1.Systemic lupus erythematosus related thrombotic microangiopathy: A retrospective study based on Chinese SLE Treatment and Research Group (CSTAR) registry.
Yupei ZHANG ; Nan JIANG ; Zhen CHEN ; Xinwang DUAN ; Xiaofei SHI ; Hongbin LI ; Zhenyu JIANG ; Yuhua WANG ; Yanhong WANG ; Jiuliang ZHAO ; Qian WANG ; Xinping TIAN ; Mengtao LI ; Xiaofeng ZENG
Chinese Medical Journal 2025;138(5):613-615
2.Effect of triglyceride-glucose index on short-term prognosis of patients with initial acute ischemic stroke
Jingfeng WANG ; Qinrong XU ; Hongxuan FENG ; Ruiyao HU ; Bodun MA ; Xiaotian YU ; Xiaofeng DONG ; Qian GUI ; Guanhui WU ; Hao ZHU
Academic Journal of Naval Medical University 2025;46(9):1121-1126
Objective To investigate the effect of triglyceride-glucose index(TyG)on the short-term prognosis of patients with initial acute ischemic stroke.Methods A total of 391 patients with initial acute ischemic stroke who were hospitalized in Kunshan Second People's Hospital and The Affiliated Suzhou Hospital of Nanjing Medical University from Jun.2020 to Jun.2023 were retrospectively included.According to the modified Rankin scale(mRS)scores at 90 d follow-up,they were assigned to good prognosis group(286 cases)or poor prognosis group(105 cases).Logistic regression and receiver operating characteristic(ROC)curve were used to evaluate the effect of TyG on the short-term prognosis of patients with initial acute ischemic stroke.Results Compared with the good prognosis group,the patients of poor prognosis group had older age,higher proportion of atrial fibrillation,higher levels of homocysteine,triglyceride,total cholesterol,low-density lipoprotein,and TyG,and higher National Institutes of Health stroke scale(NIHSS)score(all P<0.05).Multivariate logistic regression analysis showed that age,homocysteine,TyG and NIHSS score were independent risk factors for poor prognosis in patients with initial acute ischemic stroke(all P<0.05).ROC curve analysis showed that TyG combined with NIHSS score had good predictive value for poor prognosis of patients with initial acute ischemic stroke,and the area under curve value was 0.795.Conclusion The combination of TyG and NIHSS score is an independent influencing factor for poor short-term prognosis in patients with initial acute ischemic stroke.
3.Research progress on genetic factors related to lung function
Panying LI ; Xiaofeng ZHANG ; Jianyun YIN ; Xiaowei REN ; Jing YANG ; Qian NI
Journal of Clinical Medicine in Practice 2025;29(3):133-137,143
Lung function serves as a clinical indicator reflecting respiratory system function,ai-ding in the diagnosis and monitoring of pulmonary diseases.Both genetic and environmental factors ex-ert significant influences on lung function.A comprehensive understanding of the role of genetic factors in lung function is crucial for gaining deeper insights into the regulatory mechanisms of lung function.In recent years,with the application of advanced technologies such as genome-wide association stud-ies,whole-exome sequencing,whole-genome sequencing,and epigenome-wide association studies,numerous genetic loci related to lung function have been identified.This review aimed to summarize the current research progress in genetics related to lung function,providing a reference for subsequent in-depth exploration of the pathological and physiological mechanisms affecting lung function.
4.Design and clinical application of a blue cap anticoagulant blood volume measurement card
Jie ZHU ; Chunxia XIE ; Qian XIN ; Airong NIU ; Xiaofeng MOU ; Lei ZHANG
China Medical Equipment 2024;21(3):170-173
To develop a blue cap anticoagulant tube blood volume measuring card of to solve the problem of insufficient or excessive blood collection in clinical coagulation specimens.The device was composed of a measuring card,a transparent housing with a base and a tube holder.The measuring card was divided into qualified and unqualified areas,the housing was used to insert the card,the tube holder was used to place blood collection tubes.The device was used by clinical nurses to judge the adequacy of blood collection volume in blue cap anticoagulant tube.After the use of the device,the failure rate of clinical blue cap anticoagulation tube specimens submission was reduced from 6.71‰ to 2.73‰,shortened the time limit for specimen submission.At the same time,the device made the rejection judgment of department specimens more standardized and avoided the acceptance of unqualified specimens caused by subjective judgment errors.The device has simple structure,convenient operation and strong practicability,and has promotion value.
5.Application of a self-designed pre-positioned 3D honeycomb guide device in internal fixation with percutaneous cannulated screws for treatment of femoral neck fractures
Feng GAO ; Feng XU ; Zifei YIN ; Pingkang QIAN ; Chen KUANG ; Quan YANG ; Xiaofeng WU
Chinese Journal of Orthopaedic Trauma 2024;26(2):111-117
Objective:To evaluate our self-designed pre-positioned 3D honeycomb guide device in the internal fixation with percutaneous cannulated screws for femoral neck fractures.Methods:A retrospective study was conducted to analyze the data of 60 patients with femoral neck fracture who had been treated with cannulated screw fixation at Department of Orthopaedics, Kunshan Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Traditional Chinese Medicine from June 2019 to June 2022. According to the difference in intraoperative positioning for placement of cannulated screws, the patients were divided into a study group of 30 cases whose placement of cannulated screws was assisted by our self-designed pre-positioned 3D honeycomb guide device, and a control group of 30 cases whose cannulated screws were positioned freehand. In the study group, there were 17 males and 13 females with an age of (44.9±9.2) years, and 2 cases of type Ⅱ, 18 cases of type Ⅲ, and 10 cases of type Ⅳ by the Garden classification. In the control group, there were 11 males and 19 females with an age of (43.5±7.9) years), and 1 case of type Ⅱ, 16 cases of type Ⅲ, and 13 cases of type Ⅳ by the Garden classification. Closed reduction and inverted triangle internal fixation with 3 cannulated screws were conducted for all fractures. The Garden crossline index, operation time, fluoroscopy frequency, needle drillings, fracture healing time, and Harris hip functional score at the last follow-up were compared between the 2 groups. The postoperative imaging indicators in the 2 groups were measured, including screw spacing, distance from screw to neck cortex, screw coverage area, parallel deviation between screws, and deviation from screw to neck axis.Results:There were no statistically significant differences in the baseline characteristics between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (14.4±1.9) months after surgery. In the study group, operation time [(33.1±5.5) min], fluoroscopy frequency [(13.7±2.2) times], needle drillings [(3.7±0.6) times], distance from screw to neck cortex [(12.4±2.8) mm], parallel deviation between screws in the anteroposterior view (2.2°±1.1°), parallel deviation between screws in the lateral view (2.4°±1.0°), deviation from screw to neck axis in the anteroposterior view (4.0°±0.9°) and deviation from screw to neck axis in the lateral view (3.2°±0.8°) were all significantly smaller than those in the control group [(46.5±8.6) min, (23.1±5.2) times, (11.0±2.2) times, (19.0±3.3) mm, 6.5°±2.6°, 7.1°±2.9°, 7.7°±2.6°, and 9.2°±3.1°] (all P<0.05). The screw spacing [(45.7±5.8) mm] and screw coverage area [(74.1±10.9) mm 2] in the study group were both significantly larger than those in the control group [(31.3±7.7) mm and (55.5±9.0) mm 2] ( P<0.05). There was no statistically significant difference between the 2 groups in Garden crossline index, fracture healing time, follow-up time, or Harris hip functional score at the last follow-up ( P>0.05). Follow-ups revealed 1 case of bone non-union in the study group and 2 cases of bone non-union and screw withdrawal in the control group, but no such complications as infection, deep vein thrombosis, screw penetration or rupture, or femoral head necrosis in either group. Conclusion:In the internal fixation with percutaneous cannulated screws for the treatment of femoral neck fractures, our self-designed pre-positioned 3D honeycomb guide device can shorten surgical time, significantly reduce fluoroscopy frequency and needle drillings, and effectively improve accuracy of screw placement.
6.Prognosis and its influencing factors in patients with non-gastric gastrointestinal stromal tumors at low risk of recurrence: a retrospective multicenter study in China
Linxi YANG ; Weili YANG ; Xin WU ; Peng ZHANG ; Bo ZHANG ; Junjun MA ; Xinhua ZHANG ; Haoran QIAN ; Ye ZHOU ; Tao CHEN ; Hao XU ; Guoli GU ; Zhidong GAO ; Gang ZHAI ; Xiaofeng SUN ; Changqing JING ; Haibo QIU ; Xiaodong GAO ; Hui CAO ; Ming WANG
Chinese Journal of Gastrointestinal Surgery 2024;27(11):1123-1132
Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.
7.Relationship between ripretinib concentration and the prognosis of advanced gastrointestinal stromal tumors in China: a multicenter study
Hao XU ; Xiaofeng SUN ; Haoran QIAN ; Ming WANG ; Xin WU ; Ye ZHOU ; Feng WANG ; Luning SUN ; Yongqing WANG ; Fengyuan LI ; Qiang ZHANG ; Zekuan XU
Chinese Journal of Gastrointestinal Surgery 2024;27(11):1133-1140
Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.
8.Surgical treatment and prognosis analysis of hilar cholangiocarcinoma
Xiangcheng LI ; Changxian LI ; Hui ZHANG ; Feng CHENG ; Feng ZHANG ; Liyong PU ; Chuanyong ZHANG ; Ke WANG ; Lianbao KONG ; Xiaofeng QIAN ; Donghua LI ; Wenxiong LU ; Ping WANG ; Aihua YAO ; Jianfeng BAI ; Xiaofeng WU ; Ruixiang CHEN ; Xuehao WANG
Chinese Journal of Surgery 2024;62(4):290-301
Objective:To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma.Methods:This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of ( M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) μmol/L(range: 5.4 to 722.8 μmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 μmol/L to 85.5 μmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results:Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ ( P=0.009), hemi-hepatectomy and extended resection ( P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1: OR=1.43 (0.61-3.35), P=0.413;T3 vs. T1: OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions:Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.
9.Prognosis and its influencing factors in patients with non-gastric gastrointestinal stromal tumors at low risk of recurrence: a retrospective multicenter study in China
Linxi YANG ; Weili YANG ; Xin WU ; Peng ZHANG ; Bo ZHANG ; Junjun MA ; Xinhua ZHANG ; Haoran QIAN ; Ye ZHOU ; Tao CHEN ; Hao XU ; Guoli GU ; Zhidong GAO ; Gang ZHAI ; Xiaofeng SUN ; Changqing JING ; Haibo QIU ; Xiaodong GAO ; Hui CAO ; Ming WANG
Chinese Journal of Gastrointestinal Surgery 2024;27(11):1123-1132
Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.
10.Relationship between ripretinib concentration and the prognosis of advanced gastrointestinal stromal tumors in China: a multicenter study
Hao XU ; Xiaofeng SUN ; Haoran QIAN ; Ming WANG ; Xin WU ; Ye ZHOU ; Feng WANG ; Luning SUN ; Yongqing WANG ; Fengyuan LI ; Qiang ZHANG ; Zekuan XU
Chinese Journal of Gastrointestinal Surgery 2024;27(11):1133-1140
Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

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