Venkatramani Rajkumar, Murray Jeffrey, Helman Lee, Meyer William, Hicks M John, Krance Robert, Lau Ching, Jo Eunji, Chintagumpala Murali
Department of Pediatrics, Baylor College of Medicine, Texas Children's Cancer Center, Texas Children's Hospital, Houston, Texas.
Cook Children's Medical Center, Fort Worth, Texas.
Pediatr Blood Cancer. 2016 Mar;63(3):412-7. doi: 10.1002/pbc.25808. Epub 2015 Oct 26.
The outcome of localized osteosarcoma has remained constant over the past 30 years. Histological response to preoperative chemotherapy is the best predictor of outcome. Strategies to alter treatment based on histological response have not resulted in increased survival.
Patients with localized osteosarcoma received preoperative chemotherapy with cisplatin, doxorubicin, and methotrexate. Patients whose tumors had a good histological response (≥90% necrosis) continued with the same treatment postoperatively. Patients with poor histological response (<90% necrosis) received three courses of melphalan 100 mg/m(2) on day -4, cyclophosphamide 2,000 mg/m(2) on days -3, and -2 followed by stem cell infusion.
Fifty-two patients were enrolled. Median age was 14 years, and 56% of patients were male. The femur was the most common site. Forty patients underwent limb salvage surgery and amputation was performed in six patients. Forty-eight percent of tumors showed good histological response. Forty patients were evaluable for outcome; 18 patients with poor histologic response received high-dose chemotherapy. The 5-year event-free survival (EFS) and overall survival (OS) for patients treated on the high-dose chemotherapy arm were 28% (95% confidence interval [CI], 10-49) and 48% (95% CI, 23-69), respectively. The 5-year EFS and OS for patients treated on the standard chemotherapy arm were 62% (95% CI, 36-80) and 74% (95% CI, 44-90), respectively. All patients who received high-dose chemotherapy developed grade 3 or higher hematological toxicity. There were no treatment-related deaths.
Postoperative alkylator intensification with high-dose cyclophosphamide and melphalan in patients with localized osteosarcoma with poor histological response failed to improve survival.
在过去30年中，局限性骨肉瘤的治疗结果一直保持稳定。术前化疗的组织学反应是预后的最佳预测指标。基于组织学反应改变治疗策略并未提高生存率。
局限性骨肉瘤患者接受顺铂、阿霉素和甲氨蝶呤术前化疗。肿瘤组织学反应良好（坏死率≥90%）的患者术后继续相同治疗。组织学反应差（坏死率<90%）的患者在第-4天接受三疗程美法仑100mg/m²，在第-3天和-2天接受环磷酰胺2000mg/m²，随后进行干细胞输注。
共纳入52例患者。中位年龄为14岁，56%为男性。股骨是最常见的发病部位。40例患者接受了保肢手术，6例患者进行了截肢。48%的肿瘤组织学反应良好。40例患者可评估预后；18例组织学反应差的患者接受了高剂量化疗。高剂量化疗组患者的5年无事件生存率（EFS）和总生存率（OS）分别为28%（95%置信区间[CI]，10-49）和48%（95%CI，23-69）。标准化疗组患者的5年EFS和OS分别为62%（95%CI，36-80）和74%（95%CI，44-90）。所有接受高剂量化疗的患者均出现3级或更高的血液学毒性。无治疗相关死亡。
对于组织学反应差的局限性骨肉瘤患者，术后使用高剂量环磷酰胺和美法仑强化烷化剂治疗未能提高生存率。
