非小细胞肺癌免疫治疗的诊断影响因素

03低剂量应使用具体情况

肠道菌类不数在人体生物学合成全过程中会发挥抑制作用，而且还能调控免疫反应系统从而维持宿主的生理动态。低剂量虽然在病变呕吐围治疗期传染和放化时疗引来的免疫反应抑制系统性传染中会较差预防抑制作用，但其在应使用中会可进一步因素肠道菌类的适度[12]。后半期NSCLC呕吐大多较差过量史，而过量可损害支气管局部上皮的免疫反应动态和纤毛正向的黏液清除动态，更易随之而来胃部传染[13]；过量引来的小气道慢性阻塞性肝癌可引来频繁的支气管传染和慢性咳嗽、咳痰，使呕吐只能一一用药低剂量。Galli等[14]的一项关于NSCLC的医学深入研究找到，在ICI病人全过程中会若低剂量应使用延时激过ICI病人延时的4.2%时，应使用低剂量相比于未能应使用低剂量呕吐的OS(5.1个月初 vs. 13.2个月初，P<0.001)和无实质性生存期(progression-free survival，PFS)(1.9个月初 vs. 3.5个月初，P<0.001)数有突出缩短。此外，Ouaknine Krief等[15]的深入研究表明，在ICI病人NSCLC呕吐的全过程中会，未能应使用低剂量呕吐的中会位OS比早期应使用低剂量(ICI开始前2个月初至前1个月初)的相当长(13.4个月初 vs. 5.1个月初，P＝0.03)。一项关于评估低剂量在NSCLC的ICI功效的Meta深入研究中会也有类似找到，在ICI病人之前或过后应使用低剂量可使NSCLC呕吐中会位OS缩短6个月初以上，并且这种效果取决于低剂量应使用时间窗口的长短，当呕吐在ICI开始前后60 d应使用低剂量时对ICI功效的因素相当大[16]。这进一步指出在ICI病人全过程中会低剂量的应使用是NSCLC呕吐的不顺病状诱因。这可能是由于低剂量对肠道微生物学区系的破坏随之而来ICI功效降低，而良好的肠道微生物学区系可通过促进促原提呈和效应T肝细胞动态从而促进促病变免疫反应应答[17]。

04甲状腺激素应使用具体情况

由于抗病毒甲状腺激素的免疫反应抑制特性使其主要使用ICI引来的irAE，后半期NSCLC呕吐病人全过程中会可能相当只能应使用糖皮质甲状腺激素操控系统性医学呕吐如呼吸困难、胃部传染及姑息病人等[18]。Fucà等[19]在一项不属于151事例NSCLC呕吐转用ICI病人的回顾性深入研究中会找到，糖皮质甲状腺激素随之而来PFS风险升高80%(P＝0.003)。Petrelli等[20]深入研究表明，与未能过量抗病毒甲状腺激素的呕吐相比，过量甲状腺激素呕吐的OS(HR＝1.54，P＝0.01)和PFS(HR＝1.34，P＝0.03)的风险数有升高；并且找到甲状腺激素使用脑移到(HR＝1.51，P<0.01)和支持病人(HR＝2.5，P<0.01)都于OS的不顺因素诱因；但使用病人irAE时并非OS的不顺因素诱因。这可能是由于应使用皮质抗病毒进行姑息病人的亚组呕吐本身某种程度病状较差。皮质抗病毒负效应只有在病人病变系统性的姑息适应证时才明显，使用非病变系统性性肝癌，如免疫性反应性肝癌、慢性阻塞性脾肝癌发作和预防过敏反应等，则与不顺的病状无关[21]。KEYNOTE-407深入研究找到，无论是只能皮质抗病毒促过敏预处理的紫杉醇，还是不只能预处理的纳米白蛋白结合型紫杉醇，在含铂类双药化时疗可行性中会添加里斯博利珠单促数有可强化鳞状NSCLC呕吐的OS[22]。在NSCLC呕吐ICI病人全过程中会，应使用抗病毒甲状腺激素来操控病变本身引来的系统性呕吐只能谨慎。

05irAE

在免疫反应病人全过程中会irAE的时有发生是由于以致于激来时的T肝细胞随之而来免疫反应效应，对ICI有功效的呕吐中会时有发生免疫性反应毒性的可能性相当大[23]。一项针对270事例NSCLC呕吐的回顾性深入研究找到，与时有发生irAE的呕吐相比，未能时有发生irAE呕吐的中会位PFS(5.2个月初 vs. 1.97个月初，HR＝0.42，P<0.001)明显延长，客观缓解率(objective response rate，ORR)(22.9% vs. 5.7%，P<0.001)也明显增加，但irAE的严重程度与功效无关[24]。Ricciuti等[25]在一项大型回顾性深入研究中会评估了来自多中会心的195事例给与纳武利劳单促病人NSCLC呕吐的功效，43.6%的呕吐时有发生了irAE，与没有时有发生irAE的呕吐相比，时有发生irAE的呕吐在ORR(43.5% vs. 10.0%，P<0.001)、PFS(5.7个月初 vs. 2.0个月初，HR＝0.41，P<0.001)和OS(17.8个月初 vs. 4.0个月初，HR＝0.33，P<0.001)方面数有有突出强化。另一项针对NSCLC的回顾性深入研究指出，在ICI病人的早期阶段获得完全缓解或部分缓解的呕吐中会，如果用药过后未能出原为irAE，其中会位PFS只有5.6个月初，而时有发生irAE呕吐的中会位PFS为19.1个月初(P<0.01)，指出irAE是ICI功效的强力预测变异[26]。若时有发生irAE，则预示ICI病人能够取得相当好的医学功效。在医学实践中会，如果时有发生严重的irAE，往往会停止ICI病人，如何把控irAE的严重程度还只能熟悉深入研究。

06马达突变

较差原癌马达突变的NSCLC呕吐，遗传表达病人与酪氨酸激酶肽(tyrosine kinase inhibitor，TKI)相比，明显强化NSCLC呕吐的病状，但在9~14个月初后随之而来耐药[27]。Ichihara等[28]在一项不属于58事例上皮生长变异受体(epidermal growth factor receptor，EGFR)突变型NSCLC呕吐的医学深入研究中会找到，更进一步给与EGFR-TKI病人后PFS≥6个月初的呕吐比<6个月初的呕吐经ICI病人后的PFS相当短(5.3个月初 vs. 12.1个月初，P＝0.002 5)，指出在NSCLC的呕吐中会EGFR突变为不顺病状诱因。Lee等[29]在一项Meta深入研究中会指出，ICI在后半期NSCLC的二线和后续病人中会与多西他赛相比，OS风险比降低31%，进一步亚组深入研究指出在EGFR野生型呕吐中会ICI可明显延长OS(HR＝0.67，P<0.001)，但在EGFR突变型的呕吐中会OS并未能得到延长(HR＝1.11，P＝0.540)。尚有关于ICI与马达突变NSCLC呕吐的大型医学深入研究未能达到深入研究终点[30]，ICI病人在EGFR突变的NSCLC呕吐中会的医学意义还只能进一步探究。

Pyo等[31]的深入研究将ALK无呕吐的转遗传脾腺癌豚鼠随机分作促PD-1组、色瑞替尼组、促PD-1倡议色瑞替尼组，3组豚鼠PFS大致相同13 d、132 d、129 d，并没有注意到到ICI倡议遗传表达病人比单药遗传表达病人较差战术上。这可能是由于病变免疫反应微环境对病人反应的动态变化时中会，马达遗传无呕吐的NSCLC考虑到病变标记和免疫反应特异性病变远距离抑制作用变异。在伴有马达突变的NSCLC中会，应使用ICI病人病状较差，但同时应该有其他ICI敏感的突变基因型还有待于大样本遗传测序的熟悉挖掘。

07结语

年龄、性别、低剂量、抗病毒甲状腺激素、irAE、马达突变等诱因可因素ICI的功效，这些将有助于ICI病人过后的精细化时负责管理，从而强化呕吐生命密度和某种程度病状；但目前NSCLC的ICI病人仍实际上一般而言原因：考虑到有效的数学模型对上述医学诱因定性、定量及整合，不利于全面全面性预测ICI呕吐病状；考虑到有效生物学研究课题(劳其亦然摧残性研究课题)预测ICI医学功效；其他因素心脏病病状的诱因与ICI的相关性尚未能清楚，有待于多中会心大样本的医学深入研究来进一步探究。随着对因素心脏病ICI诱因的不断熟悉深入研究，熟练ICI病人将成为强化NSCLC病状的重要手段。

利益冲突所有编者数有声明不实际上利益冲突

请求注意：

PlanchardD, PopatS, KerrK, et al. Metastatic non-small cell lung cancer: ESMO cinical practice guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2018, 29(Suppl 4): iv192-iv237. DOI: 10.1093/annonc/mdy275.

KashimaJ, KitadaiR, OkumaY. Molecular and morphological profiling of lung cancer: a foundation for " next-generation" pathologists and oncologists[J]. Cancers (Basel), 2019, 11(5): 599. DOI: 10.3390/cancers11050599.

CaoJ, LiJ, YangX, et al. Transcriptomics analysis for the identification of potential age-related genes and cells associated with three major urogenital cancers[J]. Sci Rep, 2021, 11(1): 641. DOI: 10.1038/s41598-020-80065-y.

CorbauxP, MailletD, BoespflugA, et al. Older and younger patients treated with immune checkpoint inhibitors have similar outcomes in real-life setting[J]. Eur J Cancer, 2019, 121: 192-201. DOI: 10.1016/j.ejca.2019.08.027.

SpigelDR, McCleodM, JotteRM, et al. Safety, Efficacy, and patient-reported health-related quality of life and symptom burden with nivolumab in patients with advanced non-small cell lung cancer, including patients aged 70 years or older or with poor performance status (CheckMate 153)[J]. J Thorac Oncol, 2019, 14(9): 1628-1639. DOI: 10.1016/j.jtho.2019.05.010.

NishijimaTF, MussHB, ShacharSS, et al. Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: a systematic review and meta-analysis[J]. Cancer Treat Rev, 2016, 45: 30-37. DOI: 10.1016/j.ctrv.2016.02.006.

EliasR, Giobbie-HurderA, McClearyNJ, et al. Efficacy of PD-1 & PD-L1 inhibitors in older adults: a meta-analysis[J]. J Immunother Cancer, 2018, 6(1): 26. DOI: 10.1186/s40425-018-0336-8.

BrahmerJ, ReckampKL, BaasP, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer[J]. N Engl J Med, 2015, 373(2): 123-135. DOI: 10.1056/NEJMoa1504627.

BorghaeiH, GettingerS, VokesEE, et al. Five-year outcomes from the randomized, phase Ⅲ trials checkmate 017 and 057: nivolumab versus docetaxel in previously treated non-small-cell lung cancer[J]. J Clin Oncol, 2021, 39(7): 723-733. DOI: 10.1200/JCO.20.01605.

KanjanapanY, DayD, WangL, et al. Hyperprogressive disease in early-phase immunotherapy trials: clinical predictors and association with immune-related toxicities[J]. Cancer, 2019, 125(8): 1341-1349. DOI: 10.1002/cncr.31999.

ConfortiF, PalaL, BagnardiV, et al. Cancer immunotherapy efficacy and patients′ sex: a systematic review and meta-analysis[J]. Lancet Oncol, 2018, 19(6): 737-746. DOI: 10.1016/S1470-2045(18)30261-4.

ReedJP, DevkotaS, FiglinRA. Gut microbiome, antibiotic use, and immunotherapy responsiveness in cancer[J]. Ann Transl Med, 2019, 7(Suppl 8): S309. DOI: 10.21037/atm.2019.10.27.

PassaroA, AttiliI, MorgantiS, et al. Clinical features affecting survival in metastatic NSCLC treated with immunotherapy: a critical review of published data[J]. Cancer Treat Rev, 2020, 89: 102085. DOI: 10.1016/j.ctrv.2020.102085.

GalliG, TriulziT, ProtoC, et al. Association between antibiotic-immunotherapy exposure ratio and outcome in metastatic non small cell lung cancer[J]. Lung Cancer, 2019, 132: 72-78. DOI: 10.1016/j.lungcan.2019.04.008.

Ouaknine KriefJ, Helly de TauriersP, DumenilC, et al. Role of antibiotic use, plasma citrulline and blood microbiome in advanced non-small cell lung cancer patients treated with nivolumab[J]. J Immunother Cancer, 2019, 7(1): 176. DOI: 10.1186/s40425-019-0658-1.

LurienneL, CervesiJ, DuhaldeL, et al. NSCLC immunotherapy efficacy and antibiotic use: a systematic review and meta-analysis[J]. J Thorac Oncol, 2020, 15(7): 1147-1159. DOI: 10.1016/j.jtho.2020.03.002.

GopalakrishnanV, SpencerCN, NeziL, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients[J]. Science, 2018, 359(6371): 97-103. DOI: 10.1126/science.aan4236.

HaanenJBAG, CarbonnelF, RobertC, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2018, 29(suppl_4): iv264-iv266. DOI: 10.1093/annonc/mdy162.

FucàG, GalliG, PoggiM, et al. Modulation of peripheral blood immune cells by early use of steroids and its association with clinical outcomes in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors[J]. ESMO Open, 2019, 4(1): e000457. DOI: 10.1136/esmoopen-2018-000457.

PetrelliF, SignorelliD, GhidiniM, et al. Association of steroids use with survival in patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis[J]. Cancers (Basel), 2020, 12(3): 546. DOI: 10.3390/cancers12030546.

RicciutiB, DahlbergSE, AdeniA, et al. Immune checkpoint inhibitor outcomes for patients with non-small-cell lung cancer recei-ving baseline corticosteroids for palliative versus nonpalliative indications[J]. J Clin Oncol, 2019, 37(22): 1927-1934. DOI: 10.1200/JCO.19.00189.

Paz-AresL, LuftA, VicenteD, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer[J]. N Engl J Med, 2018, 379(21): 2040-2051. DOI: 10.1056/NEJMoa-1810865.

DasS, JohnsonDB. Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors[J]. J Immunother Cancer, 2019, 7(1): 306. DOI: 10.1186/s40425-019-0805-8.

GrangeonM, TomasiniP, ChaleatS, et al. Association between immune-related adverse events and efficacy of immune checkpoint inhibitors in non-small-cell lung cancer[J]. Clin Lung Cancer, 2019, 20(3): 201-207. DOI: 10.1016/j.cllc.2018.10.002.

RicciutiB, GenovaC, De GiglioA, et al. Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis[J]. J Cancer Res Clin Oncol, 2019, 145(2): 479-485. DOI: 10.1007/s00432-018-2805-3.

AkamatsuH, MurakamiE, OyanagiJ, et al. Immune-related adverse events by immune checkpoint inhibitors significantly predict durable efficacy even in responders with advanced non-small cell lung cancer[J]. Oncologist, 2020, 25(4): e679-e683. DOI: 10.1634/theoncologist.2019-0299.

SchuelerJ, TschuchC, KlingnerK, et al. Induction of acquired resistance towards EGFR inhibitor gefitinib in a patient-derived xenograft model of non-small cell lung cancer and subsequent molecular characterization[J]. Cells, 2019, 8(7): 740. DOI: 10.3390/cells8070740.

IchiharaE, HaradaD, InoueK, et al. Characteristics of patients with EGFR-mutant non-small-cell lung cancer who benefited from immune checkpoint inhibitors[J]. Cancer Immunol Immunother, 2021, 70(1): 101-106. DOI: 10.1007/s00262-020-02662-0.

LeeCK, ManJ, LordS, et al. Clinical and molecular characteristics associated with survival among patients treated with checkpoint inhibitors for advanced non-small cell lung carcinoma: a systematic review and meta-analysis[J]. JAMA Oncol, 2018, 4(2): 210-216. DOI: 10.1001/jamaoncol.2017.4427.

ReckM, MokTSK, NishioM, et al. Atezolizumab plus bevacizu-mab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial[J]. Lancet Respir Med, 2019, 7(5): 387-401. DOI: 10.1016/S2213-2600(19)30084-0.

PyoKH, LimSM, ParkCW, et al. Comprehensive analyses of immunodynamics and immunoreactivity in response to treatment in ALK-positive non-small-cell lung cancer[J]. J Immunother Cancer, 2020, 8(2): e000970. DOI: 10.1136/jitc-2020-000970.

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