• Radiation Oncology Journal
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• v.18 no.4
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• pp.300-308
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• 2000

Purpose :The aim of this study is to analysis of suwival and recurrence rates of the uterine cervical carcinoma patients whom received the radiation therapy respectively. The prognostic factors, such as Papanicolaou (Pap) smear, carcinoembriogenic antigen (CEA) and squamous cell carcinoma (SCC) antigen has been studied. Methods and Materials : From January 1981 to December 1998, eight-hundred twenty-seven uterine carvical cancer patients were treat with radiation therapy. All of the patients were divided into two groups : the radiation therapy only (S2l patients) group and the postoperative radiation therapy (326 patients) group. The age, treatment modality, clinical stage, histopathology, recurrence, follow-up Pap smears, CEA and SCC antigen were used as parameters for the evaluation. The prognostic factors such as survival and recurrence rates were peformed with the Kaplan-Meier method and the Cox hazard model, respectively. Median rollow-up was 38.6 months. Results :On the radiation therapy only group, 314 patients (60$\%$) achieved complete response (CR), 47 patients (9$\%$) showed local recurrence (LR), 78 patients (15$\%$) developed distant metastasis (DM). On the Postoperative radiation therapy group, showed 276 Patients (85$\%$) CR, 8 Patients (2$\%$) LR, 37 Patients (11$\%$) DM. The 5-year survival and recurrence rates was evaluated for all parameters. The statistically significant factors for the survival rate in univariate analysis were clinical stage (p=0.0001), treatment modality (p=0.0010), recurrence (p=0.0001), Pap smear (p=0.0329), CEA (p=0.0001) and SCC antigen (p=0.0001). Conclusion: This study indicated that after treatment, the follow-up studies of Pap smear, CEA and SCC antigen were significant parameter and prediction factors for the survival and recurrence of the uterine cervical carcinoma.

• 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.15 no.4
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• pp.369-377
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• 1997

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

• Journal of radiological science and technology
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• v.29 no.2
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• pp.83-92
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• 2006

Based on the data of cervical cancer patients who were treated by the radiotherapy with concurrent chemotherapy at the radiation oncology department of National Cancer Center from January 2002 to February 2003, we have studied the method recommended by ICRU 38 to maximize the prescription dose to the planing target volume (PTV) with minimizing the dose to surrounding normal organs. Clinical stage of the patients are 1 patient for stage IB, 3 patients for IIA, 19 patients for IIB, 3 patients for IIIA, 3 patients for IIIB and 1 patient for IV. All patients took the MRI before treatment and the maximum size of the gross tumor volume were under 4cm for 17 patients and from 4 cm to 6 cm for 12 patients and above 6 cm for 1 patient. The results show that while the irradiated volume can be reduced with optimized dose distribution using PTV treatment planning (p<0.0001) when the remained tumor size is small, the surrounding normal organs will receive unnecessarily large dose when the irradiated tumor volume is relatively large. This is because there is some limitation in controling the intensity of radiation in Fletcher Williamson Applicator. To overcome the limit of applicator and to achieve the optimal dose distribution, we have virtually applied 4 needles with Fletcher Williamson Applicator for 10 patients who have relatively large tumor and studied the change in dose distribution before and after application. The results show that this new virtual treatment plan reduces the volume covered by 100 % isodose (p=0.0608, p=0.0607) and reduces the dose of normal organs (p=0.0162, p=0.008). This evidence suggest that this method is superior than the currently used method such as PTV treatment and ICRU treatment.

• 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.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.

• 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.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.353-358
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• 2002

Purpose : To investigate the clinical usefulness of a follow-up examination using serum squamous cell carcinoma antigen (SCC) for the early detection of recurrence in patients treated for conical squamous cell carcinoma. Materials and Methods : 20 patients who were treated for recurrent cervical squamous cell carcinoma between 1997 and 1998, who had experienced a complete remission after radiotherapy and who underwent an SCC test around the time when recurrence was detected, were included in this study. The levels of SCC were measured from the serum of the patients by immunoassay and values less than 2 ng/mL were regarded as normal. The sensitivity of the SCC test for use in the detection of recurrence, the association between the SCC values and the recurrence patterns and the tumor size and stage, and the temporal relation between the SCC increment and recurrence detection were evaluated. Results : The SCC values were above normal in 17 out of 20 patients, so the sensitivity of the SCC test for the detection of recurrence was $85\%$, and the mean and median of the SCC values were 15.2 and 9.5 ng/mL, respectively. No differences were observed in the SCC values according to the recurrence sites. For 11 patients, the SCC values were measured over a period of 6 months before recurrence was detected, and the mean and median values were 13.6 and 3.6 ng/mL, respectively. The SCC values of 7 patients were higher than the normal range, and the SCC values of the other 4 patients were normal but 3 among them were above 1.5 ng/mL. At the time of diagnosis, the SCC valuess were measured for 16 of the 20 recurrent patients, and the SCC values of the patients with a bulky tumor $(\geq4\;cm)$ or who were in stage IIb or III were higher than those of the patients with a non-bulky tumor or who were in stage Ib or IIa. Conclusion : The SCC test is thought to be useful for the early detection of recurrence during the follow up period in patients treated for cervical squamous cell carcinoma. When an effective salvage treatment is developed in the future, the benefit of this follow-up SCC test will be increased.

• 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.