目的:探索不同放疗方式淋巴细胞亚群的变化及对无疾病进展生存的影响。方法:选取2019年2月至2019年10月于我院行放疗的原发性非小细胞肺癌(Non-Small Cell Lung Cancer, NSCLC)患者共45例,分为静态调强(IMRT)、动态调强(VMAT)两组;于放疗前1周内、放疗剂量至40 Gy时行外周血淋巴细胞及亚群检验;记录两组患者放疗计划参数;对患者进行随访至疾病进展。采用SPSS26.0进行统计学分析。结果:1) 淋巴细胞亚群变化:外周血淋巴细胞总数、CD3+T淋巴细胞亚群、CD3+CD4+T淋巴细胞亚群、CD4+/CD8+比值两组放疗后均减低,VMAT组下降幅度更大。两组比较淋巴细胞总数无统计学差异(P > 0.05),CD3+T淋巴细胞亚群有统计学差异(P < 0.05),CD3+CD4+T淋巴细胞亚群、CD4+/CD8+比值有显著统计学差异(P < 0.01);CD3+CD8+T淋巴细胞亚群两组放疗后均升高,VMAT组上升更明显,差异无统计学差异(P > 0.05)。2) 放疗参数:IMRT与VMAT比较,PTV体积无统计学差异(P > 0.05);双肺V5、V10、V20、V30 VMAT组受量更高(P < 0.05);双肺平均剂量(MLD)、靶区剂量均匀性、适形度指数VMAT组更好(P < 0.05)。3) PFS生存分析发现,两组患者无进展生存时间比较无统计学差异(P > 0.05)。结论:1) NSCLC患者IMRT、VMAT两种放疗方式均引起外周血淋巴细胞减少及淋巴细胞亚群再分布,VAMT组更明显;2) NSCLC患者两种放疗方式的双肺危及器官受量低剂量存在差异,VMAT组更高;双肺平均剂量、靶区剂量均匀性、适形度指数VMAT组更优;3) IMRT、VMAT两种不同的放疗方式下,两组患者无疾病进展生存期无明显差异。 Objective: The objective is to explore the variation of lymphocyte subsets between Intensity Modulated Radiation Therapy (IMRT) and Volumetric Modulated Arc Radiotherapy (VMAT), and the effect of the variation on Progression-Free Survival in patients with primary NSCLC(non-small cell lung cancer). Methods: A total of 45 patients who received radiotherapy (RT) in the radiotherapy department of our hospital from February 2019 to October 2019 were enrolled and divided into IMRT group and VMAT group. The peripheral blood lymphocyte and subgroup tests were performed at 1 week before RT and when the RT dose was up to 40 Gy. RT planning parameters of two groups were recorded. Patients were followed up for disease progression. SPSS26.0 was used for statistical analysis. Results: 1) Lymphocyte and subsets parameters: the total number of peripheral blood lymphocytes, CD3+T lymphocyte subsets, CD3+CD4+T lymphocyte subsets, CD4+/CD8+ ratio decreased, and significantly decreased in VMAT group. Comparison between groups: peripheral blood lymphocytes (P > 0.05), CD3+T lymphocyte subsets (P < 0.05), and there was significant difference in CD3+CD4+T lymphocyte subsets, CD4+/CD8+ ratio, P < 0.01. The CD3+CD8+T lymphocyte subsets increased and were more obvious in VMAT group (P > 0.05). 2) RT parameters: there was no statistical difference in PTV volume between the two groups (P > 0.05). V5, V10, V20 and V30 VMAT groups received higher doses (P < 0.05). Mean lung dose (MLD), Homogeneity Index (HI) and Conformity Index (CI) are better in VMAT group (P < 0.05). 3) PFS analysis showed that there was no difference between the two groups (P > 0.05). Conclusions: 1) Lymphocytopenia and redistribution of lymphocyte subsets in peripheral blood of patients with NSCLC were induced by different RT methods, especially in the VAMT group; 2) There are differences in the low-dose region of the double lung organs at risk in different radiotherapy modalities of IMRT and VMAT for NSCLC, which is higher in VMAT group. The mean lung dose (MLD), Homogeneity Index (HI) and Conformity Index (CI) are better in VMAT group; 3) There was no significant difference in progression-free survival between the two groups under IMRT and VMAT radiotherapy.
目的:探索不同放疗方式淋巴细胞亚群的变化及对无疾病进展生存的影响。方法:选取2019年2月至2019年10月于我院行放疗的原发性非小细胞肺癌(Non-Small Cell Lung Cancer, NSCLC)患者共45例,分为静态调强(IMRT)、动态调强(VMAT)两组;于放疗前1周内、放疗剂量至40 Gy时行外周血淋巴细胞及亚群检验;记录两组患者放疗计划参数;对患者进行随访至疾病进展。采用SPSS26.0进行统计学分析。结果:1) 淋巴细胞亚群变化:外周血淋巴细胞总数、CD3+T淋巴细胞亚群、CD3+CD4+T淋巴细胞亚群、CD4+/CD8+比值两组放疗后均减低,VMAT组下降幅度更大。两组比较淋巴细胞总数无统计学差异(P > 0.05),CD3+T淋巴细胞亚群有统计学差异(P < 0.05),CD3+CD4+T淋巴细胞亚群、CD4+/CD8+比值有显著统计学差异(P < 0.01);CD3+CD8+T淋巴细胞亚群两组放疗后均升高,VMAT组上升更明显,差异无统计学差异(P > 0.05)。2) 放疗参数:IMRT与VMAT比较,PTV体积无统计学差异(P > 0.05);双肺V5、V10、V20、V30 VMAT组受量更高(P < 0.05);双肺平均剂量(MLD)、靶区剂量均匀性、适形度指数VMAT组更好(P < 0.05)。3) PFS生存分析发现,两组患者无进展生存时间比较无统计学差异(P > 0.05)。结论:1) NSCLC患者IMRT、VMAT两种放疗方式均引起外周血淋巴细胞减少及淋巴细胞亚群再分布,VAMT组更明显;2) NSCLC患者两种放疗方式的双肺危及器官受量低剂量存在差异,VMAT组更高;双肺平均剂量、靶区剂量均匀性、适形度指数VMAT组更优;3) IMRT、VMAT两种不同的放疗方式下,两组患者无疾病进展生存期无明显差异。
非小细胞肺癌,调强放疗,容积旋转调强,淋巴细胞亚群
Jinqiu Li1*, Cong Wang1, Shanglin Dong2, Yunbo Zhang3, Xin Ji1, Zhilin Zhang1, Chengbo Ren1, Huan Ma1
1Radiotherapy Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou Hebei
2Medical Imaging Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou Hebei
3Oncology Department, Zibo Bashan Wanjie Hospital, Zibo Shandong
Received: Aug. 22nd, 2021; accepted: Sep. 12th, 2021; published: Sep. 26th, 2021
Objective: The objective is to explore the variation of lymphocyte subsets between Intensity Modulated Radiation Therapy (IMRT) and Volumetric Modulated Arc Radiotherapy (VMAT), and the effect of the variation on Progression-Free Survival in patients with primary NSCLC(non-small cell lung cancer). Methods: A total of 45 patients who received radiotherapy (RT) in the radiotherapy department of our hospital from February 2019 to October 2019 were enrolled and divided into IMRT group and VMAT group. The peripheral blood lymphocyte and subgroup tests were performed at 1 week before RT and when the RT dose was up to 40 Gy. RT planning parameters of two groups were recorded. Patients were followed up for disease progression. SPSS26.0 was used for statistical analysis. Results: 1) Lymphocyte and subsets parameters: the total number of peripheral blood lymphocytes, CD3+T lymphocyte subsets, CD3+CD4+T lymphocyte subsets, CD4+/CD8+ ratio decreased, and significantly decreased in VMAT group. Comparison between groups: peripheral blood lymphocytes (P > 0.05), CD3+T lymphocyte subsets (P < 0.05), and there was significant difference in CD3+CD4+T lymphocyte subsets, CD4+/CD8+ ratio, P < 0.01. The CD3+CD8+T lymphocyte subsets increased and were more obvious in VMAT group (P > 0.05). 2) RT parameters: there was no statistical difference in PTV volume between the two groups (P > 0.05). V5, V10, V20 and V30 VMAT groups received higher doses (P < 0.05). Mean lung dose (MLD), Homogeneity Index (HI) and Conformity Index (CI) are better in VMAT group (P < 0.05). 3) PFS analysis showed that there was no difference between the two groups (P > 0.05). Conclusions: 1) Lymphocytopenia and redistribution of lymphocyte subsets in peripheral blood of patients with NSCLC were induced by different RT methods, especially in the VAMT group; 2) There are differences in the low-dose region of the double lung organs at risk in different radiotherapy modalities of IMRT and VMAT for NSCLC, which is higher in VMAT group. The mean lung dose (MLD), Homogeneity Index (HI) and Conformity Index (CI) are better in VMAT group; 3) There was no significant difference in progression-free survival between the two groups under IMRT and VMAT radiotherapy.
Keywords:NSCLC, IMRT, VMAT, Lymphocyte Subsets
Copyright © 2021 by author(s) and Hans Publishers Inc.
This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).
http://creativecommons.org/licenses/by/4.0/
肺癌是全球癌症死亡的主要原因之一,在中国目前位于恶性肿瘤死亡第1位 [
选取2019年2月至2019年10月于我院行放疗的原发性NSCLC患者共45例纳入研究,入组标准:1) 肺癌经病理结果证实;按照AJCC8版分期为III期;2) 年龄 ≥ 18周岁;3) PS评分0~2分;4) 本地居民,配合随访。排除标准:1) 既往放疗史;2) 既往器官移植病史;3) 合并系统性免疫疾病;4) 合并活动性感染;5) 近3周内无抗肿瘤治疗。以放疗技术的不同分为两组:静态调强放疗(IMRT)组,24人;动态调强放疗(VMAT)组,21人。两组患者性别、年龄、病理类型、TNM分期(均为M0)、PS评分均无统计学差异。所有入组患者均签署知情同意书,我院医学伦理委员会批准编号:R2020275。
对入组患者分别于放疗前1周内、放疗剂量至40 Gy时行空腹外周血采集,血标本4 mL于EDTA真空抗凝管、4 mL于真空非抗凝管,常温下保存,离体4小时内抗凝管标本流式细胞仪下检测淋巴细胞亚群,非抗凝管标本全自动血液分析仪下检测淋巴细胞总数。
患者仰卧于定位床,双手交叉抱肘置额前,热塑膜体位固定,自然呼吸状态下行PIHLIPS Bigbore16排CT (荷兰飞利浦公司)扫描,扫描范围:环状软骨水平至肝下界,扫描层厚5 mm。扫描三维图像传输至Eleckta Focal工作站行靶区勾画。
根据支气管镜、胸部增强CT、PET/CT等,勾画肿瘤原发灶(GTVp)、阳性淋巴结(GTVnd)、临床靶区(CTV)、内靶区(ITV)、计划靶区(PTV)及危机器官(OAR),GTVp为支气管镜及增强CT或PET/CT提示肿瘤范围,GTVnd为阳性淋巴结,ITV为根据呼吸运动范围外扩得到的靶区范围,CTV为GTVp、GTVnd各向均匀外扩5 mm并根据解剖修正后的范围,计划靶区为靶区三维外扩5 mm得到。危机器官和组织包括:双肺、食管、脊髓、心脏。处方剂量PGTVp、PTGVnd 60~66 Gy,PTV 50~60 Gy,1.8~2.2 Gy/次,5次/周,危及器官限量:双肺V5 ≤ 58%、V20 ≤ 28%,心脏V30 ≤ 40%,脊髓Dmax ≤ 45 Gy。根据靶区剂量、靶区适形度、剂量体积直方图对放疗计划进行优化评估,要求≥95%的PTV体积接受≥99%的处方剂量,剂量冷点不在PTV内,剂量热点不在危及器官内。治疗设备为Eleckta Snegery、Eleckta Infinity。
1) 淋巴细胞指标观察两组患者外周血淋巴细胞总数、CD3+T淋巴细胞亚群,CD3+CD4+T淋巴细胞亚群,CD3+CD8+T淋巴细胞亚群,CD4+/CD8+比值。
2) 放疗指标观察两组患者PTV体积,双肺V5 (表示受5 Gy剂量照射的肺的体积占双肺总体积的百分比)、V10、V20、V30、V40、V50、肺平均剂量(Mean Lung Dose, MLD),剂量均匀性指数(Homogeneity Index, HI)、适形度指数(Conformity Index, CI)。
3) 通过随访获得所有患者无疾病进展生存数据。
采用SPSS26.0进行统计学分析,计数资料以率(%)表示,计量资料以平均数 ± 标准差( χ ¯ ± s )表示,采用卡方检验、t检验进行统计分析,生存分析采用Kalpan-Meier曲线,P < 0.05为差异有统计学意义,P < 0.01为差异有显著统计学意义。
外周血淋巴细胞总数两组患者放疗后均减低,VMAT组下降幅度更大,两组差异无统计学差异,P > 0.05;CD3+T淋巴结细胞亚群两组放疗后均减低,VMAT组下降更明显,差异有统计学差异,P < 0.05;CD3+CD4+T淋巴细胞亚群两组放疗后均减低,VMAT组下降更明显,具有显著统计学差异,P < 0.01;CD3+CD8+T淋巴细胞亚群两组放疗后均升高,VMAT组上升更明显,差异无统计学差异,P > 0.05;CD4+/CD8+比值两组放疗后均减低,VMAT组下降更明显,具有显著统计学差异,P < 0.01。详细资料见表1。
时间 | IMRT组 | VMAT组 | P值 | ||
---|---|---|---|---|---|
放疗前 | 放疗后 | 放疗前 | 放疗后 | ||
淋巴细胞总数 | 1.30 ± 0.62 | 1.04 ± 0.60 | 1.39 ± 0.66 | 1.21 ± 0.53 | 0.81 |
CD3+T | 68.43 ± 11.65 | 64.30 ± 12.37 | 69.53 ± 11.91 | 59.99 ± 10.80 | 0.04 |
CD3+CD4+T | 37.12 ± 10.50 | 31.60 ± 9.31 | 38.74 ± 8.70 | 26.00 ± 5.99 | 0.01 |
CD3+CD8+T | 30.48 ± 10.40 | 32.86 ± 12.17 | 30.20 ± 8.60 | 33.53 ± 8.85 | 0.71 |
CD4+/CD8+ | 1.38 ± 0.74 | 1.14 ± 0.67 | 1.42 ± 0.62 | 0.85 ± 0.36 | 0.01 |
表1. IMRT与VMAT两组淋巴细胞亚群放疗前后变化
IMRT、VMAT两组患者比较,PTV体积无明显差异,P > 0.05;双肺危及器官受量,V5、V10、V20有显著统计学差异,P < 0.01,V30有统计学差异,P < 0.05,VMAT组受量更高;V40、V50两组无差异,P > 0.05;双肺平均剂量,两组有显著统计学差异,P = 0.001,VMAT组受量更低。靶区剂量均匀性、适形指数VMAT组更好,差异具有统计学差异,P < 0.05。详情见表2。
生存随访至2021-5,最长随访时间18个月,最短随访时间15个月,IMRT组平均无进展生存时间11.23个月,VMAT组平均无进展生存时间11.12个月,IMRT组延长0.11个月,两组患者无进展生存时间比较无统计学差异,P值0.525。生存曲线见图1。
IMRT | VMAT | P值 | |
---|---|---|---|
PTV体积(cm3) | 319.91 ± 209.56 | 332.01 ± 130.65 | 0.824 |
V5 | 46.65 ± 11.27 | 52.41 ± 8.11 | 0.01 |
V10 | 35.36 ± 8.32 | 39.32 ± 6.51 | 0.01 |
V20 | 22.75 ± 3.70 | 25.55 ± 4.86 | 0.00 |
V30 | 16.37 ± 3.10 | 17.74 ± 4.46 | 0.04 |
V40 | 11.27 ± 2.76 | 11.88 ± 3.85 | 0.57 |
V50 | 7.10 ± 2.20 | 7.37 ± 3.12 | 0.82 |
MLD* | 1262.65 ± 235.46 | 1077.40 ± 169.27 | 0.00 |
HI* | 0.060 ± 0.017 | 0.043 ± 0.055 | 0.04 |
CI* | 0.809 ± 0.037 | 0.841 ± 0.055 | 0.03 |
表2. IMRT与VMAT两组剂量学参数的比较
*: MLD: Mean Lung Dose; HI: Homogeneity Index; CI: Conformity Index.
图1. IMRT与VMAT组平均无进展生存时间统计图
放疗在肺癌中的应用,10年前约64.3% [
放疗可以引起淋巴细胞减少已经被多项研究证实 [
综上所述,本研究通过对不同放疗方式的肺癌患者进行研究得出结论,IMRT、VMAT两种方式均引起外周血淋巴细胞计数的减低及淋巴细胞亚群的再分布;尽管VAMT具有更好的靶区适形度和剂量均匀性、更低的双肺平均剂量,IMRT在放疗低剂量弥散区V5、V10、V20、V30具有更好的优势,两组患者在PFS上无明显差异,IMRT组中位PFS延长0.11月,无实际临床意义。提示我们在局部晚期肺癌根治性放疗手段的选择上,IMRT和VMAT均可以,可以根据患者对放疗治疗时间的要求、心脏等危及器官剂量限制及双肺耐受放疗剂量的不同等多种因素,综合权衡取舍。本研究存在的缺陷在于,未考虑放疗期间化疗、营养支持、辅助治疗等因素对研究结果的干扰,以及随着随访时间的延长,疾病的无进展生存的对比结果是否能转化成总生存的结果不得而知,等待研究后续更新。
2021年度河北省医学科学研究课题计划(20210831)。
李锦秋,王 聪,董尚林,张云波,冀 鑫,张志林,任成波,马 欢. NSCLC围放疗期淋巴细胞亚群变化对无疾病进展生存期的影响Effect of Lymphocyte Subsets Variation on Progression-Free Survival of NSCLC during Peri-Radiotherapy Period[J]. 临床医学进展, 2021, 11(09): 4283-4289. https://doi.org/10.12677/ACM.2021.119627