迪利单抗对肺癌患者嗜酸性气道炎症的研究

目的 探讨信迪利单抗对肺癌患者嗜酸性气道炎症的影响。方法 选取2019年4月—2020年4月于徐州医科大学附属宿迁医院就诊的60例IV期非鳞非小细胞肺癌患者,随机分为对照组(单纯化疗组)和试验组(信迪利单抗联合化疗组);对照组给予培美曲塞500 mg/m2联合顺铂75 mg/m2静脉注射;试验组在对照组治疗方案基础上联合免疫检查点抑制剂信迪利单抗200 mg静脉注射,均21天为1个周期。6个周期治疗后检测两组患者呼出气一氧化氮(Fractional exhaled nitric oxide,FeNO)、外周血嗜酸性粒细胞计数、肺功能及动脉血气;分析信迪利单抗治疗组严重不良事件(SAE)及免疫相关性肺炎(CIP)的发生率。结果 ⑴试验组在第2、4、6周期治疗后FeNO水平、外周血嗜酸性粒细胞计数相较于基线水平出现升高趋势,但差异无统计学意义(PFeNO=0.536; PEos=0.762)。⑵两组患者经6个周期治疗后,第1秒用力呼吸容积(FEV1)、用力肺活量(FVC)、FEV1/FVC、一氧化碳弥散量占预计值百分比(DLco%)较治疗前均无明显变化(PFEV1=0.615; PFVC=0.473; PFEV1/FVC=0.637; PDLco%=0.598);动脉血气分析中PH、PaO2、PaCO2水平较治疗前均无明显变化(PPH=0.457; PPaCO2=0.242; PPaO2=0.631)。⑶试验组免疫相关SAE发生率和CIP的发生率均为0。结论 6周期治疗后信迪利单抗对肺癌患者的嗜酸性气道炎症、肺功能、动脉血气分析无明显影响,未出现免疫相关SAE及CIP。     

信迪利单抗、贝伐珠单抗联合肝动脉化疗栓塞术在中晚期肝癌患者中的临床应用

目的 探究信迪利单抗、贝伐珠单抗联合肝动脉化疗栓塞术(TACE)治疗中晚期肝癌患者的临床疗效。方法 选取2018年12月—2019年12月庆阳市中医医院收治的中晚期肝癌患者84例,采用随机数字表法分为研究组和对照组,每组42例。所有受试者接受TACE治疗,对照组采用贝伐珠单抗治疗,研究组在对照组基础上联合信迪利单抗治疗。治疗3个月后,评估两组临床疗效、肿瘤标志物[甲胎蛋白(AFP)、癌胚抗原(CEA)、糖类抗原199(CA199)]、免疫指标[CD3⁺、CD4⁺/CD8⁺、自然杀伤细胞(NK)]及药物不良反应。随访3年,记录患者无进展生存期(PFS)和总生存期(OS)。结果 研究组客观缓解率为83.33%,高于对照组的61.90%(P <0.05)。研究组、对照组疾病控制率分别为92.86%和85.71%,差异无统计学意义(P>0.05)。研究组治疗前后AFP、CEA、CA199、CD3⁺、CD4⁺/CD8⁺、NK的差值均高于对照组(P <...     

A rapid response of lung squamous cell carcinoma following treatment with sintilimab combined with recombinant humane endostatin injection and nab-paclitaxel in an elderly patient: A case report

Rationale:At present, the prognosis of patients with giant lung squamous cell carcinoma (LSCC) is poor, and there is no safe and effective treatment for elderly patients with large LSCC.Patient concerns:Here, we reported a 77-year-old man admitted to the hospital with cough for 3 months and significant chest pain. Computed tomography (CT) imaging showed a large mass in the left lung with pleural effusion.Diagnoses:Chest CT scan revealed a 12.5 cm × 7.3 cm mass in the left upper lobe adjacent to the pulmonary vein, with left pleural effusion. Pulmonary tumor markers were significantly elevated, and CT-guided percutaneous lung mass biopsy specimens showed LSCC.Interventions:After diagnosis, the patient was treated with sintilimab combined with endostar and nab-paclitaxel. After 2 cycles of treatment, the lung mass in the patient shrank rapidly and the clinical symptoms were relieved.Outcomes:The patient''s tumor dramatically shrank, and the pleural effusion was decreased after 4 cycles of treatment without any adverse effects. Meanwhile, the high-level tumor marker resumed normal.Lessons:Sintilimab combined with endostar and nab-paclitaxel may be a good treatment option for lung squamous cell cancer, especially for that in elderly patients.     

安罗替尼联合信迪利单抗对晚期非小细胞肺癌的临床疗效分析

目的 研究安罗替尼联合信迪利单抗治疗晚期非小细胞肺癌(NSCLC)的临床疗效,并作生存分析。方法 回顾性分析2018年12月—2020年12月同济大学附属上海市肺科医院收治的82例晚期NSCLC患者的临床资料,根据治疗方案分为对照组40例和实验组42例。对照组口服盐酸安罗替尼胶囊,12 mg/次,1次/d,连续14 d,21 d为1个周期;实验组在对照组基础上静脉滴注信迪利单抗注射液,200 mg/次,每21天给药1次。两组均治疗至病情进展或不可耐受药物副作用为止。比较两组的临床疗效、血清肿瘤标志物、免疫功能指标及治疗期间药物不良反应情况,记录随访1年期间患者的生存情况,Kaplan-Meier法绘制生存曲线,比较两组的累积生存率。结果研究开展期间共3例脱落。治疗后,实验组和对照组的客观缓解率分别为30.95%和12.50%,疾病控制率分别为85.71%和65.00%,两组比较,实验组均高于对照组(P <0.05)。实验组治疗前后血清CA125、CYFRA21-1差值均高于对照组(P <0.05)。实验组治疗前后CD3⁺、CD4⁺...     

信迪利单抗相关皮肤不良反应文献分析

目的 分析信迪利单抗引起的皮肤药物不良反应（CADR）的发生特点与治疗转归,为临床合理使用信迪利单抗提供参考。方法 检索中国知网（CNKI）、万方、维普（VIP）、PubMed等数据库收载的信迪利单抗致CADR的文献报道并进行数据分析。结果 收集信迪利单抗导致CADR的个案报道15篇,涉及患者15例,其中男性9例（60.00%）,女性6例（40.00%）,年龄分布以50岁以上居多（11例,73.33%）,发生时间主要集中在用药84 d以内（14例,93.33%）,CADR类型以中毒性表皮坏死松解症和大疱性类天疱疮最常见,分别有6例（40.00%）和2例（13.33%）。13例患者经停药和/或对症处理后均好转,1例患者因Stevens-Johnson综合征死亡,1例患者因中毒性表皮坏死松解症死亡。结论 信迪利单抗可诱发CADR,应注意红斑、黏膜损伤、皮疹、水疱等可能为CADR发生的信号,除了全身性糖皮质激素治疗以外,静脉注射用人免疫球蛋白和肿瘤坏死因子-α(TNF-α)抑制剂也可作为CADR的补充治疗。     

Sintilimab treatment for ureteral carcinoma following bladder cancer leads to leukopenia: a case report

Herein, we present a case report of sintilimab treatment for a patient with ureteral cancer reoccurring after bladder cancer, and exploration of the mechanism of adverse reactions from the aspects of intestinal flora and immunity. We have reported a case of leukopenia in a patient with recurrent ureteral cancer after bladder cancer who was treated with sintilimab. A 52-year-old Chinese man with a history of hypertension and diabetes presented with lower urinary tract symptoms, including painless hematuria, frequent and urgent urination, and micturition without pain. Computed tomography (CT) and 3-dimensional (3D) reconstruction suggested bladder space occupation, bladder cancer was pathologically confirmed after laser resection of the bladder tumor, which then recurred and was subject to reoperation. After 8 months, B-mode ultrasonography indicated left ureter occupation, and the patient began sintilimab immunotherapy according to the outcome of immunohistochemistry (IHC) and immune checkpoint inhibitor (ICI) evaluation. The patient was treated with sintilimab a total of 6 times. After the first treatment, the patient was in stable condition. The second treatment was discontinued due to renal insufficiency. The patient was then treated with renal and liver protection for 1.5 months, followed by 5 rounds of immunotherapy. After the sixth round of immunotherapy, the patient presented with leukopenia. In order to determine the causes of adverse reactions, we analyzed the changes of intestinal flora of patients before and after immunotherapy, and summarized the immune function indicators of patients during immunotherapy. The leucopenia induced by sintilimab may be related to intestinal flora and immunity.     

信迪利单抗不良反应文献分析

目的 分析信迪利单抗所致药品不良反应发生的规律及其临床特点,为临床安全用药提供参考。方法 通过检索Pubmed数据库、中国知网、万方数据库,收集信迪利单抗的不良反应的个案报道,并对患者的性别、年龄、原患疾病、给药方案以及不良反应的发生时间、临床表现及预后等进行统计分析。结果 检索文献得到20例患者,患者多为男性,原患疾病多为肺癌。20例均采用常规剂量治疗,单药治疗的为9例,联合其他药物化疗的共11例。信迪利单抗所致不良反应发生时间跨度较大,最快出现在用药后3 d,最迟出现在用药后405 d,用药后30～180 d发生者最多为12例。信迪利单抗致不良反应累及多个系统,免疫相关性内分泌疾病7例,表现为甲状腺功能减退、甲状腺功能亢进、自身免疫性糖尿病;1例放射召回性肺炎为新发的不良反应。16例患者通过停药、给予糖皮质激素、免疫抑制剂、保肝药等治疗后好转。结论 临床医师和药师需加强药物治疗的安全性监测,以便早期识别,保障患者用药安全。     

盐酸安罗替尼联合信迪利单抗注射液治疗对微卫星稳定型结直肠癌患者血管内皮生长因子、转化生长因子-β水平及免疫功能的影响

目的探讨盐酸安罗替尼联合信迪利单抗注射液治疗对微卫星稳定型(MSS)结直肠癌患者血管内皮生长因子(VEGF)、转化生长因子-β(TGF-β)及免疫功能的影响。方法根据治疗方法的不同将经临床标准治疗失败的36例MSS型结直肠癌患者分为单一组(n=16,接受盐酸安罗替尼治疗)和联合组(n=20,接受盐酸安罗替尼联合信迪利单抗治疗)。比较两组患者的临床疗效、不良反应发生情况、VEGF水平、TGF-β水平、T淋巴细胞亚群指标(CD8⁺、CD4⁺、CD4⁺/CD8⁺)及免疫分子含量。结果治疗后,联合组患者的有效率及CD4⁺水平、CD4⁺/CD8⁺均高于单一组患者,血清VEGF、TGF-β水平均低于单一组患者(P﹤0.05)。治疗后,联合组患者肿瘤促进分子CD168、CD133、CD151的含量均明显低于单一组,肿瘤抑制分子CD9、CD63的含量均明显高于单一组患者(P﹤0.01)。结论盐酸安罗替尼联合信迪利单抗对经临床标准治疗失败的MSS型结直肠癌患者具有较好的治疗效果,可降低VEGF、TGF-β水平,抑制肿瘤生长,并提高患者的免疫功能。     

Clinical outcomes and influencing factors of PD-1/PD-L1 in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) has an increasing incidence worldwide, and the global 5-year survival rate ranges from 5–30%. In China, HCC seriously threatens the nation''s health; the incidence of HCC ranks fourth among all theriomas, and the mortality rate is the third highest worldwide. The main therapies for HCC are surgical treatment or liver transplantation; however, most patients with HCC will experience postoperative recurrence or metastasis, eventually resulting in mortality. As for advanced or unresectable HCC, the current appropriate treatment strategy is transarterial chemoembolization; however, limited therapeutic effect and natural or acquired drug resistance affect the efficacy of this approach. Previous studies have demonstrated that PD-L1 expression on host cells and myeloid cells plays an important role in PD-L1 blocked-mediated tumor regression. Thus, further research on programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) is required. Countries including the United States, France, Britain and China have developed PD-1/PD-L1 blockers, including nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, toripalimab, sintilimab and camrelizumab. Notably, all of these blockers have therapeutic effect and influencing factors in HCC. Factors that influence the clinical outcome of PD-1 have also been discovered, such as inflammatory genes, specific receptors and signaling pathways. The discovery of these factors will help to identify novel methods, such as combination treatment, to decrease the influence of other factors on the efficacy of PD-1/PD-L1. Sorafenib and lenvatinib have been approved for first-line treatment for patients with advanced HCC. When first-line treatment frequently fails, pembrolizumab and ipilimumab plus nivolumab are used following sorafenib (but not lenvatinib) treatment in advanced HCC. Thus, tumor immunotherapy using PD-1/PD-L1 blockers exhibits promising outcomes for the treatment of HCC, and more novel PD-1/PD-L1 inhibitors are being developed to fight against this disease. The present review discusses the clinical results and influencing factors of PD-1/PD-L1 inhibitors in HCC to provide insight into the development and optimization of PD-1/PD-L1 inhibitors in the treatment of HCC.