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| A Clinical Study on Abscopal Effect after Radiotherapy in Metastatic Non-small Cell Lung Cancer Patients |
| CHENG Yi, ZHAO Xue-qi, WANG Jian-hua,et al |
| Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 430030 |
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Abstract 【Objective】To investigate the abscopal effects and associated clinical factors after local radiotherapy (RT) in patients with metastatic non-small cell lung cancer (NSCLC).【Methods】All eligible patients were treated with radiotherapy on primary or metastatic lesions concurrent with GM-CSF (granulocyte macrophage colony-stimulating factor). The tumor response, adverse events and progression-free survival (PFS) were recorded after follow-up. SPSS 18.0 software was used for statistical analysis.【Results】A total of 39 patients were enrolled in this study, in which abscopal effects after RT occurred in 19 cases, accounting for 48.7%. Of 15 patients who underwent stereotactic radiotherapy (SBRT), 10 had abscopal effects (10/15, 66.7%) after receiving RT on liver metastases. Univariate analysis showed that pathological type, RT target, RT mode, BED10 (radiation-equivalent biological dose) and single dose were significantly correlated with abscopal effects after RT. Multivariate analysis showed that RT on liver lesion, SBRT and single dose of radiatoin ≥ 8Gy were more likely to have abscopal effects. Generally, the median PFS was 10.43 (3.97~16.89) months and the 1-year PFS rate was 43.5% with 95% CI. Among them, the median (95% CI) PFS of patients with and without abscopal effects after radiotherapy were 21.33 (10.79 to 31.9) months and 7.97 (7.07 to 8.87) months, respectively. There was statistically significant (P<0.05). The incidence of adverse events for all levels was 33.3% for all the patients in this study.【Conclusion】SBRT concurrent with GM-CSF is a better treatment for metastatic NSCLC. A single large dose of radiation therapy and radiation therapy for liver lesions can stimulate more immune effects and more easily produce abscopal effects, thereby prolonging the survival time of patients.
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Received: 25 October 2019
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[1] Chen W, Zheng R, Baade PD,et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-120.
[2] Mole RH. Whole body irradiation; radiobiology or medicine[J]. Br J Radiol, 1953, 26(305):234-241.
[3] Herrera FG, Bourhis J, Coukos G. Radiotherapy combination opportunities leveraging immunity for the next oncology practice[J]. CA Cancer J Clin, 2017, 67(1): 65-85.
[4] Norian LA, Rodriguez PC, O'Mara LA, et al. Tumor-infiltrating regulatory dendritic cells inhibit CD8+ T cell function via L-arginine metabolism[J]. Cancer Res, 2009, 69(7):3086-3094.
[5] Ehlers G, Fridman M. Abscopal effect of radiation in papillary adenocarcinoma[J]. Br J Radiol,1973, 46(543):220-222.
[6] Kingsley DP. An interesting case of possible abscopal effect in malignant melanoma[J]. Br J Radiol, 1975, 48(574):863-866.
[7] Wang Q, Wang YL. Research advance of molecule associated with immunogenic death of tumor cell[J]. Chin J Cellular Mol Immu, 2013, 29(1):109-111.
[8] Vanpouillebox C, Pilones KA, Wennerberg E, et al. In situ vaccination by radiotherapy to improve responses to anti-CTLA-4 treatment. Vaccine, 2015, 33(51):7415-7422.
[9] Thompson RF, Maity A. Radiotherapy and the tumor microenvironment: Mutual influence and clinical implications[J]. Adv Exp Med Biol, 2014, 772: 147-165.
[10] Golden EB, Chhabra A, Chachoua A,et al. Local radiotherapy and granulocyte-macrophage colonystimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial[J]. Lancet Oncol, 2015, 16(7):795-803.
[11] Fuertes MB, Kacha AK, Kline J, et al. Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cells[J].J Exp Med,2011,208(10): 2005-2016.
[12] Visco C, Vassilakopoulos TP, Kliche KO, et al. Elevated serum levels of IL-10 are associated with inferior progression-free survival in patients with Hodgkin’s disease treated with radiotherapy[J]. Leuk Lymphoma,2004,45(10):2085-2092.
[13] Matsuoka Y, Nakayama H, Yoshida R, et al. IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma[J]. Br J Cancer,2016,115(10): 1234-1244.
[14] Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage Ⅲ non-small-cell lung cancer[J]. N Engl J Med, 2017, 377(20):1919-1929.
[15] Liu Y, Dong Y, Kong L, et al. Abscopal effect of radiotherapy combined with immune checkpoint inhibitors[J]. J Hematol Oncol, 2018,11(1):104-110.
[16] Dewan MZ, Galloway AE, Kawashima N, et al. Fractiouated but not single dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody[J]. Clin Cancer Res, 2009, 15(17):5379-5388.
[17] Schaue D, Ratikan JA, Wamoto KS, et al. Maximizing tumor immunity with fractionated radiation[J]. Int J Radiat Oncol Biol Phys, 2012, 83(4):1306-1310. |
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2020, Vol. 37 
