Checkpoint blockade (CPB) therapy can elicit durable clinical responses by reactivating an exhausted immune response. However, response rates remain limited, likely secondary to a lack of a tumor-reactive immune infiltrate. Chimeric antigen receptor (CAR) T cells may provide the necessary tumor-targeting immune infiltrate and a highly specific antitumor immune response. This can be further amplified by the addition of CPB agents, which serve to counteract the immune inhibitory environment undermining optimal CAR T cell efficacy. Herein, we review preclinical and clinical combination therapy with CAR T cells and CPB agents, with a focus on solid tumor malignancies.

Objective Robotic-assisted minimally invasive esophagectomy (RAMIE) is an emerging complex operation with limited reports detailing morbidity, mortality, and requirements for attaining proficiency. Our objective was to develop a standardized RAMIE technique, evaluate procedure safety, and assess outcomes using a dedicated operative team and 2-surgeon approach. Methods We conducted a study of sequential patients undergoing RAMIE from January 25, 2011, to May 5, 2014. Intermedian demographics and perioperative data were compared between sequential halves of the experience using the Wilcoxon rank sum test and the Fischer exact test. Median operative time was tracked over successive 15-patient cohorts. Results One hundred of 313 esophageal resections performed at our institution underwent RAMIE during the study period. A dedicated team including 2 attending surgeons and uniform anesthesia and OR staff was established. There were no significant differences in age, sex, histology, stage, induction therapy, or risk class between the 2 halves of the study. Estimated blood loss, conversions, operative times, and overall complications significantly decreased. The median resected lymph nodes increased but was not statistically significant. Median operative time decreased to approximately 370 minutes between the 30th and the 45th cases. There were no emergent intraoperative complications, and the anastomotic leak rate was 6% (6/100). The 30-day mortality was 0% (0/100), and the 90-day mortality was 1% (1/100). Conclusions Excellent perioperative and short-term patient outcomes with minimal mortality can be achieved using a standardized RAMIE procedure and a dedicated team approach. The structured process described may serve as a model to maximize patients’ safety during development and assessment of complex novel procedures.

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Background Neoadjuvant therapy is typically given to patients with localized disease who have T3-4 esophageal disease by endoscopic ultrasound (EUS). Previously, we noted that patients who present with dysphagia have a higher EUS T stage. We hypothesized that the presence of dysphagia is predictive of EUS T3-4 disease and that staging EUS could be eliminated for esophageal cancer patients with dysphagia. Methods We performed a prospective, intent-to-treat, single-cohort study in which patients with potentially resectable esophageal cancer completed a standardized 4-tier dysphagia score survey. EUS was performed as part of our standard evaluation. To determine whether presence of dysphagia predicted EUS T3-4 disease, the dysphagia score was compared with EUS T stage. Results A total of 114 consecutive patients were enrolled between August 2012 and February 2014: 77% (88/114) received neoadjuvant therapy, 18% (20/114) did not, and 5% (6/114) pursued treatment elsewhere. In total, 70% (80/114) underwent esophagectomy. Fifty-four percent (61/114) had dysphagia; 46% (53/114) did not. Dysphagia scores were as follows: 66% (40/61) grade 1, 25% (15/61) grade 2, and 10% (6/61) grade 3-4. Among patients with dysphagia, 89% (54/61) had T3-4 disease by EUS; among those without dysphagia, only 53% (28/53) had T3-4 disease by EUS (p<0.001). Conclusions The presence of dysphagia in patients with esophageal cancer was highly predictive of T3-4 disease by EUS. On the basis of this finding, approximately 50% of patients currently undergoing staging EUS could potentially forgo EUS before neoadjuvant therapy. In contrast, patients without dysphagia should still undergo EUS.

Objective-Robotic-assisted minimally invasive esophagectomy (RAMIE) is an emerging, complex operation with limited reports detailing morbidity, mortality, and requirements for attaining proficiency. Our objective was to develop a standardized RAMIE technique, evaluate procedure safety, and assess outcomes using a dedicated operative team and two surgeon approach. Methods-We conducted a study of sequential patients undergoing RAMIE from January 25, 2011, May 5, 2014. Intermedian demographics and perioperative data were compared between sequential halves of the experience using Wilcoxon rank sum test and Fischer's exact test. Median operative time was tracked over successive 15-patient cohorts. Results-100 of 313 esophageal resections performed at our institution underwent RAMIE during the study period. A dedicated team including two attending surgeons, and uniform anesthesia and OR staff was established. Patient demographics and outcomes are summarized in Table 1. There were no significant differences in age, gender, histology, stage, induction therapy, or risk class between the two halves of the study. Estimated blood loss, conversions, operative times, and overall complications significantly decreased. The median resected lymph nodes increased, but was not statistically significant. Median operative time decreased to approximately 370 minutes between the 30 th and the 45 th cases (Figure 1). There were no emergent intraoperative complications and the anastomotic leak rate was 6% (6/100). 30-day mortality was 0% (0/100) and 90-day mortality was 1% (1/100). Conclusions-Excellent perioperative and short-term patient outcomes with minimal mortality can be achieved using a standardized RAMIE procedure and dedicated team approach.