We enrolled patients with primary STS who underwent wide resection and immediate reconstruction between January 2011 and December 2019. Patients were excluded if they underwent delayed reconstruction or distant metastasis was observed at the time of the first diagnosis.

Each patient’s case and treatment policy was discussed by our institution’s multidisciplinary sarcoma tumor board comprising surgeons, diagnostic radiologists, pathologists, medical oncologists, and radiation oncologists. The resection procedures were most commonly performed by orthopedic surgeons. Reconstructive procedures were performed by plastic surgeons, and the reconstruction modality was determined by the attending surgeon considering the patient’s general health, preference, defect location, and defect size. Postoperative sarcoma surveillance was mostly undertaken by orthopedic surgeons and by a medical oncologist when neoadjuvant or adjuvant chemotherapy and/or radiotherapy were required. Physical examinations and imaging workups, such as computed tomography or magnetic resonance angiography, were performed every 3 months for the first year postoperative, every 6 months thereafter until postoperative 5 years.

Patient demographic data and clinical outcomes were gathered from a prospectively maintained database and electronic medical records. Patient characteristics including age, sex, body mass index (BMI), comorbidities (hypertension and diabetes), smoking status, and American Society of Anesthesiologists physical status (ASA PS) classification at the time of surgery were collected. Tumor characteristics included location, histologic subtype, size, and Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) histologic grade. Tumor size was classified according to the T (size) classification of the American Joint Committee on Cancer guidelines, 8th ed. Operation-related characteristics included margin status after final resection and the type of reconstruction procedure (local flap, free flap, or skin graft). In addition, data on whether neoadjuvant or adjuvant chemotherapy and/or neoadjuvant or adjuvant radiotherapy was administered were collected. Patients with hypertension were defined as those taking antihypertensive medication at the time of surgery. Diabetes patients were defined as those taking oral diabetes medication and/or insulin at the time of surgery. Smokers were defined as active smokers at the time of surgery.

The development of postoperative complications in the reconstructed area and the presence of sustained systemic inflammation were also assessed. Postoperative complications included an emergency return to the operating room due to a threatened flap, total flap or graft loss, partial flap or graft loss, delayed wound healing, seroma, venous thrombosis, and infection. Dehiscence was defined as an open wound requiring surgical debridement. Seroma was defined as fluid accumulation requiring aspiration and/or revision surgery. Venous thrombosis comprised postoperative deep vein thrombosis caused by a thrombus in the legs as well as pulmonary embolism. Infection was defined as the requirement for oral or intravenous antibiotics and/or surgical irrigation and debridement within 6 months of immediate reconstruction. If the C-reactive protein (CRP) level was not elevated or the infection was restricted to the reconstructed area, it was classified as a local infection, whereas if the CRP level increased or the infection spread to another part of the body, it was classified as a systemic infection. Among patients who developed postoperative complications, those with elevated CRP levels (>1.0 mg/dL) in laboratory tests until 2 weeks postoperative [6] were defined as having inflammatory postoperative complications. Patients were categorized into three groups based on the development of postoperative complications, with or without systemic inflammation: no complications, noninflammatory complications, and inflammatory complications.

The primary outcomes of interest were prognostic outcomes, which were identified from medical records. Prognostic outcomes including recurrence date and type (local and/or regional node and distant), date of the last follow-up, and disease status at that time were documented. The final follow-up date was that on which the patient had last visited the orthopedic surgeon or medical oncologist’s outpatient clinic for cancer surveillance or the date of death. Disease-free survival (DFS) was calculated as the time interval from the date of the first diagnosis to any type of the first occurrence of disease progression or death.

The baseline characteristics were compared between groups categorized by the development of postoperative inflammatory complications. Pearson chi-square test or Fisher exact test was used to analyzing categorical variables. Continuous variables were analyzed using the Mann-Whitney U-test, one-way analysis of variance, or the Kruskal-Wallis test. Survival curves for DFS were calculated and presented using the Kaplan-Meier method, and differences among the postoperative inflammatory complication groups were calculated using the log-rank test. For the DFS curve, STS recurrence and death during follow-up were analyzed. Patients were censored if relevant events did not occur during the follow-up period. Uni- and multivariate Cox regression analyses were performed to identify independent prognostic factors for oncological outcomes, with results expressed as hazard ratios (HR) and 95% confidence intervals (CI). A backward selection model was used for the multivariate analyses. The p-values <0.05 were considered statistically significant. All statistical analyses were conducted using IBM SPSS Statistics ver. 27.0 (IBM Corp., Armonk, NY, USA).