The Sequence of Chemotherapy and Toripalimab Might Influence the Efficacy of Neoadjuvant Chemoimmunotherapy in Locally Advanced Esophageal Squamous Cell Cancer—A Phase II Study

BackgroundThere is no standard neoadjuvant therapy for locally advanced esophageal cancer in China. The role of neoadjuvant chemotherapy plus immunotherapy for locally advanced esophageal cancer is still being explored.MethodsThis open-label, randomized phase II study was conducted at a single center between July 2019 and September 2020; 30 patients with locally advanced esophageal squamous cell carcinoma (ESCC) (T3, T4, or lymph-node positive) were enrolled. Patients were randomized according to the enrollment order at a 1:1 ratio to receive chemotherapy on day 1 and toripalimab on day 3 (experimental group) or chemotherapy and toripalimab on day 1 (control group). The chemotherapeutic regimen was paclitaxel and cisplatin. Surgery was performed 4 to 6 weeks after the second cycle of chemoimmunotherapy. The primary endpoint was pathological complete response (pCR) rate, and the secondary endpoint was safety and disease-free survival.ResultsThirty patients completed at least one cycle of chemoimmunotherapy; 11 in the experimental group and 13 in the control group received surgery. R0 resection was performed in all these 24 patients. Four patients (36%) in the experimental group and one (7%) in the control group achieved pCR. The experimental group showed a statistically non-significant higher pCR rate (p = 0.079). PD-L1 combined positive score (CPS) examination was performed in 14 patients; one in the control group had a PD-L1 CPS of 10, and pCR was achieved; the remaining 13 all had ≤1, and 11 of the 13 patients received surgery in which two (in the experimental group) achieved pCR. Two patients endured ≥grade 3 adverse events, and one suffered from grade 3 immune-related enteritis after one cycle of chemoimmunotherapy and dropped off the study. Another patient died from severe pulmonary infection and troponin elevation after surgery.ConclusionsAlthough the primary endpoint was not met, the initial results of this study showed that delaying toripalimab to day 3 in chemoimmunotherapy might achieve a higher pCR rate than that on the same day, and further large-sample clinical trials are needed to verify this.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT 03985670.

Long-term survival after esophagectomy with distal pancreatectomy for locally advanced esophageal cancer with pancreatic invasion: a case report

Background The treatment for the locally advanced esophageal cancer invading adjacent organs is controversial. We performed a radical surgery for a patient suffering from lower esophageal cancer with pancreatic invasion, and led to long-term survival. Case presentation A 62-year-old man with dysphagia, was endoscopically diagnosed lower esophageal cancer. Abdominal computed tomography shows that the tumor formed a mass with the solitary metastatic abdominal lymph node, which invaded pancreas body and gastric body. He was diagnosed locally advanced esophageal cancer cStage IIIC. As chemoradiotherapy was difficult because of the high risk of gastric mucosal damage, radical esophagectomy with distal pancreatectomy and reconstruction of gastric conduit were performed. The postoperative course was uneventful and the patient was discharged 16 days after operation. At present, 7 years after surgery, he is still alive with disease-free condition. Conclusion Esophagectomy with distal pancreatectomy may be feasible for locally advanced esophageal cancer with pancreatic invasion in terms of curability and long-term survival.

The ideal approach for treatment of cT1N+ and cT2Nany esophageal cancer.: a NCDB analysis

Background Neoadjuvant therapy followed by surgery is recommended for locally advanced esophageal cancer. With the inaccuracies of clinical staging particularly for cT1N+ and cT2Nany tumors, some have proposed consideration of surgery followed by adjuvant treatment. Our objective is to evaluate the efficacy of neoadjuvant therapy vs surgery followed by adjuvant therapy, and to identify the ideal sequence of treatment in patients with cT1N+ and cT2Nany tumors. Methods We performed an analysis utilizing the National Cancer Database (2006-2015) identifying all patients with cT1N+ and cT2Nany esophageal cancer undergoing esophagectomy. The treatment was stratified as: neoadjuvant therapy (NT), adjuvant therapy (AT) and combination therapy of neoadjuvant and adjuvant (CT) groups and outcomes were analyzed. Results We identified 2795 patients with 81.9% (n=2289) receiving NT, 10.2% (n=285) AT, and 7.9% (n=221) CT. There were no significant differences noted in survival among AT, NT, and CT group in cT1N+(P=0.376), cT2N-(P=0.436), cT2N+(P=0.261) esophageal cancer by multivariate analysis using Cox regression model. This relationship held true in both squamous cell carcinoma and adenocarcinoma. Conclusion In clinical T1N+, T2Nany patients, there was no evident superiority of NT over AT. Surgery followed by adjuvant therapy can be considered to be an alternative option in these patients. Further prospective studies are needed to validate these findings.