• Radiation Oncology Journal
• /
• v.9 no.2
• /
• pp.271-276
• /
• 1991

A series of 510 patients with carcinoma of the uterine cervix given the curative radiation therapy from March 1979 through December 1986 was evaluated to determine the value of intravenous pyelography (IVP), cystoscopy, sigmoidoscopy, and abdomino-pelvic CT as staging work-up prior to treatment. On IVP and cystoscopy, $10.7\%$(49/456) and $5.3\%$(24/452) showed abnormality, respectively, but only $0.7\%$(3/413) did on sigmoidoscopy. As a result of these work-ups prerequisite to FIGO staging, twenty six ($5.1\%$) out of 510 patients were upstaged from the stage determined by the findings of physical examination alone. The proportions of upstaging in each stage were as follows; none in stage IB (35), IIA (89) and IIIA (8), $7.9\%$(20/252) in stage IIB (14 patients to FIGO stage IIIB, 6 patients to FIGO stage IVA), and $4.8\%$(6/126) in stage IIIB (all to FIGO stage IVA). Positive findings of staging work-ups were found only in patients with advanced stages of stage IIB or over determined by physical examination alone but not in those with earlier stages. CT was performed in 337 patients. CT detected pelvic lymph node (LN) enlargement in $25.2\%$ (85/337) and paraaortic LN enlargement in $7.4\%$(25/337). Pelvic LN positivity was well correlated with increasing stage but paraaortic LN positivity was not. In the evaluation of parametrial involvement, CT findings were in accordance with those of physical examination only in $65.6\%$ (442/674). When compared with endoscopic studeies, CT had much lower positive predictive value than negative predicitive value in the evaluation of adjacent organ invasion. The staging work-ups should be individualized by the disease extent of each patient, and then the efficiency of work-uus may be increased without compromising the appropriate FIGO staging and treatment.

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

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.9
• /
• pp.5165-5169
• /
• 2013

Background: To evaluate the pathological characteristics of invasive margins in early-stage cervical squamous cell carcinomas and their association with other clinicopathological features including clinical outcomes. Materials and Methods: Patients with FIGO stage IB-IIA cervical squamous cell carcinomas who received surgical treatment and had available follow-up information were identified. Their histological slides were reviewed for prognostic variables including tumor size, grade, extent of invasion, lymphovascular invasion, involvement of vaginal margin or parametrium, and lymph node metastasis. The characteristics of invasive margins including invasive pattern (closed, finger-like, or spray-like type), degree of stromal desmoplasia, and degree of peritumoral inflammatory reaction were evaluated along the entire invasive fronts of tumours. Associations between the characteristics of invasive margins and other clinicopathological variables and disease-free survival were assessed. Results: A total of 190 patients were included in the study with a median follow-up duration of 73 months. Tumour recurrence was observed in 18 patients (9%). Spray-like invasive pattern was significantly more associated as compared with closed or finger-like invasive pattern (p=0.005), whereas the degree of stromal desmoplasia or peritumoral inflammatory reaction was not. Low degree of peritumoral inflammatory reaction appeared linked with lymph node metastasis (p=0.021). In multivariate analysis, a spray-like invasive pattern was independently associated with marked stromal desmoplasia (p=0.013), whilst marked desmoplasia was also independently associated with low inflammatory reactions (p=0.009). Furthermore, low inflammatory reactions were independently associated with positive margins (p=0.022) and lymphovascular invasion (p=0.034). The patients with spray-like invasive pattern had a significantly lower disease-free survival compared with those with closed or finger-like pattern (p=0.004). Conclusions: There is a complex interaction between cancer tissue at the invasive margin and changes in surrounding stroma. A spray-like invasive pattern has a prognostic value in patients with early-stage cervical squamous cell carcinoma.

• Radiation Oncology Journal
• /
• v.11 no.1
• /
• pp.43-50
• /
• 1993

We evaluated frequency and types of chromosomal aberrations by ionizing radiation in cancer patients treated with radiotherapy in our institution. Twenty-five patients with various types of carcinomas such as lung, uterine cervix, esophagus, rectum, head and neck and pancreatic cancers were studied immediately before and after external beam radiotherapy. The frequency of aberrant metaphase prior to treatment was $4.93{\%}$, which was higher than that of control group. Especially in lung cancer, the freuqency of aberrant metaphase was three times higher than control group. A comparison of chromosomal abnormalities observed before and after radiotherapy demonstrated that proportion of aberrant rnetaphases was significantly inreased to $22.13{\%}$. Major chromosomal aberrations like structural abnormalities showed remarkalbe increase from 65.45 to $88.45{\%}$ after the treatment. Also the numbers of chromosomal alterations per cell were increased by a factor of 6.5. Aberrations with two or more break points were more prominently increased, compared with aberrations with single break point. The number of chromosomal break points was noted to be higher than expected value in No.1, 3, 8 and 11 chromosomes and lower in No.13, 15, 17 and 21 chromosomes. Based on this study, we believe that the distribution of chromosomal breakage is related with gene and chromosomal rearrangement which could result in the development of cancers.

• The Journal of Korean Society for Radiation Therapy
• /
• v.18 no.1
• /
• pp.13-19
• /
• 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
• /
• v.12 no.1
• /
• pp.27-31
• /
• 1994

There are a number of reports suggesting that there may be a correlation between the clinical response to radiotherapy in various tumors and the clonogenic survival of cell lines derived from these tumors following exposure to 2 Gy(SF2). Authors conducted this study to determine SF2 for cells in primary culture from surgical specimens. The tumor tissues with squamous cell carcinoma of uterine cervix and head and neck were obtained. The tumor tissues were disaggregated to single cells by incubating with collagenase type w for 2 hours with constant stirring. Single cell suspensions were inoculated in four 24-well plates precoated with cell adhesive matrix. After 24 hours of incubation at 37$ ^{\circ}C $, rows of four wells were then irradiated, consisting of control set and five other sets each receiving doses of 1,2,3,4, and 6 Gy. After incubation for a total of 13 days, the cultures were stained with crystal violet and survival at each dose was determined by quantitative image analysis system, To determine whether cell growth was of epithelial origin, immunocytochemical staining with a mixture of cytokeratin and epithelial monoclonal antibodies were performed on cell cultures. During the period of this study, we received 5 squamous cell carcinoma specimens of head and neck and 20 of uterine cervical carcinoma. Of these, 15 yielded enough cells for radiosensitivity testing. This resulted an overall success rate of 60$ \% $. The mean SF2 value for 15 tumours was 0.55$\pm$0.17 ranging from 0.20 to 0.79. These results indicate that there is a broad range of sensitivities to radiation in same histologic type. So with a large patient population, we plan to determine whether a different SF2 value is associated with tumours that are controlled with radiotherapy than those that are not.

• Radiation Oncology Journal
• /
• v.15 no.3
• /
• pp.255-262
• /
• 1997

Purpose : This is retrospective study to compare the results of radiation therapy alone and neoadjuvant chemotherapy and radiation in advanced stage of uterine cervical cancer. Materials and Methods : Seventy-six Patients who were treated with definitive radiation therapy for locally advanced cervical cacinoma between June 1988 and December 1993 at the department of radiation oncology, Keimyung University Dong-san Hospital. Thirty six patients were treated with radiation therapy alone and forty patients were treated with cisplatin based neoadjuvant chemotherapy and radiation therapy. According to FIGO staging system. there were 48 patients in stage IIb, 3 patients in stage IIIa, 23 patients in stage lIIb and two patients in stage IVa with median age of 53 years old. Follow-up periods ranged from 7 to 95 months with median 58 months. Results : Complete response (CR) rate were $86.1\%$ in radiation alone group and $80\%$ in chemoradiation group. There was no statistical difference in CR rate between the two groups. Overall five-year survival rate was $67.3\%$. According to stage, overall five-rear survival rates were $74\%$ in stage IIb, $66.7\%$ in stage IIIa, $49.8\%$ in stage IIb, $50\%$ in stage IVa. According to treatment modality overall five year survival rates were $74.1\%$ in radiation alone and $61.4\%$ in chemoradiation group (P=0.4) Five rear local failure free survival rates were $71.5\%$ in radiation alone group and $60\%$ in chemoradiation group (P=0.17). Five year distant metastasis free survival rates were $80.7\%$ in radiation aione group and $89.9\%$ in chemoradiation group (P=0.42). Bone marrow suppression (more than noted in 3 cases of radiaion alone group and 1 case of chemoradiation group. Grade II retal complication was noted in 5 patients of radiation group and 4 patients In chemoradiation group. Bowel obstruction treated with conservative treatment (1 patient) and bowel perforation treated with surgery (1 patient) were noted in radiation alone group. There was no statistical difference in complication between two groups. Conclusion : There was no statistical difference in survival, failure and complication between neoadjuvant chemotherapy and radiation versus radiation alone in locally advanced uterine cervical carcinoma.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.11
• /
• pp.6935-6940
• /
• 2013

Background: This study aimed to develop a prognostic model in patients with early-stage cervical squamous cell carcinoma based on clinicopathological features, including invasive margin characteristics. Materials and Methods: Clinicopathological features and outcomes of 190 patients with FIGO stage IB-IIA cervical squamous cell carcinoma treated by surgery were collected and analyzed for factors associated with tumor recurrence. In addition to well-recognized pathological risk factors, the pathological characteristics of invasive margin (type of invasive pattern and degree of stromal desmoplasia and peritumoral inflammatory reaction) were also included in the analysis. Multiple scoring models were made by matching different clinicopathological variables and/or different weighting of the score for each variable. The model with the best performance in the prediction of recurrence and decreased survival was selected. Results: The model with the best performance was composed of a combined score of invasive pattern, lymphovascular space invasion (LVSI), and degree of inflammatory reaction and stromal desmoplasia (total score =10). Compared to those with score ${\leq}8$, the patients with score 9-10 had a significantly higher recurrence rate in the overall group (p<0.001) and the subgroup without adjuvant therapy (p<0.001), while the significance was marginal in the subgroup with adjuvant therapy (p=0.069). In addition, the patients with score 9-10 had a higher rate of tumor recurrence at distant sites (p=0.007). The disease-free survival was significantly lower in the patients with score 9-10 than those with score ${\leq}8$ among the overall patients (p<0.001), in the subgroup without adjuvant therapy (p<0.001), and the subgroup with adjuvant therapy (p=0.047). Conclusions: In this study, a prognostic model based on a combination of pathological characteristics of invasive margin and LVSI proved to be predictive of tumor recurrence and decreased disease-free survival in patients with early-stage cervical squamous cell carcinoma.

• Radiation Oncology Journal
• /
• v.16 no.3
• /
• pp.311-323
• /
• 1998

Purpose : Prospective, single arm, Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. Methods and Materials : From Mar 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The International Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4,140-5,040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/$m^2$/day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/$m^2$/day intravenous bolus for 3 days day 1-3, 29-31) administered starting on day 1 of RT. Results : The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52$\%$ and 64$\%$, respectively. The 5-rear actuarial survival for stage IIB and III+IVA patients were 58$\%$ and 36$\%$, respectively The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71$\%$ and 40$\%$, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9$\%$ (19/68) : local failure in 5.9$\%$ (4/68), distant metastasis in 10.3$\%$ (7/68) and both in 11.8$\%$ (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment the complete response rate was 78$\%$ (50/64). Concurrent chemoradiation appear to be a well-tolerated regimen but there were two treatment-related deaths. Conclusion : Concurrent chemotherapy of FP with high-dose definitive RT in locally advanced carcinoma of the uterine cervix is feasible and effective with acceptable toxicities. This chemoradiation regimen may offer a modest survival benefit for advanced stage. Further follow-up of these patients will evaluate the impact of this regimen on the long-term local control and their survival.

• Radiation Oncology Journal
• /
• v.17 no.2
• /
• pp.113-119
• /
• 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.