儿童骨肉瘤综合治疗的效果

Efficacy of Combined Therapy for Childhood Osteosarcoma

目的引用德国骨肉瘤协作组（COSS）-96方案治疗骨肉瘤,从临床疗效分析、药物剂量及给药方式、不良反应的防治方面,探讨国内治疗儿童骨肉瘤的最佳综合治疗方案。方法对15例初诊的骨肉瘤患儿采用COSS-96方案,进行术前、术后化疗及手术综合治疗及疗效分析;检测大剂量甲氨蝶呤（HD-MTX）给药后的血清水平,根据血药水平调整HD-MTX给药剂量及甲酰四氢叶酸（CF）解救剂量及次数。结果 15例患儿术前化疗后均有局部肿块缩小及疼痛消失等症状好转及影像学改变;肿瘤坏死组织学评估Ⅰ级2例,Ⅱ级3例,Ⅲ级6例,Ⅳ级4例;HD-MTX剂量12 g.m-2给药结束0 h血清药物水平为700~1 000μmol.L-1。随访时间5 a 10个月,中位随访时间3 a 2个月,肺转移3例,肺及多部位骨骼转移1例,死亡2例。5 a生存率71%,5 a无瘤生存率57%。结论术前化疗具有清扫转移病灶,局部肿块缩小及疼痛消失、减小手术范围和难度的作用;依据术后肿瘤坏死组织学评估制定术后化疗方案,不仅达到避免患儿因化疗敏感性差使化疗方案强度不足,肿瘤易复发而生存期缩短的目的 ,而且可避免对化疗敏感的患儿因＂过强＂化疗后的不良反应及死亡的发生;血清药物水平监测下调整HD-MTX给药剂量,在确保有效杀灭瘤细胞药物剂量的同时,也为HD-MTX不良反应的防治提供客观依据。

Objective To explore the combined therapy for childhood osteosarcoma by adopting German osteosarcoma study（COSS）-96 protocol and analyze its implications for clinical efficacy,dosage and administration of chemotherapy agents,and the prevention and treatment of toxicity and side effects.Methods COSS-96 protocol was used and efficacy was analyzed with the combined therapy of preoperative,postoperative chemotherapy and surgery of 15 patients newly diagnosed with malignant osteosarcoma.Serum concentration of high-dose methotrexate（HD-MTX） was tested to adjust HD-MTX dosage and the amount and frequency of giving citrovorum factors（CF）.Results Shrinking local osteosarcoma,pain alleviation and X-ray improvement were observed in all 15 patients after preoperative chemotherapy.Histopathological assessment of tumor were made by dividing the patients into gradeⅠ（2 cases）,Ⅱ（3 cases）,Ⅲ（6 cases） and Ⅳ（4 cases）.Serum levels of HD-MTX（12 g·m-2）at 0 hour after the administration of HD-MTX were between 700-1 000 μmol·L-1.Follow-up time was 5 years and 10 months,and the mean follow-up time was 3 years and 2 months,during which 3 patients developed lung metastasis,1 patient developed lung metastasis and bone metastasis at multiple sites,and 2 patients died.Five-year overall survival rate was 71%,and 5-year survival without osteosarcoma was 57%.Conclusions Preoperative chemotherapy helps to remove the metastasis,reduce local osteosarcoma,relieve pain and narrow the operation margin and difficulty.Postoperative chemotherapy protocol based on histopathology not only avoids insufficient intensity which results in relapse and shortens survival of insensitive patients,but also reduces the treatment-associated toxicities and death rate,which can be caused by excessive intensity for sensitive patients;dosage adjustment of HD-MTX under the serum concentration monitoring ensures dosage sufficiency and provides a scientific basis for prevention and treatment of HD-MTX toxicity and side effects.