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BACKGROUND. The authors studied a dose‐intense regimen of epirubicin and ifosfamide with hypofractionated preoperative radiotherapy for high‐risk soft tissue sarcomas. The primary objective was estimation of the rate of ≥95% pathologic necrosis. METHODS. Twenty‐five patients with intermediate‐grade or high‐grade, localized soft tissue sarcomas of the extremity or body wall measuring >5 cm were treated with epirubicin at a dose of 30 mg/m2/day on Days 1 to 4 and ifosfamide at a dose of 2.5 g/m2/day on Days 1 to 4 every 21 days for 3 preoperative and 3 postoperative cycles. A total of 28 grays of radiation was administered over 8 fractions during Cycle 2 of preoperative therapy (epirubicin was omitted). RESULTS. Sixteen patients (64%) completed all chemotherapy cycles and the average delivered dose intensity relative to intended therapy was 69%. Twenty‐one patients (84%) experienced grade 4 toxicity (using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 2.0]), which was predominantly hematologic. Notable toxicities included neutropenic fever (40%), ifosfamide‐induced encephalopathy (24%), and grade 3/4 anemia (64%). Postoperative wound complications requiring a surgical procedure occurred in 20% of patients. The rate of ≥95% pathologic necrosis was 40% (95% confidence interval [95% CI], 21–59%). Estimates of 2‐year overall and disease‐free survival were 84% (95% CI, 66–100%) and 62% (95% CI, 37–86%), respectively. CONCLUSIONS. A high rate of ≥95% pathologic necrosis was noted with this aggressive chemoradiotherapy regimen. The occurrence of significant acute toxicities limited the delivery of the intended dose intensity. Cancer 2008. ©2008 American Cancer Society.

Clear cell sarcoma (CCS) is a rare but highly malignant tumor of soft tissues often appearing as a small tender mass in the deep tissues of the distal extremities. We have studied 17 patients with such lesions treated since 1986 and have a high incidence of local recurrence and metastasis with a survival rate of only 47% despite surgery and for many of the patients, adjuvant therapy. The purpose of this article is to warn the readers of the dangers related to treating this seemingly benign lesion and urge them to perform wide surgery and utilize adjuvant therapy.

Purpose We performed a phase I trial of the addition of sorafenib to a chemoradiotherapy regimen in patients with high-risk (intermediate/high grade, >5 cm) extremity soft tissue sarcoma (STS) undergoing limb salvage surgery. We conducted a correlative study of quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess response to treatment. Experimental Design Patients were treated at increasing dose levels of sorafenib (200 mg daily, 400 mg daily, 400 mg BID) initiated 14 days prior to 3 preoperative and 3 postoperative cycles of epirubicin/ifosfamide. 28 Gy of radiation was administered during cycle 2 with epirubicin omitted. The primary objective was to determine the maximum tolerated dose (MTD) of sorafenib. DCE-MRI was performed at baseline, after 2 weeks of sorafenib, and prior to surgery. The imaging data were subjected to quantitative pharmacokinetic analyses. Results 18 subjects were enrolled, of which 16 were evaluable. The MTD of sorafenib was 400 mg daily. Common grade 3–4 adverse events included neutropenia (94%), hypophosphatemia (75%), anemia (69%), thrombocytopenia (50%), and neutropenic fever/infection (50%). 38% developed wound complications requiring surgical intervention. The rate of ≥95% histopathologic tumor necrosis was 44%. Changes in DCE-MRI biomarker ΔKtrans after 2 weeks sorafenib correlated with histologic response (R2=0.67, p = 0.012) at surgery. Conclusion The addition of sorafenib to preoperative chemoradiotherapy is feasible and warrants further investigation in a larger trial. DCE-MRI detected changes in tumor perfusion after 2 weeks of sorafenib and may be a minimally-invasive tool for rapid assessment of drug effect in STS.

Background Compressive osseointegration is as an alternative to traditional intramedullary fixation. Two-to 10-year survivorship and modes of failure have been reported; however, as a result of relatively small numbers, these studies are limited in their ability to identify risk factors for failure. Questions/purposes (1) What is survivorship free from aseptic mechanical and survivorship free from overall failure of compressive osseointegration fixation? (2) What patient factors (age, sex, body mass index [BMI], anatomic location of reconstruction, indication for reconstruction, radiation, chemotherapy) are associated with increased risk of failure?Methods Between 2006 and 2014, surgeons at one center treated 116 patients with 137 Compress 1 implants for lower extremity oncologic reconstructions, revision arthroplasty, and fracture nonunion or malunion. One hundred sixteen implants were available for review with a minimum of 2-year followup (mean, 4 years; range, 2-9 years). Kaplan-Meier survival plots were produced to examine survivorship and Cox regression modeling was used to generate hazard ratios (HRs) for potential risk factors for failure. Patient factors (age, sex, BMI, anatomic location of reconstruction, indication for reconstruction, radiation, chemotherapy) were obtained from chart review and an institutional database. Results Survivorship free from aseptic mechanical failure was 95% (95% confidence interval [CI], 91%-99%) at 18 months and 93% (95% CI, 86%-99%) at 4 years. Survivorship free from overall failure was 82% (95% CI, 75%-89%) at 18 months and 75% (95% CI, 66%-84%) at 4 years. Risk of overall failure was increased with reconstruction of the proximal tibia (HR, 4.42;) and distal femur (HR, 1.74; 95% CI, 0.50-6.09) compared to the proximal femur (HR, 1; referent; p = 0.049). Risk of aseptic mechanical failure was increased with reconstruction of the proximal tibia (HR, 1; referent) and distal femur (HR, 0.37; 95% CI, 0.08-1.77) compared with the proximal femur (HR, 0, p = 0.048). Radiation was associated with increased risk of overall failure (HR, 3.85; 95% CI, 1.84-8.02; p \ 0.003), but not aseptic mechanical failure. Age, sex, BMI, chemotherapy, and surgical indication were not associated with increased risk of aseptic or overall failure. Conclusions This study questions the use of age as a contraindication for the use of this technology and suggests this technology may be considered in proximal femoral reconstruction and for patients with indications other than

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IMPORTANCEThe use of perioperative, prophylactic, intravenous antibiotics is standard practice to reduce the risk of surgical site infection after oncologic resection and complex endoprosthetic reconstruction for lower extremity bone tumors. However, evidence guiding the duration of prophylactic treatment remains limited.OBJECTIVE To assess the effect of a 5-day regimen of postoperative, prophylactic, intravenous antibiotics compared with a 1-day regimen on the rate of surgical site infections within 1 year after surgery.DESIGN, SETTING, AND PARTICIPANTS This randomized clinical superiority trial was performed at 48 clinical sites in 12 countries from January 1, 2013, to October 29, 2019. The trial included patients with a primary bone tumor or a soft tissue sarcoma that had invaded the femur or tibia or oligometastatic bone disease of the femur or tibia with expected survival of at least 1 year who required surgical management by excision and endoprosthetic reconstruction. A total of 611 patients were enrolled, and 7 were excluded for ineligibility.INTERVENTIONS A 1-or 5-day regimen of postoperative prophylactic intravenous cephalosporin (cefazolin or cefuroxime) that began within 8 hours after skin closure and was administered every 8 hours thereafter. Those randomized to the 1-day regimen received identical saline doses every 8 hours for the remaining 4 days; patients, care providers, and outcomes assessors were blinded to treatment regimen. MAIN OUTCOMES AND MEASURESThe primary outcome in this superiority trial was a surgical site infection (superficial incisional, deep incisional, or organ space) classified according to the criteria established by the Centers for Disease Control and Prevention within 1 year after surgery. Secondary outcomes included antibiotic-related complications, unplanned additional operations, oncologic and functional outcomes, and mortality. RESULTSOf the 604 patients included in the final analysis (mean [SD] age, 41.2 [21.9] years; 361 [59.8%] male; 114 [18.9%] Asian, 43 [7.1%] Black, 34 [5.6%] Hispanic, 15 [2.5%] Indigenous, 384 [63.8%] White, and 12 [2.0%] other), 293 were randomized to a 5-day regimen and 311 to a 1-day regimen. A surgical site infection occurred in 44 patients (15.0%) allocated to the 5-day regimen and in 52 patients (16.7%) allocated to the 1-day regimen (hazard ratio, 0.93; 95% CI, 0.62-1.40; P = .73). Antibiotic-related complications occurred in 15 patients (5.1%) in the 5-day regimen and in 5 patients (1.6%) allocated to the 1-day regimen (hazard ratio, 3.24; 95% CI, 1.17-8.98; P = .02). Other secondary outcomes did not differ significantly between treatment groups.CONCLUSIONS AND RELEVANCE This randomized clinical trial did not confirm the superiority of a 5-day regimen of postoperative intravenous antibiotics over a 1-day regimen in preventing surgical site infections after surgery for lower extremity bone tumors that required an endoprosthesis. The 5-day regimen group had significantly more antibiotic-related complications.

Background Wound complications are common after resection of soft tissue sarcomas, with published infection rates ranging from 10% to 35%. Multiple studies have reported on the atypical flora comprising these infections, which are often polymicrobial and contain anaerobic bacteria, and recent studies have noted the high prevalence of anaerobic bacterial infections after soft tissue sarcoma resection [26,35]. Based on this, our institution changed clinical practice to include an antibiotic with anaerobic coverage in addition to the standard first-generation cephalosporin for prophylaxis during soft tissue sarcoma resections. The current study was undertaken to evaluate whether this change was associated with a change in major wound complications, and if the change should therefore be adopted for future patients. Questions/purposes (1) After controlling for potentially confounding variables, was the broadening of the prophylactic antibiotic spectrum to cover anaerobic bacteria associated with a lower odds of major wound complications after soft tissue sarcoma resection? (2) Was the broadening of the prophylactic antibiotic spectrum to cover anaerobic bacteria associated with a lower odds of surgical Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research® neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA approval status, of any drug or device before clinical use.