国际肿瘤学杂志››2022,Vol. 49››Issue (5): 270-275.doi:10.3760/cma.j.cn371439-20211123-00050
收稿日期:
2021-11-23修回日期:
2022-03-13出版日期:
2022-05-08发布日期:
2022-05-31通讯作者:
姚颐,宋启斌,孙娜 E-mail:yaoyi2018@whu.edu.cn;qibinsong@whu.edu.cnXiao Mengxia1, Yao Yi1,2(), Gao Likun3, Song Qibin1,2(
)
Received:
2021-11-23Revised:
2022-03-13Online:
2022-05-08Published:
2022-05-31Contact:
Yao Yi,Song Qibin E-mail:yaoyi2018@whu.edu.cn;qibinsong@whu.edu.cn摘要:
目的探索非小细胞肺癌(NSCLC)组织中肿瘤间质比(TSR)对肿瘤免疫治疗疗效预测的价值。方法收集2017年1月至2020年12月期间武汉大学人民医院接受免疫检查点抑制剂治疗的ⅢB~Ⅳ期NSCLC患者的临床和组织病理学资料,以50%为TSR界值,将患者分为低TSR组(≤50%)和高TSR组(>50%),比较两组临床病理特征、4周期客观缓解率(ORR)和疾病控制率(DCR)、6周期ORR和DCR以及无进展生存期(PFS)的差异,采用单因素及多因素Cox回归模型分析与PFS相关的预后因素。结果共纳入患者50例,其中低TSR组27例,高TSR组23例。两组年龄(χ2=0.59,P=0.441)、性别(P=0.578)、吸烟史(χ2=0.12,P=0.730)、组织类型(χ2=2.33,P=0.313)、TNM分期(χ2=0.22,P=0.636)、4周期ORR(χ2=0.48,P=0.487)和DCR(P=0.593)、6周期ORR(χ2=0.05,P=0.818)和DCR(P=0.641)差异均无统计学意义;高TSR组较低TSR组脑转移发生率更高[34.8%(8/23)vs. 7.4%(2/27),χ2=4.23,P=0.040]。Kaplan-Meier生存分析显示,与高TSR组相比,低TSR组的PFS明显更长(15.6个月vs. 10.2个月,χ2=13.84,P<0.001)。单因素分析结果显示TSR值(HR=0.29,95%CI为0.14~0.58,P<0.001)、脑转移(HR=2.38,95%CI为1.12~5.05,P=0.024)均与NSCLC患者更差的预后存在相关性。多因素Cox回归分析显示TSR值是影响NSCLC免疫治疗的独立预后因素(HR=0.32,95%CI为0.14~0.70,P=0.004)。结论TSR是NSCLC免疫治疗的独立预后因素,但是否可预测晚期NSCLC免疫治疗的近期疗效仍需进一步研究。
肖梦霞, 姚颐, 高利昆, 宋启斌. 组织TSR值对NSCLC免疫治疗疗效的预测价值[J]. 国际肿瘤学杂志, 2022, 49(5): 270-275.
Xiao Mengxia, Yao Yi, Gao Likun, Song Qibin. Predictive value of tissue TSR for the efficacy of immunotherapy in non-small lung cancer[J]. Journal of International Oncology, 2022, 49(5): 270-275.
表1
50例NSCLC患者中TSR值与不同临床病理特征及免疫治疗疗效的关系[例(%)]"
临床特征 及疗效评价 |
例数 | 低TSR组(n=27) | 高TSR组(n=23) | χ2值 | P值 |
---|---|---|---|---|---|
年龄(岁) | |||||
<60 | 21 | 10(37.0) | 11(47.8) | 0.59 | 0.441 |
≥60 | 29 | 17(63.0) | 12(52.2) | ||
性别 | |||||
男 | 45 | 24(88.9) | 21(91.3) | - | 0.578 |
女 | 5 | 3(11.1) | 2(8.7) | ||
吸烟史 | |||||
有 | 12 | 7(25.9) | 5(21.7) | 0.12 | 0.730 |
无 | 38 | 20(74.1) | 18(78.3) | ||
组织类型 | |||||
腺癌 | 24 | 11(40.7) | 13(56.5) | ||
鳞状细胞癌 | 23 | 15(55.6) | 8(34.8) | 2.33 | 0.313 |
其他 | 3 | 1(3.7) | 2(8.7) | ||
脑转移 | |||||
有 | 10 | 2(7.4) | 8(34.8) | 4.23 | 0.040 |
无 | 40 | 25(92.6) | 15(65.2) | ||
TNM分期 | |||||
Ⅲ | 9 | 6(22.2) | 3(13.0) | 0.22 | 0.636 |
Ⅳ | 41 | 21(77.8) | 20(87.0) | ||
4周期疗效评价 | |||||
iCR | 0 | 0(0) | 0(0) | ||
iPR | 30 | 15(55.6) | 15(65.2) | ||
iSD | 13 | 8(29.6) | 5(21.7) | ||
iPD | 7 | 4(14.8) | 3(13.1) | ||
客观缓解 | 30 | 15(55.6) | 15(65.2) | 0.48 | 0.487 |
疾病控制 | 43 | 23(85.2) | 20(87.0) | - | 0.593 |
6周期疗效评价 | |||||
iCR | 0 | 0(0) | 0(0) | ||
iPR | 18 | 10(43.5) | 8(40.0) | ||
iSD | 21 | 11(47.8) | 10(50.0) | ||
iPD | 4 | 2(8.7) | 2(10.0) | ||
客观缓解 | 18 | 10(43.5) | 8(40.0) | 0.05 | 0.818 |
疾病控制 | 39 | 21(91.3) | 18(90.0) | - | 0.641 |
表2
50例NSCLC患者免疫治疗预后因素分析"
变量 | 单因素分析 | 多因素分析 | |||||
---|---|---|---|---|---|---|---|
HR值 | 95%CI | P值 | HR值 | 95%CI | P值 | ||
年龄 | 0.61 | 0.32~1.19 | 0.147 | 0.82 | 0.41~1.63 | 0.575 | |
吸烟史 | 0.77 | 0.37~1.64 | 0.504 | 0.73 | 0.33~1.61 | 0.432 | |
脑转移 | 2.38 | 1.12~5.05 | 0.024 | 1.26 | 0.53~2.97 | 0.599 | |
TNM分期 | 1.22 | 0.56~2.67 | 0.619 | 1.07 | 0.47~2.45 | 0.874 | |
TSR值 | 0.29 | 0.14~0.58 | <0.001 | 0.32 | 0.14~0.70 | 0.004 |
表3
50例NSCLC患者免疫治疗相关不良反应发生情况[例(%)]"
不良反应 | 任何级别 | 1~2级 | 3~5级 |
---|---|---|---|
发热 | 3(6.0) | 3(6.0) | 0(0) |
恶心 | 7(14.0) | 7(14.0) | 0(0) |
呕吐 | 5(10.0) | 5(10.0) | 0(0) |
疲劳 | 4(8.0) | 4(8.0) | 0(0) |
头痛 | 2(4.0) | 2(4.0) | 0(0) |
咽部疼痛 | 1(2.0) | 1(2.0) | 0(0) |
腰背痛 | 4(8.0) | 4(8.0) | 0(0) |
便秘 | 5(10.0) | 5(10.0) | 0(0) |
口腔干燥症 | 2(4.0) | 2(4.0) | 0(0) |
面部浮肿 | 1(2.0) | 1(2.0) | 0(0) |
肢体浮肿 | 3(6.0) | 3(6.0) | 0(0) |
上肢肌无力 | 1(2.0) | 1(2.0) | 0(0) |
甲状腺功能减退 | 1(2.0) | 1(2.0) | 0(0) |
肝功能异常 | 3(6.0) | 3(6.0) | 0(0) |
贫血 | 14(28.0) | 11(22.0) | 3(6.0) |
白细胞计数减少 | 25(50.0) | 14(28.0) | 11(22.0) |
血小板计数减少 | 10(20.0) | 6(12.0) | 4(8.0) |
中性粒细胞计数减少 | 8(16.0) | 4(8.0) | 4(8.0) |
高钾血症 | 1(2.0) | 1(2.0) | 0(0) |
低钾血症 | 4(8.0) | 2(4.0) | 2(4.0) |
窦性心动过缓 | 1(2.0) | 1(2.0) | 0(0) |
心电图QT间期延长 | 1(2.0) | 1(2.0) | 0(0) |
心力衰竭 | 1(2.0) | 1(2.0) | 0(0) |
免疫相关性皮炎 | 4(8.0) | 4(8.0) | 0(0) |
免疫相关性心肌炎 | 1(2.0) | 0(0) | 1(2.0) |
免疫相关性肺炎 | 3(6.0) | 0(0) | 3(6.0) |
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