全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...

放疗联合免疫检查点抑制剂治疗非小细胞肺癌介入时机及安全性的研究进展
Research Progress on Interventional Time and Safety of RT Combined with ICIs for NSCLCL

DOI: 10.12677/acm.2024.1461791, PP. 420-427

Keywords: 非小细胞肺癌,放疗,免疫检查点抑制剂,介入时机,安全性
Non-Small Lung Cancer
, Radiotherapy, Immune Checkpoint Inhibitors, Interventional Time, Safety

Full-Text   Cite this paper   Add to My Lib

Abstract:

非小细胞肺癌(non-small lung cancer, NSCLC)是一种常见且致命的恶性肿瘤。放疗(Radiotherapy, RT)是NSCLC一种有效的局部治疗手段。免疫检查点抑制剂(immune checkpoint inhibitors, ICIs),尤其是抗程序性细胞死亡受体1 (PD-1)、程序性细胞死亡配体1 (PD-L1)抗体等药物,使NSCLC患者的无进展生存(progression-free survival, PFS)和总生存(overall survival, OS)有显著延长,为NSCLC患者带来新的希望。但由于一些患者对免疫治疗未产生应答,且很多患者在治疗后很快出现原发性或继发性耐药,因此单纯的ICIs对于治疗NSCLC的疗效仍不满意。近年来,基于RT可以调节免疫系统的原理,一些研究发现在NSCLC的ICIs治疗中加入RT会显现出更好的疗效,但临床上对于RT介入时间及加入RT后安全性仍有争议。本文就ICIs联合放疗的作用机制、介入时机以及安全性问题的研究进展进行总结和论述,为临床治疗提供参考。
Non-small cell lung cancer (NSCLC) is a common and fatal malignant tumor. Radiotherapy (RT) is an effective local treatment modality for NSCLC. Immune checkpoint inhibitors (ICIs), especially anti-programmed cell death receptor-1 (PD-1), and programmed cell death ligand 1 (PD-L1) antibodies, have significantly prolonged the progression-free survival (PFS) and overall survival (OS) of NSCLC patients. However, the efficacy of ICIs alone in the treatment of NSCLC is still unsatisfactory since some patients do not respond to immunotherapy and many patients develop primary or secondary drug resistance soon after treatment. In recent years, based on the principle that RT can modulate the immune system, some studies have found that adding RT to ICIs for NSCLC shows better efficacy in the treatment, but the timing of RT intervention and the safety of adding RT are still controversial in clinical practices. This article reviews and discusses the research progresses on the mechanism of the combined radiotherapy and ICIs therapy, the timing of RT intervention, and relevant safety issues, providing references for clinical treatment.

References

[1]  Qiu, H., Cao, S. and Xu, R. (2021) Cancer Incidence, Mortality, and Burden in China: A Time-trend Analysis and Comparison with the United States and United Kingdom Based on the Global Epidemiological Data Released in 2020. Cancer Communications, 41, 1037-1048.
https://doi.org/10.1002/cac2.12197
[2]  Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R.L., Soerjomataram, I., et al. (2024) Global Cancer Statistics 2022: Globocan Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 74, 229-263.
https://doi.org/10.3322/caac.21834
[3]  凌徐心仪, 张瑶, 钟华. 非小细胞肺癌免疫治疗获益人群筛选的研究进展[J]. 上海交通大学学报(医学版), 2021, 41(8): 1114-1119.
[4]  Carron, R., Gaudy-Marqueste, C., Amatore, F., Padovani, L., Malissen, N., Balossier, A., et al. (2020) Stereotactic Radiosurgery Combined with Anti-PD1 for the Management of Melanoma Brain Metastases: A Retrospective Study of Safety and Efficacy. European Journal of Cancer, 135, 52-61.
https://doi.org/10.1016/j.ejca.2020.04.028
[5]  Backlund, E., Grozman, V., Egyhazi Brage, S., Lewensohn, R., Lindberg, K. and Helgadottir, H. (2023) Radiotherapy with or without Immunotherapy in Metastatic Melanoma: Efficacy and Tolerability. Acta Oncologica, 62, 1921-1930.
https://doi.org/10.1080/0284186x.2023.2280766
[6]  Theelen, W.S.M.E., Peulen, H.M.U., Lalezari, F., van der Noort, V., de Vries, J.F., Aerts, J.G.J.V., et al. (2019) Effect of Pembrolizumab after Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients with Advanced Non-Small Cell Lung Cancer. JAMA Oncology, 5, 1276-1282.
https://doi.org/10.1001/jamaoncol.2019.1478
[7]  Yin, L., Xue, J., Li, R., Zhou, L., Deng, L., Chen, L., et al. (2020) Effect of Low-Dose Radiation Therapy on Abscopal Responses to Hypofractionated Radiation Therapy and Anti-PD1 in Mice and Patients with Non-Small Cell Lung Cancer. International Journal of Radiation Oncology Biology Physics, 108, 212-224.
https://doi.org/10.1016/j.ijrobp.2020.05.002
[8]  Brooks, E.D. and Chang, J.Y. (2018) Time to Abandon Single-Site Irradiation for Inducing Abscopal Effects. Nature Reviews Clinical Oncology, 16, 123-135.
https://doi.org/10.1038/s41571-018-0119-7
[9]  Herrera, F.G., Ronet, C., Ochoa de Olza, M., Barras, D., Crespo, I., Andreatta, M., et al. (2021) Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy. Cancer Discovery, 12, 108-133.
https://doi.org/10.1158/2159-8290.cd-21-0003
[10]  Liu, Z., Zhao, Q., Zheng, Z., Liu, S., Meng, L., Dong, L., et al. (2021) Vascular Normalization in Immunotherapy: A Promising Mechanisms Combined with Radiotherapy. Biomedicine & Pharmacotherapy, 139, Article ID: 111607.
https://doi.org/10.1016/j.biopha.2021.111607
[11]  Tian, L., Goldstein, A., Wang, H., Ching Lo, H., Sun Kim, I., Welte, T., et al. (2017) Mutual Regulation of Tumour Vessel Normalization and Immunostimulatory Reprogramming. Nature, 544, 250-254.
https://doi.org/10.1038/nature21724
[12]  Chen, J.L., Pan, C., Huang, Y., Tsai, C., Wang, C., Lin, Y., et al. (2020) Evaluation of Antitumor Immunity by a Combination Treatment of High-Dose Irradiation, Anti-PDL1, and Anti-Angiogenic Therapy in Murine Lung Tumors. Cancer Immunology, Immunotherapy, 70, 391-404.
https://doi.org/10.1007/s00262-020-02690-w
[13]  Robinson, C.G., DeWees, T.A., El Naqa, I.M., Creach, K.M., Olsen, J.R., Crabtree, T.D., et al. (2013) Patterns of Failure after Stereotactic Body Radiation Therapy or Lobar Resection for Clinical Stage I Non-Small-Cell Lung Cancer. Journal of Thoracic Oncology, 8, 192-201.
https://doi.org/10.1097/jto.0b013e31827ce361
[14]  Strauss, G.M., Herndon, J.E., Maddaus, M.A., Johnstone, D.W., Johnson, E.A., Harpole, D.H., et al. (2008) Adjuvant Paclitaxel plus Carboplatin Compared with Observation in Stage IB Non-Small-Cell Lung Cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. Journal of Clinical Oncology, 26, 5043-5051.
https://doi.org/10.1200/jco.2008.16.4855
[15]  Altorki, N.K., McGraw, T.E., Borczuk, A.C., Saxena, A., Port, J.L., Stiles, B.M., et al. (2021) Neoadjuvant Durvalumab with or without Stereotactic Body Radiotherapy in Patients with Early-Stage Non-Small-Cell Lung Cancer: a Single-Centre, Randomised Phase 2 Trial. The Lancet Oncology, 22, 824-835.
https://doi.org/10.1016/s1470-2045(21)00149-2
[16]  Kelly, K., Chansky, K., Gaspar, L.E., Albain, K.S., Jett, J., Ung, Y.C., et al. (2008) Phase III Trial of Maintenance Gefitinib or Placebo after Concurrent Chemoradiotherapy and Docetaxel Consolidation in Inoperable Stage III Non-Small-Cell Lung Cancer: Swog S0023. Journal of Clinical Oncology, 26, 2450-2456.
https://doi.org/10.1200/jco.2007.14.4824
[17]  Antonia, S.J., Villegas, A., Daniel, D., Vicente, D., Murakami, S., Hui, R., et al. (2018) Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. New England Journal of Medicine, 379, 2342-2350.
https://doi.org/10.1056/nejmoa1809697
[18]  Durm, G.A., Jabbour, S.K., Althouse, S.K., Liu, Z., Sadiq, A.A., Zon, R.T., et al. (2020) A Phase 2 Trial of Consolidation Pembrolizumab Following Concurrent Chemoradiation for Patients with Unresectable Stage III Non-Small Cell Lung Cancer: Hoosier Cancer Research Network LUN 14‐179. Cancer, 126, 4353-4361.
https://doi.org/10.1002/cncr.33083
[19]  Jabbour, S.K., Berman, A.T., Decker, R.H., Lin, Y., Feigenberg, S.J., Gettinger, S.N., et al. (2020) Phase 1 Trial of Pembrolizumab Administered Concurrently with Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer. JAMA Oncology, 6, 848-855.
https://doi.org/10.1001/jamaoncol.2019.6731
[20]  Werner-Wasik, M., Swann, R.S., Bradley, J., Graham, M., Emami, B., Purdy, J., et al. (2008) Increasing Tumor Volume Is Predictive of Poor Overall and Progression-free Survival: Secondary Analysis of the Radiation Therapy Oncology Group 93-11 Phase I-II Radiation Dose-Escalation Study in Patients with Inoperable Non-Small-Cell Lung Cancer. International Journal of Radiation Oncology Biology Physics, 70, 385-390.
https://doi.org/10.1016/j.ijrobp.2007.06.034
[21]  Wang, Y., Zhang, T., Wang, J., Zhou, Z., Liu, W., Xiao, Z., et al. (2023) Induction Immune Checkpoint Inhibitors and Chemotherapy Before Definitive Chemoradiation Therapy for Patients with Bulky Unresectable Stage III Non-Small Cell Lung Cancer. International Journal of Radiation Oncology Biology Physics, 116, 590-600.
https://doi.org/10.1016/j.ijrobp.2022.12.042
[22]  Wang, Y., Deng, L., Wang, J., Zhang, T., Wang, W., Wang, X., et al. (2024) Induction PD-1 Inhibitor Toripalimab plus Chemotherapy Followed by Concurrent Chemoradiotherapy and Consolidation Toripalimab for Bulky Locally Advanced Non-Small-Cell Lung Cancer: Protocol for a Randomized Phase II Trial (InTRist Study). Frontiers in Immunology, 14, Article ID: 1341584.
https://doi.org/10.3389/fimmu.2023.1341584
[23]  Forde, P.M., Spicer, J., Lu, S., Provencio, M., Mitsudomi, T., Awad, M.M., et al. (2022) Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. New England Journal of Medicine, 386, 1973-1985.
https://doi.org/10.1056/nejmoa2202170
[24]  Wang, Z., Wu, L., Li, B., Cheng, Y., Li, X., Wang, X., et al. (2023) Toripalimab plus Chemotherapy for Patients with Treatment-Naive Advanced Non-Small-Cell Lung Cancer: A Multicenter Randomized Phase III Trial (Choice-01). Journal of Clinical Oncology, 41, 651-663.
https://doi.org/10.1200/jco.22.00727
[25]  Zhu, X., Sun, L., Song, N., He, W., Xie, B., Hu, J., et al. (2022) Safety and Effectiveness of Neoadjuvant PD-1 Inhibitor (Toripalimab) plus Chemotherapy in Stage II-III NSCLC (LungMate 002): An Open-Label, Single-Arm, Phase 2 Trial. BMC Medicine, 20, Article No. 493.
https://doi.org/10.1186/s12916-022-02696-4
[26]  Shaverdian, N., Lisberg, A.E., Bornazyan, K., Veruttipong, D., Goldman, J.W., Formenti, S.C., et al. (2017) Previous Radiotherapy and the Clinical Activity and Toxicity of Pembrolizumab in the Treatment of Non-Small-Cell Lung Cancer: A Secondary Analysis of the Keynote-001 Phase 1 Trial. The Lancet Oncology, 18, 895-903.
https://doi.org/10.1016/s1470-2045(17)30380-7
[27]  Theelen, W.S.M.E., Peulen, H.M.U., Lalezari, F., van der Noort, V., de Vries, J.F., Aerts, J.G.J.V., et al. (2019) Effect of Pembrolizumab after Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients with Advanced Non-Small Cell Lung Cancer. JAMA Oncology, 5, 1276-1282.
https://doi.org/10.1001/jamaoncol.2019.1478
[28]  Rudin, C.M., Awad, M.M., Navarro, A., Gottfried, M., Peters, S., Cs?szi, T., et al. (2020) Pembrolizumab or Placebo plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III Keynote-604 Study. Journal of Clinical Oncology, 38, 2369-2379.
https://doi.org/10.1200/jco.20.00793
[29]  Bauml, J.M., Mick, R., Ciunci, C., Aggarwal, C., Davis, C., Evans, T., et al. (2019) Pembrolizumab after Completion of Locally Ablative Therapy for Oligometastatic Non-Small Cell Lung Cancer. JAMA Oncology, 5, 1283-1290.
https://doi.org/10.1001/jamaoncol.2019.1449
[30]  Hwang, W.L., Pike, L.R.G., Royce, T.J., Mahal, B.A. and Loeffler, J.S. (2018) Safety of Combining Radiotherapy with Immune-Checkpoint Inhibition. Nature Reviews Clinical Oncology, 15, 477-494.
https://doi.org/10.1038/s41571-018-0046-7
[31]  Kadera, B.E., Li, L., Toste, P.A., Wu, N., Adams, C., Dawson, D.W., et al. (2013) Microrna-21 in Pancreatic Ductal Adenocarcinoma Tumor-Associated Fibroblasts Promotes Metastasis. PLOS ONE, 8, e71978.
https://doi.org/10.1371/journal.pone.0071978
[32]  Levy, A., Massard, C., Soria, J. and Deutsch, E. (2016) Concurrent Irradiation with the Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Blocker Durvalumab: Single Centre Subset Analysis from a Phase 1/2 Trial. European Journal of Cancer, 68, 156-162.
https://doi.org/10.1016/j.ejca.2016.09.013
[33]  Hwang, W.L., Niemierko, A., Hwang, K.L., Hubbeling, H., Schapira, E., Gainor, J.F., et al. (2018) Clinical Outcomes in Patients with Metastatic Lung Cancer Treated with PD-1/PD-l1 Inhibitors and Thoracic Radiotherapy. JAMA Oncology, 4, 253-255.
https://doi.org/10.1001/jamaoncol.2017.3808
[34]  Tian, S., Switchenko, J.M., Buchwald, Z.S., Patel, P.R., Shelton, J.W., Kahn, S.E., et al. (2020) Lung Stereotactic Body Radiation Therapy and Concurrent Immunotherapy: A Multicenter Safety and Toxicity Analysis. International Journal of Radiation Oncology Biology Physics, 108, 304-313.
https://doi.org/10.1016/j.ijrobp.2019.12.030

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133