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 METHODS: 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 3060 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 toxicity 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 medically. 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.
Brachytherapy ; Carcinoma, Squamous Cell* ; Cervix Uteri* ; Chemoradiotherapy ; Cisplatin* ; Clinical Protocols ; Female ; Follow-Up Studies ; Humans ; Leukopenia ; Mortality ; Pelvis ; Risk Factors ; Uterine Cervical Neoplasms ; Weight Loss

PURPOSE: The objective of our study was to evaluate the immunohistochemical expression of p53 and bax proteins as prognostic markers in FIGO stage IIb invasive squamous cell carcinoma of the uterine cervix. MATERIALS AND METHODS: Sixty-five cases of squamous cell carcinoma of the cervix (stage IIb) that were diagnosed from October 1996 to December 2003 were analyzed retrospectively for the bax and p53 expression. These expressions were determined immunohistochemically and they were correlated to the patients' overall survival and disease-free survival. RESULTS: The overall 5-year survival (OS) rate and the disease-free survival (DFS) rate were 65.1% and 62.9%, respectively. p53 and bax immunoreactivity was seen in 26.2% and 52.3% of cases, respectively, with variable levels of expression. On the univariate analysis, only p53 positivity correlated with poor survival in DFS (log-rank test p=0.027), but this significance was not maintained on multivariated analysis by Cox's regression. The nine cases with the immunophenotype p53+/bax- had the poorest survival. CONCLUSION: Neither p53 nor bax expression are independent predictors of the prognosis for stage IIb cervical squamous cancers. Evaluation of p53 and bax co-expression may affect the clinical outcome and further investigation is needed.
bcl-2-Associated X Protein ; Carcinoma, Squamous Cell ; Cervix Uteri ; Disease-Free Survival ; Female ; Humans ; Prognosis ; Retrospective Studies

PURPOSE: An analysis was to compare the results of radiation alone with those of radiation with daily low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. MATERIALS AND METHODS: A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was performed. Thirty one patients received radiation alone and 28 patients received daily low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900~1,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000~3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4%) and 8 (13.6%) stages IIB and stage IIIB, respectively. RESULTS: The overall 5 year survival rate was 65.65% and according to treatment modality were 56.75% and 73.42% in the radiation alone and chemoradiation groups, respectively (p=0.180). The 5 year disease-free survival rates were 49.39% and 63.34% in the radiation alone and chemoradiatoin groups, respectively (p=0.053). The 5 year locoregional control rates were 52.34% and 73.58% in the radiation alone and chemoradiation groups, respectively (p=0.013). The 5 year distant disease-free survival rates were 59.29% and 81.46% in the radiation alone and chemoradiation groups, respectively (p=0.477). Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia (> or =3 grade) occurred in 3.2% and 28.5% of the radiation alone and chemoradiation groups, respectively (p=0.02). There were no statistical differences in the incidences of vesical, rectal and small bowel complications between two groups. CONCLUSION: Radiation therapy with low dose cisplatin did not improve the rates of survival and response rates, but did improve the rate of disease free survival and locoregional control rates in locally advanced cervical cancer. The incidence of bone marrow suppression was higher in the chemoradiation group.
Bone Marrow ; Brachytherapy ; Cervix Uteri ; Cisplatin* ; Classification ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Incidence ; Leukopenia ; Pelvis ; Retrospective Studies ; Survival Rate ; Uterine Cervical Neoplasms*

OBJECTIVE: The aim of this study was to evaluate the prognostic significance of primary tumor volume and uterine corpus invasion assessed by MRI in stage II uterine cervical cancer patients treated by concurrent chemotherapy and radiotherapy. METHODS: Fifty-two patients diagnosed with stage II cervical carcinoma were entered into the study. The tumor volume was calculated by the equation (Volume=widthXlengthXheightXpi/6) as an ellipsoid approximation. Univariate and multivariate analyses were performed to identify the prognostic factors for overall survival (OS), disease-free survival (DFS), pelvic control (PC), and distant metastasis-free survival (DMFS). RESUITS: The 5-year OS, DFS, PC, and DMFS rates were 65.8%, 59.3%, 72.6%, and 79.9%, respectively. The average volume of primary cervical tumor on MRI was 29.5 ml (5-109) and volume was not correlated with stage (p=0.180). Corpus invasion was exhibited in 50.0% and 93.8% of patients with small tumor volume (<30 ml) and large tumor volume (> or =30 ml), respectively; and strongly correlated with tumor volume (p<0.001). By univariate analyses, larger clinical tumor diameter (p=0.031), positive pelvic lymph node (p=0.033), uterine corpus invasion (p=0.045), and larger tumor volume (p=0.003) showed a statistically significantly relation to worse survival. In multivariate analyses, dividing patients according to whether the tumor volume was more or less than 30 ml predicted OS (p=0.048) and uterine corpus invasion also predicted DFS (p=0.042). CONCLUSION: Tumor volume and uterine corpus invasion determined by pre-treatment MRI examinations were significant prognostic factors for patients with invasive cervical carcinoma treated with concurrent chemotherapy and radiotherapy.
Disease-Free Survival ; Drug Therapy ; Humans ; Lymph Nodes ; Magnetic Resonance Imaging* ; Multivariate Analysis ; Radiotherapy ; Tumor Burden* ; Uterine Cervical Neoplasms*