osteosarcoma is the most common primary malignant tumor of the bone1,2 ) . in korea , advances in combination chemotherapy and surgical technique have greatly improved the survival of these patients1,2 ) . currently , more than 60% of patients with localized disease are cured1,2 ) . in this article , the clinical characteristics and treatment outcome of korean children and adolescents will be reviewed . in 2009 , the korean society of pediatric hematology and oncology conducted a retrospective study on the outcome of korean children and adolescents with osteosarcoma treated between 1989 and 20094 ) . there were 192 male and 128 female patients with a median age of 11.8 years ( range , 3.3 - 35.7 years ) at the time of diagnosis . the distal femur ( 52.3% ) was the most frequently affected site , followed by the proximal tibia ( 19.5% ) and proximal humerus ( 11.1% ) . the most common histological subtype was osteoblastic , and 64 patients ( 19.8% ) had distant metastasis at the time of diagnosis . the majority of patients ( 252 cases , 78.0% ) were treated in a standard fashion with preoperative chemotherapy followed by surgery and postoperative chemotherapy . of the 280 patients that underwent surgery , limb salvage was performed in 253 cases ( 90.4% ) . high - dose methotrexate ( hd mtx ) , cisplatin , doxorubicin , and ifosfamide were the core components of combination chemotherapy . 1 ) . postoperative chemotherapy was modified in 122 cases ( 37.8% ) due to poor histological response ( viable tumor cell>10% ) to preoperative chemotherapy . for survival analysis , data from the 225 cases followed - up for more than 2 years were evaluated using the kaplan - meier method . the probability of overall ( os ) and event - free survival ( efs ) at 5 years were 70.9% and 60.7% , respectively . the 5-year os and efs rates were better for the 184 patients who presented without metastasis at the time of diagnosis , 80.0% and 64.6% , respectively ( fig . we found that the presence of metastasis at the time of diagnosis and histological response to preoperative chemotherapy influenced survival ( table 1 ) . currently , the treatment outcomes of korean children and adolescents are comparable to those of american or european patients . despite improvements with a multidisciplinary treatment approach , 30%-40% of osteosarcoma patients still relapse and eventually succumb to the disease1,5 ) . lee et al.7 ) reported that the 5-year survival rate of 180 patients with recurrent osteosarcoma was 13% . the survival rate was influenced by the site of recurrence ( lung , 39% ; local , 0% ; lung and bone , 25% ; others , 12% ; p<0.05 ) , recurrence - free interval ( < 12 months , 13% ; 12 months , 44% , p<0.05 ) , and treatment modality after recurrence ( with surgery , 38% ; without surgery , 11% ; p<0.05 ) . generally , local control surgery is performed whenever possible and additional adjuvant chemotherapy is given . combination chemotherapy comprising ifosfamide , carboplatin , and etoposide is the most frequently used regimen6,7,8 ) . patients who experience treatment failure with this combination proceed to receive gemcitabine and docetaxel ( gemdoc ) chemotherapy8 ) . the efficacy of gemdoc has been reported in various sarcomas , including ewing sarcoma , malignant fibrous histiocytoma , synovial sarcoma , angiosarcoma and osteosarcoma9,10,11,12,13,14,15,16 ) . prompted by encouraging results from adult studies , gemdoc chemotherapy is used in children and adolescents with recurrent or refractory bone sarcomas13,14,15,16 ) . due to the rarity of bone sarcomas , case series reporting the efficacy of gemdoc chemotherapy analyzed patients with various pathologic diagnoses13,14,15,16 ) . data from the korea cancer center hospital8 ) showed that gemdoc chemotherapy had some activity in osteosarcoma , and better than expected survival after gemdoc chemotherapy was observed in patients both with and without surgery . the 28 patients ( aged 5.0 - 19.7 years ) received a total of 96 courses of chemotherapy ( median , 3 courses ; range , 1 - 8 courses ) and were followed - up for a median of 14.9 months ( range , 0.6 - 81.4 months ) . of these patients , 3 ( 17.6% ) experienced a complete response ( cr , including 2 metabolic cr ) ; 1 ( 5.9% ) , a partial response ( pr ) , and 3 ( 29.4% ) , stable disease ( sd ) . the objective response rate ( cr+pr ) and tumor control rate ( cr+pr+sd ) were 23.5% and 41.2% , respectively . the median duration of response was 11.2 months ( range , 2.8 - 14.6 months ) . os at 1 year was 53.6%9.4% and patients who received gemdoc chemotherapy as adjuvant chemotherapy fared better than those who received gemdoc chemotherapy as palliative therapy ( fig . effective local control is a crucial element in curing osteosarcoma and complete surgery is the most effective local control measure1,2,5 ) . the extremities are the most frequently affected sites of osteosarcoma1,2 ) , and complete surgery is feasible in the majority of cases . however , cases with unresectable lesions or cases where surgery will not yield an acceptable functional outcome require other local control measures . radiotherapy has been a mainstay of nonsurgical local tumor control and plays a major role in the treatment of various sarcomas , such as ewing sarcoma or rhabdomyosarcoma17 ) . osteosarcoma has a low radiosensitivity and few reports have described effective local control using radiotherapy18,19,20 ) . chemotherapeutic agents are administered concurrently or sequentially with radiotherapy and exert both systemic ( anticancer ) and local ( radiosensitizing ) effects21,22 ) . the presumed mechanisms by which chemotherapeutic agents interact with radiotherapy are as follows21,22 ) : ( 1 ) inhibition of radiation damage repair , ( 2 ) perturbation of cell cycling to increase the fraction of g2/m - phase cells , and ( 3 ) specific action on hypoxic cell populations . cisplatin , 5-fluorouracil ( 5-fu ) , ifosfamide , gemcitabine , and docetaxel are frequently used in chemoradiotherapy21 ) . the choice , optimal combination , and scheduling of chemotherapy with radiotherapy remain in evolution . for patients with unresectable recurrent or refractory osteosarcoma , sequential or concurrent chemoradiotherapy using gemcitabine showed efficacy in the treatment of nonsmall cell lung cancer23 ) . gemdoc combined with samarium-153 ethylene diamine tetramethylene phosphonate showed promising results in osteosarcoma patients24,25 ) . still , there are no data on the treatment outcome of gemdoc combined with external beam radiotherapy . we analyzed the outcomes of eight patients with unresectable recurrent or refractory osteosarcoma who were treated with radiotherapy and gemdoc chemotherapy at the korea cancer center hospital26 ) . the tumor sites were the bone in six patients and the lung in two patients . patients received a median of 3.5 courses of gemdoc chemotherapy ( range , 2 - 6 courses ) and the median dose of radiotherapy was 50.0 gy ( range , 46 - 84 gy ) . the objective response rate was 50.0% ( 2 complete metabolic responses , 1 partial response , and 1 partial metabolic response ) ( fig . responses were maintained for 4.6 , 6.1 , 6.2 , and 13.7 months , respectively . patients were followed for a median of 8.1 months ( range , 2.7 - 84.6 months ) and the median progression - free survival after treatment was 3.6 months ( range , 1.1 - 13.7 months ) . at the time of writing , two patients were alive , one was lost to follow - up , and five are deceased . despite improvements with a multidisciplinary treatment approach , 30%-40% of osteosarcoma patients still relapse and eventually succumb to the disease1,5 ) . lee et al.7 ) reported that the 5-year survival rate of 180 patients with recurrent osteosarcoma was 13% . the survival rate was influenced by the site of recurrence ( lung , 39% ; local , 0% ; lung and bone , 25% ; others , 12% ; p<0.05 ) , recurrence - free interval ( < 12 months , 13% ; 12 months , 44% , p<0.05 ) , and treatment modality after recurrence ( with surgery , 38% ; without surgery , 11% ; p<0.05 ) . generally , local control surgery is performed whenever possible and additional adjuvant chemotherapy is given . combination chemotherapy comprising ifosfamide , carboplatin , and etoposide is the most frequently used regimen6,7,8 ) . patients who experience treatment failure with this combination proceed to receive gemcitabine and docetaxel ( gemdoc ) chemotherapy8 ) . the efficacy of gemdoc has been reported in various sarcomas , including ewing sarcoma , malignant fibrous histiocytoma , synovial sarcoma , angiosarcoma and osteosarcoma9,10,11,12,13,14,15,16 ) . prompted by encouraging results from adult studies , gemdoc chemotherapy is used in children and adolescents with recurrent or refractory bone sarcomas13,14,15,16 ) . due to the rarity of bone sarcomas , case series reporting the efficacy of gemdoc chemotherapy analyzed patients with various pathologic diagnoses13,14,15,16 ) . data from the korea cancer center hospital8 ) showed that gemdoc chemotherapy had some activity in osteosarcoma , and better than expected survival after gemdoc chemotherapy was observed in patients both with and without surgery . the 28 patients ( aged 5.0 - 19.7 years ) received a total of 96 courses of chemotherapy ( median , 3 courses ; range , 1 - 8 courses ) and were followed - up for a median of 14.9 months ( range , 0.6 - 81.4 months ) . of these patients , 3 ( 17.6% ) experienced a complete response ( cr , including 2 metabolic cr ) ; 1 ( 5.9% ) , a partial response ( pr ) , and 3 ( 29.4% ) , stable disease ( sd ) . the objective response rate ( cr+pr ) and tumor control rate ( cr+pr+sd ) were 23.5% and 41.2% , respectively . the median duration of response was 11.2 months ( range , 2.8 - 14.6 months ) . os at 1 year was 53.6%9.4% and patients who received gemdoc chemotherapy as adjuvant chemotherapy fared better than those who received gemdoc chemotherapy as palliative therapy ( fig . effective local control is a crucial element in curing osteosarcoma and complete surgery is the most effective local control measure1,2,5 ) . the extremities are the most frequently affected sites of osteosarcoma1,2 ) , and complete surgery is feasible in the majority of cases . however , cases with unresectable lesions or cases where surgery will not yield an acceptable functional outcome require other local control measures . radiotherapy has been a mainstay of nonsurgical local tumor control and plays a major role in the treatment of various sarcomas , such as ewing sarcoma or rhabdomyosarcoma17 ) . osteosarcoma has a low radiosensitivity and few reports have described effective local control using radiotherapy18,19,20 ) . chemotherapeutic agents are administered concurrently or sequentially with radiotherapy and exert both systemic ( anticancer ) and local ( radiosensitizing ) effects21,22 ) . the presumed mechanisms by which chemotherapeutic agents interact with radiotherapy are as follows21,22 ) : ( 1 ) inhibition of radiation damage repair , ( 2 ) perturbation of cell cycling to increase the fraction of g2/m - phase cells , and ( 3 ) specific action on hypoxic cell populations . cisplatin , 5-fluorouracil ( 5-fu ) , ifosfamide , gemcitabine , and docetaxel are frequently used in chemoradiotherapy21 ) . the choice , optimal combination , and scheduling of chemotherapy with radiotherapy remain in evolution . for patients with unresectable recurrent or refractory osteosarcoma , a novel or third - line chemotherapeutic agent might be preferred . sequential or concurrent chemoradiotherapy using gemcitabine showed efficacy in the treatment of nonsmall cell lung cancer23 ) . gemdoc combined with samarium-153 ethylene diamine tetramethylene phosphonate showed promising results in osteosarcoma patients24,25 ) . still , there are no data on the treatment outcome of gemdoc combined with external beam radiotherapy . we analyzed the outcomes of eight patients with unresectable recurrent or refractory osteosarcoma who were treated with radiotherapy and gemdoc chemotherapy at the korea cancer center hospital26 ) . the tumor sites were the bone in six patients and the lung in two patients . patients received a median of 3.5 courses of gemdoc chemotherapy ( range , 2 - 6 courses ) and the median dose of radiotherapy was 50.0 gy ( range , 46 - 84 gy ) . the objective response rate was 50.0% ( 2 complete metabolic responses , 1 partial response , and 1 partial metabolic response ) ( fig . responses were maintained for 4.6 , 6.1 , 6.2 , and 13.7 months , respectively . patients were followed for a median of 8.1 months ( range , 2.7 - 84.6 months ) and the median progression - free survival after treatment was 3.6 months ( range , 1.1 - 13.7 months ) . at the time of writing , two patients were alive , one was lost to follow - up , and five are deceased . no other agent has come close to replacing the four standard chemotherapeutic agents : hd mtx , cisplatin , doxorubicin , and ifosfamide . etoposide has shown limited activity when administered as a single agent27 ) but may enhance the effect of other drugs such as cyclophosphamide28,29 ) . when administered as single agents , 5-azacytidine30 ) , 5-fu / leucovorin31 ) , iproplatin32,33 ) , ecteinascidin-74334 ) , and topotecan35 ) in the few reported studies , the benefits of high - dose chemotherapy and autologous peripheral blood stem cell rescue are still unproven for patients with osteosarcoma36,37 ) . the american intergroup trial int0133 evaluated the efficacy of liposomal muramyl - tripeptide - ethanolamine ( mtp ) , an immune modulator38,39 ) . a recent analysis reported a trend for better efs ( p=0.08 ) and improved os ( p=0.03 ) for the liposomal mtp arm39 ) . however , routine use is hampered due to its tremendous cost and the lack of confirmatory clinical data . inhibitors of igf1r and its downstream pathways have shown promise in preclinical models of osteosarcoma40 ) . tumor responses to anti - igf1r therapy have been published for a total of 7 patients with osteosarcoma41 ) . the outcomes of additional phase i and phase ii studies have yet to be reported . the italian sarcoma group reported that a combination of sorafenib and the mammalian target of rapamycin inhibitor everolimus showed activity as a further - line treatment for patients with advanced or unresectable osteosarcoma42 ) . the survival of korean patients with osteosarcoma has improved over the last 20 years and is comparable to that reported in major euro - american studies . however , patients with metastasis at the time of diagnosis and those with relapsed tumors have poor prognosis . currently , the search for new chemotherapeutic agents and alternative treatment strategies , such as therapies targeting biological markers , angiogenesis , and the immune system , is underway to improve the survival of these patients .
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 .