Effects Of Granulocyte-macrophage Colony-stimulating Factor Concurrent With Image-Guided Volumetric Modulated Arc Therapy On Cellular Immune Function In Patients With Metastatic Solid Tumors

Objective:Exploring the effects and safety of Granulocyte-macrophage colony-stimulating factor concurrent with Image-Guided volumetric modulated arc therapy on cellular immune function.This study was set up as a single-center,parallelled,prospective randomized controlled study.Methods:Fifty-two patients attended The Affiliated Qingdao Central Hospital of Qingdao University with stage IV Metastatic solid tumors between July 2020 and February 2021 were recruited,of whom three were ineligible.Eligible patients were assigned to the GM-CSF combined group and control groups by a random number generator in a 1:1 ratio.Patients had at least two lesions available for efficacy assessment,and one appropriate lesion was selected for intensity-modulated radiation therapy in the control group.In contrast,GM-CSF combined group was treated with GM-CSF combined with intensity modulated radiotherapy,which received GM-CSF 150μg/d subcutaneous injection concurrent single lesion intensity-modulated radiation therapy of 2Gy/d.The primary endpoint was changes in cellular immune function,including lymphocyte subsets,the NLR and eosinophil absolute value count.Secondary endpoints included short-term efficacy,grade 3 or higher adverse events,and abscopal effects.Results:Our study reached the primary endpoint.Intergroup analysis showed that the CD3~+T cells,CD4~+T cells,CD8~+T cells,activated T cells(CD3~+HLA-DR~+)and eosinophils in the GM-CSF combined group were higher than those in the control group after treatment,and the difference was statistically significant(P=0.011,P=0.003,P=0.003,P=0.015,P=0.003).After treatment,the NLR in the GM-CSF combined group was lower than that in the control group,and the difference was not statistically significant(P=0.174).Intra-group paired test found that there were no significant changes in CD3~+T cells,CD4~+T cells and CD8~+T cells in GM-CSF combined group(P=0.093,P=0.189,P=0.199),and a substantial decrease in the control group(P<0.001).The activated T cells and eosinophils in the GM-CSF combined group were significantly increased after treatment(P<0.001,P=0.007).After treatment,the NLR in both groups was higher than before,and the difference was statistically significant(P<0.001).In the GM-CSF combined group,the mean NLR increased from 3.57±2.44 to 8.27±6.22 after treatment(P<0.001).The changes of cellular immune function in the NSCLC subgroups were basically the same as that in the overall patients.The ORR was 41.6%in GM-CSF combined group(10/24)vs.12.5%in the control group(3/24,P=0.023).In the NSCLC subgroups,the ORR was 50.0%in GM-CSF combined group(7/14)vs.16.7%in the control group(1/6,P=0.325).One case of abscopal effect was observed in the GM-CSF combined group.The patients were well tolerated.Grade 3 or above leucopenia were recorded in 1 case and lymphocytopenia in 9 cases in the GM-CSF combined group.Grade 3 or higher leukopenia was recorded in 3 patients and lymphocytopenia in 9 cases in the control group.No grade 3 or higher leukopenia,thrombocytopenia and anemia was recorded in the GM-CSF combined group.No grade 3 or higher non-hematologic toxicity was recorded.Conclusions:The results of this study indicate that GM-CSF synchronous IG-VMAT can continuously improve cellular immune function before and after radiotherapy for patients with malignant tumor,and can help increase the abscopal effect and specific immune memory effect,and patients have good tolerance,which is a safe,effective and convenient combination therapy mode for promotion.