腹腔内灌注细胞因子诱导的杀伤细胞联合局部热疗治疗晚期肝癌。

Intraperitoneal perfusion of cytokine-induced killer cells with local hyperthermia for advanced hepatocellular carcinoma.

机构信息

Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510620, Guangdong Province, China.

出版信息

World J Gastroenterol. 2013 May 21;19(19):2956-62. doi: 10.3748/wjg.v19.i19.2956.

DOI:10.3748/wjg.v19.i19.2956

PMID:23704829

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3660821/

Abstract

AIM

To study the effect and tolerance of intraperitoneal perfusion of cytokine-induced killer (CIK) cells in combination with local radio frequency (RF) hyperthermia in patients with advanced primary hepatocellular carcinoma (HCC).

METHODS

Patients with advanced primary HCC were included in this study. CIK cells were perfused intraperitoneal twice a week, using 3.2 × 10⁹ to 3.6 × 10⁹ cells each session. Local RF hyperthermia was performed 2 h after intraperitoneal perfusion. Following an interval of one month, the next course of treatment was administered. Patients received treatment until disease progression. Tumor size, immune indices (CD3⁺, CD4⁺, CD3⁺CD8⁺, CD3⁺CD56⁺), alpha-fetoprotein (AFP) level, abdominal circumference and adverse events were recorded. Time to progression and overall survival (OS) were calculated.

RESULTS

From June 2010 to July 2011, 31 patients diagnosed with advanced primary HCC received intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia in our study. Patients received an average of 4.2 ± 0.6 treatment courses (range, 1-8 courses). Patients were followed up for 8.3 ± 0.7 mo (range, 2-12 mo). Following combination treatment, CD4⁺, CD3⁺CD8⁺ and CD3⁺CD56⁺ cells increased from 35.78% ± 3.51%, 24.61% ± 4.19% and 5.94% ± 0.87% to 45.83% ± 2.48% (P = 0.016), 39.67% ± 3.38% (P = 0.008) and 10.72% ± 0.67% (P = 0.001), respectively. AFP decreased from 167.67 ± 22.44 to 99.89 ± 22.05 ng/mL (P = 0.001) and abdominal circumference decreased from 97.50 ± 3.45 cm to 87.17 ± 4.40 cm (P = 0.002). The disease control rate was 67.7%. The most common adverse events were low fever and slight abdominal erubescence, which resolved without treatment. The median time to progression was 6.1 mo. The 3-, 6- and 9-mo and 1-year survival rates were 93.5%, 77.4%, 41.9% and 17.4%, respectively. The median OS was 8.5 mo.

CONCLUSION

Intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia is safe, can efficiently improve immunological status, and may prolong survival in HCC patients.

摘要

目的

研究细胞因子诱导的杀伤（CIK）细胞腹腔内灌注联合局部射频（RF）热疗治疗中晚期原发性肝癌（HCC）的疗效和耐受性。

方法

纳入中晚期原发性 HCC 患者，每周两次进行 CIK 细胞腹腔内灌注，每次 3.2×10⁹至 3.6×10⁹个细胞。腹腔内灌注后 2 小时进行局部 RF 热疗。间隔 1 个月后进行下一个疗程。患者接受治疗直至疾病进展。记录肿瘤大小、免疫指标（CD3⁺、CD4⁺、CD3⁺CD8⁺、CD3⁺CD56⁺）、甲胎蛋白（AFP）水平、腹围和不良事件。计算无进展生存期（PFS）和总生存期（OS）。

结果

2010 年 6 月至 2011 年 7 月，本研究纳入 31 例中晚期原发性 HCC 患者接受 CIK 细胞腹腔内灌注联合局部 RF 热疗。患者平均接受 4.2±0.6 个疗程（范围：1-8 个疗程）。患者随访 8.3±0.7 个月（范围：2-12 个月）。联合治疗后，CD4⁺、CD3⁺CD8⁺和 CD3⁺CD56⁺细胞分别从 35.78%±3.51%、24.61%±4.19%和 5.94%±0.87%增加至 45.83%±2.48%（P=0.016）、39.67%±3.38%（P=0.008）和 10.72%±0.67%（P=0.001）。AFP 从 167.67±22.44 ng/mL 降至 99.89±22.05 ng/mL（P=0.001），腹围从 97.50±3.45 cm 降至 87.17±4.40 cm（P=0.002）。疾病控制率为 67.7%。最常见的不良事件为低热和轻微腹部红斑，无需治疗即可缓解。中位 PFS 为 6.1 个月。3、6、9 个月和 1 年的生存率分别为 93.5%、77.4%、41.9%和 17.4%。中位 OS 为 8.5 个月。