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1、成人软组织肉瘤化疗成人软组织肉瘤化疗Contents lOverviewlDrugslTreatmentneoadjuvant chemotherapyadjuvant chemotherapyAdvanced or metastatic diseases chmeotherapytargeted therapyContents lOverviewlDrugslTreatmentneoadjuvant chemotherapyadjuvant chemotherapytargeted therapylSarcomas constitute a heterogeneous group of ra
2、re solid tumors oflmesenchymal cell origin with distinct clinical and pathological featuresl成人软组织肉瘤（成人软组织肉瘤（Soft tissue sarcomas，STSs），包），包括一组发病相对较少，组织学多样的恶性肿瘤。括一组发病相对较少，组织学多样的恶性肿瘤。l起源中胚层和外胚层。起源中胚层和外胚层。l占成人恶性肿瘤的占成人恶性肿瘤的1%和儿童恶性肿瘤的和儿童恶性肿瘤的5%。l尚无特别有效的治疗方法，需多学科联合。尚无特别有效的治疗方法，需多学科联合。Categories lSarcomas
3、of soft tissues(including fat,muscle,nerve and nerve sheath,blood vessels,and other connective tissues)l Sarcomas of bone.The anatomic site of the primary diseaselExtremities(60%)l the trunk(19%)l retroperitoneum(15%)lhead and neck(9%)Risk factorslAge.Soft tissue sarcomas can occur at any age,but ov
4、erall are more common in older adults.The average age at diagnosis is 57 years.Certain types of sarcomas are more common in children,however.lChemical exposure.Being exposed to certain chemicals,such as vinyl chloride and dioxin,can increase the risk of soft tissue sarcomas.lRadiation exposure.Previ
5、ous radiation treatment for other cancers can increase the risk of soft tissue sarcomas.Signs and symptomsla new lump or a lump that is growing anywhere in the body may or may not cause pain may include abdominal swelling or a lump in the abdomenlnausea lvomiting lheartburn labdominal pain lblood in
6、 vomit or stoolAdult soft tissue sarcoma diagnosedlIncisional biopsy:The removal of part of a lump or a sample of tissue.lCore biopsy:The removal of tissue using a wide needle.lExcisional biopsy:The removal of an entire lump or area of tissue that doesnt look normal.core needle biopsyPathology and s
7、taginglthe type of soft tissue sarcoma lthe stage of the cancer(how far the cancer has progressed)lthe grade of the tumour(how abnormal the cancer cells look and behave)lPleomorphic sarcoma also known as malignant fibrous histiocytoma(MFH)l GISTslLiposarcomal leiomyosarcomal synovial sarcomal malign
8、ant peripheral nerve sheath tumorsIncidence of Soft Tissue Sarcoma Subtypes(1978-2001)Histologic Subtype%平滑肌肉瘤23.9恶性纤维组织细胞瘤17.1脂肪肉瘤11.5皮肤纤维肉瘤10.5横纹肌肉瘤4.6血管肉瘤4.1Sites of MetastasisGadd M,et al,Ann Surg,1993Contents lOverviewlDrugslTreatmentneoadjuvant chemotherapyadjuvant chemotherapytargeted therapy
9、Chemotherapy lSingle Agents DoxorubicinIfosfamideDacarbazineGemcitabinePaclitaxelDocetaxelChemotherapyPemetrexedTemozlomideIrinotecanTopotecanPelyated liposmal doxorubicinTrabectedinDoxorubicinlThe single agent response rates(RR)are in the range of 20 to 30%lsurvival in the range of 7.7-12 months lT
10、he best response rates are seen with dosages in the range of 75 mg/m 2 to 90 mg/m 2 DoxorubicinlEpirubicin is a less cardiotoxic analog of doxorubicin,which failed to demonstrate any benefit as compared to doxorubicinlliposomal doxorubicin can be used in patients where doxorubicin is contraindicated
11、,but the response rates of this drug as a single agent are lower than the conventional doxorubicin.Ifosfamidela dose-response relationship and higher doses can be used as it lacks cardiotoxicity lmonotherapy with an identical dose(9 g/m 2),given over three days,by either continuous infusion or three
12、-hour infusions daily Dacarbazinelin combination with doxorubicin and ifosfamide(MAID)lgiven as a short infusion of 1.2 g/m 2 over 20 minutes with the availability of effective antiemetics.TemozolamidelTemozolamide,the oral equivalent of dacarbazine,appears to have the same activity against leiomyos
13、arcoma as well.Trabectedin(Ecteinascidin-743,ET743,Yondelis)lThis tetrahydroisoquinsoline molecule was derived originally from a tunicate,or sea squirt,Ecteinascidia turbinate(found in the Carribbean and Mediterranean waters)lA pooled analysis of 183 patients from the three single arm phase II studi
14、esl1.5 mg/m 2 administered as a 24-hour infusion once every three weekslIn this analysis though the ORR was only 7.7%,the rate of tumor control(i.e.,ORR plus minor responses plus disease stabilization)was 51%.Contents lOverviewlDrugslTreatmentneoadjuvant chemotherapyadjuvant chemotherapyAdvanced or
15、metastatic diseases chmeotherapytargeted therapyTreatmentlsurgery Surgery is the most common treatment for many soft tissue sarcomas.Depending on the size and location of the sarcoma,all or part of the tumour may be removed.If the whole tumour is removed,a wide margin of healthy tissue around it is
16、also removed.In many cases,limb-sparing surgery can be done for a soft tissue sarcoma that occurs in an arm or leg and amputation can be avoided.However,in some cases,soft tissue sarcoma in a limb may require the limb to be amputated.lradiation therapy Radiation therapy may be used before or after surgery or,less commonly,instead of surgery.lchemotherapy If the soft tissue sarcoma has spread to other parts of the body,chemotherapy may be used to control the cancer and relieve symptoms.Chemothera
