立体定向放疗联合信迪利单抗和贝伐珠单抗治疗不可切除原发性肝癌的效果分析

张腾; 王权; 李文刚; 段学章

doi:10.12449/JCH250111

立体定向放疗联合信迪利单抗和贝伐珠单抗治疗不可切除原发性肝癌的效果分析

DOI: 10.12449/JCH250111

中国人民解放军总医院第五医学中心肿瘤医学部放射治疗科，北京 100039

伦理学声明：本研究方案经由中国人民解放军总医院第五医学中心伦理委员会审批，批号：KY-2024-8-132-1，所纳入患者均签署知情同意书。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：张腾负责起草及撰写文章；王权负责采集数据并随访；李文刚负责统计分析；段学章负责修改文章并最终定稿。

详细信息

通信作者:
段学章， duanxuezhang2006@163.com （ORCID： 0000-0002-1941-9317）

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出版历程
- 收稿日期: 2024-06-11
- 录用日期: 2024-09-04
- 出版日期: 2025-01-25

Efficacy of stereotactic body radiotherapy combined with sintilimab and bevacizumab in treatment of unresectable hepatocellular carcinoma

Department of Radiation Oncology，Senior Department of Oncology，The Fifth Medical Center of PLA General Hospital，Beijing 100039，China

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Corresponding author: DUAN Xuezhang， duanxuezhang2006@163.com （ORCID： 0000-0002-1941-9317）

摘要

摘要: 目的探讨立体定向放疗联合信迪利单抗和贝伐珠单抗治疗不可切除肝癌的效果、安全性及预后指标。方法选取2022年3月—12月在中国人民解放军总医院第五医学中心放射治疗科接受立体定向放疗联合信迪利单抗和贝伐珠单抗类似物（双达方案）治疗的42例不可切除原发性肝癌患者，给予计划靶区处方剂量为36～50 Gy，分5～6次，连续照射，后序贯双达方案治疗，每3周为1个疗程，直至出现肿瘤进展或严重不良反应。采用Kaplan-Meier法计算总生存率和无进展生存率，并采用Log-rank检验进行比较；Cox比例风险模型分析影响预后的相关因素。结果中位随访时间为21.6个月，客观缓解率为69%，疾病控制率为85.7%，中位无进展生存期为10.0个月（95%CI：6.7～13.0），中位总生存期为23.3个月（95%CI：14.7～31.8）。不良反应多为1～2级，未发生致命性不良反应。治疗后6～8周AFP应答组中位总生存期显著优于AFP未应答组（未达到 vs 11.8个月，P=0.007）。多因素分析显示AFP应答与患者良好的预后相关（HR=0.31，95%CI：0.13～0.75，P=0.009）。结论对于不可切除肝癌患者，立体定向放疗联合双达方案可改善患者生存且安全性可控，治疗后6～8周AFP水平下降>50%可作为潜在预后指标。
- 肝肿瘤 /
- 放射疗法 /
- 甲胎蛋白类 /
- 治疗结果
Abstract: Objective To investigate the efficacy and safety of stereotactic body radiotherapy （SBRT） combined with sintilimab and bevacizumab in the treatment of patients with unresectable hepatocellular carcinoma （uHCC） and related prognostic factors. Methods A total of 42 patients with uHCC who underwent SBRT combined with sintilimab and bevacizumab in Department of Radiation Oncology， The Fifth Medical Centre of PLA General Hospital， from March to December 2022 were enrolled. The prescribed dose of planning target volume was 36‍ ‍—‍ ‍50 Gy in 5‍ ‍—‍ ‍6 fractions for continuous irradiation， followed by the regimen of sintilimab and bevacizumab. Each course of treatment was 3 weeks until the presence of tumor progression or serious adverse events. The Kaplan-Meier method was used to calculate overall survival （OS） rate and progression-free survival （PFS） rate， and the log-rank test was used for comparison between groups； the Cox proportional hazards model was used to investigate the influencing factors for prognosis. Results The median follow-up time was 21.6 months， with an objective response rate of 69%， a disease control rate of 85.7%， a median PFS of 10.0 months （95% confidence interval ［CI］： 6.7‍ ‍—‍ ‍13.0）， and a median OS of 23.3 months （95%CI： 14.7‍ ‍—‍ ‍31.8）. Most adverse events were grade 1‍ ‍—‍ ‍2 events， and there were no fatal adverse events. At 6‍ ‍—‍ ‍8 weeks after treatment， the AFP response group had a significantly better OS than the non-AFP response group （not reached vs 11.8 months， P=0.007）. The multivariate analysis showed that AFP response was associated with the good prognosis of patients （hazard ratio=0.31， 95%CI： 0.13‍ ‍—‍ ‍0.75， P=0.009）. Conclusion For patients with uHCC， SBRT combined with sintilimab and bevacizumab can improve survival with a manageable safety profile， and a >50% reduction in AFP at 6‍ ‍—‍ ‍8 weeks after treatment can be used as a potential prognostic indicator.
- Liver Neoplasms /
- Radiotherapy /
- alpha-Fetoproteins /
- Treatment Outcome

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图 1 肿瘤控制以及生存结局的泳道图

Figure 1. Swimming plots of tumor response and outcomes

下载: 全尺寸图片幻灯片

注： a，PFS；b，OS。

图 2 42例患者无进展生存率和累积生存率

Figure 2. Progression-free survival and overall survival of 42 patients

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图 3 AFP应答组和未应答组的累积生存率

Figure 3. Overall survival of AFP response group and non-response group

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表 1 42例患者基线临床资料

Table 1. The characteristics of 42 patients

指标	数值
年龄［例（%）］
≤50岁	11（26.2）
>50岁	31（73.8）
性别［例（%）］
男	39（92.8）
女	3（7.2）
慢性肝疾病［例（%）］
乙型肝炎	41（97.6）
其他	1（2.4）
PVTT［例（%）］
有	36（85.8）
无	6（14.2）
肿瘤最大径［例（%）］
≤5 cm	14（33.4）
>5 cm	28（66.6）
肝外转移［例（%）］
有	8（19.1）
无	34（80.9）
ECOG评分［例（%）］
0分	35（83.3）
1分	7（16.7）
Child-Pugh分级［例（%）］
A级	26（61.9）
B级	16（38.1）
ALBI分级［例（%）］
1级	8（19.1）
2级	34（80.9）
BCLC分期［例（%）］
B期	1（2.3）
C期	41（97.7）
AFP（ng/mL）	626.5（83.1～4 105.0）
放疗剂量（Gy）	45（45～48）

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表 2 影响OS的单因素分析

Table 2. Univariate analysis for factors affecting OS

临床特征	HR（95%CI）	P值
年龄（≤50岁/>50岁）	0.33（0.10～1.13）	0.077
性别（女/男）	0.74（0.10～5.50）	0.764
门静脉侵犯（无/有）	0.24（0.03～1.79）	0.163
肿瘤大小（≤5 cm/>5 cm）	1.25（0.52～3.01）	0.617
肝外转移（有/无）	1.03（0.35～3.08）	0.953
Child-Pugh分级（A级/B级）	0.53（0.22～1.24）	0.144
ALBI分级（1级/2级）	0.88（0.30～2.62）	0.818
AFP应答（是/否）	0.32（0.14～0.78）	0.011
门静脉侵犯（无/有）	1.11（0.61～2.03）	0.725
用药周期	0.96（0.91～1.01）	0.086
放疗剂量（Gy）	0.99（0.88～1.12）	0.912
ECOG评分（1分/0分）	0.75（0.25～2.26）	0.614

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表 3 治疗相关不良反应

Table 3. Treatment-related adverse events

不良反应	所有级别［例（%）］	3～4级［例（%）］
白细胞减少	10（23.8）	0（0.0）
血小板减少	8（19.0）	1（2.4）
高血压	2（4.8）	0（0.0）
恶心呕吐	3（7.1）	0（0.0）
消化道出血	1（2.4）	0（0.0）
蛋白尿	3（7.1）	0（0.0）
腹水	9（21.4）	1（2.4）
转氨酶升高	10（23.8）	0（0.0）
肾功能不全	1（2.4）	0（0.0）
高胆红素	4（9.5）	0（0.0）
低蛋白血症	10（23.8）	1（2.4）
免疫相关性甲状腺功能减退	3（7.1）	0（0.0）
免疫相关性皮疹	4（9.5）	0（0.0）

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