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放射性 3D 打印模板辅助 CT 引导 125I 粒子植入治疗难治性骨转移:一项关于疗效、安全性和免疫功能变化的多中心回顾性分析

英文原题:The radioactive 3D-printed template-assisted CT-guided 125I seed implantation for refractory bone metastases: A multicenter retrospective analysis of efficacy, safety, and immune function changes.

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The radioactive 3D-printed template-assisted CT-guided 125I seed implantation for refractory bone metastases: A multicenter retrospective analysis of efficacy, safety, and immune function changes.

PubMed 2026/05/11(内容时间) PLoS One Q2 · IF 2.8(JCR 2025)

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研究概要

3D 打印模板辅助 CT 引导 125I 粒子植入是治疗难治性骨转移的一种安全有效的方法。它提供了持久的局部肿瘤控制和疼痛缓解,并伴有全身免疫学变化。这些变化与临床改善相关,提示治疗效果中可能存在免疫学成分。因此,该疗法为难治性骨转移提供了一种有前景的治疗策略。

研究思路结论见上方概要

全面评估多中心队列中三维(3D)打印模板辅助CT引导125I粒子植入治疗难治性骨转移的疗效和安全性,探讨其对全身免疫功能的影响并确定潜在机制。

本回顾性分析纳入大连大学附属中山医院、临沂市肿瘤医院、徐州医科大学附属医院、大连市公共卫生临床中心及大连医科大学附属第二医院连续收治的253例难治性骨转移患者。记录疼痛缓解的起效时间和持续时间。通过比较术前和术后每日口服吗啡等效消耗量(OMEC)、疼痛数字评分量表(NRS)、生活质量(QOL)评分和卡氏功能状态(KPS)评分,以及测量术前和术后影像学上靶病灶体积和Hounsfield单位(HU)值的定量变化来评估治疗效果。根据实体瘤疗效评价标准1.1版,计算客观缓解率(ORR)和疾病控制率(DCR)以评估肿瘤反应。采用流式细胞术检测并比较术前和术后CD3+CD16+/CD56+自然杀伤样T(NKT)细胞和CD3-CD16+/CD56+ NK细胞比例、白细胞介素(IL)-17A水平及CD4+/CD8+ T细胞比值,以评估治疗后宿主免疫功能的变化。计算局部无进展生存期(LPFS)和总生存期(OS),并记录不良事件。

所有患者均完成3D打印模板辅助CT引导125I粒子植入,手术成功率为100%。治疗后临床症状改善;疼痛缓解的中位起效时间为3.5天,中位缓解持续时间为10.7个月。OMEC值和NRS评分均显著低于治疗前(P < 0.05),而QOL和KPS评分显著升高(P < 0.05)。影像学评估显示,植入后1个月和6个月的ORR和DCR分别为42.29%和69.56%,以及79.05%和88.93%。靶病灶体积显著缩小(P < 0.05),而HU值显著升高(P < 0.05),提示肿瘤坏死和成骨修复。中位LPFS为14.1个月,中位OS为19.5个月。免疫功能分析显示抗肿瘤免疫应答增强,表现为NKT细胞、NK细胞和CD8+ T细胞比例显著升高,IL-17A水平降低,CD4+/CD8+比值呈正常化趋势(P < 0.05)。不良事件主要为Common Terminology Criteria for Adverse Events 1-2级的短暂局部疼痛。未发生无法控制的大出血、针道种植或其他严重并发症,也未发生治疗相关死亡。

展开英文摘要原文

To comprehensively evaluate the efficacy and safety of three-dimensional (3D)-printed template-assisted CT-guided 125I seed implantation for refractory bone metastases in a multicenter cohort, to explore its impact on systemic immune function and to identify potential mechanisms.

This retrospective analysis was conducted on 253 patients with refractory bone metastases who were continuously admitted to Affiliated Zhongshan Hospital of Dalian University, Linyi Cancer Hospital, The Affiliated Hospital of Xuzhou Medical University, Dalian Public Health Clinical Center, and The Second Hospital of Dalian Medical University. The onset time and the duration of pain relief were recorded. The therapeutic efficacy was evaluated by comparing pre- and postoperative Daily Oral Morphine Equivalent Consumption (OMEC), Numerical Rating Scale (NRS) for pain, Quality of Life (QOL) scores, and Karnofsky Performance Status (KPS) scores, as well as by measuring the quantitative changes in target lesion volume and Hounsfield unit (HU) values on imaging before and after the procedure. According to Response Evaluation Criteria in Solid Tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were calculated to evaluate tumor response. Flow cytometry was used to detect and compare pre- and postoperative proportions of CD3+CD16+/CD56+ natural killer-like T (NKT) cells and CD3-CD16+/CD56+ NK cells, interleukin (IL)-17A level, and CD4+/CD8+ T-cell ratio, to assess the changes in host immune function after treatment. Local progression-free survival (LPFS) and overall survival (OS) were calculated, and adverse events were documented.

All patients completed 3D-printed template-assisted CT-guided 125I seed implantation, with a procedural success rate of 100%. The clinical symptoms improved after treatment; the median onset time to pain relief was 3.5 days, and the median duration of relief was 10.7 months. The OMEC values and the NRS scores were significantly lower than those before procedure (P < 0.05), whereas QOL and KPS scores were significantly higher (P < 0.05). The radiologic evaluation showed that ORR and DCR were 42.29% and 69.56%, and 79.05% and 88.93%, respectively, at 1 and 6 months after implantation. The target lesion volumes reduced significantly (P < 0.05), whereas the HU value increased significantly (P < 0.05), indicating tumor necrosis and osteoblastic repair. The median LPFS was 14.1 months, and the median OS was 19.5 months. The immune function analysis revealed enhanced antitumor immune response, reflected by significant increases in the proportions of NKT cells, NK cells, and CD8+ T cells, a decrease in IL-17A level, and a trend toward normalization of the CD4+/CD8+ ratio (P < 0.05). Adverse events mainly consisted of transient local pain of Common Terminology Criteria for Adverse Events grades 1-2. No uncontrollable major bleeding, needle-track seeding, or other severe complication, and no treatment-related death occurred.

The 3D-printed template-assisted CT-guided 125I seed implantation was a safe and effective treatment for refractory bone metastases. It provided durable local tumor control and pain relief, and was accompanied by systemic immunological changes. These changes correlated with clinical improvements, suggesting a potential immunological component to the therapeutic effect. This therapy therefore provided a promising treatment strategy for refractory bone metastases.

论文信息

作者
Zhao GS、Zhou HZ、Wang QS、Zhou XY、Sun JB、Gao F、Wang RY、Wang Z
第一作者单位
Minimally Invasive Interventional Diagnosis and Treatment Center, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning Province, China.China
通讯作者单位
Department of Interventional Radiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.China
文献类型
多中心研究
期刊
PloS one2026
原文标识
PubMed 42113827 · DOI 10.1371/journal.pone.0347893