• Radiation Oncology Journal
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• v.21 no.3
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• pp.222-226
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• 2003

Purpose: The interaction of the Fas: Fas ligand has been recognized to play an important role in radiation induced apoptosis. The purpose of this study was to investigate the role of Fas and Fas ligand mutations, in radiation-induced apoptosis in vivo. Materials and Methods: Mice with a mutation in the Fas ($C57BL/6J-Fas^{lpr}$) and its normal control (C57BL/6J) and the Fas ligand ($C3H/HeJ-Fas^{gld}$) and its normal control (C3H/HeJ), were used in this study. Eight-week old male mice were given whole body radiation. After irradiation, the mice were killed at various time intervals, and their spleens collected. Tissue sample was stained with hematoxylin-eosin, and the numbers of apoptotic cells scored. The regulating molecules of apoptosis including the p53, Bcl-2, Bax, $Bcl-X_L\;and\;Bcl-X_s$ genes were also analyzed by Western blotting. Results: With 2.5 Gy and 10 Gy of irradiation, the levels of apoptosis were lower in the $C57BL/6J-Fas^{lpr}\;and\;C3H/HeJ-Fas^{gld}$ mice than in the control mice (p<0.05). With the expression of apoptosis regulating molecules, the Bax was increased in both the C57BL/6J and C3H/HeJ mice in response to radiation; the peak levels of Bax in the C57BL6J and C3H/HeJ were 3 and 3.3-fold higher after 8hr, respectively. However the Bax was not increased in either the $C57BL/6J-Fas^{lpr}\;or\;C3H/HeJ-Fas^{gld}$mice. The p53, Bcl-X_L,\;Bcl-X_S$and Bcl-2 showed no significant changes in the $C57BL/6J-Fas^{lpr},\;C3H/HeJ-Fas^{gld}$, C57BL/6J and C3H/HeJ mice. Conclusion: The levels of radiation-induced apoptosis were lower in the lpr and gld, than the control mice, which seemed to be related to the level of Bax activation due to the radiation in the lpr and gld mice. This result suggests that Fas/Fas L plays an important role in radiation-induced apoptosis in vivo.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.288-297
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• 2004

Puporse: The aims of this study were to evaluate the change of $[^18F]fluoromisonidazole$($[^18F]FMISO$) uptake in C3H mouse squamous cell carcinoma-VII (SCC-VII) treated with mild hyperthermia ($42^{circ}C$) and nicotinamide and to assess the biodistribution of the markers in normal tissues under similar conditions. Methods and Materials: $[^18F]FMISO$ was producedby our hospital. Female C3H mice with a C3H SCC-VII tumor grown on their extremities were used. Tumors were size matched. Non-anaesthetized, tumor-bearing mice underwent control or mild hyperthermia at $42^{circ}C$ for 60 min with nicotinamide (50 mg/kg i.p. injected) and were examined by gamma counter, autoradiography and animal PET scan 3 hours after tracer i.v. injected with breathing room air, The biodistribution of these agents were obtained at 3 h after $[^18F]FMISO$ injection. Blood, tumor, muscle, heart, lung, liver, kidney, brain, bone, spleen, and intestine were removed, counted for radioactivity and weighed. The tumor and liver were frozen and cut with a cryomicrotome into 10- um sections. The spatial distribution of radioactivity from the tissue sections was determined with digital autoradiography. Results: The mild hyperthermia with nicotinamide treatment had only slight effects on the biodistribution of either marker in normal tissues. We observed that the whole tumor radioactivity uptake ratios were higher in the control mice than in the mild hyperthermia with nicotinamide treated mice for $[^18F]FMISO$ ($1.56{\pm}1.03$ vs. $0.67{\pm}0.30$; p=0.063). In addition, autoradiography and animal PET scan demonstrated that the area and intensity of $[^18F]FMISO$ uptake was significantly decreased. Conclusion: Mild hyperthermla and nicotinamide significantly improved tumor hypoxia using $[^18F]FMISO$ and this uptake reflected tumor hypoxic status.

• Journal of Korean Neurosurgical Society
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• v.50 no.4
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• pp.304-310
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• 2011

Objective : Intrathecal methotrexate (MTX) therapy combined with whole brain radiotherapy (WBRT) is one of the major treatment modalities for leukemia and lymphoma involving the central nervous system (CNS). The purpose of this study was to retrospectively determine the incidences of leukoencephalopathy and disseminated necrotizing leukoencephalopathy (DNL) following intrathecal MTX therapy for CNS lymphoma or leukemia and to assess the potential risk factors. Methods : Between January 2000 and August 2009, 143 patients with CNS lymphoma or leukemia received intrathecal MTX therapy alone or in combination with WBRT at a single institution. Patients were followed up clinically and radiologically at regular two- or three-month intervals. Medical records were reviewed to obtain information regarding the patients' demographics, medical histories, radiologic characteristics, treatments, and clinical courses. Results : On follow-up MR images, leukoencephalopathy was found in 95 of 143 patients (66.4%). The median time to develop leukoencephalopathy was 6.6 months. Among those with leukoencephalopathy, four patients showed seven extensive white-matter changes with strongly enhancing lesions demonstrating DNL. Histological confirmation was done in six lesions of three patients and radiological diagnosis alone in one patient. Four lesions spontaneously disappeared on MR images without any treatment, with a mean duration of 14 months before disappearance of DNL. Conclusion : Leukoencephalopathy is a common phenomenon that occurs following intrathecal MTX therapy; however, DNL occurs at a very low incidence. For newly developed enhancing lesions, consideration for the occurrence of DNL should be taken to avoid unnecessary invasive procedures or therapies.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.93-99
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• 2002

Purpose : We intended to decrease late CNS reaction after radical radiotherapy for an intracranial germinoma by using combined neoadjuvant chemotherapy and involved-field radiotherapy. The efficacy in terms of its acute toxicity and short-term relapse patterns was analyzed. Materials and Methods : Eighteen patients were treated with combined neoadjuvant chemotherapy and radiotherapy between 1995 and 2001. The chemotherapy regimen used was the Children's Cancer Group (CCG) 9921A (cisplatin, cyclophosphamide, VP-16, vincristine) for 5 patients younger than 16 years, BEP (bleomycin, VP-16, cisplatin) for 12 patients, and EP (VP-16, cisplatin) for 1 patient. The radiotherapy covered the whole craniospinal axis for 5 patients, the whole brain for 1, and the partial brain (involved field) for 12. the primary lesion received tumour doses between 3,960 and 5,400 cGy. Results : The male to female ratio was 16:2 and the median age was 16 years old. The tumors were located in the pineal gland in 12 patients, in the suprasellar region in 1, in the basal ganglia In 1, in the thalamus in 1. Three patients had multiple lesions and ventricular seedings were shown at MRI. In 3 patients, tumor cells were detected in the cerebrospinal fluid and MRI detected a spinal seeding in 2 patients. The response to neoadjuvant chemotherapy was complete remission in 5 patients, partial remission in 12, and no response in 1. However, after radiotherapy, all except 1 patient experienced complete remission. The toxicity during or after chemotherapy greater than or equal to grade III was remarkable; hematologic toxicity was observed in 11 patients, liver toxicity in none, kidney toxicity in none, and gastrointestinal toxicity in one. One patient suffered from bleomycin-induced pneumonitis. Radiotherapy was therefore stopped and the patient eventually died of respiratory failure. The other 17 are alive without any evidence of disease or relapse during an average of 20 months follow-up. Conclusion : A high response rate and disease control was experienced, which was the same as observed other studies and the morbidity from chemotherapy-induced toxicity was similar. With these results, the results from adjuvant chemotherapy and involved-field radiotherapy cannot be concluded to be equal to those from extended-field radiotherapy. The long term follow-up study on later complications are required in order to draw definite conclusions on the optimal management with minimum side effects.

• 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.

• Journal of Korean Neurosurgical Society
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• v.30 no.sup1
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• pp.25-29
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• 2001

Objective : Intracranial metastasis is responsible for nearly 50% of mortalities of systemic cancers. Although its frequency is increasing and there is little doubt that improving the quality and expectancy of life is the final goal, the mode of treatment is still disputed. The authors report the postoperative motor function after surgery in patients with metastatic tumors around the motor cortex. Materials and Methods : We studied 24 patients with metastatic tumors around the central sulcus during the last 22 months. Motor function was assessed pre- and post-operatively as well as its response to corticosteroids. MRI, neuronavigation system and intraoperative ultrasonography were used for tumor localization and functional MRI and cortical stimulator were used to define the motor cortex. Results : Single metastasis was found in 13 cases(54%) and 11 cases(44%) had multiple foci. Thirteen cases were located in precentral, 7 in postcentral, and 4 in superior or middle-frontal lobe. The most common primary focus was the lung(16 cases). There was no difference in postoperative motor function improvement between the steroid responsive group and non-responsive group(92% versus 90%). Ninty-two percent of the patients showed significant improvement of motor function and lived independently but there was worsening in the upper extremity in one and in another no improvement. Whole brain radiation of 3000cGy was given in all cases and 4 patients died of recurrence in primary or intracranial focus during mean follow-up periods of 14 monthes. Conclusion : Surgery may provide substantial improvement of the motor function and quality of life of the patients with metastatic tumors around the motor cortex.

• Radiation Oncology Journal
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• v.18 no.2
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• pp.79-84
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• 2000

Purpose : To evaluate the effectiveness and tolerance of postoperative e지ernai beam radiotherapy for patients with low grade glioma of the brain and define the optimal radiotherapeutic regimen. Materials and Methods : Between June, 1985 and May, 1998, 72 patients with low grade gliomas were treated with postoperative radiotherapy immediately following surgery. Median age was 37 years with range of 11 to 76 years. Forty one patients were male and 31 patients were female with male to female ratio of 1.3:1. Of those patients, 15 underwent biopsy alone and remaining 57 did subtotal resection. The distribution of the patients according to histologic type was as follows: astrocytomas-42 patients (58$\%$), mixed oligodendrogliomas-19 patients (27$\%$), oiigodendrogliomas-11 patients (15$\%$). Two patients were treated with whole brain irradiation followed by cone down boost and remaining 70 patients were treated with localized field with appropriate margin. Ail of the patients were treated with conventional once a day fractionation. Most of patients received total tumor dose of 5000 $\~$ 5500 cGy. Results : The overall 5 and 7 year survival rates for entire group of 72 patients were 61$\~$ and 50$\~$. Corresponding disease free survival rates for entire patients were 53$\~$ and 45$\~$, respectively. The 5 and 7 year overall survival rates for astrocytomas, mixed oligodendrogiiomas, and oligodendrogiiorras were 48$\%$ and 45$\%$, 76$\%$ and 56$\%$, and 80$\%$ and 52$\%$, respectively. Patients who underwent subtotal resection showed better survival rates than those who did biopsy alone. The overall 5 year survival rates for sub total resection patients and biopsy alone patients were 57$\%$ and 43$\%$, respectively. Forty six patients who were 40 years or younger survived batter than 26 patients who were 41 years or older (overall survival rate at 5 years, 69$\%$ vs 45$\%$). Although one patient was not able to complete the treatment because of neurological deterioration, there was no significant treatment related acute toxicities. Conclusion : Postoperative radiotherapy was safe and effective treatment for patients with low grade gliomas. However, we probably need prospective randomized trial to define optimal treatment timing and schedule for low grade gliomas and select patient group for different treatment philosophies.

• The Journal of Korean Society for Radiation Therapy
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• v.26 no.2
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• pp.177-182
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• 2014

Purpose : The goal of this study was to compare and analysis the dose distribution and treatment time between Tomotherapy planning with fixed jaw(FJ) and dynamic jaw(DJ). Materials and Methods : Seven patients were selected in the study including five common clinical cases(brain, head and neck(HN), lung, prostate, spine). 1) Helical Tomotherapy plans with FJ and DJ were generated with the same planning parameters such as Modulation factor, Pitch and Field width. 2) Tomo_edge plans with a larger field width were generated to compare to conventional HT delivery with fixed jaw. Dosimetric evaluation indices for target coverage are Dmin, Conformity index(CI) and for whole body including target are $V_{10%}$, $V_{25%}$, $V_{50%}$, $V_{75%}$ using Dose-volume histogram(DVH). Also, Treatment time and Cumulative MU were used for clinical review on Tomo_edge. Results : In case of using the same field width of Tomotherapy planning with FJ and DJ, the averaged variations were $V_{10%}$: -11.91%, $V_{25%}$: -7.6%, $V_{50%}$ :-4.75%, $V_{75%}$: -1.04%. Tomo_edge with a larger field width provides the averaged variations for target coverage: Dmin: -0.72%, CI: -1.25% and also shows the tendency of a sharp $V_{x%}$ decline in low dose area. The clinical improvements in the larger field width with DJ were observed in the treatment time, ranging from -51.21% to -15.11, and the Cumulative MU decrease, ranging from -57.74% to -15.31%. Conclusion : Target coverage achieved by FJ and DJ with the same field width has little differences. But integral doses on whole body efficiently decreased. Compared to the conventional HT delivery, Tomo_edge with a larger field width presents a little worse target coverage. However, it provides faster treatment delivery and improved cranial-caudal target dose conformity. Therefore, Tomo_edge mode is efficient in improving the treatment time and integral dose while maintaining comparable plan quality in clinic.

• Radiation Oncology Journal
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• v.6 no.2
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• pp.183-194
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• 1988

Twenty five patients with histologically proven medulloblastoma received craniospinal radiotherapy (CSRT) at the Seoul National University Hospital from 1979 to 1984. The extent of tumor removal was biopsy only in 2 patients, partial in 18, and near total in 5. With orthogonal technique of CSRT, mainly 55Gy was delivered to the posterior fossa (PF), 40Gy to whole brain (WB), and 30Gy to whole spine (WS). And with AP; PA technique, 50Gy to PF, 45-50Gy to WB, and 36 Gy to WS. Complete remission was obtained in $84\%$ of patients. Among 21 CR's 10 failures were observed, thus total failure rate was $56\%$ (14/25). Of 14 faiure 13 had the primary failure, 11 failed in primary site alone, 1 failure was combined with ventricular seeding, and another 1 was combined with neck node metastasis. There was 1 isolated spinal failure. Actuarial overall survival rates at 3 and 5 years were $75\%$ and $54\%$, and disease-free survival rates were $58\%$ and $36\%$, respectively. Better 5 year disease-free survival was noted in patients with 55 Gy to the posterior fossa than those with 50Gy $(62\%\;vs\;17\%,\;p<0.05)$, in patients treated with orthogonal technique than those treated with AP:PA technique $(87\%\;vs\;12\%,\;p<0.05)$, and in patients with near total removal than those with partial or less removal of tumor $(56\%\;vs\;30\%,\;N.S.)$ Re-irradiation was not satisfactory No severe late sequelae was noted among the survivors. For the higher control of medulloblastoma, dose to posterior fossa should be at least 55Gy with orthogonal CSRT to small tumor burden. And dose reduction in the subarachnoidal spaces might be safe, but optimal dose to the subarchnoidal spaces should be determined by the thorough tumor staging before radiotherapy.

• Korean Journal of Digital Imaging in Medicine
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• v.14 no.2
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• pp.23-31
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• 2012

There are AEC mode and fix mode to exposure when the whole spine antero-posterior radiography is done by using DR equipment. This study compared the utility of fix mode to AEC mode, by evaluating organ dose and effective dose and by examining the quality of radiographic image. GE DEFINIUM 8000 and ART-200X Rando Phantom manufactured by Flukebiometical were used for this study. The Rando phantom was set in front of wall detector of X-rays equipment. AEC mode was set at 80kVp and Fix mode was set at 80kVp, 25mAs, 32mAs, 40mAs, and 50mAs. Whole spine AP image were aquired by combining C, T-L and L-S spine images obtained through 3 exposures. When obtaining C, T-L and L-S spine images, were checked for Air kerma (mGy) value calculated by UNFORS Xi meter attached at the phantom surface of center of radiation field. The effective and organ doses were compared by PCXMC program (PC-Based Monte Carlo Program). The quality of obtained radiographic image was evaluated visually by 3 radiologists using resolution chart. When the effective doses was calculated based on tissue weighting factor of ICRP-103, 1.278mSv was measured by AEC mode, and Fix mode measured 0.405mSv at 25mAs, 0.518mSv at 32mAs, 0.649mSv at 40mAs, and 0.810mSv at 50mAS. In addition, the organ dose measured with esposure at 25mAs by Fix mode was almost equivalent to the organ dose by AEC mode, at the esophagus, thyroid, oral mucosa, salivaly glands located at the cervical spine part, while the organ dose by Fix mode was in general lower than the organ dose by AEC mode at the other organs. When Fix mode at 32mAs, 40mAs, and 50mAs was compared to AEC mode for organ dose in 26 organs, AEC mode had higher measurement in 21 organs but not for than brain, trachea, thyroid, oral mucosa, and salivaly glands which are located at the cervical spine part. The image quality evaluated by resolution test chart was much higher with AEC mode than the quality with Fix mode at all exposure conditions. However, while the image quality of cervical spine exposured at 50mAs by Fix mode was lower than the quality of AEC mode, thoraco-lumbar spine and lumbo-sacral spine were calculated and the quality was similar to AEC mode. Scoliosis occurs mainly at thoraco-lumbar and lumbo-sacral spine, not at cervical spine. Compared to AEC mode, Using the appropriate protocol (80kVp, 50mAs) of fix mode for whole spine AP radiography was thought to be useful because the image quality of the thoraco-lumar and lumbo-sacral spine was similar on AEC mode, Also organ and effective doses can be decreased with Fix mode. Therefore, It is considered that fix mode can be used properly with AEC mode for whole spine AP radiography when considering patient's body posture.