Soft tissue sarcoma

Extremity Soft Tissue Sarcoma : Extremity Soft Tissue Sarcoma Asawadech Sanbua 23/6/53

Slide 2 : Rare malignancies Arise from the connective tissues, any organ any anatomic location of the body.

Anatomy : Anatomy Midarm : anterior and posterior compartments Midforearm : volar and dorsal compartments

Slide 4 : (C) Midthigh : the anterior, medial, and posterior compartments (D) Midleg : anterior, lateral, posterior, and deep posterior compartments

Epidemiology, Genetics, and Risk Factors : Epidemiology, Genetics, and Risk Factors M > W African Americans > whites. Sporadic fashion, without identifiable etiology. Associated factors : Predisposing genetic mutations : Previous ionizing radiation or chemical exposures : chronic soft tissue injury or lymphedema

Slide 6 : The Li-Fraumeni Hereditary retinoblastoma Neurofibromatosis type 1 (NF1, von Recklinghausen's neurofibromatosis) Ionizing radiation exposure produces a small but detectable risk of both bone and soft tissue sarcoma.

Slide 7 : First reported in the 1920s : workers painting radium watch dials After therapeutic irradiation, reported since the 1930s : 2 -25 years within the radiation portal , histologically distinct from the primary malignancy The median latency period was 14 years, and risk was increased after high radiation doses. Absolute risk of postirradiation sarcoma with long-term follow-up was 0.03% . Most commonly : After radiation therapy for breast cance Radiation-induced sarcomas

Natural History : Natural History Local extension along muscular compartments. Fascial planes, bone : rarely violated and constitute barriers to local spread. Grossly lesions : encapsulated Subclinical disease : infiltrate adjacent tissues, extending 5 to 10 cm beyond the pseudocapsule

Slide 9 : Biopsy : change the pattern of spread if they violate an uninvolved compartment or if an extensive hematoma results . Trunk or head and neck regions : more commonly invades adjacent structures High-grade sarcomas :lymph nodes involved in <10% Routine lymph node sampling is usually not performed SCARE : Synovial cell sarcoma, clear cell sarcoma, angiosarcoma, rhabdomyosarcoma, epithelioid sarcoma : high rates of nodal spread

Slide 10 : Hematogenous metastases : High-grade sarcomas; most occur in the lungs The median time to metastasis : 1 year Metastasis >5 years after initial diagnosis is not uncommon

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Clinical Presentation : Clinical Presentation Growing, painless mass. Several-month delays in presentation to a physician Numbness, pain, or edema : tumor-induced neurovascular compromise.

Clinical Evaluation : Clinical Evaluation History : family history and previous radiation exposure. Physical examination : size, location, and depth (superficial or deep) Diagnostic imaging before tissue diagnosis : Guidance for appropriate biopsy technique.

Slide 14 : MRI: Soft tissue masses and excellent soft tissue detail CT: Bony invasion or destruction. CXR or CT chest : Distant metastases, for high-grade disease.

Slide 15 : A: Computed tomography scan in the axial plane. B: T1-weighted magnetic resonance image (with fat saturation) after contrast enhancement

Slide 16 : Biopsy should be performed by an experienced surgeon. Excisional biopsies should be avoided Incision for biopsy: along the longitudinal axis of the extremity

Staging : Staging

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Prognostic Factors : Prognostic Factors For distant metastasis and survival : grade Distance metastasis : Tumor size and depth , MPNST or leiomyosarcoma

Slide 21 : Risk factors for local recurrence : Surgical margin(+) Increased local recurrence risk : Age >50 years Locally recurrent disease MPNST or fibrosarcoma histology Presence of symptoms at presentation Deep location Withholding of radiation therapy

General Management : General Management Multimodality treatment

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Surgery : Surgery Four categories of surgical procedures An intralesional procedure : partial tumor removal with violation of the pseudocapsule; planned incisional diagnostic biopsy ; not an appropriate therapeutic procedure. A marginal procedure (simple excision or ?shellout) : removes the tumor within the confines of the pseudocapsule ; high likelihood of local recurrence due to residual subclinical disease .

Slide 31 : Wide local excision :tumor removed with a margin of normal tissue from within the same muscle compartment without removal of the entire structure of origin. Radical excisions :including compartmental resections and most amputations, remove the entire tumor and the structure of origin (entire anatomic compartment) en bloc.

Slide 32 : Local recurrence rates after surgery alone range from <10% after radical excision to 80% after marginal excision Amputation : Salvage of local recurrence after previous conservative resection and radiation therapy

Slide 33 : Surgical scars and drain sites : Risk for subclinical disease Surgical clip placement : For radiation treatment planning Prophylactic bone stabilization in anticipation of circumferential bone irradiation may reduce risk of subsequent fracture

Chemotherapy : Chemotherapy Anthracyclines (doxorubicin and epirubicin) : response rates of 15% - 25% in metastatic disease Single-agent ifosfamide : similar response rates Ifosfamide + anthracycline : higher response rates than those without ifosfamide

Radiation Therapy : Radiation Therapy External beam Brachytherapy Intraoperative electron beam Intensity-modulated radiation therapy (IMRT) Proton or other charged particle radiation

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Slide 37 : Adjuvant radiation therapy : Improve local control for both low- and high-grade tumors.

Slide 38 : Preop CCRT Preop XRT + concurrent hyperthermia Iododeoxyuridine or other radiosensitizers High linear energy transfer radiation (fast neutrons) Isolated limb perfusion with tumor necrosis factor-a, melphalan, and interferon- ? Improve local control rates in unresectable disease

Radiation Therapy Techniques : Radiation Therapy Techniques Design an immobilization CT scan the immobilized for radiotherapy planning Define the target volume(s) (on each section of the CT/MRI of the affected region). Define non-target critical structures in the treatment volume Estimate the distribution of number of tumor clonogens/unit volume of tissue throughout the target volume. Define a series of target volumes Design treatment techniques

Slide 40 : Avoid inclusion of an entire joint space. Avoid full dose irradiation of adjacent bone : reduce the risk of pathological fracture. Utilize wedges and tissue compensators : account for tissue heterogeneities and minimize dose inhomogeneity. Review the treatment plan at multiple levels along the extremity to assess dose homogeneity to the target and normal tissues

Compartmental Nature of Soft Tissue Sarcomas : Compartmental Nature of Soft Tissue Sarcomas Evaluate the extent of tumor involvement in the muscle compartment Surgical clip placement

Volume at Risk : Volume at Risk Postoperative setting : Some authorities recommend : entire compartment (origin to insertion) : hematoma in muscle compartment . Margins : < 5 cm - 15 cm (in the long axis of the extremity), based on the grade and size of the tumor .

Slide 43 : 5-10 cm : large grade-1 and small grade-2 10-15cm : large grade-2 to -3 lesions Regional lymph nodes are rarely at risk in extremity sarcomas Prophylactic lymph node irradiation is not benefit.

Positioning the Extremity : Positioning the Extremity Anterior compartment of the thigh : ?frog-leg position, with external hip rotation, separating the anterior compartment from the medial and posterior compartments.

Slide 45 : Posterior compartment of thigh : lateral decubitus position, with the affected thigh closest to the couch with flexion of the uninvolved extremity

Slide 46 : Anterior compartment of the arm (biceps) : shoulder abducted approximately 90 degrees and maximally internally rotated

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Slide 48 : Body part must be immobilized : foam cradle, plaster mold, or thermoplastic cast Limb secured above and below the treatment area : reduce the possibility of rotation in the cradle.

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Slide 50 : A: A custom-made foam cast immobilization with the patient in a lateral decubitus position demonstrates positioning that is frequently used for patients with posterior thigh or leg sarcoma. B: A custom-made foam cast immobilization with the patient's shoulder abducted approximately 90 degrees and maximally internally rotated (with the elbow flexed) is frequently used for patients with biceps sarcoma.

Treatment Planning : Treatment Planning Post op XRT Postop XRT: Resection bed + generous margins. Reduced fields : Preoperative tumor volume + smaller margins.

Slide 52 : CTV : Gross + subclinical (microscopic) disease. Postoperative CTV : Resection bed (defined by placement of surgical clips and consultation with the surgeon) + preop tumor volume (based on preoperative imaging) + extension of potential subclinical disease. : Cover resection bed + 3-6-cm margin, as well as the surgical scar and drain sites. Boost CTV : preoperative tumor volume + smaller 2- to 3cm margins.

Preop XRT : Preop XRT Preop XRT : Gross tumor + margin No field reduction is made prior to surgery Preoperative CTV : visible gross tumor volume + 3- 6 cm margin Preoperative PTV : CTV + 1 cm or more for extremity targets.

Slide 54 : If the scar is being struck tangentially by the irradiation fields, no bolus is necessary. If the scar is being irradiated with a direct perpendicular field, bolus should be applied Scar

Slide 55 : A = 1 cm strip of soft tissue in the circumference of the extremity : spared to avoid subsequent edema. Avoid circumferential bone radiation : to reduce fracture risk, and to minimize joint irradiation

Slide 56 : A large target volume extended from the left inguinal region inferiorly and medially along the thigh in a patient after resection of a high-grade soft tissue sarcoma of the sartorius muscle. (A): Six gantry angles were selected for intensity-modulated radiation therapy treatment planning to achieve the desired target coverage while limiting dose to uninvolved bone and soft tissue. (B,C and D) The isodose distributions of the intensity-modulated radiation therapy plan are shown from superior and more inferior axial slices of the planning scan.

Slide 57 : Thin regions of anatomy (e.g., hand, foot, and forearm) : Bolus to the entire treatment volume

Slide 58 : Treatment of the involved region inside a water bath : uniform dosage to the affected area

Slide 59 : With meticulous technique, limb-sparing surgery with adjuvant radiation therapy can be safely applied

Radiation Energy and Dose : Radiation Energy and Dose Lower energy (6-MV) photons : higher energies could potentially spare too much superficial tissue Postop XRT : 45 - 50 Gy + cone downs to 60 - 66 Gy 1.8- or 2.0-Gy daily fractions.

Slide 61 : Preop XRT: 45 to 50 Gy 2 to 4 weeks before resection with an intraoperative or postoperative boost as indicated by the surgical margin.

Slide 62 : Brachytherapy or intraoperative radiation therapy : combination with preoperative or postoperative EBRT EBRT 36 - 50 Gy + perioperative LDR or HDR brachytherapy 12 - 25 Gy Brachytherapy alone : 42 to 50 Gy. Unresectable sarcomas : brachytherapy alone doses >70 Gy

Truncal and Head and Neck Sarcomas : Truncal and Head and Neck Sarcomas Tumors on the chest wall and abdominal wall : oblique tangential fields. 45 Gy of photon irradiation + electron boost to the surgical bed Head and neck : 3DXRT and IMRT

Interstitial Brachytherapy : Interstitial Brachytherapy After surgical excision of the tumor Hollow plastic afterloading catheters are inserted using sharp metal trocars in a single plane at approximately 1-cm intervals within the tumor bed Surgical clips placed at the margin Catheters are secured in place. Orthogonal localization films : 2 to 4 days after surgery, Catheter positions : digitally recorded into a radiation therapy planning system.

Slide 65 : Demonstration of brachytherapy catheter placement after resection of soft tissue sarcoma involving the medial and distal thigh, which had recurred after resection alone.

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Slide 68 : CTV : clipped tumor bed + 2-cm margin The dose is prescribed to 5 to 10 mm from the implant plane. 6th postoperative day : reduce the risk of wound complications. After completion of the treatment, sources are removed and catheters are cut at one end for removal by pulling through the skin.

Slide 69 : LDR LDR implants :42 - 45 Gy used alone for high-grade lesions EBRT 45-50 Gy + LDR implant 15 - 25 Gy HDR HDR implants: twice daily at 2 - 5 Gy per fraction to 35 to 50 Gy when used alone EBRT 45-50 Gy + HDR implant 15 - 20 Gy

Results of Standard Treatment : Results of Standard Treatment Local control : intermediate and high-grade sarcomas s/p Sx + XRT 80% - 90% Limb-sparing, wide local excision, and meticulous radiation therapy techniques : high-grade lesions, a local control rate of ~ 85% Overall survival : relates to the development of distant metastases.

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Slide 72 : Metastasis-free survival in a cohort of 300 patients treated between 1982 and 1989, based on the 5th edition of the American Joint Committee on Cancer staging system. (From Wunder JS, Healey JH, Davis AM, et al. A comparison of staging systems for localized extremity soft tissue sarcoma. Cancer 2000;88:2721-2730, with permission.)

Unresectable Sarcomas : Unresectable Sarcomas Neutron radiation Carbon ion beam Photon radiation + radiosensitizing iododeoxyuridine High linear energy transfer radiation (fast neutrons) Isolated limb perfusion with tumor necrosis factor-a, melphalan, and interferon- ?

Treatment of Metastatic Disease : Treatment of Metastatic Disease Metastatic + controlled primary tumors : complete surgical resection of pulmonary metastases may be potentially curative Disease-free survival rates of 40% at 3 years The role of radiation therapy : palliation

Aggressive Fibromatosis and Dermatofibrosarcoma Protuberans : Aggressive Fibromatosis and Dermatofibrosarcoma Protuberans Aggressive fibromatosis (desmoid tumor) and dermatofibrosarcoma protuberans (DFSP) soft tissue neoplasms , never metastasize but very invasive locally. Desmoids arise within the muscle or its fascial coverings DFSPs arise within the dermis. Complete surgical excision alone : curative

Slide 76 : Desmoid tumors Postop X RT : improved local control of positive margins or gross residual disease Local recurrence :re-excised XRT alone : 50 - 55 Gy Tumor responses are rarely seen in <6 months Nonsteroidal antiinflammatory agents, hormonal agents, cytotoxic chemotherapy, and imatinib

Slide 77 : DFSP XRT enhances local control in patients with positive margins after surgery, or as sole treatment

Sequelae of Treatment : Sequelae of Treatment The most significant short-term toxicity of radiation therapy for sarcomas :moist desquamation in the high-dose volume. Major wound complications (delayed wound healing or need for surgical intervention) ~ 5% - 15% after Sx + postop XRT and perhaps more commonly with preopXRT.

Slide 79 : The long-term sequelae after conservative Sx+ XRT : Limit the function of the preserved limb : Decrease in range of motion related to fibrosis : Contracture of the joint : Edema : Pain : Bone fracture.

Slide 80 : Joint spaces should be excluded after a dose of 40 to 45 Gy to avoid fibrotic constriction of joint capsules. Truncal sarcomas : cone down fields to limit the dose to normal tissues deep to the target volume (e.g., lung and bowel)