Park Woo Yoon;Choi Doo Ho;Choi Eun Kyung;Kim Il Han;Ha Sung Whan;Park Charn Il
Radiation Oncology Journal
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v.6
no.2
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pp.169-176
/
1988
A retrospective study was performed on 15 patients with suprasellar germ cell tumors treated by megavoltage external beam irradiation between Feb. 1979 and Dec. 1985. Follow-up period of survivors was 30 to 91 months. Histologic diagnosis was obtained before radiation therapy in 10patients (9 germinomas and 1 mixed). Five patients were treated without histologic verification. In 9 patients with biopsy-proven germinomas radiation therapy was delivered to the craniospinal axis in 6, to the whole brain in 3. In 5 patients with mixed germ cell tumor or elevated tumor marker, irradiation was delievered to the craniospinal axis in 2, to the whole brain in 2, and to the primary site only in 1. Total doses ranged from 5,000 to 5,500 cGy to the primary site, 3,000 to 4,400 cGy to the whole brain, and 1,300 to 3,000 cGy to the spine. In these 14, local tumor was controlled and primary or spinal failure was not observed. One patient without elevated tumor marker was treated to the whole brain. The tumor was not controlled and he had spinal recurrence. Overall survival and disease-free survival rates were $86\%$ at 5 year. It is proven that radiation therapy is an effective treatment for suprasellar germ cell tumors. The neuroendocrinologic presentation, tumor marker status, early response to radiation measured on CT seem to be useful means for selecting patients for radiation therapy when tissue diagnosis is not available.
In an attempt to observe the Possible radioprotective actions of single or combined application of reduced glutathione (GSH) and cold exposure in mammals, the albino mouse was subjected to GSH injection, cold exposure at $-1{\pm}0.2C$ and whole-body X-irradiation with 900r either singularly or in combination, or the X-irradiation following the cold exposure and/or GSH injection. The levels of intrinsic NP-SH and NP-SS of the liver, brain and heart were measured at one hour after each application, and the results were compared with the control, i.e., non-irradiated and non-cold exposed normal animal. NP-SH was measured by the Ellman's method, and NP-SS was measured by the electrolytic reduction method described by Dohan and Woodward. The results thus obtained are summarized as follows: 1) The levels of NP-SH in the liver, brain and heart of the normal mouse was $6.35{\pm}0.61,\;2.65{\pm}0.15\;and\;3.17{\pm}0.10{\mu}\;mol/gm\;wet\;wt.$, respectively, and NP-SS was $3.09{\pm}0.11,\;2.95{\pm}0.20\;and\;0.18{\pm}0.24{\mu}\;mol/gm\;wet\;wt.$, respectively. 2) Though there were some degrees of difference among the tissues studied, a general tendency of (1) elevated NP-SH and NP-SS levels in the GSH injection group, (2) similar or slightly elevated NP-SH and NP-SS levels in the cold-exposed group, and (3) markedly decreased levels of NP-SH and NP-SS in the X-irradiated group, was observed. When GSH was injected prior to the X-irradiation, NP-SH and NP-SS in all the tissues studied showed generally higher values than in the group where the X-irradiation was given alone, and the values were close to the normal. In the group where the cold exposure was applied immediately after the X-irradiation, no significant difference was observed in the NP-SH and NP-S5 levels comparing with the X-irradiation group. On the contrary, when GSH was injected immediately prior to the X-irradiation or cold exposure, NP-SH and NP-SS levels were either similar to, or higher than, the normal value.
Purpose : To investigate the regulation of apoptosis and cell cycle in mouse brain irradiation. Materials and Methods : 8-week old male mice, C57B1/6J were given whole body $\gamma-radiation$ with a single dose of 25 Gy using Cobalt 60 irradiator. At different times 1, 2, 4, 8 and 24hr after irradiation, mice were killed and brain tissues were collected. Apoptotic cells were scored by TUNEL assay. Expression of p53, Bcl-2, and Bax and cell cycle regulating molecules; cyclins Bl, Dl, E and cdk2, cdk4, $p34^{cdc2}$ were analysed by Western blotting. Cell cycle was analysed by Flow cytometry. Results : The peak of radiation induced apoptosis is shown at 8 hour after radiation. With a single 25 Gy irradiation, the peak of apoptotic index in C57B1/6J is $24.0{\pm}0.25$ (p<0.05) at 8 hour after radiation. Radiation upregulated the expression of p53/tubulin, Bax/tubulin, and Bcl-2/tubulin with 1.3, 1.1 and 1.45 fold increase, respectively were shown at the peak level at 8 hour after radiation. The levels of cell cycle regulating molecules after radiation are not changed significantly except cyclin D1 with 1.3 fold increase. Fractions of Go-Gl, G2-M and S phase in the cell cycle does not specific changes by time. Conclusion : In mouse brain tissue, radiation induced apoptosis is particularly shown in a specific area, subependyma. These results and lack of radiation induced changes in cell cycle ofter better understanding of radiation response of noraml brain tissue.
Purpose : Radiotherapy has been the mainstay of the treatment of brain metastases. We evaluated the response rate, survival and prognostic factors of patients with brain metastases treated with radiotherapy for palliative purpose. Materials and Methods : From January 1994 through April 1997, in all 42 patients, a retrospective analysis was undertaken. Of these, 33 patients received whole brain irradiation with 30Gy in 10 daily fractions with or without a boost of 10Gy in 5 daily fractions to the site of solitary lesion. Nine patients failed to complete the planned treatment Results : Of 33 patients who finished radiotherapy, complete and partial response were observed in $4(12\%)$ patients and $22(67\%)$ ones, respectively. Overall response rate was $79\%$ and median survival was 4 months. In univariate analysis, prognostic factors affecting survival were initial neurologic function class(p=0.0136), extracranial tumor activity(p=0.042), and response after radiotherapy(p=0.001). Conclusion : We confirmed that whole brain irradiation is the effective means for treating the patient with brain metastases. initial neurologic function class, extracranial tumor activity, and response alter radiotherapy were identified as prognostic factors affecting survival.
Purpose: This study aimed to dosimetrically compare the technique of three-dimensional conformal radiotherapy (3D CRT), which is a traditional prophylactic cranial irradiation method, and the intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques used in the last few decades with the dynamic conformal arc therapy (DCAT) technique. Methods: The 3D CRT, VMAT, IMRT, and DCAT plans were prepared with 25 Gy in 10 fractions in a Monaco planning system. The target volume and the critical organ doses were compared. A comparison of the body V2, V5, and V10 doses, monitor unit (MU), and beam on-time values was also performed. Results: In planned target volume of the brain (PTVBrain), the highest D99 dose value (P<0.001) and the most homogeneous (P=0.049) dose distribution according to the heterogeneity index were obtained using the VMAT technique. In contrast, the lowest values were obtained using the 3D CRT technique in the body V2, V5, and V10 doses. The MU values were the lowest when DCAT (P=0.001) was used. These values were 0.34% (P=0.256) lower with the 3D CRT technique, 66% (P=0.001) lower with IMRT, and 72% (P=0.001) lower with VMAT. The beam on-time values were the lowest with the 3D CRT planning (P<0.001), 3.8% (P=0.008) lower than DCAT, 65% (P=0.001) lower than VMAT planning, and 76% (P=0.001) lower than IMRT planning. Conclusions: Without sacrificing the homogeneous dose distribution and the critical organ doses in IMRTs, three to four times less treatment time, less low-dose volume, less leakage radiation, and less radiation scattering could be achieved when the DCAT technique is used similar to conventional methods. In short, DCAT, which is applicable in small target volumes, can also be successfully planned in large target volumes, such as the whole-brain.
In order to evalute the effects of radiation on mammalian neuronal system, we have examined the effect of gamma-ray radiation on the monoamine oxidase (MAO) activity in monoaminergic neurons. Following the whole body irradiation, MAO activity in the rat brain was measured as well as in the liver for the comparative studies between the neuronal and nonneuronal system. The effects of some radiation protectors and sensitizers were also examined in addition to the $O_2$ effect. The results can be summarized as follows. 1) The MAO activity of rat brain was minimally affected by the radiation dose up to 1,700 cGy Radiation dose above 2,500 cGy inhibited the brain MAO activity by no less than $l0\%.$ MAO-A form was found to be particularly sensitive to radiation. The liver MAO was somewhat inhibited (by about $5\%$) but hardly dependent on the dose of radiation. 2) The inhibitory effect on the brain was initiated immediately by the radiation dose of 2,500 cGy. On the contrary, for the liver, the inhibitory effect became apparent only 2 days after irradiation. 3) Two days after a dose of 2,500 cGy, Vmax and Km of the brain mitochondrial MAO decreased. For liver, Vmax decreased while Km increased, which indicates the kinetic patterns for the neuronal and nonneruronal systems are not affected similarly by radiation. 4) The effect of several known radiation protectors and sensitizers on MAO activity was tested ut no definite results were obtained. The level of -SH group increased in some degree upon radiation but not by the compounds. 5) MAO activity was not affected by $O_2$ concentration, while an elevated level of lipid peroxidase was found under the same condition. The results described here indicate that characteristics of MAO, one of the most important central nervous system enzymes, are liable to radiation, which is partially differentiated from the liver MAO. Also indicated are that the -SH groups are hardly related to the effect of radiation but the production of the lipid peroxide seems to be somewhat correlated to the effect of radiation.
The prophylactic use of phenytoin during and after brain surgery and cranial irradiation is a common measure in brain tumor therapy. Phenytoin has been associated with variety of adverse skin reactions including urticaria, erythroderma, erythema multiforme (EM), Stevens-Johnson syndrome, and toxic epidermal necrolysis. EM associated with phenytoin and cranial radiation therapy (EMPACT) is a rare specific entity among patients with brain tumors receiving radiation therapy while on prophylactic anti-convulsive therapy. Herein we report a 41-year-old female patient with left temporal glial tumor who underwent surgery and then received whole brain radiation therapy and chemotherapy. After 24 days of continous prophylactic phenytoin therapy the patient developed minor skin reactions and 2 days later the patient returned with generalized erythamatous and itchy maculopapuler rash involving neck, chest, face, trunk, extremities. There was significant periorbital and perioral edema. Painful mucosal lesions consisting of oral and platal erosions also occurred and prevented oral intake significantly. Phenytoin was discontinued gradually. Systemic admistration of corticosteroids combined with topical usage of steroids for oral lesions resulted in complete resolution of eruptions in 3 weeks. All cutaneous lesions in patients with phenytoin usage with the radiotherapy must be evoluated with suspicion for EM.
Purpose : To assess the efficacy of craniospinal radiotherapy in patients with acute lymphoblastic leukemia (ALL) experiencing the CNS relapse. Materials and Methods: Thirty ALL patients with relapse in the central nervous system (CNS) were treated with radiotherapy and intrathecal chemotherapy. Age ranged 2 to 46. The number of males and females were all 15. Twenty-two cases were previously treated with presymptomatic radiotherapy to the whole brain. The extent of radiotherapy was the whole brain (18-24 Gy) and the whole spine (12 Gy) in 21 cases but the whole brain only in the 9 cases with poor performance. Results : The complete remission rate in the CNS was $100{\%}$. Among the 12 cases ($40{\%}$) who had secondary relapse, 9 cases had the bone marrow relapse alone, 2 cases had the CNS and bone marrow relapse, 1 cases had the CNS relapse alone. Higher CNS remission rate was observed when the initial remission duration was longer than 24 months or radiation was delivered to the whole brain and the whole spine. Survival rate at 2 year was $31.6{\%}$. Remission duration in the 10 living patients ragned from 9 to 87 months (median; 58 months).
Kim Yong Seok;Woo Chong Kyu;Lee Yong Sung;Koh Jai Kyung;Chun Ha Chung;Lee Myung Za
Radiation Oncology Journal
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v.14
no.4
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pp.265-279
/
1996
Damage produced by radiation elicits a complex response in mammalian cells, including growth rate changes and the induction of a variety of genes associated with growth control and apoptosis. At doses of 10,000 cGy or greater, the exposed individual was killed in a matter of minutes to a couple of days, with symptoms consistent with pathology of the central nervous system(CNS) including degenerative changes. The nature of the damage in irradiated cells underlies the unique hazards of ionizing radiation. Radiation injury to CNS is a rare event in clinical medicine, but it is catastrophic for the patient in whom it occurs. The incidence of cerebral necrosis has been reported as high as 16% for doses greater than 6,000 cGy. In this study, the effect of radiation on brain tissue was studied in vivo. Jun and p53 genes in the rat brain were induced by whole body irradiation of rat with 600Co in doses between 1 Gy and 100 Gy and analyzed for expression of jun and p53 genes at the postirradiation time up to 6 hours. Northern analyses were done using 1.8 Kb & 0.8 Kb-pGEM-2-JUN/Eco RI/Pst I fragments, 2.0 Kb-php53B/Bam HI fragment and ,1.1 Kb-pBluescript SK--ACTIN/Eco RI fragment as the digoxigenin or [${\alpha}^{32}P$] dCTPlabeled probes for Jun, p53 and ${\beta}$-actin genes, respectively. Jun gene seemed to be expressed near the threshold levels in 1 hour after irradiation of $^{60}$Co in dose less than 1 Gy and was expressed in maximum at 1 hour after irradiation of $^{60}$Co in dose of 30 Gy. Jun was expressed increasingly with time until 5 or 6 hours after irradiation of $^{60}$Co in doses of 1 Gy and 10 Gy. After irradiation of $^{60}$Co in dose between 20 Gr and 100 Gy, the expression of Jun was however increased to peak in 2 hours and decreased thereafter. p53 gene in this study also seemed to be expressed near the threshold levels in 1 hour after irradiation of $^{60}$Co in dose less than 1 Gy and was expressed in maximum at 6 hours after irradiation of $^{60}$Co in dose of 1 Gy, p53 was expressed increasingly with time until 5 or 6 hours after irradiation of $^{60}$Co in dose between 1 Gy and 40 Gy. After irradiation of $^{60}$Co in doses of 50 Gy and 100 Gy, the expression of p53 was however increased to peak in 2 hours and decreased thereafter. The expression of Jun and p53 genes was not correlative in the brain tissue from rats. It seemed to be very important for the establishment of the optimum conditions for the animal studies relevant to the responses of genes inducible on DNA damage to ionizing radiation in mammalian cells. But there are many limitations to the animal studies such as the ununiform patterns of gene expression from the tissue because of its complex compositions. It is necessary to overcome the limitations for development of in situ Northern analysis.
20 cases of midline pineal tumors and 3 suprasellar germinomas received radiation therapy at Yonsei University Medical College, Severance hospital from 1971 to 1982 were reviewed. 12 cases were pathologically proved; 10 germinomas, 1 pineoblastoma, and 1 pineocytoma. 11 cases received radiotherapy without biopsy confirmation. Although treatment fields varied from small field to whole brain irradiation, but not to the spinal cord, most patients received 4000-5000 rads irradiation to the primary tumor site. 17 patients are alive without evidence of disease and 5 year actuarial NED survival is 73.2%. 9 of 10 biopsy proved germinomas and all 6 presumed germinomas are alive and well. Optimum radiation dose, adequate irradiation field, tumor response to radiation observed in serial CT scan and role of radiation therapy in the management of pineal tumors are also discussed.
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