• Radiation Oncology Journal
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• v.16 no.4
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• pp.433-440
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• 1998

Purpose : Although small ceil lung cancer (SCLC) has high response rate to chemotherapy and radiotherapy (RT), the prognosis is dismal. The authors evaluated survival and failure patterns according to the prognostic factors in SCLC patients who had thoracic radiation therapy with chemotherapy. Materials and Methods : One hundred and twenty nine patients with SCLC had received thoracic radiation therapy from August 1985 to December 1990. Seventy-seven accessible patients were evaluated retrospectively among 87 patients who completed RT. Median follow-up period was 14 months (2-87months). Results : The two years survival rate was 13$\%$ with a median survival time of 14 months. The two year survival rates of limited disease and extensive disease were 20$\%$ and 8$\%$, respectively, with median survival time of 14 months and 9 months, respectively. Twenty two patients (88$\%$) of limited disease showed complete response (CR) and 3 patients (12$\%$) did partial response (PR). The two year survival rates on CR and PR groups were 24$\%$ and 0$\%$, with median survival times of 14 months and 5 months. respectively (p=0.005). No patients with serum sodium were lower than 135 mmol/L survived 2years and their median survival time was 7 months (p=0.002). Patients whose alkaline phophatase lower than 130 IU/L showed 26$\%$ of 2 year survival rate and showed median survival time of 14 months and those with alkaline phosphatase higher than 130 IU/L showed no 2 year survival and median survival time of 5 the months, respectively (p=0.019). No statistical differences were found according to the age, sex, and performance status. Among the patients with extensive disease, two rear survivals according to the metastatic sites were 14$\%$, 0$\%$, and 7$\%$ in brain, liver, and other metastatic sites, respectively, with median survival time of 9 months, 9 months, and 8 months, respectively (p>0.05). Two year survivals on CR group and PR group were 15$\%$ and 4$\%$, respectively, with a median survival time of 11 months and 7 months, respectively (p=0.01). Conclusion : For SCLC, complete response after chemoradiotherapy was the most significant prognostic tactor. To achieve this goal. there should be further investigation about hyperfractionation, dose escalation, and compatible chemo-radiation schedule such as concurrent chemo-radiation and early radiation therapy with chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1565-1570
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• 2016

Background: Central neurocytomas are rare neuronal neoplasms with a favorable prognosis. They are typically located in the lateral ventricles of the brain and mostly histologically correspond to WHO grade II with a Mib 1 labelling index of <2%. Similar tumors located in the cerebral hemispheres and spinal cord, for example, are called "extraventricular neurocytomas". A few tumors histologically show atypia, mitoses, vascular proliferation and/or necrosis and a Mib 1 index >2 % and are designated as "atypical neurocytomas. Aim: The aim of our study was to describe the common as well as unusual morphologic features and the role of various immunohistochemical stains in the diagnosis of these rare tumors. Materials and Methods: We retrieved and reviewed 35 cases diagnosed between 2001 and 2015. Results: Sixty percent of patients were males, and the mean age was 26 years. 31 cases (88.6%) were intraventricular and 4(11.4%) were extraventricular. Histologically, 6 cases (17.1%) were compatible with "atypical neurocytomas". All cases showed the classic morphology comprising nests and sheets of uniform, round cells with uniform round to oval nuclei with finely speckled chromatin and perinuclear cytoplasmic clearing (halos). All cases also showed delicate, fibrillary, neuropil-like matrices. Other common histologic features included capillary-sized blood vessels in a branching pattern in 57.1%, foci of calcification in 34.3% and perivascular pseudorosettes in 20%. Rare findings included Homer-Wright or true rosettes in 8.6% and ganglioid cells in 2.9%. Synaptophysin was the most consistent and valuable marker, being positive in almost all cases. GFAP positivity in tumor cells was seen in 25.7% of cases. Follow up was available in 13 patients. Of these 9 had histologically typical and 4 had atypical tumors. Only 1 (with an atypical neurocytoma) died, probably due to complications of surgery within one month, while 12 (including 3 with atypical neurocytomas) remained alive. Recurrence developed in 1 of these 12 patients (histologically consistent with typical morphology) almost 9 years after surgery. Only 4 patients, including 2 with atypical tumors, received postoperative radiotherapy, all with surgery in 2010 or later. Overall, prognosis was excellent with prolonged, recurrence free survival and most patients, even without receiving radiation therapy, were alive and well for many years, even a decade or more after surgery, without developing any recurrence, indicating the benign nature of these neoplasms.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5019-5024
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• 2015

Background: The purpose of this study was to assess the dosimetric and clinical feasibility of volumetric modulated arc based hypofractionated stereotactic radiotherapy (RapidArc) treatment for large acoustic schwannoma (AS >10cc). Materials and Methods: Ten AS patients were immobilized using BrainLab mask. They were subject to multimodality imaging (magnetic resonance and computed tomography) to contour target and organs at risk (brainstem and cochlea). Volumetric modulated arc therapy (VMAT) based stereotactic plans were optimized in Eclipse (V11) treatment planning system (TPS) using progressive resolution optimizer-III and final dose calculations were performed using analytical anisotropic algorithm with 1.5 mm grid resolution. All AS presented in this study were treated with VMAT based HSRT to a total dose of 25Gy in 5 fractions (5fractions/week). VMAT plan contains 2-4 non-coplanar arcs. Treatment planning was performed to achieve at least 99% of PTV volume (D99) receives 100% of prescription dose (25Gy), while dose to OAR's were kept below the tolerance limits. Dose-volume histograms (DVH) were analyzed to assess plan quality. Treatments were delivered using upgraded 6 MV un-flattened photon beam (FFF) from Clinac-iX machine. Extensive pretreatment quality assurance measurements were carried out to report on quality of delivery. Point dosimetry was performed using three different detectors, which includes CC13 ion-chamber, Exradin A14 ion-chamber and Exradin W1 plastic scintillator detector (PSD) which have measuring volume of $0.13cm^3$, $0.009cm^3$ and $0.002cm^3$ respectively. Results: Average PTV volume of AS was 11.3cc (${\pm}4.8$), and located in eloquent areas. VMAT plans provided complete PTV coverage with average conformity index of 1.06 (${\pm}0.05$). OAR's dose were kept below tolerance limit recommend by American Association of Physicist in Medicine task group-101(brainstem $V_{0.5cc}$ < 23Gy, cochlea maximum < 25Gy and Optic pathway <25Gy). PSD resulted in superior dosimetric accuracy compared with other two detectors (p=0.021 for PSD.

• Journal of Life Science
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• v.29 no.5
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• pp.530-536
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• 2019

Glioblastoma (GBM) is the most incurable brain cancer derived from the transformed glial cells. Standard anti-GBM treatment, including surgery and chemoradiotherapy, does not ensure good prognosis for the patients with GBM, because successful therapy is often impeded by presence of glioma stem cells (GSCs). GSCs, which is generally divided into proneural (PN) and mesenchymal (MES) subtype, are understood as subpopulation of cancer cells responsible for GBM initiation, progression and recurrence after standard treatments. In the present study, we demonstrate that PN subtype GSCs differentially transit to MES subtype GSCs by specific cytokines. The expression of CD44, a marker of MES subtype GSCs, was observed when GSC11 PN subtype GSCs were exposed to tumor necrosis factor alpha ($TNF-{\alpha}$) cytokine and GSC23 PN subtype GSCs were treated to transforming growth factor beta 1 ($TGF-{\beta}1$) cytokine. Ivy glioblastoma atlas project (Ivy GAP) bioinformatics database showed that $TNF-{\alpha}$ and $TGF-{\beta}1$ were highly expressed in necrotic region and perivascular region, respectively. In addition, $TNF-{\alpha}$ signaling was relatively upregulated in necrotic region, while $TGF-{\beta}$ signaling was increased in perivascular region. Taken together, our observations suggest that MES subtype GSCs can be derived from various PN subtype GSCs by multimodal cytokine stimuli provided by neighboring tumor microenvironment.

• Radiation Oncology Journal
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• v.9 no.1
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• pp.65-72
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• 1991

One hundred and thirty five patients with carcinoma of the nasopharyx were treated by radiation therapy in the Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University between August 1977 and July 1987. Of the 30 patients omitted: 8 had distant metastases at initial diagnosis or during radiotherapy; 18 Patients refused or did not receive a full course of radiation therapy, and four had not been confirmed histologically. The remaining 105 patients were analysed to determine the incidence and pattern of distant metastases. Diagnosis of distant metastases was made based on clinical signs and radiography, even though histologic confirmation was not made. Twenty-six patients developed distant metastases after definite irradiation of nasopharyx and neck, an incidence rate of $24.8\%$ . The common sites of distant metastases were, in descending order, bone, lung, liver, and brain. There was a strong correlation between Ho's N stage and distant metastases rate. But sex, age, histologic subtype (squamous cell and undifferentiated cell), AJC T and N stage, treatment modalities (radiotherapy alone and radiotherapy combined with chemotherapy) were not significant. Of those patients who developed distant metastases, $80.8\%$ were discovered within 2 years of their radical radiotherapy. The prognosis for nasopharyngeal carcinoma patients developing distant metastases was poor: median survival was nine months and $80\%$ of those patients died within two years of the initial diagnosis of distant metastasis.

• The Journal of Korean Society for Radiation Therapy
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• v.33
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• pp.117-125
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• 2021

Purpose: To purpose of this study is to find the correlation of the Set-up error according to the couch rotation and suggest additional margin setting for the GTV. Target and Method: Each scenario treatment plan was created by making the frequency of non-coplanar beams different among all beams. The set-up error value was measured by using the Exact System and the dose accuracy was evaluated by creating a re-treatment plan. Results: When the couch was rotated by 30°, 45°, 60°, and 90°, the mean of the X-axis values was measured to be 0.29 mm, 0.26 mm, 0.51 mm, and 0.08 mm, respectively. The mean of the Y-axis values was measured to be 0.75 mm, 0.5mm, 0.35 mm, and 0.29 mm, respectively. The mean of the Z-axis values was measured to be 0.5 mm, 0.28 mm, 0.22 mm, and 0.1 mm, respectively. There were dose reductions of 0.1%, 3.1%, 1.9% in D99 for 1-NC VMAT, 2-NC VMAT, and 3-NC VMAT, respectively. Conclusion: When treating with 50% or more of non-coplanar beams among total beams, image verification is required. And it is considered to make the treatment plan by adding a 1.5 mm margin to the GTV.

• The Journal of Korean Society for Radiation Therapy
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• v.18 no.1
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• pp.13-19
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• 2006

Purpose: To evaluate whether modified MUPIT applicator can effectively eradicate recurrent tumor in uterine cervix cancer and reduce rectal complication after complete radiation treatment. Materials and Methods: Modified MUPIT applicator basically consists of an acrylic cylinder with flexible brain applicator, an acrylic template with a predrilled array of holes that serve as guides for interstitial needles and interstitial needles. CT scan was peformed to determine tumor volume and the position of interstitial needles. Modified MUPIT applicator was applied to patient in operation room and the accuracy for position of interstitial needles in tumor volume was confirmed by CTscan. Brachytherapy was delivered using modified MUPIT applicator and RALS(192-lr HDR) after calculated computer planning by orthogonal film. The daily dose was 600cGy and the total dose was delivered 3,000 cGy in tumor volume by BID. Rectal dose was measured by TLD at 5 points so that evaluated the risk of rectal complication. Results: The application of modified MUPIT applicator improved dramatically dose distributions in tumor volume and follow-up of 3 month for this patient was clinically partial response without normal tissue complication, Rectal dose was measured 34.1 cGy, 57.1 cGy, 103.8 cGy, 162.7 cGy, 165.7 cGy at each points, especially the rectal dose including previous EBRT and ICR was 34.1 cGy, 57.1 cGy. Conclusion: Patients with locally recurrent tumor in uterine cervix cancel treated with modified MUPIT applicator can expect reasonable rates of local control. The advantages of the system are the fixed geometry provided by the template and cylinders. and improved dose distributions in irregular tumor volume without rectal complication.

• Radiation Oncology Journal
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• v.19 no.1
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• pp.53-65
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• 2001

Purpose : To improve the local control of patients with nasopharyngeal cancer, we have implemented 3-D conformal radiotherapy and forward intensity modulated radiation therapy (IMRT) to used of compensating filters. Three dimension conformal radiotherapy with intensity modulation is a new modality for cancer treatments. We designed 3-D treatment planning with 3-D RTP (radiation treatment planning system) and evaluation dose distribution with tumor control probability (TCP) and normal tissue complication probability (NTCP). Material and Methods : We have developed a treatment plan consisting four intensity modulated photon fields that are delivered through the compensating tilters and block transmission for critical organs. We get a full size CT imaging including head and neck as 3 mm slices, and delineating PTV (planning target volume) and surrounding critical organs, and reconstructed 3D imaging on the computer windows. In the planning stage, the planner specifies the number of beams and their directions including non-coplanar, and the prescribed doses for the target volume and the permissible dose of normal organs and the overlap regions. We designed compensating filter according to tissue deficit and PTV volume shape also dose weighting for each field to obtain adequate dose distribution, and shielding blocks weighting for transmission. Therapeutic gains were evaluated by numerical equation of tumor control probability and normal tissue complication probability. The TCP and NTCP by DVH (dose volume histogram) were compared with the 3-D conformal radiotherapy and forward intensity modulated conformal radiotherapy by compensator and blocks weighting. Optimization for the weight distribution was peformed iteration with initial guess weight or the even weight distribution. The TCP and NTCP by DVH were compared with the 3-D conformal radiotherapy and intensitiy modulated conformal radiotherapy by compensator and blocks weighting. Results : Using a four field IMRT plan, we have customized dose distribution to conform and deliver sufficient dose to the PTV. In addition, in the overlap regions between the PTV and the normal organs (spinal cord, salivary grand, pituitary, optic nerves), the dose is kept within the tolerance of the respective organs. We evaluated to obtain sufficient TCP value and acceptable NTCP using compensating filters. Quality assurance checks show acceptable agreement between the planned and the implemented MLC(multi-leaf collimator). Conclusion : IMRT provides a powerful and efficient solution for complex planning problems where the surrounding normal tissues place severe constraints on the prescription dose. The intensity modulated fields can be efficaciously and accurately delivered using compensating filters.

• Radiation Oncology Journal
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• v.22 no.3
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• pp.165-176
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• 2004

Purpose: Firstly, to analyze facto in terms of radiation treatment that might potentially cause subfrontal relapse in two patients who had been treated by craniospinal irradiation (CSI) for medulloblastoma, Secondly, to explore an effective salvage treatment for these relapses. Materials and Methods: Two patients who had high-risk disease (T3bMl, T3bM3) were treated with combined chemoradiotherapy CT-simulation based radiation-treatment planning (RTP) was peformed. One patient who experienced relapse at 16 months after CSI was treated with salvage surgery followed by a 30.6 Gy IMRT (intensity modulated radiotherapy). The other patient whose tumor relapsed at 12 months after CSI was treated by surgery alone for the recurrence. To investigate factors that might potentially cause subfrontal relapse, we evaluated thoroughly the charts and treatment planning process including portal films, and tried to find out a method to give help for placing blocks appropriately between subfrotal-cribrifrom plate region and both eyes. To salvage subfrontal relapse in a patient, re-irradiation was planned after subtotal tumor removal. We have decided to treat this patient with IMRT because of the proximity of critical normal tissues and large burden of re-irradiation. With seven beam directions, the prescribed mean dose to PTV was 30.6 Gy (1.8 Gy fraction) and the doses to the optic nerves and eyes were limited to 25 Gy and 10 Gy, respectively. Results: Review of radiotherapy Portals clearly indicated that the subfrontal-cribriform plate region was excluded from the therapy beam by eye blocks in both cases, resulting in cold spot within the target volume, When the whole brain was rendered in 3-D after organ drawing in each slice, it was easier to judge appropriateness of the blocks in port film. IMRT planning showed excellent dose distributions (Mean doses to PTV, right and left optic nerves, right and left eyes: 31.1 Gy, 14.7 Gy, 13.9 Gy, 6.9 Gy, and 5.5 Gy, respectively. Maximum dose to PTV: 36 Gy). The patient who received IMRT is still alive with no evidence of recurrence and any neurologic complications for 1 year. Conclusion: To prevent recurrence of medulloblastoma in subfrontal-cribriform plate region, we need to pay close attention to the placement of eye blocks during the treatment. Once subfrontal recurrence has happened, IMRT may be a good choice for re-irradiation as a salvage treatment to maximize the differences of dose distributions between the normal tissues and target volume.

• Korean Journal of Food Science and Technology
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• v.54 no.1
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• pp.28-34
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• 2022

Glioblastoma is the most common primary malignant brain tumor and has an extremely poor prognosis. Glioblastoma stem cells (GSCs) contribute to tumor initiation, recurrence, and resistance to therapy, and are thus a key therapeutic target. The peel of Citrus unshiu Markovich has been used in traditional medicine in East Asia to treat various diseases. In this study, we investigated the anticancer activity and molecular mechanism of the chloroform extract of this natural product (CECU) in U87MG GSCs. The results show that CECU inhibited the proliferation, tumorsphere formation, and migration of U87MG GSCs by causing cell cycle arrest at the G0/G1 phase and apoptosis. In addition, CECU downregulated key cancer stemness regulators, including CD133, Oct4, Nanog, integrin α6, ALDH1A1, and STAT3 signaling in U87MG GSCs. Furthermore, CECU significantly suppressed in vivo tumor growth of U87MG GSCs in a chorioallantoic membrane model. Therefore, CECU can be utilized as a natural medicine for the prevention and treatment of glioblastoma.