Four questions for Dr. Michelle Ghert, Professor of orthopaedic surgery at McMaster University and winner of the 2023 Kappa Delta Ann Doner Vaughn Award
Linked Orthopaedia chapter: https://www.orthopaedia.com/oncology-2/
Dr. Michelle Ghert, Professor of orthopaedic surgery at McMaster University was the winner of the 2023 Kappa Delta Ann Doner Vaughn Award for the first-ever international multi-center randomized controlled trial in orthopaedic oncology.
ORTHOPAEDIA: Congratulations on winning the Kappa Delta award for “Prophylactic Antibiotic Regimens in Tumor Surgery” [PARITY]. At first glance, the title appears a little surprising. Antibiotics are for infections, and (as far as we know!) tumors are not infectious conditions. Why is antibiotic use an important question to orthopedic oncologists?
MICHELLE GHERT: On behalf of my co-investigators, thank you! The question of post-operative antibiotics certainly resonated with the orthopaedic oncology community. It is true that we are highly focused on treating cancer and restoring limb function, not necessarily on bacteria. However, bacteria unfortunately become a barrier to both of these goals. The surgeries that we do are complex, often require extended operative time, and can be challenged by the fact that many of our patients are immunocompromised from harsh chemotherapy. As a result, surgical site infections are common. Limb salvage can fail if infection sets in, and chemotherapy has to be put on hold while we try to eradicate the infection.
The upshot is that orthopaedic oncologists are intensely focused on preventing infections. It has been established for decades that peri-operative prophylactic antibiotics can reduce the risk for a surgical site infection in joint replacement performed for arthritis. This practice is therefore the gold standard in orthopaedic oncology as well. However, the question of ‘how long should I prescribe antibiotics?’ has been lingering in our field. Surgeons performing arthroplasty for arthritis stop antibiotics after one day, but because our infection risks are higher, perhaps we should go longer. This is the background that led to the PARITY trial.
ORTHOPAEDIA: The standard of care for some tumors involves a big surgery, as your work makes clear. Do you foresee a day when big surgery will have a smaller role in the management of such tumors? Might genomics and advances in regenerative medicine play a role?
MICHELLE GHERT: As much as my colleagues and I love to operate, I would be happy to see some types of cancer surgeries taken away from us. Still, at least for now, sarcomas are almost always treated with surgery: a complete resection is needed for cure. Neoadjuvant chemotherapy (that is, chemotherapy given before surgery, to shrink the tumor) can reduce the extent of surgery required, most notably in cases of osteosarcoma and Ewing’s sarcoma. Could molecular advances and precision medicine reduce the need for surgery even more? Given the progress that has been made in other cancer types, I cannot rule that out. Nonetheless, among cancers, sarcoma is among the least clearly understood biologically. Therefore, surgery likely will be a mainstay of sarcoma treatment for many years to come.
So far, immunotherapy has been very disappointing, but methods of stimulating the immune system to fight sarcoma are promising. It is important to note that even today, some diseases can be controlled with biologic treatment. For example, Giant Cell Tumor of Bone responds to monoclonal antibody treatment. This is a development that I did not think was possible when I was in training only 20 years ago.
ORTHOPAEDIA: Your work represents a significant milestone in cooperation: coordinating a study across the world. Without taking anything away from your prodigious achievement—for it is prodigious!– one may say you started from one advantageous point: namely, that orthopaedic oncologists are professionally collaborative. After all, successful cancer treatment is highly interdisciplinary, involving the synergy of medical oncologists, radiologists, nurses, and therapists from various disciplines, among others. How would you suggest exporting your research methodology to other orthopaedic subspecialties, ones where the soloist might have a bigger role?
MICHELLE GHERT: That is an interesting perspective. It is true that orthopaedic oncologists work with large, multidisciplinary and collaborative clinical teams. However, the orthopaedic oncology specialty that I grew up in was not collaborative. In the not-so-distant past, orthopaedic oncology conferences were filled to the brim with interesting presentations from prestigious centers–but each a silo of researchers reluctant to share data or work together. The emphasis was on individual glory. It was clear to me, early on in my career, that any progress would require a paradigm shift in the approach to how our field approached clinical research.
In the end, orthopaedic oncologists are a unique group, bound together by the tragic situations that we deal with and our fascination with surgical challenges. It is this shared bond that has allowed us to work together for a common goal. We have done our best to put quests for individual glory aside and put our patients first. For that reason, I was adamant that if there was to be recognition for our work, it would be shared. Accordingly, the Kappa Delta Award lists the names of more than 100 PARITY Investigators. We have earned this award together.
As for other sub-specialists that may not have the same deep connection one to another, I still believe that collaboration is feasible. In the end, patients will benefit from our collaboration. As long as orthopaedic surgeons keep their eye on that ball, collaborative research can become a way of life. I call specific attention to the orthopaedic trauma studies done through McMaster University and by METRIC – both Kappa Delta Awardees as well. Collaborative research can be the norm.
ORTHOPAEDIA: With the rising concern of antibiotic resistance, how do you see the role of antibiotics in postoperative care evolving in orthopaedic surgery? Are there any alternative or adjunct therapies being investigated that may help reduce the reliance on antibiotics?
MICHELLE GHERT: With the administration of one peri-operative dose of intravenous antibiotics, particularly in cases in which hardware is implanted, we are doing all we can do with that one tool to prevent infections. There are many other peri-operative strategies that are used such as intra-wound antibiotic powder, antibiotic laden cement, silver-coated prostheses, betadine irrigation, negative pressure wound dressings, antibiotic coated sutures, and others. None of these have uniformly strong evidence supporting their use, but overall, they are likely to have some efficacy.
It is my humble opinion that efficient surgical technique remains the most important strategy to reduce surgical site infections. Efficient surgical technique in all orthopaedic operations includes reducing tissue trauma, ensuring hemostasis, closing wounds with minimal tension and dead space, and using surgical drains when needed. In orthopaedic oncology, efficiency additionally demands that the surgeon engage in detailed pre-operative planning, both to understand the unique 3-dimensional anatomy of the tumor and surrounding structures, and to prepare for unforeseen contingencies.
It is intuitive that local tissue concentration of antibiotics at the time of surgery is critical. To circle back to your previous question, perhaps the answer here is collaboration and cooperation with scientists and other specialists. We need to better understand individual patient drug metabolism and pharmacokinetics to perhaps apply a precision medicine technique to maximize the effect of antibiotics at the time of surgery while minimizing use, or at least avoiding overuse. I also think that implant coatings may be able to avoid infections, by preventing the development of biofilm, which is the home base for bacteria in surgical wounds. Work is being done on both approaches and I am hopeful that they will help us decrease our reliance on ‘all out’ antibiotics.