Additional neoadjuvant immunotherapy does not increase the risk of anastomotic leakage after esophagectomy for esophageal squamous cell carcinoma: a multicenter retrospective cohort study

Abstract

Purpose: Neoadjuvant chemoimmunotherapy (nICT) is a novel and promising therapy model for locally advanced esophageal squamous cell carcinoma.The objective of this study aimed to assessed the impact of additional neoadjuvant immunotherapy on patients’ short-term outcomes, particularly the incidence of anastomotic leakage (AL) and pathological response. Methods: Patients with locally advanced esophageal squamous cell carcinoma who received neoadjuvant chemotherapy (nCT)/ nICT combination with radical esophagectomy were enrolled from three medical centers in China. The authors used propensity score matching (PSM, ration:1:1, caliper=0.01) and inverse probability processing weighting (IPTW) to balance the baseline characteristics and compare the outcomes. Conditional logistic regression and weighted logistic regression analysis were used to further evaluate whether additional neoadjuvant immunotherapy would increase the risk of postoperative AL. Results: A total of 331 patients getting partially advanced ESCC receiving nCT or nICT were enrolled from three medical centers in China. After PSM/IPTW, the baseline characteristics reached an equilibrium between the two groups. After matching, there were no significant difference in the AL incidence between the two groups (P=0.68, after PSM; P=0.97 after IPTW), and the incidence of AL in the two groups was 15.85 versus 18.29%, and 14.79 versus 15.01%, respectively. After PSM/IPTW, both groups were similar in pleural effusion and pneumonia. After IPTW, the nICT group had a higher incidence of bleeding (3.36 vs. 0.30%, P=0.01), chylothorax (5.79 0.30%, P=0.001), and cardiac events (19.53 vs. 9.20%, P=0.04). recurrent laryngeal nerve palsy (7.85 vs. 0.54%, P=0.003). After PSM, both groups were similar in palsy of the recurrent laryngeal nerve (1.22 vs. 3.66%, P=0.31) and cardiac events (19.51 vs. 14.63%, P=0.41). Weighted logistic regression analysis showed that additional neoadjuvant immunotherapy was not responsible for AL (OR=0.56, 95% CI: [0.17, 1.71], after PSM; 0.74, 95% CI: [0.34,1.56], after IPTW). The nICT group had dramatically higher pCR in primary tumor than the nCT group (P=0.003, PSM; P=0.005, IPTW), 9.76 versus 28.05% and 7.72 versus 21.17%, respectively. Conclusions: Additional neoadjuvant immunotherapy could benefit pathological reactions without increasing the risk of AL and pulmonary complications. The authors require further randomized controlled research to validate whether additional neoadjuvant immunotherapy would make a difference in other complications, and determine whether pathologic benefits could translate into prognostic benefits, which would require longer follow-up.

Comparison of efficacy and safety between neoadjuvant chemotherapy and neoadjuvant immune checkpoint inhibitors combined with chemotherapy for locally advanced esophageal squamous cell carcinoma: a systematic review and meta-analysis

“…All of the studies originated in China. Among the included studies, three were dual-arm prospective trials 27 – 29 , while the remaining six were retrospective 30 – 35 . All the studies focused on comparing the efficacy and safety of NICT versus conventional NCT.…”

“…We first conducted a comprehensive meta-analysis to evaluate the pCR , MPR, and R0 resection in all included studies. Eight studies 27 , 28 , 30 – 35 were included in the pCR meta-analysis, revealing a pooled pCR rate of 8.3% for the NCT group and 26.9% for the NICT group ( P <0.00001) (Fig. 3 A).…”

Dapagliflozin in heart failure and type 2 diabetes: Efficacy, cardiac and renal effects, safety

“…This study used the propensity score matching (PSM) method to reduce selection bias due to non-randomized allocation in observational studies[ 16 ]. PSM is a statistical technique that works by estimating the probability that each participant will receive a particular treatment ( i.e.…”