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Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
Soft tissue sarcomas
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Soft tissue sarcomas

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  • SMAC- sarcoma meta analysis collaborationEORTC- european organization for reasearch and treatment of cancer.
  • Transcript

    • 1. SOFT TISSUE SARCOMAS Dr. Nikhil S.
    • 2.  Rare 1% - 2 per 100,000 persons (US)  Derived from mesenchymal tissue.  Diverse anatomically, histologically and by risk of metastasis.  Male: female = 1.1 : 1.0  Median age 50-55 years  Natural history determined by:  Anatomic location  Size  Depth  Pathological characteristics.
    • 3.  Extremities and torso: Local control good; death from lung mets 2-3 years later.  H&N: LC more difficult than extremity.  Retro peritoneum: Continued local recurrence many years after treatment.
    • 4. ETIOLOGY  Herbicide exposure  Constitutional and hormonal factors during childhood puberty and adulthood.  HIV: non-AIDS defining neoplasm.  Chemical: Thorotrast,Vinyl Cl, As.  Trauma: Study inTHR patients.  Radiation exposure: poor survival as compared to sporadic.Children: RB.  Usually in the perimeter.  RT in breast cancer: 1.5 fold increased chance of STS.  9 fold increase for angiosarcoma and MFH.  Lymphoedema: lymphangiosarcoma.
    • 5. Molecular Pathogenetic mechanisms  Simple Karyotypic sarcomas with specific genetic alterations: 1/3rd.  Translocations  Only 1 cytognentic abnormality.  Synovial sarcoma t(X;18)(p11;q11) distinguishes from MPNST.  Complex Karyotypic sarcomas without specific genetic alterations- 2/3rd.  Lacks genetic signatures  Most adult spindle cell, pleomorphic sarcoma, LMS.  High prevalence ofTP- 53, MDM-2 amplification, deletion of CDKn-2A
    • 6. Clinical features  Extremities and superficial trunk: 60%  Painless primary soft tissue mass.  Retroperitoneum: 15%  Abdominal mass  Pain:50%  Grows to large size before symptoms.  Viscera:15%  GIST: anemia, malena, abd pain, wt loss.  Uterine LMS: painless P/V bleed.  H&N: 10%  Smaller  Mechanical problems: compression or invasion of adjacent critical structures.
    • 7. WHO classification I. Fibrous tumors A. Fibromatoses 1.Superficial fibromatoses i. Palmar and plantar(dupuytren’s contrcture) ii. Penile(peyronie’s disease) iii. Knuckle pads 2. Deep fibromatoses i. Abdominal fibromatoses(Desmoid) ii. Extra abdominal desmoid iii. Intra abdominal desmoid iv. Mesenteric v. Infantile B. Fibrosarcoma 1. Adult fibrosarcoma 2. Inflammatory fibrosarcoma 3. Myxofibrosarcoma.
    • 8. Classification (contd.) II. Fibrohistiocytic tumors 1. Dermato Fibro sarcoma Protruberans 2. Heterogenous tumors without specific differentiation(Forme rly MFH) i. Undifferentitaed pleomorphic sarcoma. ii. Undifferentiated pleomorphic sarcoma with giant cells with inflammation. iii. Angiomatoid MFH.
    • 9. Classification (contd.) III. Lipomatous tumors 1. Atypical lipoma 2. Liposarcoma i. Well differentiated a. Lipoma like b. Sclerosing c. Inflammatory ii. Dedifferentited liposarcoma iii. Myxoid or round cell LS iv. Pleomorphic LS IV. Smooth muscle 1. Leiomyosarcoma 2. Epitheloid LMS V. Skeletal Muscle 1. RMS i. Embryonal ii. Botryoid iii. Spindle call iv. Alveolar v. Pleomorphic 2. RMS with ganglionic differentiation(Ectomesenchy moma)
    • 10. Classification (contd.) VI. Blood and lymph vessels 1. Epitheloid hemangioendothelioma. 2. Angiosarcoma nd lymphangiosarcoma 3. Kaposi’ s sarcoma VII. Malignant perivasular tumors 1. Malignant glomus tumor or glomangiosarcoma. 2. Malignant hemangio pericytoma VIII. Malignant synovial tumors 1. Malignant GCT of tendon sheath. IX. Malignant neural tumors 1. MPNST (Neurofibrosarcoma) 2. Malignant granular cell tumor 3. PNET(primitive NET) i. Neuroblastoma ii. Ganglioneuroblastoma iii. nauroepithelioma
    • 11. Classification (contd.) X. Paraganglionic tumors 1. Malignant paraganglioma XI. Extra skeletal Cartilaginous and oseeous tumors 1. Extra skeletal chondrosarcoma a. Myxoid b. Mesenchymal 2. Extraskeletal osteosracoma XII. Pluripotential malignant mesenchymal tumor 1. Malignant mesenchymoma 2. Alveolar soft part sarcoma 3. Epitheloid sarcoma 4. Malignant extra renal rhabdoid tumor 5. Desmoplastic small cell tumor 6. extraskeletal Ewing s sarcoma 7. Clear cell sarcoma 8. GIST 9. Synovial sarcoma
    • 12.  Myxofibrosarcoma  Myxoid variant of MFH.  Malignant fibroblastic lesion with variable myxoid stroma.  One of the MC sarcomas  Arising in the limbs of elderly adults.  Slowly enlarging painless mass.  MC sites of metastases are lung, bone and lymph nodes.
    • 13.  So- called fibrohistiocytic tumors:  This concept is challenged now.  Merely in histological appearance.  None of them show histiocytic differentiation.  DFSP  Low grade- recur locally, but rarely metastasize.  Slow and persisitent growth.  Unpredicted radial extensions.  Stains positive for CD34.  Response with Imatinib.
    • 14.  High grade undifferentiated pleomorphic sarcoma/ pleomorphic MFH.  Was the MC diagnosed STS in some series in past.  Now reserved for those undifferentiated Pleomorphic sarcomas with no line of differentiation by current technology.  Aggressive course  Many develop metastasis within 3 years of diagnosis.
    • 15.  Liposarcoma  20% of all STS  MC in thigh and retroperitoneum.  Three principal groups: 1. Atypical lipomatous tumour/ WD LS and dedifferentiated LS a. Adipocytic (lipoma like) b. Sclerosing c. Inflammatory d. Spindle cell. 2. Myxoid or round cell LS 3. Pleomorphic LS
    • 16.  Leiomyosarcoma  Malignant tumors composed of spindle cells  Showing smooth muscle features.  Location: Retroperitoneal, intra abdominal pelvic sites, MC uterus.  Smooth muscle actin and desmin.  Grading of LMS difficult.  Large tumor size, high grade and high mitotic rate are the prognostic factors.
    • 17.  Rhabdomyosarcoma  Embryonal:  Small cell tumor.  Orbit or genito urinary tract of children.  Botyriod type usually in the mucosa lined visceral organs- vagina and urinary bladder- polypoid tumour.  Also seen in adults.  But poorer prognosis than in chidren.  Alveolar type:  Extremities  Young adults and adolescents.
    • 18.  Angiosarcoma:  Malignant tumor with cells that resemble morphologically and functionally endothelial cells.  No clear distinction of those from lymphatics and capillaries.  Sometimes assoc with lymphedema.  Stewart treve syndrome: lymphangiosarcoma of skin in the lymphedematous arm post mastectomy and XRT.
    • 19.  MPNST:  Rare sporadically  But 8 to 13% in those with NF-1  Affect major nerves of extremities or chest wall.  Originate from nerve sheath.  Most are high grade  Stain positive for S-100  MPNST with RMS elements termedTriton tumor.
    • 20.  Synovial sarcoma:  Spindle cell tumor  Young adults 15-35 yrs of age  80% in extremities, 10 % in H&N  Unrelated to synovium.  Monophasic or biphasic.  Stain positive for keratin, vimentin, S- 100+/-  Epitheloid sarcoma  Unknown lineage  Adolescent and young adults  Extremity and perineal area  Tends to propogate along tendon and nerve sheaths.  Lung and lymph nodal metastasis common.  5 year survival 66%.
    • 21. Staging AJCC 7th Ed.  T1: </= 5 cm  T1a: Superficial tumor  T1b: deep tumor  T2: >/= 5cm  T2a: superficial  T2b: Deep  Stage IA:T1a/1b N0M0 Gx/G1  Stage IB:T2a/2b N0M0 Gx/G1  Stage IIA:T1a/1b NoM0 G2/G3  Stage IIB:T2a/2b N0M0 G2  Stage III:T2a/2b NoM0 G3 or N1  Stage IV: M1
    • 22. Prognostic factors 1. Tumor grade 2. Anatomic site 3. Tumor size 4. Depth 5. Histological subtype 6. Age  Sarcoma specific nomogram (Kattan et al)  Risk stratification in GIST byAFIP strategy(Armed Forces institute of pathology)  These staging systems prognostify patients for the risk of distant metastasis and/or mortality.  Risk of local recurrence is not predicted by these factors.
    • 23. Grading  Grading more significant than histo subtype  French federation of cancer centre three tire system (FNCLCC)  Parameters: 1. Differentiation score 2. Mitoses 3. Necrosis.  Greatest limitation is the differentiation score.  NA in case of undiff. tumors.  In some tumors no adnl info e.g. w/d LS, ewing  Some ungradable e.g. epitheloid, clear cell, angiosarcoma.  No diff in prognosis- MPNST.
    • 24.  US national cancer institute(NCI) system  AJCC uses French system.
    • 25. Screening and diagnosis  No screening tests. Incidence too low.  Physical exam: 1. Size of the mass 2. Mobility 3. Superficial vs deep 4. Relation to nearby NV and bony structures. 5. Regional lymph nodes.  Biopsy  Symptomatic, enlarging, >5cm or beyond 4to 6 weeks. 1. Percutaneous a. FNA- sub optimal b. Core biopsy 2. Open biopsy. a. Incisional b. Excisional: <3cm
    • 26.  Retroperitoneal mass:  Usually biopsy not required if radiographically resectable or suspecting GIST.  Biopsy indicated: 1. Unresectable disease 2. Suspicion if lymphoma or GCT. 3. Tissue diagnosis for NACT or RT. 4. Suspected mets from another primary.
    • 27. Imaging: primary site  Primary:  CT or MRI of the local site- extremity or H&N.  MRI preferred: enhances the contrast btw tumor and muscle; and with blood vessels.  Also provides multi planar definition of the lesion.  Abdominal- Spiral CT to know the relation with neuro-vascular structures.  Pelvic lesions: MRI may provide superior single modality imaging.  Role o f PET not well defined. Correlates well with CECT.  PET frequently fails to distinguish benign lesions from low grade sarcomas.
    • 28. Imaging: metastatic sites  Chest X ray: for low grade lesions <10 cm or intermediate or high grade<5cm.  CT to look for lung Mets.  Common in extremity lesions.  Retroperitoneal lesions- liver Mets.  Lymph node mets rare 3.7%  Higher in RMS, epitheloid, angiosarcoma.
    • 29. Treatment
    • 30. Rx localized disease  Surgical resection  Earlier radical ablative surgeries- amputation and compartmental resection  Now limb sparing surgeries-Wide local Excision with pre-op and/or post op XRT.  Newer advances in Sx- Micro vascular tissue transfer  Bone and joint replacement.  Vascular reconstruction.
    • 31.  STS tend to expand and form a pseudo capsule with normal tissue and tumor fimbriae.  SoWLE with a rim of normal tissue required- 30% LR without adj. Rx.  If smallT1, low grade extremity lesion, LR<10%.  Though high grade, <5cm tumors, No diff seen with adj. XRT.  LargeT2- limb sparing Sx + irradiation.
    • 32. Surgical details  Skin, sub cut.Tissue, soft tissue adjacent to tumor (2 to 3 cm margin if possible)  Any assoc drainage sites should be resected.  Bone, NV structures if adjacent may be spared adj. XRT.  If grossly involved resected en-bloc and reconstructed.  Metal clips.  Regional lymphadenectomy has no role.  If clnically or radiographically nodes are detected, should be resected in C/O embyonal RMS, angio, epitheloid ,synovial.
    • 33. radiotherapy  Pre-op RT  Advantages: 1. Small RT portals 2. Produce tumor encapsulation, allowing easy resection from vital structures. 3. Easier to spare a strip of skin. 4. Size decreased. So less amount of resection needed. 5. Lower XRT dose. 50Gy Drawbacks 1. Precise staging not possible. 2. Increased wound healing issues.
    • 34.  Post Op XRT  60 to 65 Gy over 6 to 7 weeks.  Local control 70 to 90%  Survival 70%  Limb preservation 85%  Similar rates as that of amputation.  Interstitial therapy  Ir192  As boost after EBRT 20 to 25 GY  or in place of EBRT 40 to 45 Gy.  Local control 82% vs.69% for surgery alone.
    • 35. Indications for post op XRT 1. Limb conservation or limited surgery. 2. Gross residual tumor or inadequate excision margins. 3. Grade 2 and 3 histology 4. Tumor 5 cm or more in any dimension. 5. Virtually all tumors in H&N.
    • 36. comparison  Comparable LC rates ~ 90% with pre-op, post- op or interstitial XRT.  Wound complications increased with Pre-op XRT.  If interstitial, adv is the short Rx time. 10-12 days.  Post OP EBRT takes 10 to 12 weeks (post op gap of 4-6 wk + XRT for 6-7 wk)
    • 37. Primary radiation therapy  In unresectable cases.  5year survival of 25- 40% ad LC 30%.  LC depends primarily on the size.  Atleast 65 to 70Gy  Location of the tumor important  Because of the potential for damage to sensitive structures like spinal cord.
    • 38. Retroperitoneal sarcomas  Only 50 % able to undergo complete resection.  Of these, 50% develop local recurrence.  Role of RT remains controversial due to lack of data, rarity and low doses used in many studies.  Pre-op XRT  Adv: Bowel is displaced by the tumor.  Hence less of bowel is treated, less GI toxicity.  Conformal techniques may also be used.
    • 39.  Intra-op XRT  Prospective trial by NCI  IORT foll by low dose EBRT(30-40Gy) vs. post op EBRT 35 to 40 Gy and 20 Gy boost.  Absolute LR rates were lower (p<0.05)  Post OP XRT  Doses used in extremities cannot be used here.  Most tumors are large 10 to 15cm.  3D planning and conformal techniques can be used to minimze bowel in field.
    • 40. Isolated limb perfusion  Agents MC used are melphalan andTNF-a  With or without interferon-Y-1b.  Extrapolated from protocols for melanoma.  Now approved in europe for treatment of grade 2/3 extremity sarcomas.  NetherlandsCancer institute: 63% of patients had overall response.  Toxocity was frequent but mild.
    • 41. Chemotherapy  Pre-operative  Generally ifosfamide and adriamycin containing regimes. 1. Reduction in tumor size surgical resection with less morbidity 2. Better compliance  Masachussets general hospital: 5 year freedom from distant metastasis 75% vs 44%(p=0.001)  5 year disease fee survival and overall survival was also significant.  Increased wound healing problem with chemo arm.  RTOG phase II study also with similar results.
    • 42.  Post operative chemo  Six studies- adriamycin.  All studies with patients<100  CyVADIC regime used in most.  No survival advantage could be demonstrated d/t inadequate statistical power.  Ifosfamide not studied in studies before 2000. only 1 study.  Italian co-operative group: 104pts- closed.  interim analysis showed sign. Survival advantg for chemotherapy patients.  Not reproduced in the EORTC or SMAC trials.
    • 43. Treatment of local recurrence  LR in 10 to 50% of patients after ~24 months.  Higher for Retroperitoneal(40%) and H&N(50%) vs low for extremity(10%).  Re-operation after staging evaluation.  2/3rd of patients experience longterm survival.  Adjuvant RT:  if previous RT was not given  or previous dose was sub-therapeutic  or previous fields allow further treatment.  Isolated limb perfusion.
    • 44. Treatment of limited pulmonary metastasis  Thoracotomy and metstatectomy  3 year survival is 23 to 42 %  Indicated if: 1. Primary tumor is controlled or controllable 2. Complete resection appears to be possible 3. No extra thoracic disease 4. No medical C/I.  Pre- resection chemotherapy- sometimes recommended.  No definitve proof that it helps in better resection.
    • 45. Unresectable and metastatic  Chemotherapy is the mainstay.  Single agents: 1. Doxorubicin 2. Pegylated lipodox 3. Ifosfamide 4. Dacarbazine 5. Ecteinascidin (trabectidin)  Combination chemotherapy:  Anthracycline plus an alkylating agent, dacarbazine or both.  Doxorubicin plus ifosfamide  CyVADIC  MAID
    • 46.  Combination vs single agent:  Superior response  But no survival advantage.  Pts can achieve more benefit when these agents are given sequentially than by combinations.  Gemcitabine plus docetaxel  Gemcitabine plus vinorelbine  Kinase targeted agents.
    • 47. Prognostic factors for response to therapy 1. absence of liver metastasis. 2. Younger age 3. High grade 4. liposarcoma  Better survival with; 1. Good PS 2. Absence of liver mets 3. Low grade 4. Young age 5. Long time to metastasize after primary treatment.
    • 48. THANK YOU 

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