Objective: To investigate the clinical efficacy of cryoablation combining with inhibitors in the treatment of epidermal growth factor receptor (EGFR) sensitive mutant lung adenocarcinoma. Methods: Clinical data of 55 patients with advanced lung cancer diagnosed and treated in the Second Affiliated Hospital of Xiamen Medical College from December 2019 to December 2020 were collected. 55 patients were divided into the combination group (n=25) and the monotherapy group (n=30) according to different treatment methods. The monotherapy group was given EGFR-TKI treatment, while the patients in the combination group were treated with cryoablation on the basis of EGFR-TKI treatment. The counts of total lymphocyte, neutrophil and platelet in routine blood test of all patients before treatment were recorded, then the optimal effect and the progression-free survival (PFS) of TKI therapy were recorded in the follow-up. Results: Overall effective rates of the two groups were not statistically different. However, the median PFS of the combination group was 18 months, which was much longer than 10.5 months of the monotherapy group (P＜0.05). Moreover, a Cox proportional hazards model was used to evaluate the potential influencing factors of PFS in TKI therapy. Lung mass greater than 4cm was the hazard factor to disease progression of patients with lung adenocarcinoma. The B value of argon-helium knife cryotherapy was 1.270, which had better benefits for the PFS. However, the diameter of mass greater than 4cm was adverse to the PFS of patients treated with TKI, given that the B value was -1.003. Further to analyze the intervention time of argon-helium knife cryotherapy, no statistical significance was found between the groups given argon-helium knife cryoablation treatment combined with TKI therapy, regardless of the use of TKI at the beginning or the lung mass getting stable after TKI treatment(P＞0.05). Conclusion: Argon-helium knife cryoablation combined with EGFR-TKI to treat EGFR-mutant lung adenocarcinoma could prolong the patients’ PFS. The diameter of lung mass greater than 4cm was the adverse factor to the PFS of patients treated with TKI.
[1] 权瑞泉, 张丽, 匡黎. AP化疗方案治疗EGFR-TKI一线化疗失败非小细胞肺癌患者的疗效及对预后的影响[J]. 癌症进展, 2020, 18(4): 377-379, 417.
[2] 赵秋红, 闫春良, 任冠军. 盐酸埃克替尼对中晚期表皮生长因子受体突变型非小细胞肺癌疗效及免疫指标的影响[J]. 癌症进展, 2020, 18(15): 1589-1592.
[3] Zhang YS, Niu LZ, Zhan K, et al. Percutaneous imaging-guided cryoablation for lung cancer[J]. J Thorac Dis, 2016, 8(Suppl 9): S705-S709.
[4] Mcdevitt JL, Mouli SK, Nemcek AA, et al. Percutaneous cryoablation for the treatment of primary and metastatic lung tumors: identification of risk factors for recurrence and major complications[J]. J Vasc Interv Radiol, 2016, 27(9): 1371-1379.
[5] 张春宁, 程洁茵, 吕华亮, 等. CT引导下氮气冷冻消融术治疗非小细胞肺癌[J]. 中国卫生标准管理, 2020, 11(14): 56-59.
[6] Gage AA, Baust J. Mechanisms of tissue injury in cryosurgery[J]. Cryobiology, 1998, 37(3): 171-186.
[7] 朱玲, 王志远, 赵跃峰, 等. 建立ARMS- LNA- qPCR方法检测肺癌组织中EGFR- T790M突变率[J]. 标记免疫分析与临床, 2020, 27(5): 874-878.
[8] 周怡, 陆明洋, 王琦, 等. 应用ARMS- PCR法检测非小细胞肺癌EGFR基因突变及其临床意义[J]. 标记免疫分析与临床, 2020, 27(7): 1166-1168.
[9] 孙向飞, 张晓炜, 董济民. 晚期非小细胞肺癌EGFR基因突变及其与患者临床特征的相关性[J]. 海南医学, 2020, 31(12): 1500-1503.
[10] 戴玮婧, 李洪涛, 戴丹菁. 奥希替尼对EGFR T790M突变阳性NSCLC患者的疗效及对miR-21水平的影响[J]. 国际检验医学杂志, 2020, 41(14): 1772-1775.
[11] Roeper J, Kurz S, Grohé C, et al. Optimizing therapy sequence to prevent patient attrition in EGFR mutation-positive advanced or metastatic NSCLC[J]. Future Oncol, 2021, 17(4): 471-486.
[12] 周晴, 何瀚夫, 汪晟, 等. 氩氦刀冷冻消融治疗晚期肺癌的安全性和有效性评价[J]. 介入放射学杂志, 2020, 29(1): 70-75.
[13] Succony L, Rassl DM, Barker AP, et al. Adenocarcinoma spectrum lesions of the lung: detection, pathology and treatment strategies[J]. Cancer Treat Rev, 2021, 99: 102237.
[14] Sharma SV, Bell DW, Settleman J, et al. Epidermal growth factor receptor mutations in lung cancer[J]. Nat Rev Cancer, 2007, 7(3): 169-181.
[15] 李龙飞, 柳晨, 曹生亚, 等. 氩氦刀冷冻治疗对肺癌患者免疫功能影响及临床意义[J]. 中华肿瘤防治杂志, 2021, 28(16): 1231-1235.
[16] Baust JG, Snyder KK, Santucci KL, et al. Cryoablation: physical and molecular basis with putative immunological consequences[J]. Int J Hyperthermia, 2019, 36(sup1): 10-16.
[17] 陈军, 邓爱兵, 李绚梅, 等. 氩氦刀冷冻消融联合TP化疗方案治疗肺癌对血清肿瘤标志物水平及预后的影响[J]. 中国医学装备, 2020, 17(9): 94-98.
[18] 段桦, 胡凯文, 王剑锋, 等. 晚期非小细胞肺癌氩氦刀冷冻消融联合化疗疗效和安全性Meta分析[J]. 中华肿瘤防治杂志, 2020, 27(3): 230-239.
[19] 赵海斌, 冯华松, 张绍强. CT引导下氩氦刀联合阿法替尼对肺腺癌患者的临床疗效研究[J]. 中国肿瘤外科杂志, 2019, 11(2): 116-120.
[20] 叶肖菲, 孙德彬, 钟莹. 氩氦冷冻消融、支气管动脉化疗栓塞术联合原靶向药对耐药进展晚期肺腺癌的疗效[J]. 浙江实用医学, 2020, 25(5): 340-342.
[21] 孟激光. 经皮氩氦冷冻治疗联合分子靶向药物治疗晚期非小细胞肺癌[J]. 中国临床医生杂志, 2018, 46(10): 1145-1147.
[22] 张波, 孙运军, 刘松, 等. 冷冻消融联合抑制剂治疗表皮生长因子受体敏感突变非小细胞肺癌的临床疗效[J]. 中国医刊, 2020, 55(7): 793-796.
[23] Suzuki R, Lin SH, Wei X, et al. Prognostic significance of pretreatment total lymphocyte count and neutrophil-to-lymphocyte ratio in extensive-stage small-cell lung cancer[J]. Radiother Oncol, 2018, 126(3): 499-505.
[24] 赵坤宇, 亓妍文, 秦国慧, 等. 中性粒细胞淋巴细胞比值和淋巴细胞单核细胞比值对PD-1抑制剂治疗的晚期非小细胞肺癌患者预后的预测价值[J]. 郑州大学学报(医学版), 2022, 57(3): 379-382.
[25] 周洁, 王畅, 房咏, 等. 中性粒细胞/淋巴细胞比值与小细胞肺癌放疗患者预后的关系[J]. 现代肿瘤医学, 2022, 30(12): 2191-2196.
[26] Valero C, Lee M, Hoen D, et al. Pretreatment neutrophil-to-lymphocyte ratio and mutational burden as biomarkers of tumor response to immune checkpoint inhibitors[J]. Nat Commun, 2021, 12(1): 729.
[27] Jiang T, Chu Q, Wang HJ, et al. EGFR-TKIs plus local therapy demonstrated survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive liver metastases[J]. Int J Cancer, 2019, 144(10): 2605-2612.
[28] 朱魁魁. EGFR敏感突变的晚期NSCLC患者TKI联合肺部病灶SBRT的疗效观察[D]. 武汉: 华中科技大学, 2019.
