局部晚期胰腺癌经调强放射治疗和体部立体定向放射治疗的有效性及安全性的Meta分析
DOI: 10.12449/JCH260518
Efficacy and safety of intensity-modulated radiotherapy versus stereotactic body radiotherapy in treatment of locally advanced pancreatic cancer: A meta-analysis
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摘要:
目的 系统分析调强放射治疗(IMRT)和体部立体定向放射治疗(SBRT)对局部晚期胰腺癌(LAPC)的治疗效果差异,以期为治疗决策提供依据。 方法 计算机检索PubMed、Embase、Cochrane Library、中国知网、万方数据和维普等数据库,检索时间为建库至2025年7月31日。纳入比较IMRT与SBRT治疗LAPC的前瞻性或回顾性队列研究。采用Newcastle-Ottawa量表评估研究质量,Review Manager 5.4进行Meta分析。 结果 共纳入23项研究,合计2 505例患者。在局部控制率方面,纳入13项研究(n=847),SBRT组1年局部控制率为84.5%,显著高于IMRT组的66.7%[相对危险度(RR)=1.27,95%置信区间(CI):1.03~1.56,I2 =28%,P=0.026)。在急性毒性方面,纳入15项研究,SBRT组≥3级急性毒性发生率为3.5%,显著低于IMRT组的11.0%(RR=0.32,95%CI:0.19~0.53,I2=18%,P<0.001)。在总生存期方面,SBRT组的中位值为16.8个月,IMRT组为16.3个月,无明显差异。针对局部控制率的亚组分析显示,按研究质量分层,高质量研究(9项)中SBRT组局部控制率显著高于IMRT组(RR=1.25,P<0.001),中等质量研究(4项)亦然(RR=1.31,P=0.021);按技术平台分层,采用磁共振引导技术的SBRT研究效应量最大(RR=1.40,I²=10%)。敏感性分析显示,RR范围为1.21~1.28,结果稳定。Egger回归检验提示,无明显发表偏倚(P>0.05)。 结论 SBRT在局部控制率和急性毒性方面显著优于IMRT,是LAPC患者的优选治疗方案,尤其以MR引导技术表现最优。 Abstract:Objective To systematically analyze the differences in therapeutic efficacy between intensity-modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT) for locally advanced pancreatic cancer (LAPC), and to provide a basis for treatment decision-making. Methods PubMed, Embase, the Cochrane Library, CNKI, Wanfang Data, and VIP databases were searched for prospective or retrospective cohort studies on IMRT versus SBRT for the treatment of LAPC published up to July 31, 2025. The Newcastle-Ottawa Scale was used to assess the quality of studies, and Review Manager 5.4 was used to perform the Meta-analysis. Results A total of 23 studies involving 2 505 patients were included. In terms of local control rate, an analysis of 13 studies with 847 patients showed that the SBRT group had a significantly higher 1-year local control rate than the IMRT group (84.5% vs 66.7%, relative risk [RR]=1.27, 95% confidence interval [CI]: 1.03 — 1.56, I2=28%, P=0.026). In terms of acute toxicity, an analysis of 15 studies showed that the SBRT group had a significantly lower incidence rate of grade≥3 acute toxicity than the IMRT group (3.5% vs 11.0%, RR=0.32, 95%CI: 0.19 — 0.53, I2=18%, P<0.001). There was no significant difference in overall survival between the SBRT group and the IMRT group (16.8 months vs 16.3 months). The subgroup analysis of local control rate showed that in the 9 high-quality studies, the SBRT group had a significantly higher local control rate than the IMRT group (RR=1.25, P<0.001), and a similar result was observed in the 4 moderate-quality studies (RR=1.31, P=0.021); the stratified analysis based on technique platforms showed that the MR-guided technique group showed the largest effect size (RR=1.40, I2=10%). The sensitivity analysis showed that the RR value ranged from 1.21 to 1.28, with stable results. The Egger regression analysis showed no significant publication bias (P>0.05). Conclusion SBRT is superior to IMRT in terms of local control rate and acute toxicity and is a preferred treatment option for LAPC, with the MR-guided techniques showing the best performance. -
Key words:
- Pancreatic Neoplasms /
- Radiotherapy /
- Meta-Analysis
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表 1 各技术类型研究特征
Table 1. Characteristics of studies by technology type
技术类型 研究数量(项) 前瞻性研究(项) 多中心研究(项) 患者数(例) 剂量范围 分次范围 IMRT[10-12,28,31] 5 1 1 418 48~60 Gy 15~33次 SBRT[8,13-14,16-19,21-26,29-30] 15 5 3 1 014 24~60 Gy 1~8次 技术比较[7,32] 2 1 1 1 029 混合 混合 高级技术[27] 1 1 0 44 50 Gy 5次 总计 23 8 5 2 505 24~60 Gy 1~33次 注:IMRT,调强放射治疗;SBRT,体部立体定向放射治疗。技术比较指同时纳入IMRT和SBRT患者进行比较的研究;高级技术,采用磁共振引导在线自适应放射治疗。
表 2 两组患者基线特征与治疗特征比较
Table 2. Comparison of baseline and treatment characteristics between the two groups of patients
特征 SBRT组(研究数量) IMRT组(研究数量) 评价 中位年龄(岁) 61.7~71.0(17项) 62.0~71.0(5项) 相似 男性(%) 42.0~75.0(16项) 37.0~80.0(5项) 相似 ECOG 0~1分(%) 85.0~100.0(10项) 100.0(5项) 相似 中位肿瘤直径(cm) 3.1~4.2(7项) 2.0~3.5(5项) 数据有限 联合化疗(%) 46~100(18项) 100(5项) 均较高 化疗周期数(个) 3~14(9项) 3~4(5项) 数据有限 注:SBRT,体部立体定向放射治疗;IMRT,调强放射治疗;ECOG,东部肿瘤协作组评分。研究数量包含技术比较及高级技术中涉及相应技术的研究。
表 3 SBRT研究技术平台特征
Table 3. Technical platforms of SBRT studies
第一作者 年份 设备类型 品牌 影像引导 运动管理 自适应 Schellenberg D[17] 2008年 射波刀 Accuray 金标追踪 Synchrony 否 Chang DT[16] 2009年 射波刀 Accuray 金标追踪 呼吸追踪 否 Polistina F[23] 2010年 射波刀 Accuray 金标追踪 呼吸追踪 否 Mahadevan A[22] 2010年 射波刀 Accuray 金标追踪 呼吸追踪 否 Rwigema JC[19] 2011年 射波刀 Accuray 金标追踪 呼吸门控 否 Tozzi A[18] 2013年 直线加速器 Varian CBCT 腹部加压 否 Pollom EL[29] 2014年 射波刀/直线加速器 Accuray/Varian 金标+透视+kV Synchrony/呼吸门控 否 Herman JM[13] 2015年 直线加速器 Varian CBCT ABC/门控/腹压 否 Bordeau K[26] 2022年 MR-Linac ViewRay 实时MRI 屏气 是 Tringale KR[30] 2022年 MR-Linac Elekta 实时MRI 腹部加压 是 Parikh PJ[24] 2023年 MR-Linac ViewRay 实时MRI MRI实时门控 是 Comito T[14] 2023年 直线加速器 Varian CBCT 4DCT 否 Van’t Land FR[21] 2023年 射波刀 Accuray 金标追踪 呼气CT 否 Salas B[8] 2024年 直线加速器 Varian CBCT 4DCT 否 Weisz Ejlsmark M[25] 2024年 MR-Linac Elekta 实时MRI 腹部加压 是 注:SBRT,体部立体定向放射治疗;CBCT,锥形束计算机体层成像;MR-Linac,磁共振引导直线加速器;MRI,磁共振成像;ABC,主动呼吸控制;CT,计算机体层成像;4DCT,四维计算机体层成像;kV,千伏级X线影像。
表 4 纳入研究的质量评价(Newcastle-Ottawa量表)
Table 4. Quality assessment of included studies (Newcastle-Ottawa scale)
第一作者 选择性
(分)可比性
(分)结局
(分)总分 质量 Herman JM[13] 4 2 3 9 极高 Parikh PJ[24] 4 2 3 9 极高 Salas B[8] 4 2 3 9 极高 Weisz Ejlsmark M[25] 4 2 3 9 极高 Goto Y[28] 4 2 2 8 高 Ben-Josef E[31] 3 2 3 8 高 Comito T[14] 3 2 3 8 高 Bordeau K[26] 3 2 3 8 高 Tringale KR[30] 3 2 3 8 高 Van’t Land FR[21] 3 2 2 7 高 Schellenberg D[17] 3 2 2 7 高 Polistina F[23] 3 2 2 7 高 Krishnan S[11] 3 2 2 7 高 Chang DT[16] 3 1 2 6 中等 Mahadevan A[22] 3 1 2 6 中等 Rwigema JC[19] 3 1 2 6 中等 Tozzi A[18] 3 1 2 6 中等 Pollom EL[29] 3 1 2 6 中等 Yovino S[10] 3 1 2 6 中等 Nakamura A[12] 3 2 2 7 高 Zhong J[32] 3 2 3 8 高 Lin JC[7] 3 2 3 8 高 Rudra S[27] 4 2 2 8 高 注:选择性满分4分,可比性满分2分,结局满分3分,总分为9分。
表 5 主要结局指标汇总分析
Table 5. Summary analysis of primary outcome indicators
组别 研究数量
(项)中位OS(月) 1年局部控制率
(%)≥3级毒性
(%)报道OS的
研究(项)报道局部控制
率的研究(项)报道毒性的
研究(项)IMRT组 5 14.8~17.8 59.0~73.1 0~22.0 2 2 4 SBRT组 15 11.6~25.9 27.0~96.8 0~21.4 12 11 11 技术比较组 2 11.6~20.0 0~5.6 2 0 2 高级技术组 1 16.5~25.9 0 1 0 1 注:IMRT,调强放射治疗;SBRT,体部立体定向放射治疗;OS,总生存期。技术比较组因无法单独提取各技术组局部控制率数据而未纳入局部控制率分析。
表 6 敏感性分析结果
Table 6. Results of sensitivity analysis
剔除研究 剩余研究(项) RR 95%CI P值 I2 值 剔除Herman JM[13] 12 1.23 1.07~1.55 0.001 26% 剔除Comito T[14] 12 1.25 1.02~1.52 0.006 30% 剔除Bordeau K[26] 12 1.23 1.04~1.46 0.002 18% 剔除Chang DT[16] 12 1.26 1.04~1.52 0.002 23% 剔除Salas B[8] 12 1.21 1.00~1.47 0.008 25% 剔除Tozzi A[18] 12 1.28 1.05~1.56 0.002 26% RR变化范围 1.21~1.28 1.00~1.55 0.001~0.008 15%~30% 注:RR,相对危险度;CI,置信区间;I2,异质性指数。
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