多发骨肉瘤的诊疗现状及起源问题初步探讨
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摘要
<正>骨肉瘤是青少年最常见的原发恶性骨肿瘤,其起源于成骨间叶细胞,恶性程度极高,男性好发,男女发病率比值为3∶2,早期即可转移,预后很差~([1-6])。多发骨肉瘤是一种相对少见但侵袭性更强的骨肉瘤,最早于1936年由澳大利亚的Silverman报道~([7])。定义为患者体内存在两个或者两个以上的骨肉瘤病灶但不伴有肺转移或者内脏转移,也被称为多中心骨肉瘤或者多病灶骨肉瘤~([8])。多发骨肉瘤分为两类,最初诊断时发现多病灶即定义为同时型多
To review the research and clinical status of multifocal osteosarcoma( MFOS), and discuss its origin. Osteosarcoma( OS) is one of the most common malignant bone tumors in adolescents, with metastasis in early stage and the five year survival is only about 60%. MFOS was reported by Silverman firstly in 1936, which was rare but invasive. There have been only 300 cases reported in literature till now. MFOS is characterized by the presence of tumor lesions in osseous sites without pulmonary metastasis. The MFOS patients present rapid progress, poor reaction with chemo-drugs and with a very terrible outcome. However, it has low incidence. With clinical and economic progress, the detection rate of MFOS has been promoted in recent years. Along with the development of novel research methods, deeper understanding makes the treatment much more individualized.
To review the research and clinical status of multifocal osteosarcoma( MFOS), and discuss its origin. Osteosarcoma( OS) is one of the most common malignant bone tumors in adolescents, with metastasis in early stage and the five year survival is only about 60%. MFOS was reported by Silverman firstly in 1936, which was rare but invasive. There have been only 300 cases reported in literature till now. MFOS is characterized by the presence of tumor lesions in osseous sites without pulmonary metastasis. The MFOS patients present rapid progress, poor reaction with chemo-drugs and with a very terrible outcome. However, it has low incidence. With clinical and economic progress, the detection rate of MFOS has been promoted in recent years. Along with the development of novel research methods, deeper understanding makes the treatment much more individualized.
引文
[1]Buckley JD,Pendergrass TW,Buckley CM,et al.Epidemiology of osteosarcoma and Ewing’s sarcoma in childhood:a study of 305 cases by the Children’s Cancer Group[J].Cancer,1998,83(7):1440-1448.
[2]Miller RW.Contrastingepidemiology of childhood osteosarcoma,Ewing's tumor,and rhabdomyosarcoma[J].Natl Cancer Inst Monogr,1981,56(56):9-15.
[3]Mirabello L,Troisi RJ,Savage SA.Osteosarcoma incidence and survival rates from 1973 to 2004:data from the Surveillance,Epidemiology,and End Results Program[J].Cancer,2009,115(7):1531-1543.
[4]Ottaviani G,Jaffe N.The epidemiology of osteosarcoma[J].Cancer Treat Res,2009,152:3-13.
[5]Sampo M,Koivikko M,Taskinen M,et al.Incidence,epidemiology and treatment results of osteosarc oma in Finland-a nationwide population-based study[J].Acta Oncol,2011,50(8):1206-1214.
[6]王文剑,于秀淳,韩加,等.1593例骨肉瘤流行病及治疗的回顾性分析[J].中华骨科杂志,2018,38(18):1097-1107.
[7]Silverman G.Multiple osteogenic sarcoma[J].Arch Pathol,1936,21(5):88-95.
[8]Halpert B,Russo PE,VC Hackney.Osteogenic sarcoma with multiple skeletal and visceral involvement[J].Cancer,1949,2(5):789-792.
[9]Daffner RH,Kennedy SL,Fox KR,et al.Synchronous multicentric osteosarcoma:The case for metastases[J].Skeletal Radiol,1997,26(10):569-578.
[10]Klein MJ,GP Siegal.Osteosarcoma:anatomic and histologic variants[J].Am J Clin Pathol,2006,125(4):555-581.
[11]Lucas DR.Dahlin’s bone tumors:general aspects and data on11,087 cases[J].Am J Clin Pathol,1996,106(5):693.
[12]Jaffe N,Pearson P,Yasko AW,et al.Single and multiple metachronous osteosarcoma tumors after therapy[J].Cancer,2003,98(11):2457-2466.
[13]Enneking WF,Kagan A.“Skip”metastases in osteosarcoma[J].Cancer,1975,36(6):2192-2205.
[14]Fitzgerald RH Jr,Dahlin DC,Sim FH.Multiple metachronous osteogenic sarcoma.Report of twelve cases with two long-term survivors[L].J Bone Joint Surg Am,1973,55(3):595-605.
[15]Hopper KD,Jr MR,Haseman DB,et al.Osteosarcomatosis[J].Radiology,1990,175(1):233-239.
[16]Parham DM,Pratt C,Parvey LS,et al.Childhood multifocal osteosarcoma.Clinicopathologic and radiologic correlates[J].Cancer,1985,55(11):2653-2658.
[17]Jeffree GM,Price CH,Sissons HA.The metastatic patterns of osteosarcoma[J].Br J Cancer,1975,32(1):87-107.
[18]Hasan Naqvi SG,Khan SA,Bakhshi S.Metastatic or metachronous osteosarcoma:a clinical dilemma[J].Indian JPediatr,2009,76(3):335-336.
[19]Aizawa T,Okada K,Abe E,et al.Multicentric osteosarcoma with long-term survival[J].Skeletal Radiol,2004,33(1):41-45.
[20]Corradi D,Wenger DE,Bertoni F,et al.Multicentric osteosarcoma clinicopathologic and radiographic study of 56cases[J].Am J Clin Pathol,2011,136(5):799-807.
[21]Gavane S,Price AP,Magnan H,et al.Multifocal osteosarcoma:unusual presentation and imaging findings[J].Clin Nucl Med,2017,42(4):e202-206.
[22]Tsai MH,Yang CP,Jaing TH,et al.Synchronous multifocal osteosarcoma:report of one case[J].Acta Paediatr Taiwan,2006,47(3):146-149.
[23]Boyle R,Giuffre B,Bonar SF.Multifocal low-grade central osteosarcoma:a rare case[J].Skeletal Radiol,2016,45(7):997-1006.
[24]郭卫,李大森,沈丹华,等.多中心成骨肉瘤的治疗[J].中华骨科杂志,2006,26(6):376-380.
[25]刘记存,高静,王溱河.多灶性骨肉瘤4例报告[J].实用放射学杂志,2000,16(11):701-702.
[26]张浩强,王臻,鲍莉,等.拷贝数变异对多发骨肉瘤临床分型与耐药机制的影响[J].中华骨科杂志,2015,35(4):442-449.
[27]张晶,肖砚斌,袁涛,等.多中心骨肉瘤5例治疗体会[J].广东医学,2012,33(15):2269-2271.
[28]张增亮,李南,陈秉耀,等.多中心性骨肉瘤治疗及预后六例报告[J].中国骨与关节杂志,2015(8):627-631.
[29]叶招明,李伟栩,杨迪生,等.III期骨肉瘤的治疗[J].中华骨科杂志,2005,25(6):363-367.
[30]侯博,杨素君,王玉芳,等.多中心性骨肉瘤6例[J].临床合理用药杂志,2014,7(2):118-119.
[31]董岩青,李坤成,尹建国.骨肉瘤病的影像学表现--附1例报道及文献复习[J].罕少疾病杂志,2000(1):21-23.
[32]Bielack S,Jürgens H,Jundt G,et al.Osteosarcoma:The COSSExperience[J].Cancer Treat Res,2009,152:289-308.
[33]Clark JCM,Dass CR,Choong PFM.A review of clinical and molecular prognostic factors in osteosarcoma[J].J Cancer Res Clin Oncol,2008,134(3):281-297.
[34]Jawad MU,Cheung MC,Clarke J,et al.Osteosarcoma:improvement in survival limited to high-grade patients only[J].J Cancer Res Clin Oncol,2011,137(4):597-607.
[35]Bacci G,Fabbri N,Balladelli A,et al.Treatment and prognosis for synchronous multifocal osteosarcoma in 42 patients[J].J Bone Joint Surg Br,2006,88(8):1071-1075.
[36]Wolf RE,Enneking WF.The staging and surgery of musculoskeletal neoplasms[J].Orthop Clin North Am,1996,27(3):473-481.
[37]Amstutz HC.Multiple osteogenic sarcomata--metastatic or multicentric?Report of two cases and review of literature[J].Cancer,2015,24(5):923-931.
[38]Mahoney JP,Spanier SS,Morris JL.Multifocal osteosarcoma.A case report with review of the literature[J].Cancer,1979,44(5):1897-1907.
[39]Zheng G.Present situation,problems and development in the treatment of osteosarcoma in China[J].Chin J Bone Joint,2015,4(5):338-342.
[40]张云峰,刘卫华.腓骨瓣移植治疗肱骨骨旁骨肉瘤3例报告[J].实用骨科杂志,2012,18(10):926-928.
[41]冯毅,吕智,马全平,等.大段同种异体骨移植治疗股骨干骨肉瘤的临床体会[J].实用骨科杂志,2012,18(9):854-857.
[42]Anract P,Missenard G,Jeanrot C,et al.Knee reconstruction with prosthesis and muscle flap after total arthrectomy[J].Clin Orthop Relat Res,2001,384(384):208-216.
[43]Bacci G.Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation:recent experience at the Rizzoli Institute in 57 patients treated with cisplatin,doxorubicin,and a high dose of methotrexate and ifosfamide[J].Ann Oncol,2003,14(7):1126-1134.
[44]Xiao X,Wang W,Zhang HQ,et al.Individualized chemotherapy for osteosarcoma and identification of gene mutations in osteosarcoma[J].Tumour Biol,2015,36(4):2427-2435.
[45]Omer N,Le DM,Pipernoneumann S,et al.Phase-II trials in osteosarcoma recurrences:A systematic review of past experience[J].Eur J Cancer,2017,75:98-108.
[46]Whelan JS,Bielack SS,Marina N,et al.EURAMOS-1,an international randomised study for osteosarcoma:results from pre-randomisation treatment[J].Ann Oncol,2015,26(2):407-414.
[47]Goldberg JM.Immunotherapy of sarcomas[J].Curr Opin Oncol,2013,25(4):390-397.
[48]Lussier DM,O’Neill L,Nieves LM,et al.Enhanced T-cell immunity to osteosarcoma through antibody blockade of PD-1/PD-L1 interactions[J].J Immunother,2015,38(3):96-106.
[49]Safwat A,Boysen A,Lücke A,et al.Pazopanib in metastatic osteosarcoma:significant clinical response in three consecutive patients[J].Acta Oncol,2014,53(10):1451-1454.
[50]Grignani G,Palmerini E,Ferraresi V,et al.Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment:a nonrandomised phase 2 clinical trial[J].Lancet Oncol,2015,16(1):98-107.
[51]朱兵,李建民,张清,等.我国骨肉瘤治疗现状及改进建议--17家骨肿瘤治疗中心1998~2008年资料分析[J].中国骨与关节杂志,2009,8(3):129-132.
[52]流小舟,于沂阳,施鑫,等.骨肉瘤复发患者的转归及影响长期生存的因素分析--一项基于多中心骨肉瘤复发患者的长期随访研究[J].中华骨科杂志,2018,38(18):1089-1096.
[53]Brandal P,Bjerkehagen B,Bruland OS,et al.Synchronous and metachronous skeletal osteosarcomas:the Norwegian Radium Hospital experience[J].Acta Oncol,2009,48(8):1165-1172.
[54]Iavarone A,Matthay KK,Steinkirchner TM,et al.Germline and somatic p53 gene mutations in multifocal osteogenic sarcoma[J].Proc Natl Acad Sci USA,1992,89(9):4207-4209.
[55]Yamamoto Y,Yamamoto N,Tajima K,et al.Characterization of human multicentric osteosarcoma using newly established cells derived from multicentric osteosarcoma[J].J Cancer Res Clin Oncol,2011,137(3):423-433.
[56]Kimura K,Nakano T,Park YB,et al.Establishment of human osteosarcoma cell lines with high metastatic potential to lungs and their utilities for therapeutic studies on metastatic osteosarcoma[J].Clin Exp Metastasis,2002,19(6):477-485.
[57]Zhang HQ,Li MH,Gao P,et al.Preliminary application of precision genomic medicine detecting gene variation in patients with multifocal osteosarcoma[J].Orthop Surg,2016,8(2):129-138.
[2]Miller RW.Contrastingepidemiology of childhood osteosarcoma,Ewing's tumor,and rhabdomyosarcoma[J].Natl Cancer Inst Monogr,1981,56(56):9-15.
[3]Mirabello L,Troisi RJ,Savage SA.Osteosarcoma incidence and survival rates from 1973 to 2004:data from the Surveillance,Epidemiology,and End Results Program[J].Cancer,2009,115(7):1531-1543.
[4]Ottaviani G,Jaffe N.The epidemiology of osteosarcoma[J].Cancer Treat Res,2009,152:3-13.
[5]Sampo M,Koivikko M,Taskinen M,et al.Incidence,epidemiology and treatment results of osteosarc oma in Finland-a nationwide population-based study[J].Acta Oncol,2011,50(8):1206-1214.
[6]王文剑,于秀淳,韩加,等.1593例骨肉瘤流行病及治疗的回顾性分析[J].中华骨科杂志,2018,38(18):1097-1107.
[7]Silverman G.Multiple osteogenic sarcoma[J].Arch Pathol,1936,21(5):88-95.
[8]Halpert B,Russo PE,VC Hackney.Osteogenic sarcoma with multiple skeletal and visceral involvement[J].Cancer,1949,2(5):789-792.
[9]Daffner RH,Kennedy SL,Fox KR,et al.Synchronous multicentric osteosarcoma:The case for metastases[J].Skeletal Radiol,1997,26(10):569-578.
[10]Klein MJ,GP Siegal.Osteosarcoma:anatomic and histologic variants[J].Am J Clin Pathol,2006,125(4):555-581.
[11]Lucas DR.Dahlin’s bone tumors:general aspects and data on11,087 cases[J].Am J Clin Pathol,1996,106(5):693.
[12]Jaffe N,Pearson P,Yasko AW,et al.Single and multiple metachronous osteosarcoma tumors after therapy[J].Cancer,2003,98(11):2457-2466.
[13]Enneking WF,Kagan A.“Skip”metastases in osteosarcoma[J].Cancer,1975,36(6):2192-2205.
[14]Fitzgerald RH Jr,Dahlin DC,Sim FH.Multiple metachronous osteogenic sarcoma.Report of twelve cases with two long-term survivors[L].J Bone Joint Surg Am,1973,55(3):595-605.
[15]Hopper KD,Jr MR,Haseman DB,et al.Osteosarcomatosis[J].Radiology,1990,175(1):233-239.
[16]Parham DM,Pratt C,Parvey LS,et al.Childhood multifocal osteosarcoma.Clinicopathologic and radiologic correlates[J].Cancer,1985,55(11):2653-2658.
[17]Jeffree GM,Price CH,Sissons HA.The metastatic patterns of osteosarcoma[J].Br J Cancer,1975,32(1):87-107.
[18]Hasan Naqvi SG,Khan SA,Bakhshi S.Metastatic or metachronous osteosarcoma:a clinical dilemma[J].Indian JPediatr,2009,76(3):335-336.
[19]Aizawa T,Okada K,Abe E,et al.Multicentric osteosarcoma with long-term survival[J].Skeletal Radiol,2004,33(1):41-45.
[20]Corradi D,Wenger DE,Bertoni F,et al.Multicentric osteosarcoma clinicopathologic and radiographic study of 56cases[J].Am J Clin Pathol,2011,136(5):799-807.
[21]Gavane S,Price AP,Magnan H,et al.Multifocal osteosarcoma:unusual presentation and imaging findings[J].Clin Nucl Med,2017,42(4):e202-206.
[22]Tsai MH,Yang CP,Jaing TH,et al.Synchronous multifocal osteosarcoma:report of one case[J].Acta Paediatr Taiwan,2006,47(3):146-149.
[23]Boyle R,Giuffre B,Bonar SF.Multifocal low-grade central osteosarcoma:a rare case[J].Skeletal Radiol,2016,45(7):997-1006.
[24]郭卫,李大森,沈丹华,等.多中心成骨肉瘤的治疗[J].中华骨科杂志,2006,26(6):376-380.
[25]刘记存,高静,王溱河.多灶性骨肉瘤4例报告[J].实用放射学杂志,2000,16(11):701-702.
[26]张浩强,王臻,鲍莉,等.拷贝数变异对多发骨肉瘤临床分型与耐药机制的影响[J].中华骨科杂志,2015,35(4):442-449.
[27]张晶,肖砚斌,袁涛,等.多中心骨肉瘤5例治疗体会[J].广东医学,2012,33(15):2269-2271.
[28]张增亮,李南,陈秉耀,等.多中心性骨肉瘤治疗及预后六例报告[J].中国骨与关节杂志,2015(8):627-631.
[29]叶招明,李伟栩,杨迪生,等.III期骨肉瘤的治疗[J].中华骨科杂志,2005,25(6):363-367.
[30]侯博,杨素君,王玉芳,等.多中心性骨肉瘤6例[J].临床合理用药杂志,2014,7(2):118-119.
[31]董岩青,李坤成,尹建国.骨肉瘤病的影像学表现--附1例报道及文献复习[J].罕少疾病杂志,2000(1):21-23.
[32]Bielack S,Jürgens H,Jundt G,et al.Osteosarcoma:The COSSExperience[J].Cancer Treat Res,2009,152:289-308.
[33]Clark JCM,Dass CR,Choong PFM.A review of clinical and molecular prognostic factors in osteosarcoma[J].J Cancer Res Clin Oncol,2008,134(3):281-297.
[34]Jawad MU,Cheung MC,Clarke J,et al.Osteosarcoma:improvement in survival limited to high-grade patients only[J].J Cancer Res Clin Oncol,2011,137(4):597-607.
[35]Bacci G,Fabbri N,Balladelli A,et al.Treatment and prognosis for synchronous multifocal osteosarcoma in 42 patients[J].J Bone Joint Surg Br,2006,88(8):1071-1075.
[36]Wolf RE,Enneking WF.The staging and surgery of musculoskeletal neoplasms[J].Orthop Clin North Am,1996,27(3):473-481.
[37]Amstutz HC.Multiple osteogenic sarcomata--metastatic or multicentric?Report of two cases and review of literature[J].Cancer,2015,24(5):923-931.
[38]Mahoney JP,Spanier SS,Morris JL.Multifocal osteosarcoma.A case report with review of the literature[J].Cancer,1979,44(5):1897-1907.
[39]Zheng G.Present situation,problems and development in the treatment of osteosarcoma in China[J].Chin J Bone Joint,2015,4(5):338-342.
[40]张云峰,刘卫华.腓骨瓣移植治疗肱骨骨旁骨肉瘤3例报告[J].实用骨科杂志,2012,18(10):926-928.
[41]冯毅,吕智,马全平,等.大段同种异体骨移植治疗股骨干骨肉瘤的临床体会[J].实用骨科杂志,2012,18(9):854-857.
[42]Anract P,Missenard G,Jeanrot C,et al.Knee reconstruction with prosthesis and muscle flap after total arthrectomy[J].Clin Orthop Relat Res,2001,384(384):208-216.
[43]Bacci G.Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation:recent experience at the Rizzoli Institute in 57 patients treated with cisplatin,doxorubicin,and a high dose of methotrexate and ifosfamide[J].Ann Oncol,2003,14(7):1126-1134.
[44]Xiao X,Wang W,Zhang HQ,et al.Individualized chemotherapy for osteosarcoma and identification of gene mutations in osteosarcoma[J].Tumour Biol,2015,36(4):2427-2435.
[45]Omer N,Le DM,Pipernoneumann S,et al.Phase-II trials in osteosarcoma recurrences:A systematic review of past experience[J].Eur J Cancer,2017,75:98-108.
[46]Whelan JS,Bielack SS,Marina N,et al.EURAMOS-1,an international randomised study for osteosarcoma:results from pre-randomisation treatment[J].Ann Oncol,2015,26(2):407-414.
[47]Goldberg JM.Immunotherapy of sarcomas[J].Curr Opin Oncol,2013,25(4):390-397.
[48]Lussier DM,O’Neill L,Nieves LM,et al.Enhanced T-cell immunity to osteosarcoma through antibody blockade of PD-1/PD-L1 interactions[J].J Immunother,2015,38(3):96-106.
[49]Safwat A,Boysen A,Lücke A,et al.Pazopanib in metastatic osteosarcoma:significant clinical response in three consecutive patients[J].Acta Oncol,2014,53(10):1451-1454.
[50]Grignani G,Palmerini E,Ferraresi V,et al.Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment:a nonrandomised phase 2 clinical trial[J].Lancet Oncol,2015,16(1):98-107.
[51]朱兵,李建民,张清,等.我国骨肉瘤治疗现状及改进建议--17家骨肿瘤治疗中心1998~2008年资料分析[J].中国骨与关节杂志,2009,8(3):129-132.
[52]流小舟,于沂阳,施鑫,等.骨肉瘤复发患者的转归及影响长期生存的因素分析--一项基于多中心骨肉瘤复发患者的长期随访研究[J].中华骨科杂志,2018,38(18):1089-1096.
[53]Brandal P,Bjerkehagen B,Bruland OS,et al.Synchronous and metachronous skeletal osteosarcomas:the Norwegian Radium Hospital experience[J].Acta Oncol,2009,48(8):1165-1172.
[54]Iavarone A,Matthay KK,Steinkirchner TM,et al.Germline and somatic p53 gene mutations in multifocal osteogenic sarcoma[J].Proc Natl Acad Sci USA,1992,89(9):4207-4209.
[55]Yamamoto Y,Yamamoto N,Tajima K,et al.Characterization of human multicentric osteosarcoma using newly established cells derived from multicentric osteosarcoma[J].J Cancer Res Clin Oncol,2011,137(3):423-433.
[56]Kimura K,Nakano T,Park YB,et al.Establishment of human osteosarcoma cell lines with high metastatic potential to lungs and their utilities for therapeutic studies on metastatic osteosarcoma[J].Clin Exp Metastasis,2002,19(6):477-485.
[57]Zhang HQ,Li MH,Gao P,et al.Preliminary application of precision genomic medicine detecting gene variation in patients with multifocal osteosarcoma[J].Orthop Surg,2016,8(2):129-138.