AOST2031: A Phase 3 Randomized Controlled Trial Comparing Open vs Thoracoscopic Management of Pulmonary Metastases in Patients with Osteosarcoma

Abstract Patients with osteosarcoma typically receive a combination of systemic therapy and surgical control of the primary tumor site. Surgical control of pulmonary metastases, the most common site of metastasis for patients with osteosarcoma, is also considered necessary for long term survival. Surgical resection via open surgery (thoracotomy or sternotomy) has been the mainstay of surgical management, and allows for identification, localization, and resection of all metastatic disease. With the advent of minimally invasive surgery, thoracoscopy is now applied to all aspects of chest pathology including cancer operations. The benefits of thoracoscopy include faster patient recovery and healing times, and improved quality of life. While thoracoscopy limits the use of haptic sense achieved by palpation of tissue, randomized controlled trials for adult patients with non-small cell lung cancer have not identified thoracotomy or sternotomy to be superior to thoracoscopy in thoracic event rates. Data for thoracoscopic surgery in pulmonary metastatic osteosarcoma are limited to retrospective reports.1 This study will be the first randomized controlled trial of surgical approach for pulmonary metastatic osteosarcoma. This study will reduce pulmonary disease heterogeneity by only enrolling patients with 4 or fewer CT identified nodules per lung (henceforth referred to as “oligometastatic”), and preoperative chest CTs will receive central radiologic review to confirm eligibility. Enrolled patients will be stratified by disease status at time of enrollment (newly diagnosed and recurrent disease), each further characterized by risk (considered average and poor) on the basis of the number of pulmonary nodules (1 vs ≥ 2), site of pulmonary nodules (unilateral vs. bilateral), and primary tumor histological response to chemotherapy for newly diagnosed patients (< 10% or > 10% viable tumor in resected specimen). Patients with recurrent disease will also be stratified by the treating oncologists’ intent to treat with chemotherapy for recurrence (yes vs. no). Primary outcome will be thoracic event free survival (thoracic event is defined as intrathoracic tumor recurrence by chest CT or death that results from the procedure or a complication related to the procedure). Correlative outcomes include quality of life from patient- reported outcomes, along with imaging and laboratory studies.