Dataset Information

Comparison of Prophylactic Intravenous Antibiotic Regimens After Endoprosthetic Reconstruction for Lower Extremity Bone Tumors: A Randomized Clinical Trial.

ABSTRACT:

Importance

The 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 measures

The 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.

Results

Of 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.

Trial registration

ClinicalTrials.gov Identifier: NCT01479283.

SUBMITTER: Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) Investigators

PROVIDER: S-EPMC8739829 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and objectivesFunctional outcomes are important for oncology patients undergoing lower extremity reconstruction. The objective of the current study was to describe patient reported function after surgery and identify predictors of postoperative function in musculoskeletal oncology patients undergoing lower extremity endoprosthetic reconstruction.MethodsWe performed a cohort study with functional outcome data from the recently completed Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial. We utilized the 100-point Toronto Extremity Salvage Score (TESS), which was administered pre-operatively and at 3, 6 and 12 months post-operatively. Higher scores indicate better physical functioning, and the minimally important difference is 11 points. We calculated mean functional scores at each timepoint after surgery and developed a logistic regression model to explore predictors of failure to achieve excellent post-operative function (TESS ≥ 80) at 1 year after surgery.ResultsThe 555 patients included in our cohort showed important functional improvement from pre-surgery to 1 year post-surgery (mean difference 14.9 points, 95%CI 12.2 to 17.6; p < 0.001) and 64% achieved excellent post-operative function. Our adjusted regression model found that poor (TESS 0-39) pre-operative function (odds ratio [OR] 3.3, 95%CI 1.6 to 6.6); absolute risk [AR] 24%, 95%CI 8% to 41.2%), older age (OR per 10-year increase from age 12, 1.32, 95%CI 1.17, 1.49; AR 4.5%, 95%CI 2.4% to 6.6%), and patients undergoing reconstruction for soft-tissue sarcomas (OR 2.3, 95%CI 1.03 to 5.01; AR 15.3%, 95%CI 0.4% to 34.4%), were associated with higher odds of failing to achieve an excellent functional outcome at 1-year follow-up. Patients undergoing reconstruction for giant cell tumors were more likely to achieve an excellent functional outcome post-operatively (OR 0.40, 95%CI 0.17 to 0.95; AR -9.9%, 95%CI -14.4% to -0.7%).ConclusionsThe majority of patients with tumors of the lower extremity undergoing endoprosthetic reconstruction achieved excellent function at 1 year after surgery. Older age, poor pre-operative function, and endoprosthetic reconstruction for soft tissue sarcomas were associated with worse outcomes; reconstruction for giant cell tumors was associated with better post-operative function.Level of evidenceTherapeutic Level IV.

Project description:BackgroundLimb salvage with endoprosthetic reconstruction is the current standard practice for the surgical management of lower extremity bone tumors in skeletally mature patients and typically includes tumor resection followed by the functional limb reconstruction with modular metallic and polyethylene endoprosthetic implants. However, owing to the complexity and length of these procedures, as well as the immunocompromised nature of patients treated with chemotherapy, the risk of surgical site infection (SSI) is high. The primary research objective of the Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY) trial is to assess whether a 5-day regimen of post-operative antibiotics decreases the risk of SSI at 1 year post-operatively compared to a 1-day regimen. This article describes the statistical analysis plan for the PARITY trial.Methods/designThe PARITY trial is an ongoing multi-center, blinded parallel two-arm randomized controlled trial (RCT) of 600 participants who have been diagnosed with a primary bone tumor, a soft tissue sarcoma that has invaded the bone or oligometastatic bone disease of the femur or tibia that requires surgical resection and endoprosthetic reconstruction. This article describes the overall analysis principles, including how participants will be included in each analysis, the presentation of results, adjustments for covariates, the primary and secondary outcomes, and their respective analyses. Additionally, we will present the planned sensitivity and sub-group analyses.DiscussionOur prior work has demonstrated (1) high rates of SSI after the treatment of lower extremity tumors by surgical excision and endoprosthetic reconstruction, (2) highly varied opinion and practice among orthopedic oncologists with respect to prophylactic antibiotic regimens, (3) an absence of applicable RCT evidence, (4) extensive support from international investigators to participate in a RCT, and (5) the feasibility of conducting a definitive RCT to evaluate a 5-day regimen of post-operative antibiotics in comparison with a 1-day regimen.Trial registrationClinicalTrials.gov NCT01479283 . Registered on 24 November 2011.

Project description:ObjectivesTo determine nonunion rate, fracture rate, and their risk factors following biological intercalary reconstruction for lower extremity bone tumors.MethodsA systematic review and pooled analysis were conducted. PubMed, Embase, and Wiley Cochrane Library were searched from inception up to June 01, 2020. Studies concerning biological intercalary reconstruction after resection of lower extremity bone tumors were included. Overall nonunion and fracture rates were calculated. For studies reporting patient outcomes individually with precise graft characteristics and fixation methods, the individual data were extracted. Patients with demographical and clinical characteristics, including age, sex, tumor location, graft characteristics, and fixation method, were pooled for a multivariate analysis. For each factor of interest, odds ratio (OR), 95% confidence interval (95% CI), and p-value from logistic regression were reported.ResultsA total of 2776 articles were identified from the initial literature search and 76 studies (2052 patients) were included. Sixty-nine studies were case series and seven were comparative studies. The overall nonunion rate was 19% (382/2052; range: 0%-53%), and the overall fracture rate was 17% (344/2052; range: 0%-75%). Thirty of the 76 studies (362 patients) reported patients' characteristics individually and were thus included in the pooled multivariate analysis. Intramedullary nail fixation was associated with a significantly higher nonunion rate compared to plate fixation (OR = 2.2, 95% CI: 1.23-4.10, p = 0.009). Reconstruction with a vascularized fibula graft had a statistically non-significant lower nonunion rate than reconstruction without the graft (OR = 0.6, 95% CI: 0.34-1.07, p = 0.086). Devitalized autografts had a lower fracture risk than allografts (OR = 0.3, 95% CI: 0.14-0.64, p = 0.002), and males tended to have higher fracture risk than females (OR = 2.1, 95% CI: 1.00-4.44, p = 0.049).ConclusionsReconstruction with intramedullary nail fixation is related to an elevated risk of nonunion. Allografts and males have a higher fracture risk than devitalized autografts and females, respectively. Further high-quality comparative analyses with large sample sizes and adequate follow-up duration are needed to validate these findings.

Project description:IntroductionLimb salvage with endoprosthetic reconstruction is the standard of care for the management of lower-extremity bone tumours in skeletally mature patients. The risk of deep postoperative infection in these procedures is high and the outcomes can be devastating. The most effective prophylactic antibiotic regimen remains unknown, and current clinical practice is highly varied. This trial will evaluate the effect of varying postoperative prophylactic antibiotic regimens on the incidence of deep infection following surgical excision and endoprosthetic reconstruction of lower-extremity bone tumours.Methods and analysisThis is a multicentre, blinded, randomised controlled trial, using a parallel two-arm design. 920 patients 15 years of age or older from 12 tertiary care centres across Canada and the USA who are undergoing surgical excision and endoprosthetic reconstruction of a primary bone tumour will receive either short (24 h) or long (5 days) duration postoperative antibiotics. Exclusion criteria include prior surgery or infection within the planned operative field, known colonisation with methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus at enrolment, or allergy to the study antibiotics. The primary outcome will be rates of deep postoperative infections in each arm. Secondary outcomes will include type and frequency of antibiotic-related adverse events, patient functional outcomes and quality-of-life scores, reoperation and mortality. Randomisation will be blocked, with block sizes known only to the methods centre responsible for randomisation, and stratified by location of tumour and study centre. Patients, care givers and a Central Adjudication Committee will be blinded to treatment allocation. The analysis to compare groups will be performed using Cox regression and log-rank tests to compare survival functions at α=0.05.Ethics and disseminationThis study has ethics approval from the McMaster University/Hamilton Health Sciences Research Ethics Board (REB# 12-009). Successful completion will significantly impact on clinical practice and enhance patients' lives. More broadly, this trial will develop a network of collaboration from which further high-quality trials in Orthopaedic Oncology will follow.