Bevacizumab

摘要： Objective: Anti-vascular endothelial growth factor(VEGF) monoclonal antibodies are an effective means of treating non-small cell lung cancer(NSCLC). Here, we aim to update the equivalent efficacy assessment between QL1101 and bevacizumab based on two-year follow-up data.Methods: In total, 535 eligible NSCLC patients were enrolled in this randomized controlled trial. Patients were randomly assigned 1:1 to the QL1101 group and the bevacizumab group. The full end time of this study was defined as 24 months after the last enrolled patient was randomized. The primary endpoint was the objective response rate(ORR);equivalence was confirmed if the two-sided 90% confidence interval(90% CI) of the relative risk was within the range of 0.75-1.33. The secondary endpoints were progression-free survival(PFS) and overall survival(OS).Results: The two-year updated data showed similar ORR(QL1101 vs. bevacizumab: 53.1% vs. 54.3%;relative risk=0.977;90% CI: 0.838-1.144), PFS(235 d vs. 254 d, log-rank P=0.311), and OS(577 d vs. 641 d, log-rank P=0.099) results between the QL1101 group and the bevacizumab group. The mean shrinkage ratio of targeted lesions was also similar between the QL1101 group and the bevacizumab group(22.5% vs. 23.5%). For patients who received QL1101 maintenance therapy, similar results were shown between the QL1101 group(n=157) and the bevacizumab group(n=148)(PFS: 253 d vs. 272 d, log-rank P=0.387;OS: 673 d vs. 790 d, log-rank P=0.101;mean tumor shrinkage rate: 26.6% vs. 27.5%).Conclusions: This study reported that QL1101 had similar efficacy in treating nonsquamous NSCLC in terms of ORR, PFS and OS based on two-year updated data, providing a basis for the clinical application of QL1101.

摘要： BACKGROUND In driver gene-negative non-small cell lung cancer patients who relapse following radical resection,combination chemotherapy using bevacizumab and platinumbased dual drugs is known to increase both progression-free and overall survival.Treatment initially includes bevacizumab,and if patients are able to tolerate it,bevacizumab can continue to be utilized until disease progression.Bevacizumab is a recombinant humanized monoclonal neutralizing antibody that acts against vascular endothelial growth factor(VEGF).Various anti-VEGF monoclonal antibodies,such as bevacizumab,can increase the risk of arterial thromboembolism.Current data indicate that VEGF-targeted treatment does not significantly increase the risk of venous thromboembolism events,except for bevacizumab.CASE SUMMARY A 55-year-old man underwent radical resection for cancer of the right lung.Six months following surgery,multiple metastases were observed in his left lung.Subsequently,six cycles of bevacizumab combined with pemetrexed/carboplatin chemotherapy was given.Efficacy evaluation continued to be partial relief according to RECIST 1.1 standards,and no noticeable adverse reactions were noted.After three cycles of maintenance therapy using a combination of bevacizumab and pemetrexed,the patient developed dizziness and dyspnea.The patient was diagnosed with acute cerebral infarction and pulmonary embolism following head magnetic resonance imaging,computed tomography(CT)angiography,and chest enhanced CT.Although the patient received lowmolecular-weight heparin anticoagulation and other treatment,the patient eventually died of respiratory failure 1 mo later.This case report may offer some insight into fatal arteriovenous embolism,which has not been previously reported.CONCLUSIONBevacizumab combined with chemotherapy may also increase the risk of arteriovenousthromboembolism. Accordingly, patients who receive angiogenesis inhibitor therapy should becarefully selected. Furthermore, close monitoring and timely intervention are necessary in order toreduce the risk of such toxicities.

摘要： BACKGROUND Antiangiogenic agents(AAs)are increasingly used to treat malignant tumors and have been associated with gastrointestinal(GI)bleeding and perforation.Elective surgeries and endoscopy are recommended to be delayed for 31 d until after AAs treatment.Data regarding the safety of endoscopy while on antiangiogenic agents is extremely limited.No guidelines are in place to address the concern about withholding these anti-angiogenic drugs.AIM To evaluate the risks of endoscopy in patients on antiangiogenic agents from 2015 to 2020 at our institution.METHODS This is a single centered retrospective study approved by the institutional review board statement of the institution.Patients that underwent endoscopy within 28 d of antiangiogenic agents’treatment were included in the study.Primary outcome of interest was death,and secondary outcomes included perforation and GI bleeding.Data were analyzed utilizing descriptive statistics.Fifty-nine patients were included in the final analysis and a total of eighty-five procedures were performed that were characterized as low risk and high risk.RESULTS Among the 59 patients a total of 85 endoscopic procedures were performed with 24(28.2%)categorized as high-risk and 61(71.8%)procedures as low-risk.Of the total number of patients,(50%)were on bevacizumab and the rest were on imatinib(11.7%),lenvatinib(6.7%)and,ramucirumab(5%).The average duration between administration of AAs and the performance of endoscopic procedures was 9.9 d.No procedure-related adverse events were noted among our study population.We did observe two deaths with one patient,on lenvatinib for metastatic hepatocellular carcinoma,who had persistent bleeding despite esophageal variceal banding and died 4 d later from hemorrhagic shock.Another patient was diagnosed with acute myeloid leukemia died 24 d after an esophagogastroduodenoscopy with biopsy after transition to comfort care.CONCLUSION As per this single center retrospective study,the rate of endoscopic procedure-related adverse events and death within 28 d of AA administration appears to be low.

摘要： BACKGROUND Colorectal cancer(CRC)is one of the most common and fatal cancers worldwide.Synaptophysin-like 2(SYPL2)is a neuroendocrine-related protein highly expressed in skeletal muscle and the tongue.The involvement of SYPL2 in CRC,including its level of expression and function,has not been evaluated.AIM To evaluate the correlations of SYPL2 expression with lymph node metastasis(LNM)and prognosis in patients with CRC.METHODS The levels of expression of SYPL2 in CRC and normal colorectal tissues were analyzed in multiple public and online databases.The associations between clinical variables and SYPL2 expression were evaluated statistically,and the associations between SYPL2 expression and prognosis in patients with CRC were analyzed using the Kaplan-Meier method and univariate/multivariate Cox regression analyses.SYPL2 expression was assessed in 20 paired CRC tissue and adjacent normal colorectal tissue samples obtained from Fuyang People’s Hospital,and the associations between SYPL2 expression and the clinical characteristics of these patients were investigated.Correlations between the levels of expression of SYPL2 and key targeted genes were determined by Pearson’s correlation analysis.The distribution of immune cells in these samples was calculated using the CIBERSORT algorithm.Gene set enrichment analysis(GSEA)was performed to evaluate the biofunction and pathways of SYPL2 in CRC.RESULTS SYPL2 expression was significantly lower in CRC tissue samples than in normal colorectal tissue samples(P<0.05).High SYPL2 levels in CRC tissues correlated significantly with LNM(P<0.05)and a poorer patient prognosis,including significantly shorter overall survival(OS)[hazard ratio(HR)=1.9,P<0.05]and disease-free survival(HR=1.6,P<0.05).High SYPL2 expression was an independent risk factor for OS in both univariate(HR=2.078,P=0.014)and multivariate(HR=1.754,P=0.018)Cox regression analyses.In addition,SYPL2 expression correlated significantly with the expression of KDR(P<0.0001,r=0.47)and the BRAFV600E mutation(P<0.05).Higher SYPL2 expression was associated with the enrichment of CD8 T-cells and M0 macrophages in the tumor microenvironment.GSEA revealed that SYPL2 was associated with the regulation of epithelial cell migration,vasculature development,pathways in cancer,and several vital tumor-related pathways.CONCLUSION SYPL2 expression was lower in CRC tissue than in normal colorectal tissue.Higher SYPL2 expression in CRC was significantly associated with LNM and poorer survival.

摘要： Objective:To explore the effect of bevacizumab combined with neoadjuvant chemotherapy in advanced ovarian cancer and the occurrence of adverse reactions.Methods:A total of 80 patients with advanced ovarian cancer,treated in Affiliated People''s Hospital of Inner Mongolia Medical University from June 2019 to December 2020,were randomly divided into two groups.In the chemotherapy group,40 patients were treated with neoadjuvant chemotherapy,while in the combined group,another 40 patients were treated with bevacizumab combined with neoadjuvant chemotherapy.The therapeutic effects were compared at the end of the treatment cycle.Results:There was no significant difference in the levels of CA125,CEA,and VEGF between the two groups before treatment.However,after the treatment cycle,the levels of CA125,CEA,and VEGF in the combined group were significantly better than those in the chemotherapy group(P<0.05).At the same time,the incidence of adverse reactions of the chemotherapy group was 67.50%,which was significantly higher than that of the combined group(35.00%;P<0.05).Conclusion:Bevacizumab combined with neoadjuvant chemotherapy for patients with advanced ovarian cancer has significant curative effect.The combined therapy reduces the levels of tumor markers and inflammatory factors,improves patients''quality of life,as well as reduces adverse reactions.It has high clinical promotion value.

摘要： Hepatocellular carcinoma(HCC)is the most common primary liver cancer.For advanced HCC,sorafenib was considered the standard of care for more than ten years.Recently the atezolizumab and bevacizumab combination has become standard of care for these patients without contraindications to either immune checkpoint inhibitors or antiangiogenic therapy.We now review the practical aspects of the atezolizumab and bevacizumab combination,including current evidence,indications,contraindications,management of adverse events,sequencing of this combination,areas of current knowledge gaps and future areas of active clinical research of this combination for busy clinicians in clinical practice.

摘要： BACKGROUND Breast metastases from colorectal cancer(CRC)are very uncommon.There is no unanimous consensus regarding the best treatment for this rare condition,and management is,especially in elderly patients,limited to diagnosis and palliative care.Capecitabine,an oral fluoropyrimidine derivative,might be helpful in controlling the disease and may be a treatment option for patients unable to receive more aggressive chemotherapy.CASE SUMMARY We report a case of synchronous massive breast metastasis from CRC in an 85 year old patient who came to the hospital presenting a huge mass originating from the axillary extension of the right breast.A whole body computed tomography also showed a mass in the right colon.The patient underwent a simple right mastectomy along with right hemicolectomy.The resected breast showed massive metastasis from CRC with intense and homogeneous nuclear CDX2 staining,while the colon specimen revealed poorly differentiated adenocarcinoma stage pT4a pN0 pM1(breast)(Tumor Node Metastasis 2017).Three months later she developed a subcutaneous mass at the site of the previous mastectomy.An ultrasound guided biopsy was carried out again and revealed a metastasis from CRC.The patient then started treatment with capecitabine plus bevacizumab,obtaining stable disease(RECIST criteria)and a clinical benefit after 3 mo of therapy.CONCLUSION In our experience,capecitabine and bevacizumab may be a useful treatment option for breast metastases from primary CRC in elderly patients.

摘要： BACKGROUND Bevacizumab is an antiangiogenic agent,and that synergizes with chemotherapeutic drugs.When used in combination therapies,Bevacizumab is associated with adverse events such as hemorrhage,gastrointestinal perforation,delayed wound healing,and pneumothorax.However,the molecular mechanisms underlying these adverse events are not fully understood.CASE SUMMARY A 45-year-old female with multiple lung metastases that were derived from primary breast cancer,was placed on Bevacizumab+paclitaxel therapy,since this combination has a potent antitumor effect.She reported dyspnea before cycle 3,day 1 and we therefore ran a chest X-ray,which detected a right pneumothorax.The coronal plane computed tomography revealed that one solid mass rapidly necrosed and was replaced by a cavity that passed through the bronchus in the right lower lobe.The cavity eventually ruptured the pleura and made the bronchopleural fistula that led to this pneumothorax.Thoracic cavity drainage using an intercostal catheter was performed.On the 7th day of drainage,the patient was discharged from our hospital on recovery.Recurrence of pneumothorax was not reported,and continuation of chemotherapy was made possible by changing the regimen.CONCLUSION Patients with lung metastases surrounding the bronchi and on the pleura should be monitored for pneumothorax by Bevacizumab-containing chemotherapies.

摘要： Left ventricular assist devices(LVAD)are increasingly become common as life prolonging therapy in patients with advanced heart failure.Current devices are now used as definitive treatment in some patients given the improved durability of continuous flow pumps.Unfortunately,continuous flow LVADs are fraught with complications such as gastrointestinal(GI)bleeding that are primarily attributed to the formation of arteriovenous malformations.With frequent GI bleeding,antiplatelet and anticoagulation therapies are usually discontinued increasing the risk of life-threatening events.Small bowel bleeds account for 15%as the source and patients often undergo multiple endoscopic procedures.Treatment strategies include resuscitative measures and endoscopic therapies.Medical treatment is with octreotide.Novel treatment options include thalidomide,angiotensin converting enzyme inhibitors/angiotensinⅡreceptor blockers,estrogen-based hormonal therapies,doxycycline,desmopressin and bevacizumab.Current research has explored the mechanism of frequent GI bleeds in this population,including destruction of von Willebrand factor,upregulation of tissue factor,vascular endothelial growth factor,tumor necrosis factor-α,tumor growth factor-β,and angiopoetin-2,and downregulation of angiopoetin-1.In addition,healthcare resource utilization is only increasing in this patient population with higher admissions,readmissions,blood product utilization,and endoscopy.While some of the novel endoscopic and medical therapies for LVAD bleeds are still in their development stages,these tools will yet be crucial as the number of LVAD placements will likely only increase in the coming years.

摘要： BACKGROUND Primary tumor location is a prognostic factor for metastatic colorectal cancer(m CRC).Post hoc analyses of m CRC clinical trials,including FIRE-3,CALGB/SWOG 80405,suggest that primary tumor location is also predictive of survival benefit with cetuximab or bevacizumab in combination with 5-fluorouracil-based chemotherapy.AIM Evaluate prognostic/predictive roles of primary tumor location in real-world m CRC patients treated with cetuximab or bevacizumab plus 5-fluorouracil-based chemotherapy.METHODS This retrospective cohort study selected patients with KRAS wild-type m CRC who initiated first-line therapy with cetuximab or bevacizumab in combination with 5-fluorouracil/leucovorin/irinotecan(FOLFIRI)or 5-fluorouracil/leucovorin/oxaliplatin(FOLFOX)between January 2013 and April 2017 from the Flatiron Health electronic health record-derived database of de-identified patientlevel data in the United States.Primary tumor location was abstracted from patients’charts.Left-sided primary tumor location(LPTL)was defined as tumors that originated in the splenic flexure,descending colon,sigmoid colon,or rectum;right-sided primary tumor location(RPTL)was defined as tumors that originated from the appendix,cecum,ascending colon,hepatic flexure,or transverse colon.Propensity score matching was used to balance the baseline demographic and clinical characteristics between patients treated with cetuximab and patientstreated with bevacizumab.Kaplan-Meier and Cox regression methods were used for survival analyses.RESULTS A total of 1312 patients met the selection criteria.Of 248 cetuximab plus FOLFIRI or FOLFOX patients,164 had LPTL and 84 had RPTL;of 1064 bevacizumab plus FOLFIRI or FOLFOX patients,679 had LPTL and 385 had RPTL.Cetuximab LPTL and RPTL patients were more likely to receive FOLFIRI vs bevacizumab patients(LPTL:64.0%vs 24.3%;RPTL:76.2%vs 24.9%,P<0.001).Stage at initial diagnosis was different between cetuximab RPTL vs bevacizumab RPTL patients(P<0.001);cetuximab RPTL patients were more likely to have stage III disease(44.0%vs 22.6%),while bevacizumab RPTL patients were more likely to have stage IV disease(65.7%vs 48.8%).Cetuximab RPTL patients were more likely to have a documented history of adjuvant chemotherapy vs bevacizumab RPTL patients(47.6%vs 22.3%,P<0.001).In the propensity score-matched sample,median overall survival(OS)was 29.7 mo(95%CI:26.9-35.2)for LPTL patients vs 18.3 mo(95%CI:15.8-21.3)for RPTL patients(P<0.001).Median OS was 29.7 mo(95%CI:27.4-NA)for cetuximab LPTL patients vs 29.1 mo(95%CI:26.6-35.6)for bevacizumab LPTL patients(HR=0.87;95%CI:0.63-1.19;P=0.378)and 17.0 mo(95%CI:12.0-32.6)for cetuximab RPTL patients vs 18.8 mo(95%CI:15.8-22.3)for bevacizumab RPTL patients(HR=1.00;95%CI:0.68-1.46;P=0.996).The interaction of treatment and primary tumor location was not significant in the Cox regression.CONCLUSION In this real-world m CRC cohort,the prognostic role of primary tumor location was substantiated,but not the predictive role for treatment with cetuximab vs bevacizumab in combination with 5-fluorouracil-based chemotherapy.

摘要： 目的探讨抑制肝癌淋巴管形成及抑制肿瘤生长的作用. 方法建立LCI-D20高转移潜能肝癌组织原位移植裸鼠模型,给予治疗剂量的Bevacizumab和对照组处理.28d后处死裸鼠,测量肿瘤负荷,免疫组织化学方法检测肿瘤组织微淋巴管密度(Lymphaticmicrovesseldensity,LMVD). 结果Bevacizumab治疗组肿瘤负荷低于对照组,统计学上具有显著性差异(P＜0.001);Bevacizumab治疗组肿瘤内LMVD亦低于对照组,有统计学显著性意义(P＜0.001). 结论Bevacizumab可有效地抑制肝癌淋巴管形成降低肿瘤负荷,为临床治疗肝癌治疗提供新的靶点.

摘要： 目的探讨抑制肝癌淋巴管形成及抑制肿瘤生长的作用. 方法建立LCI-D20高转移潜能肝癌组织原位移植裸鼠模型,给予治疗剂量的Bevacizumab和对照组处理.28d后处死裸鼠,测量肿瘤负荷,免疫组织化学方法检测肿瘤组织微淋巴管密度(Lymphaticmicrovesseldensity,LMVD). 结果Bevacizumab治疗组肿瘤负荷低于对照组,统计学上具有显著性差异(P＜0.001);Bevacizumab治疗组肿瘤内LMVD亦低于对照组,有统计学显著性意义(P＜0.001). 结论Bevacizumab可有效地抑制肝癌淋巴管形成降低肿瘤负荷,为临床治疗肝癌治疗提供新的靶点.

摘要： 目的探讨抑制肝癌淋巴管形成及抑制肿瘤生长的作用. 方法建立LCI-D20高转移潜能肝癌组织原位移植裸鼠模型,给予治疗剂量的Bevacizumab和对照组处理.28d后处死裸鼠,测量肿瘤负荷,免疫组织化学方法检测肿瘤组织微淋巴管密度(Lymphaticmicrovesseldensity,LMVD). 结果Bevacizumab治疗组肿瘤负荷低于对照组,统计学上具有显著性差异(P＜0.001);Bevacizumab治疗组肿瘤内LMVD亦低于对照组,有统计学显著性意义(P＜0.001). 结论Bevacizumab可有效地抑制肝癌淋巴管形成降低肿瘤负荷,为临床治疗肝癌治疗提供新的靶点.

摘要： 目的探讨抑制肝癌淋巴管形成及抑制肿瘤生长的作用. 方法建立LCI-D20高转移潜能肝癌组织原位移植裸鼠模型,给予治疗剂量的Bevacizumab和对照组处理.28d后处死裸鼠,测量肿瘤负荷,免疫组织化学方法检测肿瘤组织微淋巴管密度(Lymphaticmicrovesseldensity,LMVD). 结果Bevacizumab治疗组肿瘤负荷低于对照组,统计学上具有显著性差异(P＜0.001);Bevacizumab治疗组肿瘤内LMVD亦低于对照组,有统计学显著性意义(P＜0.001). 结论Bevacizumab可有效地抑制肝癌淋巴管形成降低肿瘤负荷,为临床治疗肝癌治疗提供新的靶点.

摘要： 目的探讨抑制肝癌淋巴管形成及抑制肿瘤生长的作用. 方法建立LCI-D20高转移潜能肝癌组织原位移植裸鼠模型,给予治疗剂量的Bevacizumab和对照组处理.28d后处死裸鼠,测量肿瘤负荷,免疫组织化学方法检测肿瘤组织微淋巴管密度(Lymphaticmicrovesseldensity,LMVD). 结果Bevacizumab治疗组肿瘤负荷低于对照组,统计学上具有显著性差异(P＜0.001);Bevacizumab治疗组肿瘤内LMVD亦低于对照组,有统计学显著性意义(P＜0.001). 结论Bevacizumab可有效地抑制肝癌淋巴管形成降低肿瘤负荷,为临床治疗肝癌治疗提供新的靶点.

摘要： 目的探讨抑制肝癌淋巴管形成及抑制肿瘤生长的作用. 方法建立LCI-D20高转移潜能肝癌组织原位移植裸鼠模型,给予治疗剂量的Bevacizumab和对照组处理.28d后处死裸鼠,测量肿瘤负荷,免疫组织化学方法检测肿瘤组织微淋巴管密度(Lymphaticmicrovesseldensity,LMVD). 结果Bevacizumab治疗组肿瘤负荷低于对照组,统计学上具有显著性差异(P＜0.001);Bevacizumab治疗组肿瘤内LMVD亦低于对照组,有统计学显著性意义(P＜0.001). 结论Bevacizumab可有效地抑制肝癌淋巴管形成降低肿瘤负荷,为临床治疗肝癌治疗提供新的靶点.