Management of Sarcomas Soft Tissue Sarcomas: A Multi-Disciplinary Strategy of Care Darin J. Davidson, MD, MHSc, FRCSC Department of Orthopaedics and Sports Medicine Assistant Professor, University of Washington School of Medicine Orthopedic Oncologist, Seattle Cancer Care Alliance October 25, 2014 Missoula, Montana

CASE STUDY -- 62 year old male with right posterior arm soft tissue mass

Close approximation to radial nerve Close approximation to humerus

Image guided needle biopsy- synovial sarcoma Neoadjuvant chemotherapy Pazopanib trial Neoadjuvant radiation therapy Planned positive margin on radial nerve and humerus No increased risk of local recurrence Preserve function

Excision Negative margin Innervated latissimus flap to restore function

Sarcoma: Multi-disciplinary Team Treatment decisions not made independently by one specialty Essential to have multidisciplinary discussion Surgeon(s) Radiation oncologist Medical oncologist Radiologist Pathologist All have input into management of every case One modality may optimize management of another

SCCA: Multi-disciplinary Sarcoma Program Medical Oncology Orthopaedic Oncology Radiation Oncology General Surgery Jones, Robin Conrad, Ernest ‘Chappie’ Kane, Gabrielle Mann, Gary Loggers, Elizabeth Davidson, Darin Kim, Edward Pillarisetty, Venu Pollack, Seth Lindberg, Antoinette Pathology Radiology Pediatrics Plastic Surgery Hoch, Ben Ha, Alice Hawkins, Doug Neligan, Peter

How to contact us Scheduling Contact: Leslie Fischer Telephone: 206.288.2018 Fax: 206.288.6996 Email: lfischer@seattlecca.org; pccsarcoma@seattlecca.org Nursing Email: sarcomarn@seattlecca.org Darin Davidson Telephone: 206.543.3690 Email: djdavi@uw.edu

Soft Tissue Sarcoma Benign soft tissue masses much more common than malignant masses Approximately 100:1 Red flags for STS vs benign mass Large (>5cm) Deep to fascia Age, presence of symptoms, duration not contributory

Clinical Presentation And Assessment Usually painless mass Pain suggestive of neural origin, rapid growth History- NF, sarcoma associated syndromes (Li-Fraumeni, Retinoblastoma) Key on physical exam Depth of lesion relative to fascia

Imaging MRI is preferred imaging modality Sarcoma suggested by signal intensity heterogeneity Imaging characteristics are not typical of particular type of soft tissue sarcoma Fluid signal may be present in setting of necrosis or hemorrhage

High grade soft tissue sarcoma with areas of hemorrhage and necrosis

Management Local and systemic staging MRI of affected area Biopsy CT chest Mainstay of treatment is surgical resection Adjuvants Radiation therapy Chemotherapy

Indications for Biopsy Aggressive or malignant appearing bone or soft tissue lesions Soft tissue mass- >5cm, deep to fascia or overlying bone or neurovascular structures Except definitive imaging of benign mass (eg. lipoma) Unclear diagnosis in symptomatic patient Solitary bone lesion in a patient with a history of carcinoma Even if fractured!! Just need to confirm not sarcoma

Biopsy Principles An asymptomatic (latent) or symptomatic bone lesion (active) that appears entirely benign on imaging does not need a biopsy A soft tissue lesion that appears entirely benign on MRI (lipoma, hemangioma) does not need a biopsy When in doubt, it is safer to do a biopsy

Biopsy Principles Extensile incision – longitudinal in extremities Tract needs to be excised Avoid developing planes Use involved compartment Do not expose neurovascular structures Meticulous hemostasis Release tourniquet prior to wound closure If using drain, bring out in line with incision For bone lesions, ok to biopsy soft tissue mass Frozen section

Importance of the Biopsy Whatever is exposed to the tumor is potentially contaminated and must be excised at definitive treatment When biopsy principles aren’t followed Increased risk of Wrong diagnosis Altered treatment Altered outcome Complications Local recurrence of STS Mankin et al, 1996 Noria et al, 1996

Surgical Resection Goal is complete resection of tumor with ‘adequate’ margin Definition of adequate margin controversial Use of preoperative radiation can affect extent of margin required Marginal excision of STS- LR >30% Marginal excision of STS after neoadjuvant XRT- LR <10% Consideration for preservation of vital (major nerves, vessels, bone) structures to preserve function Gerrand et al, JBJS-B 2001

Radiation Therapy Neoadjuvant XRT ‘sterilizes’ reactive zone surrounding the tumor Allows for closer margin (still complete resection with negative margin) Preserve critical structures and improve function Neoadjuvant XRT uses lower dose (50 Gy) compared to postop (66 Gy) Decreased fibrosis, edema (Davis et al, JCO 2002) Decreased risk of radiation induced fracture (Holt et al, JBJS-A 2005)

Overall survival comparing preoperative and postoperative XRT, indicating slightly higher overall survival in the preoperative group. O’Sullivan et al, Lancet, 2002

Radiation Therapy The downside to neoadjuvant XRT Higher risk of wound healing complications, infection RCT of neoadjuvant vs adjuvant XRT (O’Sullivan et al, Lancet 2002) comparing wound healing complications requiring return to OR Neoadjuvant XRT 35% Adjuvant XRT 17%

Radiation Therapy Decision between neoadjuvant and adjuvant is balance of risks Edema and fibrosis are not treatable and are disabling Radiation associated fracture can be difficult to treat Wound complications can be managed (may require prolonged treatment, multiple procedures)

Local Control Goal of local treatment is local control Traditional predictors of local recurrence Grade, size, depth Competing risk model demonstrates margin status at resection is the most important predictor of local control (Biau et al, 2012) Multi-modal local treatment

Chemotherapy Role of chemotherapy Role in metastatic disease Controversial for localized disease Meta-analyses have shown slight survival advantage with chemotherapy

Meta-analysis of adjuvant chemotherapy in localized soft tissue sarcoma Lancet , 1997

Hazard ratio of survival for meta-analysis of adjuvant chemotherapy in localized soft tissue sarcoma Pervaiz et al, Cancer 2008

Outcome Outcome best considered on basis of initial disease Localized disease Superficial, low grade ≈ 100% 5 year survival Deep, high grade ≈50% 5 year survival Metastatic disease at presentation (Ferguson et al, Cancer 2010) Pulmonary mets- 8% 5 year survival Lymph node mets- 59% 5 year survival

Soft Tissue Sarcoma Pitfalls Soft tissue sarcoma grow quickly and are painful Synovial sarcoma known for slow growth Well circumscribed, smooth border of mass = benign and infiltrative, irregular border = sarcoma

47 year old male with well circumscribed mass; biopsy proven synovial sarcoma

Fibromatosis

Summary Benign soft tissue masses are far more common than sarcoma, but beware Large mass Deep mass MRI is imaging modality of choice Biopsy principles essential Surgical resection is mainstay of treatment of localized soft tissue sarcoma XRT- consider advantages and disadvantages to preoperative vs postoperative Chemotherapy- slight survival advantage