1.Effects of T helper type 1 cells to T helper type 2 cells ratio and the related cytokines on the prognosis of patients with colorectal cancer
Xibei JIA ; Linchun WEN ; Longzhen ZHANG
Cancer Research and Clinic 2021;33(10):772-776
Objective:To explore effects of T helper type 1 cells (Th1) to T helper type 2 cells (Th2) ratio and the related cytokines on the prognosis of patients with colorectal neoplasms.Methods:A total of 98 colorectal neoplasms patients undergoing the surgery admitted in Suqian Hospital Affiliated to Xuzhou Medical University from December 2015 to December 2017 were enrolled, and all patients were selected as the colorectal cancer group. According to Dukes staging criteria, patients were divided into stage A (25 cases), stage B (30 cases) and stage C (43 cases). In addition, 72 healthy subjects who underwent physical examination in Suqian Hospital Affiliated to Xuzhou Medical University during the same period were selected as the healthy control group. Preoperative venous blood on an empty stomach was extracted from the healthy control group and the colorectal cancer group. Flow cytometry was used to analyze the Th1/Th2 ratio in peripheral blood. The levels of cytokines interferon (IFN)-γ, interleukin (IL)-2, IL-4 and IL-10 in serum samples were detected by using enzyme-linked immunosorbent assay (ELISA). After operation, patients were followed up by telephone or outpatient service. The Th1/Th2 ratio and levels of IFN-γ, IL-2, IL-4 and IL-10 of both groups at different stages of both groups were compared. The correlation between Th1/Th2 ratio and the clinicopathological characteristics of colorectal cancer patients was analyzed. Kaplan-Meier method was used to make survival analysis and Cox regression model was used to analyze influencing factors for overall survival (OS).Results:The Thl/Th2 ratio in colorectal cancer patients was lower than that in the healthy control group (5.13±2.04 vs. 11.82±2.76, t = 18.177, P < 0.01). The lymphovascular invasion and Dukes stage C ratio in patients with decreased Th1/Th2 ratio were higher than those in patients with increased Th1/Th2 ratio ( χ2 values were 16.403, 16.248, both P < 0.01). The levels of IFN-γ and IL-2 in serums of colorectal patients were (95±15) ng/L and (78±10) ng/L, respectively, which were lower than those in the healthy control group [(157±17) ng/L and (123±12) ng/L, t values were 25.160, 26.622, all P < 0.01]. The levels of IL-4 and IL-10 in the colorectal cancer group were (87±16) ng/L and (178±18) ng/L, respectively, which were higher than those in the healthy control group [(46±9) ng/L and (124±12) ng/L] ( t values were 19.577, 22.095, all P < 0.01). The follow-up time ranged from 31.0 to 55.0 months, and the median follow-up time was 37.2 months and the median OS time was 21.0 months. Survival analysis showed that the OS of patients with increased Th1/Th2 ratio was better than that of patients with reduced Th1/Th2 ratio ( χ2 = 7.287, P = 0.007). Multivariate Cox regression analysis showed that lymph node metastasis, tumor stage, and Th1/Th2 ratio were independent influencing factors for OS in colorectal cancer patients ( OR values were 8.541, 3.442, 1.275, all P < 0.05). Conclusion:The imbalance of related cytokines secreted by Th1 and Th2 cells and the decrease in the ratio of Th1/Th2 are related to the progression and the poor prognosis of colorectal cancer.
2.Efficacy of osimertinib combined with tislelizumab in treatment of advanced non-small cell lung cancer and the survival status of patients
Liying GU ; Liang ZHAO ; Linchun WEN
Cancer Research and Clinic 2023;35(9):653-657
Objective:To investigate the clinical efficacy of osimertinib combined with tislelizumab in the treatment of advanced non-small cell lung cancer (NSCLC) and the survival status of patients.Methods:A total of 108 patients with advanced NSCLC in Suqian Hospital of Nanjing Drum Tower Hospital Group from February 2019 to January 2022 were prospectively selected, and they were divided into osimertinib combined with tislelizumab treatment group (study group) and osimertinib treatment group (control group) by random number table method, with 54 cases in each group. Three weeks were 1 cycle. The curative effect was observed after 3 cycles of treatment in both groups. The clinical efficacy, levels of tumor markers, immune function and adverse reactions were compared between the two groups. After 1 year of follow-up, the overall survival (OS) and progression-free survival (PFS) of the two groups were analyzed by Kaplan-Meier method and compared by log-rank test.Results:After 3 cycles of treatment, the disease control rate of the study group was higher than that of the control group [81.48% (44/54) vs. 59.26% (32/54), χ2 = 6.40, P = 0.011], and the objective remission rate of the study group was higher than that of the control group [57.41% (31/54) vs. 37.04% (20/54), χ2 = 4.50, P = 0.034]. Before treatment, the differences in the levels of cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), squamous cell carcinoma antigen (SCC-Ag) and tissue polypeptide antigen (TPA) between the two groups were not statistically significant (all P > 0.05), and after treatment, the levels of tumor markers were lower than those before treatment in both groups (all P < 0.05), and they were lower in the study group than those in the control group (all P < 0.05). Before treatment, there were no statistically significant differences in the proportions of CD3 + T cells, CD4 + T cells and CD8 + T cells between the two groups (all P > 0.05), and after treatment, the proportions of CD3 + T cells and CD4 + T cells were higher than those before treatment in both groups (both P < 0.05), and they were higher in the study group than those in the control group (both P < 0.001), and the proportion of CD8 + T cells before treatment in both groups was lower than that after treatment ( P < 0.05), and it was lower in the study group than that in the control group ( P < 0.001). The differences in the incidence of neutropenia, leukopenia, immune-associated pneumonia, and liver function injury between the two groups were not statistically significant (all P > 0.05). At 1 year of follow-up, there was 1 case of loss of follow-up in the study group and 2 cases of loss of follow-up in the control group, with a follow-up rate of 97.22% (105/108); there were 9 deaths in the study group with an OS rate of 83.02% and 20 deaths in the control group with an OS rate of 61.54%. OS and PFS in the study group were better than those in the control group [median OS time: 11 months (95% CI 6-11 months) vs. 8 months (95% CI 3-11 months), χ2 = 12.32, P < 0.001; median PFS time: 9 months (95% CI 4-11 months) vs. 5 months (95% CI 4-11 months), χ2 = 6.84, P < 0.001]. Conclusions:Osimertinib combined with tislelizumab can reduce the level of tumor markers and improve immune function in patients with advanced NSCLC with good short-term efficacy, and it doesn't increase the adverse effects and can result in a survival benefit.
3.Correlation between early adverse reactions of intensity-modulated radiotherapy and diabetes after radical mastectomy for breast cancer
Lu XU ; Liyou HUANG ; Linchun WEN
Cancer Research and Clinic 2022;34(3):194-197
Objective:To investigate the effect of diabetes on the occurrence of early adverse reactions of intensity-modulated radiotherapy in patients after radical mastectomy for breast cancer.Methods:The clinical data of 102 breast cancer patients who underwent intensity-modulated radiotherapy after radical mastectomy for breast cancer in Nanjing Drum Tower Hospital Group Suqian Hospital from October 2014 to December 2020 were retrospectively analyzed, including 32 cases in the diabetes group and 70 cases in the non-diabetes group. The incidence of early adverse reactions of intensity-modulated radiotherapy in the two groups was compared, the effects of blood glucose before radiotherapy on the early adverse reactions of intensity-modulated radiotherapy and the lymphocyte count before and after intensity-modulated radiotherapy were analyzed.Results:There were 9 cases (28.1%) and 1 case (3.1%) of grade 1 and 2 acute radiation pneumonitis in the diabetes group, and 6 cases (8.6%) and 1 case (1.4%) in the non-diabetes group, respectively, and there was a statistical difference between the two groups ( χ2 = 7.22, P = 0.027). Grade 1-3 acute radiation dermatitis occurred in 16 cases (50.0%), 13 cases (43.8%) and 3 cases (6.2%) in the diabetes group, and 53 cases (75.7%), 15 cases (21.4%) and 2 cases (2.9%) in the non-diabetes group, respectively, and the difference between the two groups was statistically significant ( χ2 = 6.99, P = 0.030). According to the level of fructosamine before radiotherapy, the patients with diabetes were divided into normal blood glucose control group (fructosamine ≤2.5 mmol/L) and poor blood glucose control group (fructosamine >2.5 mmol/L), and there was statistical difference in the morbidity of acute radiation dermatitis between the two groups ( P = 0.039). Before radiotherapy, there was no significant difference in lymphocyte count between the normal and poor blood glucose control groups ( P > 0.05). After radiotherapy, the lymphocyte count in both groups was significantly lower than that before radiotherapy, and the decrease was more obvious in the poor blood glucose control group, the difference was statistically significant ( P = 0.021). Conclusions:The postoperative patients with breast cancer complicated with diabetes have a high incidence of acute radiation pneumonia and acute radiation dermatitis. Patients with poor blood glucose control are more likely to have acute radiation dermatitis.
4.Clinical efficacy of preoperative SIB-IMRT for 26 cases of locally-advanced low rectal cancer
Qiteng LIU ; Linchun FENG ; Baoqing JIA ; Xiaohui DU ; Hongyi LIU ; Guanghai DAI ; Jing CHEN ; Yongqiang YANG ; Ke WEN ; Yunlai WANG ; Tao YANG ; Yuyan GAO
Chinese Journal of Radiation Oncology 2018;27(10):906-910
Objective To evaluate the feasibility and clinical efficacy of preoperative simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with neoadjuvant chemotherapy of capecitabine in patients with locally-advanced low rectal cancer.Methods Between 2015 and 2016,26 patients admitted to 301 Hospital who were diagnosed with locally-advanced low rectal cancer,which was located within 5 cm from the anal verge,were enrolled in this investigation.Dose fractionation pattern was delivered:58.75 Gy in 25 fractions (2.35 Gy/fraction) for rectal cancer and lymph node metastasis and 50 Gy in 25 fractions for the pelvic lymphatic drainage area and simultaneously combined with capecitabine chemotherapy (825 mg/m2,bid d 1-5 weekly).One cycle of capecitabine (1 250 mg/m2,twice daily,d 1-14)was given at one week after the completion of chemoradiotherapy (CRT).Total mesorectal excision (TME)was performed at 6 to 8 weeks after the completion of CRT.The primary endpoints included pathological complete response rate (ypCR) and sphincter-preserving rate.The secondary endpoints included acute toxicity,tumor downstaging rate and postoperative complications.Results Twenty-six patients successfully completed neoadjuvant CRT,25 of them underwent surgical resection and one patient failed to receive surgery due to pxrianal edema.Postoperative ypCR rate was 32% (8/25),the sphincter-preserving rate was 60% (15/25),the tumor downstaging rate was 92% (23/25) and the R0 resection rate was 100%.During the period of CRT,grade 1 and 2 adverse events occurred in 24 patients,grade 3 radiation dermatitis was noted in 2 cases.No ≥ grade 4 acute adverse event was observed.Postoperative complications included ureteral injury in one case and intestinal obstruction in one patient.Conclusions Preoperative SIB-IMRT combined with neoadjuvant chemotherapy of capecitabine is a feasible and safe treatment for patients with locallyadvanced low rectal cancer,which yields expected ypCR rate,R0 resection rate and sphincter-preserving rate.Nevertheless,the long-term clinical benefits remain to be elucidated.Clinical Trial Registry Chinese Clinical Trial Registry,registration number:ChiCTR-ONC-12002387.
5.A dosimetric study of volumetric modulated arc therapy with a simultaneous integrated boost for preoperative chemoradiotherapy in patients with locally advanced rectal cancer
Qiteng LIU ; 101149北京,首都医科大学附属北京潞河医院放疗科 ; Qian HAN ; Tao YANG ; Jing CHEN ; Ke WEN ; Mingyue ZENG ; Jinyuan WANG ; Xiaohu CONG ; Linchun FENG
Chinese Journal of Radiation Oncology 2017;26(11):1313-1317
Objective To investigate the dosimetric feasibility of volumetric modulated arc therapy (VMAT)with a simultaneous integrated boost(SIB-VMAT58.75 Gy)for preoperative chemoradiotherapy in patients with locally advanced rectal cancer(LARC),and to provide a basis for clinical practice.Methods Nine patients with stage Ⅱ-Ⅲ rectal cancer who underwent preoperative concurrent chemoradiotherapy were involved in the study,and two plans were performed for each patient:SIB-VMAT58.75 Gy and VMAT50.00 Gy. For the SIB-VMAT58.75 Gy plan,the prescribed dose was 58.75 Gy(2.35 Gy/fraction)for the local rectal tumor and positive lymph nodes(GTV 58.75 Gy),and 50 Gy(2 Gy/fraction)for the regions at high risk of harboring microscopic disease(pelvic lymphatic drainage area)(PTV 50Gy).For the VMAT50.00 Gy plan,the prescribed dose was 50 Gy(2 Gy/fraction)for the regions at high risk of harboring microscopic disease(pelvic lymphatic drainage area)without a boost. The conformity index(CI),homogeneity index (HI),and dose for target areas and organs at risk(OAR)were assessed according to the dose-volume histogram. The paired t-test or nonparametric rank test was used to compare the differences between the two plans. Results Both plans met the prescription goal for PTV dose coverage. There was no significant difference in CI for the PTV between the two plans(1.0±0.0 vs. 1.0±0.0,P>0.05).The SIB-VMAT58.75 Gy plan had a worse HI than the VMAT50.00 Gy plan(0.2± 0.2 vs. 0.1± 0.0,P<0.05).There was no significant difference in V10-V50of the small intestine,bladder,femoral heads,and pelvis between the two plans(P>0.05),but D 2 cm3of the small intestine was significantly higher in the SIB-VMAT58.75 Gy plan than in the VMAT50.00 Gy plan(P=0.038). Conclusions The SIB-VMAT58.75 Gy plan for LARC achieves required target volume dose coverage and OAR dose constraints,which is safe and feasible in terms of dosimetry,and its clinical efficacy and adverse effects need further evaluation.