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    08 April 2025, Volume 52 Issue 4 Previous Issue   
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    Original Article
    Differential diagnosis model construction of invasive degree of lung adenocarcinoma manifesting as ground-glass nodules with no or little solid component based on energy spectrum CT features
    Liu Yiyong, Huo Fengzhi
    2025, 52 (4):  197-201.  doi: 10.3760/cma.j.cn371439-20240215-00033
    Abstract ( 12 )   HTML ( 1 )   PDF (1105KB) ( 4 )   Save

    Objective To construct the differential diagnosis model of invasive degree of lung adenocarcinoma manifesting as ground-glass nodules (GGNs) with no or little solid component based on energy spectrum CT features,and to provide reference for the follow-up clinical diagnosis and treatment. Methods A retrospective study was conducted on 145 patients who underwent surgical treatment for lung adenocarcinoma at the 969th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army and Inner Mongolia Hospital of Peking University Cancer Hospital from January 2019 to December 2022,presenting with CT findings of no or little solid component GGNs. The patients were divided into invasive group (51 cases) and microinvasive group (94 cases) based on the invasive degree. Logistic regression was used to conduct a multivariate analysis of factors affecting the differential diagnosis of invasive degree of lung adenocarcinoma manifesting as GGNs with no or little solid component,and construct a logistic regression model. Receiver operator characteristic (ROC) curve was used to analyze the predictive efficiency of each index. Results Univariate analysis showed that the maximum diameter of nodules (t=-6.30,P<0.001),average CT value of nodules (t=-5.43,P<0.001),air bronchial sign (χ2=23.21,P<0.001),microvascular CT imaging type (χ2=27.94,P<0.001) were predictors of invasive degree of lung adenocarcinoma manifesting as GGNs with no or little solid component. Multivariate logistic regression analysis showed that the maximum diameter of nodules (OR=1.72,95%CI:1.33-2.23,P<0.001),average CT value of nodules (OR=1.01,95%CI:1.01-1.02,P<0.001),air bronchial sign (OR=4.92,95%CI:1.59-15.21,P=0.006) and microvascular CT imaging type Ⅲ (OR=14.01,95%CI:2.97-66.06,P=0.001) were independent predictors of invasive degree of lung adenocarcinoma manifesting as GGNs with no or little solid component. A logistic regression model was constructed based on the results of the above multiple factor analysis:logit (P)=0.54×maximum diameter of the nodule+0.01×average CT value of the nodule+1.59×air bronchogram sign+2.64×microvascular CT imaging type (type Ⅲ)-3.33. ROC curve analysis showed that the areas under the curve for differential diagnosis of invasive degree of lung adenocarcinoma manifesting as GGNs with no or little solid component based on the maximum diameter of nodules,average CT value of nodules,air bronchogram sign,microvascular CT imaging type,and logistic regression model P-value were 0.759,0.751,0.686,0.741,and 0.918,respectively. Conclusions The energy spectrum CT features,including the maximum diameter of nodules,average CT value of nodules,air bronchial sign,and microvascular CT imaging type,can be used for differential diagnosis of invasive degree of lung adenocarcinoma manifesting as GGNs with no or little solid component. The logistic regression model constructed using the above four factors has shown good performance in predicting the invasive degree of patient.

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    A predictive model for immunotherapy efficacy in non-small cell lung cancer constructed based on CT image-weighted radiomics score
    Liu Haiyan, Zhang Chao
    2025, 52 (4):  202-208.  doi: 10.3760/cma.j.cn371439-20240618-00034
    Abstract ( 7 )   HTML ( 1 )   PDF (1310KB) ( 3 )   Save

    Objective To construct a predictive model for the efficacy of immunotherapy in non-small cell lung cancer (NSCLC) based on CT image-weighted radiomics score. Methods A total of 185 patients with NSCLC who received immunotherapy in Affiliated Shuyang Hospital of Xuzhou Medical University from January 2021 to December 2023 were selected as the study objects. All patients underwent 3 consecutive cycles of nivolumab (240 mg) treatment,and therapeutic efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1. The patients were divided into treatment-effective group and treatment-ineffective group based on therapeutic outcomes. Based on pre-treatment arterial phase CT images,all volume regions of interest were resampled using PyRadiomics tool,and image preprocessing was performed (including methods such as Wavelet transform and Laplacian filtering). The multi-focal imaging radiomics features of the two groups of patients were extracted,and standardized processing of the extracted features was carried out on the Dr. Wise research platform. At the same time,a CT image-weighted radiomics score model was constructed using an attention-based multi-instance learning (a-MIL) algorithm,the least absolute shrinkage and selection operator (LASSO) regression,and logistic regression,and the CT image-weighted radiomics score of each patient was calculated. The nomogram was plotted using R software (version R4.3.3) and the rms package. The concordance index (C-index) was used to evaluate the concordance of the model. Receiver operator characteristic (ROC) curve was used to evaluate the performance of the nomogram model in predicting immunotherapy efficacy in NSCLC. The calibration curve was used to evaluate the consistency of the predicted probabilities with the actual outcomes,while the decision curve was used to evaluate net benefit of the model across different thresholds. Results There were statistically significant differences in sex (χ²=3.86,P=0.049),pathological type (χ²=8.41,P=0.015),smoking history (χ²=5.70,P=0.017),and pre-treatment pulmonary metastasis (χ²=5.88,P=0.015) between the treatment-effective group (n=66) and treatment-ineffective group (n=119). The original multi-focal radiomics features were weighted and summated by a-MIL algorithm at case level,and a total of 342 imaging radiomics features were extracted,162 features among which had good consistency (intra-class correlation coefficient >0.80). After variance analysis,134 features were eliminated,28 features remained. After dimensionality reduction by LASSO regression,7 imaging radiomics features were obtained. They were GLCMEnergy_angle45_offset,ShortRunEmphasis_angle90_offset1,maximum gray value,Spiculation,GLCMEnergy_angle45_offset7,Sphericity,and Vessel. Based on the above imaging radiomics features,the weighted radiomics score model was constructed as follows:Radscore=0.624+0.022×GLCMEnergy_angle45_offset-0.227×ShortRunEmphasis_angle90_offset1+0.395×maximum gray value-8.687×Spiculation+0.384×GLCMEnergy_angle45_offset7-0.012×Sphericity-0.284×Vessel. The CT image-weighted radiomics score in the treatment-effective group (0.75±0.10) was significantly higher than that in the treatment-ineffective group (0.43±0.14),with a statistically significant difference (t=18.00,P<0.001). ROC curve analysis showed that the area under the curve (AUC) of CT image-weighted radiomics score for predicting immunotherapy efficacy of NSCLC was 0.96 (95%CI:0.92-0.98),and the optimal cutoff value was 0.62. Multivariate analysis showed CT image-weighted radiomics score ≥0.62 (OR=14.77,95%CI:3.25-22.35,P<0.001),pathological type (squamous cell carcinoma) (OR=1.74,95%CI:1.35-3.52,P=0.035),smoking history (OR=4.01,95%CI:1.05-15.30,P=0.042),and pre-treatment pulmonary metastasis (OR=1.20,95%CI:1.01-1.38,P=0.010) were all independent predictors of immunotherapy effectiveness in NSCLC. Based on the above 4 variables,a nomogram model was constructed to predict the immunotherapy efficacy of NSCLC,and the model validation results showed that the C-index was 0.96 (95%CI:0.93-0.99). Calibration curve analysis showed good consistency of the predicted probabilities with the actual probabilities,closely aligning with the ideal curve. ROC curve analysis showed that AUC was 0.97 (95%CI:0.94-0.99). Decision curve analysis showed that the model had a net benefit within the prediction range of 2% to 100%. Conclusion The nomogram model based on CT image-weighted radiomics score is effective in predicting immunotherapy efficacy of NSCLC patients.

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    Clinical efficacy and safety of radiotherapy combined with chemotherapy and immunotherapy for HER2-negative locally advanced or advanced gastric cancer
    Liu Qianyi, Dong Hongmin, Wang Wenling, Wang Gang, Chen Wanghua
    2025, 52 (4):  209-216.  doi: 10.3760/cma.j.cn371439-20240820-00035
    Abstract ( 5 )   HTML ( 1 )   PDF (916KB) ( 4 )   Save

    Objective To explore the clinical efficacy and safety of a multimodal treatment regimen integrating radiotherapy,chemotherapy,and immunotherapy in patients with human epidermal growth factor receptor 2 (HER2)-negative locally advanced or advanced gastric cancer. Methods A total of 34 patients with unresectable,HER2-negative,locally advanced or metastatic gastric/gastroesophageal junction (G/GEJ) adenocarcinoma admitted to the Affiliated Cancer Hospital of Guizhou Medical University from September 2021 to March 2024 were selected as study objects. Participants received one cycle of either XELOX regimen (capecitabine + oxaliplatin) or SOX regimen (S-1 + oxaliplatin) with immunotherapy (sintilimab or nivolumab). The process was succeeded by radiotherapy targeted at the primary G/GEJ tumor and regional lymph nodes. In selected cases,sequential radiotherapy was also administered for distant metastases. The primary endpoint was Objective response rate (ORR),and secondary endpoints were disease control rate (DCR),clinical symptom response,changes in Karnofsky performance status (KPS) score,progression-free survival (PFS),and adverse reactions. Clinical efficacy was assessed in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. Adverse reactions were assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 and the Chinese Society of Clinical Oncology guidelines for management of immune checkpoint inhibitor-related toxicity. With a median follow-up of 7 months (range:2.3 to 30 months),the final evaluation considered the best response documented throughout follow-up. Survival curves were constructed utilizing Kaplan-Meier analysis. Results By the end of follow-up,an overall ORR of 58.8% (20/34) and DCR of 70.6% (24/34) were observed. The ORR of lesions by radiotherapy reached 73.8% (48/65) and the DCR reached 92.3% (60/65). Univariate analysis showed that the ORR of female patients (84.6%,11/13) was higher than that of male patients (42.9%,9/21),and the ORR of patients with distant lymph node metastasis alone (83.3%,15/18) was higher than that of patients with distant lymph node metastasis combined with organ metastasis or organ metastasis alone (18.2%,2/11),with statistically significant differences (P=0.030; P=0.010). There were no statistically significant differences in ORR among patients with different age (P=0.487),KPS score (P=0.198),primary tumor location (P=0.280),histological differentiation (P=0.668),chemotherapy regimen (P=0.728),or immunotherapy regimen (P>0.999). Twenty-two of 23 (95.7%) patients with upper abdominal pain were relieved,10 of 21 (47.6%) patients with appetite loss were relieved,15 of 17 patients with upper abdominal distension were relieved,13 of 14 patients with melena were relieved,6 of 7 patients with eating obstruction were relieved,3 of 4 patients with metastatic site pain were relieved,and 2 patients with hematemesis were relieved. KPS score enhanced in 82.4% (28/34) of patients,remained stable in 11.8% (4/34),and declined in 5.8% (2/34). The median PFS of the 34 patients was 7.9 months. The most common adverse reactions during radiotherapy combined with chemotherapy and immunotherapy were hematological adverse reactions,in which neutropenia accounted for the highest proportion (91.2%,31/34),followed by anemia (50.0%,17/34). Fatigue was the most common non-hematological adverse reaction (50.0%,17/34),followed by nausea and vomiting (26.5%,9/34). The adverse reactions of 6 patients receiving immune monotherapy maintenance were anemia,hypothyroidism,transaminase elevation,proteinuria,fatigue,and rash,all of which were grade 1-2. Conclusions Radiotherapy combined with chemotherapy and immunotherapy shows good short-term clinical efficacy in patients with HER2-negative locally advanced or advanced gastric cancer,and the overall adverse reactions are tolerable. Female or patients with distant lymph node metastasis alone may be the preferred population for this study protocol.

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    Analysis of pancreatic cancer incidence and mortality in China from 1992 to 2021 based on the age-period-cohort model
    Hu Jiabao, Hua Sha, Chen Wei, Ma Lina
    2025, 52 (4):  217-223.  doi: 10.3760/cma.j.cn371439-20241030-00036
    Abstract ( 8 )   HTML ( 1 )   PDF (2171KB) ( 0 )   Save

    Objective To analyze the incidence and mortality of pancreatic cancer in China from 1992 to 2021,and to explore the effects of age,period,and cohort on pancreatic cancer incidence and mortality. Methods Data from the Global Burden of Disease Study (GBD) 2021 database were used to analyze the incidence and mortality of pancreatic cancer in China from 1992 to 2021. The Joinpoint software was applied to analyze the time trends of standardized incidence and mortality rates,and to calculate the average annual percentage change. An age-period-cohort model was constructed to analyze the effects of age,period,and birth cohort on the trends of pancreatic cancer incidence and mortality. The disease burden of pancreatic cancer deaths attributed to risk factors such as hyperglycemia and smoking was analyzed. Results In 2021,the incidence of pancreatic cancer in China was 8.34/100 000,and the mortality rate was 8.41/100 000,representing increases of 150.45% and 145.19%,respectively,compared to 1992 (3.33/100 000 and 3.43/100 000). By sex,the incidence (9.93/100 000) and mortality (9.91/100 000) rates in males in 2021 were higher than those in females (6.68/100 000 and 6.83/100 000). From 1992 to 2021,the standardized incidence and mortality rates of pancreatic cancer in China showed upward trends,with average annual increases of 0.80% and 0.62%,respectively,both of which were statistically significant (both P<0.001). Age effect results indicated a general increasing trend in pancreatic cancer incidence,with a steady rise in the 15-49 age group,a sharp increase after the age of 50,and a peak in the over 85 age group at 68.64/100 000. The mortality rate showed a slow increase in the 15-79 age group,with a marked rise and peak in the 80-84 age group at 196.51/100 000. Period effect results showed an overall upward trend in the period relative risk (RR) for pancreatic cancer incidence,with the highest risk in 2017-2021 (RR=1.09,95%CI:1.05-1.13,P=0.012),compared to the reference period 2002-2006 (RR=1). The RR for pancreatic cancer mortality showed a fluctuating trend,with the highest risk in 2012-2016 (RR=1.60,95%CI:1.07-2.38,P=0.021),compared to the reference period 2002-2006 (RR=1). The results of cohort effect showed that the incidence and mortality risk of pancreatic cancer in China generally increased with the increase of years. With the 1952-1956 birth cohort as the reference cohort (RR=1),the incidence (RR=1.18,95%CI:0.99-1.40,P=0.032) and mortality (RR=1.63,95%CI:0.12-11.53,P=0.042) risk of pancreatic cancer were the highest in the 1987-1991 birth cohort, and showed decreasing trends after the 1992-1996 birth cohort. The proportion of pancreatic cancer deaths attributable to high blood glucose showed an increasing trend,while those attributable to smoking showed a decreasing trend. Conclusions From 1992 to 2021,the standardized incidence and mortality rates of pancreatic cancer in China have continued to rise,with males having higher incidence and mortality rates than females. Age,period,and cohort all significantly influence the trends in pancreatic cancer incidence and mortality. The trend in pancreatic cancer deaths attributable to high blood glucose is increasing.

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    Changes of T lymphocyte subsets and the relationship with postoperative lymph node metastasis in patients with stage Ⅰ and Ⅱ cervical cancer
    Zhou Xiaoyu, Pu Xuefeng, Long Shulin, Li Lu, He Wenying
    2025, 52 (4):  224-230.  doi: 10.3760/cma.j.cn371439-20240704-00037
    Abstract ( 4 )   HTML ( 1 )   PDF (819KB) ( 0 )   Save

    Objective To investigate the changes of T lymphocyte subsets in patients with stage Ⅰ and Ⅱ cervical cancer after surgery and their relationship with postoperative lymph node metastasis according to the International Federation of Gynecology and Obstetrics (FIGO) stage (2014). Methods A total of 192 patients with FIGO stage ⅠA,ⅠB1,ⅠB2 and ⅡA1 who received radical cervical cancer resection and pelvic lymph node dissection in People's Hospital of Yuechi County of Sichuan Province and West China Guang'an Hospital of Sichuan University from November 2018 to November 2020 were selected for this study. According to FIGO stage,patients were divided into stage Ⅰ group (n=85) and stage Ⅱ group (n=107). The dynamic changes of T lymphocytes subsets in patients with different FIGO stages were compared before and after surgery. Repeated measurement of variance was used to analyze the levels of T lymphocytes subsets in patients of different stages during treatment. Logistic regression was used to analyze the influencing factors of postoperative lymph node metastasis in patients with cervical cancer. Multivariate logistic regression was used to analyze the relationship between T lymphocytes subsets and postoperative lymph node metastasis. Receiver operator characteristic (ROC) curve was used to analyze the predictive efficacy of T lymphocytes level in postoperative lymph node metastasis. Results The postoperative lymph node metastasis rate in stage Ⅱ patients [32.71% (35/107)] was higher than that in stage Ⅰ patients [14.12% (12/85)],with a statistically significant difference (χ2=8.86,P=0.003). Compared with the stage Ⅱ group,the levels of CD3+,CD4+ T lymphocytes and CD4+/CD8+ ratio were significantly higher in the stage Ⅰ group 1 day before surgery (all P<0.001),and the level of CD8+ T lymphocytes was significantly lower (P<0.001). The levels of CD3+,CD4+,CD8+ T lymphocytes and the ratio of CD4+/CD8+ showed dynamic changes at different stages after surgery. On 1,7 and 30 days after surgery,the levels of CD3+,CD4+ T lymphocytes and the ratio of CD4+/CD8+ in stage Ⅰ group were higher than those in stage Ⅱ group (all P<0.001),CD8+ T cell levels were lower than those in stage Ⅱ group (all P<0.001). There were statistically significant differences in T lymphocytes subsets CD3+,CD4+,CD8+ and CD4+/CD8+ time effect,intergroup effect and interaction effect between the two groups (all P<0.001). Univariate analysis showed that the pathological type (OR=1.85,95%CI:1.14-2.33,P=0.015),differentiation degree (OR=1.93,95%CI:1.18-2.67,P=0.024),depth of myometrial invasion (OR=2.08,95%CI:1.26-2.59,P=0.012),tumor morphology (OR=2.17,95%CI:1.57-2.63,P=0.009),parametrial invasion (OR=1.95,95%CI:1.43-2.76,P=0.036) and lymphovascular space invasion (OR=2.03,95%CI:1.28-2.57,P=0.021) were the influencing factors for postoperative lymph node metastasis in patients with FIGO stage Ⅰ and Ⅱ cervical cancer. Multivariate analysis showed that the degree of differentiation (OR=1.75,95%CI:1.08-2.03,P=0.015),depth of myometrial invasion (OR=2.30,95%CI:1.43-2.84,P=0.021),parametrial invasion (OR=2.50,95%CI:1.76-2.97,P=0.018) and lymphovascular space invasion (OR=1.96,95%CI:1.03-2.51,P=0.033) were independent factors for postoperative lymph node metastasis in patients with FIGO stage Ⅰ and Ⅱ cervical cancer. Multivariate logistic regression analysis showed that the levels of CD3+,CD4+,CD8+ T cells and the ratio of CD4+/CD8+ in patients with stage Ⅰ and stage Ⅱ cervical cancer 1 day before surgery were independent influencing factors for postoperative lymph node metastasis (all P<0.05). ROC curve analysis showed that the areas under the curve of CD3+,CD4+,CD8+ T lymphocytes levels and the ratio of CD4+/CD8+ in stage Ⅰ patients 1 day before surgery for predicting postoperative lymph node metastasis were 0.86,0.82,0.83,0.89,respectively,and those in stage Ⅱ patients were 0.90,0.93,0.87,0.95,respectively. CD4+/CD8+ ratio was significantly more effective in predicting postoperative lymph node metastasis than other indexes (all P<0.001). Conclusions The levels of CD3+,CD4+ T lymphocytes,and the CD4+/CD8+ ratio in patients with FIGO stage Ⅰ and Ⅱ cervical cancer are significantly higher in 1-30 days after surgery than before,while the level of CD8+ T lymphocytes is significantly lower than before. There is a significant correlation between T lymphocytes subsets and lymph node metastasis after surgery. In addition,low differentiation,depth of myometrial invasion ≥1/2,parametrial invasion,and lymphovascular space invasion are independent risk factors for postoperative lymph node metastasis.

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    Review
    Impacts of radiotherapy on anti-tumor immunity:a comprehensive review from the fundamental to the clinical
    Wen Yingmei, Xia Jinxiong, Wang Yuanyuan, Yao Yi
    2025, 52 (4):  231-236.  doi: 10.3760/cma.j.cn371439-20240727-00038
    Abstract ( 7 )   HTML ( 1 )   PDF (836KB) ( 4 )   Save

    Radiotherapy is a crucial component of the treatment of tumors. In addition to directly causing DNA damage in tumor cells and inducing cell apoptosis,radiotherapy is also involved in the regulation of systemic immune status. Increasing evidence indicates that radiotherapy can remodel the tumor immune microenvironment (TIME) and reverse the immunosuppressive state,thereby enhancing anti-tumor effects and demonstrating stronger immune responses and therapeutic benefits when combined with immune checkpoint inhibitors. Taking lung cancer as an example to explore the impacts and potential mechanisms of radiotherapy on the TIME and anti-tumor immunity,which can provide a scientific basis for optimizing the treatment strategies of lung cancer.

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    Research updates of RET proto-oncogene in non-small cell lung cancer
    Tang Lei, Cai Zongyou, Chang Jianhua
    2025, 52 (4):  237-241.  doi: 10.3760/cma.j.cn371439-20241115-00039
    Abstract ( 4 )   HTML ( 2 )   PDF (820KB) ( 1 )   Save

    The RET protein encoded by RET proto-oncogene is a receptor tyrosine kinase that serves as a potential therapeutic target in non-small cell lung cancer (NSCLC). In NSCLC,the incidence of RET fusions variants ranges from 1%-2% and is more common in younger,non-smoking patients. Traditional chemotherapy,immunotherapy,and multitarget kinase inhibitors have shown limited efficacy in treating RET fusion-positive NSCLC patients. However,selective RET inhibitors,such as selpercatinib and pralsetinib,have significantly improved the prognosis of those patients. The treatment strategy following resistance to selective RET inhibitors is a future research direction.

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    Progress in the study of fructose-bisphosphate aldolase A in lung cancer
    Lu Bing, Xiong Siyu, Jiang Wenhong, Yu Tingting
    2025, 52 (4):  242-245.  doi: 10.3760/cma.j.cn371439-20240727-00040
    Abstract ( 9 )   HTML ( 2 )   PDF (793KB) ( 1 )   Save

    Various metabolic enzymes and signaling molecules in the reprogramming process of glucose metabolism are involved in the occurrence and development of lung cancer. The study of these metabolic enzymes and signaling molecules is one of the hot spots and directions in the clinical diagnosis and treatment of lung cancer. Fructose-bisphosphate aldolase A (ALDOA) is an important catalytic enzyme in the reprogramming of glucose metabolism,and the abnormal expression of ALDOA is intricately related to the occurrence and development of lung cancer. Systematically exploring of the role of ALDOA in lung cancer metabolism may provide new ideas for predicting the metastasis,prognosis,and treatment after drug resistance of lung cancer.

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