Sarcoma

Epidemiology and Etiology

Sarcomas of the soft tissues, bones, and joints are estimated to account for 16,730 new cases and 16,830 deaths in the year 2020.¹ Predisposing factors include age, prior radiation, chemical and chemotherapy exposure, genetic/hereditary syndromes, Paget disease of the bone, HIV/human herpesvirus 8 (HHV8) infection (Kaposi sarcoma), and chronic lymphedema (lymphangiosarcoma [Stewart-Treves syndrome]).

Pathology

Soft tissue sarcomas consist of at least 70 different types of histologies. Review by a pathologist who has expertise in the diagnosis of sarcoma is recommended.

Clinical Presentation

Symptoms depend on the site of disease. Sarcomas arising in extremities can present as a painless soft tissue mass. Visceral sarcomas can be associated with GI bleeding, early satiety, dysphagia, dyspepsia, or vaginal bleeding depending on the organs involved. Retroperitoneal tumors may result in early satiety, nausea, paresthesias, or an abdominal mass.

Diagnostic Testing

Initial imaging studies include MRI for sarcomas involving the extremities or pelvis, and CT for retroperitoneal or visceral sarcomas. PET CT may be useful in staging high-grade sarcomas. Chest imaging with CT is important to rule out pulmonary metastases, which is the most common site of distant disease in sarcomas.

Staging

TNM staging is specific to the sarcoma histology and sites of disease. Additionally, the tumor grade

(taking into account the degree of differentiation, mitotic count, and necrosis score) factors into the stage of disease.

TREATMENT

• Early stage, nonvisceral soft tissue sarcomas (stages I-III): Surgical excision is the mainstay of therapy. Adjuvant radiotherapy is often indicated in patients with large tumors and positive or equivocal margins when re-excision is not feasible. Neoadjuvant and adjuvant chemotherapy may be considered in select cases.³¹

• Metastatic soft tissue sarcoma: Palliative chemotherapy is the primary mode of treatment. Doxorubicin, ifosfamide, gemcitabine, docetaxel, dacarbazine, eribulin, and trabectedin are commonly used. Targeted agents may also include crizotinib, ceritinib, or brigatinib (if ALK translocation present); larotrectinib and entrectinib (if NTRK gene fusion present); as well as pazopanib, sorafenib, sunitinib, bevacizumab, pexidartinib, imatinib, palbociclib, sirolimus, ripretinib, avapritib, everolimus, and temsirolimus in certain subtypes of sarcoma.³¹ Metastasectomy can be considered in patients with oligometastatic disease.

• GI stromal tumors (GIST) commonly harbor mutations in KIT and are highly responsive to imatinib. Adjuvant and/or neoadjuvant imatinib may be considered in select patients.

• Ewing sarcoma differs from many soft tissue sarcomas in that it has a high cure rate and highly responsive to chemotherapy and radiation. Metastatic disease can be potentially cured with chemotherapy in some cases.