• Radiation Oncology Journal
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• v.13 no.2
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• pp.181-189
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• 1995

Pupose: Radiation therapy(RT) is conventionally standard treatment for locally advanced stage for uterine cervix cancer. Recently to improve treatment results, combined chemotherapy and radiation therapy was tried We retrospectively analysed our experience of 122 patients. Comparision of the results in 45 patients treated with RT alone and 77 patients treated with RT plus chemotherapy was made Materials and Mathods: From January 1985 to December 1991 122 patients with cervix cancer were treated with whole pelvic external RT and ICR(34 1 ICR, 77 2 ICR, 11 high dose rate ICR) in our department. Forty five patients were treated with RT alone, and 77 patients were treated with combined RT plus chemotherapy Mean age was 58 years(range:29-81). Histologic types were 111 squamous cell carcinoma, 5 large cell carcinoma, 3 adenocarcinoma, and 2 adenosquamous cell carcinoma. According to the FIGO stage 6 had stage $IA(4.9\%),$ 11 had $IIA(9.0\%),$ 37 had $IIB(30.3\%),$ 3 had $IIIA(2.5\%),$ 63 had $IIIB(51.6\%).$ and 2 had stage $IV(1.6\%).$ In 77 patients with RT Plus chemotherapy, 36 patients were treated with VBP(vinblastin, bleomycin, cisplatinum) , 39 patients with cisplatinum plus 5-FU and 2 patients with 5-FU. Results: Complete response after external RT (3960cGy-5500cGy) was achieved in 61 patients$(50\%).$ The actuarial 5 year and 9 rear survival rate was $57.8\%\;and\;53.9\%,$ respectively. Five rear actuarial survival rate was $63.1\%$with RT alone(n=45) and $55.9\%$ with RT plus chemotherapy(n=77). The 5 rear survival rate was $35.5\%$ for 1 course of ICR and $67\%$ for 2 courses of ICR. There was statistically significant advantage of survival with RT alone group who were treated with 2 courses of ICR and dose to the A Point)=8000cGy (4/25 died). In RT plus chemotherapy group, dose response was not seen and there was no difference in 5 year survival between 1 course and 2 course of ICR $(50\%\;vs\;56.8\%),$ and dose to point A less than 8000 cGy and more than 8000 $cGy(55.6\%\;vs\;55.7\%).$ There was no significant difference in survival between RT alone and RT plus chemotherapy for patients with tumor size greater than 3cm in size. Five year survival rate for early stage (Stage IB and IIA) with RT alone group and with RT Plus chemotherapy group was $60\%\;and\;77.0\%,$ respectively In advanced stage (stage IIB, IIIA, IIIB, IVA) the 5 year actuarial survival rate were $62.6\%,$ for RT alone group vs $53.6\%$ for RT plus chemotherapy group. Conclusion: Present study demonstrates that there is no survival advantage with adding chemotherapy in advanced stage of uterine cervix cancer. RT alone is considered as treatment of choice for patients with locally advanced cervix cancer. There was increased survival in RT alone group treated with RT dose above 8000 cGy to point A and 2 course of ICR. but 2 course of ICR and RT dose above 8000 cGy to point A did not affect survival advantage in RT plus chemotherapy group.

• Childhood Kidney Diseases
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• v.3 no.1
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• pp.11-19
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• 1999

Purpose: MCNS is found in approximately $85\%$ of the idiopathic nephrotic syndrome in children and shows good prognosis with initial steroid therapy. MCNS most commonly appears between the ages of 2 and 10 yr. But the incidence and prognosis in adolescent MCNS are different from those found in young children; the prognosis and the response to therapy is unfavorable with increasing ages. So we compared the prevalence and the clinical manifestations of adolescent MCNS with that of childhood MCNS for management of adolescent MCNS. Methods: We conducted a retrospective study with a review of histopathologic findings and clinical manifestations of the 216 cases with MCNS which were divided into children group and adolescent group by their age of onset; under 12 years(childhood) and between 12-18 years(adolescent). Results: 1) The number of childhood idiopathic nephrotic syndrome was 245 cases, and that of adolescent idiopathic nephrotic syndrome was 55 cases. 188 cases($77\%$) showed MCNS, 30 cases($12\%$) FSGS, 4 cases($1.6\%$) MSPCN in childhood idiopathic nephrotic syndrome; 28 cases($51\%$) showed MCNS, 12 cases($22\%$) FSGS in adolescent idiopathic nephrotic syndrome. 2) The mean onset age was $7.53{\pm}5.5$ years, and the male to female ratio was 3.8:1 in childhood onset and 2.5:1 in adolescent onset with male predominance. 3) Hematuria was associated with $17\%$ of childhood onset and $39.3\%$ of adolescent onset disease(P=0.005). Hypertension appeared in $0.5\%\;and\;7\%$ in each group without significant difference between the groups. 4) 24 hour urine protein, SPI, albumin, BUN, cholesterol level showed no significant difference. 5) The response of childhood onset and adolescent onset MCNS to steroid therapy showed complete remission in $11.7\%\;&\;14.7\%$, infrequent relapsing in $29.2\%\;&\;28.5\%$, frequent relapsing in $23.9\%\;&\;14.7\%$, steroid dependent in $21.8\%\;&\;28.6\%$ each. Steroid resistant showed $13.3\%\;&\;14.7\%$ with no significance. 6) Immunosuppresant therapy was performed $57\%$ in childhood onset and $65\%$ in adolescent onset. 7) Mean number of relapse and duration from onset to first relapse showed no significance between two groups. Conclusion : Our results indicate that the incidence of hematuria, the rate of steroid dependent and frequent relapsing, and the recurrence rate were higher in adolescent MCNS; showed poorer steroid responsiveness and prognosis. Our data also point to the need for a more aggressive therapy to treat and make recommendations for the adolescent population as a whole.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.108-115
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• 2002

Purpose : A retrospective study was undertaken to determine the role of conventional radiotherapy with or without surgery for treating a supraglottic carcinoma in terms of the local control and survival. Materials and Methods : From Jan. 1986 to Oct. 1996, a total of 134 patients were treated for a supraglottic carcinoma by radiotherapy with or without surgery. Of them, 117 patients who had completed the radiotherapy formed the base of this study. The patients were redistributed according to the revised AJCC staging system (1997). The number of patients of stage I, II, III, IVA, IVB were $6\;(5\%),\;16\;(14\%),\;53\;(45\%),\;32\;(27\%),\;10\;(9\%)$, respectively. Eighty patients were treated by radical radiotherapy in the range of $61.2\~79.2\;Gy$ (mean : 69.2 Gy) to the primary tumor and $45.0\~93.6\;Gy$ (mean : 54.0 Gy) to regional lymphatics. All patients with stage I and IVB were treated by radiotherapy alone. Thirty-seven patients underwent surgery plus postoperative radiotherapy in the range of $45.0\~68.4\;Gy$ (mean : 56.1 Gy) to the primary tumor bed and $45.0\~59.4\;Gy$ (mean : 47.2 Gy) to the regional lymphatics. Of them, 33 patients received a total laryngectomy (${\pm}lymph$ node dissection), three had a supraglottic horizontal laryngectomy (${\pm}lymph$ node dissection), and one had a primary excision alone. Results : The 5-year survival rate (5YSR) of all patients was $43\%$. The 5YSRs of the patients with stage I+II, III+IV were $49.9\%,\;41.2\%$, respectively (p=0.27). However, the disease-specific survival rate of the patients with stage I (n=6) was $100\%$. The 5YSRs of patients who underwent surgery plus radiotherapy (S+RT) vs radiotherapy alone (RT) in stage II, III, IVA were $100\%\;vs\;43\%$ (p=0.17), $62\%\;vs\;52\%$ (p=0.32), $58\%\;vs\;6\%$ (p<0.001), respectively. The 5-year actuarial locoregional control rate (5YLCR) of all the patients was $57\%$. The 5YLCR of the patients with stage I, II, III, IVA, IVB was $100\%,\;74\%,\;60\%,\;44\%,\;30\%$, respectively (p=0.008). The 5YLCR of the patients with S+RT vs RT in stage II, III, IVA was $100\%\;vs\;68\%$ (p=0.29), $67\%\;vs\;55\%$ (p=0.23), $81\%\;vs\;20\%$ (p<0.001), respectively. In the radiotherapy alone group, the 5YLCR of the patients with a complete, partial, and minimal response were $76\%,\;20\%,\;0\%$, respectively (p<0.001). In all patients, multivariate analysis showed that the N-stage, surgery or not, and age were significant factors affecting the survival rate and that the N-stage, surgery or not, and the ECOG performance index were significant factors affecting the locoregional control. In the radiotherapy alone group, multivariate analysis showed that the radiation response and N-stage were significant factors affecting the overall survival rate as well as locoregional control. Conclusion : In early stage supraglottic carcinoma, conventional radiotherapy alone is an equally effective modality compared to surgery plus radiotherapy and could preserve the laryngeal function. However, in the advanced stages, radiotherapy combined with concurrent chemotherapy for laryngeal preservation or surgery should be considered. In bulky neck disease, all the possible planned neck dissections after induction chemotherapy or before radiotherapy should be attempted.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.265-274
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• 1998

Purpose : This prospective study has been conducted to assess the value of three dimensional conformal radiation therapy (3DCRT) for lung cancer and to determine its potential advantage over current treatment approaches. Specific aims of this study were to 1) find the most ideal 3DCRT technique 2) establish the maximum tolerance dose that can be delivered with 3DCRT and 3) identify patients at risk for development of radiation pneumonitis. Materials and Methods : Beginning in Nov. 1994, 95 patients with inoperable non-small cell lung cancer (stage I; 4, stage II; 1, stage IIIa; 14, stage IIIb; 76) were entered onto this 3D conformal trial Areas of known disease and elective nodal areas were initially treated to 45 Gy and then using 3DCRT technique 65 to 70 Gy of total dose were delivered to the gross disease. Sixty nine patients received 65 Gy of total dose and 26 received 70 Gy Seventy eight patients (82.1$\%$) also received concurrent MVP chemotherapy. 3DCRT plans were compared with 2D plans to assess the adequacy of dose delivery to target volume, dose volume histograms for normal tissue, and normal tissue complication Probabilities (NTCP). Results : Most of plans (78/95) were composed of non-coplanar multiple (4-8) fields. Coplanar segmented conformal therapy was used in 17 pateints, choosing the proper gantry angle which minimize normal lung exposure in each segment. 3DCRT gave the full dose to nearly 100$\%$ of the gross disease target volume in all patients. The mean NTCP for ipsilateral lung with 3DCRT (range; 0.17-0.43) was 68$\%$ of the mean NTCP with 2D treatment planning (range; 0.27-0.66). DVH analysis for heart showed that irradiated volume of heart could be significantly reduced by non-coplanar 3D approach especially in the case of left lower lobe lesion. Of 95 patients evaluable for response, 75 (79$\%$), showed major response including 25 (26$\%$) with complete responses and 50 (53$\%$) with partial responses. One and two rear overall survivals of stage III patients were 62.6$\%$ and 35.2$\%$ respectively. Twenty percent (19/95) of patients had pneumonitis; Eight patients had grade 1 pneumonitis and 11 other patients had grade 2. Comparison of the average of NTCP for lung showed a significant difference between patients with and without radiation pneumonitis. Average NTCP for Patients without complication was 62$\%$ of those with complications. Conclusions : This study showed that non-coplanar multiple fields (4-8) may be one of the ideal plans for 3DCRT for lung cancer. It also suggested that 3DCRT may provide superior delivery of high dose radiation with reduced risk to normal tissue and that NTCP can be used as a guideline for the dose escalation.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.311-323
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• 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
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• v.10 no.1
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• pp.7-14
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• 1992

Between August 1988 and December 1991, 24 patients with intracranial tumors were treated with stereotactic radiosurgery(RS) using a 10 MV linear accelerator at Severance Hospital, Yonsei University College of Medicine. There were 5 meningiomas, 3 craniopharyngiomas, 9 glial tumors, 2 solitary metastases, 2 acoustic neurinomas, 2 pineal tumors, and 1 non-Hodgkin's lymphoma. Ten patients were treated as primary treatment after diagnosis with stereotactic biopsy or neuroimaging study. Nine patients underwent RS for post-op. residual tumors and three patients as a salvage treatment for recurrence after external irradiation. Two patients received RS as a boost followed by fractionated conventional radiotherapy. Among sixteen patients who were followed more than 6 months with neuroimage, seven patients (2 meningiomas, 4 benign glial tumors, one non-Hodgkin's lymphoma) showed complete response on neuroimage after RS and nine patients showed decreased tumor size. There was no acute treatment related side reaction. Late complications include three patients with symptomatic peritumoral brain edema and one craniopharyngioma with optic chiasmal injury. Through this early experience, we conclude that stereotactically directed single high doses of irradiation to the small intracranial tumors is effective for tumor control. However, in order to define the role of radiosurgery in the management of intracraniai tumors, we should get the long-term results available to demonstrate the benefits versus potential complications of this therapeutic modality.

• Korean Journal of Head & Neck Oncology
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• v.10 no.1
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• pp.13-24
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• 1994

Despite optimal local therapy such as surgery and/or radiotherapy, the long term outcome is poor for patients with advanced squamous cell carcinomma of head and neck, due to frequent loco-regional recurrence and distant metastases. We studied to determine whether the combination chemotherapy, especially as an adjuvant chemotherapy, would improve the survival of these patients. Between January, 1986 and December, 1992, 57 patients with previously untreated, locally advanced squamous cell arcinoma of head and neck were assigned to receive 2-3 cycles of induction chemotherapy consisting of 5-fluorouracil(F) and cisplatin(P) every 3 weeks and standard local therapy such as surgery and/or radiotherapy followed by adjuvant chemotherapy with the same FP regimens. Of the 57 enroled patients, 45 patients were evaluable. The obtained results were as following: 1) Among 45 evaluable patients, 18 patients finished all treatment protocol including adjuvant chemotherapy and 27 patients had no adjuvant chemotherapy. The difference of age, sex, performance status, disease stage, and tumor differentiation was not significant statistically between adjuvant chemotherapy group and no-adjuvant chemotherapy group. 2) After induction chemotherapy, 7/45(15.4%), 30/45(67%) achieved complete remission and partial remission respectively with 82.4% overall response rates in entire patients. 3) The 4year progression free survival was 43.3% in adjuvant chemotherapy group and 24.1% in no-adjuvant chemotherapy group(p>0.05). The 4year overall survival was 56.9% and 25.5% respectively(p>0.05). There was no significant different in the patterns of local recurrence and distant metastasis between the two groups. 4) Adverse reactions from combination chemotherapy included nausea, vomiting, mucositis, diarrhea and hematologic bone marrow depression. These were mild and tolerated by patients, and these was no episode of any life threatening toxicities. In conclusion, adjuvant chemotherapy after induction chemotherapy and local therapy did not show statistically significant survival improvement, but there was trend of prolongation of survival when compared to no adjuvant chemotherapy. Thus, large scale phase III randomized controlled studies are strongly recommended.

• Proceedings of the KSAR Conference
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• 2000.10a
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• pp.10-12
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• 2000

Members of the glycoprotein family, which includes CG, LH, FSH and TSH, comprise two noncovalently linked $\alpha$- and $\beta$-subunits. Equine chorionic gonadotropin (eCG), known as PMSG, has a number of interesting and unique characteristics since it appears to be a single molecule that possesses both LH- and FSH-like activities in other species than the horse. This dual activity of eCG in heterologous species is of fundamental interest to the study of the structure-function relationships of gonadotropins and their receptors. CG and LH $\beta$ genes are different in primates. In horse, however, a single gene encodes both eCG and eLH $\beta$-subunits. The subunit mRNA levels seem to be independently regulated and their imbalance may account for differences in the quantities of $\alpha$ - and $\beta$ -subunits in the placenta and pituitary. The dual activities of eCG could be separated by removal of the N-linked oligosaccharide on the $\alpha$-subunit Asn 56 or CTP-associated O-linked oligosaccharides. The tethered-eCG was. efficiently secreted and showed similar LH-like activity to the dimeric eCG. Interestingly, the FSH-like activity of the tethered-eCG was increased markedly in comparison with the native and wild type eCG. These results also suggest that this molecular can implay particular models of FSH-like activity not LH-like activity in the eCG/indicate that the constructs of tethered molecule will be useful in the study of mutants that affect subunit association and/or secretion. A single-chain analog can also be constructed to include additional hormone-specific bioactive generating potentially efficacious compounds that have only FSH-like activity. The LH/CG receptor (LH/CGR), a membrane glycoprotein that is present on testicular Leydig cells and ovarian theca, granulosa, luteal, and interstitial cells, plays a pivotal role in the regulation of gonadal development and function in males as well as in nonpregnant and pregnant females. The LH/CGR is a member of the family of G protein-coupled receptors and its structure is predicted to consist of a large extracellular domain connected to a bundle of seven membrane-spanning a-helices. The LH/CGR phosphorylation can be induced with a phorbol ester, but not with a calcium ionophore. The truncated form of LHR also was down-regulated normally in response to hCG stimulation. In contrast, the cell lines expressing LHR-t63I or LHR-628, the two phosphorylation-negative receptor mutant, showed a delay in the early phase of hCG-induced desensitization, a complete loss of PMA-induced desensitization, and an increase in the rate of hCG-induced receptor down-regulation. These results clearly show that residues 632-653 in the C-terminal tail of the LHR are involved in PMA-induced desensitization, hCG-induced desensitization, and hCG-induced down-regulation. Recently, constitutively activating mutations of the receptor have been identified that are associated with familial male-precocious puberty. Cells expressing LHR-D556Y bind hCG with normal affinity, exhibit a 25-fold increase in basal cAMP and respond to hCG with a normal increase in cAMP accumulation. This mutation enhances the internalization of the free and agonist-occupied receptors ~2- and ~17-fold, respectively. We conclude that the state of activation of the LHR can modulate its basal and/or agonist-stimulated internalization. Since the internalization of hCG is involved in the termination of hCG actions, we suggest that the lack of responsiveness detected in cells expressing LHR-L435R is due to the fast rate of internalization of the bound hCG. This statement is supported by the finding that hCG responsiveness is restored when the cells are lysed and signal transduction is measured in a subcellular fraction (membranes) that cannot internalize the bound hormone.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.1
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• pp.23-29
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• 2009

Purpose: To provide the primary data for reaching a consensus on the adequate duration of treatment of lamivudine in children with HBeAg negative chronic hepatitis B. Methods: Seven of 83 children/adolescents with chronic hepatitis B were diagnosed with HBeAg-negative and HBV DNA-positive chronic hepatitis B and treated with lamivudine. Six children/adolescents were enrolled among 7 patients, who had been treated with lamivudine over 2 years. The primary goal of treatment was HBV DNA clearance and normalization of the serum ALT level; the final goal of treatment was the durability of the complete response after discontinuation of lamivudine. It was planned to continue lamivudine for more than two additional years after HBV DNA negativity and normalization of ALT. Results: The mean duration of lamivudine treatment was 32.2 months (range, 26~40 months) and the mean duration of follow-up was 59.5 months (range, 26~110 months). HBV DNA levels became undetectable (<0.5 pg/mL) in 6 patients within 3 months of treatment. ALT levels were normalized in 3.5 months (range, 2~7 months) in all 6 patients. Biochemical breakthrough developed in 1 patient 18 months after the initiation of lamivudine treatment. No evidence of relapse could be found in 4 patients with a mean follow-up of 23.8 months (range, 4~75 months) after cessation of lamivudine treatment. Conclusion: Suppression of HBV replication and normalization of serum ALT levels were effectively achieved with long-term lamivudine treatment in children/adolescents with HBeAg-negative chronic hepatitis B. Two additional years of lamivudine may be needed after HBV DNA clearance and ALT normalization in HBeAg-negative chronic hepatitis B in order to decrease the relapse rate.

• Tuberculosis and Respiratory Diseases
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• v.39 no.5
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• pp.400-406
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• 1992

Background: It has been known that see antigen was used in diagnosis of uterine cervical cancer and also known to be higher in squamous cell lung cancer. There has been no report about see antigen in squamous cell lung cancer in Korea. This study was designed to evaluate the usefulness of see antigen as a diagnostic tool and index for follow up after treatment. Method: The serum level of see antigen was measured in 12 cases with squamous cell lung carcinoma, 9 patients with other types of lung cancer, 7 patients with benign lung disease and 7 normal subjects by radioimmunoassay with Abott see Riabeap radioimmunoassay kit. We also measured see antigen after treatment in 6 patients who had received chemotherapy or sugery. Result: 1) The level of see antigen ($mean{\pm}1$ SD) was $2.27{\pm}1.53$, $0.67{\pm}0.38$, $0.62{\pm}0.53$, $0.53{\pm}0.36\;ng/ml$ respectively. 2) The see antigen activity in squamous cell lung carcinoma according to stage were as gollows. I; $2.07{\pm}1.56$, $III_a$; $5.04{\pm}0.53$ $III_b$; $1.94{\pm}0.7$ IV; $1.07{\pm}0.64$ (ng/ml). 3) In squamous cell lung cancer, 5 of 12 (42%) cases was shown more than 2.0 ng/ml see antigen. (sensitivity; 42%), but there was no case in any other type of lung cancer, benign lung disease, and in control groups (specificity; 100%). 4) The serum sec antigen level after treatment was significantly decreased in patients with partial or complete remission (p<0.01). Conclusion; It was suggested that see antigen might be used as a useful tumor marker for the response of treatment and assessment of prognosis in squamous cell lung cancer, but further study should be performed for the clinical use of see antigen.