Prognostic impacts of the estimated dose of radiation to immune cells (EDRIC) on limited-stage small-cell lung cancer with different tumor burdens
Lai Jianian, Guan Song, Yan Meng, Meng Chunliu, Zhang Zhen, Zhang Jiaqi, Zhao Lujun
Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
Abstract：Objective To investigate the effects of estimated dose of radiation to immune cells (EDRIC) on overall survival (OS), local progression-free survival (LPFS) and distant metastasis-free survival (DMFS) in limited-stage small-cell lung cancer (LS-SCLC) with different tumor burdens. Methods Clinical data of 216 patients with LS-SCLC who initially received conventional fractionated radiotherapy of the chest for radical treatment in Tianjin Medical University Cancer Institute and Hospital from 2013 to 2019 were retrospectively analyzed. EDRIC was calculated based on the model developed by Jin et al. and tumor burdens were assessed by gross tumor volume (GTV) or clinical stage. The study endpoints were OS, LPFS and DMFS, which were calculated from the date of diagnosis. The optimal cut-off value of EDRIC was calculated by R language. The correlation between EDRIC and tumor burdens was analyzed using Spearman's correlations. Survival analysis was performed by Cox proportional hazards regression model and Kaplan-Meier curve. Results The median follow-up time for the whole group was 47.8 months, and the median OS and DMFS was 34.6 months and 18.5 months, respectively, while the median LPFS did not reach. The optimal cut-off value of EDRIC was 6.8 Gy. Cox multivariate analysis showed that EDRIC was an independent prognostic factor affecting OS and DMFS. EDRIC was weakly correlated with GTV or clinical stage. Stratified by the median GTV, OS (P=0.021) and DMFS (P=0.030) were significantly shortened and LPFS had a tendency of shortening (P=0.107) when EDRIC>6.8 Gy compared with those when EDRIC ≤ 6.8 Gy in the GTV ≤ 34.6 cm3 group; EDRIC had little effect on OS, LPFS, and DMFS (P=0.133, 0.420, 0.374) in the GTV>34.6 cm3 group. Stratified by clinical stage, OS (P=0.003) and DMFS (P=0.032) were significantly shortened and LPFS (P=0.125) tended to shorten when EDRIC>6.8 Gy in stage I, II and IIIA groups; EDRIC exerted slight effect on OS, LPFS, and DMFS (P=0.377, 0.439, 0.484) in stage IIIB and IIIC groups. Conclusion EDRIC is an important factor affecting prognosis and exerts more significant impact on prognosis in patients with smaller tumor burden.
Lai Jianian,Guan Song,Yan Meng et al. Prognostic impacts of the estimated dose of radiation to immune cells (EDRIC) on limited-stage small-cell lung cancer with different tumor burdens[J]. Chinese Journal of Radiation Oncology, 2023, 32(7): 584-591.
[1] Cytlak UM, Dyer DP, Honeychurch J, et al. Immunomodulation by radiotherapy in tumour control and normal tissue toxicity[J]. Nat Rev Immunol, 2022,22(2):124-138. DOI: 10.1038/s41577-021-00568-1. [2] Jin JY, Mereniuk T, Yalamanchali A, et al. A framework for modeling radiation induced lymphopenia in radiotherapy[J]. Radiother Oncol, 2020,144:105-113. DOI: 10.1016/j.radonc.2019.11.014. [3] Ladbury CJ, Rusthoven CG, Camidge DR, et al. Impact of radiation dose to the host immune system on tumor control and survival for stage III non-small cell lung cancer treated with definitive radiation therapy[J]. Int J Radiat Oncol Biol Phys, 2019,105(2):346-355. DOI: 10.1016/j.ijrobp.2019.05.064. [4] Yin XM, Luo J, Xu C, et al. Is a higher estimated dose of radiation to immune cells predictive of survival in patients with locally advanced non-small cell lung cancer treated with thoracic radiotherapy?[J]. Radiother Oncol, 2021,159:218-223. DOI: 10.1016/j.radonc.2021.03.026. [5] Xu C, Jin JY, Zhang M, et al. The impact of the effective dose to immune cells on lymphopenia and survival of esophageal cancer after chemoradiotherapy[J]. Radiother Oncol, 2020,146:180-186. DOI: 10.1016/j.radonc.2020. 02.015. [6] Chen F, Jin JY, Hui T, et al.Radiation induced lymphopenia is associated with the effective dose to the circulating immune cells in breast cancer[J]. Front Oncol, 2022,12:768956. DOI: 10.3389/fonc.2022.768956. [7] Yu Y, Fu P, Jin JY, et al. Impact of effective dose to immune cells (EDIC) on lymphocyte nadir and survival in limited-stage SCLC[J]. Radiother Oncol, 2021,162:26-33. DOI: 10.1016/j.radonc.2021.06.020. [8] Xu C, Li M, Cai XW, et al.Practice patterns of treatment strategy of limited-stage small-cell lung cancer: survey of Chinese oncologists[J]. Front Oncol, 2022,12:872324. DOI: 10.3389/fonc.2022.872324. [9] Jin JY, Hu C, Xiao Y, et al.Higher radiation dose to the immune cells correlates with worse tumor control and overall survival in patients with stage III NSCLC: a secondary analysis of RTOG0617[J]. Cancers (Basel), 2021,13(24) :6193. DOI: 10.3390/cancers13246193. [10] Bruni D, Angell HK, Galon J. The immune contexture and immunoscore in cancer prognosis and therapeutic efficacy[J]. Nat Rev Cancer, 2020,20(11):662-680. DOI: 10.1038/s41568-020-0285-7. [11] Damen P, Kroese TE, van Hillegersberg R, et al. The influence of severe radiation-induced lymphopenia on overall survival in solid tumors: a systematic review and meta-analysis[J]. Int J Radiat Oncol Biol Phys, 2021,111(4):936-948. DOI: 10.1016/j.ijrobp.2021.07.1695. [12] Kim N, Myoung Noh J, Lee W, et al. Proton beam therapy reduces the risk of severe radiation-induced lymphopenia during chemoradiotherapy for locally advanced non-small cell lung cancer: a comparative analysis of proton versus photon therapy[J]. Radiother Oncol, 2021,156:166-173. DOI: 10.1016/j.radonc.2020.12.019. [13] Navarro-Martín A, Galiana IL, Berenguer Frances MA, et al. Preliminary study of the effect of stereotactic body radiotherapy (SBRT) on the immune system in lung cancer patients unfit for surgery: immunophenotyping analysis[J]. Int J Mol Sci, 2018,19(12) :3963. DOI: 10.3390/ijms19123963. [14] Sun GY, Wang SL, Song YW, et al. Radiation-induced lymphopenia predicts poorer prognosis in patients with breast cancer: a post hoc analysis of a randomized controlled trial of postmastectomy hypofractionated radiation therapy[J]. Int J Radiat Oncol Biol Phys, 2020,108(1):277-285. DOI: 10.1016/j.ijrobp.2020.02.633. [15] Chow R, Simone CB.Radiation induced lymphopenia in head and neck cancer: the importance of rigorous statistical analysis, radiation field size, and treatment modality[J]. Radiother Oncol, 2022,170:242. DOI: 10.1016/j.radonc.2022.02.027. [16] Xu H, Lin MS, Hu YY, et al. Lymphopenia during definitive chemoradiotherapy in esophageal squamous cell carcinoma: association with dosimetric parameters and patient outcomes[J]. Oncologist, 2021,26(3):e425-e434. DOI: 10.1002/onco.13533. [17] Wang SH, Zimmermann S, Parikh K, et al. Current diagnosis and management of small-cell lung cancer[J]. Mayo Clin Proc, 2019,94(8):1599-1622. DOI: 10.1016/j.mayocp.2019.01.034. [18] Sabari JK, Lok BH, Laird JH, et al. Unravelling the biology of SCLC: implications for therapy[J]. Nat Rev Clin Oncol, 2017,14(9):549-561. DOI: 10.1038/nrclinonc.2017.71. [19] Bradley JD, Hu C, Komaki RR, et al. Long-term results of NRG oncology RTOG0617: standard- versus high-dose chemoradiotherapy with or without cetuximab for unresectable stage III non-small-cell lung cancer[J]. J Clin Oncol, 2020,38(7):706-714. DOI: 10.1200/JCO.19.01162. [20] Jung HA, Noh JM, Sun JM, et al. Real world data of durvalumab consolidation after chemoradiotherapy in stage III non-small-cell lung cancer[J]. Lung Cancer, 2020,146:23-29. DOI: 10.1016/j.lungcan.2020.05.035.
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