The Addition of Pembrolizumab to Neoadjuvant Chemoradiotherapy and the Risk of Developing Postoperative Anastomotic Leakage for ESCC: An Analysis from a Prospective Cohort

<h3>Purpose/Objective(s)</h3> Currently, the standardized treatment option for locally advanced esophageal squamous cell cancer (ESCC) is neoadjuvant chemoradiotherapy (NCRT) followed by esophagectomy. Multiple studies have been performed to investigate the efficacy of combination of NCRT with immune checkpoint inhibitors for ESCC patients. However, concerns have raised regarding potentially increased risk of postoperative anastomotic leakage (AL) after NCRT. In the present study, we aim to compared to the difference of postoperative AL rate between NCRT with pembrolizumab and NCRT group, and investigate the risk factors of developing AL for locally advanced ESCC. <h3>Materials/Methods</h3> The gastric fundus (GF) was contoured on the pretreatment planning computed tomography and dosimetric parameters were retrospectively calculated. Univariate and multivariate logistic regression analysis was performed to determine the independent risk predictors for the entire cohort. A nomogram risk prediction model for postoperative AL was established. <h3>Results</h3> A total of 160 ESCC patients were included for analysis. Of them, 112 were treated with NCRT with pembrolizumab and 44 patients with NCRT. Seventeen (10.6%) patients experienced postoperative AL with a rate of 10.7% (12/112) in NCRT with pembrolizumab and 11.4% (5/44) in NCRT group. For the entire cohort, mean, D50, Dmax, V5, V10 and V20 GF dose were statistically higher in those with AL (all p<0.05). Multivariate logistic regression analysis indicated that tumor length (p = 0.012), volume of GF (<i>p</i> = 0.003) and mean dose of GF (<i>p</i> = 0.007) were independently predictors for postoperative AL. Using receiver operating characteristics analysis, the mean dose limit on the GF was defined as 14 Gy. <h3>Conclusion</h3> Based on our prospective database, no significantly difference of developing AL were observed between NCRT with pembrolizumab and NCRT group. We established an individualized nomograms based on mean GF dose combined with clinical indicators to predict AL in the early postoperative period.