• Radiation Oncology Journal
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• v.9 no.2
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• pp.285-291
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• 1991

One hundred and twenty six patients with early uterine cervical cancer who had been treated at Departmen of Radiation Oncology of Korea University Hospital from Jan.1981 to Dec.1988 were analysed retrospectively by the treatment result and pattern of of failures. All patients had stage Ia to IIa disease and were grouped whether they had combination of operation and postop irradiation or radiation therapy alone. 1) Sixty six patients belonged to the combination treatment group and 60 patients to the radiation alone group. 2) Combination group consisted of $18.1\%$(12/66) stage Ia, $71.2\%$(47/66) stage Ib and $10.6\%$ (7/66) stage IIa patients. There were no stage Ia, 18.8$\%$(l1/60) stage Ib and 81.6$\%$(49/60) stage IIa patients for RT alone gronp. 3) There were total 23$\%$(29/126) treatment failures,13 patients in combination group and 16 patients in RT alone group. In 66 patients of combination group, they were found to have 5 locoregional failures, 7 distant failures and 1 at both sites. In 60 patients of RT alone group, 9 locoreginal failure and 7 distant failures occured. Eighty six percent (25/29) of total failures appeared within 18 month after completion of treatment. About 60$\%$ of the patients with regional recurrences which were located at pelvic side wall or pelvic lymph nodes paesented their recurrent disease after 1 year of completion of treatment, whereas same percent of distant failures appeared within 6 month. 5) In RT alone group, the first sites of distant failure were mostly para-aortic lymph node and/or left supraclavicular lymph node (71.4$\%$,5/7). In combination group, various sites such as inguinal lymph node, mediastinal lymph node, liver, lung and bone appeared first or at the same time with para-aortic and supraclavicular lymph node metastasis. 6) Logistic regression analysis was done for multivariate analysis of the factors contributing to locoregional and distant failures. In combination group, adequacy of the resection margin and the presence of positive pelvic node were found to be the most significant factors (p=0.0423 & 0.0060 respectively). In RT alone group, less than complete regression of the tumor at the end of treatment was the only significant contributing factor for the treatment failures (p=0.0013) with good liklihood ratio.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.113-119
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• 1999

Purpose : To evaluate possible acute toxicity and early response of concurrent radiation therapy and low dose daily cisplatin as a radiosensitizer in patients with locally advanced uterine cervical carcinomas. Materials and Method : From December 1996 to January 1999, 38 previously untreated Patients with locally advanced squamous cell carcinoma of the uterine cervix (from stage IIB to stage IIIB) were treated at Inha University Hospital. All patients underwent standard pretreatment staging Procedures after the initial evaluation by gynecologists and radiation oncologists. Sixteen Patients with huge cervical mass (>4 cm) were submitted to the group treated with concurrent radiation therapy and low dose daily cisplatin while the remainder was treated with radiation therapy alone. Radiation therapy consisted of 4500 cGy external beam irradiation to whole pelvis (midline block after 3000 cGy), 900$\~$1000 cGy boost to involved parametrium, and high dose-rate intracavitary brachytherapy (a total dose of 3000$\~$3500 cGy/500 cGy per fraction to point A, twice per week). In the group treated with low dose cisplatin concurrently, 10 mg of daily intravenous cisplatin was given from the 1st day of radiation therapy to the 20th day of radiation therapy. Acute toxicity was measured according to expanded common toxicity criteria of the NCI (C) Clinical Trials. Early response data were analyzed at minimum 4 weeks' follow-up after completion of the treatment protocol. Results: Hematolgic toxici쇼 was more prominent in patients treated with radiation therapy and cisplatin. Six of 16 patients (37.5$\~$) treated with radiation therapy and cisplatin and one of 22 patients (4.5$\~$) treated with radiation therapy alone experienced grade 3 leukopenia. In Fisher's exact test, there was statistically significant difference between two groups regarding leukopenia (P=0.030). There was no apparent difference in the frequency of gastrointestinal and genitourinary toxicity between two groups (P=0.066). Three of 16 patients (18.7$\~$) treated with radiation therapy and cisplatin and two of 22 patients (9.1$\~$) treated with radiation therapy alone experienced more than 5 kg weight loss during the treatment. There was no statistically significant difference on weight loss between two groups (P=0.63). Two patients on each group were not evaluable for the early response because of incomplete treatment. The complete response rate at four weeks' follow-up was 80$\~$(16/20) for the radiation therapy alone group and 78$\~$ (11/14) for the radiation therapy and cisplatin group. There was no statistically significant difference in early response between two treatment groups (P=0.126). Conclusion : This study led to the conclusion that the hematologic toxicity from the treatment with concurrent radiation therapy and low dose daily cisplatin seems to be more prominent than that from the treatment of radiation therapy alone. There was no grade 4 hematologic toxicity or mortality in both groups. The hematologic toxicity in both treatment groups seems to be well managable modically. Since the risk factors were not balanced between two treatment groups, the direct comparison of early response of both groups was not possible. However, preliminary results regarding early response for patients with bulky cervical tumor mass treated with radiation therapy and low dose daily cisplatin was encouraging. Longer follow-up is necessary to evaluate the survival data. A phase III study is needed to evaluate the efficacy of concurrent daily low dose cisplatin with radiation therapy in bulky cervical cancer.

• The Journal of Korean Society for Radiation Therapy
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• v.16 no.1
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• pp.73-77
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• 2004

Purpose of the radio-therapy is maximize the radiation dose to the tumor while minimizing the dose to the critical organ. Carcinoma of the uterine cervix treatment are external irradiation or an interstitial brachtheraphy make use of isotope. Brachytherapy is a method of radiotherapy in advantage to achieve better local control with minimum radiation toxicity in comparison with external irradiation because radiation dose is distributed according to the inverse square low of gamma-ray emitted from the implanted sources. Authors make use of the patients data which 192Ir gives medical treatment intrcavity. Intracavitary radiation of the uterine cervix cancer, critical organ take $20\%$ below than exposure dose of A point in the ICRU report. None the less of the advice, Radiation proctitis and radiation cystitis are frequent and problematic early complications in patients treated with radiation for the uterine cervix cancer. In brachytherapy of uterine cervical cancer using a high dose rate remote afterloading system, it is of prime importance to deliver a accurate dose in each fractionated treatment by minimizing the difference between the pre-treatment planned and post-treatment calculated doses. Use of packing to reduce late complications intracavitary radiation of the uterine cervix cancer. Bladder and rectum changes exposure dose rate by radiotherphy make use of packing.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7633-7640
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• 2015

Background: Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and it is responsible for most cases of cervical uterine cancer. Although HPV infections of the cervix do not always progress to cancer, 90% of cervical cancer cases have been found to be associated with high risk HPV (HR-HPV) infection. HPV DNA testing is widely used, along with Papanicolaou (Pap) testing, to screen for cervical abnormalities. However, there are no data on the prevalence of genotype-specific HPV infections assessed by measuring HPV E6/E7 mRNA in women representative of the Chinese population across a broad age range. Materials and Methods: In the present study, we compared the results with the CervicGen HPV RT-qDx assay, which detects 16 HR-HPV genotypes (Alpha-9: HPV 16, 31, 33, 35, 52, and 58; Alpha-7: HPV 18, 39, 45, 51, 59, and 68; and Alpha-5, 6: HPV 53, 56, 66, and 69), and the REBA HPV-ID assay, which detects 32 HPV genotypes based on the reverse blot hybridization assay (REBA) for the detection of oncogenic HPV infection according to cytological diagnosis. We also investigated the prevalence and genotype distribution of HPV infection with a total of 324 liquid-based cytology samples collected in western Shandong province, East China. Results: The overall HPV prevalences determined by HPV DNA and HPV E6/E7 mRNA assays in this study were 79.9% (259/324) and 55.6% (180/324), respectively. Although the positivity of HPV E6/E7 mRNA expression was significantly lower than HPV DNA positivity, the HPV E6/E7 mRNA assay showed greater specificity than the HPV DNA assay (88.6% vs. 48.1%) in normal cytology samples. The prevalence of Alpha-9 (HPV 16, 31, 33, 35, 52, and 58) HPV infection among these women accounted for up to 80.3% and 76.1% of the high-grade lesions detected in the HPV mRNA and DNA tests, respectively. The HR-HPV genotype distribution, based on HPV DNA and E6/E7 mRNA expression by age group in patients with cytologically confirmed lesions, was highest in women aged 40 to 49 years (35.9% for cytologically confirmed cases, Pearson correlation r value=0.993, p<0.001) for high-grade lesions. Among the oncogenic HR-HPV genotypes for all age groups, there was little difference in the distribution of HPV genotypes between the HPV DNA (HPV -16, 53, 18, 58, and 33) and HPV E6/E7 mRNA (HPV -16, 53, 33, 58, and 18) assays. HPV 16 was the most common HPV genotype among women with high-grade lesions. Conclusions: Our results suggest that the HPV E6/E7 mRNA assay can be a sensitive and specific tool for the screening and investigation of cervical cancer. Furthermore, it may provide useful information regarding the necessity for early cervical cancer screenings and the development of additional effective HPV vaccines, such as one for HPV 53 and 58. Additionally, gaining knowledge of HPV distribution may also inform us about ecological changes in HPV after the vaccination.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.3
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• pp.132-139
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• 2015

Recently, $p16^{INK4a}$/Ki-67 dual immunostaining has been introduced as a new biomarker protocol for early detection of uterine cervical dysplasia and cancer in liquid-based cytology (LBC). We performed the $p16^{INK4a}$/Ki-67 dual immunostaining using a CINtec$^{(R)}$ PLUS kit in a total of 109 LBC cases of cervicovaginal smear and compared its results with those from LBC, HPV hybrid capture II (HC II) test and histological diagnosis. Expression of $p16^{INK4a}$ and Ki-67 was significantly associated with cases of LSIL or higher in cytological diagnosis and cases of cervical intraepithelial neoplasia (CIN) 1 or higher in histological diagnosis (p<0.001 and p<0.001, respectively). Among forty-six cases of atypical squamous cells of undetermined significance (ASCUS) in LBC, $p16^{INK4a}$ and Ki-67 was expressed in 31 (67.4%), which were positively associated with cases of CIN I lesion or higher in histology. The sensitivity of $p16^{INK4a}$/Ki-67 dual immunostaining for finding lesions of CIN 1 or higher was 89.0%, which was higher than LBC. The specificity was 73.5%, which was higher than that of the HC II test. Based on these results, the $p16^{INK4a}$/Ki-67 dual immunostaining method can be a useful diagnostic marker for improving the sensitivity of LBC and the specificity of HC II test.

• Radiation Oncology Journal
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• v.19 no.4
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• pp.335-344
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• 2001

Purpose : The aim of this study was to clarify the role of VEGF expression as an independent prognostic factor and to identify the patients at high risk for poor prognosis in stage IB cervical cancer. Materials and methods : A total of 118 patients with stage IB cervical cancer who had radical hysterectomy and pelvic lymph node dissection were included in the study. All known high risk factors of the patients were pathologically confirmed from the surgical specimen. Of the 118 patients, n patients were treated with postoperative radiotherapy and/or chemotherapy. VEGF expression was examined using immunohistochemistry in formalin-fixed, paraffin-embedded specimens of post-hysterectomy surgical materials. A semiquantitative analysis was made using a scoring system of 0, +, ++, and +++ for increasing intensity of stain. We classified the patients with scores from 0 to ++ as low VEGF expression and the patients with a score of +++ as high VEGF expression. Results : Of the 118 patients, 35 patients $(29.7\%)$ showed high VEGF expression. Strong correlations were found between the high VEGF expression and both deep stromal invasion (p=0.01) and the positive pelvic node (p=0.03). The 5-year overall and disease-free survival rates for all 118 patients were $95.5\%\;and\;93.8\%$. The 5-year overall (p=0.03) and disease-free survival (p<0.001) rates were $98.5\%\;and\;100%$ for low VEGF expression (0, +, and ++) and $85.5\%\;and\;79.7\%$ for high VEGF expression, respectively. Pelvic and distant failures for low versus high VEGF expression were $1.2\%$ versus $17.1\%$, (p=0.001) and $0\%$ versus $14.3\%$ (p<0.001), respectively. In a Cox multivariate analysis of survival, the high VEGF expression (p=0.02) and the bulky mass (p=0.02) were significant prognostic factors for overall survival. The high VEGF expression (p=0.002), and bulky mass (p=0.01) demonstrated as significant prognostic indicators for disease free survival. Conclusion : These results showed that VEGF expression was a highly significant predictor for pelvic and distant failure and the most significant prognostic factor of overall and disease free survival for the patients with stage IB cervix cancer treated with radical surgery. We strongly suggest that the immune-histochemistry for VEGF expression be performed in a routine clinical setting in order to identify the patients at high risk for poor prognosis in early stage cervical cancer. Furthermore, postoperative and/or chemotherapy did not reduce the pelvic failure and distant metastasis. To improve the cure rate for the patients with high VEGF expression in stage IB cervical cancer, antiangiogenic therapy including anti-VEGF Ab may be new treatment option.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.136-141
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• 2001

Purpose : To evaluate the significance of serum SCC for the monitoring of treatment response and the early detection of distant metastasis during radiotherapy (RT). Materials and Methods : In 13 patients with histologically proven primary squamous cell carcinoma of uterine cervix, serum SCC values were checked in pre-RT point, weekly during RT, and in post-RT point. Results : In 4 of 13 cases, metastasis appeared at the end of external RT, so that intracavitary radiation couldn't be peformed.01 these 4 cases,3 with elevated pre-RT SCC level, who resulted in lung metastasis on chest PA at the end of external RT showed decreased post-RT SCC value despite of metastasis. Of all 10 cases with elevated pre-RT SCC value (including 3 with metastasis at the end of external RT), SCC value was higher than pre-RT value in 7 at 9 Gy and the difference was statistically significant. At 18 Gy, SCC was higher in 4 and lower in 6 than pre-RT value. After 18 Gy, SCC value decreased continuously to the end of RT in all 10 cases. Conclusion : During RT, SCC value increased initially at 9 Gy. To 18 Gy, SCC value decreased to the nearly same with pre-RT value. After 18 Gy, to the end of RT, SCC value decreased continuously and normalized in completely responded cases. In cases with appearance of lung metastasis, SCC value also decreased with the disappearance of main mass of uterine cervix despite metastasis.

• Radiation Oncology Journal
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• v.7 no.1
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• pp.59-70
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• 1989

Cervix cancer is the most common female cancer in Korea. In spite of their relatively local invasive tendency, still $44\%$ of patient will develop recurrent cancer. This result suggests that more aggressive local treatment may increase the cure rate but increased complication risk also cannot be avoidable. Various institutions proposed different treatment regimen, but recommended dose were about 4500 cGy for whole pelvis and 8000 cGy at point A, even though they agreed that those doses may not be satisfactory for control of bulky disease. 96 cases of invasive cervical cancer, treated with postoperative or primary radiation therapy were analyzed to determine the complication rate and prognostic factor in our treatment regimen Which is $5500\~1000 CGy$ higher than Other institution. Mean follow up duration was 21 months. Symptomatic patients including mild but persistent abdominal discomfort was $46\%$, but only 1 patient $(1\%)$ had operative treatment because of incomplete obstruction of small bowel. Most symptoms appeared within 12 months and most common complaints were frequent bowel movement. Barium enema and sigmoidoscopy were performed for persistent symptomatic patients. Only one patient had abnormal finding in barium enema which showed inefficiency of this method for detecting bowel complication. Patient's age, total tumor dose, total TDF, rectal dose were not significant risk factors for complication, but boost dose, previous history of operation had some relationship with complication risk. Even though dose of point A and rectum is $500\~1,000cGy$ higher than other institution, such a low rate of severe complications may suggest that fear of complications should not be overestimated than cure rate and the possibility of more aggressive treatment for better local control should not be underestimated.

• Radiation Oncology Journal
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• v.13 no.1
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• pp.41-48
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• 1995

Purpose : The adjuvant postoperative radiotherapy has been usually applied to the patients with unfavorable prognostic factors after radical operation in early cervical cancer. We focused on the evaluation of the survival status and failure patterns of the patients with postoperative radiotherapy. Materials and Methods : We retrospectively analyzed ninety patients with FIGO stage IB and IIA cervix cancer who received postoperative pelvic irradiation at Chonnam University Hospital between August 1985 and December 1988, Seventy-eight patients had adequate follow-up information for survival analysis. Median follow-up time of these patients was 64 months. Results : The 5 year overall and disease free survival rate of ninety patients was $80.0\%$ and $80.2\%$, respectively. The prognostic significance to the survival was determined by multivariate analysis. Adequacy of resection margin(p=0.005) and lymph node status(p=0.005) appeared to be independent prognostic factors. Recurrence occurred in 13 patients, 5 in the pelvis and 8 at distant sites. The median time to recurrence was 19 months(range:3-39 months). The pelvic recurrence was more prevalent in the group of patients with adenocarcinoma, depth of stromal invasion more than 10mm and use of chemotherapy. The distant failure was more prevalent in the group of positive resection margin or positive lymph node with statistical significance. Conclusion : Patients with pelvic lymph node or surgical margin involvement clearly constitute a high risk group in this analysis and should be considered as candidates for some form of adjuvant therapy.

• Radiation Oncology Journal
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• v.6 no.1
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• pp.63-73
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• 1988

One hundred fifty-four patients with the carcinoma of the uterine cervix were studied retrospectively to assess the result and impact of treatment at Department of Radiation Oncology, Korea University, Hae-Wha Hospital from Feb 1981 through Dec. 1986. Prior to radiotherapy, the patients were evaluated and staged by recommendation of FIGO including physical examination, pelvic examination, cystoscopy, rectosigmoidoscopy, chest X-ray, IVP. Ba enema. Also, an additional pelvic CT scan was obtained for some of the patients. The patients were treated by radiotherapy alone or adjuvant postoperative irradiation; in case of radiation therapy only, whole pelvic irradiation was given with Co-60 teletherapy unit via AP and PA parallel opposing fields or 4-oblique fields, 180 cGy per day, 5 days per week and intracavitary insertion was performed. In satges Ia, Ib, and IIa with small primary lesion, external irradiation was initially given to pelvis up to $2,000\~3,000\;cGy/2frac{1}{2}\;-3frac{1}{2}$ weeks and then intracavitary insertion was performed using Fletcher-Mini-Declos Applicator with cesium-137 cources and followed by external irradiation of $1,000\~2,000\;cGy/1frac{1}{2}\;-2frac{1}{2}$weeks via AP and PA parallel opposing fields with midline shield to spare of bladder and rectum. However, if the primary lesion is large, external irradiation was given without midline shield. More than stages IIb, the patients were treated by external beam irradiation up to 5,400cGy/30f for 6 weeks via 4-oblique portals and at the dose of 5,040cGy/28f the field was cut 5cm from the top margin for spare of small bowel, and followed by intracavitary irradiation, If there was residual tumor an additional dose of $900\~l,200cGy/5\~7f$ was given to parametrium and/or residual tumor area. Total dose of radiation to A and B-point were as follows; A-point; In early stages, Ia, Ib, IIa; $8,000\~9,000$ B-point $5,000\~6,000 cGy$ A-point; In advanced stages IIb, IIIa, IIIb; $9,000\~10,000$ B-point $60,000\~7,000cGy$ The results were obtained and as fellows; 1 The patients distribution according to FIGO staging system were stage Ia 6, Ib 27, IIa 28, IIb 54, IIIa 12, IIIb 18, and stage IVa 9. 2. Value of CT scan were demonstration of cervix tumor mass, parametrial and pelvic side wall tumor spread, pelvic and inguinal lymph nodes metastases, and hydronephrosis. Three dimensional quantitative demonstration of tumor volume is also important in planning radiation therapy. Another advantage of CT scan was detection of recurrent tumor after radiation or surgery. 3. Local control rate of tumor according to the size was $91.3\%$ for less than 5cm in size and $44.6\%$ in tumor over 5cm (p<0.0068). 4. Thirty out of 50 recurrent sites has locoregional failures and 17 cases has distant metastases. And the para-aortic lymph nodes were the most common site for distant metastases. 5. The most common complication was temporal rectal bleeding which was controlled most by conservative management. However, 4 patients required for endoscopic cauterization. 6. The 5-year survival rates showed; stage la and Ib $95\%,\;stage\;IIa\;81\%\;stage\;lIb\;67\%,\;stage\;IIIa\;37.7\%,\;stage\;IIIb\;23\%$ and 3-year survival rate of stage IVa showed $11.6%$, retrospectively.