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Soft tissue sarcomas are a rare and heterogeneous group of solid tumors of mesenchymal origin that account for only 1% of all adult malignancies (AIOM 2021). Wide surgical excision of the tumor, with appropriate negative margins, is the mainstay treatment of localized STS, while neoadjuvant radiotherapy (nRT) – with or without chemotherapy – is recommended in selected high-grade STS (G2-G3) to reduce the stage of large tumors and achieve function-sparing radical excision. nRT may reduce tumor volume and/or make the pseudocapsule thicker and acellular, decreasing the risk of recurrence and seeding during surgical manipulation (Sampath et al). nRT is usually administered in 25 fractions for a total dose of 45 Gy (long-term nRT), but recently short-term administration with hypofractionation in 6 fractions for a total of 36 Gy has been proposed, with comparable effects. Surgery is performed 4-8 weeks after long-term nRT or 2 weeks after short-term nRT (Gronchi et al).Side effects of radiotherapy develop from the first administration and depend on the radiosensitivity of the treated site and the extent of irradiation. These effects are most noticeable in tissues with high cell remodeling, so surgical wounds are particularly exposed to these risks. Short-term wound complications (such as dehiscence, delayed healing, infection) are described in 35% of cases after nRT in STS (AIOM 2021). The main causes can be attributed to cell death, tissue ischemia caused by thrombosis of small vessels, or alterations in inflammatory and tissue healing processes. Radiation alters the normal inflammatory processes of wound healing, inducing an uncontrolled accumulation of extracellular matrix and fibrosis, due to the overexpression of cytokines and growth factors such as VEGF and TGF-beta. (Haubner et al). Increased oxidative stress and reduced metalloproteases result in a slowing of the healing process and scar fragility, while microvascular damage can cause hypoperfusion with ischemic damage, fibrosis, atrophy or necrosis (Haubner et al). The side effects of nRT can also occur in the long term after surgery, with loss of sweat and sebaceous glands, skin atrophy, lymphedema, telangiectasias, difficulty in movement, weakness and pain. (Dormand et al).Our retrospective analysis, conducted on 243 patients, confirmed the incidence of 65% short-term complications (including seroma and dehiscence) and 71% long-term complications in patients undergoing extensive excision for radiotreated limb sarcoma.Several strategies have been proposed to treat radiogenic wounds with delayed or inadequate healing, including the application of special advanced dressings, the administration of nutritional or growth factors, and the use of hyperbaric oxygen therapy (Haubner et al). Negative pressure wound therapy (TNP) involves the application of controlled negative pressure (sub-atmospheric) around both open and closed wounds, with the application of polyurethane fillers and/or disposable medications. TNP may play a role in the treatment of chronic and complicated wounds that do not heal, significantly improving healing by reducing edema or improving blood flow and granulation tissue formation or mechanical edge approximation (Shehata et al).We suggest that preventive application of a single-use NPWT, such as PICO 14 (Smith and Nephew), in patients undergoing radical surgery with primary wound closure, could improve wound care outcomes.We propose the application of a single-use negative pressure dressing (sNPWT) after extensive excision of a radiotreated high-grade limb sarcoma, in order to counteract the side effects of radiation. sNPWT is widely used in the treatment of complicated or non-healing wounds, with interesting effects. We suggest the application of sNPTW after wound closure in the operating room. Afterwards, a regular change of dressing is prevented on the 4th, 8th and 14th post-operative days. Wound characteristics will be assessed based on the ASEPSIS score at each dressing change and then at the 30th postoperative day. The preventive application of sNPTW in patients who received neoadjuvant radiotherapy, followed by surgery, at the level of the surgical wound could significantly contribute to improved wound healing by supporting tissue regeneration.