• Asian Pacific Journal of Cancer Prevention
• /
• 제14권2호
• /
• pp.1101-1106
• /
• 2013

Background: Osteosarcoma is the most common primary bone tumor in childhood and adolescence. Carboplatin, a platinum-derived agent, is used as neoadjuvant chemotherapy for pediatric osteosarcoma because of its anti-tumor activity and had low toxicity as compared to cisplatin. Objective: To determine demographic data, prognostic factors and outcome of childhood osteosarcoma treated with a carboplatin-based chemotherapeutic protocol at Chiang Mai University. Method: A retrospective analysis was conducted on 34 osteosarcoma patients aged less than 18 years and treated between 2003 and 2011. Results: Overall limb-salvage and amputation rates were 23.5% and 70.6%, respectively. With the mean follow-up time of 29.5 months (1.5-108.9), the Kaplan-Meier analysis for 3-year disease-free survival (DFS) and 3-year overall survival (OS) were $20.2{\pm}7.7%$ and $47.1{\pm}9.5%$ respectively. Patients who had initial pulmonary metastasis were at significantly greater risk for developing recurrence (p=0.02, OR=7; 1.2-40.1) and had a tendency to have lower 3-year OS compared to those without initial pulmonary metastasis ($28.1{\pm}13%$, $63.1{\pm}12.3%$, respectively, p=0.202). On univariate analysis, age at diagnosis >14 years and patients who were declined surgery were significantly associated with lower 3-year OS (p=0.008 and <0.05, respectively). However, age at diagnosis, sex, tumor size and histological subtypes were not found to significantly affect recurrence or survival. Conclusions: In our study, the survival rate was far lower than those reported from developed countries. These might indicate the ineffectiveness of carboplatin in combination with doxorubicin as frontline treatment of pediatric osteosarcoma, especially in those with initial pulmonary metastasis. Refinement in risk and treatment stratification and dose intensification for pediatric osteosarcoma constitutes a future challenge to improve outcomes, especially in metastatic patients who may need a more intensive regimen.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권8호
• /
• pp.4595-4598
• /
• 2013

We conducted a comprehensive study to investigate the role of genes involved in transport pathways in response to chemotherapy and clinical outcome of osteosarcoma cases. Genotyping of six SNPs was performed in a 384-well plate format on the Sequenom MassARRAY platform for 208 osteosarcoma patients to reveal any correlations of the six SNPs with response to chemotherapy and clinical outcome. Individuals with the ABCB1 rs1128503 TT and ABCC3 rs4148416 TT genotypes had a higher probability of responding poorly to chemotherapy, indicated by odds ratios (ORs) of 2.46 (95%CI, 1.21-5.74) and 3.78 (95% CI, 1.20-13.85), respectively. Moreover, the ABCB1 rs1128503 TT and ABCC3 rs4148416 TT genotypes were significantly associated with shorter diseasefree survival (DFS) and overall survival (OS). Our study found the two SNPs in two transporter genes and one phase II metabolism enzyme to be associated with response to chemotherapy and overall survival in osteosarcoma patients, suggesting potential prognostic biomarker applications of the two SNPs.

• Clinical and Experimental Pediatrics
• /
• 제58권4호
• /
• pp.123-128
• /
• 2015

Osteosarcoma is the most frequent primary bone tumor. Advances in combination chemotherapy and 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-year event-free survival rate of Korean children and adolescents with localized disease is 64.6%, comparable to that of American or European patients. This article provides an overview of current therapies for osteosarcoma in Korea.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권15호
• /
• pp.5967-5976
• /
• 2014

Treating the osteosarcoma (OSA) remains a challenge. Current strategies focus on the primary tumor and have limited efficacy for metastatic OSA. A better understanding of the OSA pathogenesis may provide a rational basis for innovative treatment strategies especially for metastases. The aim of this review is to give an overview of the molecular mechanisms of OSA tumorigenesis, OSA cell proliferation, apoptosis, migration, and chemotherapy resistance, and how improved understanding might contribute to designing a better treatment target for OSA.

• Clinical and Experimental Pediatrics
• /
• 제62권2호
• /
• pp.62-67
• /
• 2019

Purpose: We aimed to determine the prognostic significance of lymphocyte counts and the lymphocytemonocyte ratio (LMR) in pediatric patients with osteosarcoma. Methods: We retrospectively reviewed the medical records of 27 pediatric patients with localized extremity osteosarcoma, treated at the Korea Cancer Center Hospital between May 2002 and March 2016. Leukocyte counts and LMR before treatment and on day 14 (LMR14) of the first cisplatin-doxorubicin chemotherapy round were evaluated. Patients were dichotomized according to the median value of these parameters, and survival rates were compared. Results: The median age of the 27 patients was 9.9 years (range, 3.2-14.1 years) and tumor sites were: distal femur (n=14), proximal humerus (n=7), proximal tibia (n=2), proximal fibula (n=2), and elsewhere (n=2). Patients were followed up on for a median of 76.4 months (range, 4.5-174.7 months), and 5-year overall (OS) and event-free survival (EFS) rates were $66.0%{\pm}9.8%$ and $60.9%{\pm}9.7%$, respectively. Patients with a higher pretreatment lymphocyte count (${\geq}2,320/{\mu}L$) had better OS (90.9% vs. 46.2%, P=0.04) and EFS (83.9% vs. 38.5%, P=0.02). However, the day 14 lymphocyte count was not associated with survival. While no survival difference was observed between patients grouped according to pretreatment LMR (median value, 6.3), patients with a higher LMR14 (${\geq}5$) fared better than those with lower LMR14 (5-year OS: 83.3% vs. 46.3%, P=0.04). Conclusion: Pretreatment lymphocyte count and LMR during chemotherapy had prognostic significance in pediatric osteosarcoma patients. Further studies involving larger cohorts are necessary to validate our findings.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권22호
• /
• pp.9823-9829
• /
• 2014

Background: High-dose methotrexate (HD-MTX) is recognized as an efficient component of therapy against pediatric osteosarcoma in combination with other drugs such as cisplatin (CDP), carboplatin (CBDCA), doxorubicin (ADM), etoposide (VP-16) and ifosfamide (IFO). Objectives: To demonstrate the feasibility and effectiveness of the HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)] protocol comparable to CDP/ADM/CBDCA/IFO [MTX(-)] for treating childhood osteosarcoma at Ramathibodi Hospital (1999-2014). Materials and Methods: A retrospective analysis was conducted of osteosarcoma patients aged less than 18 years treated with two chemotherapeutic regimens between 1999 and 2014. A total of 45 patients received the MTX(-) and 21 the MTX(+) protocol. Results: Overall limb-salvage and amputation rate were 12.9% and 77.7%, respectively. Kaplan-Meier analysis results for 3-year disease free survival (DFS) and overall survival (OS) regardless of treatment regimens were $43.4{\pm}6.0%$ and $53.2{\pm}6.1%$ respectively. The 3-year DFS and OS were improved significantly with the MTX(+) protocol compared to MTX(-) protocol (p=0.010 and p=0.009, log rank test) [$69.8{\pm}10.5%$, $79.8{\pm}9.1%$ for MTX(+) and $31.1{\pm}6.9%$, $42.2{\pm}7.4%$ for MTX(-) protocol, respectively]. Patients with metastatic osteosarcoma treated with the MTX(+) protocol had statistically significant higher 3-year DFS and OS than those treated with the MTX(-) protocol ($66.7{\pm}13.6%$ and $15.0{\pm}8.0%$ for 3-year DFS, p=0.010, $73.3{\pm}13.2%$ and $20{\pm}8.9%$ for 3-year OS, p=0.006, respectively). The independent risk factors for having inferior 3-year DFS and OS were poor histological response (tumor necrosis <90%) and treatment with the MTX(-) protocol. The multivariate analysis identified only the treatment with the MTX(-) protocol as an independent predictor of inferior OS with a hazard ratio (HR) of 3.53 (95% confidence interval of 1.2-10.41, p=0.022). Conclusions: Our study demonstrated the tolerability, feasibility and efficacy of the HDMTX-based regimen improving the survival rate in pediatric osteosarcoma cases, in line with reports from developed countries.

• Clinical and Experimental Pediatrics
• /
• 제59권9호
• /
• pp.374-380
• /
• 2016

Purpose: Patients with unresectable, relapsed, or refractory osteosarcoma need a novel therapeutic agent. Metformin is a biguanide derivative used in the treatment of type II diabetes, and is recently gaining attention in cancer research. Methods: We evaluated the effect of metformin against human osteosarcoma. Four osteosarcoma cell lines (KHOS/NP, HOS, MG-63, U-2 OS) were treated with metformin and cell proliferation was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were evaluated using flow cytometric analysis, and migration and wound healing assay were performed. Fourteen female Balb/c-nude mice received KHOS/NP cell grafts in their thigh, and were allowed access to metformin containing water (2 mg/mL) ad libitum. Tumor volume was measured every 3-4 days for a period of 4 weeks. Results: Metformin had a significant antiproliferative effect on human osteosarcoma cells. In particular, metformin inhibited the proliferation and migration of KHOS/NP cells by activation of AMP-activated protein kinase and consequent inhibition of the mammalian target of rapamycin pathway. It also inhibited the proliferation of cisplatin-resistant KHOS/NP clone cells. Analysis of KHOS/NP xenograft Balb/c-nude models indicated that metformin displayed potent in vivo antitumor effects. Conclusion: Further studies are necessary to explore metformin's therapeutic potential and the possibilities for its use as an adjuvant agent for osteosarcoma.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권9호
• /
• pp.4281-4284
• /
• 2012

Background: Osteosarcoma is the most common bone cancer in children, responsible for a high rate of amputation and death. This is the first long-term, population-based, epidemiologic and survival study in Thailand. Objective: To study the incidence and survival rates of pediatric osteosarcoma in Khon Kaen. Method: Childhood osteosarcoma cases (0-19 years) diagnosed between 1985-2010 were reviewed. The data were retrieved from the population-based data set of the Khon Kaen Cancer Registry and medical records from Srinagarind Hospital, Faculty of Medicine, Khon Kaen University. All cases were censored until the end of April 2012. The age-standardized incidence rate (ASR) was calculated using the standard method. Survival experience was analyzed using the standard survival function (STATA 9.0) and presented with a Kaplan-Meier curve. Results: 58 cases were enrolled. The overall ASR was 14.1 per million. Males and females were equally affected. The peak incidence was for 15-19 year-olds in both sexes (ASR=10.4 per million in males and 8.5 in females). The 5-year overall survival rate was 27.6% (95% CI: 15.8-40.8%). The median survival time was 1.6 years (95% CI: 1.2-2.1). In a subgroup analysis, the patients who received only chemotherapy survived longer (5-year survival 45.7%, median survival time 4.1 years, p=0.12). Conclusion: The incidence rate for childhood osteosarcoma was slightly less than those reported for Western countries. The survival rate was also lower than reports from developed countries. Further evaluation of the treatment protocol and risk factor stratification is needed.

• Clinical and Experimental Pediatrics
• /
• 제49권5호
• /
• pp.565-569
• /
• 2006

Rothmund-Thomson 증후군은 상염색체 열성질환으로 다형피부증(poikiloderma), 희박한 모발과 눈썹, 저신장, 골격계 이상, 유소년기 백내장과 악성종양의 위험이 높은 것으로 특징지어지는 증후군이다. 골격계의 이상은 RTS 환아의 68%에서 보고되었고 신체전반의 골격계 이형성으로 형성부전이나 기형으로 나타난다. 요골형성부전, 엄지손가락 저형성, 골감소증, 슬개골 저형성이나 슬개골 형성 부전 등이 보고되어 있다. 흔치 않은 증상으로는 말안장코와 삼각형의 얼굴 등이 보고되어있다. RTS에서 골육종을 포함한 악성종양의 발생빈도가 높고 면역학적 이상이 보고되어 있다. 피부종양이 가장 흔하며 상피세포암, 기저세포암, Bowen's disease 등이 있고 두 번째로는 육종이 흔하다. 저자들은 전신적으로 혈관확장 및 과색소침착을 보이는 다형 피부 소견과 함께 요골형성부전, 척골기형, 엄지손가락형성부전, 슬개골 형성부전의 골격계 기형이 있으면서 이후 좌측 경골에 골육종이 발생한 Rothmund-Thomson 증후군을 경험하였기에 보고하는 바이다.

• Journal of Hospice and Palliative Care
• /
• 제3권2호
• /
• pp.152-155
• /
• 2000

The authors reported a case of terminal pediatric cancer patient. The patient was ten-year-old girl, and she was diagnosed as osteosarcoma with multiple metastasis to lung and bones. She was markedly depressed and had severe bone and chest pain. The patient was treated with hypnotherapy once or twice a week for two months. There was marked improvement in pain control and emotional reactions, and the hospice team could establish good rapport with her. Hypnotherapy would be one of the effective treatment modalities in assisting patients.