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不可切除肝细胞癌的外照射放疗

External beam radiotherapy for unresectable hepatocellular carcinoma.

作者信息

Abdel-Rahman Omar, Elsayed Zeinab

机构信息

Clinical Oncology, Faculty of Medicine, Ain Shams University, Lofty Elsayed Street, Cairo, Egypt, 11335.

出版信息

Cochrane Database Syst Rev. 2017 Mar 7;3(3):CD011314. doi: 10.1002/14651858.CD011314.pub2.


DOI:10.1002/14651858.CD011314.pub2
PMID:28267205
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6464365/
Abstract

BACKGROUND: Hepatocellular carcinoma is the most common liver neoplasm, the sixth most common cancer worldwide, and the third most common cause of cancer mortality. Moreover, its incidence has increased dramatically in the past decade. While surgical resection and liver transplantation are the main curative treatments, only around 20% of people with early hepatocellular carcinoma may benefit from these therapies. Current treatment options for unresectable hepatocellular carcinoma include various ablative and transarterial therapies in addition to the drug sorafenib. OBJECTIVES: To assess the benefits and harms of external beam radiotherapy in the management of localised unresectable hepatocellular carcinoma. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (OvidSP), Embase (OvidSP), Science Citation Index Expanded (Web of Science), and clinicaltrials.gov registry. We also checked reference lists of primary original studies and review articles manually for further related articles (cross-references) up to October 6, 2016. SELECTION CRITERIA: Eligible studies included all randomised clinical trials comparing external beam radiotherapy either as a monotherapy or in combination with other systemic or locoregional therapies versus placebo, no treatment, or other systemic or locoregional therapies for people with unresectable hepatocellular carcinoma. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We used a random-effects model as well as a fixed-effect model meta-analysis but in case of discrepancy between the two models (e.g. one giving a significant intervention effect, the other no significant intervention effect), we reported both results; otherwise, we reported only the results from the fixed-effect model meta-analysis. We assessed risk of bias of the included trials using predefined risk of bias domains; assessed risks of random errors with Trial Sequential Analysis; and presented the review results incorporating the methodological quality of the trials using GRADE. MAIN RESULTS: Nine randomised clinical trials with 879 participants fulfilled our inclusion criteria. All trials were at high risk of bias, and we rated the evidence as low to very low quality. All of the included trials compared combined external beam radiotherapy plus chemoembolisation versus chemoembolisation alone in people with unresectable hepatocellular carcinoma; moreover, three of the trials compared external beam radiotherapy alone versus chemoembolisation alone. All trials were conducted in China. The median age in most of the included trials was around 52 years, and most trial participants were male. The median follow-up duration ranged from one to three years. None of the trials reported data on cancer-related mortality, quality of life, serious adverse events, or time to progression of the tumour. For the comparison of radiotherapy plus chemoembolisation versus chemoembolisation alone, the risk ratio for one-year all-cause mortality was 0.51 (95% confidence interval (CI) 0.41 to 0.62; P < 0.001; 9 trials; low-quality evidence); for complete response rate was 2.14 (95% CI 1.47 to 3.13; P < 0.001; 7 trials; low-quality evidence); and for overall response rate defined as complete response plus partial response was 1.58 (95% CI 1.40 to 1.78; P < 0.001; 7 trials; low-quality evidence), all in favour of combined treatment with external beam radiotherapy plus transarterial chemoembolisation and seemingly supported by our Trial Sequential Analysis. Additionally, the combined treatment was associated with a higher risk of elevated total bilirubin and elevated alanine aminotransferase. The risk ratio for the risk of elevated alanine aminotransferase was 1.41 (95% CI 1.08 to 1.84; P = 0.01; very low-quality evidence), while for elevated total bilirubin it was 2.69 (95% CI 1.34 to 5.40; P = 0.005; very low-quality evidence). For the comparison of radiotherapy versus chemoembolisation, the risk ratio for one-year all-cause mortality was 1.21 (95% CI 0.97 to 1.50; 3 trials; I = 0%; very low-quality evidence) which was not supported by our Trial Sequential Analysis.In addition, we found seven ongoing randomised clinical trials evaluating different external beam radiotherapy techniques for people with unresectable hepatocellular carcinoma. AUTHORS' CONCLUSIONS: We found very low- and low-quality evidence suggesting that combined external beam radiotherapy and chemoembolisation may be associated with lower mortality and increased complete and overall response rates, despite an increased toxicity as expressed by a higher rise of bilirubin and alanine aminotransferase. A high risk of systematic errors (bias) as well as imprecision and inconsistency suggest that these findings should be considered cautiously and that high-quality trials are needed to assess further the role of external beam radiotherapy for unresectable hepatocellular carcinoma.

摘要

背景:肝细胞癌是最常见的肝脏肿瘤,是全球第六大常见癌症,也是癌症死亡的第三大常见原因。此外,其发病率在过去十年中急剧上升。虽然手术切除和肝移植是主要的治愈性治疗方法,但只有约20%的早期肝细胞癌患者可能从这些治疗中获益。目前,不可切除肝细胞癌的治疗选择包括各种消融和经动脉治疗以及药物索拉非尼。 目的:评估外照射放疗在局限性不可切除肝细胞癌治疗中的益处和危害。 检索方法:我们检索了Cochrane肝胆组对照试验注册库、Cochrane图书馆中的Cochrane中央对照试验注册库(CENTRAL)、MEDLINE(OvidSP)、Embase(OvidSP)、科学引文索引扩展版(Web of Science)以及clinicaltrials.gov注册库。我们还手动检查了主要原始研究和综述文章的参考文献列表,以查找截至2016年10月6日的其他相关文章(交叉参考文献)。 入选标准:符合条件的研究包括所有随机临床试验,这些试验比较了外照射放疗作为单一疗法或与其他全身或局部区域疗法联合使用与安慰剂、不治疗或其他全身或局部区域疗法,用于不可切除肝细胞癌患者。 数据收集与分析:我们采用了Cochrane期望的标准方法程序。我们使用随机效应模型以及固定效应模型进行荟萃分析,但如果两种模型之间存在差异(例如,一种模型显示有显著的干预效果,另一种模型没有显著的干预效果),我们会报告两种结果;否则,我们仅报告固定效应模型荟萃分析的结果。我们使用预定义的偏倚风险领域评估纳入试验的偏倚风险;使用试验序贯分析评估随机误差风险;并使用GRADE呈现纳入试验方法学质量的综述结果。 主要结果:9项随机临床试验共879名参与者符合我们的纳入标准。所有试验都存在较高的偏倚风险,我们将证据质量评为低至极低。所有纳入试验均比较了不可切除肝细胞癌患者接受外照射放疗联合化疗栓塞与单纯化疗栓塞的效果;此外,其中3项试验比较了单纯外照射放疗与单纯化疗栓塞的效果。所有试验均在中国进行。大多数纳入试验的中位年龄约为52岁,大多数试验参与者为男性。中位随访时间为1至3年。没有一项试验报告与癌症相关的死亡率、生活质量、严重不良事件或肿瘤进展时间的数据。对于放疗联合化疗栓塞与单纯化疗栓塞的比较,1年全因死亡率的风险比为0.51(95%置信区间(CI)0.41至0.62;P<0.001;9项试验;低质量证据);完全缓解率为2.

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[2]
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Biomolecules. 2024-6-25

[3]
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[4]
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Eur J Med Res. 2024-2-7

[5]
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Ann Transl Med. 2022-1

[6]
Outcome and Safety after 103 Radioembolizations with Yttrium-90 Resin Microspheres in 73 Patients with Unresectable Intrahepatic Cholangiocarcinoma-An Evaluation of Predictors.

Cancers (Basel). 2021-10-27

[7]
Overexpression of ADAM9 decreases radiosensitivity of hepatocellular carcinoma cell by activating autophagy.

Bioengineered. 2021-12

[8]
Effect of radiotherapy on survival in advanced hepatocellular carcinoma patients treated with sorafenib: a nationwide cancer-registry-based study.

Sci Rep. 2021-1-15

[9]
2019 Update of Indian National Association for Study of the Liver Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri II Recommendations.

J Clin Exp Hepatol. 2020

[10]
Knockdown of LINC00473 Enhances Radiosensitivity in Hepatocellular Carcinoma via Regulating the miR-345-5p/FOXP1 Axis.

Onco Targets Ther. 2020-1-8

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Cochrane Database Syst Rev. 2017-2-16

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