Malignant Bone Tumors
Malignant bone tumors (bone sarcomas) often affect adolescents and young adults. Care of patients with bone sarcomas is carried out in specialty centers, as these are rare forms of cancer. In Canada, bone sarcomas affect 4 to 5 patients per million persons each year. Long-bone sarcomas were historically managed with amputations, but the current standard is limb salvage surgery, which involves wide tumor resection followed by functional reconstruction. With the aid of modern imaging techniques and chemotherapeutic regimens, limb salvage is possible in 95% of patients. The most common type of functional reconstruction involves the use of tumor endoprostheses - modular metallic and polyethylene implants that replace surgically resected bones and joints.
Due to the complexity and length of musculoskeletal tumor surgeries, as well as the immunocompromised nature of patients treated with chemotherapy, the risk for deep post-operative infection remains high and the outcomes following infection can be devastating. These infections require staged endoprosthetic revision surgery and long-term intravenous antibiotic therapy. Even following this management, repeat infection and ultimate amputation are not uncommon. Up to 50% of these cases end in amputation. Patients’ function and quality of life are dramatically impacted, as are health care costs.
International Collaborative Trials
The rarity of sarcomas of the long bones dictates that multi-center international collaborations are essential in order to adequately power surgical trials in this field, but there is no precedent for such an undertaking in this field. The PARITY (Prophylactic Antibiotics in Tumor Surgery) trial is the first large-scale randomized surgical trial in Orthopaedic Oncology, and its rigorous design, organization, and execution will set a high benchmark for future research.
In large clinical trials, small treatment effects may frequently be “statistically significant” without demonstrating patient-important benefit that would warrant changes in management. Data collected in the PARITY trial will be used in a sub-study to estimate the “Minimal Important Differences” MIDs for commonly used musculoskeletal oncology functional outcome scores. These MIDs will clarify treatment effect sizes and enhance clinical decision-making, as well as provide a useful guide to sample size calculations for subsequent large trials. Ultimately, this work will enhance the methodological rigor of clinical investigation in Orthopedic Oncology and improve the outcomes of patients with primary bone sarcomas.
Metastatic Bone Disease
Of all the new cases of invasive cancers diagnosed each year, approximately 50% eventually metastasize to bones. Breast, prostate, lung, thyroid and renal cancer account for an estimated 42,600 new metastatic bone disease cases each year in Canada alone. Metastatic bone lesions predispose to pathological fracture, which exposes patients to extreme pain, urgent hospitalization, and the risks of surgery in less than ideal circumstances. High-risk lesions can be treated with radiation, drugs, or surgery. Predicting an impending fracture and performing prophylactic surgical fixation in an elective setting are critical to avoid debilitating complications, but current predictive scoring systems are limited. Our current studies aim to characterize the typical indicators for prophylactic fixation and develop a robust, reliable, and practical methodology for identifying patients with metastatic bone disease who would benefit from surgery.
The objectives of the Orthopaedic Oncology and sarcoma team are:
- To establish the first international collaborative trials network in the field of orthopaedic oncology.
- To determine the optimal dosing of antibiotics in patients undergoing limb salvage surgery.
- To determine the Minimal Important Differences for the commonly used musculoskeletal tumor surgery functional outcome measures.
- To develop a practical, reproducible, and accurate way to predict fracture risk for metastatic bone lesions.