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.
程熠, 赵雪琪, 王建华, 席青松, 胡广原, 赵荆. 晚期转移性非小细胞肺癌患者接受放疗后产生远隔效应的临床观察[J]. 医学临床研究, 2020, 37(2): 174-178.
CHENG Yi, ZHAO Xue-qi, WANG Jian-hua,et al. A Clinical Study on Abscopal Effect after Radiotherapy in Metastatic Non-small Cell Lung Cancer Patients. JOURNAL OF CLINICAL RESEARCH, 2020, 37(2): 174-178.
[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.