多病灶SBRT联合免疫检查点抑制剂在晚期NSCLC寡转移中应用进展

doi:10.3760/cma.j.cn113030-20210204-00054

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Abstract In recent years, the application of immune checkpoint inhibitors (PD‐1/PD‐L1/CTLA‐4, etc.) in the treatment of non‐small cell lung cancer (NSCLC) has developed rapidly. However, the response rate of immune checkpoint inhibitors alone is as low as 15%‐30%. There are still many problems in clinical practice, such as limited benefit population, lack of effective biomarkers and treatment resistance, etc. Compared with conventional fractionated radiotherapy, stereotactic body radiation therapy (SBRT) has the characteristics of higher single dose, less irradiation times and stronger immune activation ability. It has shown good anti‐tumor effect in patients with advanced NSCLC oligometastasis. The combination of immune checkpoint inhibitors and SBRT is the development trend of tumor therapy. Preclinical and clinical studies show that SBRT can enhance the efficacy of immunotherapy in patients with NSCLC. In the initial study, single‐lesion SBRT was first recommended to reduce potential toxicity. However, more and more studies have confirmed the feasibility and necessity of multi‐lesion SBRT. In this review, we not only elucidated the mechanism and the latest progress upon combined use of SBRT and immune checkpoint inhibitors in advanced NSCLC oligometastasis, but also explored the basic and clinical research of multi‐lesion SBRT combined with immunotherapy, aiming to guide clinical practice.

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	Yang Yang
	Zheng Xiaoli
	Ge Hong

Key words： Carcinoma,non‐small‐cell lung Neoplasm oligo metastasis Stereotactic body radiation therapy Immune checkpoint inhibitors

Received: 04 February 2021

Fund:Surface Project from National Natural Science Foundation of China (81373230); Scientific and Technological Project in Henan Province (222102310015); Medical Science and Technology Project in Henan Province (SBGJ202102056)

Corresponding Authors: Ge Hong, Email: gehong666@126.com

Cite this article:

Yang Yang,Zheng Xiaoli,Ge Hong. Progress on multisite SBRT combined with immune checkpoint inhibitor in oligometastasis of advanced NSCLC[J]. Chinese Journal of Radiation Oncology, 2022, 31(9): 843-847.

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http://journal12.magtechjournal.com/Jweb_fszlx/EN/10.3760/cma.j.cn113030-20210204-00054 OR http://journal12.magtechjournal.com/Jweb_fszlx/EN/Y2022/V31/I9/843

[1] Siegel R, Miller K, Jemal A. Cancer statistics, 2020[J]. CA, 2020, 70(1):7‐30. DOI: 10.3322/caac. 21601
[2] Wanqing C, Rongshou Z, Baade PD, et al. Cancer statistics in China, 2015[J]. CA, 2016, 66(2):115‐132. DOI: 10.3322/caac. 21332
[3] Grossi F, Kubota K, Cappuzzo F, et al. Future scenarios for the treatment of advanced non‐small cell lung cancer: focus on taxane‐containing regimens[J]. Oncologist, 2010,15(10):1102‐1112. DOI: 10.1634/theoncologist. 2010‐0322.
[4] Hellman S, Weichselbaum RR. Oligometastases[J]. J Clin Oncol, 1995, 13(1):8‐10. DOI: 10.1200/JCO.1995.13.1.8.
[5] Gomez DR, Blumenschein GR, Lee JJ, et al. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non‐small‐cell lung cancer without progression after first‐line systemic therapy: a multicentre, randomised, controlled, phase 2 study[J]. Lancet Oncol, 2016, 17(12):1672‐1682. DOI: 10.1016/S1470‐2045(16)30532‐0.
[6] Gomez DR, Tang C, Zhang J, et al. Local consolidative therapy vs. maintenance therapy or observation for patients with oligometastatic non‐small‐cell lung cancer: long‐term results of a multi‐institutional, phase ii, randomized study[J]. J Clin Oncol, 2019, 37(18):1558‐1565. DOI: 10.1200/JCO.19.00201.
[7] Collen C, Christian N, Schallier D, et al.Phase II study of stereotactic body radiotherapy to primary tumor and metastatic locations in oligometastatic nonsmall‐cell lung cancer patients[J]. Ann Oncol, 2014, 25(10):1954‐1959. DOI: 10.1093/annonc/mdu370.
[8] Li D, Zhu X, Wang H, et al. Should aggressive thoracic therapy be performed in patients with synchronous oligometastatic non‐small cell lung cancer? A meta‐analysis[J]. J Thorac Dis, 2017, 9(2):310‐317. DOI: 10.21037/jtd.2017.02.21.
[9] Palma DA, Olson R, Harrow S, et al.Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR‐COMET): a randomised, phase 2, open‐label trial[J]. Lancet, 2019, 393(10185):2051‐2058. DOI: 10.1016/S0140‐6736(18)32487‐5.
[10] Sharabi AB, Nirschl CJ, Kochel CM, et al. Stereotactic radiation therapy augments antigen‐specific PD‐1‐mediated antitumor immune responses via cross‐presentation of tumor antigen[J]. Cancer Immunol Res, 2015, 3(4):345‐355. DOI: 10.1158/2326‐6066.CIR‐14‐0196.
[11] Sato H, Okonogi N, Nakano T. Rationale of combination of anti‐PD‐1/PD‐L1 antibody therapy and radiotherapy for cancer treatment[J]. Int J Clin Oncol, 2020, 25(5):801‐809. DOI: 10.1007/s10147‐020‐01666‐1.
[12] Rapoport BL, Anderson R. Realizing the clinical potential of immunogenic cell death in cancer chemotherapy and radiotherapy[J]. Int J Mol Sci, 2019, 20(4)DOI: 10.3390/ijms20040959.
[13] Golden EB, Apetoh L. Radiotherapy and immunogenic cell death[J]. Semin Radiat Oncol, 2015, 25(1):11‐17. DOI: 10.1016/j.semradonc.2014.07.005.
[14] Weichselbaum RR, Liang H, Deng L, et al. Radiotherapy and immunotherapy: a beneficial liaison?[J]. Nat Rev Clin Oncol, 2017, 14(6):365‐379. DOI: 10.1038/nrclinonc.2016.211.
[15] Luke JJ, Lemons JM, Karrison TG, et al. Safety and clinical activity of pembrolizumab and multisite stereotactic body radiotherapy in patients with advanced solid tumors[J]. J Clin Oncol, 2018, 36(16):1611‐1618. DOI: 10.1200/JCO.2017.76.2229.
[16] Lumniczky K, Sáfrány G. The impact of radiation therapy on the antitumor immunity: local effects and systemic consequences[J]. Cancer Lett, 2015, 356(1):114‐125. DOI: 10.1016/j.canlet.2013.08.024.
[17] Garg AD, Krysko DV, Verfaillie T, et al. A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death[J]. EMBO J, 2012, 31(5):1062‐1079. DOI: 10.1038/emboj.2011.497.
[18] Sharabi AB, Lim M, DeWeese TL, et al. Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy[J]. Lancet Oncol, 2015, 16(13):e498‐509. DOI: 10.1016/S1470‐2045(15)00007‐8.
[19] Vanpouille‐Box C, Alard A, Aryankalayil MJ, et al. DNA exonuclease Trex1 regulates radiotherapy‐induced tumour immunogenicity[J]. Nat Commun, 2017, 8:15618. DOI: 10.1038/ncomms15618.
[20] Bernstein MB, Krishnan S, Hodge JW, et al. Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach?[J]. Nat Rev Clin Oncol, 2016, 13(8):516‐524. DOI: 10.1038/nrclinonc.2016.30.
[21] Yuan Z, Fromm A, Ahmed KA, et al. Radiotherapy rescue of a nivolumab‐refractory immune response in a patient with PD‐L1‐negative metastatic squamous cell carcinoma of the lung[J]. J Thorac Oncol, 2017, 12(9):e135‐e136. DOI: 10.1016/j.jtho.2017.04.029.
[22] Brooks ED, Chang JY. Time to abandon single‐site irradiation for inducing abscopal effects[J]. Nat Rev Clin Oncol, 2019, 16(2):123‐135. DOI: 10.1038/s41571‐018‐0119‐7.
[23] Huang AC, Postow MA, Orlowski RJ, et al. T‐cell invigoration to tumour burden ratio associated with anti‐PD‐1 response[J]. Nature, 2017, 545(7652):60‐65. DOI: 10.1038/nature22079.
[24] Deng L, Liang H, Burnette B, et al. Irradiation and anti‐PD‐L1 treatment synergistically promote antitumor immunity in mice[J]. J Clin Invest, 2014, 124(2):687‐695. DOI: 10.1172/JCI67313.
[25] Theelen W, Heike M, Ferry L, et al. Effect of pembrolizumab after stereotactic body radiotherapy vs pembrolizumab alone on tumor response in patients with advanced non‐small cell lung cancer: results of the PEMBRO‐RT phase 2 randomized clinical trial[J]. JAMA Oncol, 2019,5(9):1276‐1282. DOI: 10.1001/jamaoncol. 2019.1478.
[26] Welsh J, Menon H, Chen D, et al. Pembrolizumab with or without radiation therapy for metastatic non‐small cell lung cancer: a randomized phase I/II trial[J]. J Immunother Cancer, 2020, 8(2)DOI: 10.1136/jitc‐2020‐001001.
[27] Theelen W, Chen D, Verma V, et al. Pembrolizumab with or without radiotherapy for metastatic non‐small‐cell lung cancer: a pooled analysis of two randomised trials[J]. Lancet Respir Med, 2021, 9(5):467‐475. DOI: 10.1016/S2213‐2600(20)30391‐X.
[28] Tang C, Welsh JW, de Groot P, et al. Ipilimumab with stereotactic ablative radiation therapy: phase I results and immunologic correlates from peripheral T cells[J]. Clin Cancer Res, 2017, 23(6):1388‐1396. DOI: 10.1158/1078‐0432.CCR‐16‐1432.
[29] Britschgi C, Riesterer O, Burger IA, et al.Report of an abscopal effect induced by stereotactic body radiotherapy and nivolumab in a patient with metastatic non‐small cell lung cancer[J]. Radiat Oncol, 2018, 13(1):102. DOI: 10.1186/s13014‐018‐1049‐3.
[30] Luke JJ, Lemons JM, Karrison TG, et al. Safety and clinical activity of pembrolizumab and multisite stereotactic body radiotherapy in patients with advanced solid tumors[J]. J Clin Oncol, 2018, 36(16):1611‐1618. DOI: 10.1200/JCO.2017.76.2229.
[31] Menon H, Chen D, Ramapriyan R, et al.Influence of low‐dose radiation on abscopal responses in patients receiving high‐dose radiation and immunotherapy[J]. J Immunother Cancer, 2019, 7(1):237. DOI: 10.1186/s40425‐019‐0718‐6.
[32] Yin L, Xue J, Li R, et al. 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[J]. Int J Radiat Oncol Biol Phys, 2020, 108(1):212‐224. DOI: 10.1016/j.ijrobp.2020.05.002.
[33] Markovsky E, Budhu S, Samstein RM, et al. An antitumor immune response is evoked by partial‐volume single‐dose radiation in 2 murine models[J]. Int J Radiat Oncol Biol Phys, 2019, 103(3):697‐708. DOI: 10.1016/j.ijrobp.2018.10.009.
[34] Cushman TR, Gomez D, Kumar R, et al. Combining radiation plus immunotherapy to improve systemic immune response[J]. J Thorac Dis, 2018, 10(Suppl 3):S468‐S479. DOI: 10.21037/jtd.2018.01.130.
[35] Chen Y, Gao M, Huang Z, et al.SBRT combined with PD‐1/PD‐L1 inhibitors in NSCLC treatment: a focus on the mechanisms, advances, and future challenges[J]. J Hematol Oncol, 2020, 13(1):105. DOI: 10.1186/s13045‐020‐00940‐z.