• Radiation Oncology Journal
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• v.24 no.3
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• pp.171-178
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• 2006

[ $\underline{Purpose}$ ]: To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. $\underline{Materials\;and\;Methods}$: From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range $34{\sim}74$) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follows: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of $45{\sim}50.4\;Gy$ (median: 50.4 Gy) over $5{\sim}5.5$ weeks. Ir-192 HDR intracavitary brachytherapy (ICBT) was given after a total dose of 41.4 Gy. HDR-ICBT was performed twice a week, with a fraction point A dose of 4 Gy and median dose to point A was 28 Gy (range: $16{\sim}32\;Gy$) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT+ICBT) was $88\;Gy_{10}$ (range: $77{\sim}94\;Gy_{10}$). The median cumulative BED at ICRU 38 reference point (EBRT+ICBT) was $131\;Gy_3$ (range: $122{\sim}140\;Gy_3$) at point A, $109\;Gy_3$ (range: $88{\sim}125\;Gy_3$) at the rectum and $111\;Gy_3$ (range: $91{\sim}123\;Gy_3$) at the urinary bladder. Cisplatin ($60\;mg/m^2$) and 5-FU ($1,000\;mg/m^2$) was administered intravenously at 3 weeks interval from the first day of radiation for median 5 (range: $2{\sim}6$) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range: $8{\sim}50$ months). $\underline{: The complete response rate after concurrent chemoradiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure rate was 13% and distant metastatic rate was 3.3%. The crude rate of minor hematologic complications (RTOG grade 1-2) occurred in 3 patients (10%) and one patient had suffered from severe leukopenia (RTOG grade 4) during concurrent treatment. Acute minor enterocolitis (RTOG grade 1-2) occurred in 11 patients (37%) and one patient (3%) was suffered from colon perforation during radiation therapy. Late colitis of RTOG grade 1 occurred in 5 patients (15%). Acute cystitis of RTOG grade 1 occurred in 12 patients (40%) and late cystitis of RTOG grade 2 occurred in one patient (3%). No treatment related death was seen. $\underline{Conclusion}$: The results of this study suggest that the concurrent chemoradiation therapy with HDR brachytherapy could be accepted as an effective and safe treatment for 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.

• 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.

• Journal of Radiation Protection and Research
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• v.23 no.4
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• pp.259-266
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• 1998

There are three different types of gynecological applicator sets available in microSelectron-high dose-rate(HDR) System by Nucletron; standard applicator set(SAS), standard shielded applicator set(SSAS), and Fletcher-Williamson applicator set(FWAS). Shielding effect of a SAS without shielding material was compared with that of a SSAS with shielding material made of stainless steel(density ${\varrho}=8,000kg/m^3$) at the top and bottom of each ovoid, and of a FWAS with shielding material made of tungsten alloy(density ${\varrho}=14,000kg/m^3$ at the top and bottom of each ovoid. The shielding effects to the rectum and bladder of these two shielded applicator sets were to be measured at reference points with an ion chamber and specially designed supporting system for applicator ovoids inside of the computerized 3-dimensional water phantom. To determine the middle point of two ovoids the measurement was performed with the reference tip of ion chamber placed at the same level and at the middle point from the two ovoids, while scanning the dose with the ion chamber on each side of ovoids. The doses to the reference points of rectum were measured at 20(Rl), 25(R2), 30(R3), 40(R4), 50(R5), and 60(R6) mm located posteriorly on the vertical line drawn from M5(the middle dwell position of ovoid), and the doses to the bladder were measured at 20(Bl), 30(B2), 40(B3), 50(B4), and 60(B5) mm located anteriorly on the vertical line drawn from M5. The same technique was employed to measure the doses on each reference point of both SSAS and FWAS. The differences of measured rectal doses at 25 mm(R2) and 30 mm(R3) between SAS and SSAS were 8.0 % and 6.0 %: 25.0% and 23.0 % between SAS and FWAS. The differences of measured bladder doses at 20 mm(Bl) and 30 mm(B2) between SAS and SSAS were 8.0 % and 3.0 %: 23.0 % and 17.0 % between SAS and FWAS. The maximum shielding effects to the rectum and bladder of SSAS were 8.0 % and 8.0 %, whereas those of FWAS were 26.0 % and 23.0 %, respectively. These results led to the conclusion that FWAS has much better shielding effect than SSAS does, and when SSAS and FWAS were used for gynecological intracavitary brachytherapy in microSelectron-HDR system, the dose to the rectum and bladder was significantly reduced to optimize the treatment outcome and to lower the complication rates in the rectum and bladder.

• Progress in Medical Physics
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• v.20 no.2
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• pp.112-118
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• 2009

The source position and source dwelling time in a given source arrangement in the applicators is very high effect to determine the expose time which in general is derived from the brachytherapy planning system. In high dose rate (HDR) intracavitary radiation therapy (ICRT), the treatment is often performed in based out-patient during the whole fractionation irradiations. However, the patient should be waited on coutch for ICR treatment in first start fraction as unconvinent and immobilized state until perform the dose plannings. In our experiments, the HDR source contributed dose for$55.89{\pm}4.20%$ for straight tandem source, $38.14{\pm}4.46%$ for the right ovoid soucre on the fornix and$5.97{\pm}0.50%$ for left ovoid source. It also showed the $60.33{\pm}6.53%$ for the tandem, $33.10{\pm}6.74%$ for right ovoid and $6.58{\pm}0.30%$ for the left ovoid source in 10 degrees of applicator. The authors designed the source template dose planning software for ICRT of uterine cervix results average $-0.55{\pm}2.15%$ discrepancy of the full charged brachytherapy dose planning. Developed Source temperate ICRT plaanning software guide a minimized the complains and operating times within a ${\pm}3%$ of dose discrepancies.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5957-5961
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• 2015

Background: We designed this randomized controlled trial (RCT) to assess whether lobaplatin-based concurrent chemotherapy might be superior to cisplatin-based concurrent chemotherapy for FIGO stage II and III cervical cancer in terms of efficacy and safety. Materials and Methods: This prospective, open-label RCT aims to enroll 180 patients with FIGO stage II and III cervical cancer, randomly allocated to one of the three treatment groups (cisplatin $15mg/m^2$, cisplatin $20mg/m^2$ and lobaplatin $35mg/m^2$), with 60 patients in each group. All patients will receive external beam irradiation (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT). Patients in cisplatin $15mg/m^2$ and $20mg/m^2$ groups will be administered four cycles of $15mg/m^2$ or $20mg/m^2$ cisplatin intravenously once weekly from the second week to the fifth week during EBRT, while patients inthe lobaplatin $35mg/m^2$ group will be administered two cycles of $35mg/m^2$ lobaplatin intravenously in the second and fifth week respectively during pelvic EBRT. All participants will be followed up for at least 12 months. Complete remission rate and progression-free survival (PFS) will be the primary endpoints. Overall survival (OS), incidence of adverse events (AEs), and quality of life will be the secondary endpoints. Results: Between March 2013 and March 2014, a total of 61 patients with FIGO stage II and III cervical cancer were randomly assigned to cisplatin $15mg/m^2$ group (n=21), cisplatin $20mg/m^2$ group (n=21) and lobaplatin $35mg/m^2$ group (n=19). We conducted a preliminary analysis of the results. Similar rates of complete remission and grades 3-4 gastrointestinal reactions were observed for the three treatment groups (P=0.801 and 0.793, respectively). Grade 3-4 hematologic toxicity was more frequent in the lobaplatin group than the cisplatin group. Conclusions: This proposed study will be the first RCT to evaluate whether lobaplatin-based chemoraiotherapy will have beneficial effects, compared with cisplatin-based chemoradiotherapy, on complete remission rate, PFS, OS, AEs and quality of life for FIGO stage II and III cervical cancer.

• The Journal of Korean Society for Radiation Therapy
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• v.18 no.1
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• pp.13-19
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• 2006

Purpose: To evaluate whether modified MUPIT applicator can effectively eradicate recurrent tumor in uterine cervix cancer and reduce rectal complication after complete radiation treatment. Materials and Methods: Modified MUPIT applicator basically consists of an acrylic cylinder with flexible brain applicator, an acrylic template with a predrilled array of holes that serve as guides for interstitial needles and interstitial needles. CT scan was peformed to determine tumor volume and the position of interstitial needles. Modified MUPIT applicator was applied to patient in operation room and the accuracy for position of interstitial needles in tumor volume was confirmed by CTscan. Brachytherapy was delivered using modified MUPIT applicator and RALS(192-lr HDR) after calculated computer planning by orthogonal film. The daily dose was 600cGy and the total dose was delivered 3,000 cGy in tumor volume by BID. Rectal dose was measured by TLD at 5 points so that evaluated the risk of rectal complication. Results: The application of modified MUPIT applicator improved dramatically dose distributions in tumor volume and follow-up of 3 month for this patient was clinically partial response without normal tissue complication, Rectal dose was measured 34.1 cGy, 57.1 cGy, 103.8 cGy, 162.7 cGy, 165.7 cGy at each points, especially the rectal dose including previous EBRT and ICR was 34.1 cGy, 57.1 cGy. Conclusion: Patients with locally recurrent tumor in uterine cervix cancel treated with modified MUPIT applicator can expect reasonable rates of local control. The advantages of the system are the fixed geometry provided by the template and cylinders. and improved dose distributions in irregular tumor volume without rectal complication.

• Radiation Oncology Journal
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• v.14 no.1
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• pp.41-52
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• 1996

Purpose : This paper reports a dosimetric study of 88 patients treated with a combination of external radiotherapy and high dose rate ICR for FIGO stage IIB carcinoma of the cervix. The purpose is to investigate the correlation between the radiation doses to the rectum, external radiation dose to the whole pelvis, ICR reference volume, TDF BED and the incidence of late rectal complications, retrospectively. Materials and Methods : From November 1989 through December 1992, 88 patients with stage IIB cervical carcinoma received radical radiotherapy at Department of Radiation Oncology in Yonsei University Hospital. Radiotherapy consisted of 44-54 Gy(median 49 Gy) external beam irradiation plus high dose rate intracavitary brachytherapy with 5 Gy per fraction twice a week to a total dose of 30 Gy on point A. The maximum dose to the rectum by contrast(r, R) and reference rectal dose by ICRU 38(dr, DR) were calculated. The ICR reference volume was calculated by Gamma Dot 3.11 HDR planning system, retrospectively The time-dose factor(TDF) and the biologically effective dose (BED) were calculated. Results : Twenty seven($30.7\%$) of the 88 patients developed late rectal complications:12 patients($13.6\%$) for grade 1, 12 patients($13.6\%$) for grade 2 and 3 patients($3.4\%$) for grade 3. We found a significant correlation between the external whole pelvis irradiation dose and grade 2, 3 rectal complication. The mean dose to the whole pelvis for the group of patients with grade 2, 3 complication was Higher, $4093.3\pm453.1$ cGy, than that for the patients without complication, $3873.8\pm415.6$ (0.05$7163.0\pm838.5$ cGy, than that for the Patients without rectal complication, $0772.7\pm884.0$ (p<0.05). There was no correlation of the rate of grade 2, 3 rectal complication with the iCR rectal doses(r, dr), ICR reference volume, TDF and BED. Conclusion : This investigation has revealed a significant correlation between the dose calculated at the rectal dose by ICRU 38(DR) or the most anterior rectal dose by contrast(R) dose to the whole pelvis and the incidence of grade 2, 3 late rectal complications in patients with stage IIB cervical cancer undergoing external beam radiotherapy and HOR ICR. Thus these rectal reference points doses and whole pelvis dose appear to be useful Prognostic indicators of late rectal complication in high dose rate ICR treatment in cervical carcinoma.

• 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.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.