Radioembolization With Chemotherapy for Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase III Trial.

PURPOSE: To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM). METHODS: In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and KRAS mutation status. RESULTS: Four hundred twenty-eight patients from 95 centers in North America, Europe, and Asia were randomly assigned to chemotherapy with or without TARE; this represents the intention-to-treat population and included 215 patients in the TARE plus chemotherapy group and 213 patients in the chemotherapy alone group. The hazard ratio (HR) for PFS was 0.69 (95% CI, 0.54 to 0.88; 1-sided P = .0013), with a median PFS of 8.0 (95% CI, 7.2 to 9.2) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. The HR for hPFS was 0.59 (95% CI, 0.46 to 0.77; 1-sided P < .0001), with a median hPFS of 9.1 (95% CI, 7.8 to 9.7) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. Objective response rates were 34.0% (95% CI, 28.0 to 40.5) and 21.1% (95% CI, 16.2 to 27.1; 1-sided P = .0019) for the TARE and chemotherapy groups, respectively. Median overall survival was 14.0 (95% CI, 11.8 to 15.5) and 14.4 months (95% CI, 12.8 to 16.4; 1-sided P = .7229) with a HR of 1.07 (95% CI, 0.86 to 1.32) for TARE and chemotherapy groups, respectively. Grade 3 adverse events were reported more frequently with TARE (68.4% v 49.3%). Both groups received full chemotherapy dose intensity. CONCLUSION: The addition of TARE to systemic therapy for second-line CLM led to longer PFS and hPFS. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.

A longitudinal social network analysis of peer influence, peer selection, and smoking behavior among adolescents in British schools.

OBJECTIVE: Similarity in smoking behavior among adolescent friends could be caused by selection of friends on the basis of behavioral similarity, or by influence processes, where behavior is changed to be similar to that of friends. The main aim of the present study is to disentangle selection and influence processes and study changes over time in these processes using new methods of longitudinal social network analysis. METHODS: The sample consists of 1716 adolescents (mean age at baseline = 12.17 years, SD = .38) in 11 British schools participating in the control group of the ASSIST (A Stop Smoking in School Trial) study. The design was longitudinal with three observations at one-year intervals. At each observation, participants were asked to report on their smoking behavior and friendship networks. An actor-based model of friendship network and smoking behavior coevolution (a statistical model for the simultaneously occurring changes in friendship nominations and smoking) was analyzed, capable of modeling possible changes occurring between observations, allowing alternative influence and selection mechanisms to be investigated, and avoiding the violation of assumptions of statistical independence of observed data. RESULTS: Adolescent's tendency to select friends based on similar smoking behavior was found to be a stronger predictor of smoking behavior than friends' influence. The proportion of smoking behavior similarity explained by smoking-based selection of friends increased over time, whereas the proportion explained by influence of friends decreased. CONCLUSIONS: Smoking prevention should not solely focus on social influence but also consider selection processes and changes in both processes over time during adolescence.