Michelle Ghert, M.D. and the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) Investigators have been honored with the 2023 Kappa Delta Ann Doner Vaughn Award for the first-ever international multicenter randomized controlled trial (RCT) in orthopedic oncology.
The award, which recognizes research excellence in the musculoskeletal arena with great potential to advance patient care, was presented at the recent annual meeting of the American Academy of Orthopaedic Surgeons (AAOS).
Their work focused on the prevention of surgical site infections (SSIs) through antibiotic prophylaxis following oncologic reconstruction surgery for bone tumors. It represents the largest collaborative effort in orthopedic surgery as far as the number of countries participating.
“In the field of medicine, conducting a 600-patient randomized study isn’t out of the ordinary,” said Dr. Ghert, principal investigator, professor, Department of Surgery, McMaster University, Hamilton, Ontario, Canada. “However, in orthopaedic oncology, where we treat rare diseases, it was a shift in our research paradigm.”
“While initially there wasn’t much optimism that this study would work, we believed it was time to move forward for our patients and the research question really resonated. I give a lot of credit to the first few clinical sites that joined the study as they took a leap of faith.”
The research group consisted of experts from orthopedic oncology, infectious diseases, clinical epidemiology, biostatistics and health research methodology. The investigators, from 55 clinical centers in 12 countries, sought to fill in the information gap on studies looking at the role of antibiotic regimens for surgical reconstruction of lower extremity bone tumors.
The research team enrolled 604 patients who were diagnosed with primary bone or soft-tissue sarcoma or oligometastatic (a more treatable form of metastatic cancer) bone disease in the femur or tibia with an expected survival of one year who required surgical resection and implant reconstruction.
Patients were randomized to a one- or five-day regimen (311 to one day and 293 to five day) of postoperative intravenous antibiotics within eight hours of skin closure—and then administered every eight hours after that.
The PARITY researchers found that 15% of patients on the five-day regimen and 16.7% on the one-day regimen had a surgical site infection, with the most common causes being Staphylococcus aureus and coagulase-negative Staphylococci. They found a significant increase in antibiotic-related complications in the five-day regimen group, with the main complication reported to be antibiotic-associated diarrhea caused by Clostridioides difficile.
“The risk for surgical site infections was not significantly different for five days or one day, so when surgeons write post-operative orders, they have that information to work with,” said Dr. Ghert. “However, one of the secondary outcomes demonstrated you could actually hurt the patient by causing severe antibiotic-related complications that can be life altering. When you have a patient who is already going through a very difficult time, chemotherapy and morbid surgery, surgeons need to weigh the risk before prescribing prolonged antibiotics as they can cause added gastrointestinal issues that can be chronic.”
When OTW asked about some of the hurdles they faced early on in the process, Dr. Ghert said, “First of all, there was a lack of precedence in the field and therefore trepidation of the unknown. In addition, we had to contend with a lack of experience and resources at individual clinical sites for participating in investigator initiated randomized trials.”
“Canada and Europe required regulatory approval in order to use intravenous cephalosporin. We experienced long delays in start-up at individual sites due to complex ethics approvals and contract negotiations. At times there was investigator fatigue and slow enrollment, as well as a lack of equipoise at some clinical sites that chose not to participate.”
As for any challenges related to diffusing this information and getting it adopted into practice, she added, “While the results of the study are fairly well known in the field, the fear of infection may overcome the known risk of antibiotic-related complications and surgeons may simply decide to continue with prolonged antibiotics in the attempt to avoid infection. Higher risk cases will likely still be considered indications for longer antibiotics, although there is still no evidence to support this practice.”
And what did Dr. Ghert tell OTW in the form of advice for up-and-coming orthopedic oncologists-researchers? “For prospective principal investigators: focused research training at centers such as at McMaster University, is essential. For prospective participating clinical sites: be passionate about participating in studies, be an advocate at your hospital and push through challenges with the help of the coordinating center and research team, stay engaged.”
