soft tissue sarcoma

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Slide 1 :

Soft tissue sarcoma management Richard Baker Royal Free Hospital, Departmental Teaching 1st July 2011

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Contents Introduction Epidemiology Types of sarcoma Clinical features Aetiology Diagnosis – imaging & histology Management Surgery Radiotherapy Chemotherapy

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MCQs

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1. STSs Are ectodermal in origin Derive from fibroblasts Arise from multiple germ lines Are from mesenchymal lineage Are mesodermal in origin

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2. Which of these cell types does not give rise to STSs? Merkel cell Fibroblast or myofibroblast Adipocyte Endothelial cell Schwann cell

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3. Average age of diagnosis is 21 years 57 years 65 years 13 years There are two peaks in median age of diagnosis

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4. Incidence of STS in UK is 12, 000 cases per year 120, 000 cases per year 2400 cases per year 24, 000 cases per year 1200 cases per year

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5. Which of these possible aetiologies are STSs not associated with? Peutz-Jeghers syndrome Chlorophenoxy herbicides Tuberous sclerosis Neurofibromatosis Li-Fraumeni syndrome

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6. Preferred imaging for diagnosis of STS is Contrast enhanced CT scanning USS PET scanning MRI MRA

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7. Which of these histological characteristics does not influence STS grade? Cellularity Vascularity Cell subtype Pleomorphism Necrosis

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8. According to AJCC/UICC staging, a stage IIB STS is Low grade, small, superficial or deep High grade, small, superficial or deep Low grade, large, superficial or deep Low grade, small or large, deep High grade, small, superficial or deep

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9. Accepted wide excision margins for STS excision are 2-3cm Whole muscle compartment Whole muscle compartment preserving one muscle and one nerve 1cm Through reactive zone

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10. Follow-up for STSs should be Longer in low grade tumours Longer in high grade tumours Annually for 10 years Less than 8 years Depends on type

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Introduction Greek meaning ‘fleshy growth’ Heterogeneous Mesodermal origin Rare, < 1% of all malignant tumours 50% mortality Differentiating benign from possibly malignant lesions can be difficult Benign:malignant ratio is 100:1 (upper limb)

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Introduction II GP will see about 1 case every 24 years of practice Prognosis related to size at presentation Early recognition, referral to a specialist and appropriate treatment improve outcomes Delays in referral MDT

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Epidemiology 1% adult / 10-15% child malignancies 1200 cases/yr/UK Differentially affects Caucasians & males 60-70yrs 60% in extremities (2/3 LL; 1/3 UL) Significant morbidity & mortality

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Types of Soft Tissue Sarcoma Type Myxofibrosarcoma Liposarcoma Leiomyosarcoma Rhabdomyosarcoma Angiosarcoma Malignant peripheral nerve sheath tumour Synovial sarcoma Ewing’s sarcoma origin Fibroblast or myofibroblast Adipocyte Smooth muscle Skeletal muscle Endothelial cell Schwann cell Unknown Unknown

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History and examination

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Clinical features Often non-specific Commonest painless mass ± recent growth Misdiagnosis (infection / ganglion / lipoma) Varied appearance / consistency, but usually appear encapsulated

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Signs of malignancy Any soft tissue lump exhibiting any 4 clinical features malignant until proved otherwise: increasing in size size >5cm deep to the deep fascia (fixed with muscle contraction) Painful (Recurrence after excision) More features = greater risk of malignancy Increasing size best indicator

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Aetiology Usually no obvious aetiology Known associations with: Environment -radiation exposure -chemicals (chlorophenoxy herbicides) Genetics -tuberous sclerosis -neurofibromatosis -Li-Fraumeni syndrome Immunosuppressive states Chronically oedematous limbs

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Diagnosis of Soft Tissue Sarcomas

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Any patient with suspected STS should be referred to diagnostic centre for triple assessment (& discussed in MDT) clinical history imaging biopsy

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Imaging

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Imaging I Plain X rays (extremity + chest) soft tissue calcification in 1/3 Ultrasound CT (staging) Head/neck/chest MRI preferred for assessment of lesion

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Imaging II for special circumstances Angiography Radionuclide scanning

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Tissue diagnosis

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Biopsy Core needle biopsies (multiple) – preferred Surgeon or radiologist Incisional Excisional – superficial, <5 cm FNAC useful for suspected recurrence Plan so biopsy tract removed with specimen to prevent seeding

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Histology & Grading Histology – ie type Grade – cellularity, differentiation, pleomorphism, Mitotic rate, vascularity, cell:stroma ratio, necrosis Histological classification based on similarity to normal soft tissues Grade more important - correlates with survival No universally agreed grading system

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Grading In Europe, the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system is generally used Because of tumour heterogeneity, a core biopsy may not provide accurate information about grade Before and after surgery

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FNCLCC histological grading criteria Sum of the three scores gives grade: Grade 1 – 2,3, grade 2 – 4,5 ; grade 3 -6,7,8

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Pathology report Royal College of Pathologists recommend record: Margins - intralesional, marginal, wide, or radical Distance from edge of specimen Presence of an anatomical barrier

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Pathology guidelines Freeze tumour samples for future research new molecular assessment techniques may become available that could yield new information Assessment of tumour response to therapy

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Staging To direct treatment and determine prognosis Several staging systems described Enneking Musculoskeletal Tumor Society (MSTS) American Joint Commission on Cancer (AJCC) MSKCC (AJCC/UICC) combined

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AJCC TNM classification(2002) TNM incorporating grade = GTNM G: G1 or G2 and G3 or G4 T: Tx, T0, T1<5cm a – superficial, b - deep; T2a & b >5cm N: Nx, N0 no nodal disease N1 nodal disease (histo) M: Mx, M0 no metastases M1 distant metastases

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Staging – AJCC/UICC (combines grade and TNM classification) 1A Low grade, small, superficial or deep (T1 a-b, N0, M0) 1B Low grade, large, superficial (T2a, N0, M0) IIA Low grade, large, deep (T2b, N0, M0) IIB High grade, small, superficial or deep (T1a-b, N0, M0) IIC High grade, large, superficial (T2a, N0, M0)

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AJCC/UICC Stage III High grade, large, deep (T2b, N0, M0) Stage IV Any metastasis (any T, N1, or M1)

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Enneking staging (Musculoskeletal Tumour Society staging system) Widely used in extremity sarcomas Stage 1 - low grade A - intra-compartmental B - extra-compartmental Stage 2 - high grade A - intra-compartmental B - extra-compartmental Stage 3 - regional or distant metastases (Clin Orthop 1980, 1986)

Slide 39 :

Key Recommendations (UK guidelines) MRI and core needle biopsy prior to definitive sx CT thorax for lung metastases prior to radical tx All patients with suspected STS should be managed by Sarcoma MDT (NICE)

Slide 40 :

Management of soft tissue sarcomas

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Main therapeutic goals Long-term survival Avoidance of local recurrence Maximising function Minimising morbidity

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Surgery Surgical WLE ± adjuvant (mainly radio-) therapy Primary amputation largely historical Several types excision: -intra-capsular (enucleation) -marginal (limited margin) -wide local -radical-compartmental -functional compartmental (1 m, 1 n)

Slide 43 :

Margins

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Why wide local excision? Satellite lesions Local extension along NV bundles Fascial planes

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Surgery - margins Excise tumour with margin of normal tissue Accepted as 1 cm soft tissue or equivalent (e.g., a layer of fascia) But if critical anatomical structures would be sacrificed leave a planned microscopic positive surgical margin (+/- Dxt) Discuss pros & cons with patient

Slide 46 :

Sarcoma surgery today Evolved to limb sparing resection If +ve margins, consider re-excision or amputation Functional reconstruction (microsurgical)

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Surgery cont: Borderline resectable tumours – consider down staging treatment (neo-adjuvant) Dxt/chemo depending on histo + pt Amputation sometimes most appropriate option to obtain local control and cure

Slide 48 :

European Society of Medical Oncology (ESMO) recommend’ns IA & IB - Surgery: wide excision IIA - Sx: WE ± adjuvant Dxt IIB & IIC - Sx: WE ± Dxt or compartmental resection III - Sx: WE ± Dxt or compartmental resection (+/- chemo) IV (local recurrence) - Sx: WE ± Dxt or compartmental resection (+/- chemo) [+/- ILP]

Slide 49 :

ILP Isolated Limb Perfusion may permit limb salvage in some cases where amputation is the only conventional surgical approach

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Radiotherapy Variable response depending on type Neo-adjuvant (low dose) 6/52 Adjuvant 6/52 to reduce risk local recurrence -Brachytherapy -implants -shorter treatment -External beam – longer treatment

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Chemotherapy Variable response depending on type Role unclear Neo-adjuvant may shrink primary allowing resection Adjuvant may reduce recurrence / death Palliative for mets / resection lung nodules

Slide 52 :

Prognosis and Follow-up

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Prognosis and follow-up Research needed Prognosis related to grade, depth, size, type, age Local recurrence related to grade, margins, Dxt Events most likely to occur within 5 yrs High grade tumours – f/up 8 yrs min Low grade tumours more likely to recur late so f/up longer

Slide 54 :

European Society for Medical Oncology guidelines Year since diagnosis High grade tumours 1-3 4-5 More than 5 Low grade tumours 3-5 More than 5 Frequency of follow-up 3-4 months 6 months Annually 4-6 month Annually

Slide 55 :

References Grimer, Judson, Peake, Seddon. Guidelines for the Management of Soft Tissue Sarcomas. Sarcoma; Volume 2010, Article ID 506182, 15 pages Sinha, Howard, Peach. Diagnosis and management of soft tissue sarcoma. BMJ; JANUARY 2011, VOL 342 , 157-162

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Management of soft tissue sarcoma, aimed at plastic surgeons
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