Efficacy and safety of chemotherapy combined with bevacizumab in Chinese patients with metastatic colorectal cancer:A prospective,multicenter,observational,non-interventional phaseⅣtrial

Objective:Bevacizumab has an important and evolving role in improving outcomes in patients with metastatic colorectal cancer(mCRC)worldwide and was approved in China in 2010.However,there are limited real-world data on the efficacy and safety of chemotherapy regimens combined with bevacizumab in Chinese patients with mCRC.This observational,phase IV trial study aimed to obtain more experience on the efficacy and safety of bevacizumab combined with chemotherapy in Chinese mCRC patients.Methods:Between September 2013 and November 2016,patients with histologically confirmed mCRC were enrolled in a prospective,multicenter,observational,non-interventional phase IV trial at 26 centers across China.Eligible patients received different chemotherapeutic regimens combined with bevacizumab.The efficacy and safety data in the intention-to-treat study population were analyzed.Results:A total of 611 patients were included in the efficacy analysis.The median overall survival and median progression-free survival was 18.00 and 10.05 months,respectively.The objective response rate was 21.00%and disease control rate was 89.40%.In subgroup analyses,the survival differences were observed according to metastatic status,duration of treatment and elevation in blood pressure.A total of 613 patients were evaluable for safety assessments.And 569(92.82%)patients reported at least one adverse event(AE),and 151(24.63%)experienced grade 3 or higher AEs.The incidence of bevacizumab-associated AEs of special interest was reported in 31(5.06%)patients with hypertension(n=12),abscesses and fistulae(n=7),bleeding(n=6),proteinuria(n=3),gastrointestinal perforation(n=2)and venous thrombotic events(n=1).Conclusions:This observational phase IV trial broadens our experience and knowledge of bevacizumab in the Chinese population and provides a good indication of its overall efficacy and safety.Bevacizumab in combination with chemotherapy offers clinical benefits to Chinese patients with mCRC and has an acceptable and manageable safety profile.

Residue substitution enhances the immunogenicity of neoepitopes from gastric cancers

Objective:Neoantigens arising from gene mutations in tumors can induce specific immune responses,and neoantigen-based immunotherapies have been tested in clinical trials.Here,we characterized the efficacy of altered neoepitopes in improving immunogenicity against gastric cancer.Methods:Raw data of whole-exome sequencing derived from a patient with gastric cancer were analyzed using bioinformatics methods to identify neoepitopes.Neoepitopes were modified by P1Y(the first amino acid was replaced by tyrosine)and P2L(the second amino acid was replaced by leucine).T2 binding and stability assays were used to detect the affinities between the neoepitopes and the HLA molecules,as well as the stabilities of complexes.Dendritic cells(DCs)presented with neoepitopes stimulated naïve CD8+T cells to induce specific cytotoxic T lymphocytes.ELISA and carboxyfluorescein succinimidyl ester were used to detect IFN-γand TNF-αlevels,and T cell proliferation.Perforin was detected by flow cytometry.The cytotoxicity of T cells was determined using the lactate dehydrogenase assay.Results:Bioinformatics analysis,T2 binding,and stability assays indicated that residue substitution increased the affinity between neoepitopes and HLA molecules,as well as the stabilities of complexes.DCs presented with altered neoepitopes stimulated CD8+T cells to release more IFN-γand had a greater effect on promoting proliferation than wild-type neoepitopes.CD8+T cells stimulated with altered neoepitopes killed more wild-type neoepitope-pulsed T2 cells than those stimulated with wild-type neoepitopes,by secreting more IFN-γ,TNF-α,and perforin.Conclusions:Altered neoepitopes exhibited greater immunogenicity than wild-type neoepitopes.Residue substitution could be used as a new strategy for immunotherapy to target neoantigens.

Ensemble learning system to identify nutritional risk and malnutrition in cancer patients without weight loss information

Dear Editor,Malnutrition is a prevalent disease in oncology practice(Arends et al.,2017).With its cancer-specific prevalence ranging from 21%–72%,malnutrition is responsible for 10%–20% cancer deaths(Yin et al.,2021b).However,malnutrition is often underestimated,misclassified,or left untreated in cancer care(Hébuterne et al.,2014).