1.Clinical Value of Tumor-Stroma Ratio Combined with KRAS/NRAS/BRAF Gene Status in Prognostic Assessment of Patients with Colorectal Cancer
Ziyang ZHANG ; Yuanfei LI ; Yuntong GUO ; Gen ZHU ; Guang YANG ; Yu WANG
Cancer Research on Prevention and Treatment 2025;52(8):676-681
Objective To investigate the clinical value of tumor-stroma ratio (TSR) in combination with KRAS, BRAF, NRAS, and microsatellite status for prognostic assessment of patients with colorectal cancer. Methods A total of 51 colorectal cancer cases meeting the inclusion and exclusion criteria were enrolled in this study. TSR levels were evaluated through optical microscopy. The KRAS/NRAS/BRAF mutation profiles and microsatellite status were determined in accordance with genetic testing results. Clinical data, pathological characteristics, and survival outcomes were systematically recorded. Results Among the 51 patients with colorectal cancer, 19 (37.3%) were categorized into the low stromal group and 32 (62.7%) into the high stromal group. Statistically significant differences were observed between the two groups in drug resistance, M stage, TNM stage, neural invasion, and microsatellite status (P<0.05). Compared with patients exhibiting high TSR, those with low TSR demonstrated significantly increased recurrence rates (5 vs. 21 cases, P=0.007), shortened disease-free survival (34.21 vs. 14.34 months, P=0.001), and reduced overall survival (38.79 vs. 23.09 months, P=0.021). Multivariate Cox regression analysis identified N stage, M stage, TNM stage, neural invasion, lymphovascular invasion, and TSR as independent risk factors for disease-free survival. N stage, M stage, neural invasion, lymphovascular invasion, and TSR emerged as independent prognostic factors for overall survival (P<0.05). Although the combined models of TSR with KRAS, NRAS, BRAF, and microsatellite status, respectively, demonstrated overall statistical significance (P<0.05), none of the dummy variables in these models reached individually statistical significance (P>0.05), and therefore cannot be considered independent prognostic factors. Conclusion TSR serves as an independent predictor of poor prognosis in advanced colorectal cancer, with patients exhibiting low TSR demonstrating a significantly higher risk of recurrence and metastasis than those with high TSR. For patients with colon cancer undergoing first-line palliative chemotherapy after postoperative recurrence, histopathological assessment of TSR in primary tumor sites holds prognostic value and may serve as a relevant factor for evaluating treatment resistance in clinical management.
2.The evaluation of alpha-fetoprotein response on efficacy and prognosis in targeted therapy combined with immunotherapy for intermediate-to-advanced hepatocellular carcinoma: a multicenter clinical study
Kongying LIN ; Qingjing CHEN ; Luobin GUO ; Yun YANG ; Yufeng CHEN ; Jianxi ZHANG ; Fuqun WEI ; Hui ZHANG ; Zhiqing CHENG ; Yuntong LI ; Congren WANG ; Yabin JIANG ; Kecan LIN ; Weiping ZHOU ; Yongyi ZENG
Chinese Journal of Digestive Surgery 2024;23(2):248-256
Objective:To investigate the evaluation efficacy and predictive prognostic value of alpha-fetoprotein (AFP) response in tyrosine kinase inhibitors (TKIs) in combination with PD-1 inhibitors (α-PD-1) for intermediate-to-advanced hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 205 patients with intermediate-to-advanced HCC who were admitted to 9 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from March 2020 to July 2022 were collected. There were 178 males and 27 females, aged (52±12)years. Based on AFP response at 6-8 weeks after treatment, patients were divided into the AFP response group (AFP level decreased by ≥50% compared to baseline) and the AFP no response group (AFP level decreased by <50% compared to baseline). Observation indicators: (1) AFP response evaluation of anti-tumor efficacy; (2) comparison of patient prognosis; (3) analysis of factors affecting patient prognosis. Measurement data with normal distrubution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) and M( Q1, Q3). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional risk model was used for univariate analysis and the COX stepwise regression model was used for multivariate analysis. Results:(1) AFP response evaluation of anti-tumor efficacy. Before treatment, all 205 patients were positive of AFP, with a baseline AFP level of 1 560(219,3 400)μg/L. All 205 patients were treated with TKIs in combination with α-PD-1, and the AFP level was 776(66,2 000)μg/L after 6 to 8 weeks of treatment. Of the 205 patients, 88 cases were classified as AFP response and 117 cases were classified as AFP no response. According to the response evaluation criteria in solid tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were 42.05%(37/88) and 94.32%(83/88) in patients of the AFP response group and 16.24% (19/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=16.846, 25.950, P<0.05). According to the modified response evaluation criteria in solid tumors, the ORR and DCR were 69.32% (61/88) and 94.32% (83/88) in patients of the AFP response group and 33.33% (39/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=26.030, 25.950, P<0.05). (2) Comparison of patient prognosis. All 205 patients were followed up for 12.4(range, 2.4-34.0)months after treatment. The median progression free survival time and total survival time were 5.5 months and 17.8 months, respectively. The 1-year, 2-year progression free survival rates were 20.8% and 7.2%, and the 1-year, 2-year overall survival rates were 68.7% and 31.5%, respectively. The median progression free survival time, 1-year and 2-year progression free survival rates were 9.7 months, 39.6% and 14.2% in patients of the AFP response group and 3.7 months, 7.8% and 2.0% in patients of the AFP no response group, showing a significant difference in progression free survival between them ( χ2=43.154, P<0.05). The median overall survival time, 1-year and 2-year overall survival rates were not reached, 85.2% and 56.3% in patients of the AFP response group and 14.6 months, 56.3% and 14.5% in patients of the AFP no response group, showing a significant difference in overall survival between them ( χ2=33.899, P<0.05). (3) Analysis of factors affecting patient prognosis. Results of multivariate analysis showed that invasion of large blood vessels, extrahepatic metastasis, combined hepatic artery intervention therapy, and AFP response were independent factors influencing progression free survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio=1.474, 1.584, 0.631, 0.367, 95% confidence interval as 1.069-2.033, 1.159-2.167, 0.446-0.893, 0.261-0.516, P<0.05), and Eastern Cooperative Oncology Group score, invasion of large blood vessels, extrahepatic metastasis, and AFP response were independent factors influencing overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio= 1.347, 1.914, 1.673, 0.312, 95% confidence interval as 1.041-1.742, 1.293-2.833, 1.141-2.454, 0.197-0.492, P<0.05). Conclusions:AFP response at 6-8 weeks after treatment can effectively evaluate anti-tumor efficacy of TKIs in combination with α-PD-1 for intermediate-to-advanced HCC. AFP response is the independent factor influencing progression free survival and overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1.
3.Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus
ZHANG HAO ; WANG XINSHU ; HU BO ; LI PEICHENG ; ABUDUAINI YIERFAN ; ZHAO HONGMEI ; JIEENSIHAN AYINAER ; CHEN XISHUANG ; WANG SHIYU ; GUO NUOJIN ; YUAN JIAN ; LI YUNHUI ; LI LEI ; YANG YUNTONG ; LIU ZHONGMIN ; TANG ZHAOSHENG ; WANG HUA
Journal of Zhejiang University. Science. B 2024;25(7):568-580,中插1-中插3
Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.
4.Preliminary application of volumetric-modulated arc therapy dosimetry verification system based on three-dimensional dose reconstruction of patient anatomical structures
Yangguang MA ; Rizhen MAI ; Yuntong PEI ; Yuexin GUO
Chinese Journal of Radiation Oncology 2022;31(2):170-175
Objective:To perform testing and clinical application of a volumetric-modulated arc therapy (VMAT) dosimetry verification system based on three-dimensional dose reconstruction of patient anatomical structures.Methods:ArcCheck array calibration was performed. Then, 200 MU was delivered with a 10 cm×10 cm field when the source to center of ArcCheck was 100 cm to calibrate the absolute dose and the dose was simultaneously measured by a FC65-G detector in the center of the ArcCheck. The absolute dose calibration value or the CT value of ArcCheck was adjusted to minimize the differences between the planning and measurement values of FC65-G, reconstructed value by 3DVH and reconstructed percent depth dose by 3DVH. 10 lung and 10 cervical cancer VMAT cases were selected and measured by ArcCheck and FC65-G under the delivery of a TrueBeam LINAC. The three-dimensional doses of all cases were reconstructed by 3DVH and compared with the planning and measurement values.Results:Different array calibration files of ArcCheck exerted different effect upon the two-dimensional dose measured by ArcCheck and three-dimensional dose reconstructed by 3DVH. The optimal reconstructed dose was obtained when self-calibration file was adopted and 249.96 cGy was regarded as the absolute dose calibration value. The deviations of the mean dose (D mean) and D 95% of the target were within ±4.2% and parameters of some organs at risk significantly differed compared with the reconstructed and planning dose for all cases. A negative mean point dose difference was obtained and the reconstructed dose was closer to the measured value. The γ-passing rate of the target for some cases was low, the proportion of regions irradiated by 50% prescription dose was slightly higher and the proportion of other organs was relatively high. Conclusion:The 3DVH model can be accurately established and tested with the acceptance test method in the present study, which can provide detailed information for dose verification.
5.The application and correlation study of γ rule and DVH evaluation for VMAT dose verification evaluation of cervical cancer patients
YangGuang MA ; Rizhen MAI ; Yuntong PEI ; Fangna WANG ; Lele LIU ; Yuexin GUO
Chinese Journal of Radiation Oncology 2022;31(5):450-455
Objective:To evaluate the volumetric modulated arc therapy (VMAT) dose verification of cervical cancer based on γ rule and dose volume histogram (DVH) and to perform correlation analysis between the evaluation results and the dose differences.Methods:Twenty cervical cancer VMAT plans were selected and performed on TrueBeam Linac. The delivered point and surface dose was measured by FC-65 G and ArcCheck and the results were compared to those calculated by Eclipse. The dose of patients was reconstructed by 3DVH. Then, differences between the reconstructed and plan value of D mean, D 95%, D 98% and D 2% of PTV, V 20Gy of left and right femoral head, V 40Gy of rectum, D 1cm 3 of cord, D 98%, D 2% and D 50% of the 50% prescription iso-dose volume (IDV), were evaluated and 3-dimensional (3D) γ was assessed for each organ. Lastly, Pearson’s correlation coefficient was used to analyze the relationship between point dose difference, 2D γ pass-rate (γ%), γ mean and 3D γ% of each organ and the dose difference. Results:Small differences were found between the point dose measured, reconstructed and the plan value. Differences between D mean of PTV, all dose parameters of IDV and plan values were all within 3% and V 40Gy of rectum showed the largest difference. As for the 3D γ%, the maximum pass rate was found for the left and right femoral head and the maximum variance for cord D 1cm 3. There was a moderate correlation between measured and reconstructed point dose deviation and dose difference of each organ, while no significant correlation was found for 2D γ%. Strong correlation was found between 3D γ% of target and D 50% of PTV/IDV and no correlation was found for other organs. Conclusion:The performance of both γ-and DVH-based evaluation can reveal dose error for dose verification, but both of them have some limitations and should be combined in clinical practice.
6.Efficacy observation of Da Vinci robotic thyroidectomy in treatment of the unilateral papillary thyroid microcarcinoma
Jin ZHANG ; Wenjun ZHAO ; Yuntong GUO ; Zhensu LI ; Jing LIU
Cancer Research and Clinic 2021;33(10):763-766
Objective:To investigate the advantages of Da Vinci robotic thyroidectomy in treatment of the unilateral papillary thyroid microcarcinoma (PTMC).Methods:The clinical data of 49 patients with unilateral thyroid cancer admitted to the First Hospital of Shanxi Medical University from June 2018 to March 2020 were retrospectively analyzed, and they were divided into Da Vinci robotic group (the experimental group, 18 cases) and conventional surgery group (the control group, 31 cases) according to the surgical method. The clinicopathological characteristics, perioperative and postoperative related indexes changes, length of hospital stay, incidence of surgical complications, and operation cost of both groups of patients were analyzed. Visual analogue scale (VAS) was used to evaluate postoperative pain.Results:There were statistically significant differences in age, marriage and education background of both groups (all P < 0.05). There were statistically significant differences in the number of central lymph node dissection [(4.3±2.0) vs. (6.5±3.9)], operation time [198.5 min (166.3 min, 228.5 min) vs. 82.0 min (60.0 min, 102.0 min)], pain score of 24 h after surgery [3 scores (3 scores, 4 scores) vs. 2 scores (2 scores, 3 scores)], postoperative total drainage volume [49.0 ml (40.8 ml, 56.5 ml) vs. 37.0 ml, (29.0 ml, 44.0 ml)], operation cost [33,200 yuan (33,100 yuan, 34,000 yuan) vs. 5,200 yuan (4,200 yuan, 5,900 yuan)], and differences were statistically significant (all P < 0.05). No postoperative complications such as hemorrhage, fat liquefaction and subcutaneous ecchymosis occurred in all patients of the two groups. Conclusion:Da Vinci robotic thyroidectomy is safe and reliable in treatment of the unilateral PTMC, and it has good therapeutic effects.
7.The impact factors of longitudinal dose fall-off outside the target with helical tomotherapy
Haiyang WANG ; Yifei PI ; Bin HAN ; Fei JIA ; Lele LIU ; Fangna WANG ; Fanyang KONG ; Yuntong PEI ; Jinyan HU ; Yuexin GUO
Chinese Journal of Radiological Medicine and Protection 2021;41(3):183-187
Objective:To study the changing characteristics and impact factors of helical tomotherapy (HT)for longitudinal dose fall-off outside the target, in order to guide the plan junction or pretreatment target and implementation efficiency in clinical.Methods:Eight patients with head and neck tumors admitted to the Department of Oncology Radiotherapy of the First Affiliated Hospital of Zhengzhou University in December 2019 were retrospectively selected as the research objects. The planning target area and dose drop structure were outlined in the head and neck images with a thickness of 1 mm obtained by Siemens SOMATOM Definition AS positioning computerized tomography (CT). Different field widths (FW, 5.0 cm/2.5 cm/1.0 cm) and pitches (0.430/0.287/0.215) were assembled for planning with the same modulation factor (1.8), finest does calculation grid (0.195 cm ×0.195 cm) and other planning parameters were consistent. The plans were designed by different parameters, and the result was analyzed by univariate analysis.Results:The that different pitch curves coincided under the same field width by comparative analyzing, so pitchs had no effect on dose drop. The different field width curves were independent of each other, indicating that the field width had an effect on dose drop in the head and foot direction. The relationship between the longitudinal dose drop speed outside the target and the change of the field width was inversely correlated: the larger field widths meant the slower dose fall-off and the larger penumbra, while the smaller field widths meant the faster fall-off and the smaller penumbra. When the dose fall-off to 50% of the prescribed dose, the distance from the target was approximately equal to half the field widths, and the pitchs had not affect the rate of dose-drop, while the dose at different distances from the target boundary could be calculated by the fitting formulas. The field widths and pitchs had little effect on the CI and HI index of the target, relatively, the target area was best when the field width was 2.5 cm. The total beam-on time gradually decreased with the increase of the field widths and pitches.Conclusions:When segment target therapy needs to consider planning junction, execution efficiency, and controlling longitudinal dose fall-off and considered the execution, the optimal planned parameters such as field widths and pitches could be selected or the target at the junction regions could be adducted according to the longitudinal dose drop formula, so as to achieve the ideal dose distribution.
8.Evaluation the combined effect of three dose reconstruction systems on VMAT dosimetry verification of lung cancer
Yangguang MA ; Rizhen MAI ; Yuntong PEI ; Jinyan HU ; Fanyang KONG ; Xuemin WANG ; Yuexin GUO
Chinese Journal of Radiation Oncology 2021;30(1):76-80
Objective:To evaluate the combined effect of an trajectory log field based(LBF)and two commercial dose reconstruction systems on volume-modulated arc therapy(VMAT)dose verification of lung cancer.Methods:An in-house program was developed to introduce errors in trajectory log of TrueBeam to the origin plan and recalculate the dose of the error plan in treatment planning system(TPS). A total of 18 lung cancer cases treated by two-arc VMAT were selected to perform on LINAC and measured by ArcCheck simultaneously. Then, the reconstructed doses were obtained by 3DVH. The mode of reconstruction was calculated by LFB and Compass. Five of the 18 cases were performed on LINAC two times in four hours and measured by ArcCheck to evaluate the stability of the TrueBeam performance. The 18 plans were recalculated and performed on LINAC with a solid water phantom with 5 cm build-up, 4 cm back scattering thickness and a FC65-G detector in the center. The measured dose by detector was compared with the reconstructed dose by three systems.Results:TheTruebeam performance was stable. For all of the 18 cases, the point dose measured by FC65-G and reconstructed by three systems had a deviation of less than 2% to the TPS calculated. For all of the organs reconstructed by LBF and most organs reconstructed by 3DVH and Compass, the γ pass rate between them and TPS all exceeded 90% under all criteria, as well as the ArcCheck measured results. For all the organ dose difference between reconstructed and TPS, LBF system had the smallest difference, followed by the Compass system except the lung, and the 3DVH had the highest difference.Conclusions:LBF, 3DVH and Compass can reflect the VMAT dose verification results of lung cancer from different perspectives. The combined application of three systems can demonstrate the verification results in an intuitive manner, which is beneficial for subsequent analysis.
9.Comparative study of the effects of laparoscopic and open colorectal cancer surgery on intestinal barrier function
Yuntong GUO ; Wei LIU ; He HUANG
Chinese Journal of Clinical Nutrition 2020;28(1):27-31
Objective:To compare and investigate the effects of laparoscopy and open colorectal cancer on the intestinal barrier function in patients with colorectal cancer.Methods:Sixty-two patients with colorectal cancer admitted in our hospital from January 2015 to October 2016 were selected and divided into laparoscopic surgery group with thirty-four patients and open surgery group with twenty-eight patients. The changes of postoperative intestinal barrier function were compared between the two groups.Result:The levels of plasma D-lactate, plasma diamine oxidase (DAO) and bacterial endotoxin in the laparoscopic surgery group were significantly lower than those in the open surgery group ( P<0.05). Conclusion:Laparoscopic and open colorectal cancer surgery can cause damage to intestinal barrier function, but the damage of laparoscopic colorectal cancer surgery is lower than that of open colorectal surgery.
10. A quantitative evaluation on the image-quality parameters and quality assurance thresholds setting of accelerator on-board imaging system
Jinyan HU ; Yuntong PEI ; Yangguang MA ; Haiyang WANG ; Lele LIU ; Yuexin GUO
Chinese Journal of Radiation Oncology 2019;28(12):919-923
Objective:
To achieve quantitative analysis of image quality parameters and establish warning and action thresholds for the on-board imaging (OBI) system of linear accelerator.
Methods:
The Catphan604 phantom was repeatedly scanned in the Full-Fan and Half-Fan CBCT scanning modes on a Varian EDGE linear accelerator, and the software based on Python language development in-house was utilized to analyze image quality parameters, such as CT number linearity, geometric consistency, slice thickness, spatial resolution, uniformity and low-contrast resolution. The quantitative analysis results of each image quality parameter obtained from 16 times of scanning within 16 months were normalized to the mean and the standard deviations were recorded. A run chart analysis was created to determine the warnings and action thresholds.
Results:
The software built in-house can quantitatively analyze the image parameters of the two scanning modes of OBI system. The low-contrast resolution of Half-Fan was better than that of Full-Fan, whereas the spatial resolution of Full-Fan was superior to that of Half-Fan. One standard deviation (1σ) was set as the warning threshold and 2 standard deviations (2σ) as the action threshold, respectively. The tolerance level of Half-Fan was smaller than that of Full-Fan.
Conclusion
Self-developed software enables quantitative analysis of accelerator image quality parameters, establishes warning and action tolerance of quality assurance and provides guidance for image quality assurance under image-guided radiotherapy specification.

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