Annals of Oncology20(Supplement4):iv140–iv142,2009
doi:10.1093/annonc/mdp155 clinical recommendations
Ewing’s sarcoma of the bone:ESMO Clinical Recommendations for diagnosis,treatment and
follow-up
M.Paulussen1,S.Bielack2,H.Ju¨rgens3&P.G.Casali4
On behalf of the ESMO Guidelines Working Group*
1Department of Pediatric Oncology and Hematology,University Children’s Hospital Basel,Switzerland;2Department of Pediatric Oncology and Hematology, Olgahospital,Stuttgart;3Department of Pediatric Hematology and Oncology,University Children’s Hospital Mu¨nster,Mu¨nster,Germany;4Department of Cancer Medicine,Istituto Nazionale dei Tumori,Milan,Italy
incidence
Ewing sarcoma(ES)/primitive neuroectodermal tumor(PNET) of bone is the second most common primary malignant bone cancer in children and adolescents,but is also seen in adults, particularly the extraskeletal variety.The median age at diagnosis is15years and there is a male predilection of1.5/1. ES is diagnosed in white Caucasians at an incidence of
0.3/100000per year,but is very uncommon in the African and Asian population.
diagnosis
Thefirst symptom of bone ES is usually pain—often erroneously attributed to trauma.Plain radiographs in two planes,complemented by computed tomography(CT)and/or magnetic resonance imaging(MRI)are indicative of
a malignant tumor.Before biopsy patients with suggestive亚克力纸巾盒
findings should be sent to a reference centre with particular experience in the disease.The definitive diagnosis is made by biopsy,providing sufficient material for conventional histology, immunohistochemistry and molecular biology(fresh,unfixed material).ES is a small blue round-cell tumor,PAS-and CD99 (MIC2)-positive.All ES are high-grade tumors.While the degree of neuronal diff
erentiation used to be applied to distinguish between classical ES and PNET,molecular biology studies have now shown that all these tumors share a common gene rearrangement involving the EWS gene on chromosome 22,so that this distinction is now obsolete.In most cases,
a reciprocal translocation t(11;22)(q24;q12)is found,but t(21;22)(q22;q12)and others may also occur[t(7;22),t(17;22) and t(2;22)translocations and inv(22)].
staging and risk assessment
Before biopsy,the description of the local extent of a bone tumor requires radiographic and CT/MRI of the entire involved bone,including adjacent joints and soft tissues.For planning of local therapy,the precise involvement of bone, bone marrow and soft tissues including the relationship to critical structures like nerves or vessels,must be specified.A chest CT scan is required to rule out lung or pleural metastases. The assessment for bone and bone marrow metastases is to include99mTc bone scintigraphy,to detect osseous metastases, and light microscopical examination of bone marrow aspirates and biopsies taken at sites distant from the primary tumor. Positron emission tomography(PET)scanning for bone metastases and PCR techniques to investigate for bone marrow metastases are sensitive methods currently under evaluation. Additional appropriate imaging studies
and biopsies should be taken from suspicious sites,as the exact staging of the disease has an impact on treatment and outcome[III,B].
About20%of patients have ES of the pelvic bones,while 50%show extremity tumors.ES may involve any bone and(less commonly in non-adult patients)soft tissues.Between20% and25%of the patients are diagnosed with metastatic disease (10%lung,10%bones/bone marrow,5%combinations or others).
With surgery or radiotherapy alone,5-year survival is<10%. With treatment in current multimodality trials including chemotherapy,survival is 60–70%in localized and 20–40% in metastatic disease.Bone metastases confer a poorer outcome than lung/pleura metastases(<20%compared with20–40%5-year survival)[IIa,B].Other known prognostic factors are tumor size or volume,serum lactate dehydrogenase(LDH) levels,axial localization or older age(>15years).Under treatment,poor histological response to preoperative chemotherapy,and incomplete or no surgery for local therapy are further adverse prognostic factors[IIa,B].
*Correspondence to:ESMO Guidelines Working Group,ESMO Head Office,Via
L.Taddei4,CH-6962Viganello-Lugano,Switzerland;
E-mail:
Approved by the ESMO Guidelines Working Group:August2002,last update
December2008.This publication supercedes the previously published version—Ann
Oncol2008;19(Suppl2):ii97–ii98.
Conflict of interest:Prof.Paulussen and Prof.Ju¨rgens have reported no conflicts of
interest.Dr Bielack has not reported any conflicts of interest.Dr Casali has reported that
he is currently conducting research sponsored by Pfizer and Schering Plough.
ªThe Author2009.Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.For permissions,please email:journals. by guest on April 9, 2012 / Downloaded from
1工业除湿机treatment plan
As ES is a rare cancer,and its management is complex,the accepted standard is treatment in reference centres or within reference networks.
localized disease
Multimodal approaches within clinical trials,employing combination chemotherapy and surgery and/or radiotherapy, have raised5-year survival rates from<10%to>60%.All current trials employ three to six cycles of initial chemotherapy after biopsy,followed by local therapy and another six to ten cycles of chemotherapy usually applied at3-week intervals. Treatment duration is thus8–12months.Agents considered most active include doxorubicin,cyclophosphamide, ifosfamide,vincristine,dactinomycin and etoposide.Virtually all active protocols are based on four-to six-drug combinations of these substances.Protocols that have proved to be most effective include at least one alkylating agent(ifosfamide or cyclophosphamide)and doxorubicin[Ib,A].
Despite lively debate,complete surgery,where feasible,is regarded as the best modality of local control.Radiotherapy should be applied if complete surgery is impossible,and should be discussed where histological response in the surgical specimen was >10%viable tumor cells)[IV,C].In one large series it was found that incomplete surgery followed by radiotherapy was not superior to ra
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diotherapy alone. Radiotherapy is applied at doses of40–45Gy for microscopic residues and50–60Gy for macroscopic disease[III,B]. Treatment of patients with extraskeletal ES follows the same principles as for bone ES.Criteria for pathologic tumor response assessment are less established.Radiation therapy is used more extensively after surgery.
Treatment of adult patients follows the same principles. However,tolerability of therapies in adults needs to be taken into account when transferring treatment protocols conceived for children and patients of age£30–40years.
metastatic and recurrent disease
Outside specific clinical trials,patients with metastatic disease ought to receive similar therapy to that given for localized disease,with appropriate local treatment of metastases, commonly applied as radiotherapy.Several non-randomized trials have assessed the value of more intensive,time-compressed or high-dose chemotherapy approaches,followed by autologous stem cell rescue,but evidence of benefi resulting from randomized trials,is lacking[III,B].In patients with lung metastases,the resection of residual metastases after chemotherapy,and possibly whole lung irradiation,may confer a survival advantage[III,B].Patients with bone or bone marrow metastases and patients with recurrent disease still fare poorly,with5-year survival rates of£20%.
The only prognostic factor identified in relapse seems to be time to relapse:patients relapsing later than2years from initial diagnosis have a better outcome[III,B].Doxorubicin therapy is usually no longer feasible due to previously achieved cumulative doses.Chemotherapy regimens in relapse situations are not standardized and are commonly based on alkylating agents(cyclophosphamide,ifosfamide)in combination with topoisomerase inhibitors(etoposide,topotecan)or irinotecan with temozolomide[III,B].
follow-up
Most relapses occur in thefirst3years of follow-up;late relapses have rarely been observed even after15years or longer. Besides the detection of relapse,long-term sequelae of treatment are the main concern in long-term follow-up. Impaired renal function may be observed early in follow-up, but cardiac or pulmonary damage may become apparent later. Secondary cancers may arise in irradiated sites.Secondary leukemia,particularly acute myeloid leukemia may rarely be observed independent of previous irradiation as early as2–5 years after treatment[III,B].Follow-up intervals should be2–3 months during thefirst3years,6months until5years and at least once yearly thereafter.
note
Levels of evidence[I–V]and grades of recommendation[A–D] as used by the American Society of Clinical Oncology are given in square brackets.Statements without grading were considered justified standard clinical practice by the experts and the ESMO faculty.
literature
1.Bacci G,Ferrari S,Bertoni F et al.Prognostic factors in nonmetastatic Ewing’s
sarcoma of bone treated with adjuvant chemotherapy:analysis of359patients at the Istituto Ortopedico Rizzoli.J Clin Oncol2000;18:4–11.
2.Bernstein ML,Devidas M,Lafreniere D et al.Intensive therapy with growth factor
support for patients with Ewing tumor metastatic at diagnosis:Pediatric Oncology Group/Children’s Cancer Group Phase II Study9457:a report from the
Children’s Oncology Group.J Clin Oncol2006;24:152–159.
自行车防盗架
释放器3.Pinkerton CR,Bataillard A,Guillo S et al.Treatment strategies for metastatic
Ewing’s sarcoma.Eur J Cancer2001;37:1338–1344.
4.Cotterill SJ,Ahrens S,Paulussen M et al.Prognostic factors in Ewing’s tumor of
bone:analysis of975patients from the European Intergroup Cooperative Ewing’s Sarcoma Study Group.J Clin Oncol2000;18:3108–3114.
5.Nesbit ME Jr,Gehan EA,Burgert EO et al.Multimodal therapy for the
management of primary,nonmetastatic Ewing’s sarcoma of bone:
a long-term follow-up of thefirst Intergroup study.J Clin Oncol1990;8:
1664–1674.
6.Burgert EO Jr,Nesbit ME,Garnsey LA et al.Multimodal therapy for the
management of nonpelvic,localized Ewing’s sarcoma of bone:Intergroup study IESS-II.J Clin Oncol1990;8:1514–1524.
7.Grier HE,Krailo MD,Tarbell NJ et al.Addition of ifosfamide and etoposide to
standard chemotherapy for Ewing’s sarcoma and primitive neuroectodermal tumor of bone.N Engl J
Med2003;348:694–701.
8.Schuck A,Ahrens S,Paulussen M et al.Local therapy in localized Ewing tumors:
results of1058patients treated in the CESS81,CESS86,and EICESS92trials.
Int J Radiat Oncol Biol Phys2003;55:168–177.
9.Bacci G,Forni C,Longhi A et al.Long-term outcome for patients with non-
0663.usmetastatic Ewing’s sarcoma treated with adjuvant and neoadjuvant
chemotherapies:402patients treated at Rizzoli between1972and1992.Eur J Cancer2004;40:73–83.
10.Paulussen M,Ahrens S,Craft AW.Ewing’s tumors with primary lung metastases.
Survival analysis of114(European Intergroup)Cooperative Ewing’s Sarcoma Study patients.J Clin Oncol1998;16:3044–3052.
Annals of Oncology clinical recommendations
Volume20|Supplement4|May2009doi:10.1093/annonc/mdp155|iv141 by guest on April 9, 2012 / Downloaded from
11.Cangir A,Vietti TJ,Gehan EA et al.Ewing’s sarcoma metastatic at diagnosis.
Results and comparisons of two intergroup Ewing’s sarcoma studies.Cancer 1990;66:887–893.
12.EURO-E.W.I.N.G.99treatment manual euro-ewing.klinikum.uni-
muenster.de/(last accessed18June2008).13.Wagner LM,McAllister N,Goldsby RE et al.Temozolomide and intravenous
irinotecan for treatment of advanced Ewing sarcoma.Pediatr Blood Cancer 2007;48:132–139.
14.Bernstein M,Kovar H,Paulussen M et al.Ewing’s sarcoma family of tumors:
current management.Oncologist2006;11:503–519.
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