Background Surgery with both neoadjuvant and adjuvant chemotherapy represents the standard of care for extremity osteosarcoma despite a lack of high-quality evidence for its use, and trial evidence that suggests that up-front surgery may result in better outcomes. This study estimated the difference in overall survival for the standard of care (“Neoadjuvant First”) vs upfront surgery first followed by adjuvant chemotherapy (“Surgery First”). Patients and methods Using Surveillance, Epidemiology, and End Results data, we identified patients age 5-29, diagnosed with a primary cancer of upper or lower extremity osteosarcoma between 2007 and 2019 who received surgery and chemotherapy. Our primary endpoint was the 5-year survival difference between the Surgery First and Neoadjuvant First groups. Results Adjusted 5-year survival was 74% for Surgery First patients and 67% for Neoadjuvant First patients, with a survival difference of 6.9% (95% CI -4.2% - 16.1%). In sensitivity analyses of 5-year survival, the results were consistent, showing a 6.8% to 13.7% higher 5-year survival in Surgery First patients. Significant mortality risk factors included older age, larger tumor size, the type of resection (salvage vs amputation), and stage 3-4 disease (vs stage 1-2 disease). Conclusion The evidence supporting neoadjuvant therapy in osteosarcoma care is weak. However, there is evidence that pausing chemotherapy in the peri-surgical period might affect outcomes. Consequently, this study, and its consistency with the results from the only randomized trial, suggests that there is reason to revisit a prospective, randomized trial of osteosarcoma treatment regarding the timing of surgery and chemotherapy.

中文翻译：

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化疗和手术时机对上下肢骨肉瘤死亡率的影响


背景 新辅助和辅助化疗的手术代表了四肢骨肉瘤的护理标准，尽管缺乏其使用的高质量证据，并且试验证据表明预先手术可能会产生更好的结果。这项研究估计了标准护理（“新辅助优先”）与先行手术后辅助化疗（“手术优先”）的总生存率差异。患者和方法利用监测、流行病学和最终结果数据，我们确定了 2007 年至 2019 年间诊断患有上肢或下肢骨肉瘤原发性癌症并接受手术和化疗的 5-29 岁患者。我们的主要终点是先手术组和先新辅助组之间的 5 年生存率差异。结果 首次手术患者的调整后 5 年生存率为 74%，首次新辅助治疗患者的调整后 5 年生存率为 67%，生存率差异为 6.9% (95% CI -4.2% - 16.1%)。在 5 年生存率的敏感性分析中，结果是一致的，显示手术优先患者的 5 年生存率提高了 6.8% 至 13.7%。显着的死亡风险因素包括年龄较大、肿瘤尺寸较大、切除类型（挽救与截肢）以及 3-4 期疾病（与 1-2 期疾病）。结论 支持骨肉瘤护理中新辅助治疗的证据薄弱。然而，有证据表明围手术期暂停化疗可能会影响结果。因此，这项研究及其与唯一随机试验结果的一致性表明，有理由重新审视关于手术和化疗时机的骨肉瘤治疗前瞻性随机试验。