外源p53基因联合热疗和放射治疗76例晚期软组织肉瘤临床研究

目的 评价重组人p53基因(rAdp53)注射液在不可切除晚期软组织肉瘤的临床疗效及安全性。方法 2005-2012年间共收治不可切除的晚期软组织肉瘤患者76例,其中rAdp53+放疗、热疗(p53组)41例,放疗、热疗(对照组)35例。rAdp53瘤内注射或腔内灌注,1 次/周,1~2×10¹² VP/次,平均8次。放疗2 Gy/次,5 次/周,平均PTV剂量p53组为(56.3±5.3) Gy,对照组为(58.1±4.2) Gy (P>0.05)。热疗采用浅部或深部热疗,2 次/周,平均8次。分别比较两组临床特征、有效率、疾病进展时间、OS期及不良反应。应用Kaplan-Meier法计算OS并Logrank检验和单因素分析,余用χ²检验。结果 p53组较对照组疗后2个月获益率(PR+CR+SD)和LC率明显提高(85%∶54%,P=0.003和49%∶23%,P=0.020),疾病进展时间及OS明显延长(12个月∶5个月,P=0.010及48个月∶31个月,P=0.049)。除一过性发热外,未见加重的放疗及热疗不良反应(P>0.05)。结论 软组织肉瘤采用重组人p53基因注射液结合放疗、热疗是安全而有效的。

Clinical efficacy and safety of recombinant adenovirus-p53 combined with concurrent radiotherapy and hyperthermia in treatment of advanced soft tissue sarcoma:a study of 76 patients

Objective To evaluate the efficacy and safety of recombinant adenovirus-p53(rAdp53) injection combined with radiotherapy and hyperthermia in the treatment of unresectable advanced soft tissue sarcoma.Methods In this retrospective study, we evaluated 76 patients with unresectable advanced primary or recurrent soft tissue sarcoma treated in our hospital from November 2005 to November 2012.These patients received radiotherapy and hyperthermia with rAdp53(p53 group, n=41) or without rAdp53(control group, n=35).rAdp53((1-2)×1012viral particles each time, once a week, 8 times on average) was injected into the tumor or infused into the pelvic cavity.Radiotherapy (2 Gy each time, 5 times a week) was performed for the planning target volume at 56.3±5.3 Gy in the p53 group and 58.1±4.2 Gy in the control group, with no significant difference between the two groups (P>0.05).Superficial or deep thermotherapy was employed 8 times on average (twice a week).Clinical features, response rate, time to progression (TTP), overall survival (OS), and adverse events were compared between the two groups (P>0.05).The Kaplan-Meier method was used to calculate OS;the log-rank test was used for survival difference analysis and univariate prognostic analysis;the chi-square test was used for comparison of categorical data.Results At 2 months after treatment, the p53 group had significantly increased response rate (partial response+ complete response+ stable disease)(85% vs.54%, P=0.003) and local control rate (49% vs.23%, P=0.020) as well as prolonged TTP (12 months vs.5 months, P=0.010) and OS (48 months vs.31 months, P=0.049), as compared with the control group.No adverse events caused by radiotherapy and hyperthermia except transient fever were seen in the two groups.Conclusions Concurrent radiotherapy and hyperthermia combined with rAdp53 injection is effective and safe for patients with advanced soft tissue sarcoma.