Hai-Dong Zhu

Conventional stents versus stents loaded with 125iodine seeds for the treatment of unresectable oesophageal cancer: a multicentre, randomised phase 3 trial

BACKGROUND The combination of stent insertion and single high-dose brachytherapy is a feasible and safe palliative treatment regimen in patients with unresectable oesophageal cancer. We aimed to further assess the efficacy of this treatment strategy compared to a conventional covered stent in patients with dysphagia caused by unresectable oesophageal cancer. METHODS In this multicentre, single-blind, randomised, phase 3 trial, we enrolled patients with unresectable oesophageal cancer from 16 hospitals in China. We included adult patients (aged ≥ 20 years) with progressive dysphagia, unresectable tumours due to extensive lesions, metastases, or poor medical condition, and with clear consciousness, cooperation, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-3. Eligible patients were randomly assigned (in 1:1 ratio, no stratification) to receive either a stent loaded with (125)iodine radioactive seeds (irradiation group) or a conventional oesophageal stent (control group). The primary endpoint was overall survival. Survival analyses were done in a modified intention-to-treat group. This study is registered with ClinicalTrials.gov, number NCT01054274. FINDINGS Between Nov 1, 2009, and Oct 31, 2012, 160 patients were randomly assigned to receive treatment with either an irradiation stent (n=80) or a conventional stent (n=80). During a median follow-up of 138 days (IQR 72-207), 148 stents (73 in the irradiation group and 75 in the control group) were successfully placed into the diseased oesophagus in 148 participants. Median overall survival was 177 days (95% CI 153-201) in the irradiation group versus 147 days (124-170) in the control group (p=0.0046). Major complications and side-effects of the treatment were severe chest pain (17 [23%] of 73 patients in the irradiation group vs 15 [20%] of 75 patents in the control group), fistula formation (six [8%] vs five [7%]), aspiration pneumonia (11 [15%] vs 14 [19%]), haemorrhage (five [7%] vs five [7%]), and recurrent dysphagia (21 [28%] vs 20 [27%]). INTERPRETATION In patients with unresectable oesophageal cancer, the insertion of an oesophageal stent loaded with (125)iodine seeds prolonged survival when compared with the insertion of a conventional covered self-expandable metallic stent.

A novel biliary stent loaded with 125I seeds in patients with malignant biliary obstruction: Preliminary results versus a conventional biliary stent

BACKGROUND & AIMS Stenting is a palliative therapy method for relieving malignant biliary obstruction. The aim of this study was to evaluate the safety and effectiveness of an irradiation stent compared to a conventional biliary stent in patients with biliary obstruction caused by both primary and metastatic adenocarcinomas. METHODS Participants were randomly assigned to receive treatment with a biliary irradiation stent (irradiation stent group) or a conventional biliary stent (control group). After stent implantation, the outcomes were measured in terms of relief of obstructive jaundice, survival time, complications related to the procedure. A p value of less than 0.05 indicated a significant difference. RESULTS The stents were successfully placed in all the 23 patients. The obstructive jaundice was relieved in all patients except three in the control group. The median and mean overall survivals in the irradiation stent group were higher than those in the control group (7.40 months versus 2.50 months, 8.03 months versus 3.36 months, p=0.006). The patients with stent patent at 3, 6, and 12 months in the irradiation stent group were 11 (91.7%), 7 (58.3%), and 1 (8.3%), respectively. While in the control group, 4 (36.4%), 1 (9.1%), and 0 (0%), respectively. There were no significant differences in the complications related to stent insertion between the two groups. CONCLUSIONS This interim analysis shows that treatment with the biliary intraluminal irradiation stent in patients with biliary obstruction caused by adenocarcinomas appears safe and technically feasible, has benefits in relieving jaundice, and seems to extend survival when compared to a conventional biliary stent.

Early Sorafenib-related Biomarkers for Combination Treatment with Transarterial Chemoembolization and Sorafenib in Patients with Hepatocellular Carcinoma

Purpose To identify early biomarkers for the prediction of the therapeutic response in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) and sorafenib (referred to as TACE plus sorafenib) and establish an effective prognostic nomogram. Materials and Methods The study was approved by the institutional ethics review boards at both participating centers. This retrospective study included all patients with HCC who underwent TACE plus sorafenib therapy between January 2010 and December 2013 at two institutions. On the basis of the overall survival (OS), early biomarkers were identified with univariate and multivariate analyses; then, a prognostic nomogram was established and internally validated by using the concordance c statistic. Results Ninety-seven patients (mean age, 55.0 years; range, 27-89 years) were included. Of these patients, 84 (86.6%) were men. The median OS was 25.7 months. After univariate and multivariate analyses, the onset of sorafenib-induced hypertension and/or dermatologic adverse events (AEs) (grade ≥2) within the first month of sorafenib initiation were demonstrated as independent predictors of OS. The median OS of patients with either of the two independent risk factors was 32.2 months, which was significantly longer than for those patients without (19.8 months; P = .005). Survival analyses showed that the earlier the AEs (sorafenib-related dermatologic AEs or hypertension) occurred, the better the outcome of the combination therapy. A prognostic nomogram was established and showed high accuracy of the nomogram with the c statistic of 0.73. Conclusion The early onset of hypertension and/or sorafenib-related dermatologic AEs are early biomarkers for the clinical prognosis of patients with HCC treated with TACE plus sorafenib.

Irradiation stents vs. conventional metal stents for unresectable malignant biliary obstruction: A multicenter trial

BACKGROUND & AIMS Placement of an irradiation stent has been demonstrated to offer longer patency and survival than an uncovered self-expandable metallic stent (SEMS) in patients with unresectable malignant biliary obstruction (MBO). We aim to further assess the efficacy of an irradiation stent compared to an uncovered SEMS in those patients. METHODS We performed a randomized, open-label trial of participants with unresectable MBO at 20 centers in China. A total of 328 participants were allocated in parallel to the irradiation stent group (ISG) or the uncovered SEMS group (USG). Endpoints included stent patency (primary), technical success, relief of jaundice, overall survival, and complications. RESULTS The first quartile stent patency time (when 25% of the patients experienced stent restenosis) was 212 days for the ISG and 104 days for the USG. Irradiation stents were significantly associated with a decrease in the rate of stent restenosis (9% vs. 15% at 90 days; 16% vs. 27% at 180 days; 21% vs. 33% at 360 days; p = 0.010). Patients in the ISG obtained longer survival time (median 202 days vs. 140 days; p = 0.020). No significant results were observed in technical success rate (93% vs. 95%; p = 0.499), relief of jaundice (85% vs. 80%; p = 0.308), and the incidence of grade 3 and 4 complications (8.5% vs. 7.9%; p = 0.841). CONCLUSIONS Insertion of irradiation stents instead of uncovered SEMS could improve patency and overall survival in patients with unresectable MBO. LAY SUMMARY For patients with unresectable malignant biliary obstruction (MBO), placement of a self-expandable metallic stent (SEMS) is a recommended palliative modality to relieve pruritus, cholangitis, pain, and jaundice. However, restenosis is a main pitfall after stent placement. Data from this first multicenter randomized controlled trial showed that insertion of an irradiation stent provided longer patency and better survival than a conventional metal stent. ClinicalTrials.gov ID: NCT02001779.

A Modified Model for Assessment for Retreatment with Transarterial Chemoembolization in Chinese Hepatocellular Carcinoma Patients

PURPOSE To develop a modified assessment for retreatment with transarterial chemoembolization (mART) score that may be more suitable for Chinese patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS Chinese patients with HCC who were treated with transarterial chemoembolization in four hospitals were included. A univariate analysis and a multivariate forward Cox regression analysis were used to identify significant prognostic factors of overall survival (OS). A point scoring model was subsequently developed from the training cohort, and the validation process was performed in the validation cohort. RESULTS The study included 259 patients (124 patients in the training cohort and 135 patients in the validation cohort). Increase in Child-Pugh scores relative to the baseline (P < .001), Barcelona Clinic Liver Cancer (BCLC) stage B before first transarterial chemoembolization (P = .001), and absence of radiologic tumor response (P < .001) were identified as negative prognostic factors for OS and were used to create the mART scores. BCLC staging was substituted for aspartate aminotransferase increase in the mART scores. The mART scores differentiated two groups with distinct prognosis by a cutoff score of 2.5 points (22.9 mo [95% confidence interval (CI), 17.4-28.4] vs 8.9 mo [95% CI, 7.5-10.3] in median survival; P < .001). In the validation cohort, the C index in assessment for retreatment with transarterial chemoembolization (ART) criteria was 0.64, whereas it was 0.82 in mART criteria. CONCLUSIONS In Chinese patients with HCC, mART score of > 2.5 before second transarterial chemoembolization was associated with poor prognosis. The mART score was probably better validated compared with the ART score.

A Novel Tracheobronchial Stent Loaded with 125 I Seeds in Patients with Malignant Airway Obstruction Compared to a Conventional Stent: A Prospective Randomized Controlled Study

Background To evaluate the safety and efficacy of a novel radioactive bare metal stent (RBMS) compared with a conventional bare metal stent (CBMS) in patients with inoperable malignant airway obstruction. Methods This prospective study was approved by the Institutional Ethics Committee, and informed consent was obtained from each participant. Patients with malignant airway obstruction who had dyspnea were randomly assigned to receive RBMS or CBMS placement. The primary endpoint was stenosis grade, while the secondary endpoints were technical success, overall survival, and complications. A p value of <0·05 was considered statistically significant. Results Between September 2013 and July 2015, 66 patients with inoperable malignant airway obstruction received stent placement fluoroscopically (33 in either group). The median follow-up time was 154 days (range, 15–335 days). The baseline stenosis was immediately relieved in both groups after stent placement, and the stenosis grades in the RBMS group were significantly lower than that in the CBMS group since the second month (p < 0·05). The technical success rates of stent placement were 100% in both groups. The median survival in the RBMS group was significantly longer than that in the CBMS group (170 days vs. 123 days, p < 0·05). There was no significant difference in the incidence of complications between the two groups (p < 0·05). Conclusions The placement of RBMS in patients with inoperable malignant airway obstruction is feasible and safe, and it significantly reduces restenosis and improves overall survival compared with the placement of CBMS.

Palliative treatment with radiation-emitting metallic stents in unresectable Bismuth type III or IV hilar cholangiocarcinoma

Background The emerging data for stenting in combination with brachytherapy in unresectable hilar cholangiocarcinoma are encouraging. The aim of this study was to evaluate the efficacy and safety of radiation-emitting metallic stents (REMS) for unresectable Bismuth type III or IV hilar cholangiocarcinoma. Patients and methods Consecutive patients who underwent percutaneous placement with REMS or uncovered self-expandable metallic stent (SEMS) for unresectable Bismuth type III or IV hilar cholangiocarcinoma between September 2011 and April 2016 were identified into this retrospective study. Data on patient demographics and overall survival, functional success, stent patency and complications were collected at the authors’ hospital. Results A total of 59 patients were included: 33 (55.9%) in the REMS group and 26 (44.1%) in the SEMS group. The median overall survival was 338 days in the REMS group and 141 days in the SEMS group (p<0.001). The median stent patency time was 385 days for REMS and 142 days for SEMS (p<0.001). The functional success rate (87.9% vs 84.6%, p=0.722) and incidence of overall complications (27.3% vs 26.9%, p=0.999) did not differ in the two groups. Conclusions Placement with REMS is safe and effective in palliation for unresectable Bismuth type III or IV hilar cholangiocarcinoma, and seems to prolong survival as well as patency of stent in these patients.