Kobys V L, Konovalenko V F, Repinа N V, Golovko T S, Gulak L O, Tarasova T O, Zaharycheva E V, Matyushok O F
Municipal Clinical Oncological Center, Kyiv, Ukraine.
Exp Oncol. 2013 Jun;35(2):105-8.
To improve the treatment results of patients with locally advanced osteosarcoma with large volume using neoadjuvant chemotherapy (NACT) (ifosfamide at a dose of 18 g/ml) and planning of organ-conserving surgery by evaluating the state of tumor pseudocapsule.
A study group included 46 children aged from 7 to 18 years, mean age - 12 years. In 68% of the patients tumor volume was larger or significantly larger than 200 ml (from 27 to 2400 ml), mean tumor volume was 342 ml. All patients have been examined by X-ray radiography, CT, Doppler ultrasound. Convenient chemotherapy consisted of methotrexate at a dose of 12 g/ml, cisplatin (120 mg/ml) in combination with doxorubicin (75 mg/ml). If such chemotherapy was considered ineffective with the use of an algorithm for determination of chemotherapy efficacy, 2 cycles of chemotherapy with ifosfamide at a dose of 18 g/ml per course have been applied. At the stage of planning of organ-conserving surgery, the state of tumor pseudocapsule was analyzed. In 6 months post-operative chemotherapy was carried out with the use of methotrexate, cisplatin with doxorubicin, ifosfamide at the same doses.
Myelotoxicity of ifosfamide treatment at a dose of 18 g/ml is comparable to that of to a course of doxorubicin + cisplatin: the depth of leucopenia was significantly higher (p < 0.05), the duration of agranulocytosis is similar after such therapies. In the study group, 69.6% patients have reached grade 3-4 pathomorphosis. Organ-conserving surgery was performed in 86.9% of the patients. Local tumor recurrence was registered in 15.2% patients of the study group. 5-year relapse-free survival was achieved in 62 ± 10% (p = 0.02), the overall 5-year survival - 76.5 ± 9% (p = 0.02).
Introduction of ifosfamide at a dose of 18 g/ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-operative chemotherapy, pre-operative analysis of NACT efficacy and the state of tumor pseudocapsule during planning stage of organ-conserving surgery significantly improves efficacy of the therapy in patients with large tumor volume.
通过新辅助化疗（NACT）（剂量为18 g/ml的异环磷酰胺）并评估肿瘤假包膜状态来规划保器官手术，以提高大体积局部晚期骨肉瘤患者的治疗效果。
研究组包括46名7至18岁的儿童，平均年龄为12岁。68%的患者肿瘤体积大于或显著大于200 ml（27至2400 ml），平均肿瘤体积为342 ml。所有患者均接受了X线摄影、CT、多普勒超声检查。常规化疗包括剂量为12 g/ml的甲氨蝶呤、顺铂（120 mg/ml）联合阿霉素（75 mg/ml）。如果根据化疗疗效判定算法认为这种化疗无效，则应用2个疗程、剂量为18 g/ml的异环磷酰胺化疗。在规划保器官手术阶段，分析肿瘤假包膜状态。术后6个月，使用相同剂量的甲氨蝶呤、顺铂联合阿霉素、异环磷酰胺进行化疗。
剂量为18 g/ml的异环磷酰胺治疗的骨髓毒性与阿霉素+顺铂疗程的骨髓毒性相当：白细胞减少深度显著更高（p<0.05），粒细胞缺乏持续时间在这些治疗后相似。研究组中，69.6%的患者达到3-4级病理形态改变。86.9%的患者进行了保器官手术。研究组15.2%的患者出现局部肿瘤复发。5年无复发生存率为62±10%（p=0.02），总体5年生存率为76.5±9%（p=0.02）。
在局部晚期骨肉瘤患儿的治疗方案中引入剂量为18 g/ml的异环磷酰胺，同时进行术前化疗个体化、术前分析NACT疗效以及在保器官手术规划阶段分析肿瘤假包膜状态，可显著提高大肿瘤体积患者的治疗效果。
