Monitoring of sunitinib blood concentration and analysis of its safety and efficacy in Chinese patients with metastatic renal cell carcinoma / 中华泌尿外科杂志

Objective:To investigate the safety and efficacy of individualized sunitinib schedule for patients with metastatic renal cell carcinoma (mRCC) according to the monitoring results of plasma drug concentration.Methods:The clinical data of patients with mRCC who received sunitinib treatment in our center from January 2014 to December 2020 were retrospectively analyzed, including 20 patients who underwent monitoring of plasma drug concentration (monitoring group), and 45 patients, matched by propensity score matching, received sunitinib but did not undergo monitoring of plasma drug concentration during the same period (unmonitored group). In the monitoring group, there were 12 males and 8 females. The mean age was 52.9 years, and ECOG score ≤1 in 16 cases (80%). Three patients were in the IMDC favorable-risk group, 15 patients were in the intermediate-risk group, and 2 patients were in the high-risk group. There were 18 cases of clear cell carcinoma and 2 cases of non-clear cell carcinoma, 5 cases of ISUP grade 1-2 and 11 cases of grade 3-4. In the unmonitored group, there were 31 males and 14 females. The mean age was 57.7 years, and 30 patients had ECOG score ≤1, 15 cases ≥2. There were 10 cases in IMDC favorable-risk group, 23 cases in intermediate-risk group, and 12 cases in high-risk group. Thirty-seven cases were clear cell carcinoma and 8 cases were non-clear cell carcinoma, 8 cases were in ISUP grade 1-2 and 28 cases in grade 3-4. There were no statistically significant differences between the two groups in the above parameters ( P>0.05). The monitoring group used the regimen of taking sunitinib for 4 weeks and stopping for 2 weeks (4/2 week) in the first cycle. The blood concentration of sunitinib was monitored before the first cycle and on days 4, 7, 10, 14, 21 and 28, and personalized medication plan was formulated according to the curve of the blood concentration. The 4/2 week scheme was adopted in the undetected monitoring group.The two groups were compared in the incidence of adverse events (AEs), progression-free survival (PFS), overall survival (OS), tumor treatment response and other clinical outcomes. Results:In the monitoring group, 90% (18/20) of patients receiving sunitinib had a steady-state plasma concentration of more than 150ng/ml, of which 10 patients (50%) had a plasma concentration of 150-200 ng/ml and 8 patients (40%) had a plasma concentration of more than 200 ng/ml. Meanwhile, all patients with plasma concentration higher than 150 ng/ml developed severe AEs (grade 3 and above) after treatment. The other two patients' plasma concentration were 100-150 ng/ml, and did not have severe AEs.All patients in the monitoring group received individualized medication schedule adjustment according to the plasma drug concentration and the occurrence point of severe AEs, ensuring that the peak plasma drug concentration was maintained at about 100-150 ng/ml. Among them, 6 patients were changed to take 2 weeks and stop for 1 week (2/1 week schedule), 4 patients were changed to take 10 days and stop for 5 days (10/5 d schedule), 7 patients were changed to take 7 days and stop for 3 days (7/3 d schedule), and 3 patients were changed to take 5 days and stop for 2 days (5/2 d schedule). The incidence of severe AEs significantly decreased from 90% (18/20) to 35% (7/20), and the difference was statistically significant ( P=0.003), while the incidence of grade 3 and higher AEs was 55.6% (25/45) in the standard group, which was statistically significant compared with the incidence of severe AEs before adjustment in the monitoring group ( P=0.006). Further analysis of the efficacy difference between the two groups showed that the overall objective response rate in the monitoring group (40%, 8/20) was higher than that in the standard group (20%, 9/45), although the difference was not statistically significant ( P=0.09). Median PFS and OS were significantly longer in the monitored group than in the standard group (PFS: 23 vs. 10 months, P=0.002; OS: not reached vs.25 months, P=0.005). Conclusions:The bioavailability of sunitinib is high in mRCC patients, which may lead to higher plasma drug concentration, adjustment of medication regimen based on blood concentration monitoring significantly improved patient safety and clinical outcomes. However, further validation by larger-scale, multi-center and prospective studies is needed.

Classification of COVID-19 by Compressed Chest CT Image through Deep Learning on a Large Patients Cohort.

Corona Virus Disease (COVID-19) has spread globally quickly, and has resulted in a large number of causalities and medical resources insufficiency in many countries. Reverse-transcriptase polymerase chain reaction (RT-PCR) testing is adopted as biopsy tool for confirmation of virus infection. However, its accuracy is as low as 60-70%, which is inefficient to uncover the infected. In comparison, the chest CT has been considered as the prior choice in diagnosis and monitoring progress of COVID-19 infection. Although the COVID-19 diagnostic systems based on artificial intelligence have been developed for assisting doctors in diagnosis, the small sample size and the excessive time consumption limit their applications. To this end, this paper proposed a diagnosis prototype system for COVID-19 infection testing. The proposed deep learning model is trained and is tested on 2267 CT sequences from 1357 patients clinically confirmed with COVID-19 and 1235 CT sequences from non-infected people. The main highlights of the prototype system are: (1) no data augmentation is needed to accurately discriminate the COVID-19 from normal controls with the specificity of 0.92 and sensitivity of 0.93; (2) the raw DICOM image is not necessary in testing. Highly compressed image like Jpeg can be used to allow a quick diagnosis; and (3) it discriminates the virus infection within 6 seconds and thus allows an online test with light cost. We also applied our model on 48 asymptomatic patients diagnosed with COVID-19. We found that: (1) the positive rate of RT-PCR assay is 63.5% (687/1082). (2) 45.8% (22/48) of the RT-PCR assay is negative for asymptomatic patients, yet the accuracy of CT scans is 95.8%. The online detection system is available: http://212.64.70.65/covid .

The impact of different metastatic sites on the prognosis of mRCC patients and its value for modification of International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model / 中华泌尿外科杂志

Objective:To evaluate the impact of metastatic site on the prognosis in patients with metastatic renal cell carcinoma (mRCC), and it′s value for modifying the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria.Methods:The data of 218 patients pathologically diagnosed with mRCC were analyzed retrospectively in West China Hospital from Jan. 2009 to Dec. 2019. Among all patients, 71.6%(156/218) were male, and 89.0% (194/218) underwent nephrectomy. Most of the patients were pathologically diagnosed with renal clear cell carcinoma (176 patients, 80.7%). Lung (137/218, 62.8%) was the most observed metastatic site, following by bone (47/218, 26.1%), lymph node (37/218, 17.0%) and liver (23/218, 10.6%). All patients were classified into favorable (26 patients, 11.9%), intermediate (126 patients, 57.8%) or poor (37 patients, 17.0%) risk group according to IMDC criteria. Endpoints of this study were progression-free survival (PFS), overall survival (OS) and tumor response. The impact of metastatic sites on patients’ prognosis was analyzed, and those that had significant relationship with prognosis were then added into IMDC criteria and a modifying IMDC model was established. Predictive value of this model was further evaluated by calculating concordance index (C-index).Results:In the whole cohort, median PFS and OS were 13.0 and 33.0 months. Survival analysis suggested that patients with bone ( P=0.004), brain ( P=0.042) and liver ( P=0.046) had significantly shorter OS. Thus, patients were divided into two groups: patients with bone/brain/liver metastasis (82 patients, 37.6%) and patients with other metastatic sites (136 patients, 62.4%). Compared with patients with other metastatic sites, those who with bone/brain/liver metastasis had inferior tumor response by TKIs treatment (disease control rate: 51.2% vs. 73.5%, P=0.004). Multivariate analysis suggested that bone/brain/liver metastasis had negative impact on OS (25.0 vs. 47.0 mo, P=0.039). Furthermore, bone/brain/liver metastasis also showed significant relationship with shorter OS in IMDC low (30.0 vs. 62.0 months, P=0.036), intermediate (31.0 vs. 48.0 months, P=0.048) or high (7.0 vs. 18.0 months, P=0.037) risk group, indicating that metastatic site had predictive value for prognosis of mRCC patients. Based on that, bone/brain/liver metastasis were added into the IMDC criteria, and weighting each parameter was weighted according to its coefficient to patients’ OS. Finally, a modified IMDC scoring system were established. C-index of this modified model was 0.669 (0.599 for current IMDC criteria). Conclusions:Bone/brain/liver metastasis in mRCC patients indicated a shorter OS duration. When adding bone/brain/liver metastasis as a predictive parameter for prognosis of mRCC patients into IMDC criteria, the modified IMDC criteria could offer more accurate prediction for patients’ survival.

Efficacy of 125I seed implantation combined with intravenous chemotherapy in treatment of stage Ⅲ b and Ⅳ non-small cell lung cancer / 中国介入影像与治疗学

Objective To investigate the efficacy of implantation of radioactive iodine-125 (125I) seeds combined with chemotherapy in treatment of stage Ⅲb and Ⅳ non-small cell lung cancer (NSCLC).Methods Ninety patients with stage Ⅲb and Ⅳ NSCLC were divided into two groups.The combined group (n=43) received chemotherapy with TP (paclitaxe plus cispla tin) or GP (gemcitabine plus cisplatin) 3 days after 125I particles implantation,and the control group (n=47) only received TP or GP chemotherapy.The effective rate,1-year and 2-year survival rate,the median survival time were compared between the 2 groups.Results The total effective rates of the combined group and the control group of stage Ⅲ b NSCLC were 84.00％ and 48.28％,and the effective rates of stage Ⅵ NSCLC were 72.22％ and 33.33％ (both P＜0.05).The 1-year and 2-year survival rate of the combined group and control group of stage Ⅲb NSCLC were 67.80％,36.00％ and 37.90％,13.83％,respectively (both P＜0.05).The median survival time was 15.7 months and 8.6 months.However,the survival rates of the combined group and the control group of stage Ⅳ NSCLC were 44.44％,16.70％ and 22.22％,11.10％,respectively,while the difference was not statistically significant (P＞0.05).The median survival time was 8.9 and 6.0 months.Conclusion The implantation of radioactive 125I seeds combined with chemotherapy can obtain a significant efficacy in the treatment of stage Ⅲb and stage Ⅳ NSCLC.For patients with stage Ⅲb NSCLC,combined therapy can improve the survival rate.

Efficacy of 125I seed implantation combined with intravenous chemotherapy in treatment of stage Ⅲ b and Ⅳ non-small cell lung cancer / 中国介入影像与治疗学

Objective To investigate the efficacy of implantation of radioactive iodine-125 (125I) seeds combined with chemotherapy in treatment of stage Ⅲb and Ⅳ non-small cell lung cancer (NSCLC).Methods Ninety patients with stage Ⅲb and Ⅳ NSCLC were divided into two groups.The combined group (n=43) received chemotherapy with TP (paclitaxe plus cispla tin) or GP (gemcitabine plus cisplatin) 3 days after 125I particles implantation,and the control group (n=47) only received TP or GP chemotherapy.The effective rate,1-year and 2-year survival rate,the median survival time were compared between the 2 groups.Results The total effective rates of the combined group and the control group of stage Ⅲ b NSCLC were 84.00％ and 48.28％,and the effective rates of stage Ⅵ NSCLC were 72.22％ and 33.33％ (both P＜0.05).The 1-year and 2-year survival rate of the combined group and control group of stage Ⅲb NSCLC were 67.80％,36.00％ and 37.90％,13.83％,respectively (both P＜0.05).The median survival time was 15.7 months and 8.6 months.However,the survival rates of the combined group and the control group of stage Ⅳ NSCLC were 44.44％,16.70％ and 22.22％,11.10％,respectively,while the difference was not statistically significant (P＞0.05).The median survival time was 8.9 and 6.0 months.Conclusion The implantation of radioactive 125I seeds combined with chemotherapy can obtain a significant efficacy in the treatment of stage Ⅲb and stage Ⅳ NSCLC.For patients with stage Ⅲb NSCLC,combined therapy can improve the survival rate.

Interventional chemoembolization for primary hepatocelluar carcinoma complicated by arteriovenous shunting：retrospective analysis of 62 cases / 介入放射学杂志

Objective To retrospectively analyze the effect of interventional embolization for hepatocelluar carcinoma (HCC) associated with arteriovenous shunting (AVS), and to discuss the factors influencing the therapeutic results. Methods The clinical data of 62 cases with HCC associated with AVS , who were treated with interventional chemoembolization , were retrospectively analyzed. Based on the type and extent of AVS identified by angiographic manifestations, appropriate obstruction of the shunt and Lipiodol chemoembolization of HCC were conducted. The curative effect of the shunt embolization was assessed by DSA at one or two months after the treatment. The relevant factors influencing the prognosis of embolization were analyzed by using univariate and multivariate Cox regression analysis methods. Results Of the 62 patients, arterioportal shunting (APS) was detected in 44, hepatic arterio-venous shunting (HAVS) in 11, APS together with HAVS in 4, and hepatic artery-pulmonary artery shunting (HAPAS) in 3. Re-examination with DSA was carried out in 53 patients at 1 - 2 months after the treatment , which showed that the shunting disappeared in 18 cases, obvious reduction of the shunt flow was seen in 19 cases, the lesion remained stable in 9 cases and the disease became worse in 7 cases. Univariate analysis indicated that the kind of embolic material and the presence of tumor thrombus could affect the obstructive result of the shunt , while multivariate Cox regression analysis showed that portal tumoral thrombus was an independent risk factor. The embolization effect of polyvinyl alcohol (PVA) particles and Lipiodol-ethanol mixture, used as the embolic agents, was better than that of gelatin sponge particles. Conclusion To ensure a successful interventional chemoembolization for HCC combined with AVS the procedure should be individualized according to the type and extent of the arteriovenous shunting. The type of embolic materials used for embolization can affect the results to a certain degree.

Establishment of pig avascular necrosis of femoral head model by transcatheter arterial embolization / 中国介入影像与治疗学

ObjectiveTo evaluate the technical feasibility of animal model of avascular necrosis of femoral head (ANFH)with transcatheter arterial embolization (TAE).MethodsTwenty experimental pigs were randomly divided into experimental group and control group (each n= 10).Experimental group:A 5F Cobra catheter was inserted into left femoral artery,and the feeding arteries of femoral head were superselectively inserted.The feeding arteries were embolismed through transcatheter arterial injecting the segments of silk measuring about 500μm.Control group:The arterial embolization was not performed,and the other treatment was identical to experimental group.The articulation of hip in all pigs underwent plain X-ray examination,CT and MR scanning 2 weeks and 4 weeks after treatment,respectively.Histological examination was made in 4 weeks to evaluate volume of bone trabecula (TBV) and percentage of bone lacuna (PBL) at unit area under microscope.The data were compared between the two groups.Results In experimental group,CT and MRI showed swolling in hip soft tissue and high T1 in hip joint cavity,while no obvious abnormalities were found in plain X-ray film 2 weeks after feeding arteries were embolized.Four weeks after feeding arteries embolization,plain X-ray film,CT and MR showed typical necrosis of femoral head in the experimental group,while no obvious abnormalities were found in control group.The histology examination revealed there were obvious karyopyknosis and anachromasis in the bone cells.The quantity of bone cells decreased obviously or disappeared.PBL increased and TBV decreased significantly compared with those of control group (P＜0.05).ConclusionThe animal model of ANFH in pigs can be induced by TAE.It can preferably mimic the pathological situation of ANFH.

The therapeutic effects and experience of tracheal stent implantation in managing severe tracheal stenosis / 介入放射学杂志

Objective To evaluate the therapeutic effects and experience of the tracheal stent implantation for the management of severe tracheal stenosis.Materials Thirteen patients with severe tracheal stenosis of various causes underwent high kilovoltage radiography and computed tomography for evaluating the site,form and extent of the stenosis including 10 at the trachea,1 at the right main bronchus and 2 at left main bronchus.The C2 catheter assisted with ultra-slipping guide wire was inserted into the trachea under fluoroscopy and then a replaced high shoring guide wire was pushed through the stenotic segment and retained the stent. Results All stents were implanted successfully with successful rate 100% together with dyspneic improvements.The mean survival time was 6.2 months for patients with malignant neoplasm.One patient with benign tracheal stenosis has been followed-up for 5 years without restenosis. Conclusions The tracheal stent implantation is an effective means for severe tracheal stenosis.