Abstract
Historically, patients with localized soft tissue sarcomas (STS) of the extremities would undergo limb amputation. It was subsequently determined that the addition of radiation therapy (RT) delivered prior to (neoadjuvant) or after (adjuvant) a limb-sparing surgical resection yielded equivalent survival outcomes to amputation in appropriate patients. Generally, neoadjuvant radiation offers decreased volume and dose of high-intensity radiation to normal tissue and increased chance of achieving negative surgical margins—but also increases wound healing complications when compared to adjuvant radiotherapy. This review elaborates on the current neoadjuvant/adjuvant RT approaches, wound healing complications in STS, and the potential application of novel radioprotective agents to minimize radiation-induced normal tissue toxicity.
Highlights
Soft tissue sarcomas (STS) are a relatively rare group of malignancies with multiple histological subtypes [1]
Fibroblasts activated by platelets and macrophages migrate into the wound and bind matrix components via their integrin receptor, change morphology, and begin secreting matrix metalloproteinases (MMPs) which clear a path for the fibroblasts movement from the extracellular matrix (ECM) into the wound site [100]
Exogenous superoxide dismutase (SOD) mimetics are a class of compounds that can act as radiosensitizers in cancer cells and radioprotectors in normal cells [160]
Summary
Soft tissue sarcomas (STS) are a relatively rare group of malignancies with multiple histological subtypes [1]. Amputation was the primary treatment modality for can be locally infiltrative with microscopic tumor deposits extending up to 4 cm beyond the STS of theSTS extremities until limb-sparing surgeries combined with radiotherapy (RT) showed similar primary tumor [28,54], limiting the ability of surgeons to preserve limbs without risking microscopic outcomes [55]. While RT acute wound complications and radiation dermatitis [30,36,51,58,59], as well as late toxicities of fibrosis, improves survival and local control outcomes, it increases the risks of acute sequelae including necrosis, edema, pathologic fractures, and long term decrease in limb function [11,30,36,51,52,58,59]. We will examine radiotherapy in STS by radiation modality, clinical regimen (neoadjuvant vs. adjuvant), and anatomic disease site with associated toxicity outcomes
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