顺铂高温灌注治疗骨肉瘤时肿瘤坏死率的相关研究

Relations of chemotherapy-induced tumor necrosis to plasma platin concentration and primary tumor temperature in patients with osteosarcoma in the lower extremities treated by hyperthermic isolation limb perfusion with cisplatin

目的 探讨顺铂高温隔离肢体灌注 (HILP)治疗肢体骨肉瘤时肿瘤细胞坏死率与患肢血顺铂浓度、肿瘤内温度以及最终无瘤生存率间的关系。 方法 15例下肢ⅡB期骨肉瘤患者 ,男性10例 ,女性 5例 ;年龄 13～ 2 9岁 ,中位年龄 18岁 ;均接受包括一次顺铂高温隔离灌注 (顺铂剂量 15 0mg/m2 )在内的新辅助化疗。手术方法 :9例行保肢术 ,6例行截肢手术。所有切除标本均以多切片作肿瘤细胞坏死率评估。 结果 15例患者在HILP过程中肿瘤内最高温度为 41 2～ 43 0℃ (平均 42 3± 0 46℃ ) ,患肢血铂浓度于给予顺铂后 10、40、6 0min 3次的平均浓度为 4 5 6～ 14 6 6 μg/ml(平均8 93± 3 16 μg/ml)。肿瘤细胞坏死率为 86 3%～ 98 2 % ,完全反应者 (>90 % ) 13例 ,反应不佳者 2例 ,分别为 87 2 %和 86 3%。 15例患者均经 5年以上随访 ,5年无瘤生存者 8例。回归分析显示肿瘤细胞坏死率与患肢血铂浓度、肿瘤内温度有显著相关 (均为P <0 0 1) ,而相关分析显示无瘤生存率与肿瘤细胞坏死率、血铂浓度和肿瘤内温度无显著相关 (均为P >0 .0 5 )。 结论 HILP对肿瘤原发灶有显著的杀灭作用 ,有利于肿瘤的切除 ;但是同样的高温、高药浓度条件无法应用于远处的转移灶 ,因此由于各种原因需截肢的病例术前无需行HILP。

Objectives[WT5”BZ] To study the relations of chemotherapy induced tumor necrosis to plasma concentration of platin and primary tumor temperature in hyperthermic isolation limb perfusion (HILP) with cisplatin, and to investigate the correlation between the tumor necrosis rate and the relapse free survival (RFS). [WT5”HZ]Methods[WT5”BZ] Fifteen patients with II B osteosarcoma in the lower extremities were treated with neoadjuvant chemotherapy. Among them, 10 were male and 5 female. The average age was 18 years (ranging from 13 to 29). Chemotherapy included a single bonus dose of HILP with cisplatin (CDDP, 15 mg/m 2). The plasma concentration of platin and the tumor temperature in the affected limb were measured during the course of the HILP with CDDP. Limb salvage surgery was performed in 9 patients and amputation in 6. After surgery, serial sections of the excised tumor specimens were made to determine the tumor necrosis rate. All of the patients were followed up for more than 5 years. [WT5”HZ]Results[WT5”BZ] The highest attained tumor temperature was between 41 4℃ 43 0℃(mean 42 3℃±0 46℃), and the platin concentration ranged from 4 56 μg/mL to 14 66 μg/mL (mean 8 93 μg/mL±3 16 μg/mL)during the course of HILP with CDDP. Thirteen patients with a necrosis rate of over 90% were well responsed, and the remaining two with a mecrosis rate 87.2% and 86.3% were poor responsed. Eight patients remained tumor free for 5 years. Primary tumor temperature and platin concentration were significantly related to the tumor necrosis rate ( P =0.001 and P <0.001, respectively). No significant correlation was noted between the long term survival rate and the three parameters in the regression analysis. [WT5”HZ]Conclusions[WT5”BZ] HILP with CDDP is useful in the treatment of primary osteosarcoma. Increased tumor necrosis ensure a successtul surgical excision of tumor. HILP however is still limited to the patients who are not candidates for lime salvage surgery, because the same condition of high temperature and high concentration of platin are not applicable to distant metastasis. [WT5”HZ]