The Survival of Osteosarcoma Patients 10 Years Old or Younger Is Not Worse than the Survival of Older Patients:A Retrospective Analysis

이준아,김동호,임정섭,박경덕,송원석,이수용,전대근 대한암학회 2007 Cancer Research and Treatment Vol.39 No.4

Purpose: This study aimed to assess whether a young age at the time of diagnosis with osteosarcoma has value to predict the prognosis.Materials and Methods: Sixty-seven children with stage II osteosarcoma were stratified according to the age of 10. There were 32 preadolescents (≤10 years) and 35 adolescents (10〈age≤15 years). The patients were analyzed for their clinical characteristics, the histologic response to preoperative chemotherapy, event-free survival (EFS) and the patterns of relapse.Results: After a median follow-up of 54 months (range: 6∼153 months), the 5-year EFS of the preadolescent and adolescent groups was 64.5±9.3% and 58.2±9.1%, respectively, and age did not have any statistical significance for survival (p=0.55). Cox regression analysis revealed that both the serum level of alkaline phosphatase and the histologic response to preoperative chemotherapy were significantly related to survival of the 67 patients. Those patients aged less than 7 years responded poorly to preoperative chemotherapy and their rate of amputation was 43%. However, their 5-year EFS was not statistically different from the older patients (57.1±18.7 vs 67.7±6.3%, respectively, p=0.58).Conclusions:We could not find any statistical difference in the clinical characteristics and survival from osteosarcoma for the preadolescents and adolescents, so the current approach of having the same protocol for both groups of patients seems to be reasonable. (Cancer Res Treat. 2007;39:160-164)

Serum methotrexate level is inversely related to the outcome of osteosarcoma patients

이준아,김민석,김동호,홍영준,송원석,조완형,이수용,임중섭,박경덕,전대근,이진경 대한소아청소년과학회 2009 Clinical and Experimental Pediatrics (CEP) Vol.52 No.5

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 (12 g/m2), cisplatin (100 mg/m2), and doxorubicin (60 mg/m2). Results : Totally, 204 courses of HD MTX were administered. The serial MTX levels (mean±SE) at 4 h (peak), 24 h, 48 h, and 72 h were 1292.14±12.83 µM, 9.29±3.89 µM, 1.73±1.37 µM, and 0.58±0.44 µM, respectively. The peak MTX serum level was 1292.14±12.83 µM. 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 µM) 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 µM (P=0.002) and mean 24-h MTX level of less than 3.4 µM (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. 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 (12 g/m2), cisplatin (100 mg/m2), and doxorubicin (60 mg/m2). Results : Totally, 204 courses of HD MTX were administered. The serial MTX levels (mean±SE) at 4 h (peak), 24 h, 48 h, and 72 h were 1292.14±12.83 µM, 9.29±3.89 µM, 1.73±1.37 µM, and 0.58±0.44 µM, respectively. The peak MTX serum level was 1292.14±12.83 µM. 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 µM) 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 µM (P=0.002) and mean 24-h MTX level of less than 3.4 µM (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.

소아 급성 골수성 백혈병에서 자가 말초혈액 조혈모세포이식

이준아,신희영,안효섭 대한조혈모세포이식학회 1999 대한조혈모세포이식학회지 Vol.4 No.2

연구배경: 급성 골수성 백혈병의 치료에 있어 조혈모세포이식이 장기간 관해상태를 유지할수 잇는 효과적인 치료방법으로 알려져 있다. 조혈모세포의공급원으로 골수를 사용하여 왔으나 조직적합형이 일치하는 골수를 얻을 수 있는 환자의수는 제한적이다. 말초혈액에도 조혈모세포가 존재한다는 사실이 알려졌는데, 말초혈액 조혈모세포는 이식후 생착이 빠르며 이식편대 숙주반응 등의 합병증이 적고 골수 공여자가 없는 환자들에서 자가골수채취에 비해 쉽게 얻을 수 있다. 본 연구는 소아연령의 급성 골수성 백혈병에서 말초혈액 조혈모세포이식이 골수이식을 대체할 수 있는 조혈모세포이식의 방법인지 알아보기 위하여 시행되었다. 방법: 1996년 1월부터 1998년 12월까지 서울대학교 어린이병원 소아과에서 말초혈액 조혈모세포이식을 받은 18명(남 13, 여 5)의 급성 골수성 백혈병 환아들을 대상으로 하였다. 이식시 정중 연령은 8년 6개월 (1년 10개월-15년 7개월)이었고, FAB 분류에 따른 아형은 M4 7명, M4E 4명,M5a 2명, M2, M6가 각 1명씩이었다. Cytarabine, etoposide와 G-CSF를 사용하여 조혈모세포를 가동화시켜 급성 골수성 백혈병의 관해 159일(20-242일)째부터 분반채집을 시행하였고, 이로부터 33일 (23-65일)후에 이식을 시행하였다. 각 환아에게 투여한 조혈모세포의 양은 단핵세포수 16.04×10^(8)/kg (5.45-32.39×10^(8)/kg), CD34 양성세포 11.24×10^(6)/kg (0.93-46.9×10^(6)) 이었다. 결과: 이식 수 과립구수가 500㎕, 1,000㎕ 이상이 되기까지 각각 10일 (8-23일), 11일(9-41일0, 혈소판이 5,000㎕, 100,000㎕ 이상이 되기까지는 각각 35일 (10-71일), 43일(14-136일)이 걸렸다. 한편 제 28일, 제100일에 시행한 골수검사에서 재발한 환아들을 제외하고는 모두 생착의 소견이 관찰되었다. 조혈모세포 주입시의 부작용으로 혈색소뇨증(78%), 오심/구토(78%), 고혈압(39%), 두통(33%), 복통(28%), 서맥(17%), 현기증(17%), 저혈압(11%), 발열(11%) 등이 발생하였다. 생착이 되기 전 15명 (83%)에서 발열이 있었으며, 이중 3명에서 균이 검출되었다. 15명이 설사를 하였고, 9명(50%)에서 구강점막염이 발견되었다. 이외 고용량의 항암제 투여와 관련하여 SIADH(3명), 출혈성 방광염(1명)이 발생하였으며 DMSO 독성으로 인한 간효소의 상승(1명)이 있었다. 이식후 추적관찰 기간은 487일(85-1,237일)로 이중 14명이 생존하고 있으며, 3년 무병생존율이 70.5%, 5명이 재발되어 1년째 재발확률은 29.5%이었다. 결론: 본 연구에서 말초혈액 조혈모세포이식 후의 무병생존율이 지금까지 보고된 동종골수이식의 성적(55-70%)과 비슷하며 자가골수이식의 성정(30-50%)과 비교하여도 우수한 성적이었다. 또한 생착에 소요된 기간도 짧고 이식에 따르는 부작용도 적어 급성 골수성 백혈병에서 골수이식을 대체할 수 있는 치료방법이라고 생각된다. 그러나 동종 골수이식에 비해 재발률이 놓았기에 향후 치료성적의 향상을 위해서는 미세잔존암 검색기술의 개발과 이식 전 조혈모세포의 purging이 필요할 것으로 보인다. Background: Stem cell transplantation can lead to cure and long-term survival of patients with acute myelogenous leukmia (AML). We investigated whether peripheral blood stem cell (PBSC) could be used instead of allogemeic of autologous bone marrow (BM0 in the treatment of AML in children. Methods: Data from 18 patients (13 boys, 5 girls) who underwent autologous peripheral blood stem cell transplantation (PBSCT) were analysed. Their median age was 8 years and 3 months (1 year 10 months-15 year 7 months) and FAB subtype were; M2(1), M3(2), M4(7), M4E(4), M5a(3), M6(1). The median amount of stem cells infused was 16.04×10^(8)/kg (5.45-32.39×10^(8)/kg), 11.24×10^(6)/kg (0.93-46.9×10^(6)) in CD34^(+) cells. Results: The median number of days to reach absolute neutrophil count greater than 500㎕ and 1000㎕ were 10 days (8-23 days) and 11 days (9-41 days), respectively. Thirty- two days (10-71 days) and 43 days (14-136+ days) were needed to reach platelet count greater than 50,000/㎕ and 100,000㎕, respectively. When cryopreseved stem cells were infused, hemoglobinria (73%) nausea/vomiting (73%), hypertension(40%), headache(33%), abdominal pain(27%), bradycardia (20%) were observed, but they were mind and resolved by supportive management. Before hematologic reconstitution, 15 patients developed fever, three of whom were blood culture positive. Fifteen patients suffered from diarrhea and 9 had oral mucositis. Median days of follow-up after PBSCT was 487 days (85-1,237 days). Four patients died of disease relapse. At present, 13 children are alive without evidence of disease, and one is under treatment due to leukemia relapse. The actuarial probability of disease free survival (DFS) at 3 years is 70.5% and probability of disease relapse at 1 year is 29.5%. Three-year DFS of patients who were in first complete remission at the time of transplantation of 79.3%. Conclusion: The survival rate was comparable to that of allogeneic BMT and hematopoietic recovery was faster. Accordingly, we conclude that autoligous PBSCT can be adopted as a standard treatment modality in acute myelogenous leukemia in children. But as we observed 5 patients with leukemia relapse, we should try to develop techniques that could detect minimal residual disease (MRD) and techniques of purging to reduce the risk of leukemic relapse.

청년 및 중년남성 근로자 중 1년 이상 금연 유지 성공군 및실패군 간 개인적 ․ 사회적 ․ 환경적 특성 차이 분석: 제6기 국민건강영양조사 1차년도(2013년) 자료를 바탕으로

이준아,이인숙 한국지역사회간호학회 2016 지역사회간호학회지 Vol.27 No.2

Purpose: This study examined the characteristics differences associated with 1-year continuous smoking abstinence in Korean young adult and middle-aged male workers. Methods: ‘Korea National Health and Nutrition Examination Survey (KNHANES)’ is an ongoing surveillance system that assesses the health and nutritional status of Koreans. For a secondary analysis of cross-sectional data from KNHANES VI-1, this study selected 683 Korean male workers as a subpopulation, who were young adult or middle-aged. The subpopulation was composed of success or failure group of 1-year continuous smoking abstinence. Binomial logistic regression analysis was performed. Results: Success group was more likely to be older, live in urban areas, rate their health status as excellent or good, and have ever been diagnosed with hypertension than failure group. Additionally, Success group was less likely to have used electronic cigarettes (e-cigarettes), drink more than once a month, and have been exposed to secondhand smoking in workplace within a week. Conclusion: Developing smoking cessation programs requires consideration of resources in rural areas, promoting self-efficacy, restricting e-cigarettes and drinking, and promoting a smoke-free workplace.

Osteosarcoma in Korean children and adolescents

이준아 대한소아청소년과학회 2015 Clinical and Experimental Pediatrics (CEP) Vol.58 No.4

Osteosarcoma is the most frequent primary bone tumor. Advances in combination chemotherapyand surgical technique have greatly improved the survival of patients with osteosarcoma. In Korea,improvements in osteosarcoma treatment have been made over the past two decades. The 5-yearevent-free survival rate of Korean children and adolescents with localized disease is 64.6%, comparableto that of American or European patients. This article provides an overview of current therapiesfor osteosarcoma in Korea.

Solid Tumors in Children and Adolescents

이준아 대한의학회 2018 Journal of Korean medical science Vol.33 No.41

Cancer is the major cause of death in children and adolescents.1 According to the 2015 Korea Central Cancer Registry data, 1,353 children and adolescents (< 18 years) were diagnosed with cancer.2 Solid tumor comprises almost half of the cancer cases, with brain tumor being the most common tumor type.2 Solid tumors in children and adolescents are different from those of adults in clinical features and diversity of cellular origins.3 In adults, cancer rates tend to increase rapidly with increasing age. However, incidence pattern of childhood solid tumor follows an age-specific pattern.1 In early childhood, embryonal type solid tumors are common, such as retinoblastoma, neuroblastoma, hepatoblastoma, Wilms tumor, and medulloblastoma.1 In adolescents, solid tumors often arise from bone and soft tissues (osteosarcoma, Ewing sarcoma), germ cells (germ cell tumor) and epithelial cells (thyroid carcinoma).

-80℃ 냉동고를 이용한 제대혈 조혈모세포의 급속냉동법

이준아,유건희,김동현,성기웅,정혜림,구홍회,박규은,김대원 大韓輸血學會 2001 大韓輸血學會誌 Vol.12 No.1

간호의향 및 관련 개념분석

이준아 한국간호과학회 2018 한국간호과학회 학술대회 Vol.2018 No.10

Epidermal Growth Factor Receptor: Is It a Feasible Target for the Treatment of Osteosarcoma?

이준아,고윤미,김동호,임중섭,Chang-Bae Kong,Wan Hyeong Cho,Dae-Geun Jeon,Soo-Yong Lee,고재수 대한암학회 2012 Cancer Research and Treatment Vol.44 No.3

Purpose Features of epidermal growth factor receptor (EGFR) expression in osteosarcoma and in vitro efficacies of EGFR inhibitors against osteosarcoma cells were evaluated. Materials and Methods Thirty biopsy samples of osteosarcoma patients were retrospectively analyzed for EGFR protein expression by immunohistochemistry. Relationships between EGFR expression and clinicopathologic characteristics and treatment outcomes were evaluated. Four osteosarcoma cell lines were analyzed for EGFR and p-EGFR expression by western blotting. Efficacies of gefitinib and BIBW2992 on osteosarcoma cells were evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tyrosine kinase domains in exons 18 to 21 were sequenced and gene expression analyses of EGFR and PTENwere performed in four osteosarcoma cell lines. Results EGFR protein was expressed in 27 (90%) samples (6 low, 12 intermediate, 9 high) and in three cell lines. Intermediate or high staining for EGFR was related to a tumor volume<150 mL (p<0.001)and histologic subtype other than osteoblastic type (p=0.03). However, EGFR expression was not associated with histologic response to preoperative chemotherapy or survival. Gefitinib and BIBW 2992 did not have any significant inhibitory effect on cell viabilities. DNA sequencing analysis revealed three osteosarcoma cell lines have single base changes at codon 2361 of exon 20 (G to A), without affecting translation results. Furthermore, no mutation was found to be associated with constitutive EGFR activation. Conclusion In the present study, gefitinib and BIBW2992 were not effective against osteosarcoma cells. However, as osteosarcoma cells express EGFR, further studies are necessary to explore the potential of other therapeutic agents targeting EGFR.

뼈의 통증이 있을 때 감별해야 할 악성종양

이준아 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.8

Bone pain in a child could be associated with cancer as an initial manifestation of the disease. The childhood malignancies that frequently present bone pain are leukemia, neuroblastoma, and primary bone tumors such as osteosarcoma and Ewing sarcoma. Persistent bone or joint pain associated with swelling, mass, or limitation of motion implies underlying serious causes. Systemic manifestations such as lymphadenopathy, hepatosplenomegaly, fever, fatigue, night sweat, and laboratory abnormalities are also suggestive of malignancy. The index of suspicion tends to be low since less than 1% of children who complain of bone pain are diagnosed as cancer. Nonetheless, pediatricians should be alert to the possibilities of cancer since early detection and prompt treatment might reduce mortality. (Korean J Pediatr 2008;51:792-796)