新辅助化疗治疗肢体软组织肉瘤28例报告

Neoadjuvant chemotherapy for extremity soft tissue sarcomas: twenty-eight cases report

目的：分析探讨新辅助化疗治疗肢体软组织肉瘤（softtissuesarcoma，STS）的临床疗效及价值。方法选取2009年5月至2012年6月，我科经新辅助化疗[术前顺铂＋异环磷酰胺＋阿霉素（cisplatin＋ifosfamide＋adriamycin，DDP＋IFO＋ADM，DIA ）化疗2个周期＋手术治疗＋术后 DIA 化疗6个周期]治疗的28例肢体STS患者，其中男18例，女10例；年龄15～62岁，中位年龄35岁。DIA 1个周期的化疗方案为：第1天DDP 120 mg/m2，第7～9天每天按序均给予ADM 30 mg/m2、IFO 2.0 g/m2，第10～11天IFO 2.0 g / m2。对所有患者进行随访，复查肺部 CT 及病变部位 X 线片，记录复发、转移、死亡情况。参照实体瘤疗效评价标准（ response evaluation criteria in solid tumour，RECIST ）1.1评价化疗疗效；按照化疗常见不良反应事件评价标准（ common terminology criteria for adverse events，CTCAE ）4.0对化疗期间的不良反应进行评价。结果本组28例手术均进行顺利，总失血量50～600ml，平均260ml，切口如期愈合。DIA化疗方案进行了术前2个周期、术后6个周期化疗，持续时间为38周，28例共进行了224个化疗周期。28例随访12～59个月，随访结束时，存活23例，其中无瘤生存20例，带瘤生存3例。本组2年无瘤生存率71.4%，2年总生存率82.1%。术后转移5例，均肺部转移而死亡；4例术后复发，复发率12.3%。4例复发患者与3例肺转移患者，于发现后先辅助三维适行放疗。经过术前化疗，肿瘤体积平均缩小（30.2±11.3）%，尤其肿瘤直径＞15 cm的22例，肿瘤体积平均缩小（42.7±7.8）%；28例中完全缓解（ complete remssion，CR ）0例，部分缓解（ partial remission，PR ）12例，稳定（ stable disease，SD ）14例，疾病进展（ progression diseas，PD ）2例，客观缓解率（ objective response rate，ORR ）为42.9%，疾病控制率（ disease control rate，DCR ）为92.9%；患者对化疗耐受性良好，主要化疗不良反应均为一过性，经用药对症处理后症状消失。结论新辅助化疗方案治疗肢体STS，术前化疗可明显缩小STS的体积，减轻肿瘤周围的软组织水肿，可控制微小转移灶，很好地配合STS的手术切除；能够提高患者的总生存率及无瘤生存率，有利于肢体STS 的保肢治疗；其近、中期疗效满意，不良反应可耐受，是治疗STS重要有效的方法。

Objective To investigate and analyze the clinical effects and value of neoadjuvant chemotherapy in the treatment of extremity soft tissue sarcomas （ STS ）.Methods A total of 28 patients with extremity STS were treated by neoadjuvant chemotherapy from May 2009 to June 2012, namely preoperative chemotherapy for 2 cycles, surgical treatment and postoperative chemotherapy for 6 cycles. There were 18 males and 10 females, whose median age was 35 years old （ range： 15-62 years ）. Combination therapy with cisplatin （ DDP ）, ifosfamide （ IFO ） and adriamycin （ ADM ） was performed before and after the surgery, which was also called DIA chemotherapy. The patients were treated with DDP 120 mg/m2 on the 1st day, ADM 30 mg/m2 and IFO 2.0 g/m2 on the 7th-9th day in sequence and IFO 2.0 g/m2 on the 10th-11th day for a cycle. All the patients were followed up, and CT scans of the lungs and X-ray iflms of the lesion sites were reviewed. The cases of recurrences, metastases and death were recorded. The chemotherapeutic effects were evaluated according to Response Evaluation Criteria in Solid Tumors （ RECIST 1.1 ） guidelines. Common Terminology Criteria for Adverse Events, Version 4.0 （ CTCAE 4.0 ） was used to observe the adverse reaction of chemotherapy.Results All the surgeries were successful, and complete wound healing was achieved as scheduled in all the cases. The mean total blood loss was 260 ml （ range： 50-600 ml ）. It took 38 weeks in DIA chemotherapy, including 2 cycles of preoperative chemotherapy and 6 cycles of postoperative chemotherapy. A total of 224 cycles of chemotherapy were carried out in the 28 patients. They were followed up for 12-59 months.At the end of the follow-up, 23 patients survived. Disease-free survival was realized in 20 patients and survival with tumors in 3 patients, and the survival time was 24-59 months. The 2-year disease-free survival rate was 71.4% and the overall 2-year survival rate was 82.1%. Postoperative metastases were noticed in 5 patients, who all died of lung metastases. Postoperative recurrences were found in 4 patients, and the recurrence rate was 12.3%. Three dimensional conformal radiation therapy was performed on 4 patients with recurrences and 3 patients with lung metastases. The size of tumors was reduced by （ 30.2±11.3 ） % on average after the preoperative chemotherapy, which was reduced by （ 42.7±7.8 ） % in 22 patients whose tumors were more than 15cm in the diameter. Complete remssion （ CR ） was noticed in 0 case, partial remission （ PR ） in 12 cases, stable disease （ SD ） in 14 cases and progression disease （ PD ） in 2 cases. The objective response rate （ ORR ） was 42.9%, and the disease control rate （ DCR ） was 92.9%. The chemotherapy was well tolerated in all the patients, whose main adverse reaction was transient. And the symptoms disappeared after drug treatment.Conclusions The neoadjuvant chemotherapy is important and effective in the treatment of extremity STS. The size of STS can be signiifcantly reduced and the surrounding soft tissue edema can be relieved after the preoperative chemotherapy. The micrometastases can be inhibited, which helps the surgical resection. Both the overall survival rate and disease-free survival rate are improved, which beneifts the limb salvage therapy. The short- and medium-term effects are satisfactory and the adverse reactions are tolerable.