• Radiation Oncology Journal
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• v.11 no.2
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• pp.295-301
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• 1993

Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer (NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hyperfractionated radiotherapy (120 cGy/fx BID, 6480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 $mg/m^2,$ Vinblastin 6 $mg/m^2,$ Cisplatin 60 $mg/m^2$) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient's refusal, 39 completed planned therapy. Twenty-three $(58\%)$ patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy,1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hyperfractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 39 patients who completed induction chemotherapy and radiotherapy, 25 patients $(64\%)$ including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radio-therapy. Nine Patients were allocated to adjuvant chemotherapy group and 4/9 showed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant chemotherapy group and observation group in distant metastasis rate and survival. Median survival time was 13 months. Actuarial survival rates at 6,12 and 18 months of 39 patients who completed this study were $84.6\%,\;53.7\%\;and\;40.3\%,$ respectively. The partial and complete responders from induction chemotherapy showed significantly better survival than non-responders (p=0.028). Incidence of radiation pneumonitis in this study group was less than that in historical control group inspite of induction chemotherapy. All patients tolerated hypertractionated radiotherapy without definite increase of acute complications compared with conventional radiotherapy group. The longer follow up is needed to evaluate the efficacies of induction and maintenance chemotherapy and survival advantage by hyperfractionated radiotherapy but authors are encouraged with an excellent tolerance, higher response rate and improvement of one year survival rate in patients of this study.

• 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.

• Clinical and Experimental Pediatrics
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• v.53 no.7
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• pp.766-769
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• 2010

Dense deposit disease (DDD) is a rare disorder characterized by the deposition of abnormal electron-dense material within the glomerular basement membrane of the kidneys. The diagnosis is made in most patients between 5 and 15 years of age, and within 10 years, approximately half of the affected patients progress to end-stage renal disease. We report a rare case of regressive DDD without C3 deposition after steroid therapy in an 11-year-old boy. The patient presented with edema, gross hematuria, and nephrotic-range proteinuria. Laboratory testing revealed a serum creatinine level of 1.17 mg/dL, albumin level of 2.3 g/dL, and serum C3 level of 125 mg/dL (range 90-180 mg/dL). The results of the renal biopsy were consistent with DDD without C3 deposition. After 6 weeks of steroid therapy, the nephrotic syndrome completely resolved. The follow-up renal biopsy showed a significant reduction in mesangial proliferation and disappearance of electron-dense deposits in the GBM.

• Clinical and Experimental Pediatrics
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• v.53 no.9
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• pp.830-833
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• 2010

Crohn's disease is characterized by chronic inflammation involving any portion of the gastrointestinal tract. Treating Crohn's disease is a major challenge for clinicians, as no curative therapy currently exists. Pediatric Crohn's disease is characterized by frequent relapses, a wide extent of disease, a high prevalence of extraintestinal manifestations, and a severe clinical course. The classic therapeutic approach is known as the 'step-up' strategy, and follows a progressive course of treatment intensification as disease severity increases. Although this approach is usually effective for symptom control, many patients become either resistant to or dependent on corticosteroids. The efficacy of infliximab suggests that, rather than a progressive course of treatment, early intense induction may reduce complications associated with conventional treatment and improve quality of life. Intensive early therapy with infliximab is known as the 'top-down' strategy. Such therapy offers the potential for altering the natural history of Crohn's disease, and is changing treatment paradigms. However, the relatively new concept of an early aggressive or 'top-down' treatment approach is not yet widely accepted, especially in pediatric patients. The results of our current study demonstrate that early and intensive treatment of pediatric Crohn's disease patients with infliximab, at initial diagnosis, was more effective for maintaining remission and reducing flares.

• Clinical and Experimental Pediatrics
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• v.53 no.11
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• pp.957-964
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• 2010

Purpose: Our study attempted to determine the prognostic significance of minimal residual disease (MRD) detected by a simplified flow cytometric assay during induction chemotherapy in children with B-cell acute lymphoblastic leukemia (B-ALL). Methods: A total of 98 patients were newly diagnosed with precursor B-ALL from June 2004 to December 2008 at the Asan Medical Center (Seoul, Korea). Of those, 37 were eligible for flow cytometric MRD study analysis on day 14 of their induction treatment. The flow cytometric MRD assay was based on the expression intensity of CD19/CD10/CD34 or aberrant expression of myeloid antigens by bone marrow nucleated cells. Results: Thirty-five patients (94.6%) had CD19-positive leukemic cells that also expressed CD10 and/or CD34, and 18 (48.6%) had leukemic cells with aberrant expression of myeloid antigens. Seven patients with ${\geq}1%$ leukemic cells on day 14 had a significantly lower relapse-free survival (RFS) compared to the 30 patients with lower levels (42.9 % [18.7%] vs. 92.0% [5.4%], $P$=0.004). Stratification into 3 MRD groups (${\geq}1%$, 0.1-1%, and <0.1%) also showed a statistically significant difference in RFS (42.9% [18.7%] vs. 86.9% [8.7%] vs. 100%, $P$=0.013). However, the MRD status had no significant influence on overall survival. Multivariate analysis demonstrated that the MRD level on day 14 was an independent prognostic factor with borderline significance. Conclusion: An MRD assay using simplified flow cytometry during induction chemotherapy may help to identify patients with B-ALL who have an excellent outcome and patients who are at higher risk for relapse.

• Korean Journal of Head & Neck Oncology
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• v.16 no.2
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• pp.172-176
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• 2000

Objectives: To improve local control and reduce toxicity, 3-D conformal radiotherapy was used as a boost the primary tumor site following fractionated radiotherapy in patients with nasopharyngeal carcinoma. Materials and Methods: Eight patients with previously untreated nasopharyngeal carcinomas were treated with 3-D conformal radiotherapy following fractionated radiotherapy from September 1998 to April 2000. All patients had biopsy confirmation of disease before radiation therapy. Stages were II in 1, III in 5, and IV in 2. Two patients received cisplatin based chemotherapy in addition to radiation therapy; induction chemotherapy in 1, concurrent chemoradiation in 1. 3-D conformal radiotherapy delivered using 6MV Linac as a boost(range 25.2-28.8Gy, median 25.7Gy) following conventionally fractionated radiotherapy(range 50.4Gy). Average total dose ranged from 75.6-79.2Gy(median 76Gy). Follow-up time was 4-21 months(median 9.6 months). Results: Seven of 8 patients were evaluated radiologically within 3 months after completion of radiation therapy. All 7 patients were seen complete remission. One of 7 patients had distant metastasis after 5 months and local failure after 7 months. The tree interval of local recurrence was ranged from 4 - 21 months(median 10.2 months). One patient without radiological evaluation got complete remission clinically. Treatment related toxicity was grade 1-3 xerostomia, dysphagia, and mucositis. During 3-D conformal radiotherapy, there was no aggravation of any toxicity. Conclusion: Although the number of patients was small and follow-up period was short, 3-D conformal radiotherapy following conventional radiotherapy improved tumor control and dose escalation without increased toxicity. Survival and late toxicity should be evaluated through long term follow-up. In addition, it is necessary to confirm the benefits of 3-D conformal radiotherapy in nasopharyngeal carcinoma with randomized trial.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2707-2712
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• 2015

Background: The human homologue of the mouse double minute 2 (MDM2) gene is a negative regulator of Tp53. MDM2-309T>G a functional promoter polymorphism was found to be associated with overexpression thereby attenuation of Tp53 stress response and increased cancer susceptibility. We have planned to evaluate the possible role of MDM2-309T>G polymorphism with risk and response to chemotherapy in AML. Materials and Methods: A total of 223 de novo AML cases and 304 age and sex matched healthy controls were genotyped for the MDM2-309T>G polymorphism through the tetra-primer amplification refractory mutation system (ARMS)-PCR method. In order to assess the functional relationship of -309T>G SNP with MDM2 expression level, we quantified MDM2 mRNA in 30 primary AML blood samples through quantitative RT-PCR. Both the (-309T>G) genotypes and the MDM2 expression were correlated with disease free survival (DFS) rates among patients who have achieved complete remission (CR) after first induction chemotherapy. Results: MDM2-309T>G polymorphism was significantly associated with AML development (p<0.0001). The presence of either GG genotype or G allele at MDM2-309 confered 1.79 (95% CI: 1.12-2.86; p<0.001) and 1.46 fold (95%CI: 1.14-1.86; p= 0.003) increased AML risk. Survival analysis revealed that CR+ve cases with GG genotype had significantly increased DFS rates (16months, p=0.05) compared to CR+ve TT (11 months) and TG (9 months) genotype groups. Further, MDM2 expression was also found to be significantly elevated in GG genotype patients (p=0.0039) and among CR+ve cases (p=0.0036). Conclusions: The MDM2-309T>G polymorphism might be involved in AML development and also serve as a good prognostic indicator.

• Radiation Oncology Journal
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• v.7 no.2
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• pp.269-277
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• 1989

CNS prophylaxis with 18 or 24 Gy cranial irradiation plus intrathecal methotrexate was given to 134 childhood acute lymphoblastic leukemia patients who had got bone marrow remission (M1) after remission induction chemotherapy from August 1979 to December 1986. The rate of initial total CNS relapse was 14.2% (19/134), the rate of isolated CNS relapse was 5.2% (7/134), and the rate of CNS relapse concomittantly combined with bone marrow relapse or testicular relapse was 9% (12/134). Male sex or older age was accociated with higher CNS relapes and the initial peripheral leukocyte count over 50,000/ul had higher relapse rate. Relapse with radiation dose of 18Gy was somewhat lower than that with 24Gy. Within 4 years after CNS prophylaxis occurred 89% of the total CNS relapses, 100% of the isolated CNS relapses, and 83% of the combined CNS relapses. Adjusted to exposed cases to risk of CNS relapse, the total CNS relapse rate was 11.9% during maintenance chemotherapy and 4.9% after maintenance chemotherapy.

• Childhood Kidney Diseases
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• v.3 no.1
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• pp.48-56
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• 1999

Purpose : This multicenter collaboratory study was conducted to see the therapeutic efficacy and side effect of cyclosporine A (Cipol-$N^{(R)}$, Chong Kun Dang) on children with idiopathic nephrotic syndrome who experienced frequently relapsing (FR), steroid dependent (SD), or steroid resistant (SR) pattern. Patients and methods : Thirty-nine children with SD/FR NS and 3 children with SR NS were enrolled in the study. After induction of remission (SD/FR NS) with steroid or after 4 weeks of steroid therapy (SR NS), cyclosporine A was started in a dose of 4-5 mg/Kg/day in two divided dose and steroid (prednisolone or equivalent dose of deflazacort) was tapered slowly. During 16 weeks of study period, monthly check up of physical examination and various laboratory tests including BUN, creatinine, Ccr and cyclosporine blood level were done. Results : Out of 39 children with SD/FR NS, 35($89.7\%$) maintained sustained remission and at 4 weeks after therapy, values of serum protein, albumin, cholesterol, and 24 hours urinary protein excretion showed normal values. Two out of 3 children with SR NS showed and sustained remission with cyclosporine A therapy. Side reaction to cyclosporine A therapy showed hypertrichosis in 8 cases and hyperuricemia in 5 cases. However, other laboratory tests including CBC, liver profile, BUN, creatinine and GFR (creatinine clearance utilizing 24 hour urine) did not show any abnormalities during the 16 weeks of study period. Conclusion : Cyclosporine A (Cipoi-$N^{(R)}$ Chong Kun Dang) can be utilized quite effectively on children with SD/FR or SR NS and further trial of cyclosporine A on long-term basis (1-2 year period) is needed to determine it's efficacy and side effect (especially nephrotoxicity) of long-term administration of cyclosporine A.

• Tuberculosis and Respiratory Diseases
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• v.57 no.6
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• pp.557-566
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• 2004

Background : To find out effectiveness of multimodality treatments based on induction chemotherapy(CTx) in patients with clinical stage IIIA NSCLC Methods : From 1997 to 2002, 74 patients with clinical stage IIIA NSCLC underwent induction CTx at the hospital of Chungnam National University. Induction CTx included above two cycles of cisplatin-based regimens(ectoposide, gemcitabine, vinorelbine, or taxol) followed by tumor evaluation. In 30 complete resection group, additional 4500-5000cGy radiotherapy(RTx) was delivered in 15 patients with pathologic nodal metastasis. 29 out of 44 patients who were unresectable disease, refusal of operation, and incomplete resection were followed by 60-70Gy RTx in local treatment. Additional 1-3 cycle CTx were done in case of induction CTx responders in both local treatment groups. Results : Induction CTx response rate were 44.6%(complete remission 1.4% & partial response 43.2%) and there was no difference of response rate by regimens(p=0.506). After induction chemotherapy, only 33 out of resectable 55 ones(including initial resectable 37 patients) were performed by surgical treatment because of 13 refusal of surgery by themselves and 9 poor predicted reserve lung function. There were 30(40.5%) patients with complete resection, 2(2.6%) persons with incomplete resection, and 1(1.3%) person with open & closure. Response rate in 27 ones with chest RTx out of non-operation group was 4.8% CR and 11.9% PR. In complete resection group, relapse free interval was 13.6 months and 2 year recur rate was 52%. In non-complete resection(incomplete resection or non-operation) group, disease progression free interval was 11.2 months and 2 year disease progression rate was 66.7%. Median survival time of induction CTx 74 patients with IIIA NSCLC was 25.1months. When compared complete resection group with non-complete resection group, the median survival time was 31.7 and 23.4months(p=0.024) and the 2-year overall survival rate was 80% and 41%. In the complete resection group, adjuvant postoperative RTx subgroup significantly improved the 2-year local control rate(0% vs. 40%, p= 0.007) but did not significantly improve overall survival(32.2months vs. 34.9months, p=0.48). Conculusion : Induction CTx is a possible method in the multimodality treatments, especially followed by complete resection, but overall survival by any local treatment(surgical resection or RTx) was low. Additional studies should be needed to analysis data for appropriate patient selection, new chemotherapy regimens and the time when should RTx be initiated.