-year event-free survival (EFS) rate of the patients intended for HDCT was 76.9%, whereas the 3-year EFS rate of the patients who received HDCT was 100%. No treatment-related mortality occurred during HDCT.
Although the follow-up period was short and the patient cohort was small in size, the results of this study are encouraging. The limited toxicity and favorable EFS rate observed in children treated with reduced-dose CSRT followed by HDCT and ASCR warrant further exploration in a larger study population.
PMCID: PMC2983022  PMID: 21120191
Radiotherapy; High-dose chemotherapy; Autologous stem cell transplantation; Medulloblastoma; Supratentorial primitive neuroectodermal tumor; Children
25.  Improved Outcome of Central Nervous System Germ Cell Tumors: Implications for the Role of Risk-adapted Intensive Chemotherapy 
Journal of Korean Medical Science  2010;25(3):458-465.
To determine the impact of treatment protocols on the outcome of central nervous system germ cell tumors (CNS-GCTs), we reviewed the medical records of 53 patients who received front-line chemotherapy from September 1997 to September 2006. Pure germinoma, normal alpha-fetoprotein level and beta-human chorionic gonadotropin level <50 mIU/mL were regarded as low-risk features and the others as high-risk. Patients from different time periods were divided into 3 groups according to the chemotherapy protocols. Group 1 (n=19) received 4 cycles of chemotherapy comprising cisplatin, etoposide and bleomycin. Group 2 (n=16) and group 3 (n=18) received 4 cycles of chemotherapy with cisplatin, etoposide, cyclophosphamide and vincristine in the former and with carboplatin, etoposide, cyclophosphamide and bleomycin in the latter. In group 2 and group 3, high-risk patients received double doses of cisplatin, carboplatin and cyclophosphamide. Radiotherapy was given after chemotherapy according to the clinical requirements. The event-free survivals of groups 1, 2, and 3 were 67.0%, 93.8%, and 100%, respectively (group 1 vs. 2, P=0.06; group 2 vs. 3, P=0.29; group 1 vs. 3, P=0.02). Our data suggest that risk-adapted intensive chemotherapy may improve the outcome of patients with malignant CNS-GCTs.
PMCID: PMC2826748  PMID: 20191048
Neoplasms, Germ Cell and Embryonal; Central Nervous System; Drug Therapy; Survival

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