• Radiation Oncology Journal
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• v.34 no.2
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• pp.96-105
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• 2016

Purpose: The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45-50 Gy in 25-28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. Materials and Methods: A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil. Radical resection was scheduled for 8 weeks after concurrent chemoradiotherapy. Results: Between September 2010 and August 2013, 175 patients were treated with preoperative chemoradiotherapy at our institution. Among those patients, 154 were eligible for analysis (55, 50, and 49 patients in groups A, B, and C, respectively). After the median follow-up period of 29 months (range, 5 to 48 months), no differences were found between the 3 groups regarding pathologic complete remission rate, tumor regression grade, treatment-related toxicity, 2-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, or overall survival. The circumferential resection margin width was a prognostic factor for 2-year locoregional recurrence-free survival, whereas ypN category was associated with distant metastasis-free survival, disease-free survival, and overall survival. High tumor regression grading score was correlated with 2-year distant metastasis-free survival and disease-free survival in univariate analysis. Conclusion: Three different radiation dose fractionation schedules, within the dose range recommended by the National Comprehensive Cancer Network, had no impact on pathologic tumor regression and early clinical outcome for locally advanced rectal cancer.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.357-366
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• 1998

Brachytherapy is an essential part of radiotherapy for uterine cervical cancer. The low dose rate (LDR) regimen has been the major technique of intracavitary therapy for cervical cancer. However, there has been an expansion in the last 20 years of high dose rate (HDR) machines using Ir-192 sources. Since 1979, HDR brachytherapy has been used for the treatment of uterine cervical cancer in Korea. The number of institutions employing HDR has been increasing, while the number of low dose rate system has been constant. In 1995, there was a total 27 HDR brachytherapy units installed and 1258 cases of patients with cervical cancer were treated with HDR Most common regimens of HDR brachytherapy are total dose of 30-39 Gy at point A with 10-13 fractions in three fractions per week. 24-32 Gy with 6-8 fractions in two fractions per week, and 30-35 Gy with 6-7 fractions in two fractions per week. The average fractionation regimen of HDR brachytherapy is about 8 fractions of 4.1 Gy each to Point A. In Korea, treatment results for HDR brachytherapy are comparable with the LDR series and appears to be a safe and effective alternative to LDR therapy for the treatment of cervical carcinoma. Studies from the major centers report the five-year survival rate of cervical cancer as. 78-86$\%$ for Stage 1, 68-85$\%$ for stage 11, and 38-56$\%$ for Stage III. World-wide questionnaire study and Japanese questionnaire survey of multiple institutions showed no survival difference in any stages and dose-rate effect ratio (HDR/LDR) was calculated to be 0.54 to 0.58. However the optimum treatment doses and fractionation schemes appropriate to generate clinical results comparable to conventional LDR schemes have yet to be standardized. In conclusion, HDR intracavitary radiotherapy is increasingly practiced in Korea and an effective treatment modality for cervical cancer. To determine the optimum radiotherapy dose and fractionation schedule, a nation-wide prospective study is necessary in Korea. In addition, standardization of HDR application (clinical, computer algorithms, and dosimetric aspects) is necessary.

• Radiation Oncology Journal
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• v.4 no.1
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• pp.67-73
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• 1986

To access the result of radiation therapy for 8 years experiences, 21 patients who were treated with superior vena cava syndrome had been analysed according to dose fractionation and total dose. The results are as follows; 1. In high fractionate dose group, six of eleven patients $(54.5\%)$ exhibited relief of symptoms in 1-2 days, and additional three patients of nine $(81.7\%)$ within 34 days, while standard fractionated dose treatment is not effective to achieve initial relief of symptoms. 2. Graded response by total dose was correlated with total dose rather than dose fractionation. 3. Overall one year survival rate with superior vena cava syndrome was $9.1\%$ and mean survival was 4.2 months.

• Radiation Oncology Journal
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• v.12 no.3
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• pp.387-392
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• 1994

Purpose : This study was done to confirm the reference point variation according to variation in applicator configuration in each fractioation of HDR ICR. Materials and Methods : We analyzed the treatment planning of HDRICR for 33 uterine cervical cancer patients treated in department of therapeutic radiology from January 1992 to February 1992. Analysis was done with respect to three view points-Interfractionation A point variation, interfractionation bladder and rectum dose ratio variation, interfractionation treatment volume variation. Interfractionation A point variation was defined as difference between maximum and minimum distance from fixed rectal point to A point in each patient. Interfractionation bladder and rectum dose ratio variation was defined as difference between maximum and minimum dose ratio of bladder or rectum to A point dose in each patient, Interfractionation treatment volume variation was defined as difference between miximum and minimum treatment volume which absorbed over the described dose-that is, 350 cGy or 400 cGy-in each patient. Results The mean of distance from rectum to A point was 4.44cm, and the mean of interfractionation distance variation was 1.14 cm in right side,1.09 cm in left side. The mean of bladder and rectum dose ratio was $63.8\%$ and $63.1\%$ and the mean of interfractionation variation was $14.9\%$ and $15.8\%$ respectively. With fixed planning administration of same planning to all fractionations as in first fractionation planning-mean of bladder and rectum dose ratio was $64.9\%$ and $72.3\%$.and the mean of interfraction variation was $28.1\%$ and $48.1\%$ reapectively. The mean of treatment volume was $84.15cm^3$ and the interfractionation variation was $21.47cm^2$. Conclusion : From these data, it was confirmed that there should be adapted planning for every fractionation ,and that confirmation device installed in ICR room would reduce the interfractionation variation due to more stable applicator configuration.

• Journal of Yeungnam Medical Science
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• v.4 no.1
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• pp.25-32
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• 1987

The object of this study was to determine the difference of radiation effect in different fractional doses and to establish optimal fractionation schedule on the whole-abdominal X-ray irradiation. Total 160 mice were irradiated with 150 KVP, 15 mA orthovoltage x-ray machine and two different fractionation (100 cGy/Fr. and 200 cGy/Fr.) were used. Body weight, hemoglobin and WBC count with differential count were analyzed according to the same amount of total dose, same field size and two different fractionation schedules. The result of this study were summarized as follows: There was no significant difference in body weight and hemoglobin concentration by sex or fractional dose. Leukopenic change was prominent in the 3,000 cGy irradiation group and the proportion of decrease was remarkable in the 200 cGy/Fr, group than 100 cGy/Fr, group. Progressive decrease of lymphocyte count and reciprocal increase of neutrophil count were noted as dose increment. The effect of the fractional does on WBC count and proportion of lymphocyte were significant. This suggests that judicious selection of fractional dose may be important in clinical radiotherapeutic practice.

• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.1
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• pp.65-68
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• 2004

The purpose of the present study was to examine the efficacy and mechanism of fraction IV cold ethanol fractionation and pasteurization (60$^{\circ}C$ heat treatment for 10 h), involved in the manufacture of albumin from human plasma, in the removal and/or inactivation of the hepatitis A virus (HAV). Samples from the relevant stages of the production process were spiked with HAV and the amount of virus in each fraction then quantified using a 50% tissue culture infectious dose (TCID$\_$50/). HAV was effectively partitioned from albumin during the fraction IV cold ethanol fractionation with a log reduction factor of 3.43. Pasteurization was also found to be a robust and effective step in inactivating HAV, where the titers were reduced from an initial titer of 7.60 log TCID$\_$50/ to undetectable levels within 5 h of treatment. The log reduction factor achieved during pasteurization was $\geq$4.76. Therefore, the current results indicate that the production process for albumin has sufficient HAV reducing capacity to achieve a high margin of virus safety.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7167-7170
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• 2015

Background: Although 3D image based brachytherapy is currently the standard of treatment in cervical cancer, most of the centres in developing countries still practice orthogonal intracavitary brachytherapy due to financial constraints. The quest for optimum dose and fractionation schedule in high dose rate (HDR) intracavitary brachytherapy (ICBT) is still ongoing. While the American Brachytherapy Society recommends four to eight fractions of each less than 7.5 Gy, there are some studies demonstrating similar efficacy and comparable toxicity with higher doses per fraction. Objective: To assess the treatment efficacy and late complications of HDR ICBT with 9 Gy per fraction in two fractions. Materials and Methods: This is a prospective institutional study in Southern India carried on from $1^{st}$ June 2012 to $31^{st}$ July 2014. In this period, 76 patients of cervical cancer satisfying our inclusion criteria were treated with concurrent chemo-radiation following ICBT with 9 Gy per fraction in two fractions, five to seven days apart. Results: The median follow-up period in the study was 24 months (range 10.6 - 31.2 months). The 2 year actuarial local control rate, disease-free survival and overall survival were 88.1%, 84.2% and 81.8% respectively. Although 38.2% patients suffered from late toxicity, only 3 patients had grade III late toxicity. Conclusions: In our experience, HDR brachytherapy with 9 Gy per fraction in two fractions is an effective dose fractionation for the treatment of cervical cancer with acceptable toxicity.

• Radiation Oncology Journal
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• v.23 no.3
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• pp.143-156
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• 2005

Background: The best dose-fractionation regimen of the definitive radiotherapy for cervix cancer remains to be clearly determined. It seems to be partially attributed to the complexity of the affecting factors and the lack of detailed information on external and intra-cavitary fractionation. To find optimal practice guidelines, our experiences of the combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) were reviewed with detailed information of the various treatment parameters obtained from a large cohort of women treated homogeneously at a single institute. Materials and Methods: The subjects were 743 cervical cancer patients (Stage IB 198, IIA 77, IIB 364, IIIA 7, IIIB 89 and IVA 8) treated by radiotherapy alone, between 1990 and 1996. A total external beam radiotherapy (EBRT) dose of $23.4\~59.4$ Gy (Median 45.0) was delivered to the whole pelvis. High-dose-rate intracavitary brachytherapy (HDR-IBT) was also peformed using various fractionation schemes. A Midline block (MLB) was initiated after the delivery of $14.4\~43.2$ Gy (Median 36.0) of EBRT in 495 patients, while In the other 248 patients EBRT could not be used due to slow tumor regression or the huge initial bulk of tumor. The point A, actual bladder & rectal doses were individually assessed in all patients. The biologically effective dose (BED) to the tumor ($\alpha/\beta$=10) and late-responding tissues ($\alpha/\beta$=3) for both EBRT and HDR-ICBT were calculated. The total BED values to point A, the actual bladder and rectal reference points were the summation of the EBRT and HDR-ICBT. In addition to all the details on dose-fractionation, the other factors (i.e. the overall treatment time, physicians preference) that can affect the schedule of the definitive radiotherapy were also thoroughly analyzed. The association between MD-BED $Gy_3$ and the risk of complication was assessed using serial multiple logistic regression models. The associations between R-BED $Gy_3$ and rectal complications and between V-BED $Gy_3$ and bladder complications were assessed using multiple logistic regression models after adjustment for age, stage, tumor size and treatment duration. Serial Coxs proportional hazard regression models were used to estimate the relative risks of recurrence due to MD-BED $Gy_{10}$, and the treatment duration. Results: The overall complication rate for RTOG Grades $1\~4$ toxicities was $33.1\%$. The 5-year actuarial pelvic control rate for ail 743 patients was $83\%$. The midline cumulative BED dose, which is the sum of external midline BED and HDR-ICBT point A BED, ranged from 62.0 to 121.9 $Gy_{10}$ (median 93.0) for tumors and from 93.6 to 187.3 $Gy_3$ (median 137.6) for late responding tissues. The median cumulative values of actual rectal (R-BED $Gy_3$) and bladder Point BED (V-BED $Gy_3$) were 118.7 $Gy_3$ (range $48.8\~265.2$) and 126.1 $Gy_3$ (range: $54.9\~267.5$), respectively. MD-BED $Gy_3$ showed a good correlation with rectal (p=0.003), but not with bladder complications (p=0.095). R-BED $Gy_3$ had a very strong association (p=<0.0001), and was more predictive of rectal complications than A-BED $Gy_3$. B-BED $Gy_3$ also showed significance in the prediction of bladder complications in a trend test (p=0.0298). No statistically significant dose-response relationship for pelvic control was observed. The Sandwich and Continuous techniques, which differ according to when the ICR was inserted during the EBRT and due to the physicians preference, showed no differences in the local control and complication rates; there were also no differences in the 3 vs. 5 Gy fraction size of HDR-ICBT. Conclusion: The main reasons optimal dose-fractionation guidelines are not easily established is due to the absence of a dose-response relationship for tumor control as a result of the high-dose gradient of HDR-ICBT, individual differences In tumor responses to radiation therapy and the complexity of affecting factors. Therefore, in our opinion, there is a necessity for individualized tailored therapy, along with general guidelines, in the definitive radiation treatment for cervix cancer. This study also demonstrated the strong predictive value of actual rectal and bladder reference dosing therefore, vaginal gauze packing might be very Important. To maintain the BED dose to less than the threshold resulting in complication, early midline shielding, the HDR-ICBT total dose and fractional dose reduction should be considered.

• Archives of Plastic Surgery
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• v.42 no.5
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• pp.588-595
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• 2015

Background Radiotherapy treatment after keloidectomy is known to be an effective method for reducing the rate of recurrence. However, to date, the appropriate total radiation dose and fractionation have not yet been confirmed. The authors performed a retrospective analysis to identify the appropriate radiation dose and fractionation in post-keloidectomy radiotherapy. Methods From May 2000 to February 2011, postoperative radiotherapy was performed on 39 lesions in 28 patients after total keloidectomy. The keloid lesions were confined to the ear lobes. Between May 2000 and May 2004, 14 keloids were treated with surgical excision, followed by a total radiation dose of 1,200 cGy in three fractions over four to five days (group 1). Between June 2004 to February 2011, 25 keloids were treated with surgical excision, followed by a total radiation dose of 1,500 cGy in three fractions over four to five days (group 2). Patients were given a survey asking them to report their experiences regarding reoperation, recurrence of symptoms, recurrence of the lesion, and satisfaction with the operation. Results Of the 28 patients who were treated, 20 underwent follow-up. Group 2 had more cases showing elevation with erythematous changes, whereas group 1 had more cases showing progressive stages of elevation than group 2. These differences were statistically significant. Moreover, a correlation was observed between the level of keloid elevation and the extent of symptoms. Conclusions We suggest 1,500 cGy of radiation in three fractions following keloidectomy for ear lobe keloids. A further randomized study is needed to assess the recurrence of keloids after radiotherapy.

• Journal of Microbiology and Biotechnology
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• v.10 no.6
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• pp.858-864
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• 2000

The purpose of the present study was to examine the efficacy and mechanism of the fraction IV cold ethanol fractionation and pasteurization ($60^{\circ}C$ heat treatment for 10h) steps, involved in the manufacture of albumin from human plasma, in the removal and/or inactivation of blood-born viruses. A variety of experimental model viruses for human pathogenic viruses, including the Bovine viral diarrhoea virus (BVDV), Bovine herpes virus (BHV), Murine encephalomyocarditis virus (EMCV), and Porcine parvovirus (PPV), were selected for this study. Samples from the relevant stages of the production process were spiked with the viruses, and the amount of virus in each fraction was then quantified using a 50% tissue culture infectious dose ($TCID_{50}$). The mechanism of reduction for the enveloped viruses (BHV and BVDV) during fraction IV fractionation was inactivation rather than partitioning, however, it was partitioning in the case of the non-enveloped viruses (EMCV and PPV). The log reduction factors achieved during fraction IV fractionation were ${\geq}6.9$ BHV, $\geq5.2$ for BBDV, 4.9 for EMC, and 4.0 for PPV. Pasteurization was found to be a robust and effective step in inactivating the enveloped viruses as well as EMCV. The log reduction factors achieved during pasteurization were $\geq7.0$ for BHV, $\geq6.1$ for BVDV, $\geq6.3$ for EMCV, and 1.7 for PPV. These results indicate that the production process for albumin has sufficient virus-reducing capacity to achieve a high margin for virus safety.