Transcatheter arterial chemoembolization combined with PD-1 inhibitors and Lenvatinib for hepatocellular carcinoma with portal vein tumor thrombus

BACKGROUND Hepatocellular carcinoma(HCC)patients complicated with portal vein tumor thrombus(PVTT)exhibit poor prognoses and treatment responses.AIM To investigate efficacies and safety of the combination of PD-1 inhibitor,transcatheter arterial chemoembolization(TACE)and Lenvatinib in HCC subjects comorbid with PVTT.METHODS From January 2019 to December 2020,HCC patients with PVTT types Ⅰ-Ⅳ were retrospectively enrolled at Beijing Ditan Hospital.They were distributed to either the PTL or TACE/Lenvatinib(TL)group.The median progression-free survival(mPFS)was set as the primary endpoint,while parameters like median overall survival,objective response rate,disease control rate(DCR),and toxicity level served as secondary endpoints.RESULTS Forty-one eligible patients were finally recruited for this study and divided into the PTL(n=18)and TL(n=23)groups.For a median follow-up of 21.8 months,the DCRs were 88.9%and 60.9%in the PTL and TL groups(P=0.046),res-pectively.Moreover,mPFS indicated significant improvement(HR=0.25;P<0.001)in PTL-treated patients(5.4 months)compared to TL-treated(2.7 months)patients.There were no treatment-related deaths or differences in adverse events in either group.CONCLUSION A triplet regimen of PTL was safe and well-tolerated as well as exhibited favorable efficacy over the TL regimen for advanced-stage HCC patients with PVTT types Ⅰ-Ⅳ.

Present and prospect of transarterial chemoembolization combined with tyrosine kinase inhibitor and PD-1 inhibitor for unresectable hepatocellular carcinoma

In this editorial,we comment on the article(World J Gastrointest Oncol 2024;16:1236-1247),which is a retrospective study of transarterial chemoembolization(TACE)combined with multi-targeted tyrosine kinase inhibitor(TKI)and programmed cell death protein-1(PD-1)inhibitor for the treatment of unresectable hepatocellular carcinoma(HCC).Herein,we focus specifically on the mechanisms of this triple therapy,administration sequence and selection of each medication,and implications for future clinical trials.Based on the interaction mechanisms between medications,the triple therapy of TACE+TKI+PD-1 is proposed to complement the deficiency of each monotherapy,and achieve synergistic antitumor effects.Although this triple therapy has been evaluated by several retrospective trials,it is still controversial whether the triple therapy achieves better clinical benefits,due to the flawed study design and heterogeneity in medications.In addition,the administration sequence,which may greatly affect the clinical benefit,needs to be fully considered at clinical decision-making for obtaining better prognosis.We hope that this editorial could contribute to the design and optimization of future trials.

PD-1 inhibitor in combination with fruquintinib therapy for initial unresectable colorectal cancer:A case report

BACKGROUND PD-1 inhibitors in combination with fruquintinib have not previously been reported as neoadjuvant therapy for patients with colorectal cancer.In this case report,the combination of a PD-1 inhibitor and fruquintinib demonstrated good efficacy in patients with MSI-H colorectal cancer.CASE SUMMARY The patient was a young man in his 30s who had MSI-H type colon cancer.The patient underwent four cycles of neoadjuvant therapy with a PD-1 inhibitor combined with fruquintinib before surgery,resulting in regression of the mass and a successful surgery.CONCLUSION Some patients with colorectal cancer have the MSI-H type,and the first-line chemotherapy regimen is not effective.However,PD-1 monoclonal antibody immunotherapy has a good therapeutic effect,which can be improved by combination therapy with fruquintinib.We recommend that patients with a history of colon or rectal cancer receive universal MSI testing;then,neoadjuvant therapy should be used.

Successful re-challenge of PD-1 inhibitors in combination with bevacizumab and pemetrexed for multiple primary NSCLC progressing on prior PD-1 inhibitor therapy:one case report

Lung cancer is a malignant tumor with high incidence and mortality rates in China and worldwide.Approximately 10%of these diseases are caused by multiple primary non-small cell lung cancers(NSCLC).Traditional antitumor therapies,such as chemotherapy,radiotherapy,and targeted therapy,have limited efficacy in the treatment of advanced synchronous multiple primary NSCLC.Immunotherapy is considered the standard of care for advanced or recurrent NSCLC,however,approximately 60%of patients develop primary or secondary resistance to treatment.There are no standard recommendations for overcoming immune resistance.We describe a case of simultaneous multiple primary NSCLC in a patient who received programmed death factor-1(PD-1)inhibitor monotherapy and developed brain metastases.After receiving second-line treatment with a combination of another PD-1 inhibitor,pemetrexed,and bevacizumab,the patient achieved complete remission,although they experienced grade 3 immune-related adverse reactions.Immune re-challenge is safe and feasible,and choosing a synergistic combination regimen is one of the options to overcome immune resistance.A larger sample size is needed to confirm the effectiveness and safety of this strategy in patients with NSCLC resistant to prior PD-1 inhibitors.

Tumor Local Microenvironment Is a Key Factor Affecting the Efficacy of PD-1 Inhibitor in Advanced Cervical Cancer: A Case Report and Literature Review

Introduction: Conventional radiotherapy or chemotherapy is ineffective in the treatment of recurrent and metastatic cervical cancer. In recent years, immunotherapy has shown promise in the treatment of various solid tumours, including cervical cancer. The overall response rate of the PD-1/PD-L1 inhibitor in cervical cancer is 14% - 27%, and when combined with radiotherapy or conventional chemotherapy, the overall response rate can be further improved. Case presentation: We report here a case of a 49-year-old female patient presenting with two metastatic lesions of cervical cancer after postoperative radiotherapy, the first was located in the para-aortic region and the second in the presacral region. The enlarged para-aortic lymph nodes had not previously received radiotherapy, while the enlarged presacral lymph nodes had previously received postoperative radiotherapy. Treatment results showed that the recurrent presacral mass did not respond to the PD-1 inhibitor (camrelizumab) alone, whereas the metastatic para-aortic lymph nodes responded favourably to camrelizumab combined with low-intensity radiotherapy. Conclusion: PD1/PD-L1 inhibitors combined with radiotherapy should make it possible to overcome the bottleneck of conventional radiotherapy, improve patient prognosis or achieve better local control rates with lower radiotherapy doses.

共抑制分子TIGIT/CD155和PD-1在慢性淋巴细胞白血病中的表达及临床意义

目的:探讨共抑制分子TIGIT/CD155和PD-1在慢性淋巴细胞白血病(CLL)患者外周血CD4^(+)T细胞和Treg细胞上的表达,并分析其临床意义。方法:选取40例CLL患者和20例健康人员,采用流式细胞术检测CD4^(+)T细胞和Treg细胞表面抑制性分子PD-1、TIGIT的表达水平,并检测受试者外周血B细胞和DC细胞上CD155的表达水平。结果:CLL患者组外周血PD-1^(+)TIGIT^(+)CD4^(+)T细胞、PD-1^(+)TIGIT^(+)Treg细胞、CD155^(+)DC细胞比例均明显高于健康对照组(P<0.05)。CLL患者的PD-1^(+)TIGIT^(+)CD4^(+)T细胞和PD-1^(+)TIGIT^(+)Treg细胞比例均明显高于PD-1^(+)TIGIT-CD4^(+)T细胞和PD-1^(+)TIGIT-Treg细胞(P<0.05)。PD-1^(+)TIGIT^(+)CD4^(+)T细胞和PD-1^(+)TIGIT^(+)Treg细胞均与CD155^(+)DC细胞水平呈正相关(r=0.742,r=0.766)。随着Binet分期进展,PD-1^(+)TIGIT^(+)CD4^(+)T细胞、PD-1^(+)TIGIT^(+)Treg细胞、CD155^(+)DC细胞比例逐渐增加(P<0.05),CD38≥30%、IGVH未突变、染色体异常的预后不良组患者的上述三种细胞比例均增高(P<0.05)。结论:PD-1和TIGIT共抑制分子可能参与了CLL晚期患者的免疫耗竭,具有临床预后参考价值。双抑制分子靶向治疗为CLL个体化治疗提供了新的方向。

Analysis of efficacy and safety for the combination of regorafenib and PD-1 inhibitor in advanced hepatocellular carcinoma:A real-world clinical study

Background and aims:Hepatocellular carcinoma(HCC)is a prevalent and deadly disease with limited treatment options.Regorafenib,a tyrosine kinase inhibitor,has shown promise in HCC treatment but faces limitations as a monotherapy.Combining regorafenib with PD-1 inhibitor may improve efficacy and survival outcomes for patients.This retrospective analysis was conducted to explore its efficacy and safety,providing reference experience for better application of this combination therapy.Methods:This retrospective single-center study evaluated the efficacy and safety of combining regorafenib with PD-1 blockade for patients with HCC.Efficacy was evaluated according to the RECIST 1.1 evaluation criteria.Safety was assessed using CTCAE 4.0.Data was analyzed to compare survival status in different subgroups.Results:Generally,there were 76 patients with HCC elected to receive the regorafenib plus PD-1 blockade treatment during the study period.The objective response rate was 21.1%(n?16),and the disease control rate was 56.6%(n?43).Median progression-free survival(PFS)was 6.8 months,and median overall survival had not yet been reached.All patients suffered of at least 1 adverse event.Grade3 adverse events occurred in 31.6%of patients(n?24),with the most common being hand-foot syndrome,decreased appetite,and abdominal distension.Subgroup analyses showed no significant differences in PFS based on cirrhosis status or previous treatment lines.Conclusion:With manageable safety,regorafenib combined PD-1 inhibitor could bring survival benefits for advanced HCC who have received systemic treatment.Further,the Cox analysis showed that HBV infection,metastasis,etc.did not have significant effects on the survival benefits.

多激酶抑制剂联合PD-1抑制剂在肝胆管结石合并胆管癌患者中的疗效与安全性研究

目的探讨酪氨酸激酶抑制剂(TKI)联合程序性死亡蛋白-1(PD-1)抑制剂在肝胆管结石合并胆管癌患者中的疗效与安全性。方法研究选取了2021年2月至2024年2月期间在南阳市中心医院接受治疗的81例肝胆管结石合并胆管癌患者,根据治疗方式分为观察组(TKI联合PD-1抑制剂治疗)39例和对照组(TKI单独治疗)42例。比较两组患者的一般资料(性别、年龄、病程、主要症状、肝功能分级、肿瘤分期及TKI使用情况)、疗效评估,以及不良反应发生情况,结果两组患者一般资料(性别比例、年龄、病程、主要症状、肝功能分级、肿瘤分期及TKI使用情况)比较,差异无统计学意义(P>0.05)。观察组患者的疾病控制率明显高于对照组,差异具有统计学意义(P<0.05),但两组客观缓解率比较,差异无统计学意义(P>0.05)。两组患者的不良反应(肝功能异常、皮疹、血小板减少、恶心呕吐、免疫性肝损伤、中性粒细胞减少、白细胞减少)发生情况比较,差异无统计学意义(P>0.05)。结论TKI联合PD-1抑制剂在治疗肝胆管结石合并胆管癌患者中具有一定疗效,疾病控制率较优,且安全性较好,不会额外增加不良反应。

PD-1抑制剂治疗对宫颈恶性肿瘤患者血液细胞免疫因子影响的分析

目的:探讨PD-1抑制剂治疗宫颈恶性肿瘤效果与血液细胞免疫因子变化的关系。方法:经广西医科大学附属肿瘤医院伦理委员会批准(审查编号:LW2024142),回顾性分析2020年01月至2022年09月在该院确诊并接受PD-1抑制剂治疗的35例远处转移的晚期子宫颈癌及41例复发性子宫颈癌(recurrent cervical cancer,RCC)患者临床病历资料。根据实体瘤治疗疗效评价标准,将患者分为完全缓解组、部分缓解组、疾病稳定组、疾病进展组。比较不同治疗效果患者治疗前后血液系统细胞免疫因子的变化及其相关性。结果:部分缓解组患者在治疗后血CD3^(+)T细胞比例明显下降,差异有统计学意义(t=2.554,P<0.05)。疾病稳定组患者在治疗后血CD3+T细胞比例明显下降(t=2.814,P<0.05)、CD3-CD56^(+)CD16+T细胞比例升高明显(t=-2.427,P<0.05),差异有统计学意义;疾病进展组患者在治疗后血液系统CD3^(+)CD4^(+)T细胞比例明显下降,差异有统计学意义(t=6.247,P<0.05),其余T细胞比例变化无统计学意义。结论:复发或远处转移的晚期宫颈恶性肿瘤患者在PD-1抑制剂治疗后,血液CD3^(+)T细胞比例下降、CD3-CD56^(+)CD16^(+)T细胞比例升高是预后保护性因素,CD3^(+)CD4^(+)T细胞比例下降是预后不良因素。

SII、CRP/Alb及D-二聚体对PD-1抑制剂联合化疗的晚期非小细胞肺癌患者预后的评估价值

目的探究外周血免疫炎症指数(systemic immune inflammation index,SII)、CRP/Alb及D二聚体(D-Dimer)对接受PD-1抑制剂(PD-1 inhibitors)联合化疗治疗的Ⅲ期~Ⅳ期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的预后评估价值。方法收集安徽医科大学附属安庆第一人民医院呼吸与危重症医学科2021年1月1日至2023年10月20日接受两个及以上周期PD-1抑制剂联合化疗Ⅲ期~Ⅳ期的88例NSCLC患者,对其临床资料进行回顾性分析,使用ROC曲线确定SII、CRP/Alb及D-二聚体的最佳截断值,Kaplan-Meier法绘制生存曲线,比较不同SII、CRP/Alb及D-二聚体水平对客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)及中位无进展生存期(median progression-free survival,mPFS)的影响,并分析mPFS的影响因素。结果入组的Ⅲ期~Ⅳ期NSCLC患者,SII最佳截断值为484.78,高、低SII组患者的肿瘤分期、ECOG-PS评分比较,差异有统计学意义(P均<0.05);CRP/Alb最佳截断值为0.08,高、低CRP/Alb组患者的ECOG-PS评分、疗效比较,差异有统计学意义(P均<0.05);D-二聚体最佳截断值为1.71mg/L,高、低D-二聚体组患者的ECOG-PS评分比较,差异有统计学意义(P均<0.05)。高CRP/Alb组患者的ORR和DCR均低于低CRP/Alb组患者,差异有统计学意义(P均<0.05),高SII组、高CRP/Alb组和高D-二聚体组患者的mPFS均低于低SII组、低CRP/Alb组和低D-二聚体组患者,差异有统计学意义(P均<0.05)。多因素Cox回归分析结果显示,高SII、高CRP/Alb和高D-二聚体是接受PD-1抑制剂联合化疗的Ⅲ期~Ⅳ期NSCLC患者预后不良的预测因素。结论高SII、高CRP/Alb和高D-二聚体与晚期NSCLC患者缩短的mPFS相关,其可能是晚期NSCLC患者接受PD-1抑制剂联合化疗潜在有价值的预后危险因素;而高CRP/Alb与近期疗效较差独立相关,可作为判断晚期NSCLC患者接受PD-1抑制剂联合化疗治疗近期疗效的炎性指标。

胃癌患者术前血清GINS4、PD-1水平与临床病理特征及预后的相关性

目的 探讨胃癌患者术前血清GINS复合物4 (GINS4)、PD-1水平与临床病理特征及预后的关系。方法 选取我院2016年8月至2018年8月治疗的95例胃癌患者,并根据患者生存情况分为生存组和死亡组;选取同期95例健康体检者作为对照组。采用酶联免疫吸附试验(ELISA)检测术前血清PD-1水平。采用实时定量PCR检测术前血清GINS4 m RNA水平;采用Kaplan-Meier法分析胃癌患者术前血清GINS4 mRNA、PD-1水平与5年生存率的关系;采用Cox回归分析胃癌预后的影响因素。结果 胃癌组血清GINS4 mRNA、PD-1水平显著高于对照组(P <0.05)。组织低分化、TNM分期Ⅲ~Ⅳ期、有淋巴结转移胃癌患者血清GINS4mRNA、PD-1水平显著高于组织中/高分化、TNM分期Ⅰ~Ⅱ期和无淋巴结转移患者(P <0.05)。死亡组血清GINS4 mRNA、PD-1水平及TNM分期Ⅲ~Ⅳ期、有淋巴结转移患者比例显著高于生存组(P <0.05)。Kaplan-Meier法分析结果显示,胃癌患者血清中GINS4 mRNA高表达、PD-1高表达患者5年生存率低于GINS4 mRNA低表达、PD-1低表达患者(P <0.05)。GINS4 mRNA、PD-1水平是胃癌患者死亡的独立危险因素(P <0.05)。结论 胃癌患者血清GINS4 m RNA、PD-1水平升高,二者与组织分化程度、TNM分期、淋巴结转移及预后密切相关。

GS方案联合PD-1+益生菌治疗胰腺癌根治术后患者的效果观察

目的 探讨GS方案联合PD-1+益生菌治疗胰腺癌根治术后患者的治疗效果。方法 将80例行胰腺癌根治术的患者随机分为对照组(GS方案联合PD-1)和观察组(GS方案联合PD-1+益生菌)各40例。比较两组炎症指标(血清NLR)、NK细胞和T细胞亚群(NK细胞、CD3^(+)、CD4^(+)、CD8^(+))、肿瘤标记物(CA199、CEA、CA125)、不良反应及复发率。结果 治疗后,观察组血清NLR、CD8^(+)及CA199、CEA、CA125均低于对照组,而NK细胞、CD3^(+)、CD4^(+)水平均高于对照组(P<0.05);观察组不良反应发生率及复发率均低于对照组(P<0.05)。结论 GS方案联合PD-1+益生菌治疗胰腺癌根治术后患者的效果较好,可降低不良反应发生率及复发率,调节炎症水平和肿瘤标记物水平,改善免疫功能。

榄香烯口服乳联合PD-1抑制剂治疗晚期食管鳞状细胞癌的临床效果

目的:探讨榄香烯口服乳联合程序性死亡受体1(PD-1)抑制剂治疗晚期食管癌患者的临床效果及安全性。方法:选取2020年6月—2022年5月于海安市中医院肿瘤科就诊的60例晚期食管癌患者,随机分为观察组、对照组,各30例。对照组采用PD-1抑制剂治疗,观察组在对照组基础上加用榄香烯口服乳治疗。比较两组的治疗效果、生活质量、不良反应及外周血CD4~+CD25~+Treg水平。结果:观察组疾病控制率(DCR)高于对照组,但两组间比较,差异无统计学意义(P>0.05);观察组客观缓解率(ORR)高于对照组(P<0.05)。治疗前,两组Karnofsky功能状态(KPS)评分、CD4~+CD25~+Treg细胞水平比较,差异均无统计学意义(P>0.05);治疗后,两组KPS评分均高于治疗前,CD4~+CD25~+Treg细胞水平均低于治疗前,且观察组KPS评分高于对照组,CD4~+CD25~+Treg细胞水平低于对照组(P<0.05)。观察组G1、G2级肺炎和肠炎发生率均低于对照组(P<0.05),两组其余不良反应发生率比较,差异均无统计学意义(P>0.05)。结论:榄香烯口服乳联合PD-1抑制剂治疗晚期食管癌的效果较好,可改善患者生活质量,且安全性高。

Programmed cell death 1 inhibitor sintilimab plus S-1 and gemcitabine for liver metastatic pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.

Programmed cell death receptor 1 inhibitor Pembrolizumab in the treatment of advanced gastric cancer

This editorial discusses Christodoulidis et al's article,which appeared in the most recent edition.The clinical trials have demonstrated the programmed cell death receptor 1(PD-1)inhibitor Pembrolizumab involved combination therapy can improve the efficacy of advanced gastric cancer(AGC).Pembrolizumab combined with chemotherapy can enhance its sensitivity,and further eliminate tumor cells that develop resistance to chemotherapy.The combination of Pembrolizumab and Trastuzumab targeting human epidermal growth factor receptor 2 showed improved prognosis.The overall toxic effects of Pembrolizumab are significantly lower than traditional chemotherapy,and the safety is controllable.PD-1 inhibitor Pembrolizumab sheds a light on the treatment of AGC and brings new hope to the clinical practice.

Granulomatosis with polyangiitis induced by the anti-programmed cell death-1 inhibitor tislelizumab:A case report

BACKGROUND Immune checkpoint inhibitors(ICIs)are a new class of antitumor agents.They enhance antitumor effects by blocking inhibitory receptors and related ligands expressed on T cells.ICIs also modulate regular immune cell activity,affecting the immune system and causing immune-related adverse events.The renal system is sometimes affected by these adverse events.Currently,the literature on ICIs-related glomerular injuries is scarce.CASE SUMMARY We present a patient who developed granulomatosis with polyangiitis(GPA)3 weeks after treatment with the anti-programmed cell death-1 inhibitor,tislel-izumab.The patient experienced proteinuria,hematuria,and acute kidney injury without pulmonary hemorrhage and tested positive for anti-neutrophil cyto-plasmic antibody(ANCA)-cytoplasmic type.Renal biopsy confirmed ANCA-associated vasculitis,and GPA was finally diagnosed.The patient received pulse treatment with glucocorticoids and cyclophosphamide,and renal function improved.After self-discontinuation of the drug,the disease recurred,and the original treatment regimen was continued.However,the patient’s renal function continued to deteriorate.CONCLUSION Glucocorticoids plus cyclophosphamide are effective for treating GPA induced by tislelizumab.However,follow-up and patient education are needed.

PD-1靶向纳米投递系统对胃癌细胞活性及T细胞免疫应答因子的影响

目的探讨PD-1靶向纳米投递系统对胃癌细胞活性及T细胞免疫应答因子的影响。方法取胃癌细胞,将其分为空白对照组、程序性细胞死亡蛋白-1(Programmed Cell Death-1,PD-1)抑制剂组和PD-1靶向组3组。用乳化溶剂挥发法制备PD-1靶向纳米投递系统,荧光倒置显微镜下观察转染情况,MTT法检测细胞增殖,流式细胞仪检测细胞凋亡,实时PCR法及免疫印迹法检测T细胞免疫应答因子表达。结果与空白对照组相比,PD-1抑制剂组、PD-1靶向组的转染率和凋亡率依次升高,且差异均有统计学意义(P<0.05)。与空白对照组相比,PD-1抑制剂组、PD-1靶向组细胞增殖率依次降低,且差异均有统计学意义(P<0.05)。与空白对照组相比,PD-1抑制剂组、PD-1靶向组细胞INF-γ、IL-2、CD80的mRNA表达及蛋白表达依次升高,TNF-α、TGF-β1、PD-1的mRNA表达及蛋白表达依次降低,且差异均有统计学意义(P<0.05)。结论PD-1靶向纳米投递系统可高效传送PD-1抑制剂到胃癌细胞,并有效改善细胞活性,调控T细胞免疫应答因子表达,可为胃癌治疗领域的进一步研究和临床应用提供新的思路和方向。

Efficacy of sodium-glucose cotransporter-2 inhibitors and glucagonlike peptide-1 receptor agonists on proteinuria and weight in a diabetes cohort

BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose cotransporter-2 inhibitor(SGLT2i)and/or glucagon like peptide-1 receptor agonists(GLP-1RAs)for renal protection.The real-world efficacy of the two medications on the urinary albumin-creatinine ratio(UACR)and estimated glomerular filtration rate(eGFR)remains to be explored.AIM To evaluate the SGLT2i and GLP-1RA application rates and UACR alterations after intervention in a real-world cohort of patients with diabetes.METHODS A cohort of 5482 patients with type 2 diabetes were enrolled and followed up at the Integrated Care Clinic for Diabetes of Peking University First Hospital for at least 6 months.Propensity score matching was performed,and patients who were not recommended for GLP-1RA or SGLT2i with comparable sex categories and ages were assigned to the control group at a 1:2 ratio.Blood glucose,body weight,UACR and eGFR were evaluated after 6 months of treatment in real-world clinical practice.RESULTS A total of 139(2.54%)patients started GLP-1RA,and 387(7.06%)received SGLT2i.After 6 months,the variations in fasting blood glucose,prandial blood glucose,and glycosylated hemoglobin between the GLP-1RA group and the SGLT2i and control groups were not significantly different.UACR showed a tendency toward a greater reduction compared with the control group,although this difference was not statistically significant(GLP-1RA vs control,-2.20 vs 30.16 mg/g,P=0.812;SGLT2i vs control,-20.61 vs 12.01 mg/g,P=0.327);eGFR alteration also showed no significant differences.Significant weight loss was observed in the GLP-1RA group compared with the control group(GLP-1RA vs control,-0.90 vs 0.27 kg,P<0.001),as well as in the SGLT2i group(SGLT2i vs control,-0.59 vs-0.03 kg,P=0.010).CONCLUSION Compared with patients who received other glucose-lowering drugs,patients receiving SGLT2i or GLP-1RAs presented significant weight loss,a decreasing trend in UACR and comparable glucose-lowering effects in realworld settings.

Radiotherapy enhances efficacy of PD-1 inhibitors in advanced hepatocellular carcinoma:A propensity-matched real-world study

Background:To address the need for immunotherapy in patients with advanced primary hepatocellular carcinoma(HCC),combination with radiotherapy(RT)has emerged as a promising strategy.In preclinical studies,irradiated tumors released tumor antigens to synergistically increase the antitumor effect of immunotherapy.Hence,we investigated whether RT enhances the efficacy of anti-programmed death receptor-1(PD-1)inhibitors in advanced HCC in real-world practice.Methods:Between August 2018 and June 2021,172 patients with advanced primary HCC were enrolled in the tertiary center(Zhongshan Hospital of Fudan University);95 were treated with a combination of RT and the inhibitor of PD-1(RT-PD1 cohort),and 77 were administered anti-PD-1 therapy(PD1 cohort).The first cycle of PD-1 inhibitors was administered within 60 days or concurrently with RT.Propensity score matching for bias reduction was used to evaluate the clinical outcomes.Results:Among 71 propensity-matched pairs,median progression-free survival was 5.7 months in the RT-PD1 cohort vs.2.9 months in the PD1 cohort(P<0.001).Median overall survival was 20.9 months in the RT-PD1 cohort vs.11.2 months in the PD1 cohort(P=0.018).Compared with patients in the PD1 cohort,patients in the RT-PD1 cohort had significantly higher objective response rates(40.8%,29/71 vs.19.7%,14/71,P=0.006)and disease control rates(62.0%,44/71 vs.31.0%,22/71,P<0.001).The incidences of toxic effects were not significantly different between the two cohorts.Conclusions:RT plus anti-PD-1 therapy is well tolerated.RT enhances the efficacy of anti-PD-1 therapy in patients with advanced primary HCC by improving survival outcomes without increased toxic effects.

PD-1抑制剂治疗进展期胃癌的预后及其预测列线图模型的构建

目的探讨进展期胃癌患者应用程序性死亡受体-1(PD-1)抑制剂治疗的预后,并构建列线图模型进行预测和验证。方法回顾性收集完成PD-1抑制剂治疗的112例进展期胃癌患者的临床资料,患者均完成2年随访,依据患者生存情况将其分为生存组和病死组。比较2组基线资料,采用Cox回归分析进展期胃癌患者PD-1抑制剂治疗预后的相关影响因素,根据回归分析结果构建风险预测模型,利用R软件构建列线图,对其区分度和准确度做内部验证。结果随访期间,112例患者中病死27例,病死率为24.11%。病死组肿瘤直径>5 cm、人表皮生长因子受体2表达阳性、淋巴结转移患者占比及血清糖类抗原(CA)19-9、CA72-4、中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)水平均高于生存组,差异有统计学意义(P<0.05);组间其他基线资料比较,差异无统计学意义(P>0.05);经Cox回归分析显示,肿瘤直径>5 cm、人表皮生长因子受体-2表达阳性、合并淋巴结转移、高水平NLR、高水平PLR是进展期胃癌PD-1抑制剂治疗预后不良的危险因素(OR>1,P<0.05)。绘制列线图构建进展期胃癌PD-1抑制剂治疗预后的风险预测模型,验证模型的区分度显示C-index=0.932,具有良好的区分度;绘制标准曲线,显示,校准曲线和Y-X直线相近,模型准确度良好。结论肿瘤直径>5 cm、人表皮生长因子受体-2表达阳性、合并淋巴结转移、NLR水平高、PLR水平高是进展期胃癌PD-1抑制剂治疗预后不良的影响因素,且基于上述因素构建的进展期胃癌患者PD-1抑制剂治疗预后不良风险预测模型具有较好的预测价值。