Clinical implication of naive and memory T cells in locally advanced cervical cancer:A proxy for tumor biology and short-term response prediction

Background:This study was designed to investigate the feasibility of tumor-infiltrating immune cells with different phenotypic characteristics for predicting short-term clinical responses in patients with locally advanced cervical cancer(LACC).Methods:Thirty-four patients who received concurrent chemoradiotherapy and twenty-one patients who merely underwent radiotherapy were enrolled in this study.We retrospectively analyzed the T cell markers(i.e.,CD3,CD4,CD8),memory markers(i.e.,CD45,CCR7),and differentiation markers(i.e.,CD27)in the peripheral blood and tumor tissues of patients with LACC before treatment based on flow cytometry.We also analyzed the relationship of T cell subsets between peripheral blood and tumor tissues,and their correlation with complete response or partial response.Results:The percentage of central memory CD8^(+)TCM(CD8^(+)CD45RA^(−)CD27^(+)CCR7^(+))cells in LACC patients was significantly lower than that of the control group.The percentage of CD8^(+)TN in the peripheral blood of LACC patients was significantly higher than that of tumor tissues.CD8^(+)TEM in the peripheral blood was significantly lower than that of tumor tissues.The percentage of CD8^(+)TN and CD8^(+)TCM in human papillomavirus(HPV)positive samples was significantly higher than that of HPV-negative samples.Similarly,the percentage of CD8^(+)TCM in tumor tissues was significantly higher in cancer tissue samples with lymph nodes compared with those without.Conclusion:A higher proportion of CD4^(+)TCM and a lower proportion of CD8^(+)TN in the tumor microenvironment of LACC may contribute to the therapy response prediction.

Spinal cord biological safety of image-guided radiation therapy versus conventional radiation therapy

Tumor models were simulated in purebred Beagles at the T9-10 levels of the spinal cord and treated with spinal image-guided radiation therapy or conventional radiation therapy with 50 or 70 Gy total radiation. Three months after radiation, neuronal injury at the T9-10 levels was observed, including reversible injury induced by spinal image-guided radiation therapy and apoptosis induced by conventional radiation therapy. The number of apoptotic cells and expression of the proapoptotic protein Fas were significantly reduced, but expression of the anti-apoptotic protein heat shock protein 70 was significantly increased after image-guided radiation therapy compared with the conventional method of the same radiation dose. Moreover, the spinal cord cell apoptotic index positively correlated with the ratio of Fas/heat shock protein 70. These findings indicate that 3 months of radiation therapy can induce a late response in the spinal cord to radiation therapy; image-guided radiation therapy is safer and results in less neuronal injury compared with conventional radiation therapy.

Predicting late radiation-induced xerostomia in nasopharyngeal carcinoma based on radiomics features extracted from T2WI images of parotids

Objective:To explore the value of radiomics features extracted from the T2-weighted imaging(T2WI)images of parotids in predicting late radiation-induced xerostomia in nasopharyngeal carcinoma(NPC)patients after radiotherapy(RT).Methods:A retrospective analysis was conducted for 123 NPC patients who received RT at the Affiliated Tumour Hospital of Xinjiang Medical University from January 2019 to March 2021.All the patients underwent MRI pre-RT and post-RT.They were randomly divided into a training set and a testing set at a ratio of 4:1 using a random number table,with the former and the latter comprising 98 and 25 cases,respectively.The ipsilateral parotid gland(iPG)and the contralateral parotid gland(cPG)were delineated on T2WI images pre-RT and post-RT as regions of interest(ROIs).A total of 851 radiomics features were extracted from each ROI.Spearman analysis was used to remove redundant features,and the recursive feature elimination(RFE)method was then used to determine useful features.Using radiomics features extracted from images pre-treatment,images post-treatment,and differences between images pre-and post-treatment,this study constructed three radiomic models,namely the pre-treatment radiomics model(preRT),the post-treatment radiomics model(postRT),and the deltaradiomics model(DeltaRT).Then,this study plotted the receiver operating characteristic(ROC)curves based on the late radiation-induced xerostomia grades of patients post-RT.Furthermore,the models’effectiveness and performance in predicting late radiation-induced xerostomia and advanced radioactive xerostomia was evaluated.In addition,the area under the curve(AUC),sensitivity,specificity,accuracy,precision,and negative predictive value(NPV)were calculated.Results:Among the features extracted from bilateral parotid glands(PGs),20 were determined pre-RT(six from iPG and 14 from cPG),19 were determined post-RT(six from iPG and 13 from cPG),and 20 were derived from the DeltaRT(20 from cPG).The PGs pre-RT and post-RT in the training set had AUCs of 0.902(95%CI:0.895-0.909)and 0.761(95%CI:0.744-0.778),respectively,while those in the testing set had AUCs of 0.740(95%CI:0.504-0.983)and 0.701(95%CI:0.478-0.924),respectively.In contrast,the AUC of the cPG derived from the DeltaRT was 0.867(95%CI:0.856-0.878)in the training set and 0.851(95%CI:0.697-0.999)in the testing set.Conclusions:There are significant correlations between radiomics features extracted from MRI T2WI images of parotids and late radiation-induced xerostomia in NPC patients.Among the radiomics features,the changes in cPG features pre-RT and post-RT have higher accuracy in predicting late radiation-induced xerostomia.