• Radiation Oncology Journal
• /
• v.11 no.2
• /
• pp.355-361
• /
• 1993

Since May 1991, authors have conducted a pilot study to determine the feasibility and evaluate the effect of concurrent radiation therapy and chemotherapy with 5-FU and Cis-platinum for locally advanced cervical cancer (stage IIB-IVA). Radiation therapy consisted of external irradiation to whole pelvis (4140 cGy/23 fx) in 4.5 weeks followed by high dose rate intracavitary radiation therapy (HDR ICRT) to deliver a dose of 30 to 35 Gy to A point in 6 to 7 fractions. After the intracavitary radiation therapy, parametrial boost was delivered for B point dose of 60 Gy in Stage IIB and 65 Gy in stage IIIB. 5-FU (1000 $mg/m^2/24hr$ for 96 hour iv infusion) and Cis-platinum (20 $mg/m^2/day$ IV bolus for 3 days) were given during the second week of external RT and the second course chemotherapy administered at the first HDR ICRT with the same method as the first chemotherapy. Sixteen patients (10 stage IIB,4 stage IIIB,2 stage IVA) were registered to this protocol. Among these 16 patients, two refused treatment after 2 fractions of external irradiation, and one could not continue intracavitary irradiation because of treatment related genitourinary toxicity. So 14 patients were evaluated for toxicity and 13 patients were evaluated for response analysis. Five of 14 patients developed grade 3 gastrointestinal toxicity but 4 of them recovered at the completion of treatment. One stage IIIB patient with inguinal lymph node metastasis who received higher dose of radiation in spite of initial poor performance status did not recover from gastrointestinal toxicity at the completion of treatment. And she died of distant metastasis at one month after the completion of treatment. Two of 14 evaluable patients showed weight loss, more than $10\%$ of initial weight. One patient developed grade 3 leukopenia. In this study, the average total treatment period of completely treated patients was 75 days and three of them took more than 80 days (84, 84, 89 days). Toxicities were generally acceptable and there were no treatment related death. At the last follow-up, complete response was achieved in $62\%(8/13)$ and especially of nine patients with stage IIB, eight patients showed complete response. This study suggests that concurrent radiation therapy and chemotherapy (5-FU and Cis-platinum) is tolerable and effective. Further follow-up is needed to determine whether this protocol will have a favorable impact on survival and to evaluate the late effect on normal tissues. In future, prospective randomized trials are needed to compare the standard radiation therapy alone with concurrent chemotherapy and radiation therapy for locally advanced cervical carcinoma.

• Radiation Oncology Journal
• /
• v.24 no.1
• /
• pp.37-43
• /
• 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
• /
• v.20 no.4
• /
• pp.343-352
• /
• 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.

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

• Development and Reproduction
• /
• v.10 no.1
• /
• pp.55-61
• /
• 2006

There is growing concern that dietary soy intake is associated with protection of breast cancer. However, questions persist on the potential adverse effects of the main soy constituent genistein(GS) on female reproductive physiology. In this study, we examined whether prepubertal exposure to GS affected on the onset of puberty and the associated reproductive parameters such as hormone receptor expressions in female rats. GS(100mg/kg/day) was administrated daily from postnatal day 25(PND 25) to the day when the first vaginal opening(VO) was observed, and the animals were sacrificed on the day after VO occurred. Gross anatomy and tissue weight were compared to test the GS's effect on the cell proliferation. Furthermore, histological studies were performed to assess the structural alterations in tissues. Specific radioimmunoassay(RIA) were carried out to measure serum LH levels. To determine the transcriptional changes in progesterone receptors(PR), total RNAs were extracted from ovary and uterus and were applied to semi-quantitative reverse transcription polymerase chain reaction(RT-PCR). As a results, advanced VO was shown in the GS group(PND $31.2{\pm}0.6$) compared to the vehicle group (PND $35.3{\pm}0.7$). GS treatment significantly increased wet weight of ovaries and uteri compared to the vehicle group. Increased serum LH levels were also shown in the GS group. Graafian follicles and corpora lutea(CL) were observed only in the ovaries from GS treated animals. Similarly, hypertrophy of luminal and glandular uterine epithelium were found only in the GS group. Collectively, these effects were probably due to the estrogenic effects of GS. In the semi-quantitative RT-PCR studies, the transcriptional activities of PR in both ovary and uterus from GS-treated group were significantly higher than those from the vehicle group. The present studies demonstrated that acute exposure to GS, at levels comparable to the ranges of human exposure, during the critical period of prepubertal stage activates the reproductive system resulting precocious puberty in immature female rats.

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

• Progress in Medical Physics
• /
• v.21 no.3
• /
• pp.253-260
• /
• 2010

Most brachytherapy treatment planning systems employ a dosimetry formalism based on the AAPM TG-43 report which does not appropriately consider tissue heterogeneity. In this study we aimed to set up a simple Monte Carlo-based intracavitary high-dose-rate brachytherapy (IC-HDRB) plan verification platform, focusing particularly on the robustness of the direct Monte Carlo dose calculation using material and density information derived from CT images. CT images of slab phantoms and a uterine cervical cancer patient were used for brachytherapy plans based on the Plato (Nucletron, Netherlands) brachytherapy planning system. Monte Carlo simulations were implemented using the parameters from the Plato system and compared with the EBT film dosimetry and conventional dose computations. EGSnrc based DOSXYZnrc code was used for Monte Carlo simulations. Each $^{192}Ir$ source of the afterloader was approximately modeled as a parallel-piped shape inside the converted CT data set whose voxel size was $2{\times}2{\times}2\;mm^3$. Bracytherapy dose calculations based on the TG-43 showed good agreement with the Monte Carlo results in a homogeneous media whose density was close to water, but there were significant errors in high-density materials. For a patient case, A and B point dose differences were less than 3%, while the mean dose discrepancy was as much as 5%. Conventional dose computation methods might underdose the targets by not accounting for the effects of high-density materials. The proposed platform was shown to be feasible and to have good dose calculation accuracy. One should be careful when confirming the plan using a conventional brachytherapy dose computation method, and moreover, an independent dose verification system as developed in this study might be helpful.

• The Journal of Korean Society for Radiation Therapy
• /
• v.17 no.1
• /
• pp.57-71
• /
• 2005

Purpose : To evaluate radiation dose and accuracy with TLD and diode detector when treat total skin with electron beam. Materials and Methods : Using Stanford Technique, we treated patient with Mycosis Fungoides. 6 MeV electron beam of LINAC was used and the SSD was 300 cm. Also, acrylic speller(0.8 cm) was used. The patient position was 6 types and the gantry angle was 64, 90 and $116^{\circ}$. The patient's skin dose and the output were detected 5 to 6 times with TLD and diode. Result : The deviations of dose detected with TLD from tumor dose were CA $+\;6\%$, thigh $+\;8\%$, umbilicus $+\;4\%$, calf $-\;8\%$, vertex $-\;74.4\%$, deep axillae $-\;10.2\%$, anus and testis $-\;87\%$, sole $-\;86\%$ and nails shielded with 4mm lead $+4\%$. The deviations of dose detected with diode were $-4.5\%{\sim}+5\%$ at the patient center and $-1.1\%{\sim}+1\%$ at the speller. Conclusion : The deviation of total skin dose was $+\;8\%{\sim}-\;8\%$ and that deviation was within the acceptable range(${\pm}\;10\%$). The boost dose was irradiated for the low dose areas(vertex, anus, sole). The electron beam output detected at the sootier was stable. It is thought that the deviation of dose at patient center detected with diode was induced by detection point and patient position.

• Radiation Oncology Journal
• /
• v.15 no.4
• /
• pp.349-356
• /
• 1997

Purpose : To evaluate the efficacy of hyperfractionated radiation therapy in carcinoma of the cervix, especially on huge exophytic and endophytic stage Ib, IIa and IIb Materials and Materials : Fourty one patients with carcinoma of the cervix treated with hyperfractionated radiation therapy at the Department of Therapeutic Radiology, Dongsan Hospital, Keimyung University. School of Medicine from Jul, 1991 to Apr, 1994. According to FIGO s1aging system, therewere stage Ib (3 patients) IIa (6 patients) with exophytic ($\geq$5cm in dinmeter) and huge endophytic mass. and IIb (32 patients) with median age of 55 yeavs old. Radiation therapy consisted of hyperfractionated external irradition to the whole pelvis (120cGy/fraction, 2 fraction/day (minimum interval of 6 hours), 3600-5520cGy) and boost parametrial doses (for a total of 4480-6480cGy) with midline shield $(4\times10cm)$, and combined with intracavitary irradiation (up to 7480-8520cGy in Ib, IIa and 8480-9980cGy in IIb to point A). The maximum and mean follow up durations were 70 and 47 months respectively . Results : Five year local control rate was $78\%$ and the actuarial overall five year survival rate was $66.1\%$ for all patients, $44.4\%$ for stage Ib, IIa and $71.4\%$ for stage IIb. In bulky IIb (above 5cm in tumor size, 11 patients) five year local control rate and five rear survival rate was $88.9\%,\;73\%$ respectively Pelvic lymph node status (negative : $74\%,\;positive:25\%$, p=0.0015) was significant Prognostic factor affecting to five rear survival rate. There was marginally significant survival difference by total dose to A point ($>84Gy\;:\;70\%,\;>84Gy\;:\;42.8\%$, p=0.1). We consider that the difference of total dose to A point by stage (mean Ib,IIa : 79Gy. IIb 89Gy P=0.001) is one of the causes in worse local control and survival of Ib,IIa than IIb The overall recurrence rate was $39\%$ (16/41). The rates of local failure alone. distant failure alone. and combined local and distant failure were $9.7\%,\;19.5\%,\;and\;9.7\%$, respectively. Two Patients developed leukopenia ($\geq$ grade 3) and Three patients develoued grade 3 gastrointestinal complication. Above grade 3 complication was not noted. There was no treatment related death noted. Conclusion : We thought that it may be necessary to increase A point dose to more than 85Gy in hyperfractionated radiotherapy of huge exophytic and endophvtic stage Ib,IIa. We considered that hyperfractionated radiation therapy may be tolerable in huge exophytic and endophytic stage IIb cervical carcinoma with acceptable morbidity and possible survival gain but this was results in small patient group and will be confirmed by long term follow up in many patients.