• Radiation Oncology Journal
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• v.13 no.4
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• pp.359-368
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• 1995

Purpose : This is a retrospective analysis for pattern of failure, survival rate and prognostic factors of 114 patients with histologically proven invasive cancer of the uterine cervix treated with definitive irradiation. Materials and Methods : One hundred fourteen patients with invasive carcinoma of the cervix were treated with a combination of intracavitary irradiation using Fletcher-Suit applicator and external beam irradiation by 6MV X-ray at the Ewha Womans University Hospital between March 1982 and Mar 1990. The median age was 53 years(range:30-77 years). FIGO stage distribution was 19 for IB, 23 for IIA, 42 for IIB, 12 for IIIA and 18 for IIIB. Summation dose of external beam and intracavitary irradiation to point A was 80-90 Gy(median:8580 cGy) in early stage(IB-IIA) and 85-100 Gy(median:8850 cGy) in advanced stage(IIB-IIIB). Kaplan-Meier method was used to estimate the survival rate and multivariate analysis for progrostic factors was performed using the Log likelihood for Weibull Results : The pelvic failure rates by stage were $10.5{\%}$ for IB. $8.7{\%}$ for IIA, $23.8{\%}$ for IIB, $50.0{\%}$ for IIIA and $38.9{\%}$ for IIIB. The rate of distant metastasis by stage were $0{\%}$ for IB, $8.7{\%}$ for IIA, $4.8{\%}$ for IIB. $0{\%}$ for IIIA and $11.1{\%}$ for IIIB. The time of failure was from 3 to 50 months and with median of 15 months after completion of radiation therapy. There was no significant coorelation between dose to point A($\leq$90 Gy vs >90 Gy) and pelvic tumor control(P>0.05). Incidence rates of grade 2 rectal and bladder complications were $3.5{\%}$(4/114) and $7{\%}$(8/114), respectively and 1 patient had sigmoid colon obstruction and 1 patient had severe cystitis. Overall 5-year survival rate was $70.5{\%}$ and disease-free survival rate was $53.6{\%}$. Overall 5-year survival rate by stage was $100{\%}$ for IB, $76.9{\%}$ for IIA, $77.6{\%}$ for IIB $87.5{\%}$ for IIIA and $69.1{\%}$ for IIIB. Five-rear disease-free survival rate by stage was $81.3{\%}$ for IB, $67.9{\%}$ for IIA, $46.8{\%}$ for IIB, $45.4{\%}$ for IIIA and $34.4{\%}$ for IIIB. The prognostic factors for disease-free survival rate by multivariate analysis was performance status(p= 0.0063) and response rate after completion of radiation therapy(p= 0.0026) but stage, age and radiation dose to point A were not siginificant. Conclusion : The result of radiation therapy for early stage of the uterine cervix cancer was relatively good but local control rate and survival rate in advanced stage were poor inspite of high dose irradiation to point A above 90 Gy. Prospective randomized studies are recommended to establish optimal tumor doses for various stages and volume of carcinoma of uterine cervix, And ajuvant chemotherapy or radiation-sensitizing agents must be considered to increase the pelvic control and survival rate in advanced cancer of uterine cervix.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.409-423
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• 1998

Purpose : This retrospective study was tried to evaluate the clinical characteristics of patients, patterns of failure, survival rates, prognostic factors affecting survival, and treatment related toxicities when non-small cell lung cancer patients was treated by definitive radiotherapy alone or combined with chemotherapy. Materials and Methods : We evaluated the treatment results of 70 patients who were treated by definitive radiation therapy for non-small cell lung cancer at the Department of Radiation Oncology, Ewha Womans University Hospital, between March 1982 and April 1996. The number of patients of each stage was 2 in stage I, 6 in stage II, 30 in stage III-A, 29 in stage III-B, 3 in stage IV. Radiation therapy was administered by 6 MV linear accelerator and daily dose was 1.8-2.0 Gy and total radiation dose was ranged from 50.4 Gy to 72.0 Gy with median dose 59.4 Gy. Thirty four patients was treated with combined therapy with neoadjuvant or concurrent chemotherapy and radiotherapy, and most of them were administered with the multi-drug combined chemotherapy including etoposide and cisplatin. The survival rate was calculated with the Kaplan-Meier methods. Results : The overall 1-year, 2-year, and 3-year survival rates were 63$\%$, 29$\%$, and 26$\%$, respectively. The median survival time of all patients was 17 months. The disease-free survival rate for 1-year and 2-year were 23$\%$ and 16$\%$, respectively. The overall 1-year survival rates according to the stage was 100$\%$ for stage I, 80$\%$ for stage II, 61$\%$ for stage III, and 50$\%$ for stage IV. The overall 1-year 2-year, and 3-year survival rates for stage III patients only were 61$\%$, 23$\%$, and 20$\%$, respectively. The median survival time of stage III patients only was 15 months. The complete response rates by radiation therapy was 10$\%$ and partial response rate was 50$\%$. Thirty patients (43$\%$) among 70 patients assessed local control at initial 3 months follow-up duration. Twenty four (80$\%$) of these 30 Patients was possible to evaluate the pattern of failure after achievement of local control. And then, treatment failure occured in 14 patients (58$\%$): local relapse in 6 patients (43$\%$), distant metastasis in 6 patients (43$\%$) and local relapse with distant metastasis in 2 patients (14$\%$). Therefore, 10 patients (23$\%$) were controlled of disease of primary site with or without distant metastases. Twenty three patients (46$\%$) among 50 patients who were possible to follow-up had distant metastasis. The overall 1-year survival rate according to the treatment modalities was 59$\%$ in radiotherapy alone and 66$\%$ in chemoirradiation group. The overall 1-year survival rates for stage III patients only was 51$\%$ in radiotherapy alone and 68$\%$ in chemoirradiation group which was significant different. The significant prognostic factors affecting survival rate were the stage and the achievement of local control for all patients at univariate- analysis. Use of neoadjuvant or concurrent chemotherapy, use of chemotherapy and the achievement of local control for stage III patients only were also prognostic factors. The stage, pretreatment performance status, use of neoadjuvant or concurrent chemotherapy, total radiation dose and the achievement of local control were significant at multivariate analysis. The treatment-related toxicities were esophagitis, radiation pneunonitis, hematologic toxicity and dermatitis, which were spontaneously improved, but 2 patients were died with radiation pneumonitis. Conclusion : The conventional radiation therapy was not sufficient therapy for achievement of long-term survival in locally advanced non-small cell lung cancer. Therefore, aggressive treatment including the addition of appropriate chemotherapeutic drug to decrease distant metastasis and preoperative radiotherapy combined with surgery, hyperfractionation radiotherapy or 3-D conformal radiation therapy for increase local control are needed.

• Journal of Plant Biotechnology
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• v.33 no.1
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• pp.57-62
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• 2006

Several methods for determining the response of corn to glyphosate were investigated to provide a fast and reliable method for identifying glyphosate-resistant corn in vivo. Two bioassays were developed. One assay is named 'whole plant / leaf growth assay', in which the herbicide glyphosate is applied on the upper part of 3rd leaf and the growth of herbicide-untreated 4th leaf is measured at 3 day after treatment. in this assay, the leaf growth of conventional corn was inhibited in a dose dependent from 50 to $1600{\mu}g/mL$ of glyphosate and growth inhibition at $1600{\mu}g/mL$ was 55% of untreated control. The assay has the potential to be used especially in the case that the primary cause of glyphosate resistance is related with a reduction of the herbicide translocation. Another assay is named 'leaf segment / shikimate accumulation assay', in which the four excised leaf segments ($4{\times}4mm$) are placed in each well of a 48-well microtiter plate containing $200{\mu}L$ test solution and the amount of shikimate is determined after incubation for 24 h in continuous light at $25^{\circ}C$. In this assay, 0.33% sucrose added to basic test solution enhanced a shikimate accumulation by 3 to 4 times and the shikimate accumulation was linearly occurred from 2 to $8{\mu}g/mL$ of glyphosate, showing an improved response to the method described by Shaner et al. (2005). The leaf segment / shikimate accumulation assay is simple and robust and has the potential to be used as a high throughput assay in the case that the primary cause of glyphosate resistance is related with EPSPS, target site of the herbicide. Taken together, these two assays would be highly useful to initially select the lines obtained after transformation, to investigate the migration of glyphosate-resistant gene into other weeds and to detect a weedy glyphosate-resistant corn in field.

• Radiation Oncology Journal
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• v.10 no.2
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• pp.193-204
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• 1992

During the period between March 1983 and December 1990, 74 patients with esophageal carcinoma (EG) were treated with radiation therapy (RT) at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. Of these, 6 patients were lost to follow-up, and 13 patients were interrupted. So the remaining 55 patients were analyzed, retrospectively. 32 patients were irradiated with curative aim, 12 patients with palliative intent, 10 patients postoperatively, and 1 patient pre- and post-operatively. Among these 55 patients, 28 patients were treated with chemoradiation modality, and 27 patients with RT alone. All patients were followed for a minimum of 20 months or until death. Of 32 patients irradiated by curative aim, 22 patients (69%) showed partial remission (PR), 6 patients (19%) complete remission (CR). Overall mean survival and two-year survival rate were 15.6 months and 22%. With respect to sex, age, pathologic differentiation, tumor location, tumor size, stage, RT aim, RT response, RT dose, use of chemotherapy and functional categories (FC) of dysphagia at initiation of RT and at finishing RT: Tumor size, stage, RT response had great influences on prognosis and FC at finishing RT had a slight influence on prognosis. Especially, the mean survival and 2-year survival rate in patients with postoperative RT were 24.7 months and 63%, which could be compared with 29.1 months and 43% in radically treated patients with CR. And the mean survival duration and 2-year survival rate in patients irradiated with doses more than 60 Gy were 22.4 months and 29%, and 50~60 Gy were 12.2 months and 12%, respectively. However, no significant difference was shown statistically. Among 12 patients treated with palliative intent, 9 patients (75%) had good improvement in dysphagia and the mean duration of palliative response was 10.6 months.

• Radiation Oncology Journal
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• v.27 no.2
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• pp.64-70
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• 2009

Purpose: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced unresectable pancreatic cancer. However, the introduction of gemcitabine and the recognition of a benefit in patients with advanced disease stimulated the design of trials that compare chemotherapy alone to concurrent chemoradiation. Therefore, we evaluated role of CCRT for locally advanced unresectable pancreatic cancer. Materials and Methods: We carried out a retrospective analysis of treatment results for patients with locally advanced unresectable pancreatic cancer between January 2000 and January 2008. The radiation was delivered to the primary tumor and regional lymph nodes with a 1~2 cm margin at a total dose of 36.0~59.4 Gy (median: 54 Gy). The chemotherapeutic agent delivered with the radiation was 5-FU (500 mg/$m^2$). The patients who underwent chemotherapy alone received gemcitabine (1,000 mg/$m^2$) alone or gemcitabine with 5-FU. The follow-up period ranged from 2 to 38 months. The survival and prognostic factors were analyzed using Kaplan-Meier method and log-rank test, respectively. Results: Thirty-four patients received concurrent chemoradiotherapy, whereas 21 patients received chemotherapy alone. The median survival time was 12 months for CCRT patients, compared to 11 months for chemotherapy alone patients (p=0.453). The median progression-free survival was 8 months for CCRT patients, compared to 5 months for chemotherapy alone patients (p=0.242). The overall response included 9 partial responses for CCRT and 1 partial response for chemotherapy alone. In total, 26% of patients from the CCRT group experienced grade 3~4 bowel toxicity. In contract, no grade 3~4 bowel toxicity was observed in the chemotherapy alone group. The significant prognostic factors of overall survival were lymph node status, high CA19-9, and tumor location. Conclusion: The response rate and progression-free survival were more favorable in the CCRT group, when compared with the chemotherapy alone group. Therefore, radiation therapy seems to be an effective tool for local tumor control.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.230-240
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• 2002

Background : The majority of chemotherapy-treated small cell lung cancers(SCLC) patients eventually recur. Although many patients are in excellent physical condition at the time of recurrence, few drugs or drug combinations are capable of effecting a tumor regression in this setting. Topotecan, a topoisomerase I inhibitor, is one of the more widely studied single afents in SCLC. The aim of this study was to determine the response rate, survival and toxicity of topotecan as a second line traeatment SCLC. Materials and Methods : 19 patients with measurable SCLC, progressive during the first line chemotherapy (9 cases) or recurrent after the first line chemotherpy(10 cases), were enrolled in this study. Topotecan was administered as a 30-minute daily infusion at a dose of 1.5mg/$m^2$ for 5 consecutive days, every 3 weeks. Results : The overall response rate was 26.3%(5/19, CR 2, PR 3, SD 3, PD 11). The median survival was 24 weeks. The response rate and survival were poor in the nonresponders during first chemotherapy, those who were refractory to the first chemotherapy(recurrent within 3 months after completion of first chemotherapy) and extensive disease, but the results were not statistically significant. The toxicities were mainly hematologic and anemia grade III 1/90, leukopenia grade III 6/90 IV 4/90, thrombocytopenia grade III 1/90 IV 1/90, vomiting grade III 1/90 of cycles were occurred. There was no treatment-related deaths due to severe myelosuppression. Conclusion : Topotecan can be an active second line chemotherapeutic agent for treating SCLC.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.123-129
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• 2002

Purpose : The purpose of this study 띤as to determine the potential role of three-dimensional conformal radiotherapy (3D-CRT) in the treatment of primary unresectable hepatocellular carcinoma. The preliminary results on the efficacy and the toxicity of 3D-CRT are reported. Materials and Methods : Seventeen patients were enrolled in this study, which was conducted prospectively from January 1995 to June 1997. The exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child-Pugh classification C, tumors occupying more than two thirds of the entire liver, and a performance status of more than 3 on the ECOG scale. Two patients were treated with radiotherapy only while the remaining 15 were treated with combined transcatheter arterial chemoembolization. Radiotherapy was given to the field including the tumor plus a 1.5 cm margin using a 3D-CRT technique. The radiation dose ranged from $36\~60\;Gy$ (median; 59.4 Gy). Tumor response was based on a radiological examination such as the CT scan, MR imaging, and hepatic artery angiography at $4\~8$ weeks following the completion of treatment. The acute and subacute toxicities were monitored. Results : An objective response was observed in 11 out of 17 patients, giving a response rate of $64.7\%$. The actuarial survival rate at 2 years was $21.2\%$ from the start of radiotherapy (median survival; 19 months). Six patients developed a distant metastasis consisting of a lung metastasis in 5 patients and bone metastasis in one. The complications related to 30-CRT were gastro-duodenitis $(\geq\;grade\;2)$ in 2 patients. There were no treatment related deaths and radiation induced hepatitis. Conclusion : The preliminary results show that 3D-CRT is a reliable and effective treatment modality for primary unresectable hepatocellular carcinoma compared to other conventional modalities. Further studies to evaluate the definitive role of the 3D-CRT technique in the treatment of primary unresectable hepatocellular carcinoma are needed.

• Korean Journal of Veterinary Research
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• v.34 no.4
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• pp.735-744
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• 1994

Catheters were placed into the external jugular veins of immature female rats. On the following day (day 28 of age), the animals were injected subcutaneously with pregnant mare serm gonadotropin(PMSG): 4IU(control) or 20IU(superovulation). Each animal was sequentially bled at Ohr and 12hr and subsequently at 6hr intervals until sacrifice at 72hr after PMSG. The superovulatory dose of PMSG significantly(P<0.05) increased the ovulatory response by 4.0 fold above controls. On the other hand, superovulated oocytes displayed considerably different stages of meiotic maturation: prophase I (14.7%), anaphase I (36.2%), telophase I (10.3%), metaphase I/II (32.4%), while in control rats a majority of the oocytes examined(94.0%) consistently showed a metaphase II configuration. Serum luteinizing hormone(LH) levels were determined by RIA. Both groups exhibited a similar time relationship with two distinct peaks: an initial slight rise at 0-18hr and a second sharp rise at 54-60hr. However, there was a marked change in the magnitude of LH levels between the two groups. In superovulated animals, prior to the second peak, overall LH levels were significantly(P<0.001) higher than controls. In contrast, at the peak occurring at 60hr, LH concentrations were significantly(P<0.001) reduced by 54% below that of control. Additionally, a maximum increase of mean ${\Delta}LH$ between two peaks was much less in superovulated as compared to control rats. The initial prolonged elevation of serum LH before 54hr in superovulated rats was found to result from actual cross-reaction of the injected PMSG with LH antibody in the assay, while a precipitous second elevation between 54hr and 60hr resulted primarily from an endogenous LH surge. This study clearly defines time-course features of serum LH in PMSG-treated rats. The overall results indicate that, following superovulatory treatment with PMSG, the increased ovulatory response is primarily associated with PMSG-derived intrinsic gonadotropin, and that the recovery of immature or asynchronously mature oocytes at ovulation may reult from the circulatory alteration of LH activity characterized by an initial prolonged elevation of serum LH and its subsequent attenuation.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.475-484
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• 2002

Background : Unresectable non-small cell lung cancer has a poor response to chemotherapy and has an unfortunate prognosis. More effective and less toxic cytotoxic agents are needed to improve the outcome of these patients. The efficacy and safety of vinorelbine monotherapy in these advanced lung cancer patients was evaluanted. Materials and Methods : Sixteen patients with non-small cell lung cancer in stage III or IV, who received vinorelbine alone as an initial anticancer chemotherapy from June 1996 to December 2000 were enrolled in this study. Vinorelbine was given intravenously at a dose 30mg/$m^2$ every week. Results : A mong the sixteen patients, six had a partial response(38%) and the median survival was 16 weeks. The median response duration was 27 weeks (95% CI 6-47), and the time to progression was 16 weeks(95% CI 6-26). Among a total of 112 cycles, neutropenia(WHO grade 3 or 4) and anemia(grade 3) occurred in 9% and 3%, respectively. Only 1 patient required hospitalization for neutropenic fever. Non-hematologic toxicity was minor and was easily controlled. Conclusion : Vinorelbine monotherapy was well tolerated, and moderately effective in patients with advanced non-small cell lung cancer.

• Clinical and Experimental Pediatrics
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• v.52 no.5
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• pp.581-587
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• 2009

Purpose : To evaluate the correlation between serum methotrexate (MTX) peak levels and clinical outcome of osteosarcoma, as well as to determine the correlation of these levels with the histologic response and event-free survival (EFS). Methods : To maintain the homogeneity of the study population, we selected 52 patients with localized extremity osteosarcoma who had received two cycles of neoadjuvant chemotherapy consisting of high-dose (HD) MTX ($12g/m^2$), cisplatin ($100mg/m^2$), and doxorubicin ($60mg/m^2$). Results : Totally, 204 courses of HD MTX were administered. The serial MTX levels ($mean{\pm}SE$) at 4 h (peak), 24 h, 48 h, and 72 h were $1292.14{\pm}12.83{\mu}m$, $9.29{\pm}3.89{\mu}m$, $1.73{\pm}1.37{\mu}m$, and $0.58{\pm}0.44{\mu}m$, respectively. The peak MTX serum level was $1292.14{\pm}12.83{\mu}m$. Neither the continuous average MTX peak level nor the dichotomized MTX peak level was related to the histologic response. However, the patients with a high 24-h MTX level ($3.4{\mu}m$) had a poor histologic response (P=0.044). An inverse relationship was observed between MTX levels and survival: the EFS was better in the patients with a mean MTX peak level of less than $1,400{\mu}m$ (P=0.002) and mean 24-h MTX level of less than $3.4{\mu}m$ (P=0.011). Conclusion : The inverse correlation between the MTX level and the outcome is an unexpected finding. Further study on the pharmacokinetics of MTX is required to substantiate our findings and elucidate the mechanism involved.