• Radiation Oncology Journal
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• v.19 no.2
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• pp.163-170
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• 2001

Purpose : The measurement of radiation survival using a clonogenic assay, the established standard, can be difficult and time consuming. In this study, We have used the MTT assay, based on the reduction of a tetrazolium salt to a purple formazan precipitate by living cells, as a substitution for clonogenic assay and have examined the optimal condition for performing this assay in determination of radiation sensitivity. Materials and Methods : Four human cancer cell lines - PCI-1, SNU-1066, NCI-H630 and RKO cells have been used. For each cell line, a clonogenic assay and a MTT assay using Premix WST-1 solution, which is one of the tetrazolium salts and does not require washing or solubilization of the precipitate were carried out after irradiation of 0, 2, 4, 6, 8, 10 Gy. For clonogenic assay, cells in $25\;cm^2$ flasks were irradiated after overnight incubation and the resultant colonies containing more than 50 cells were scored after culturing the cells for $10\~14$ days. For MTT assay, the relationship between absorbance and cell number, optimal seeding cell number, and optimal timing of assay was determined. Then, MTT assay was performed when the irradiated cells had regained exponential growth or when the non-irradiated cells had undergone four or more doubling times. Results : There was minimal variation in the values gained from these two methods with the standard deviation generally less than $5\%$, and there were no statistically significant differences between two methods according to t-test in low radiation dose (below 6 Gy). The regression analyses showed high linear correlation with the $R^2$ value of $0.975\~0.992$ between data from the two different methods. The optimal cell numbers for MTT assay were found to be dependent on plating efficiency of used cell line. Less than 300 cells/well were appropriate for cells with high plating efficiency (more than $30\%$). For cells with low plating efficiency (less than $30\%$), 500 cells/well or more were appropriate for assay. The optimal time for MTT assay was after 6 doubling times for the results compatible with those of clonogenic assay, at least after 4 doubling times was required for valid results. In consideration of practical limits of assay (12 days, in this study) cells with doubling time more than 3 days were inappropriate for application. Conclusion : In conclusion, it is found that MTT assay can successfully replace clonogenic assay of tested cancer cell lines after irradiation only if MTT assay was undertaken with optimal assay conditions that included plating efficiency of each cell line and doubling time at least.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.142-145
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• 2001

Purpose : Acute leukemia with hyperleukocytosis (more than $10^5/mm^3$) is at high risk of early sudden death, usually from intracerebral hemorrhage. Emergency cranial irradiation is a relatively simple approach to solve this the problem. We summarized our experience of cranial irradiation in 24 leukemic children who presented with hyperleukocytosis. Methods and Materials : Between 1990 and 1998, 40 children with acute leukemia presenting with hyperleukocytosis were referred for emergency cranial irradiation. Among these patients, 24 children were evaluable. There were 16 boys and eight girls, their ages ranged from 2 to 13 years (median 9.5 years). The initial leukocyte counts ranged $109,910/mm^3\;to\;501,000/mm^3$. Peripheral blood smear was peformed in all patients and noted the morphology of the blast. Introduction of emergency cranial irradiation was determined by the leukocyte counts (more than 100,000/mm) and the existence of the blast in peripheral blood smear. All patients were treated with intravenous hydration with alkaline fluid and oral allopurinol. Cranial irradiation started on the day of diagnosis. With 2 Gy in one fraction in 4 patients, 4 Gy in two fractions in 20 patients. Results : The WBC count had fallen in 19 patients (83%) and no intracerebral hemorrhage occurred after irradiation. There were five cases of early deaths. Four patients died of metabolic complications, and one patient with intracerebral hemorrhage. He died 5 hours after cranial irradiation. No patient had any immediate side effect from cranial irradiation. Conclusion : Our data suggest, that emergency cranial irradiation can be safely chosen and effective in childhood leukemic patients presenting with high leukocyte counts.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.113-117
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• 2001

Purpose : To evaluate effect of postoperative radiotherapy on survival and local control for patients with non-small cell lung cancer (NSCLC). Materials and Methods : Ninety two NSCLC patients with N1or N2 involvement who were treated with postoperative radiotherapy following surgery with curative intent from May 1987 to October 1999 were retrospectively analyzed. Age of the patients was ranged from 32 to 78 years. According to TNM Stage, 35 patients had Stage II and 57 had Stage III disease. There were 49 patients with N1 involvement and 43 patients with N2 involvement. Fifty six patients were noted to have $T1\~2$ tumors and 36 patients to have $T3\~4$ tumors. Delivered total dose was ranged from 40 to 60 Gy. Majority of patients received 50 Gy or 50.4 Gy. Follow-up period was ranged from 9 month to 7 years with median follow-up of 26 months. Results : Overall survival rates at 3 and 5 years for entire group of patients were $46\%\;and\;38\%$, respectively. Corresponding disease free survival rates were $44\%\;and\;36\%$. There was significant difference in survival between patients with Stage II and Stage III disease ($50\%\;vs\;28\%$ at 5-year). Five year survival rates for N1 and N2 patients were $52\%\;and\;20\%$, respectively (p<0.05). These were $40\%\;and\;34\%$ for patients with $T1\~2$ tumors and $T3\~4$ tumors. There were documented local relapses in $13\%$ of the patients. For patients with N1 and N2 Stage, local relapse rates were $8\%\;and\;18\%$, respectively. Conclusion : Our study confirms that postoperative radiotherapy for patients with non-small cell lung cancer improves local control. However, influence of postoperative radiotherapy on long-term survival is less clear. More effective systemic treatment to prevent distant metastasis should be investigated in future study to improve long-term survival.

• Radiation Oncology Journal
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• v.10 no.1
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• pp.35-41
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• 1992

Forty eight patients with adenoid cystic carcinoma (ACC) in the head and neck treated between 1979 and 1990 were reviewed according to treatment modalities and clinical courses. The common site of origin was minor salivary gland ($69\%$), mostly hard palate and maxillary sinus. 11 patients received radiation therapy (RT) alone and 37 patients received combined surgery and radiation therapy. The follow-up period of the survivors ranged from 4 to 118 months (median 49.5 months). The 5 year local control rate was $69.3\%$, $67.3\%$ and 83.9$\%$ in RT alone, conservative operation (OP)+RT and radical OP+RT group, respectively (p>0.05). The control of local disease was best achieved with radical OP+RT. In postoperative RT, high dose ($\ge$60 Gy) and generous field size($\ge$64 cm$^2$) yielded a better local control rate. Actuarial overall survival rate was $79.0\%$, at 5 years and $19.2\%$ at 10 years. Distant metastases (DM) developed in $40\%$ of patients, mostly in the lung. Disease-free (NED) survival rate was $45.8\%$ at 5 years and significant differences did not exist according to primary sites and treatment options. Survival rate after the onset of DM was $19.5\%$ at 5 years. Occurrence of DM tends to lower survival significantly. In an effort to find the role of RT in the treatment of ACC, our data suggest that a well-planned postoperative RT employing a high dose and generous field size can produce high local control rate and remaining urgent problem of distant metastasis demands more effective chemotherapy for the purpose of improving survival of ACC patients.

• Radiation Oncology Journal
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• v.10 no.1
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• pp.59-67
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• 1992

From March 1979 through December 1986, 124 patients with early stage carcinoma of the uterine cervix received curative radiation therapy. According to FIGO classification, 35 patients were stage IB and 89 were stge II A. In stage IB, five year locoregional control, five year disease free survival, and five year overall survival was $79.0\%$, $76.4\%$ and $81.8\%$, respectively. In stage II A, five year locoregional control, five year disease free survival, and five year overall survival were $78.0\%$, $66.8\%$, and $72.1\%$, respectively. To identify prognostic factors, pretreatment parameters including age, ECOG performance status, number of pregnancies, history of diabetes mellitus and hypertension, histology, size and shape of primary tumor, CT findings and blood parameters were retrospectively analyzed in terms of locoregional control, disease free survival and overall survival using univariate analysis and multivariate analysis. In univariate analysis, tumor size on physicai examination and rectal invasion on CT significantly affected locoregional control, disease free survival and overall survival. Parametrial involvement on CT was a significant prognostic factor on locoregional control and disease free survival. Hemoglobin level affected disease free survival and overall survival. Histology and age were significant prognostic factors on locoregional control. In multivariate analysis excluding CT finding, tumor size on physical examination was a significant factor in terms of locoregioal control and overall survival. Hemoglobin level was significant in terms of disease free survival. In multivariate analysis including CT, histology was a prognostic factor on locoregional control and disease free survival. Hemoglobin level and rectal invasion on CT were significant factors on locoregional control.

• Radiation Oncology Journal
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• v.13 no.1
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• pp.95-100
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• 1995

Purpose : To evaluate the effect on surface dose due to Aquaplast used for immobilizing the patients with head and neck cancers in photon beam radiotherapy Materials and Methods: To assess surface and buildup region dose for 6MV X-ray from linear accelerator(Siemens Mevatron 6740), we measured percent ionization value with the Markus chamber model 30-329 manufactured by PTW Frieburg and Capintec electrometer, model WK92. For measurement of surface ionization value, the chamber was embedded in $25{\times}25{\times}3cm^3$ acrylic phantom and set on $25{\times}25{\times}5cm^3$ polystyrene phantom to allow adequate scattering. The measurements of percent depth ionization were made by placing the polystyrene layers of appropriate thickness over the chamber. The measurements were taken at 100cm SSD for $5{\times}5cm^2$, $10{\times}10cm^2$ and $15{\times}15cm^2$ field sizes, respectively. Placing the layer of Aquaplast over the chamber, the same procedures were repeated. We evaluated two types of Aquaplast: 1.6mm layer of original Aquaplast(manufactured by WFR Aquaplast Corp.) and transformed Aquaplast similar to moulded one for immobilizing the patients practically. We also measured surface ionization values with blocking tray in presence or absence of transformed Aquaplast. In calculating percent depth dose, we used the formula suggested by Gerbi and Khan to correct overresponse of the Markus chamber. Results : The surface doses for open fields of $5{\times}5cm^2$, $10{\times}10cm^2$, and $15{\times}15cm^2$ were $79\%$, $13.6\%$, and $18.7\%$, respectively. The original Aquaplast increased the surface doses upto $38.4\%$, $43.6\%$, and $47.4\%$, respectively. For transformed Aquaplast, they were $31.2\%$, $36.1\%$, and $40.5\%$, respectively. There were little differences in percent depth dose values beyond the depth of Dmax. Increasing field size, the blocking tray caused increase of the surface dose by $0.2\%$, $1.7\%$, $3.0\%$ without Aquaplast, $0.2\%$, $1.9\%$, $3.7\%$ with transformed Aquaplast, respectively. Conclusion: The original and transformed Aquaplast increased the surface dose moderately. The percent depth doses beyond Dmax, however, were not affected by Aquaplast. In conclusion, although the use of Aquaplast in practice may cause some increase of skin and buildup region dose, reductioin of skin-sparing effect will not be so significant clinically.

• Radiation Oncology Journal
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• v.20 no.1
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• pp.34-40
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• 2002

Purpose : This study was undertaken to retrospectively evaluate white blood ceil kinetics, especially lymphocyte depression after different treatments, and to find the correlation between immunosuppression and large blood volume and dynamic blood flow within the mediastinal radiotherapy (RT) field in lung cancer. Materials and Methods : Thirty-four patients with lung cancer were retrospectively evaluated; 10 patients had only radiotherapy (RT group), 8 had chemotherapy (CT group) and 16 fad chemotherapy and radio-therapy (RT/CT group). The mean follow-up periods of the RT-including groups (RT group and RT/CT group) and the RT-excluding group (CT group) were 6 and 8 months, respectively. Complete blood cell counts including lymphocyte percentage $(\%)$ were checked weekly during RT but less frequently during CT and after RT and after RT. Results : Changes in total white blood cell counts were not significantly different among the three groups. The lymphocyte count and lymphocyte $\%$ were much lower in the RT-including groups than in the RT-excluding group. The difference between pre-treatment and final lymphocyte count and the difference between pre-treatment and final lymphocyte $\%$ were significant (p=0.044 and p=0.037) between the RT-including groups and the RT-excluding group. Conclusion : lymphopenia was more marked after treatment containing RT than CT only. Lymphopenia may be one cause of a compromised immune system after mediastinal irradiation in lung cancer. We suggest cautiously that previous studies showing evidence of lymphocyte apoptosis after low-dose irradiation and large blood volume and dynamic blood flow within the RT fields could be somewhat related to lymphopenia after mediastinal irradiation.

• Radiation Oncology Journal
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• v.20 no.1
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• pp.62-67
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• 2002

Purpose : This study was undertaken to analyze the efficacy and sphincter preservation rate of platinum based neoadjuvant chemotherapy Plus radiotherapy versus abdominoperineal resection and Postoperative radiotherapy for anal cancer. Materials and Methods : Data of forty-two patients with anal cancer were retrospectively analyzed. Among thirty-eight patients with epidermoid histology, four patients received radiotherapy, and nineteen patients received abdominoperineal resection and adjuvant radiotherapy with or without chemotherapy $(APR+RT{\pm}CT)$, and fifteen patients received neoadjuvant chemotherapy and radiotherapy (CRT). The CRT regimen was composed of three cycles of 5-fluorouracil $(1,000\;mg/m^2\;bolus\;on\;D1\~5)$ and cisplatin $(60\;mg/m^2\;bolus\;on\;D1)$ followed by 50.4 Gy to the tumor bed and regional lymphatics over 5.5 weeks. Both inguinal lymphatics were treated with an identical dose schedule. Residual disease was treated with an additional three cycles of identical adjuvant chemotherapy. An identical dose schedule was used for post-operative radiotherapy. Median follow-up period was eighty-five months. Results : Overall five-year survival rates were $80.3\%$, 88.9 and $79.4\%$ for entire patients, $APR+RT{\pm}CT$ group, and the CRT group, respectively. No significant difference was found between the two groups (p=0.49). Anus preservation rate for the CRT group was $86.7\%$. Age (0=0.0164) and performance status (p=0.0007) were found to be significant prognostic factors by univariate analysis. Age (p=0.0426), performance status (p=0.0008), and inguinal lymph node metastasis (e=0.0093) were statistically significant prognostic factors by multivariate analysis. No case of RTOG grade 3 complication or higher was reported. Conclusion : This and other recent studies have shown that combined chemotherapy plus radiotherapy for anal cancer results in a high rate of anal sphincter preservation as well as local control and survival. Furthermore, neoadjuvant use of chemotherapy with a cisplatin based regimen rather than a concurrent regimen may lead to a decrease in complications.

• Radiation Oncology Journal
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• v.10 no.2
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• pp.171-180
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• 1992

The precise role of radiotherapy for low grade gliomas including the optimal radiation dose and timing of treatment remains unclear. The information given by a retrosepctive analysis may be useful in the design of prospective randomized studies looking at radiation dose and time of surgical and radiotherapeutic treatment. The records of 56 patients (M:F = 29:27) with histologically verified cerebral low grade gliomas (47 cases of grade 1 or 2 astrocytomas and 9 oligodendrogliomas) diagnosed between 1979 and 1989 were retrospectively reviewed. The extent of surgical tumor removal was gross total or radical subtotal in 38 patients ($68\%$) and partial or biopsy only in the remaining 18 patients ($32\%$). Postooperative radiation therapy was given to 36 patients ($64\%$) of the total 56 patients with minimum dose of 5000 cGy (range=1250 to 7220 cGy). The 5-and 10-year survival rates for the total 56 patients were $44\%$ and $32\%$ respectively with a median survival of 4.1 years. According to the histologic grade the 5- and 10-year survivals were $52\%$ and $35\%$ for the 24 patients respectively with grade I astrocytomas compared to $20\%$ and $10\%$ for the 23 patients with grade II astrocytomas. Survival of oligodendroglioma patients was greater than those with astrocytoma ($65\%$ vs $36\%$ at 5 years), and the difference was also remarkable in the long term period of follow up ($54\%$ vs $23\%$ at 10 years). Those who received high-dose radiation therapy ($\geq$5400 cGy) had significant better survival than those who received low-dose radiation (< 5400cGy) or surgery alone (p<0.05). The 5- and 10-year survival rates were, respectively $59\%$ and $46\%$ for the 23 patients receiving high-dose radiation, $36\%$ and $24\%$ for the 13 patients receiving low-dose radiation, and $35\%$ and $26\%$ for the 20 patients with surgery alone. Survival rates by the extent of surgical resection were similar at 5 years ($46\%$ vs $41\%$), but long term survival was quite different (p<0.01) between total/subtotal resection and partial resection/biopsy ($41\%$ and $12\%$, resepctively). Previously published studies have identified important prognostic factors in these tumor: age, extent of surgery, grade, performance status, and duration of symptoms. But in our cases statistical analysis revealed that grade I histology (p<0.025) and young age (p<0.001) were the most significant good prognostic variables.

• Radiation Oncology Journal
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• v.17 no.4
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• pp.321-328
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• 1999

Purpose : Total body irradiation (TBI) or whole body irradiation is used to acquire immune suppression, to treat malignant lymphoma and leukemia, and as an conditioning regimen for bone marrow transplantation. For these purposes, many methods were developed to obtain homogenous dose distribution. The objective of this study was to analyze and confirm the accuracy and the homogeneity of the treatment setup, the parallel opposed lateral technique, currently used in Seoul National University Hospital. Materials and Metheods : Surface dose data, measured with a thermoluminescent dosimeter, of 8 patients among 10 patients, who were given total body irradiation with the parallel opposed lateral technique between September 1996 to August 1998, at Seoul National University Hospital were analyzed. Surface doses were measured at the head, neck, axilla, thigh, and ankle level. Surface and midline doses were measured with similar set-up and technique in the Humanoid phantom. Results : Measured surface doses relative to prescribed dose for the head, neck, axilla, thight, and ankle leve were $91.3{\pm}7.8,{\;}98.3{\pm}7.5,{\;}95.1{\pm}6.3,{\;}98.3{\pm}5.5$, and $95.3{\pm} 6.3\%$, respectively. The midline doses of the head, neck, axilla, thigh, and ankle level estimated from the surface-to-midline ratios in the Humanoid Phantom were $103.4{\pm}9.0,{\;}107.8{\pm}10.5,{\;}91.1{\pm}6.1,{\pm} 93.8{\pm}4.5,{\;}and{\;}104.5{\pm}9.3\%$, respectively. Measured surface doses and estimated midline doses ranged from $-8.9\%$ to $+7.8\%$. Midline doses at the neck and the axilia level deviated more than $5\%$ from the prescribed doses. The difference of the estimated midline doses at the neck and the axilla level and the actual doses were attributed to the thickness differences between the Humanoid phantom and the patients. Conclusion Distribution of the midline doses as well as the suface doses were measured to be within $-8.7\~{\pm}7.8\%$ range. Actual dose distribution in the patient is expected to be better than the measured dose range mainly attributed to thickness difference between the patient and the Humanoid phantom.