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Almonertinib and alflutinib show novel inhibition on rare EGFR S768I mutant cells. 阿莫替尼和阿氟替尼对罕见的表皮生长因子受体 S768I 突变细胞有新的抑制作用。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-30 DOI: 10.1007/s12094-024-03494-5
Xiangkai Wei, Guoliang Zhang, Qian Liu, Zhiyuan Niu, Chunhong Chu, Chenxue Liu, Ke Wang, Lanxin Li, Rui Wang, Wenrui Cui, Huixia Xu, Chenyang Liu, Ying Wang, Lei An

Purpose: EGFR classical mutations respond well to EGFR tyrosine kinase inhibitors. However, it is uncertain whether currently available EGFR-TKIs are effective against rare EGFR mutations and compound mutations. Herein, the effectiveness of almonertinib and alflutinib, the third-generation tyrosine kinase inhibitors developed in China, on rare EGFR S768I mutations and compound mutations is identified.

Methods: In this study, using CRISPR method, four EGFR S768I mutation cell lines were constructed, and the sensitivity of EGFR to almonertinib and alflutinib was tested, with positive controls being the 1st (gefitinib), 2nd (afatinib), and 3rd (osimertinib) generation drugs.

Results: The present results indicate that almonertinib and alflutinib can effectively inhibit cell viability and proliferation in rare EGFR S768I mutations through the ERK or AKT pathways in a time-dependent manner, by blocking the cell cycle and inhibiting apoptosis.

Conclusions: These findings suggest that almonertinib and alflutinib may be potential therapeutic options for non-small cell lung cancer patients with the EGFR S768I mutation.

目的:表皮生长因子受体经典突变对表皮生长因子受体酪氨酸激酶抑制剂反应良好。然而,目前可用的表皮生长因子受体酪氨酸激酶抑制剂对罕见的表皮生长因子受体突变和复合突变是否有效尚不确定。在此,本研究确定了中国开发的第三代酪氨酸激酶抑制剂阿莫替尼和阿氟替尼对罕见EGFR S768I突变和复合突变的有效性:本研究采用CRISPR方法构建了4个EGFR S768I突变细胞系,以第一代药物(吉非替尼)、第二代药物(阿法替尼)和第三代药物(奥西美替尼)为阳性对照,检测了EGFR对阿莫替尼和阿氟替尼的敏感性:本研究结果表明,阿莫替尼和阿氟替尼可通过ERK或AKT通路,以时间依赖性方式有效抑制罕见表皮生长因子受体S768I突变的细胞活力和增殖,阻滞细胞周期并抑制细胞凋亡:这些研究结果表明,对于表皮生长因子受体(EGFR)S768I突变的非小细胞肺癌患者,阿莫替尼和阿氟替尼可能是潜在的治疗选择。
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引用次数: 0
Efficacy and safety evaluation of combined therapies incorporating whole-brain radiotherapy in patients with brain metastases: a systematic review and meta-analysis. 脑转移瘤患者全脑放疗联合疗法的疗效和安全性评估:系统综述和荟萃分析。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-24 DOI: 10.1007/s12094-024-03525-1
Qi Yan, Rong Li, Jiayang Yang, Xueqi Bai, Xiudong Guo, Xin Yang, Jianbo Song

Background: Whole-brain radiotherapy (WBRT) is a standard and effective approach for brain metastases, but it is linked to neurocognitive complications, specifically issues related to the hippocampus. Innovative strategies are being explored to enhance outcomes. However, a consensus is yet to be reached in this field. Our aim is to investigate the efficacy and safety of WBRT combined with simultaneous integrated boost (SIB), memantine, and hippocampal avoidance (HA) techniques in treatment of brain metastases.

Methods: In this systematic review and meta-analysis, we comprehensively searched PubMed, MEDLINE, Embase, and Cochrane for studies reporting the efficacy and toxicity of WBRT-based combination therapies from inception to September 19, 2023. Data were pooled using random-effects models. Results were reported as risk ratios (RRs) and risk differences (RDs) for dichotomous outcomes, along with their 95% confidence intervals (CIs). Heterogeneity was evaluated using the I2 statistic.

Results: Among 2175 articles, 29 studies involving 3460 patients were included. The meta-analysis revealed that compared to WBRT alone, combination therapies significantly mitigated neurocognitive function decline (RD = -0.09, 95% CI [-0.18-0.01]; P = 0.03) and intracranial control failure (RR = 0.86, 95% CI [0.52-1.44]; P = 0.02), without increasing the risk of hippocampal recurrence or high-grade toxicities. Notably, HA-WBRT + SIB/memantine demonstrated improved neurocognitive outcomes and survival benefits.

Conclusion: WBRT-based combination therapies demonstrate improved efficacy and comparable safety to WBRT alone, with specific emphasis on the effectiveness of HA-WBRT + Memantine and HA-WBRT + SIB in optimizing therapeutic outcomes for brain metastases.

背景:全脑放射治疗(WBRT)是治疗脑转移瘤的一种标准而有效的方法,但它与神经认知并发症有关,特别是与海马有关的问题。目前正在探索创新策略,以提高治疗效果。然而,这一领域尚未达成共识。我们的目的是研究WBRT结合同步综合增强(SIB)、美金刚和海马回避(HA)技术治疗脑转移瘤的有效性和安全性:在这项系统综述和荟萃分析中,我们全面检索了PubMed、MEDLINE、Embase和Cochrane上从开始到2023年9月19日报道基于WBRT的联合疗法疗效和毒性的研究。采用随机效应模型对数据进行了汇总。结果以二分结果的风险比 (RR) 和风险差异 (RD) 及其 95% 置信区间 (CI) 的形式报告。使用 I2 统计量评估异质性:在 2175 篇文章中,共纳入了 29 项研究,涉及 3460 名患者。荟萃分析表明,与单用WBRT相比,联合疗法可显著缓解神经认知功能下降(RD = -0.09,95% CI [-0.18-0.01];P = 0.03)和颅内控制失败(RR = 0.86,95% CI [0.52-1.44];P = 0.02),且不会增加海马复发或高级别毒性反应的风险。值得注意的是,HA-WBRT + SIB/美金刚表现出更好的神经认知结果和生存获益:结论:基于WBRT的联合疗法与单用WBRT相比,疗效更好,安全性相当,特别强调HA-WBRT + Memantine和HA-WBRT + SIB在优化脑转移瘤治疗效果方面的有效性。
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引用次数: 0
The clinical features and prognostic implications of the co-mutated TP53 gene in advanced non-small cell lung cancer. 晚期非小细胞肺癌 TP53 基因共突变的临床特征和预后影响。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-13 DOI: 10.1007/s12094-024-03533-1
Bing Bai, Xia An, Qinghui Qu, Xin Liu, Yuanyuan Liu, Li Wei

Background: TP53 is a frequently mutated oncogene within non-small cell lung cancer (NSCLC). However, the clinical and prognostic significance of co-mutations in TP53 in patients with advanced NSCLC has not been fully elucidated.

Methods: A total of 174 patients with advanced NSCLC were enrolled in this study. All patients were subjected to sequencing analysis of tumor-related genes and information such as PD-L1 expression, TMB, and co-mutation changes were collected. Patients were categorized into TP53 mutant and TP53 wild-type groups according to their TP53 mutation status and then statistically analyzed.

Results: TP53 mutations were the most common among all patients, accounting for 56.32%, followed by epidermal growth factor receptor mutations at 48.27%. The most common mutation sites in the TP53 mutation group were exons 5-8.TP53 mutations were significantly associated with PD-L1 and TMB levels. Univariate Cox analysis showed that gender and EGFR mutation affected the prognosis of TP53-mutated NSCLC patients, and multivariate Cox regression analysis identified EGFR mutation as an independent risk factor. The OS of NSCLC patients in the TP53 mutation group was significantly shorter than that of the TP53wt group. Survival curves in the TP53/EGFR combined mutation group showed that patients with combined EGFR mutation had a lower survival rate.

Discussion: TP53 mutations are associated with different clinical indicators and have important implications in clinical treatment. TP53 is a poor prognostic factor for NSCLC patients, and TP53/EGFR co-mutation will affect the survival time of patients. TP53/EGFR co-mutation may be a new prognostic marker for NSCLC.

背景TP53是非小细胞肺癌(NSCLC)中经常发生突变的癌基因。然而,TP53共突变在晚期NSCLC患者中的临床和预后意义尚未完全阐明:方法:本研究共纳入了 174 例晚期 NSCLC 患者。所有患者均接受了肿瘤相关基因的测序分析,并收集了 PD-L1 表达、TMB 和共突变变化等信息。根据TP53突变情况将患者分为TP53突变组和TP53野生型组,然后进行统计学分析:所有患者中最常见的是 TP53 突变,占 56.32%,其次是表皮生长因子受体突变,占 48.27%。TP53突变组中最常见的突变位点是5-8号外显子,TP53突变与PD-L1和TMB水平显著相关。单变量Cox分析显示,性别和表皮生长因子受体突变会影响TP53突变NSCLC患者的预后,多变量Cox回归分析发现表皮生长因子受体突变是一个独立的危险因素。TP53突变组NSCLC患者的OS明显短于TP53wt组。TP53/EGFR联合突变组的生存曲线显示,EGFR联合突变患者的生存率较低:讨论:TP53突变与不同的临床指标相关,对临床治疗有重要影响。TP53是NSCLC患者的不良预后因素,TP53/EGFR联合突变会影响患者的生存时间。TP53/EGFR联合突变可能是NSCLC新的预后标志物。
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引用次数: 0
Dynamic change of gut microbiota in head and neck concurrent chemoradiotherapy patients and its potential value in the prediction of acute oral mucositis grade as well as quality of life. 头颈部同期化放疗患者肠道微生物群的动态变化及其在预测急性口腔黏膜炎等级和生活质量方面的潜在价值。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-06 DOI: 10.1007/s12094-024-03542-0
Ying Chen, Xianghua Ye, Xinke Li, Fang Wang, Jinsong Yang, Xiaoli Sun, Senxiang Yan

Purpose: Radiotherapy is the major therapy for head and neck squamous cell carcinoma (HNSCC). However, whether gut microbiota changes in HNSCC patients who received concurrent chemoradiotherapy remains unclear. This study aimed to investigate the dynamic change of gut microbiota composition, construct the first radiotherapy-related gut microbiota database in these patients and identify the potential value of the gut microbiota changing in the prediction of acute oral mucositis grade as well as patients' life quality.

Methods: We enrolled 47 HNSCC patients who scheduled with concurrent chemoradiotherapy. The field was irradiated with a total dose of 66-70 Gy in 33-35 fractions. All the patients received 2-3 cycles of platinum-based chemotherapy. After feces specimens collected, bacterial genomic DNA was isolated using magnetic beads and then analyzed by the Illumina MiSeq Sequencing System based on the V3-V4 hypervariable regions of the 16S rRNA gene.

Results: 194 genera which belonged to 27 phyla were found in 141 samples. Increased abundance of microbiota in diversity and richness was observed in mid-radiotherapy group. Bacteroides, Blautia, Phascolarctobacterium were three main genera in all three groups and the mid-radiotherapy group had the highest relative abundance of Phascolarctobacterium. What is more, most significantly altered bacteria shared the same variation pattern which was increased in mid-radiotherapy while decreased to the almost same level of as pre-radiotherapy in post-radiotherapy group. Further analysis indicated that Bacteroidetes showing an upward trend while Proteobacteria declining in higher grade of acute mucositis. Moreover, relatively low abundant Proteobacteria was significantly correlated with high-grade acute oral mucositis. As for the quality of life, Lactobacillales and Actinomycetales were specifically found in better life quality group. However, Clostridia_UCG_014, Eubacteriaceae, UCG_010 and Moraxellaceae were unique abundantly present in worse life quality group.

Conclusion: Chemoradiotherapy can affect the composition of the gut microbiota in HNSCC patients during the mid-term of treatment. Yet self-stabilized ability maintained the gut microbiota homeostasis. Dynamic change of specific species could help predict acute oral mucositis grade and characterize different quality of life group in these patients.

目的:放疗是头颈部鳞状细胞癌(HNSCC)的主要治疗方法:放疗是头颈部鳞状细胞癌(HNSCC)的主要疗法。然而,同时接受放化疗的 HNSCC 患者的肠道微生物群是否会发生变化仍不清楚。本研究旨在调查肠道微生物群组成的动态变化,在这些患者中建立首个与放疗相关的肠道微生物群数据库,并确定肠道微生物群变化在预测急性口腔黏膜炎等级以及患者生活质量方面的潜在价值:方法:我们纳入了47名计划同时接受放化疗的HNSCC患者。所有患者均接受了 2-3 个周期的化疗。所有患者均接受了 2-3 个周期的铂类化疗。采集粪便标本后,使用磁珠分离细菌基因组 DNA,然后使用 Illumina MiSeq 测序系统根据 16S rRNA 基因的 V3-V4 超变区进行分析:结果:在 141 份样本中发现了 194 个属,隶属于 27 个门。放疗中期组微生物群的多样性和丰富度均有所增加。Bacteroides、Blautia和Phascolarctobacterium是所有三组中的三个主要菌属,而放疗中期组中Phascolarctobacterium的相对丰度最高。此外,大多数明显改变的细菌具有相同的变异模式,即放疗中期增加,而放疗后组减少到与放疗前几乎相同的水平。进一步的分析表明,在急性粘膜炎程度较高的人群中,类杆菌呈上升趋势,而变形菌则呈下降趋势。此外,相对较少的变形杆菌与高级别急性口腔黏膜炎有显著相关性。在生活质量方面,乳杆菌科和放线菌科特别出现在生活质量较好的组别中。结论:化疗会影响急性口腔黏膜炎的组成:结论:化疗放疗会在治疗中期影响 HNSCC 患者肠道微生物群的组成。然而,肠道微生物群的自我稳定能力可维持肠道微生物群的平衡。特定物种的动态变化有助于预测急性口腔黏膜炎的等级,并描述这些患者不同生活质量组别的特征。
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引用次数: 0
Unleashing the potential: transarterial chemoembolization combined with intra-arterial infusion of bevacizumab for unresectable hepatocellular carcinoma. 释放潜能:经动脉化疗栓塞术联合动脉内输注贝伐单抗治疗不可切除的肝细胞癌。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-27 DOI: 10.1007/s12094-024-03498-1
Qu Xie, Yanzhen Yang, Weiyuan Hao, Cong Luo

Background: The purpose of this study is to compare the efficacy and safety of transarterial chemoembolization (TACE) alone with transarterial chemoembolization combined with the arterial infusion of bevacizumab (TACE + Bev) in patients with unresectable hepatocellular carcinoma (uHCC).

Methods: A retrospective analysis was conducted on 446 uHCC patients treated with TACE or TACE + Bev between January 2021 and March 2023. The study evaluated objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events in both treatment groups.

Results: Finally, the TACE group comprised 295 patients, and the TACE + Bev group comprised 151 patients. Patients in the TACE + Bev group exhibited significantly prolonged median PFS (7.9 months vs. 10.3 months, P = 0.013) and median OS (16.1 months vs. 21.4 months, P = 0.041), improved ORR (26.8% vs. 37.7%, P = 0.017) and DCR (71.5% vs. 80.8%, P = 0.033) compared to the TACE group. Multifactorial Cox analysis identified alpha-fetoprotein (AFP) > 400 ng/ml as an independent prognostic factor for PFS and OS. Meanwhile, portal vein cancer thrombosis and distant metastasis are poor prognostic factors for OS. The overall incidence of adverse events was similar between the two groups.

Conclusion: In comparison with the TACE group, the TACE + Bev group demonstrated efficacy in improving outcomes for patients with uHCC with a manageable safety profile.

研究背景本研究旨在比较单独经动脉化疗栓塞术(TACE)与经动脉化疗栓塞术联合动脉输注贝伐单抗(TACE + Bev)对不可切除肝细胞癌(uHCC)患者的疗效和安全性:对2021年1月至2023年3月期间接受TACE或TACE + Bev治疗的446例uHCC患者进行了回顾性分析。研究评估了两个治疗组的客观反应率(ORR)、疾病控制率(DCR)、无进展生存期(PFS)、总生存期(OS)和不良事件:最终,TACE组有295名患者,TACE + Bev组有151名患者。与 TACE 组相比,TACE + Bev 组患者的中位 PFS(7.9 个月 vs. 10.3 个月,P = 0.013)和中位 OS(16.1 个月 vs. 21.4 个月,P = 0.041)明显延长,ORR(26.8% vs. 37.7%,P = 0.017)和 DCR(71.5% vs. 80.8%,P = 0.033)有所改善。多因素 Cox 分析发现,甲胎蛋白(AFP)> 400 ng/ml 是 PFS 和 OS 的独立预后因素。同时,门静脉癌栓和远处转移是OS的不良预后因素。两组患者的不良反应总发生率相似:结论:与 TACE 组相比,TACE + Bev 组在改善 uHCC 患者预后方面具有疗效,且安全性可控。
{"title":"Unleashing the potential: transarterial chemoembolization combined with intra-arterial infusion of bevacizumab for unresectable hepatocellular carcinoma.","authors":"Qu Xie, Yanzhen Yang, Weiyuan Hao, Cong Luo","doi":"10.1007/s12094-024-03498-1","DOIUrl":"10.1007/s12094-024-03498-1","url":null,"abstract":"<p><strong>Background: </strong>The purpose of this study is to compare the efficacy and safety of transarterial chemoembolization (TACE) alone with transarterial chemoembolization combined with the arterial infusion of bevacizumab (TACE + Bev) in patients with unresectable hepatocellular carcinoma (uHCC).</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 446 uHCC patients treated with TACE or TACE + Bev between January 2021 and March 2023. The study evaluated objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events in both treatment groups.</p><p><strong>Results: </strong>Finally, the TACE group comprised 295 patients, and the TACE + Bev group comprised 151 patients. Patients in the TACE + Bev group exhibited significantly prolonged median PFS (7.9 months vs. 10.3 months, P = 0.013) and median OS (16.1 months vs. 21.4 months, P = 0.041), improved ORR (26.8% vs. 37.7%, P = 0.017) and DCR (71.5% vs. 80.8%, P = 0.033) compared to the TACE group. Multifactorial Cox analysis identified alpha-fetoprotein (AFP) > 400 ng/ml as an independent prognostic factor for PFS and OS. Meanwhile, portal vein cancer thrombosis and distant metastasis are poor prognostic factors for OS. The overall incidence of adverse events was similar between the two groups.</p><p><strong>Conclusion: </strong>In comparison with the TACE group, the TACE + Bev group demonstrated efficacy in improving outcomes for patients with uHCC with a manageable safety profile.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3075-3084"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The value of combined MRI, enhanced CT and 18F-FDG PET/CT in the diagnosis of recurrence and metastasis after surgery for ovarian cancer. 联合磁共振成像、增强 CT 和 18F-FDG PET/CT 在诊断卵巢癌术后复发和转移中的价值。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-05-23 DOI: 10.1007/s12094-024-03499-0
Yong Hong, Jianfeng Peng, Yanni Zeng, Xuewen Deng, Wanjun Xu, Juanting Wang

Objective: The purpose of this article was to investigate the value of combined MRI, enhanced CT and 18F-FDG PET/CT in the diagnosis of recurrence and metastasis after surgery for ovarian cancer.

Methods: Ninety-five ovarian cancer patients were selected as the study subjects, all of them underwent surgical treatment, and MRI, enhanced CT and 18F-FDG PET/CT were performed on all of them in the postoperative follow-up, and the pathological results after the second operation were used as the diagnostic "gold standard". The diagnostic value (sensitivity, specificity, accuracy, negative predictive value and positive predictive value) of the three examination methods alone or in combination for the diagnosis of postoperative recurrence and metastasis of ovarian cancer was compared, and the detection rate was calculated when the lesion was the unit of study, so as to compare the efficacy of the three methods in the diagnosis of postoperative recurrent metastatic lesions of ovarian cancer.

Results: The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the combined group were higher than those of MRI and enhanced CT for recurrence and metastasis of ovarian cancer after surgery, and the specificity, accuracy and positive predictive value of the combined group were higher than those of the 18F-FDG PET/CT group, and those of the 18F-FDG PET/CT group were higher than those of the enhanced CT group (all P < 0.05). When the postoperative recurrent metastatic lesions of ovarian cancer were used as the study unit, the detection rate of lesions in the combined group was higher than that of the three examinations detected individually, and the detection rate of lesions in 18F-FDG PET/CT was higher than that of enhanced CT and MRI (P < 0.05).

Conclusion: The combination of MRI, enhanced CT and 18F-FDG PET/CT can accurately diagnose recurrence and metastasis of ovarian cancer after surgery, detect recurrent metastatic lesions as early as possible, and improve patients' prognosis.

目的本文旨在探讨MRI、增强CT和18F-FDG PET/CT联合应用在卵巢癌术后复发和转移诊断中的价值:方法:选取95例卵巢癌患者作为研究对象,所有患者均接受了手术治疗,术后随访时均进行了MRI、增强CT和18F-FDG PET/CT检查,并将第二次手术后的病理结果作为诊断 "金标准"。比较三种检查方法单独或联合诊断卵巢癌术后复发和转移的诊断价值(敏感性、特异性、准确性、阴性预测值和阳性预测值),以病灶为研究单位计算检出率,从而比较三种方法在卵巢癌术后复发转移病灶诊断中的疗效:联合组对卵巢癌术后复发和转移的敏感性、特异性、准确性、阳性预测值和阴性预测值均高于MRI和增强CT,联合组的特异性、准确性和阳性预测值均高于18F-FDG PET/CT组,18F-FDG PET/CT组的特异性、准确性和阳性预测值均高于增强CT组(均P 18F-FDG PET/CT的特异性、准确性和阳性预测值均高于增强CT和MRI(P 结论:MRI、增强CT和联合组对卵巢癌术后复发和转移的敏感性、特异性、准确性、阳性预测值和阴性预测值均高于MRI和增强CT:MRI、增强CT和18F-FDG PET/CT联合应用可准确诊断卵巢癌术后复发和转移,尽早发现复发转移病灶,改善患者预后。
{"title":"The value of combined MRI, enhanced CT and <sup>18</sup>F-FDG PET/CT in the diagnosis of recurrence and metastasis after surgery for ovarian cancer.","authors":"Yong Hong, Jianfeng Peng, Yanni Zeng, Xuewen Deng, Wanjun Xu, Juanting Wang","doi":"10.1007/s12094-024-03499-0","DOIUrl":"10.1007/s12094-024-03499-0","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this article was to investigate the value of combined MRI, enhanced CT and <sup>18</sup>F-FDG PET/CT in the diagnosis of recurrence and metastasis after surgery for ovarian cancer.</p><p><strong>Methods: </strong>Ninety-five ovarian cancer patients were selected as the study subjects, all of them underwent surgical treatment, and MRI, enhanced CT and <sup>18</sup>F-FDG PET/CT were performed on all of them in the postoperative follow-up, and the pathological results after the second operation were used as the diagnostic \"gold standard\". The diagnostic value (sensitivity, specificity, accuracy, negative predictive value and positive predictive value) of the three examination methods alone or in combination for the diagnosis of postoperative recurrence and metastasis of ovarian cancer was compared, and the detection rate was calculated when the lesion was the unit of study, so as to compare the efficacy of the three methods in the diagnosis of postoperative recurrent metastatic lesions of ovarian cancer.</p><p><strong>Results: </strong>The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the combined group were higher than those of MRI and enhanced CT for recurrence and metastasis of ovarian cancer after surgery, and the specificity, accuracy and positive predictive value of the combined group were higher than those of the <sup>18</sup>F-FDG PET/CT group, and those of the <sup>18</sup>F-FDG PET/CT group were higher than those of the enhanced CT group (all P < 0.05). When the postoperative recurrent metastatic lesions of ovarian cancer were used as the study unit, the detection rate of lesions in the combined group was higher than that of the three examinations detected individually, and the detection rate of lesions in <sup>18</sup>F-FDG PET/CT was higher than that of enhanced CT and MRI (P < 0.05).</p><p><strong>Conclusion: </strong>The combination of MRI, enhanced CT and <sup>18</sup>F-FDG PET/CT can accurately diagnose recurrence and metastasis of ovarian cancer after surgery, detect recurrent metastatic lesions as early as possible, and improve patients' prognosis.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3013-3019"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multi-index comprehensive evaluation of the efficacy and response mechanism of immunotherapy in non-small cell lung cancer. 多指标综合评价免疫疗法对非小细胞肺癌的疗效和反应机制
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-01 DOI: 10.1007/s12094-024-03519-z
Jieqiong Fan, Tao Zhang

Objective: This research conducted multi-index comprehensive evaluations of the immunotherapeutic efficacy and response in non-small cell lung cancer (NSCLC).

Methods: Forty-five patients with epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) wild-type advanced NSCLC who received immunotherapy were included. Immunohistochemistry was adopted to detect the expression levels of programmed death ligand 1 (PD-L1) with X-ray cross-complementing protein 1 (XRCC1) and excision repair cross-complementing group 1 (ERCC1) proteins in tumor tissues. Flow cytometry was utilized to measure the levels of T-cell subsets in peripheral blood before and after treatment. PCR-RELP method was employed to evaluate XRCC1 and ERCC1 gene polymorphisms in peripheral blood. According to the treatment effect, patients evaluated as complete response (CR), partial response (PR), and stable disease (SD) were categorized into the immune response group, and patients evaluated as progressive disease (PD) were categorized into the immune unresponsive group. The correlation between PD-L1 protein expression, XRCC1 and ERCC1 protein expression, gene polymorphisms, T-cell subpopulation levels, and treatment efficacy was analyzed.

Results: The therapeutic efficacy of patients with positive PD-L1 expression was better than that of patients with negative PD-L1 expression (P < 0.05). After treatment, peripheral blood CD3+ and CD4+ cell levels and Thl/Th2 cell levels were higher and CD8+ T cells were lower in the immune response group than in the immune unresponsive group (P < 0.05). Among the patients in the immune response group, peripheral blood CD3+ and CD4+ cell levels were higher and CD8+ T cells were lower in patients with positive PD-L1 expression than in patients with negative PD-L1 expression (P < 0.05). In the XRCC1 gene, the proportion of patients in the immune response group carrying the Arg/Trp + Trp/Trp genotype was higher than that of patients in the immune unresponsive group (P < 0.05). In the ERCC1 gene, the proportion of patients in the immune response group carrying the C/T + T/T genotype was higher than that of patients in the immune unresponsive group (P < 0.05). The positive expression rates of XRCC1 and ERCC1 in patients in the immune unresponsive group were higher than those in the immune response group (P < 0.05).

Conclusion: PD-L1 protein expression, XRCC1 and ERCC1 protein expression, and gene polymorphisms are associated with immunotherapy outcome in EGFR/ALK wild-type advanced NSCLC patients, and may be biological indicators for predicting immunotherapy outcome in EGFR/ALK wild-type advanced NSCLC patients.

研究目的该研究对非小细胞肺癌(NSCLC)的免疫治疗效果和反应进行了多指标综合评价:纳入45例接受免疫治疗的表皮生长因子受体(EGFR)/无性淋巴瘤激酶(ALK)野生型晚期NSCLC患者。免疫组化法检测了肿瘤组织中程序性死亡配体1(PD-L1)、X射线交叉互补蛋白1(XRCC1)和切除修复交叉互补组1(ERCC1)蛋白的表达水平。流式细胞术用于测量治疗前后外周血中 T 细胞亚群的水平。采用 PCR-RELP 方法评估外周血中 XRCC1 和 ERCC1 基因的多态性。根据治疗效果,将完全应答(CR)、部分应答(PR)和病情稳定(SD)的患者分为免疫应答组,将病情进展(PD)的患者分为免疫无应答组。分析了PD-L1蛋白表达、XRCC1和ERCC1蛋白表达、基因多态性、T细胞亚群水平与疗效之间的相关性:PD-L1阳性表达患者的疗效优于PD-L1阴性表达患者(P +),免疫反应组的CD4+细胞水平和Thl/Th2细胞水平高于免疫无反应组(P +),CD4+细胞水平和CD8+T细胞水平低于PD-L1阴性表达组(P 结论:PD-L1阳性表达患者的疗效优于PD-L1阴性表达患者(P +),免疫反应组的CD4+细胞水平和Thl/Th2细胞水平高于免疫无反应组(P +),CD4+细胞水平和CD8+T细胞水平低于免疫无反应组(P +):PD-L1蛋白表达、XRCC1和ERCC1蛋白表达以及基因多态性与EGFR/ALK野生型晚期NSCLC患者的免疫治疗结果相关,可能是预测EGFR/ALK野生型晚期NSCLC患者免疫治疗结果的生物学指标。
{"title":"Multi-index comprehensive evaluation of the efficacy and response mechanism of immunotherapy in non-small cell lung cancer.","authors":"Jieqiong Fan, Tao Zhang","doi":"10.1007/s12094-024-03519-z","DOIUrl":"10.1007/s12094-024-03519-z","url":null,"abstract":"<p><strong>Objective: </strong>This research conducted multi-index comprehensive evaluations of the immunotherapeutic efficacy and response in non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>Forty-five patients with epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) wild-type advanced NSCLC who received immunotherapy were included. Immunohistochemistry was adopted to detect the expression levels of programmed death ligand 1 (PD-L1) with X-ray cross-complementing protein 1 (XRCC1) and excision repair cross-complementing group 1 (ERCC1) proteins in tumor tissues. Flow cytometry was utilized to measure the levels of T-cell subsets in peripheral blood before and after treatment. PCR-RELP method was employed to evaluate XRCC1 and ERCC1 gene polymorphisms in peripheral blood. According to the treatment effect, patients evaluated as complete response (CR), partial response (PR), and stable disease (SD) were categorized into the immune response group, and patients evaluated as progressive disease (PD) were categorized into the immune unresponsive group. The correlation between PD-L1 protein expression, XRCC1 and ERCC1 protein expression, gene polymorphisms, T-cell subpopulation levels, and treatment efficacy was analyzed.</p><p><strong>Results: </strong>The therapeutic efficacy of patients with positive PD-L1 expression was better than that of patients with negative PD-L1 expression (P < 0.05). After treatment, peripheral blood CD3<sup>+</sup> and CD4<sup>+</sup> cell levels and Thl/Th2 cell levels were higher and CD8<sup>+</sup> T cells were lower in the immune response group than in the immune unresponsive group (P < 0.05). Among the patients in the immune response group, peripheral blood CD3<sup>+</sup> and CD4<sup>+</sup> cell levels were higher and CD8<sup>+</sup> T cells were lower in patients with positive PD-L1 expression than in patients with negative PD-L1 expression (P < 0.05). In the XRCC1 gene, the proportion of patients in the immune response group carrying the Arg/Trp + Trp/Trp genotype was higher than that of patients in the immune unresponsive group (P < 0.05). In the ERCC1 gene, the proportion of patients in the immune response group carrying the C/T + T/T genotype was higher than that of patients in the immune unresponsive group (P < 0.05). The positive expression rates of XRCC1 and ERCC1 in patients in the immune unresponsive group were higher than those in the immune response group (P < 0.05).</p><p><strong>Conclusion: </strong>PD-L1 protein expression, XRCC1 and ERCC1 protein expression, and gene polymorphisms are associated with immunotherapy outcome in EGFR/ALK wild-type advanced NSCLC patients, and may be biological indicators for predicting immunotherapy outcome in EGFR/ALK wild-type advanced NSCLC patients.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3124-3130"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141187128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Constructing a prognostic model for colorectal cancer with synchronous liver metastases after preoperative chemotherapy: a study based on SEER and an external validation cohort. 构建术前化疗后同步肝转移的结直肠癌预后模型:基于 SEER 和外部验证队列的研究。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-04 DOI: 10.1007/s12094-024-03513-5
Yixin Ding, Xiaoxi Han, Shufen Zhao, Shasha Wang, Jing Guo, Chuanyu Leng, Xiangxue Li, Kongjia Wang, Wensheng Qiu, Weiwei Qi
<p><strong>Background: </strong>The combination of preoperative chemotherapy and surgical treatment has been shown to significantly enhance the prognosis of colorectal cancer with liver metastases (CRLM) patients. Nevertheless, as a result of variations in clinicopathological parameters, the prognosis of this particular group of patients differs considerably. This study aimed to develop and evaluate Cox proportional risk regression model and competing risk regression model using two patient cohorts. The goal was to provide a more precise and personalized prognostic evaluation system.</p><p><strong>Methods: </strong>We collected information on individuals who had a pathological diagnosis of colorectal cancer between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) Database. We obtained data from patients who underwent pathological diagnosis of colorectal cancer and got comprehensive therapy at the hospital between January 1, 2010, and June 1, 2022. The SEER data collected after screening according to the inclusion and exclusion criteria were separated into two cohorts: a training cohort (training cohort) and an internal validation cohort (internal validation cohort), using a random 1:1 split. Subgroup Kaplan-Meier (K-M) survival analyses were conducted on each of the three groups. The data that received following screening from the hospital were designated as the external validation cohort. The subsequent variables were chosen for additional examination: age, gender, marital status, race, tumor site, pretreatment carcinoembryonic antigen level, tumor size, T stage, N stage, pathological grade, number of tumor deposits, perineural invasion, number of regional lymph nodes examined, and number of positive regional lymph nodes. The primary endpoint was median overall survival (mOS). In the training cohort, we conducted univariate Cox regression analysis and utilized a stepwise regression approach, employing the Akaike information criterion (AIC) to select variables and create Cox proportional risk regression models. We evaluated the accuracy of the model using calibration curve, receiver operating characteristic curve (ROC), and area under curve (AUC). The effectiveness of the models was assessed using decision curve analysis (DCA). To evaluate the non-cancer-related outcomes, we analyzed variables that had significant impacts using subgroup cumulative incidence function (CIF) and Gray's test. These analyses were used to create competing risk regression models. Nomograms of the two models were constructed separately and prognostic predictions were made for the same patients in SEER database.</p><p><strong>Results: </strong>This study comprised a total of 735 individuals. The mOS of the training cohort, internal validation cohort, and QDU cohort was 55.00 months (95%CI 46.97-63.03), 48.00 months (95%CI 40.65-55.35), and 68.00 months (95%CI 54.91-81.08), respectively. The multivariate Cox regression analysis revealed that age, N
背景:事实证明,术前化疗和手术治疗相结合可显著改善伴肝转移的结直肠癌(CRLM)患者的预后。然而,由于临床病理参数的不同,这一特殊群体患者的预后也有很大差异。本研究旨在利用两个患者队列建立并评估 Cox 比例风险回归模型和竞争风险回归模型。目的是提供一个更精确、更个性化的预后评估系统:我们从监测、流行病学和最终结果(SEER)数据库中收集了 2000 年至 2019 年期间病理诊断为结直肠癌的患者信息。我们从 2010 年 1 月 1 日至 2022 年 6 月 1 日期间接受病理诊断并在医院接受综合治疗的结直肠癌患者中获取数据。根据纳入和排除标准进行筛选后收集的 SEER 数据被分成两个队列:训练队列(training cohort)和内部验证队列(internal validation cohort),采用 1:1 随机分割法。对三个组别分别进行了分组卡普兰-梅耶(K-M)生存分析。医院筛查后获得的数据被指定为外部验证队列。我们选择了以下变量进行额外检查:年龄、性别、婚姻状况、种族、肿瘤部位、治疗前癌胚抗原水平、肿瘤大小、T分期、N分期、病理分级、肿瘤沉积数量、神经周围侵犯、区域淋巴结检查数量和区域淋巴结阳性数量。主要终点是中位总生存期(mOS)。在训练队列中,我们进行了单变量考克斯回归分析,并采用逐步回归法,利用阿凯克信息准则(AIC)选择变量并创建考克斯比例风险回归模型。我们使用校准曲线、接收者工作特征曲线(ROC)和曲线下面积(AUC)来评估模型的准确性。利用决策曲线分析(DCA)评估了模型的有效性。为了评估与癌症无关的结果,我们使用亚组累积发生率函数(CIF)和格雷氏检验分析了具有显著影响的变量。这些分析用于创建竞争风险回归模型。分别构建了两个模型的提名图,并对 SEER 数据库中的相同患者进行了预后预测:本研究共纳入 735 人。训练队列、内部验证队列和 QDU 队列的 mOS 分别为 55.00 个月(95%CI 46.97-63.03)、48.00 个月(95%CI 40.65-55.35)和 68.00 个月(95%CI 54.91-81.08)。多变量 Cox 回归分析显示,年龄、N 分期、是否存在神经周围浸润、肿瘤沉积物数量和阳性区域淋巴结数量被确定为独立的预后风险变量(p 结论:我们建立了一个预后模型,用于预测接受术前化疗和手术的同步性 CRLM 患者的生存率。该模型已经过内部和外部测试,证实了其准确性和可靠性。
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引用次数: 0
Clinical effects of re-evaluating a lung SBRT failure mode and effects analysis in a radiotherapy department. 放疗科重新评估肺部 SBRT 失败模式及影响分析的临床效果。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-03 DOI: 10.1007/s12094-024-03539-9
Sergi Benavente, Alexandra Giraldo, Alejandro Seoane, Mónica Ramos, Ramona Vergés

Purpose: The increasing complexity of radiation treatments can hinder its clinical success. This study aimed to better understand evolving risks by re-evaluating a Failure Mode and Effects Analysis (FMEA) in lung SBRT.

Methods: An experienced multidisciplinary team conducted an FMEA and made a reassessment 3 years later. A process map was developed with potential failure modes (FMs) identified. High-risk FMs and their possible causes and corrective actions were determined. The initial FMEA analysis was compared to gain a deeper perspective.

Results: We identified 232 FMs. The high-risk processes were plan approval, target contouring, and patient evaluation. The corrective measures were based on stricter standardization of plan approval, pre-planning peer review, and a supporting pretreatment checklist, which substantially reduced the risk priority number in the revised FMEA. In the FMEA reassessment, we observed that the increased complexity and number of patients receiving lung SBRT conditioned a more substantial presence of human factors and communication errors as causal conditions and a potential wrong dose as a final effect.

Conclusions: Conducting a lung SBRT FMEA analysis has identified high-risk conditions that have been effectively mitigated in an FMEA reanalysis. Plan approval has shown to be a weak link in the process. The increasing complexity of treatments and patient numbers have shifted causal factors toward human failure and communication errors. The potential of a wrong dose as a final effect augments in this scenario. We propose that digital and artificial intelligence options are needed to mitigate potential errors in high-complexity and high-risk RT scenarios.

目的:放射治疗的复杂性不断增加,可能会阻碍其临床成功。本研究旨在通过重新评估肺部 SBRT 的故障模式和影响分析 (FMEA),更好地了解不断变化的风险:一个经验丰富的多学科团队进行了一次 FMEA 分析,并在 3 年后进行了重新评估。绘制了流程图,确定了潜在的故障模式(FMs)。确定了高风险故障模式及其可能的原因和纠正措施。对最初的 FMEA 分析进行比较,以获得更深入的视角:结果:我们确定了 232 个故障模式。结果:我们发现了 232 个故障,其中高风险流程包括计划审批、目标轮廓和患者评估。纠正措施基于更严格的计划审批标准化、计划前同行评审和支持性预处理清单,这大大降低了经修订的 FMEA 中的风险优先级编号。在对 FMEA 的重新评估中,我们注意到,接受肺部 SBRT 治疗的患者的复杂性和数量增加,人为因素和沟通错误作为因果条件的存在更为严重,而潜在的错误剂量则是最终影响因素:进行肺部 SBRT FMEA 分析发现了高风险情况,这些情况在 FMEA 重新分析中得到了有效缓解。计划审批是整个流程中的薄弱环节。治疗的复杂性和患者人数的增加使人为失误和沟通错误成为致因。在这种情况下,错误剂量作为最终结果的可能性会增加。我们建议需要数字和人工智能方案来减少高复杂性和高风险 RT 方案中的潜在错误。
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引用次数: 0
Stereotactic ablative radiotherapy (SABR) for patients with lung tumor and severe pulmonary function impairment. 为肺部肿瘤和肺功能严重受损的患者提供立体定向消融放射治疗(SABR)。
IF 2.8 3区 医学 Q2 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-13 DOI: 10.1007/s12094-024-03557-7
Abraham André Arturo Geng-Cahuayme, Blanca Peregrín-Pastor, Mónica Ramos-Albiac, Enar Recalde-Vizcay, Juan Sebastián Parada-Zuluaga, Jordi Giralt-López de Sagredo, Xavier Maldonado-Pijoan, Alexandra Giraldo-Marín

Purpose: To evaluate clinical outcomes after SABR in a cohort of early-stage non-small cell lung cancer (NSCLC) or pulmonary metastases in chronic obstructive pulmonary disease (COPD) patients with forced expiratory volume in the first second predicted (FEV1) ≤ 50%.

Methods: Retrospective single-center study was performed to analyze clinical outcomes and toxicities in COPD patients with severe lung dysfunction treated with SABR from 1st June 2015 to 31st October 2022.

Results: Thirty four patients (forty locations) were enrolled for analysis. Median follow-up was 2.9 years. Median age was 73.5 years (range, 65.6-80.1). FEV1 was 38% (range, 28.2-50.0) prior to radiotherapy. Median overall survival (OS) was 41.1 months (95% CI 38.9-not reached). OS rates at 2-, 3-, and 5- years were 79%, 71%, and 36%, respectively. Cancer-specific survival rates at 2-, 3-, and 5- years were 96%, 96%, and 68%, respectively. Local control rates at 2-, 3-, and 5- years were 88%, 83%, and 83%, respectively. No grade 4 or 5 toxicity was observed. The most common acute toxicity was pneumonitis (38.2%), of which only 1 patient (2.9%) reported grade 3 acute toxicity.

Conclusions: Lung SABR in patients with poor pulmonary function may be effective with acceptable toxicity.

目的:评估第一秒用力呼气容积(FEV1)预测值≤50%的慢性阻塞性肺病(COPD)早期非小细胞肺癌(NSCLC)或肺转移患者SABR治疗后的临床疗效:回顾性单中心研究,分析2015年6月1日至2022年10月31日期间接受SABR治疗的严重肺功能障碍COPD患者的临床结果和毒性反应:34名患者(40个地点)被纳入分析。中位随访时间为 2.9 年。中位年龄为 73.5 岁(65.6-80.1 岁)。放疗前FEV1为38%(范围为28.2-50.0)。中位总生存期(OS)为 41.1 个月(95% CI 38.9-未达到)。2年、3年和5年的OS率分别为79%、71%和36%。2年、3年和5年的癌症特异性生存率分别为96%、96%和68%。2年、3年和5年的局部控制率分别为88%、83%和83%。未观察到 4 级或 5 级毒性。最常见的急性毒性是肺炎(38.2%),其中只有一名患者(2.9%)报告了3级急性毒性:结论:对肺功能较差的患者进行肺SABR可能有效,且毒性可接受。
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引用次数: 0
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Clinical & Translational Oncology
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