Background: Immunotherapy is effective in treating unresectable esophageal squamous cell carcinoma (ESCC), but little is known about its role in the preoperative setting. The aim of this study was to evaluate the safety, feasibility and efficacy of neoadjuvant treatment with camrelizumab plus chemotherapy in locally advanced ESCC.Methods: Patients diagnosed with locally advanced ESCC were retrospectively included if they had received neoadjuvant camrelizumab plus nab-paclitaxel and S1 capsule followed by radical esophagectomy between November, 2019 and June, 2020 at Sun Yat-sen University Cancer Center. Primary endpoints were safety and feasibility. In addition, pathological response and the relationship between tumor immune microenvironment (TIME)/tumor mutational burden (TMB) and treatment response were also investigated.Results: Twelve patients were included and they all received three courses of preoperative treatment with camrelizumab plus nab-paclitaxel/S1. No grade 3 or higher toxicities occurred. No surgical delay or perioperative death was reported. Nine patients (75%) responded to the treatment, four with a complete pathological response (pCR) and five with a major pathological response (MPR). Neither programmed death-ligand 1 (PD-L1) expression nor TMB was correlated with treatment response. TIME analysis revealed that a higher abundance of CD56dim natural killer cells was associated with better pathological response in the primary tumor, while lower density of M2-tumor-associated macrophages was associated with better pathological response in the lymph nodes (LNs).Conclusions: Neoadjuvant camrelizumab plus nab-paclitaxel and S1 is safe, feasible and effective in locally advanced ESCC and is worth further investigation.
A more common and noninvasive predicting biomarker for programmed cell death 1 (PD-1) antibody remains to be explored. We assessed 46 patients with advanced gastric cancer who received PD-1 antibody immunotherapy and 425-genes next-generation sequencing (NGS) testing. Patients who had a > 25% decline in maximal somatic variant allelic frequency (maxVAF) had a longer progression free survival (PFS) and higher response rate than those who did not (7.3 months vs 3.6 months, p = 0.0011; 53.3% vs 13.3%, p = 0.06). The median PFS of patients with undetectable and detectable post-treatment circulating tumor DNA (ctDNA) was 7.4 months vs. 4.9 months (p = 0.025). Mutation status of TGFBR2, RHOA, and PREX2 in baseline ctDNA influenced the PFS of immunotherapy (p < 0.05). Patients with alterations in CEBPA, FGFR4, MET or KMT2B (p = 0.09) gene had greater likelihood of immune-related adverse events (irAEs). ctDNA can serve as a potential biomarker of the response to immunotherapy in advanced gastric cancers, and its potential role in predicting irAEs worth further exploration.
Oligometastasis is defined as a transitional state between localized and widespread systemic metastatic cancers. In colorectal cancer, the prognostic factors and prognostic value of preoperative serum carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) for patients with colorectal liver oligometastases (CLOM) undergoing hepatic resection have not been well explored. Therefore, the present study included 141 patients with CLOM (≤5 liver metastases) who underwent R0 resection from 2005 to 2012. The association of clinicopathological factors including preoperative CA19-9 and CEA levels with overall survival (OS) was analyzed with univariate and multivariate analyses. Kaplan-Meier analysis showed that patients with high CA19-9 levels tended to have poorer OS than those with low levels (median OS 21.5 vs. 64.0 months, P = 0.002). Preoperative CEA levels were not significantly associated with OS (P > 0.05). Univariate and multivariate analyses demonstrated that larger tumor size of liver metastases (HR 1.911; 95 % CI 1.172-3.114; P = 0.009), bilobar distribution (HR 1.776; 95 % CI 1.097-2.873; P = 0.019), and higher preoperative CA19-9 levels (HR 1.954; 95 % CI 1.177-3.242; P = 0.010) were independent predictors of poor OS for patients with CLOM. Our study identified tumor size, distribution, and preoperative CA19-9 levels as independent prognostic factors for OS of patients with CLOM. In particular, measurement of preoperative CA19-9 levels offers an easy tool that could help identify high-risk patients and aid in improving the management of patients with CLOM.
Background Several programmed cell death ligand 1 (PD‐L1)/programmed cell death protein 1 (PD‐1) antibodies have been approved for cancer treatment worldwide. Their pharmacokinetic and pharmacodynamic characteristics have been reported mainly in western countries, but related data in Chinese patients are limited. This study was conducted to investigate the safety, efficacy, pharmacokinetics, and pharmacodynamics of an anti‐PD‐1 antibody, toripalimab, in Chinese patients. Methods A single‐center phase I study was conducted in Sun Yat‐sen University Cancer Center. Eligible patients were adults with histologically confirmed, treatment‐refractory, advanced, solitary malignant tumors. Toripalimab was intravenously infused every 2 weeks in dose‐escalating cohorts at 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 240 mg. The study followed standard 3 + 3 design. Results Between 15 th March 2016 and 27 th September 2016, 25 patients were enrolled, of whom 3 (12.0%), 7 (28.0%), 6 (24.0%), 6 (24.0%), 3 (12.0%) received 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 240 mg toripalimab, respectively. After a median follow‐up time of 5.0 months (range: 1.5‐19.8 months), we observed that the commonest treatment‐related adverse events (TRAEs) were fatigue (64.0%) and rash (24.0%). No grade 3 or higher TRAEs were observed. No dose‐limiting toxicity, treatment‐related serious adverse events (SAEs), or treatment‐related death occurred. Objective response rate was 12.5%. The half‐life of toripalimab was 150‐222 h after a single dose infusion. Most patients, including those from the 0.3 mg/kg group, maintained complete PD‐1 receptor occupancy (> 80%) on activated T cells since receiving the first dose of toripalimab. Conclusions Toripalimab is a promising anti‐PD‐1 antibody, which was well tolerated and demonstrated anti‐tumor activity in treatment‐refractory advanced solitary malignant tumors. Further exploration in various tumors and combination therapies is warranted.
The objective of this study was to compare the efficacy and tolerability of palonosetron and granisetron in a Chinese population receiving highly emetogenic cisplatin-based chemotherapy or moderately emetogenic chemotherapy. Patients were stratified by chemotherapy with cisplatin (yes/no) and then randomly assigned to receive either palonosetron (0.25 mg i.v.) in the first cycle followed by granisetron (3 mg i.v.) in the second cycle or vice versa. The primary efficacy endpoint was the proportion of patients with complete response 0-24 h post-chemotherapy administration. The proportions of patients with complete response 24-120 and 0-120 h following chemotherapy were also compared. Of the 144 patients randomized, 36 (25%) received 60-80 mg/m(2) cisplatin; 66 of 72 patients in the palonosetron to granisetron group and 56 of 72 patients in the granisetron to palonosetron group completed treatment with both antiemetics. The efficacy and safety analyses included 128 palonosetron treatments and 138 granisetron treatments. Palonosetron consistently produced numerically higher complete response rates than granisetron in the acute phase (0-24 h, 71.09 vs. 65.22%), the delayed phase (24-120 h, 60.16 vs. 55.80%), and overall (0-120 h, 53.13 vs. 50.00%) though the differences were not significant. Both palonosetron and granisetron were well tolerated. Palonosetron was well tolerated and effective in preventing acute and delayed chemotherapy-induced nausea and vomiting in a Chinese population. When used as monotherapy, 0.25-mg palonosetron was not inferior to 3-mg granisetron for preventing vomiting following highly or moderately emetogenic chemotherapy.
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