BACKGROUND:Immune checkpoint inhibitors (ICIs), especially those targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), have introduced a new treatment landscape for many types of tumors. However, they only achieve a limited therapeutic response. Hence, identifying patients who may benefit from ICIs is currently a challenge.METHODS:47 tumor patients harboring ARID1A mutations were retrospectively studied. The genomic profiling data through next-generation sequencing (NGS) and relevant clinical information were collected and analyzed. Additionally, bioinformatics analysis of the expression of immune checkpoints and immune cell infiltration levels was conducted in ARID1A-mutant gastric cancer (GC).RESULTS:ARID1A mutations frequently co-occur with mutations in DNA damage repair (DDR)-associated genes. Among the 35 ARID1A-mutant patients who received immunotherapy, 27 were evaluable., with the objective response rate (ORR) was 48.15% (13/27), and the disease control rate (DCR) was 92.59% (25/27). Moreover, survival assays revealed that ARID1A-mutant patients had longer median overall survival (mOS) after immunotherapy. In ARID1A-mutated GC patients, receiving ICIs treatment indicated longer progressive-free survival (PFS). Additionally, the incidence of microsatellite instability-high (MSI-H), high tumor mutation burden (TMB-H) and Epstein‒Barr virus (EBV) infection was elevated. Bioinformatic analysis showed significant enrichment of immune response and T cell activation pathway within differentially expressed genes in ARID1A-mutant GC group. Finally, ARID1A mutations status was considered to be highly correlated with the level of tumor infiltrating lymphocytes (TILs) and high expression of immune checkpoints.CONCLUSIONS:Patients with tumors harboring ARID1A mutations may achieve better clinical outcomes from immunotherapy, especially in GC. ARID1A mutations can lead to genomic instability and reshape the tumor immune microenvironment (TIME), which can be used as a biomarker for immunotherapy.
Objective:To explore the clinical manifestation, treatments, and outcomes of immune checkpoint inhibitor (ICI)-induced immune-mediated liver injury (IMLI).Methods:The patients with ICI- related IMLI and hospitalized in the Department of Oncology, the Affiliated Hospital of Qingdao University from January 2018 to November 2022 were collected. The basic information, tumor treatments, clinical manifestation, treatments and outcomes of the patients with IMLI were retrospectively analyzed.Results:A total of 29 patients were included in the study, including 17 males (58.6%) and 12 females (41.4%), with a median age of 65 years. The median treatment cycle from the use of ICI to the occurrence of liver injury was 3 cycles, and the median time was 78 days. In patients with IMLI, 48.3% (14/29) had no obvious symptoms and 51.7% (15/29) had symptoms such as decreased appetite, nausea, abdominal distension, fatigue, fever and jaundice; 44.8% (13/29) were accompanied by other immune-related adverse events. The clinical classification of IMLI was hepatocellular type in 18 patients (62.1%), cholestasis type in 4 patients (13.8%), and mixed type in 7 patients (24.1%). According to the Common Terminology Criteria for Adverse Events (CTCAE) classification, severe liver injury (≥ grade 3) accounted for 86.2% (25/29), while according to the Chinese Diagnosis and Treatment Guideline on Drug-Induced Liver Injury (DILI guidelines) classification, severe liver injury (≥ grade 2) accounted for 34.5% (10/29). All 29 patients discontinued the treatment of ICIs after occurrence of IMLI, and 28 patients were treated with glucocorticoids, 7 of which were combined with mycophenolate mofetil and/or human immunoglobulin and artificial liver; 22 patients (75.9%) were improved. In the other 7 patients that did not recover, 4 discharged automatically, 2 died, and 1 could not be judged. ICI was rechallenged in 3 patients after liver function improvement, and IMLI did not recur. Conclusions:The IMLIs often occur 2 to 3 months after the start of ICI treatment, the most common clinical type is hepatocyte type, and the severity of clinical symptoms in patients vary from mild to severe. After discontinuing ICIs and receiving glucocorticoid treatments, most patients may have a good prognosis.
对皮下隧道技术在经外周静脉置入中心静脉导管(PICC)置管中的国内外应用现状进行综述,为经PICC置管选择更佳的穿刺血管,将导管的出口位置放置于更加安全、舒适的部位,并扩大PICC适用范围,提高置管成功率及降低导管相关性血栓、感染、穿刺点渗血、导管移位等并发症的发生提供参考.
总结我院10例中重度PICC脱管患者转变为中长导管的护理经验.脱管后,通过拍摄胸部X线确认导管尖端位置位于锁骨下静脉或腋静脉胸段,进行修剪固定,按照中长导管使用.评估药物性质,做好针对性防脱管措施.结果 10例脱管患者均完成既定化疗任务,无感染及血栓等并发症发生.
e15512 Background: The high gastric cancer mortality rate is largely due to the lack of effective medical treatment. The development of next generation sequencing (NGS) technology provides a high-throughput and systematic method to identify the genetic alterations in the cancer genome. In this study, we used a broad, hybrid capture-based NGS to discover targetable genetic alterations from advanced gastric cancer (AGC) tissue so that approved molecular target drugs or available agents on clinical trials could be selected. Methods: 31 AGC patients were enrolled and cancer tissue samples were collected after informed consent provided by all patients. 7708 exons of 508 tumor related genes and 78 introns of 19 frequently rearranged genes were assessed for base substitutions, indels, copy number alterations, and gene fusions. The average median sequencing depth was 470×. Results: Somatic mutations were detected in 100% of patients. 9.7% (3/31) could select NCCN guideline approved targeted drugs according to the identified actionable genetic alterations (HER2 gene amplification/ mutation). Remarkably, other targetable genetic alterations were detected in 13 of 31 (41.9%) AGC patients, which applied to mTOR inhibitors, PARP inhibitors, FGFR inhibitors, etc. Conclusions: 51.6% (16/31) of AGC patients harbored at least one actionable genetic alteration identified by NGS testing. NGS based targetable alterations detection might help identify available targeted drugs to personalize target therapy for AGC patients. Targeted genetic alterations identified by NGS in AGC. Targeted genetic alterations No. Rates Therapeutic implications HER2 (mut/CNV) 3 9.7% Trastuzumab ATM (mut) 2 6.5% PARP inhibitors FGFR2 (CNV) 2 6.5% FGFR inhibitors KRAS (mut) 2 6.5% Selumetinib TP53 (mut) 2 6.5% APR-246 MK-1775 CCNE1 (CNV) 1 3.2% CDK4/6 inhibitors EGFR (mut) 1 3.2% TKI inhibitors EGFR (CNV) 1 3.2% anti-EGFR therapy ERBB3 (mut) 1 3.2% Sapitinib FBXW7 (mut) 1 3.2% mTOR inhibitors MET (CNV) 1 3.2% Crizotinib MLH1 (mut) 1 3.2% Pembrolizumab NF1 (mut) 1 3.2% mTOR inhibitors PIK3CA (mut) 1 3.2% mTOR inhibitors PTEN (mut) 1 3.2% mTOR inhibitors RB1 (mut) 1 3.2% CDK4/6 inhibitors
我科收治的1例非小细胞肺癌病人行第一周期化疗,使用紫杉醇后出现即刻过敏反应,经及时对症处理,取得满意效果,现将护理体会报告如下.
胃癌是最常见的肿瘤,发病率占全部肿瘤首位.早在20世纪30年代就有研究报道,约有20%以上的肿瘤患者直接死亡原因是为营养不良.营养对肿瘤治疗和改善肿瘤患者的预后和生活质量方面均具有重要作用.2005年3月~2007年2月,我们针对147例胃癌患者普遍存在营养饮食知识缺乏的情况,给予有针对性的护理干预,取得满意效果.现报告如下.