Surveillance AFter Extremity Tumor surgerY (SAFETY): A Protocol for an International Randomized Controlled Trial

Abstract

Title: Surveillance AFter Extremity Tumor surgerY International Randomized Controlled TrialShort Title: SAFETYMethodology: Multi-center, 2 x 2 factorial superiority randomized controlled trial (RCT).Coordinating Center: This study will be centrally coordinated by the Methods Center at the Center for Evidence-Based Orthopaedics (CEO) at McMaster University in Hamilton, Ontario Canada. Clinical Sites: We are expecting ten clinical sites to be involved in the pilot phase. Further sites will be recruited for the definitive phase.Primary Objectives: The overall objective is to determine the effect of surveillance strategy on patient survival after surgery for a soft-tissue sarcoma of the extremity by comparing the effectiveness of: A) a surveillance frequency of every three months vs. every six months; and B) CT scans vs. chest radiographs.Secondary Objectives: We will explore: A) the effects of the post-operative surveillance strategies on patient-important outcomes (patient anxiety, overall satisfaction and quality of life), oncologic outcomes (local recurrence- and metastasis-free survival) and treatment-related complications (chemotherapy- and thoracotomy-related complications); and B) the net costs of post-operative surveillance strategies and of metastasis treatment and treatment-related complications. Treatment Groups: This study will compare two surveillance frequencies (every three months vs. every six months) and two imaging modalities (CT scan vs. chest radiograph) for a total of four treatment groups: 1)Surveillance visit and chest CT scan every three months for two years;2)Surveillance visit and chest CT scan every six months for two years; 3)Surveillance visit and chest radiograph every three months for two years; or4)Surveillance visit and chest radiograph every six months for two years. Study Outcome: The primary outcome is overall survival at five years post-randomization. Follow-Up: Upon completion of the two-year intervention phase, study participants will be followed every six months for another three years. Sample Size: Pilot - 200 participants | Definitive - 830 participantsEstimated Study Duration: Pilot - September 2019 – January 2023 | Definitive - TBDSignificance: Following treatment for a primary extremity sarcoma, patients remain at risk for the development of local and systemic disease recurrence. Metastasis (distant recurrence) to the lung is the most frequent single location of disease recurrence in sarcoma patients, occurring in almost half of all patients. Therefore, careful post-operative surveillance is an integral element of patient care. However, the detection of metastases does not necessarily affect long-term survival and may negatively impact quality of life. Surveillance strategies have not been well researched and have been identified as the top research priority in the extremity sarcoma field. The SAFETY trial will provide the necessary evidence to develop evidence-based surveillance guidelines, and is poised to have a significant impact on the post-operative care and outcomes of extremity soft-tissue sarcoma patients.