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Supplementary Data from Pembrolizumab in Combination with Neoadjuvant Chemoradiotherapy for Patients with Resectable Adenocarcinoma of the Gastroesophageal Junction

Supplementary Table from Pembrolizumab in Combination with Neoadjuvant Chemoradiotherapy for Patients with Resectable Adenocarcinoma of the Gastroesophageal Junction

Purpose:This phase Ib/2 trial investigated pembrolizumab-containing trimodality therapy in patients with gastroesophageal junction (GEJ) adenocarcinoma.Patients and Methods:Patients with GEJ adenocarcinoma (cT1–3NanyM0) received neoadjuvant pembrolizumab-containing chemoradiation (CROSS regimen) followed by surgical resection and adjuvant pembrolizumab. The primary endpoints were tolerability in the first 16 patients and pathologic complete response [pCR (ypT0N0)]. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). An independent propensity-score-matched cohort (treated with CROSS without immunotherapy) was used for comparison. Exploratory analyses included immune biomarkers in the tumor microenvironment (TME) and plasma.Results:We enrolled 31 eligible patients, of whom 29 received all expected doses of neoadjuvant pembrolizumab and 28 underwent R0 resection. Safety endpoints were met. The primary efficacy endpoint was not met [7/31 (22.6%) achieved pCR]. Patients with high [i.e., combined positive score (CPS) ≥ 10] baseline expression of programmed death (PD)-L1 in the TME had a significantly higher pCR rate than those with low expression [50.0% (4/8) vs. 13.6% (3/22); P = 0.046]. Patients with high PD-L1 expression also experienced longer PFS and OS than propensity-score-matched patients. Among trial patients with PD-L1 CPS < 10, unprespecified analysis explored whether extracellular vesicles (EV) could identify further responders: an elevated plasma level of PD-L1–expressing EVs was significantly associated with higher pCR.Conclusions:Adding pembrolizumab to trimodality therapy showed acceptable tolerability but did not meet the pre-specified pCR endpoint. Exploratory analyses suggested that high PD-L1 expression in the TME and/or on EVs may identify patients most likely to achieve tumor response.

Supplementary Figure from Pembrolizumab in Combination with Neoadjuvant Chemoradiotherapy for Patients with Resectable Adenocarcinoma of the Gastroesophageal Junction

Every effort must be made by the leaders in our field, as well as by every individual cardiothoracic surgeon, to assure equal opportunity for all cardiothoracic surgeons, regardless of race, gender or any other sociodemographic source of bias. Every effort must be made by every surgeon, not just those in particular leadership roles. Opportunities for advancement must be equal in multiple domains, including clinical practice, patient referral, clinical leadership, academic leadership, institutional leadership and leadership in professional medical and surgical societies. Such actions to minimize bias and promote inclusivity will also ensure that cardiothoracic surgical care is provided by a workforce that represents the diversity of patients whom we serve. In the final analysis, it is an absolute fact that gender differences in payments to cardiothoracic surgeons are absolutely unacceptable and cannot be tolerated.

Purpose: This phase Ib/2 trial investigated pembrolizumab-containing trimodality therapy in patients with gastroesophageal junction (GEJ) adenocarcinoma. Patients and Methods: Patients with GEJ adenocarcinoma (cT1–3NanyM0) received neoadjuvant pembrolizumab-containing chemoradiation (CROSS regimen) followed by surgical resection and adjuvant pembrolizumab. The primary endpoints were tolerability in the first 16 patients and pathologic complete response [pCR (ypT0N0)]. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). An independent propensity-score-matched cohort (treated with CROSS without immunotherapy) was used for comparison. Exploratory analyses included immune biomarkers in the tumor microenvironment (TME) and plasma. Results: We enrolled 31 eligible patients, of whom 29 received all expected doses of neoadjuvant pembrolizumab and 28 underwent R0 resection. Safety endpoints were met. The primary efficacy endpoint was not met [7/31 (22.6%) achieved pCR]. Patients with high [i.e., combined positive score (CPS) ≥ 10] baseline expression of programmed death (PD)-L1 in the TME had a significantly higher pCR rate than those with low expression [50.0% (4/8) vs. 13.6% (3/22); P = 0.046]. Patients with high PD-L1 expression also experienced longer PFS and OS than propensity-score-matched patients. Among trial patients with PD-L1 CPS < 10, unprespecified analysis explored whether extracellular vesicles (EV) could identify further responders: an elevated plasma level of PD-L1–expressing EVs was significantly associated with higher pCR. Conclusions: Adding pembrolizumab to trimodality therapy showed acceptable tolerability but did not meet the pre-specified pCR endpoint. Exploratory analyses suggested that high PD-L1 expression in the TME and/or on EVs may identify patients most likely to achieve tumor response.

This study seeks to determine whether a 6-hour abdominal radiograph after oral Gastrografin is a reliable indicator for nonoperative treatment in patients with a clinically equivocal small bowel obstruction. We collected retrospective data from medical records. Patients who received a Gastrografin transit time (GGTT) study between January 1995 and September 1998 were included in the study. Patients who did not appear to be obvious operative candidates, but had signs of intestinal obstruction, underwent a GGTT study. Serial plain abdominal radiographs were taken. If the contrast was in the colon within 6 hours, then the result was negative. A total of 418 GGTT studies were reviewed. Contrast reached the colon within 6 hours in 283 (68%) patients, and 247 (88%) of these patients were managed nonoperatively. The positive predictive value, negative predictive value, sensitivity, and specificity of Gastrografin reaching the colon within 6 hours were 48, 87, 64, and 78, respectively. False negatives included high-grade partial obstructions that ultimately required surgery. Recent operation preceded the GGTT in 128 (31%) cases. Of these 128 patients, only 17 (14%) received an operation. Although the decision to operate or not should never be based on a GGTT study alone, GGTT studies are of significant help in the clinical management of patients suspected to have a small bowel obstruction. GGTT allows for the judicious selection of the appropriate patient for nonoperative management. GGTT studies are cost effective, safe, and clinically useful when attempting to treat patients conservatively.