Early-stage gastric and gastroesophageal junction cancer: Is there a survival benefit to neoadjuvant therapy?

BACKGROUND: Several randomized controlled trials have evaluated the efficacy of neoadjuvant chemotherapy in the management of resectable gastric cancer. Most patients in these studies had node-positive disease or more advanced T stage. The benefit of neoadjuvant therapy in patients with early-stage gastric cancer remains unclear. METHODS: We queried the National Cancer Data Base to identify patients presenting with clinical stage IB gastric adenocarcinoma between 2006 and 2015. Multivariable logistic regression was used to identify factors associated with receipt of neoadjuvant therapy. Patients undergoing neoadjuvant therapy were 1:1 propensity matched for age, year of diagnosis, Charlson index, insurance, tumor location, tumor grade, surgical approach, lymph nodes examined, and receipt of adjuvant therapy. Log rank testing was used to evaluate differences in overall survival between matched cohorts. RESULTS: A total of 1,258 patients met the inclusion criteria; 402 (32%) received neoadjuvant therapy. On multivariable logistic regression, increasing age (odds ratio 0.52, 95% confidence interval 0.34-0.80) was associated with reduced adjusted odds of undergoing neoadjuvant therapy, whereas proximal tumor location (odds ratio 3.67, 95% confidence interval 2.71-4.99) and poorly differentiated histology (odds ratio 1.78, 95% confidence interval 1.00-3.16) were associated with an increased adjusted odds of undergoing neoadjuvant therapy. A total of 271 patients undergoing neoadjuvant therapy were successfully matched to 271 patients undergoing upfront resection. There was no statistically significant difference in 5-year overall survival (58.8% vs 50.3%, P = .512) between matched cohorts. CONCLUSION: Neoadjuvant therapy does not appear to be associated with an overall survival benefit in patients with stage IB stage gastric cancer.

Systematic improvements in lentiviral transduction of primary human natural killer cells undergoing ex vivo expansion.

Transduction of primary human natural killer (NK) cells with lentiviral vectors has historically been challenging. We sought to evaluate multiple parameters to optimize lentiviral transduction of human peripheral blood NK cells being expanded to large numbers using a good manufacturing practice (GMP)-compliant protocol that utilizes irradiated lymphoblastoid (LCL) feeder cells. Although prestimulation of NK cells with interleukin (IL)-2 for 2 or more days facilitated transduction with vesicular stomatitis virus glycoprotein (VSVG)-pseudotyped lentivirus, there was a subsequent impairment in the capacity of transduced NK cells to proliferate when stimulated with LCL feeder cells. In contrast, incubation of human NK cells with LCL feeder cells plus IL-2 before transduction in the presence of the TBK1 inhibitor BX795 resulted in efficient lentiviral integration (mean of 23% transgene+ NK cells) and successful subsequent proliferation of the transduced cells. Investigation of multiple internal promoter sequences within the same lentiviral vector revealed differences in percentage and level of transgene expression per NK cell. Bicistronic lentiviral vectors encoding both GFP and proteins suitable for the isolation of transduced cells with magnetic beads led to efficient transgene expression in NK cells. The optimized approaches described herein provide a template for protocols that generate large numbers of fully functional and highly purified lentivirus-transduced NK cells for clinical trials.

Comparing Activity Trackers With vs. Without Alarms to Increase Postoperative Ambulation: A Randomized Control Trial.

Early ambulation is a key component to postoperative recovery; however, measuring steps taken is often inconsistent and nonstandardized. This study aimed to determine whether an activity tracker with alarms would increase postoperative ambulation in patients after elective colorectal procedures. Forty-eight patients were randomly assigned to either trackers with 5 daily alarms or activity trackers alone. Over 223 total patient days, the trackers recorded a complete data set for 216 patient days (96.9%). Increasing the postoperative day significantly affected the number of steps taken, while age, sex, Risk Analysis Index score, and approach (laparoscopic versus open) did not show a significant effect. The mean steps per day in the intervention group were 1468 (median 495; interquartile range (IQR) 1345) and in the control group was 1645 (median 1014; IQR 2498). The use of trackers with alarms did not significantly affect the number of daily steps compared to trackers alone (ANOVA, P = .93). Although activity trackers with alarms did not increase postoperative ambulation compared with trackers with no alarms, we demonstrated a strategy to operationalize the use of trackers into postoperative care to provide a quantitative value for ambulation. This enables quantification of a key component in the Enhanced Recovery After Surgery protocol.