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08 August 2024, Volume 51 Issue 8 Previous Issue    Next Issue

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Relationship between TFA-irAE after anti-PD-1 therapy and survival in advanced cancer patients Guo Wei, Wang Donghui, Wang Zhenhua, Xue Zhaojun 2024, 51 (8):  481-486.  doi: 10.3760/cma.j.cn371439-20240215-00080 Abstract ( 51 )   HTML ( 11 )   PDF (831KB) ( 34 )   Save Objective To investigate the relationship between thyroid function abnormality-immune related adverse event （TFA-irAE） and treatment efficacy and survival in advanced cancer patients treated with programmed death-1 （PD-1） inhibitors. Methods The clinical data of 90 patients with advanced cancer who received 6 cycles of PD-1 inhibitor treatment from January 2021 to June 2022 in Department of Oncology of Yuncheng Central Hospital Affiliated to Shanxi Medical University were collected. Serum levels of thyroid stimulating hormone （TSH），free thyroxine （FT4），thyroid peroxidase antibody （TPOAb），and thyroglobulin antibody （TGAb） were measured by chemiluminescence immunoassay in patients after PD-1 inhibitor treatment，and the incidence of TFA-irAE was observed in the patients after 6 cycles of therapy. According to the occurrence of TFA-irAE，the patients were divided into TFA-irAE occurrence group （n=40） and TFA-irAE non-occurrence group （n=50），the therapeutic efficacy and survival of the two groups were calculated and compared. The thyroid function indexes of patients with different efficacy （33 cases in effective group and 57 cases in ineffective group） and patients with different prognosis （30 cases in survival group, 60 cases in death group） were compared，and the influencing factors of efficacy and survival were analyzed by multivariate logistic regression and Cox analysis. Kaplan-Meier survival curve was drawn，and the survival of TFA-irAE occurrence group and TFA-irAE non-occurrence group were compared by log-rank test. Results One year after treatment，the treatment effective rate of TFA-irAE occurrence group and TFA-irAE non-occurrence group were 42.5% （17/40），32.0% （16/50），respectively，with no statistically significant difference （χ2=1.06，P=0.304）. After 6 cycles of PD-1 inhibitor treatment，serum levels of TSH [（2.56±0.41） mU/ml vs. （3.11±0.53） mU/ml]，TPOAb [（56.78±5.72） U/ml vs. （62.67±6.31） U/ml] and TGAb [（81.57±8.23） U/ml vs. （92.34±9.31） U/ml] in the effective group were significantly lower than those in the ineffective group，with statistically significant differences （t=4.45，P<0.001； t=3.89，P<0.001； t=5.29，P<0.001）. The serum levels of TSH [（2.69±0.46） mU/ml vs. （3.06±0.65） mU/ml]，FT4 [（10.45±1.13） pmol/L vs. （11.50±1.36） pmol/L]，TPOAb [（56.27±5.61） U/ml vs. （62.47±6.34） U/ml] and TGAb [（81.62±8.31） U/ml vs. （91.73±9.35） U/ml] in the survival group were significantly lower than those in the death group，with statistically significant differences （t=2.27，P=0.025； t=3.02，P=0.003； t=3.79，P<0.001； t=4.19，P<0.001）. Multivariate logistic regression analysis showed that TSH （OR=1.52，95%CI：1.13-2.05，P=0.006），TPOAb （OR=1.42，95%CI：1.13-1.78，P=0.002） and TGAb （OR=1.35，95%CI：1.05-1.73，P=0.018） were all independent factors affecting the efficacy of patients with advanced cancer treated with PD-1 inhibitors. Multivariate Cox regression analysis showed that TSH （HR=1.42，95%CI：1.06-1.92，P=0.030），TPOAb （HR=1.31，95%CI：1.05-1.64，P=0.018），TGAb （HR=1.41，95%CI：1.09-1.83，P=0.008） and FT4 （HR=1.36，95%CI：1.02-1.81，P=0.038） were all independent factors affecting the survival of patients with advanced cancer treated with PD-1 inhibitors. Survival analysis showed that the median overall survival in the TFA-irAE occurrence group and the TFA-irAE non-occurrence group were 10.8 and 8.0 months，respectively，with a statistically significant difference （χ2=9.53，P=0.002）. Conclusion Although the occurrence of TFA-irAE may have less effect on the efficacy of advanced tumor patients treated with PD-1 inhibitors，it may affect the survival of patients. TSH，TPOAb and TGAb are all independent influencing factors for the efficacy of patients with advanced tumors treated with PD-1 inhibitors，while TSH，TPOAb，TGAb and FT4 are independent influencing factors for the survival of patients with advanced tumors treated with PD-1 inhibitors. Figures and Tables | References | Related Articles | Metrics

Analysis of changes in serum miR-499 and miR-362 levels and their relationship with prognosis in advanced NSCLC patients Ni Guoying, Huang Qian, Liang Hongxiang, Yang Zhiyong, Ding Yingli 2024, 51 (8):  487-492.  doi: 10.3760/cma.j.cn371439-20240318-00081 Abstract ( 32 )   HTML ( 12 )   PDF (916KB) ( 33 )   Save Objective To explore the changes in serum levels of miR-499 and miR-362 in patients with advanced non-small cell lung cancer （NSCLC） and their relationship with prognosis. Methods A total of 103 patients with advanced NSCLC at Shanghai University of Medicine & Health Sciences Affiliated Chongming Hospital from January 2020 to October 2021 were selected as the NSCLC group，and 100 healthy volunteers who underwent physical examinations at our hospital during the same period were selected as the control group. Fluorescent quantitative PCR was used to determine and compare the levels of serum miR-499 and miR-362 in the two groups，and the relationship between the two indexes and different clinical characteristics of NSCLC patients was analyzed. According to the clinical outcome of 2-year follow-up，the patients were divided into survival group and death group，and the levels of serum miR-499 and miR-362 were compared between the two groups. The predictive value of miR-499 and miR-362 levels on the prognosis of advanced NSCLC patients were analyzed using receiver operator characteristic （ROC） curves. Results The serum miR-499 level in the NSCLC group （0.34±0.10） was lower than that in the control group （1.25±0.21），while the miR-362 level （1.13±0.27） was higher than that in the control group （0.63±0.15） （t=18.26，P<0.001；t=16.32，P<0.001）. There were statistically significant differences in serum miR-499 and miR-362 levels among patients with different degrees of differentiation （t=11.12，P<0.001； t=16.35，P<0.001），TNM staging （t=13.64，P=0.002； t=8.73，P=0.010） and lymph node metastasis （t=10.02，P=0.003； t=9.65，P=0.004）. The serum miR-499 level in the death group （n=77） （0.24±0.06） was lower than that in the survival group （n=26） （0.35±0.09），while the miR-362 level （1.54±0.32） was higher than that in the survival group （1.08±0.21），with statistically significant differences （t=8.06，P=0.006； t=8.67，P=0.005）. ROC curve analysis showed that the sensitivity of miR-499 and miR-362 in predicting the prognosis of advanced NSCLC patients was 73.46% and 75.85%，respectively，with specificity of 64.42% and 65.61%，AUC of 0.739 （95%CI：0.662-0.805） and 0.743 （95%CI：0.640-0.793）； the sensitivity，specificity，and AUC of serum miR-499 combined with miR-362 in predicting the prognosis of advanced NSCLC patients were 87.63%，85.34%，and 0.875 （95%CI：0.698-0.897），respectively； the combined prediction of miR-499 and miR-362 for AUC area was higher than the individual prediction （Z=4.83，P=0.013； Z=5.17，P=0.009）. Conclusion Advanced NSCLC patients show significant abnormal serum level of miR-499 and miR-362，and as the severity of the disease progressed，the serum level of miR-499 is downregulated more significantly and miR-362 is upregulated more significantly. The combined detection of miR-499 and miR-362 levels has certain predictive value for the prognosis of advanced NSCLC patients. Figures and Tables | References | Related Articles | Metrics

Risk factors and prediction model construction of pulmonary IFD in patients with NSCLC after radiotherapy Lyu Jun, Xiong Hao, Zheng Yanqiu, Dong Li 2024, 51 (8):  493-497.  doi: 10.3760/cma.j.cn371439-20240422-00082 Abstract ( 34 )   HTML ( 18 )   PDF (936KB) ( 34 )   Save Objective To investigate the risk factors of pulmonary invasive fungal disease （IFD） in patients with primary non-small cell lung cancer （NSCLC） after radiotherapy and to construct predictive model. Methods A total of 298 patients with primary NSCLC who received radiotherapy in the Second People's Hospital of Yibin of Sichuan from January 2020 to January 2024 were retrospectively included as the study objects. The incidence of pulmonary IFD after radiotherapy was analyzed. Univariate and multivariate analyses were performed on the risk factors of pulmonary IFD in patients with primary NSCLC after radiotherapy. A logistic prediction model was constructed according to the results of multivariate analysis，and the predictive efficacy of each index was evaluated by receiver operator characteristic （ROC） curve. Results There were 61 cases with pulmonary IFD after radiotherapy in all 298 patients，with the incidence of 20.47%. And 73 strains fungi were detected，including 57 strains for Candida and 16 strains for Aspergillus. There were statistically significant differences in age （χ2=23.13，P<0.001），whether they had type 2 diabetes （χ2=19.28，P<0.001），whether they underwent invasive procedures （χ2=17.49，P<0.001），and concurrent chemoradiotherapy （χ2=18.48，P<0.001） between IFD patients and non-IFD patients. Multivariate analysis showed that age≥65 years （OR=4.64，95%CI：2.12-10.13，P<0.001），combined type 2 diabetes （OR=5.63，95%CI：2.19-14.48，P<0.001），concurrent chemoradiotherapy （OR=3.73，95%CI：1.74-8.02，P=0.001） and invasive procedures （OR=5.11，95%CI：2.33-11.19，P<0.001） were independent risk factors for pulmonary IFD in patients with primary NSCLC after radiotherapy. Based on the above indexes，the logistic prediction model was constructed as follows：logit（P）=-4.59+1.53×age+1.73×combined type 2 diabetes+1.32×concurrent chemoradiotherapy+ 1.63×acceptance of invasive procedures （R2=0.852）. ROC curve analysis showed that the area under the curve of pulmonary IFD in patients with primary NSCLC who were≥65 years old，combined with type 2 diabetes，receiving invasive procedures，concurrent chemoradiotherapy，and regression model P value were 0.68，0.63，0.68，0.68，0.82，respectively. Conclusion The incidence of pulmonary IFD in patients with primary NSCLC after radiotherapy is independently related to age，type 2 diabetes，invasive procedures and concurrent chemoradiotherapy. The prediction model constructed by using the above four factors has good efficacy in predicting IFD in patients' lungs. Figures and Tables | References | Related Articles | Metrics

Diagnostic value of detection of serum G-17，sB7-H3，and DKK1 for early gastric cancer Liu Wenhui, Yin Ping, Qi Jie 2024, 51 (8):  498-503.  doi: 10.3760/cma.j.cn371439-20240304-00083 Abstract ( 35 )   HTML ( 11 )   PDF (943KB) ( 28 )   Save Objective To explore the diagnostic value of detection of serum gastrin-17 (G-17),soluble B7-H3 (sB7-H3),and Dickkopf-1 (DKK1) in early gastric cancer (EGC). Methods A total of 95 patients with EGC admitted to the Hospital of 81st Group Army of the Chinese People's Liberation Army from April 2021 to April 2023 were selected as the EGC group,95 gastritis patients as the gastritis group,and 95 healthy individuals as the control group. The serum levels of G-17,sB7-H3,and DKK1 were compared among the three groups of subjects,and serum G-17,sB7-H3 and DKK1 levels of patients with different pathological characteristics in EGC group were also compared. Receiver operator characteristic (ROC) curve was applied to analyze the diagnostic value of serum G-17,sB7-H3,and DKK1 levels for EGC. Multivariate logistic regression was applied to analyze the risk factors of EGC. Results The proportions of Helicobacter pylori infection in the control group,gastritis group,and EGC group were 20.00% (19/95),35.79% (34/95),and 61.05% (58/95),respectively,with a statistically significant difference (χ2=34.26,P<0.001). The serum G-17 levels were (6.98±0.55),(8.39±0.95),and (9.46±1.38) pmol/L,respectively,with a statistically significant difference (F=141.82,P<0.001). The levels of sB7-H3 were (18.86±1.64),(20.34±2.16),(22.44±2.62) ng/ml,respectively,with a statistically significant difference (F=64.86,P<0.001). The levels of DKK1 were (12.87±1.96),(14.75±2.09),(6.93±2.24) ng/ml,respectively,with a statistically significant difference (F=88.95,P<0.001). Pairwise comparison showed that the proportion of Helicobacter pylori infection in the control group,gastritis group and EGC group increased in turn,and the levels of serum G-17,sB7-H3 and DKK1 increased in turn (all P<0.05). There were no significant difference in age and gender between EGC patients with different serum G-17,sB7-H3 and DKK1 levels (all P>0.05),and there were statistically significant differences in tumor diameter (χ2=5.74,P=0.017; χ2=4.98,P=0.026; χ2=5.74,P=0.017),tumor invasion (χ2=10.94,P=0.001; χ2=16.16,P<0.001; χ2=21.16,P<0.001),lymph node metastasis (χ2=6.75,P=0.009; χ2=10.68,P=0.001; χ2=4.74,P=0.029) and differentiation type (χ2=7.00,P=0.008; χ2=4.26,P=0.039; χ2=27.18,P<0.001). ROC curve analysis showed that the area under the curve (AUC) of G-17,sB7-H3 and DKK1 in the diagnosis of EGC was 0.825,0.763 and 0.785,respectively. The AUC of the combined detection of the three indicators was 0.933,which was better than that of the three separate tests (Z=3.22, P=0.001; Z=4.94, P<0.001; Z=4.53, P<0.001). Multivariate logistic regression analysis showed that the levels of G-17(OR=3.82,95%CI: 1.73-8.44, P<0.001), sB7-H3(OR=3.96, 95%CI:1.75-8.96, P<0.001), DKK1(OR=3.85, 95%CI:1.77-8.41,P<0.001) were the independent risk factors of EGC. Conclusion Serum G-17,sB7-H3,and DKK1 have certain auxiliary diagnostic value of three indexes for EGC,and the combined detection value is higher. Figures and Tables | References | Related Articles | Metrics

Differential diagnostic value of transvaginal ultrasound elastography combined with serum miR-144-3p，CMTM6 for cervical precancerous lesions and cervical cancer Wang Yan 2024, 51 (8):  504-509.  doi: 10.3760/cma.j.cn371439-20231130-00084 Abstract ( 22 )   HTML ( 12 )   PDF (965KB) ( 23 )   Save Objective To explore the differential diagnostic value of transvaginal ultrasound elastography combined with serum microRNA-144-3p （miR-144-3p） and CKLF-like MARVEL transmembrane domain containing protein 6 （CMTM6） for cervical precancerous lesions and cervical cancer. Methods A total of 110 patients with cervical cancer admitted to Shanxi Women and Children Hospital from September 2021 to September 2023 were collected as cervical cancer group，105 patients with cervical intraepithelial neoplasia （CIN） admitted to our hospital were selected as the CIN group，another 100 healthy individuals who underwent physical examinations in hospital during the same period were regarded as the control group. Color Doppler ultrasound diagnostic instrument was applied to all research objects for transvaginal ultrasound elastography examination，real-time fluorescence quantitative PCR was applied to measure serum miR-144-3p level，enzyme-linked immunosorbent assay was applied to detect serum CMTM6 level，and receiver operator characteristic （ROC） curve was applied to analyze the significance of differential diagnosis of ultrasound elastography score combined with serum miR-144-3p and CMTM6 levels for cervical precancerous lesions and cervical cancer. Results The ultrasound elastography scores of control group，CIN group and cervical cancer group were 1.45±0.22，3.16±0.34 and 3.62±0.41，respectively，with a statistically significant difference （F=1 197.26，P<0.001）. The levels of miR-144-3p were 1.02±0.12，0.72±0.13，0.57±0.12，respectively，with a statistically significant difference （F=357.65，P<0.001）. The CMTM6 levels were （15.89±3.46），（25.82±6.59） and （34.73±8.52） pg/ml，respectively，with a statistically significant difference （F=213.05，P<0.001）. Further pairwise comparison showed that the elastography scores and CMTM6 levels in the control group，CIN group and cervical cancer group were increased successively，while the levels of miR-144-3p were decreased successively （all P<0.05）. The ultrasound elastography scores of CIN Ⅰ grade （n=21），CIN Ⅱ grade （n=44） and CIN Ⅲ grade （n=40） patients were 2.86±0.30，3.16±0.33 and 3.32±0.35，respectively，with a statistically significant difference （F=13.20，P<0.001）. The levels of miR-144-3p were 0.80±0.09，0.73±0.08，0.67±0.07，respectively，with a statistically significant difference （F=19.37，P<0.001）. CMTM6 levels were （20.35±2.58），（25.76±2.71） and （28.76±2.96） pg/ml，respectively，with a statistically significant difference （F=62.84，P<0.001）. Further pairwise comparison showed that with the CIN grade （levels Ⅰ，Ⅱ and Ⅲ） increased，the ultrasound elastography scores and CMTM6 levels of CIN patients increased in turn，while the levels of miR-144-3p decreased in turn （all P<0.05）. The ultrasound elastography scores of International Federation of Gynecology and Obstetrics （FIGO） stage Ⅰ （n=36），Ⅱ （n=42） and Ⅲ-Ⅳ （n=32） patients were 3.39±0.35，3.65±0.38 and 3.84±0.40，respectively，with a statistically significant difference （F=12.31，P<0.001）. The levels of miR-144-3p were 0.64±0.07，0.58±0.06 and 0.48±0.06，respectively，with a statistically significant difference （F=54.65，P<0.001）. CMTM6 levels were （31.58±3.39），（34.62±3.75），（38.42±4.02） pg/ml，respectively，with a statistically significant difference （F=28.69，P<0.001）. Further pairwise comparison showed that with the increase of FIGO stage （stage Ⅰ，stage Ⅱ，stage Ⅲ-Ⅳ） of cervical cancer，the ultrasound elastography scores and CMTM6 levesl of cervical cancer patients increased in turn，and the levels of miR-144-3p decreased in turn （all P<0.05）. ROC curve analysis showed that the area under the curve （AUC） of ultrasound elastography score，miR-144-3p，CMTM6 levels，and the above three combined for differential diagnosis of CIN and cervical cancer was 0.781，0.793，0.818，and 0.930，respectively，the combined differential diagnostic value of the three was better than that of single diagnosis （Z=6.18，P<0.001； Z=4.79，P=0.026； Z=4.49，P=0.031）. Conclusion Compared with CIN group and control group，the transvaginal ultrasound elastography score increases，the serum miR-144-3p level decreases and the CMTM6 level increases in cervical cancer patients. The combination of the three has certain differential diagnostic value for CIN and cervical cancer. Figures and Tables | References | Related Articles | Metrics

Reviews

Research progress of immune checkpoint inhibitor-related multi-organ adverse events Wang Qiushi, Xu Ruitao, Li Song, Chu Jiahui, Liu Lian 2024, 51 (8):  510-514.  doi: 10.3760/cma.j.cn371439-20240515-00085 Abstract ( 45 )   HTML ( 11 )   PDF (760KB) ( 49 )   Save Tumor immune checkpoint inhibitors （ICIs） present a dual nature，offering therapeutic benefits alongside possible toxic side effects. Despite their significant clinical advantages，immune-related adverse events （irAEs） are major concern. In particular，the multi-organ irAEs （MO-irAEs） caused by ICIs present complex clinical manifestations，affecting a high proportion of critically ill patients. There is a lack of clinical awareness and attention towards these adverse events，making management relatively difficult，thus potentially threatening the life of patients. Reasonable application of hormones and immune modulators，along with symptomatic and supportive treatment，as well as careful monitoring and long-term follow-up are crucial measures to control MO-irAEs. Clinical characteristics，peripheral blood indicators，and genetic predisposition can serve as predictive markers for MO-irAEs occurrence and progression to some extent. A comprehensive understanding of clinical features，intervention measures，prognosis，potential molecular mechanisms and predictive factors of MO-irAEs can help to effectively control MO-irAEs，ultimately improving patient outcomes. References | Related Articles | Metrics

Oral microbiota：a biomarker for the diagnosis and prognosis of oral squamous cell carcinoma Meng Kexin, Lu Haijun 2024, 51 (8):  515-519.  doi: 10.3760/cma.j.cn371439-20240304-00086 Abstract ( 24 )   HTML ( 8 )   PDF (715KB) ( 22 )   Save The oral microbiota has been dynamically changing in the process of formation，development and prognosis of oral squamous cell carcinoma （OSCC），and the two promote and complement each other inseparably. Oral microbiota is different in healthy people，patients with precancerous lesions of OSCC，and patients with OSCC，which means it can be used as a biomarker for the diagnosis of precancerous lesions of OSCC or OSCC. In addition，there are differences in the levels of oral microbiota both at baseline and after treatment among different OSCC patients，which can be used as a prognostic biomarker for OSCC. Furthermore，the modulation of oral microbiota can be used as a microbial therapy to improve the prognosis of OSCC patients by being added to the existing standard therapies. References | Related Articles | Metrics

Research progress of the combined application of immune checkpoint inhibitors in the treatment of hepatocellular carcinoma with portal vein tumor thrombus Mo Huimin, Cai Yusen, Zhang Zengrui, Zhu Wentian 2024, 51 (8):  520-525.  doi: 10.3760/cma.j.cn371439-20240328-00087 Abstract ( 27 )   HTML ( 5 )   PDF (738KB) ( 16 )   Save Portal vein tumor thrombus （PVTT） is one of the common complications of hepatocellular carcinoma （HCC） with a high mortality rate. Several studies have shown that active implementation of effective treatment can significantly improve the quality of life and prolong survival of HCC patients with PVTT. In recent years，with the continuous development of molecular biology and molecular immunology，the treatment of advanced liver cancer has shifted from single agent to combination therapy，among which，the combination of immune checkpoint inhibitors and other systemic or local therapies has attracted much attention. This treatment strategy has shown good efficacy in some large-scale clinical trials. With the deepening of relevant research，it is believed that this treatment scheme will bring more hope and opportunities to such patients. References | Related Articles | Metrics

Research progress on the anti-cancer effect of traditional Chinese medicine polyphenols on colorectal cancer Li Zhiwei, Zhai Chunbao 2024, 51 (8):  526-531.  doi: 10.3760/cma.j.cn371439-20240407-00088 Abstract ( 20 )   HTML ( 5 )   PDF (765KB) ( 11 )   Save Colorectal cancer （CRC） is one of the most common digestive system tumors and the second most common tumor in the world in terms of mortality. The current chemotherapeutic drugs applied in clinical treatment seriously affect the survival quality of patients due to adverse reaction and susceptibility to chemoresistance. Therefore，it is necessary to search for novel anti-CRC drugs. As natural compounds，polyphenols components of traditional Chinese medicine can exert anti-CRC properties through various mechanisms，such as promoting apoptosis，inhibiting cell proliferation，and inducing iron death. In addition，it can reverse the resistance of CRC cells to chemotherapeutic drugs. Further exploration of the anti-CRC action mechanism of polyphenols constituents of traditional Chinese medicine may provide a certain reference basis for clinical application. References | Related Articles | Metrics

Research progress of radiomics in cervical cancer Peng Dan, Lyu Lu, Sun Pengfei 2024, 51 (8):  532-537.  doi: 10.3760/cma.j.cn371439-20240304-00089 Abstract ( 30 )   HTML ( 3 )   PDF (734KB) ( 8 )   Save Cervical cancer is the most common malignant tumor of the female reproductive system，early diagnosis and accurate efficacy prediction have important clinical value for the development of treatment plans. Traditional imaging inspection plays an irreplaceable role in the diagnosis and efficacy assessment of cervical cancer，however，it is somewhat subjective，while cervical biopsy is an invasive examination and can only evaluate the pathological histological characteristics of local tumor tissue. Therefore，there is a strong demand to develop a non-invasive，continuously detectable biomarker that can accurately predict tumor characteristics before and during treatment. Radiomics is used to make disease diagnosis，efficacy evaluation and prognosis prediction by means of high-throughput extraction of CT，MRI and PET-CT image data as well as deep excavation of the data information in the images. The aim of this discussion is to explore the latest application and clinical research progress of imaging omics for cervical cancer，which can provide reference for decision-making in the treatment of cervical cancer. References | Related Articles | Metrics