• Radiation Oncology Journal
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• v.24 no.1
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• pp.44-50
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• 2006

Puroose: This study evaluated the late rectal complications in cervix cancer patients following treatment with external beam radiotherapy (EBRT) and high dose rate intracavitary radiation (HDR ICR). The factors affecting the risk of developing late rectal complications and its incidence were analyzed and discussed. Materials and Methods: The records of 105 patients with cervix cancer who were treated with radical radiotherapy using HDR ICR between July, 1995 and December, 2001 were retrospectively reviewed. The median dose of EBRT was 50.4Gy $(41.4{\sim}56.4 Gy)$ with a daily fraction size of 1.8Gy. A total of $5{\sim}7$ (median: 6) fractions of HDR ICR were given twice weekly with a fraction size of $4{\sim}5 Gy$ (median: 4Gy) to A point using an Ir (Iridium)-192 source. The median dose of ICR was 24 Gy $(20{\sim}35 Gy)$. During HDR ICR, the rectal dose was measured in vivo by a semiconductor dosimeter. The median follow-up period was 32 months, ranging from 5 to 84 months. Results: Of the 105 patients, 12 patients (11%) developed late rectal complications: 7 patients with grade 1 or 2, 4 patients with grade 3 and 1 patient with grade 4. Rectal bleeding was the most frequent chief complaint. The complications usually began to occur $5{\sim}32$ (median: 12) months after the completion of radiotherapy. Multivariate analysis revealed that the measured cumulative rectal BED over 115 Gy3 (Deq over 69 Gy) and the depth (D) of a 5 Gy isodose volume more than 50 mm were the independent predictors for late rectal complications. Conclusion: With evaluating the cumulative rectal BED and the depth of a 5 Gy isodose volume as predictors, we can individualize treatment planning to reduce the probability of late rectal complications.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3281-3285
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• 2012

Objectives: To evaluate the clinicopathologic correlation and prognostic value of HPV18 DNA viral load in patients with early-stage cervical neuroendocrine carcinoma (NECA). Methods: Formalin-fixed, paraffin-embedded tissue of cervical NECA patients with known HPV18 infection and clinicopathologic data including follow-up results were collected. The HPV18 DNA load was assessed with quantitative PCR targeting the HPV18 E6E7 region. Results: Twenty-one patients with early-stage (IB-IIA) cervical NECA were identified. HPV18 DNA viral load ranged from 0.83 to 55,174 copies/cell (median 5.90). Disease progression, observed in 10 cases (48%), was not significantly associated with any clinicopathologic variables. However, the group of patients with progressive disease tended to have a higher rate of pelvic lymph node metastasis (50% versus 9%, p=0.063) and a lower median value of HPV18 DNA viral load (4.37 versus 8.17 copies/cell, p=0.198) compared to the non-recurrent group. When stratified by a cut-off viral load value of 5.00 copies/cell, the group of patients with viral load ${\leq}5.00$ copies/cell had a significantly shorter disease-free survival than the group with viral load >5.00 copies/cell (p=0.028). The group with a lower viral load also tended to have a higher rate of disease progression (75% versus 31%, p=0.080). No significant difference in the other clinicopathologic variables between the lower and higher viral load groups was identified. Conclusion: HPV18 DNA viral load may have a prognostic value in patients with early-stage NECA of the cervix. A low viral load may be predictive of shortened disease-free survival in these patients.

• Radiation Oncology Journal
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• v.21 no.4
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• pp.276-282
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• 2003

Purpose: Although high-dose-rate intracavitary radiotherapy (HDR ICR) has been used in the treatment of cervical cancer, the potential for increased risk of late complication, most commonly in the rectum, is a major concern. We have previously reported on 136 patients treated with HDR brachytherapy between 1995 and 1999. The purpose of this study is to upgrade the previous data and confirm the correlation between late rectal complication and rectal dose in cervix cancer patients treated with HDR ICR. Materials and Methods: A retrospective analysis was peformed for 222 patients with cevix cancer who were treated for curative intent with external beam radiotherapy (EBRT) and HDR ICR from July 1995 to December 2001. The median dose of EBRT was 50.4 (30.6$\~$56.4) Gy with a daily fraction size 1.8 Gy. A total of six fractions of HDR ICR were given twice weekly with fraction size of 4 (3$\~$5.5) Gy to A point by Iridium-192 source. The rectal dose was calculated at the rectal reference point using the barium contrast criteria. in vivo measurement of the rectal dose was peformed with thermoluminescent dosimeter (TLD) during HDR ICR. The median follow-up period was 39 months, ranging from 6 to 90 months. Results: Twenty-one patients (9.5$\%$) experienced late rectal bleeding, from 3 to 44 months (median, 13 months) after the completion of RT. The calculated rectal doses were not different between the patients with rectal bleeding and those without, but the measured rectal doses were higher in the complicated patients. The differences of the measured ICR rectal fractional dose, ICR total rectal dose, and total rectal biologically equivalent dose (BED) were statistically significant. When the measured ICR total rectal dose was beyond 16 Gy, when the ratio of the measured rectal dose to A point dose was beyond 70$\%$, or when the measured rectal BED was over 110 Gy$_{3}$, a high possibility of late rectal complication was found. Conclusion: Late rectal complication was closely correlated with measured rectal dose by in vivo dosimetry using TLD during HDR ICR. If data from in vivo dosimetry shows any possibility of rectal bleeding, efforts should be made to reduce the rectal dose.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.477-483
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• 1998

Purpose : Radiation proctitis and radiation cystitis are frequent and problematic late complications in patients treated with radiation for the uterine cervix cancer. Authors tried to find out the better patient's position in high dose rate intracavitary radiation to reduce the radiation dose of bladder and rectum. Materials and Methods : In 13 patients, Foley Catheters were inserted to patient's bladder and rectum and were ballooned with radioopaque dye. After insertion of a tandem and two ovoids, semi-orthogonal anteroposterior and lateral films were taken in both lithotomy and supine position. The rectal point and bladder point were defined according to the criteria recommended in the ICRU Report 38 with modification. Using these films, all patients' bladder and rectal dose were calculated in both positions (the radiation dose of A point was set to 400 cGy). And also, the distance of bladder and rectum from uterine cervical os was calculated in both positions. Results : The average radiation dose of rectum was 240.7 cGy in lithotomy position and 278.3 cGy in supine position, and the average radiation dose of bladder was 303.5 cGy in lithotomy position and 255.8 cGy in supine position. After the paired t-test, the radiation dose of rectum in lithotomy position was marginally significantly lower than that in supine position, while the radiation dose of bladder in lithotomy position was significantly higher than that in supine position. On the other hand, the average distance between rectum and cervical os was 35.2 mm in lithotomy position and 32.3 mm in supine position. and the average distance between bladder and cervical os was 30.4 mm in lithotomy position and 34.0 mm in supine position. After the paired t-test. the distance between rectum and cervical os in lithotomy position was significantly longer than that in supine position, while the distance between bladder and cervical os in lithotomy position was significantly shorter than that in supine position. Conclusion : The radiation dose of bladder can be reduced in supine position and the radiation dose of rectum can be reduced in lithotomy position, so we can choose appropriate position in each patient.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6115-6120
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• 2014

Background: To compare the KKU-model rectal tube (KKU-tube) and the conventional rectal tube (CRT) for checking rectal doses during high-dose-rate intracavitary brachytherapy (HDR-ICBT) of cervical cancer. Materials and Methods: Between February 2010 and January 2011, thirty -two patients with cervical cancer were enrolled and treated with external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT). The KKU-tube and CRT were applied intrarectally in the same patients at alternate sessions as references for calculation of rectal doses during ICBT. The gold standard references of rectum anatomical markers which are most proximal to radiation sources were anterior rectal walls (ARW) adjacent to the uterine cervix demonstrated by barium sulfate suspension enema. The calculated rectal doses derived from actual anterior rectal walls, CRT and the anterior surfaces of the KKU-tubes were compared by using the paired t-test. The pain caused by insertion of each type of rectal tube was assessed by the visual analogue scale (VAS). Results: The mean dose of CRT was lower than the mean dose of ARW ($Dmean_0-Dmean_1$) by $80.55{\pm}47.33cGy$ (p-value <0.05). The mean dose of the KKU-tube was lower than the mean dose of ARW ($Dmean_0-Dmean_2$) by $30.82{\pm}24.20cGy$ (p-value <0.05). The mean dose difference [($Dmean_0-Dmean_1$)-($Dmean_0-Dmean_2$)] was $49.72{\pm}51.60cGy$, which was statistically significant between 42.32 cGy -57.13 cGy with the t-value of 13.24 (p-value <0.05). The maximum rectal dose by using CRT was higher than the KKU-tube as much as 75.26 cGy and statistically significant with the t-score of 7.55 (p-value <0.05). The mean doses at the anterior rectal wall while using the CRTs and the KKU-tubes were not significantly different (p-value=0.09). The mean pain score during insertion of the CRT was significantly higher than the KKU-tube by a t-score of 6.15 (p-value <0.05) Conclusions: The KKU-model rectal tube was found to be an easily producible, applicable and reliable instrument as a reference for evaluating the rectal dose during ICBT of cervical cancer without negative effects on the patients.

• Biomedical Science Letters
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• v.22 no.2
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• pp.37-45
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• 2016

High risk human papillomavirus (HR-HPV) is major risk factor for uterine cervical cancer. There are approximately 15 types of HR-HPV. Liquid based cytology samples (116 samples) with high grade cervical lesions belonging to cervical intraepithelial neoplasia (CIN) 2, CIN 3, carcinoma in situ (CIS) and squamous cell carcinoma (SCC) were used after histologic confirmation. HR-HPV genotype assay was conducted using DNA chips. The HR-HPV infection rate was 81.9% with SCC samples showing the highest HR-HPV infection rate of 31%. CIN 3, CIS and CIN 2 showed infection rates of 25%, 16.4% and 9.5%, respectively. According to age with HR HPV infection rate, the 30~39 years-old group showed the highest infection rate by 92.3%. According to distribution with HR HPV genotyping, HPV 16 showed the highest infection rate by 42.3% whereas HPV 33 and HPV 58 showed infection rates of 11.7% and 10.8%, respectively. HPV 18 which is the second most common infected HPV genotype in the world showed 3.6%. Of the three most common oncogenic HR-HPV genotypes in CIN 2, we detected HPV 16, 35, 58; CIN 3 was HPV 16, 33, 58; CIS was HPV 16, 58, 33 (35/52); and SCC was HPV 16, 33, and 18 (31/52/58). Among the HPV 18, CIN 2, CIN 3, CIS and SCC showed 0.9%, 0.9%, 0% and 1.8%, respectively. The most often used preventive vaccines for cervical cancers use HPV 16 and HPV 18 as targets. However, results derived from this study suggest that a preventive vaccine against HPV 16 and HPV 18 would not be optimal for populations in this study.

• Radiation Oncology Journal
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• v.28 no.2
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• pp.91-98
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• 2010

Purpose: Troglitazone (TRO), a PPAR-$\gamma$ agonist, can reduce heat shock protein (HSP) 70 and increase the antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, which might affect thermal sensitivity. Here, we investigated whether TRO modifies thermal sensitivity in uterine cervical cancer cells, which is most commonly treated by hyperthermia (HT). Materials and Methods: HeLa cells were treated with $5{\mu}M$ TRO for 24 hours before HT at $42^{\circ}C$ for 1 hour. Cell survival was analyzed by clonogenic assay. The expression of HSPs was analyzed by Western blot. SOD and catalase activity was measured and reactive oxygen species (ROS) was measured using 2',7'-dichlorofluorescin diacetate and dihydroethidium. Results: The decreased cell survival by HT was increased by preincubation with TRO before HT. Expression of HSP 70 was increased by HT however, it was not decreased by preincubation with TRO before HT. The decreased Bcl-2 expression by HT was increased by preincubation with TRO. SOD and catalase activity was increased by 1.2 and 1.3 times,respectively with TRO. Increased ROS by HT was decreased by preincubation with TRO. Conclusion: TRO decreases thermal sensitivity through increased SOD and catalase activity, as well as scavenging ROS in HeLa cells.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.369-377
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• 1997

Purpose : This study was Performed to identify the histopathologic feature by the reevaluation of the Pathologic specimen of the cervical tumors and to evaluate the clinical findings and the treatment results of the patients with small cell carcinoma of the cervix treated by radiotherapy. Materials and Methods : 2890 patients with cervical carcinoma received radiotherapy at the Department of Radiation Oncology. Yonsei Cancer Center, Yonsei University College of Medicine between October 1981 and April 1995. Of the 2890 patients in this data base, sixty were found to have small cell carcinomas $(2.08\%)$. Among them thirty six patients were transferred from other hospitals. the biopsy specimens of those Patients were not available. So we could review the slides of the other twenty four patients who were diagnosed at our hospital. Twenty four patients with small cell carcinoma of the cervix were analyzed retrospectively based on the assessment of H & E staining and other four immunohistochemical stains for neuroendocrine differentiation (neuron specific enolase, chromogranin. synaptophysin and Grimelius stain). And we also evaluate the Patients and tumor characteristics. response to radiation. patterns of failures, 5 year overall and disease free survival rates. Results : Thirteen tumors were neuroendocrine carcinomas(13/24 = $54.2\%$) and eleven tumors were squamous carcinomas, small cell type (11/24 = $47.8\%$) based on the assessment of H & E staining and other four neuroendocrine marker studies. So we classified the Patients two groups as neuroendocrine carcinoma and small cell type of squamous carcinoma, Among the 13 neuroendocrine carcinomas, five were well to moderately differentiated tumors and the other eight were Poorly differentiated or undifferentiated ones. The median age was 54 years old (range 23-79 years). Eight Patients had FIGO stage IB disease, 12 had stage 11, 3 had stage III and one had stage IV disease, Pelvic lymph node metastases were found in five Patients $(20.8\%)$. three of them were diagnosed by surgical histologic examination and the other two were diagnosed by CT scan. There was no difference between two histopathologic groups in terms of patients and tumor characteristics. response to radiation. 5 year overall and disease free survival rates. However the distant metastases rate was higher in neuroendocrine carcinoma Patients (6/13:$46.2\%$) than in small cell type of squamous carcinoma Patients (2/11:$18.2\%$), but there was no statistically significant difference because of the small number of patients (P>0.05). Conclusion : More than half of the small cell carcinoma of the cervix patients were neuroendocrine carcinoma (13/24 : $54.1\%$) by reevaluation of the biopsy specimen of the cervical tumors. The tendency of distant metastases of the neurolndocrine carcinoma was greater than those of the small cell type of squamous carcinoma $(46.2\%\;vs.\;18.2\%)$. But there were no differences in the patients and tumor characteristics and other clinical treatment results in both groups. These data suggest that radical local treatment such as radiotherapy or radical surgery combined with combination systemic cytotoxic chemotherapy might provide these patients with the best chance for cure.

• 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.11 no.2
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• pp.387-395
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• 1993

To identify pretreatment prognostic factors in carcinoma of the uterine cervix, a retrospective analysis was undertaken of 510 patients treated with curative radiation therapy in Seoul National University Hospital during the 7 year period, from March 1979 through December 1986. According to FIGO classification,35 patients were stage I B,89 were stage IIA, 232 were stage IIB,8 were stage IIIA, 134 were IIIB, and 12 were stage IVA. Five year locoregional control (LRC) rates in stage I B, II A, II B, IIIA, IIIB, and IVA were $79\%,78\%,70\%,58\%,51\%\;and\;27\%,$ respectively. Five year disease free survival (DFS) rates were $76\%,67\%,60\$,57\%,40\%,\;and\;25\%,$ respectively. Overall survival (OS) rates at five years were $82\%,72\%,67\%,67\%,51\%,\;and\;33\%,$ respectively. In univariate analyses, stage, age, initial hemoglobin level, type of histology, tumor size, and several CT findings including pelvic lymph node (LN) status, paraaortic lymph node (PAN) status, extent of parametrial invasion, bladder invasion, and rectal invasion were significant factors in terms of LRC. All these factors and elevation of BUN or creatinine were associated with DFS. In terms of overall survival, stage, initial hemoglobin level, type of histology, tumor size, elevation of BUN or creatinine, and five CT findings associated with LRC were prognostically significant. In multivariate analysis excluding CT findings, stage IV disease, non-squamous histology, and tumor size $\ge$4 cm were associated with poor LRC and DFS. Stage IV disease and tumor size significantly affected OS. in multivariate analysis including CT findings, histology, tumor size, and pelvic LN status on CT were uniformly significant in terms of LRC, DFS, and 05, PAN status on CT affected overall survival only.