Discussion
cancers, tumor, GEJ cancers, esophagus or GEJ cancerIn this study, rash, esophagus or GEJ adenocarcinoma, myelosuppression, tumors, gastroesophageal cancerNK
CANCERS, TUMOR, SOLID TUMORS, ADENOCARCINOMAS, CPS, CHRONIC INFLAMMATION, TUMORS, GASTROESOPHAGEAL CANCER
The role of immunotherapy plus cCRT in the perioperative treatment of G/GEJ cancers is unknown. In this study, we evaluated the efficacy and safety of neoadjuvant sintilimab and cCRT followed by gastrectomy and adjuvant sintilimab and chemotherapy in patients with locally advanced G/GEJ cancers. Our results met the pre-specified primary endpoint, with a pCR rate of 38.2%. A total of 79.4% of patients achieved MPR, and all patients received R0 resection. The median DFS and EFS were 17.0 months and 21.1 months, respectively. In addition, biomarker analysis showed that the level of CD56In the neoadjuvant setting, the CROSS trial reported a pCR rate of 23% specifically in patients diagnosed with esophagus or GEJ adenocarcinoma, while the POET trial reported a pCR rate of 15.6% in patients with esophagus or GEJ cancerIn this study, 13 patients had pCR, whose rate was significantly higher than the null hypothesis (38.2% vs. 15.0%, PD-L1 CPS was proven to predict outcomes in metastatic gastroesophageal cancerNK cells play a crucial role in early antitumor immunity by directly killing tumor cellsA TLS is an ectopic lymphoid organ induced by chronic inflammation and tumors, mainly composed of CD20Regarding survival, the 6-month and 1-year OS rates in this study were 100.0% and 92.6%, respectively. One-year OS rates of 79.8% and 75% were reported for patients with GEJ cancers using neoadjuvant cCRT in the CROSS and POET studies, respectivelyThe most common TEAE during the neoadjuvant period in this study was myelosuppression, followed by nausea/vomiting and rash, corroborating previous studiesNab-paclitaxel was selected in the present study for several reasons. First, there is evidence of the efficacy of paclitaxel in gastric cancerIn the present study, radiotherapy was given according to local physicians’ preferences, according to guidelines, experience, and tumor board discussions. Future studies could look into specific radiotherapy regimens for preoperative sintilimab in combination with cCRT. Different doses and fractionation regimens could yield different results and should be explored in the future.This study had some limitations. This was a single-arm trial with a limited sample size, and no control group was included. Although this study showed promising short-term outcomes (e.g., pCR rate) and middle-term outcomes (e.g., DFS and EFS), the long-term efficacy of the combination perioperative therapy was not assessed. A follow-up study is ongoing, and survival data will be reported in the future. This study was a preliminary exploratory phase II trial, and selecting the pCR as the primary endpoint is common in such trials of solid tumors as it provides an answer more rapidly than survivalIn this multicenter, single-arm trial, sintilimab in combination with cCRT demonstrated promising efficacy and a favorable safety profile in the perioperative setting for locally advanced G/GEJ adenocarcinomas. Further large-scale randomized clinical trials are warranted to confirm the survival benefit.