• 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.26 no.4
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• pp.271-279
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• 2008

Purpose: To evaluate the efficacy of a belly-board device (BBD) in reducing the volume of small bowel during four-field pelvic irradiation. Materials and Methods: Twenty-two cancer patients (14 uterine cervical cancer, 6 rectal cancer, and 2 endometrial cancer) scheduled to receive pelvic irradiation were selected for this study. Two sets of CT images were taken with and without the belly-board device using the Siemens 16 channel CT scanner. All patients were set in the prone position. The CT images were transferred to a treatment planning system for dose calculation and volume measurements. The external surfaces of small bowel and the bladder were contoured on all CT scans and the 4-pelvic fields were added. The dose-volume-histogram of the bladder and small bowel, with and without the BBD, were plotted and analyzed. Results: In all patients, the total small bowel volume included in the irradiated fields was reduced when the BBD was used. The mean volume reduction was 35% (range, $1{\sim}79%$) and was statistically significant (p<0.001). The reduction in small bowel volume receiving $10{\sim}100%$ of the prescribed dose was statistically significant when the BBD was used in all cases. Almost no change in the total bladder volume involved was observed in the field (<8 cc, p=0.762). However, the bladder volume receiving 90% of the prescribed dose was 100% in 15/22 patients (68%) and $90{\sim}99%$ in 7/22 patients (32%) with the BBD. In comparison, the bladder volume receiving 90% of the prescribed dose was 100% in 10/22 patients (45%), $90{\sim}99%$ in 7/22 patients (32%), and $80{\sim}89%$ in 5/22 patients (23%) without the BBD. When the BBD was used, an increase in the bladder volume receiving a high dose range was observed Conclusion: This study shows that the use of a BBD for the treatment of cancer in the pelvic area significantly improves small bowel sparing. However, since the BBD pushed the bladder into the treatment field, the bladder volume receiving the high dose could increase. Therefore it is recommended to be considerate in using the BBD when bladder damage is of concern.

• Radiation Oncology Journal
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• v.10 no.2
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• pp.213-217
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• 1992

Locally advanced cervical carcinoma has shown high rate of local failure and poor survival rate despite the advances in modern radiation therapy techniques. Combination of chemotherapy and radiation therapy demonstrated benefit in improving local control and possibly the overall survival. Twelve patients with advanced stages (Figo stage III, IV) or 11b with bulky tumors (>5 cm in diameter) were treated with combination of radiation therapy and concurrent weekly cisplatin between May of 1988 and September of 1991 at Inje University Paik Hospital. Cisplatin was administered in bolus injections of 50 mg at weekly intervals during the courses of radiation therapy. Median follow-up period was 34 months with ranges from 3 to 53 months. Eleven patients were evaluable for the estimation of response. Response was noted in all the 11 patients: complete response (CR) in 7 ($64\%$), partial response (PR) in 4 ($36\%$). Of the 7 patients with CR, all maintained local control, whereas only 1 of 4 with PR showed local control. Six of 7 with CR are alive disease free on the completion of follow-up. Eight of 11 patients ($73\%$) maintained local control in the pelvis. The median survival for CR patient is 27 months and 9 months for the PR patients. Analysis of survival by stage shows 11 b 4/5, III 2/3 and IV 1/3. Overall survival rate was $61\%$. Three patients recurred: 1 at local, 1 in distant site and 1 with local and distant site. Toxicity for the combination therapy was not excessive. These results are preliminary, but definitely encouraging in view of markedly improved response rate compared with the results of historical control group.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.37-43
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• 2006

Purpose: We wanted to determine the clinical characteristics and prognosis according to the VEGF expression in stage II cervical carcinoma patients treated with definitive radiotherapy. Materials and Methods: We enrolled 31 patients who were diagnosed with cervical cancer from 1995 to 2003 at Samsung Medical Center and their paraffin block tissue samples were available for study. The median age of the patients was 65 years. The mean tumor size was 4.1 cm $(range:\;1.2{\sim}8.2cm)$. Seven patients (22.6%) were suspected of having pelvic lymph node metastasis. An external beam irradiation dose of 45-56.4 Gy was administered to the whole pelvis with a 15 MV linear accelerator, and an additional 24 Gy was given to point A by HDR intracavitary brachytherapy. VEGF staining was defined as positive when more than 10% of the tumor cells were stained. The median follow-up duration was 58 months. Results: A positive VEGF expression was observed in 21 patients (67.7%), There was no significant correlation between the VEGF expression and pelvic lymph node metastasis, tumor size and the response of radiotherapy. During follow-up, 7 patients had recurrence. The complete response rate was not significant between the VEGF(-) and VEGF(+) tumors. However, the VEGF(+) tumors showed a significantly higher recurrence rate in comparison with the VEGF(-) tumors (p=0.040), The three year disease-free survival rates were 100% and 66.7%, respectively, for patients with VEGF(-) or VEGF(+) tumor (p=0.047), Conclusion: The VEGF expression was a significant factor for recurrence and disease-free survival. However, the significance of the VEGF expression is still controversial because of the various definitions of VEGF expression and the mismatches of the clinical data in the previous studies.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.349-357
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• 1995

Purpose : To analyze survival rate and late rectal and bladder complication for patients with stage I and II carcinoma of uterine cervix treated by radiation alone or combined with chemotherapy Materials and Methods : Between November 1984 and December 1993, 127 patients with stage I and II carcinoma of uterine cervix treated by radiation alone or combined therapy of radiation and chemotherapy. Retrospective analysis for survival rate was carried out on eligible 107 patients and review for complication was possible in 91 patients. The median follow-up was 47 months (range 3-118) and the median age of patiens was 56 years (range 31-76). 26 patients were stage IB by FIGO classification, 40 were stage IIA and 41 were stage IIB. 86 cases were treated by radiation alone and 21 were treated by radiation and chemotherapy. 101 patients were treated with intracavitary radiation therapy (ICRT), of these, 80 were received low dose rate (LDR) ICRT and 21 were received high dose rate (HDR) ICRT. Of the patients who received LDR ICRT, 63 were treated by 1 intracavitary insertion and 17 were underwent 2 insertions And we evaluated the external radiation dose and midline shield. Results : Actuarial survival rate at 5 years was $92{\%}$ for stage IB, $75{\%}$ for stage IIA, $53{\%}$ for stage IIB and $69{\%}$ in all patients Grade 1 rectal complications were developed in 20 cases ($22{\%}$), grade 2 were in 22 cases ($24{\%}$). 22 cases ($24{\%}$) of grade 1 urinary complications and 17 cases ($19{\%}$) of grade 2 urinary complications were observed But no patient had severe complications that needed surgical management or admission care. Maximum bladder dose for the group of patients with urinary complications was higher than that for the patients without urinary complications (7608 cGy v 6960cGy. p<0.01) Maximum rectal dose for the group of patients with rectal complications was higher than that for the patients without rectal complications (7041cGy v 6269cGy, p<0.01). While there was no significant difference for survival rate or bladder complication incidence as a function of dose to whole pelvis, Grade 2 rectal complication incidence was significantly lower for the patients receiving less than 4500cGy ($6.3{\%}$ v $25.5{\%}$, p<0.05). There was no significant differance between HDR ICRT group and LDR ICRT group for survival rate according to stage, on the other hand complication incidence was higher in the HDR group than LDR group, This was maybe due to different prescription doses between HDR group and LDR group. Midline shield neither improved survival rate nor decreased complication rate. The number of insertion in LDR ICRT group did not affect on survival and compication rate. Conclusion : In stage I and II carcinoma of uterine cervix there was no significant differance for 5 year survival rate by radiation therapy technique. Rectal complication incidence was as a function of dose to whole pelvis and there were positive correlations of maximum dose of rectum and bladder and each complication incidence. So we recommand whole pelvis dose less than 4500cGy and maximum dose of rectum and bladder as low as possible.

• 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.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.277-284
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• 1991

Survival data, prognostic factors, and patterns of failure were retrospectively analyzed for a total of 76 patients with adenocarcinoma of the uterine cervix treated between January 1981 and December 1987, which represents $4.1\%$ of all primary cervical carcinomas treated, at Department of Radiation Oncology, Yensei Cancer Center, Yonsei University College of Medicine. The mean age of the patients was 49 years (range, $27\~79$ years) and the peak incidence was in the group 50 to 59 years of age. More half of the patients were postmenopausal (46/76= $60.5\%$). Most patients ($76\%$) had abnormal vaginal bleeding either alone or in combination with other symptoms. The proportion of stage IIb was $43.4\%$. There were 4 major histologic subtypes: pure adenocarcinoma (48/76=$63.2\%$), adenosquamous carcinoma (20/76=$26.3\%$), papillary (5/76=$6.6\%$) and clear cell carcinoma (3/76=$3.9\%$). Of the many clinicopathologic variables evaluated for prognosis, the most significant prognostic factors were stage of disease and the size of tumor. The overall 5-year survival rate was $68\%$, and the 5-year survival rates for stage Ib, II and III were $90\%,\;66\%\;and\;54\%$, respectively. Control of pelvic tumors was achieved in $93.8\%,\;90.2\%\;and\;50.0\%$ of cases of stage Ib, II and III disease, respectively. In present study, treatment modalities (radiation therapy alone/combined operative and radiation therapy) did not affect the local control of tumor and the survival.

• Journal of Radiation Protection and Research
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• v.19 no.1
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• pp.51-68
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• 1994

It is good method to use frequency of chromosome aberration in Lymphocytes for a biological dosimetry in cases of accidental exposure to radiation. But in cases of past exposure, biological dosimetry is limited because the frequency of aberration decreases by time after exposure. To provide a basic data for estimation of past radiation exposure, the changing pattern of frequency of unstable chromosome aberration by time interval after exposure was studied. Observation was made on peripheral lymphocytes of 41 blood samples from 20 patients treated for uterine cervical carcinoma and endometrial carcinoma. The patients received 50.4Gy radiation to whole pelvis. Elapsed times after the completion of radiation therapy were 1 day, 3, 6, 9, 12, 24, 52, 104, 156, 208, 260 and 520 weeks. All the blood sample were microcultured. The Ydr, Qdr and Qdra were calculated from frequency of unstable aberration. Ydr did not decrease for 3 weeks after radiation therapy, and thereafter, decreased very rapidly and reached 0.05 at two years after radiation therapy and decreased very slowly until 5 years after radiation therapy. Relationship between unstable chromosome aberration and time interval after radiation therapy was described as $Ydr=0.259{\times}exp(-0.0429T)+0.0560{\times}exp(-0.00106T)$ (time in weeks) Qdr remained constant at 1.51 until 24 weeks after radiation therapy and then decreased to 1.17 at 52 weeks. Therafter, it did not change. Qdra remained constant at 1.10 for 12 weeks after radiation therapy and decreased to 0.81 at 52 weeks. Thereafter, it remained constant. Two superimposed exponential Ydr disappearance rate suggests that it is possible to calculate the past exposure dose. When the elapsed time after exposure is short, Qdr and Qdra are useful papameters for biological dosimetry for past radiation exposure.

• 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.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.343-352
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• 2002

Purpose : Radiotherapy is the main treatment modality for uterine cervix cancer. Since the rectum is in the radiation target volume, rectal bleeding is a common late side effect. This study evaluates the risk factors of radiation induced rectal bleeding and discusses its optimal management. Materials and Methods : total of 213 patients who completed external beam radiation therapy (EBRT) and intracavitary radiation (ICR) between September 1994 and December 1999 were included in this study. No patient had undergone concurrent chemo-radiotherapy. Ninety patients received radiotherapy according to a modified hyperfractionated schedule. A midline block was placed at a pelvic dose of between 30.6 Gy to 39.6 Gy. The total parametrial dose from the EBRT was 51 to 59 Gy depending on the extent of their disease. The Point A dose from the HDR brachytherapy was 28 Gy to 30 Gy $(4\;Gy\times7,\;or\;5\;Gy\times6)$. The rectal point dose was calculated either by the ICRU 38 guideline, or by anterior rectal wall point seen on radiographs, with barium contrast. Rectal bleeding was scored by the LENT/SOMA criteria. For the management of rectal bleeding, we opted for observation, sucralfate enema or coagulation based on the frequency or amount of bleeding. The median follow-up period was 39 months $(12\~86\;months)$. Results : The incidence of rectal bleeding was $12.7\%$ (27/213); graded as 1 in 9 patients, grade 2 in 16 and grade 3 in 2. The overall moderate and severe rectal complication rate was $8.5\%$. Most complications $(92.6\%)$ developed within 2 years following completion of radiotherapy (median 16 months). No patient progressed to rectal fistula or obstruction during the follow-up period. In the univariate analysis, three factors correlated with a high incidence of bleeding an icruCRBED greater than 100 Gy $(19.7\%\;vs.\;4.2\%)$, an EBRT dose to the parametrium over 55 Gy $(22.1\%\;vs.\;5.1\%)$ and higher stages of III and IV $(31.8\%\;vs.\;10.5\%)$. In the multivariate analysis, the icruCRBED was the only significant factor (p>0.0432). The total parametrial dose from the EBRT had borderline significance (p=0.0546). Grade 1 bleeding was controlled without further management (3 patients), or with sucralfate enema 1 to 2 months after treatment. For grade 2 bleeding, sucralfate enema for 1 to 2 months reduced the frequency or amount of bleeding but for residual bleeding, additional coagulation was peformed, where immediate cessation of bleeding was achieved (symptom duration of 3 to 10 months). Grade 3 bleeding lasted for 1 year even with multiple transfusions and coagulations. Conclusion : Moderate and several rectal bleeding occurred in $8.5\%$ of patients, which is comparable with other reports. The most significant risk factor for rectal bleeding was the accumulated dose to the rectum (icruCRBED), which corrected with consideration to biological equivalence. Prompt management of rectal bleeding, with a combination of sucralfate enema and coagulation, reduced the duration of the symptom, and minimized the anxiety/discomfort of patients.