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Pancreatic ductal adenocarcinoma: exploring clinicopathological trends and racial disparities in a comprehensive U.S. population-based study 胰腺导管腺癌:在一项基于美国人口的综合研究中探索临床病理学趋势和种族差异
Pub Date : 2024-04-14 DOI: 10.1007/s12094-024-03484-7
Abdul Qahar Khan Yasinzai, Bisma Tareen, Katharine Tracy, Nimra Jamil, Marjan Khan, Hafeez Ullah, Muhammad Raza, Amin Ullah Khan, Dauod Arif, Abdul Waheed, Feroze Sidhwa, Subhasis Misra, Nabin Raj Karki, Nagla Abdel Karim, Ludimila Cavalcante, Asad Ullah

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy about 50% of PDAC are metastatic at presentation. In this study, we evaluated PDAC demographics, annual trend analysis, racial disparities, survival rate, and the role of different treatment modalities in localized and metastatic disease.

Methods

A total of 144,824 cases of PDAC were obtained from the SEER database from 2000 to 2018.

Results

The median age was 69 years, with a slightly higher incidence in males (52%) and 80% of all cases were white. Among cases with available data, 43% were grade III tumors and 57% were metastatic. The most common site of metastasis was the liver (15.7%). The annual incidence has increased steadily from 2000 to 2018. The overall observed (OS) 5-year survival rate was 4.4% (95% CI 4.3–4.6%), and 5 years cause-specific survival (CSS) was 5% (95% CI 5.1–5.4%). The 5-year survival with multimodal therapy (chemotherapy, surgery, and radiation) was 22% (95% CI 20.5–22.8%). 5-year CSS for the blacks was lower at 4.7% (95% CI 4.2–5.1%) compared to the whites at 5.3% (95% CI 5.1–5.4%). Multivariate analysis found male gender and black race associated with worse prognosis. Kaplan–Meier survival analysis found multimodal therapy to have the best outcomes in all three stages.

Conclusion

PDAC is an aggressive malignancy with male gender and black race are associated with a poor prognosis. Surgery with chemoradiation was associated with the best overall survival. With steadily increasing rates of PDAC, improved treatment modalities are paramount to improving survival in these patients.

导言胰腺导管腺癌(PDAC)是一种侵袭性极强的恶性肿瘤,约 50% 的 PDAC 在发病时已发生转移。在这项研究中,我们评估了PDAC的人口统计学、年度趋势分析、种族差异、存活率以及不同治疗方式在局部和转移性疾病中的作用。结果中位年龄为69岁,男性发病率略高(52%),80%的病例为白人。在有数据可查的病例中,43%为III级肿瘤,57%为转移性肿瘤。最常见的转移部位是肝脏(15.7%)。从2000年到2018年,年发病率稳步上升。总体观察(OS)5年生存率为4.4%(95% CI 4.3-4.6%),5年病因特异性生存率(CSS)为5%(95% CI 5.1-5.4%)。采用多模式疗法(化疗、手术和放疗)的 5 年生存率为 22%(95% CI 20.5-22.8%)。黑人的5年CSS为4.7%(95% CI为4.2-5.1%),低于白人的5.3%(95% CI为5.1-5.4%)。多变量分析发现,男性和黑人的预后较差。Kaplan-Meier生存分析发现,在所有三个分期中,多模式疗法的疗效最好。手术联合化疗的总生存率最高。随着PDAC发病率的稳步上升,改进治疗方法对提高这些患者的生存率至关重要。
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引用次数: 0
Prevalence and risk factors of thyroid nodules in breast cancer women with different clinicopathological characteristics: a cross-sectional study 具有不同临床病理特征的乳腺癌妇女甲状腺结节的患病率和风险因素:一项横断面研究
Pub Date : 2024-04-12 DOI: 10.1007/s12094-024-03488-3
Chen-yu Ma, Xin-yu Liang, Liang Ran, Lei Hu, Fan-ling Zeng, Rui-ling She, Jun-han Feng, Zhi-yu Jiang, Zhao-xing Li, Xiu-quan Qu, Bai-qing Peng, Kai-nan Wu, Ling-quan Kong

Background

Association between breast cancer (BC) and thyroid nodules (TNs) is still unclear. This research was to estimate the prevalence and risk factors of TN in Chinese BC women at initial diagnosis.

Methods

1731 Chinese early-stage BC women at initial diagnosis underwent thyroid ultrasound and 1:1 age-matched Chinese healthy women underwent health examination in corresponding period were enrolled for analysis.

Results

Prevalence of TN and TI-RADS ≥ 4 TN in BC patients (56.27% and 9.76%) were higher than healthy people (46.04% and 5.49%), respectively, P < 0.001. Among BC patients, prevalence of TN and TI-RADS ≥ 4 TN in hormone receptor (HR)-positive patients (59.57% and 11.81%) were higher than HR-negative patients (48.77% and 5.10%), respectively, P < 0.001, while without difference between HR-negative patients and healthy people. After adjusting for age and BMI, HR-positive patients had higher risk of TN (OR = 1.546, 95%CI 1.251–1.910, P < 0.001) and TI-RADS ≥ 4 TN (OR = 3.024, 95%CI 1.943–4.708, P < 0.001) than HR-negative patients. Furthermore, the risk of TI-RADS ≥ 4 TN was higher in patients with estrogen receptor (ER) positive (OR = 2.933, 95%CI 1.902–4.524), progesterone receptor (PR) positive (OR = 1.973, 95%CI 1.378–2.826), Ki-67 < 20% (OR = 1.797, 95%CI 1.280–2.522), and tumor size < 2 cm (OR = 1.804, 95%CI 1.276–2.552), respectively, P < 0.001.

Conclusions

Prevalence of TN, especially TI-RADS ≥ 4 TN, in Chinese early-stage BC women was higher than healthy people. HR-positive patients had higher prevalence and risk of TN, while without difference between HR-negative patients and healthy people. The increased risk of TN was correlated with ER-positive, PR-positive, lower Ki-67 expression, and smaller tumor size.

背景乳腺癌(BC)与甲状腺结节(TNs)之间的关系尚不清楚。方法1731名初诊的中国早期BC女性接受甲状腺超声检查,并与1:1年龄匹配的中国健康女性接受同期健康检查进行分析。结果BC患者TN和TI-RADS≥4 TN的患病率(56.27%和9.76%)分别高于健康人群(46.04%和5.49%),P < 0.001。在 BC 患者中,激素受体(HR)阳性患者 TN 和 TI-RADS ≥ 4 TN 的发生率(59.57% 和 11.81%)分别高于 HR 阴性患者(48.77% 和 5.10%),P< 0.001,而 HR 阴性患者与健康人之间无差异。调整年龄和体重指数后,HR 阳性患者比 HR 阴性患者有更高的 TN 风险(OR = 1.546,95%CI 1.251-1.910,P < 0.001)和 TI-RADS ≥ 4 TN 风险(OR = 3.024,95%CI 1.943-4.708,P < 0.001)。此外,雌激素受体(ER)阳性(OR = 2.933,95%CI 1.902-4.524)、孕激素受体(PR)阳性(OR = 1.973,95%CI 1.378-2.826)、Ki-67 < 20% (OR = 1.797,95%CI 1.280-2.522),肿瘤大小< 2 cm(OR = 1.804,95%CI 1.276-2.552),P< 0.001.结论中国早期BC女性TN,尤其是TI-RADS≥4 TN的患病率高于健康人群。HR阳性患者的TN患病率和患病风险均较高,而HR阴性患者与健康人之间无差异。TN风险的增加与ER阳性、PR阳性、较低的Ki-67表达和较小的肿瘤大小相关。
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引用次数: 0
Exploring research progress in studying serum exosomal miRNA-21 as a molecular diagnostic marker for breast cancer 探索将血清外泌体 miRNA-21 作为乳腺癌分子诊断标志物的研究进展
Pub Date : 2024-04-11 DOI: 10.1007/s12094-024-03454-z
Hang Li, Xiao-jing Tie

Breast cancer is one of the most prevalent malignancies affecting women globally and poses a significant public health challenge. Early clinical detection plays a pivotal role in providing optimal treatment opportunities and favorable prognoses, crucial for reducing breast cancer mortality and enhancing patients’ quality of life. Therefore, the timely identification and diagnosis of breast cancer are imperative. Conventional tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3), serve as reliable methods for actively monitoring disease progression and have become a routine auxiliary diagnostic approach in clinical settings. However, these biomarkers exhibit limitations in sensitivity and specificity, particularly in the early screening and diagnosis of tumors, often yielding results inconsistent with clinical manifestations. In recent years, research has increasingly focused on exosomes released by tumor cells as potential new biomarkers for early stage breast cancer screening. Exosomes carry various components, including tumor-derived proteins, nucleic acids, and lipids. This paper delves into the specific utilization of serum exosomal microRNA-21 (miR-21) as a biomarker for early detection and diagnosis of breast cancer, evaluating its efficacy within this framework.

乳腺癌是影响全球妇女最普遍的恶性肿瘤之一,对公共卫生构成重大挑战。早期临床检测在提供最佳治疗机会和良好预后方面发挥着关键作用,对于降低乳腺癌死亡率和提高患者生活质量至关重要。因此,及时发现和诊断乳腺癌势在必行。传统的肿瘤标志物,如癌胚抗原(CEA)和碳水化合物抗原 15-3(CA15-3),是积极监测疾病进展的可靠方法,已成为临床上常规的辅助诊断方法。然而,这些生物标志物在灵敏度和特异性方面存在局限性,尤其是在肿瘤的早期筛查和诊断中,其结果往往与临床表现不一致。近年来,越来越多的研究关注肿瘤细胞释放的外泌体,将其作为早期乳腺癌筛查的潜在新生物标记物。外泌体携带多种成分,包括肿瘤衍生蛋白、核酸和脂质。本文探讨了血清外泌体 microRNA-21 (miR-21) 作为乳腺癌早期检测和诊断生物标记物的具体用途,并在此框架内评估了其功效。
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引用次数: 0
Explainable and visualizable machine learning models to predict biochemical recurrence of prostate cancer 预测前列腺癌生化复发的可解释和可视化机器学习模型
Pub Date : 2024-04-11 DOI: 10.1007/s12094-024-03480-x
Wenhao Lu, Lin Zhao, Shenfan Wang, Huiyong Zhang, Kangxian Jiang, Jin Ji, Shaohua Chen, Chengbang Wang, Chunmeng Wei, Rongbin Zhou, Zuheng Wang, Xiao Li, Fubo Wang, Xuedong Wei, Wenlei Hou

Purpose

Machine learning (ML) models presented an excellent performance in the prognosis prediction. However, the black box characteristic of ML models limited the clinical applications. Here, we aimed to establish explainable and visualizable ML models to predict biochemical recurrence (BCR) of prostate cancer (PCa).

Materials and methods

A total of 647 PCa patients were retrospectively evaluated. Clinical parameters were identified using LASSO regression. Then, cohort was split into training and validation datasets with a ratio of 0.75:0.25 and BCR-related features were included in Cox regression and five ML algorithm to construct BCR prediction models. The clinical utility of each model was evaluated by concordance index (C-index) values and decision curve analyses (DCA). Besides, Shapley Additive Explanation (SHAP) values were used to explain the features in the models.

Results

We identified 11 BCR-related features using LASSO regression, then establishing five ML-based models, including random survival forest (RSF), survival support vector machine (SSVM), survival Tree (sTree), gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and a Cox regression model, C-index were 0.846 (95%CI 0.796–0.894), 0.774 (95%CI 0.712–0.834), 0.757 (95%CI 0.694–0.818), 0.820 (95%CI 0.765–0.869), 0.793 (95%CI 0.735–0.852), and 0.807 (95%CI 0.753–0.858), respectively. The DCA showed that RSF model had significant advantages over all models. In interpretability of ML models, the SHAP value demonstrated the tangible contribution of each feature in RSF model.

Conclusions

Our score system provide reference for the identification for BCR, and the crafting of a framework for making therapeutic decisions for PCa on a personalized basis.

目的机器学习(ML)模型在预后预测方面表现出色。然而,ML 模型的黑箱特性限制了其临床应用。在此,我们旨在建立可解释、可视化的 ML 模型,以预测前列腺癌(PCa)的生化复发(BCR)。采用 LASSO 回归法确定临床参数。然后,以0.75:0.25的比例将队列分成训练数据集和验证数据集,并将BCR相关特征纳入Cox回归和五种ML算法,以构建BCR预测模型。通过一致性指数(C-index)值和决策曲线分析(DCA)评估每个模型的临床实用性。结果我们利用 LASSO 回归确定了 11 个 BCR 相关特征,然后建立了 5 个基于 ML 的模型,包括随机生存森林(RSF)、生存支持向量机(SSVM)、生存树(sTree)、梯度提升决策树(GBDT)、极端梯度提升(XGBoost)和 Cox 回归模型,C-index 分别为 0.846(95%CI 0.796-0.894)、0.774(95%CI 0.712-0.834)、0.757(95%CI 0.694-0.818)、0.820(95%CI 0.765-0.869)、0.793(95%CI 0.735-0.852)和 0.807(95%CI 0.753-0.858)。DCA 结果表明,RSF 模型与所有模型相比具有显著优势。结论我们的评分系统为确定 BCR 提供了参考,并为制定个性化的 PCa 治疗决策提供了框架。
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引用次数: 0
Clinical features and treatment outcomes of PD-1 inhibitor therapy in elderly patients (≥ 65 years) with advanced esophageal squamous cell carcinoma: a real-world study 晚期食管鳞状细胞癌老年患者(≥ 65 岁)的临床特征和 PD-1 抑制剂治疗效果:一项真实世界研究
Pub Date : 2024-04-11 DOI: 10.1007/s12094-024-03453-0
Yi Yu, Tao Wu, Wei Gan, Can Liu, Ran Zhang, Jinxiu Zheng, Jianping Xiong, Jun Chen, Junhe Li

Purpose

This study aims to determine the clinical features and outcomes of PD-1 inhibitor therapy as the initial treatment in patients aged 65 years or older with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC).

Materials and methods

The retrospective study conducted a comprehensive analysis of elder patients diagnosed with locally advanced or metastatic ESCC who underwent combined immunochemotherapy in the first affiliated hospital of Nanchang University from January 2019 to January 2023. The main efficacy measures were the objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints were disease control rate (DCR) and overall survival (OS). The evaluation of safety was based on the assessment of adverse events (AEs).

Results

A total of 88 patients were enrolled in the study. All patients received PD-1 inhibitors combined with chemotherapy including taxane and platinum as the first-line treatment. The median PFS was 6.2 months (95% CI: 5.1–7.3), and the median OS was 15.3 months (95% CI: 12.9–17.7). The ORR and DCR were 42.0% and 72.7%, correspondingly. 68 (77.3%) patients experienced treatment-related adverse events (TRAEs) of various degrees, with neutrophil count decreased (21, 23.9%) being the most frequent. TRAEs of grade 3 or 4 occurred in 13 (14.8%) patients.

Conclusion

The study demonstrated that individuals older than 65 years with locally advanced or metastatic ESCC have a survival benefit from the first-line treatment of PD-1 inhibitors combined therapy, with a manageable safety profile.

目的本研究旨在确定PD-1抑制剂治疗作为65岁或以上局部晚期或转移性食管鳞状细胞癌(ESCC)患者初始治疗的临床特征和疗效。材料和方法本回顾性研究对2019年1月至2023年1月在南昌大学第一附属医院接受联合免疫化疗的确诊为局部晚期或转移性ESCC的老年患者进行了全面分析。主要疗效指标为客观反应率(ORR)和无进展生存期(PFS)。次要终点为疾病控制率(DCR)和总生存期(OS)。安全性评估基于不良事件(AEs)的评估。所有患者均接受了PD-1抑制剂联合化疗(包括紫杉类药物和铂类药物)的一线治疗。中位PFS为6.2个月(95% CI:5.1-7.3),中位OS为15.3个月(95% CI:12.9-17.7)。ORR和DCR分别为42.0%和72.7%。68例(77.3%)患者出现了不同程度的治疗相关不良事件(TRAEs),其中以中性粒细胞计数下降(21例,23.9%)最为常见。结论该研究表明,65 岁以上的局部晚期或转移性 ESCC 患者可从 PD-1 抑制剂联合疗法的一线治疗中获得生存获益,且安全性可控。
{"title":"Clinical features and treatment outcomes of PD-1 inhibitor therapy in elderly patients (≥ 65 years) with advanced esophageal squamous cell carcinoma: a real-world study","authors":"Yi Yu, Tao Wu, Wei Gan, Can Liu, Ran Zhang, Jinxiu Zheng, Jianping Xiong, Jun Chen, Junhe Li","doi":"10.1007/s12094-024-03453-0","DOIUrl":"https://doi.org/10.1007/s12094-024-03453-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>This study aims to determine the clinical features and outcomes of PD-1 inhibitor therapy as the initial treatment in patients aged 65 years or older with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC).</p><h3 data-test=\"abstract-sub-heading\">Materials and methods</h3><p>The retrospective study conducted a comprehensive analysis of elder patients diagnosed with locally advanced or metastatic ESCC who underwent combined immunochemotherapy in the first affiliated hospital of Nanchang University from January 2019 to January 2023. The main efficacy measures were the objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints were disease control rate (DCR) and overall survival (OS). The evaluation of safety was based on the assessment of adverse events (AEs).</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 88 patients were enrolled in the study. All patients received PD-1 inhibitors combined with chemotherapy including taxane and platinum as the first-line treatment. The median PFS was 6.2 months (95% CI: 5.1–7.3), and the median OS was 15.3 months (95% CI: 12.9–17.7). The ORR and DCR were 42.0% and 72.7%, correspondingly. 68 (77.3%) patients experienced treatment-related adverse events (TRAEs) of various degrees, with neutrophil count decreased (21, 23.9%) being the most frequent. TRAEs of grade 3 or 4 occurred in 13 (14.8%) patients.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The study demonstrated that individuals older than 65 years with locally advanced or metastatic ESCC have a survival benefit from the first-line treatment of PD-1 inhibitors combined therapy, with a manageable safety profile.</p>","PeriodicalId":10166,"journal":{"name":"Clinical and Translational Oncology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140584806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Heterogeneity and interplay: the multifaceted role of cancer-associated fibroblasts in the tumor and therapeutic strategies 异质性与相互作用:癌症相关成纤维细胞在肿瘤中的多方面作用及治疗策略
Pub Date : 2024-04-11 DOI: 10.1007/s12094-024-03492-7
Qiaoqiao Liu, Fei Yao, Liangliang Wu, Tianyuan Xu, Jintong Na, Zhen Shen, Xiyu Liu, Wei Shi, Yongxiang Zhao, Yuan Liao

The journey of cancer development is a multifaceted and staged process. The array of treatments available for cancer varies significantly, dictated by the disease's type and stage. Cancer-associated fibroblasts (CAFs), prevalent across various cancer types and stages, play a pivotal role in tumor genesis, progression, metastasis, and drug resistance. The strategy of concurrently targeting cancer cells and CAFs holds great promise in cancer therapy. In this review, we focus intently on CAFs, delving into their critical role in cancer's progression. We begin by exploring the origins, classification, and surface markers of CAFs. Following this, we emphasize the key cytokines and signaling pathways involved in the interplay between cancer cells and CAFs and their influence on the tumor immune microenvironment. Additionally, we examine current therapeutic approaches targeting CAFs. This article underscores the multifarious roles of CAFs within the tumor microenvironment and their potential applications in cancer treatment, highlighting their importance as key targets in overcoming drug resistance and enhancing the efficacy of tumor therapies.

癌症的发展历程是一个多方面、分阶段的过程。癌症的类型和阶段不同,治疗方法也大相径庭。癌症相关成纤维细胞(CAFs)普遍存在于各种癌症类型和阶段,在肿瘤发生、发展、转移和耐药性方面起着关键作用。同时靶向癌细胞和成纤维细胞的策略在癌症治疗中大有可为。在这篇综述中,我们将重点关注 CAFs,深入研究它们在癌症进展中的关键作用。我们首先探讨了 CAFs 的起源、分类和表面标志物。随后,我们强调了癌细胞与 CAFs 之间相互作用所涉及的关键细胞因子和信号通路,以及它们对肿瘤免疫微环境的影响。此外,我们还探讨了目前针对 CAFs 的治疗方法。本文强调了 CAFs 在肿瘤微环境中的多种作用及其在癌症治疗中的潜在应用,突出了它们作为克服耐药性和提高肿瘤疗法疗效的关键靶点的重要性。
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引用次数: 0
Effect of immune checkpoint inhibitors at different treatment time periods on prognosis of patients with extensive-stage small-cell lung cancer 不同治疗时间段的免疫检查点抑制剂对广泛期小细胞肺癌患者预后的影响
Pub Date : 2024-04-10 DOI: 10.1007/s12094-024-03471-y
Song Mi, Yunxin Yang, Xin Liu, Shaotong Tang, Ning Liang, Jinyue Sun, Chao Liu, Qidong Ren, Jihong Lu, Pingping Hu, Jiandong Zhang

Background

The application of immune checkpoint inhibitors (ICIs) in treating patients with extensive-stage small-cell lung cancer (ES-SCLC) has brought us new hope, but the real-world outcome is relatively lacking. Our aim was to investigate the clinical use, efficacy, and survival benefit of ICIs in ES-SCLC from real-world data analysis.

Methods

A retrospective analysis of ES-SCLC patients was conducted between 2012 and 2022. Progression-free survival (PFS) and overall survival (OS) were assessed between groups to evaluate the value of ICIs at different lines of treatment. PFS1 was defined as the duration from initial therapy to disease progression or death. PFS2 was defined as the duration from the first disease progression to the second disease progression or death.

Results

One hundred and eighty patients with ES-SCLC were included. We performed landmark analysis, which showed that compared to the second-line and subsequent-lines ICIs-combined therapy group (2SL-ICIs) and non-ICIs group, the first-line ICIs-combined therapy group (1L-ICIs) prolonged OS and PFS1. There was a trend toward prolonged OS in the 2SL-ICIs group than in the non-ICIs group, but the significance threshold was not met (median OS 11.94 months vs. 11.10 months, P = 0.14). A longer PFS2 was present in the 2SL-ICIs group than in the non-ICIs group (median PFS2 4.13 months vs. 2.60 months, P < 0.001).

Conclusion

First-line ICIs plus chemotherapy should be applied in clinical practice. If patients did not use ICIs plus chemotherapy in first-line therapy, the use of ICIs in the second line or subsequent lines of treatment could prolong PFS2.

背景免疫检查点抑制剂(ICIs)在治疗广泛期小细胞肺癌(ES-SCLC)患者中的应用给我们带来了新的希望,但真实世界的结果却相对缺乏。我们的目的是通过真实世界的数据分析,研究 ICIs 在 ES-SCLC 中的临床应用、疗效和生存获益。对不同组间的无进展生存期(PFS)和总生存期(OS)进行评估,以评价ICIs在不同治疗方案中的价值。PFS1定义为从初始治疗到疾病进展或死亡的持续时间。结果 共纳入180例ES-SCLC患者。我们进行了标志性分析,结果显示,与二线及后续线 ICIs 联合治疗组(2SL-ICIs)和非 ICIs 组相比,一线 ICIs 联合治疗组(1L-ICIs)延长了 OS 和 PFS1。与非 ICIs 组相比,2SL-ICIs 组有延长 OS 的趋势,但未达到显著性阈值(中位 OS 11.94 个月 vs. 11.10 个月,P = 0.14)。2SL-ICIs组的PFS2长于非ICIs组(中位PFS2为4.13个月 vs. 2.60个月,P < 0.001)。如果患者在一线治疗中没有使用 ICIs 加化疗,那么在二线或后续治疗中使用 ICIs 可延长 PFS2。
{"title":"Effect of immune checkpoint inhibitors at different treatment time periods on prognosis of patients with extensive-stage small-cell lung cancer","authors":"Song Mi, Yunxin Yang, Xin Liu, Shaotong Tang, Ning Liang, Jinyue Sun, Chao Liu, Qidong Ren, Jihong Lu, Pingping Hu, Jiandong Zhang","doi":"10.1007/s12094-024-03471-y","DOIUrl":"https://doi.org/10.1007/s12094-024-03471-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>The application of immune checkpoint inhibitors (ICIs) in treating patients with extensive-stage small-cell lung cancer (ES-SCLC) has brought us new hope, but the real-world outcome is relatively lacking. Our aim was to investigate the clinical use, efficacy, and survival benefit of ICIs in ES-SCLC from real-world data analysis.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>A retrospective analysis of ES-SCLC patients was conducted between 2012 and 2022. Progression-free survival (PFS) and overall survival (OS) were assessed between groups to evaluate the value of ICIs at different lines of treatment. PFS1 was defined as the duration from initial therapy to disease progression or death. PFS2 was defined as the duration from the first disease progression to the second disease progression or death.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>One hundred and eighty patients with ES-SCLC were included. We performed landmark analysis, which showed that compared to the second-line and subsequent-lines ICIs-combined therapy group (2SL-ICIs) and non-ICIs group, the first-line ICIs-combined therapy group (1L-ICIs) prolonged OS and PFS1. There was a trend toward prolonged OS in the 2SL-ICIs group than in the non-ICIs group, but the significance threshold was not met (median OS 11.94 months vs. 11.10 months, <i>P</i> = 0.14). A longer PFS2 was present in the 2SL-ICIs group than in the non-ICIs group (median PFS2 4.13 months vs. 2.60 months, <i>P</i> &lt; 0.001).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>First-line ICIs plus chemotherapy should be applied in clinical practice. If patients did not use ICIs plus chemotherapy in first-line therapy, the use of ICIs in the second line or subsequent lines of treatment could prolong PFS2.</p>","PeriodicalId":10166,"journal":{"name":"Clinical and Translational Oncology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140584456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of TET2 in solid tumors and its therapeutic potential: a comprehensive review TET2 在实体瘤中的作用及其治疗潜力:全面综述
Pub Date : 2024-04-10 DOI: 10.1007/s12094-024-03478-5
Wenxin Da, Ziyu Song, Xiaodong Liu, Yahui Wang, Shengjun Wang, Jie Ma

Indeed, tumors are a significant health concern worldwide, and understanding the underlying mechanisms of tumor development is crucial for effective prevention and treatment. Epigenetics, which refers to changes in gene expression that are not caused by alterations in the DNA sequence itself, plays a critical role in the entire process of tumor development. It goes without saying that the effect of methylation on tumors is a significant aspect of epigenetics. Among the methylation modifications, DNA methylation is an important part, which plays a regulatory role in tumor-related genes. Ten-eleven translocation 2 (TET2) is a highly influential protein involved in the modification of DNA methylation. Its primary role is associated with the suppression of tumor development, making it a significant player in cancer research. However, TET2 is frequently mentioned in hematological diseases, its role in solid tumors has received little attention. Studying the changes of TET2 in solid tumors and the regulatory mechanism will facilitate its investigation as a clinical target for targeted therapy and may also provide directions for clinical treatment of malignant tumors.

事实上,肿瘤是全球关注的重大健康问题,而了解肿瘤发生的内在机制对于有效预防和治疗肿瘤至关重要。表观遗传学(Epigenetics)是指并非由 DNA 序列本身的改变引起的基因表达变化,它在肿瘤发生发展的整个过程中起着至关重要的作用。毋庸置疑,甲基化对肿瘤的影响是表观遗传学的一个重要方面。在甲基化修饰中,DNA 甲基化是重要的一部分,它对肿瘤相关基因起着调控作用。十-十一易位 2(TET2)是一种参与 DNA 甲基化修饰的极具影响力的蛋白质。它的主要作用与抑制肿瘤发生有关,因此在癌症研究中占有重要地位。然而,TET2 在血液病中经常被提及,但它在实体瘤中的作用却很少受到关注。研究 TET2 在实体瘤中的变化及其调控机制,有助于将其作为靶向治疗的临床靶点进行研究,也可为恶性肿瘤的临床治疗提供方向。
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引用次数: 0
ECLIM-SEHOP: how to develop a platform to conduct academic trials for childhood cancer ECLIM-SEHOP:如何开发儿童癌症学术试验平台
Pub Date : 2024-04-10 DOI: 10.1007/s12094-024-03445-0
Antonio Juan-Ribelles, Francisco Bautista, Adela Cañete, Alba Rubio-San-Simón, Anna Alonso-Saladrigues, Raquel Hladun, Susana Rives, Jose Luís Dapena, Jose María Fernández, Álvaro Lassaletta, Ofelia Cruz, Gemma Ramírez-Villar, Jose Luís Fuster, Cristina Diaz de Heredia, Miguel García-Ariza, Eduardo Quiroga, María del Mar Andrés, Jaime Verdú-Amorós, Antonio Molinés, Blanca Herrero, Mónica López, Catalina Márquez, María Toboso, Frencisco Lendínez, Jose Gómez Sirvent, María Tallón, Guiomar Rodríguez, Tomás Acha, Lucas Moreno, Ana Fernández-Teijeiro

Introduction

ECLIM-SEHOP platform was created in 2017. Its main objective is to establish the infrastructure to allow Spanish participation into international academic collaborative clinical trials, observational studies, and registries in pediatric oncology. The aim of this manuscript is to describe the activity conducted by ECLIM-SEHOP since its creation.

Methods

The platform’s database was queried to provide an overview of the studies integrally and partially supported by the organization. Data on trial recruitment and set-up/conduct metrics since its creation until November 2023 were extracted.

Results

ECLIM-SEHOP has supported 47 studies: 29 clinical trials and 18 observational studies/registries that have recruited a total of 5250 patients. Integral support has been given to 25 studies: 16 trials recruiting 584 patients and nine observational studies/registries recruiting 278 patients. The trials include front-line studies for leukemia, lymphoma, brain and solid extracranial tumors, and other key transversal topics such as off-label use of targeted therapies and survivorship. The mean time from regulatory authority submission to first patient recruited was 12.2 months and from first international site open to first Spanish site open was 31.3 months.

Discussion

ECLIM-SEHOP platform has remarkably improved the availability and accessibility of international academic clinical trials and has facilitated the centralization of resources in childhood cancer treatment. Despite the progressive improvement on clinical trial set-up metrics, timings should still be improved. The program has contributed to leveling survival rates in Spain with those of other European countries that presented major differences in the past.

导言ECLIM-SEHOP平台创建于2017年。其主要目标是建立基础设施,使西班牙能够参与儿科肿瘤学的国际学术合作临床试验、观察研究和登记。本手稿旨在描述ECLIM-SEHOP自创建以来开展的活动。方法通过查询该平台的数据库,了解由该组织整体或部分支持的研究概况。结果ECLIM-SEHOP共支持了47项研究:29项临床试验和18项观察性研究/登记,共招募了5250名患者。对 25 项研究提供了综合支持:其中 16 项试验招募了 584 名患者,9 项观察性研究/登记招募了 278 名患者。这些试验包括针对白血病、淋巴瘤、脑肿瘤和颅外实体瘤的一线研究,以及其他关键横向课题,如标示外使用靶向疗法和生存期。讨论ECLIM-SEHOP平台显著提高了国际学术临床试验的可用性和可及性,促进了儿童癌症治疗资源的集中化。尽管临床试验设置指标在逐步改善,但时间安排仍有待改进。该计划为西班牙与其他欧洲国家的存活率持平做出了贡献,而其他欧洲国家的存活率在过去存在很大差异。
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引用次数: 0
Can neoadjuvant systemic therapy provide additional benefits for T1 HER2+ breast cancer patients: a subgroup analysis based on different high-risk signatures 新辅助系统疗法能否为 HER2+ 乳腺癌 T1 期患者带来额外益处:基于不同高风险特征的亚组分析
Pub Date : 2024-04-09 DOI: 10.1007/s12094-024-03472-x
Lidan Chang, Dandan Liu, Xuyan Zhao, Luyao Dai, Xueting Ren, Qian Hao, Peinan Liu, Hao Wu, Xiaobin Ma, Huafeng Kang

Introduction

Neoadjuvant systemic therapy (NAST) is vital in the management of HER2-positive (HER2+) breast cancer. Nevertheless, the indications for NAST in tumors <2 cm remain controversial.

Method

A total of 7961 patients were screened from the Surveillance, Epidemiology, and End Result database. Independent prognostic factors were identified using multivariate Cox analysis. Subgroup analyses and Kaplan–Meier analyses were used to simulate whether NAST would provide a survival benefit with different high-risk characteristics. Nomograms were constructed, and an internal validation cohort was employed.

Results

Of the 7961 included patients, 1137 (14.3%) underwent NAST. In the total population, NAST was associated with poorer overall survival (OS) and breast cancer-specific survival (BCSS) (OS: P = 0.00093; BCSS:  < 0.0001). Multivariate Cox analysis confirmed that NAST markedly affected the prognosis of enrolled patients. Besides, a direct association between T, N, age, subtype, and prognosis was observed. Subgroup analyses yielded in these three subgroups, T1c, hormone receptor-negative, and 61–69 years of age, NAST and AST had comparable OS, while NAST possessed worse BCSS. Notably, even in the N3, we still did not observe any additional benefit of NAST. The calculated C-index of 0.72 and 0.73 confirmed the predictability of the nomograms. The AUCs exhibit consistency in the training and validation cohorts.

Conclusion

Our findings suggest that NAST does not provide additional benefit to patients with T1 HER2+ breast cancer, even in the presence of lymph node metastasis, T1c, or hormone receptor negativity. This study facilitates the implementation of individualized management strategies.

导言新辅助系统疗法(NAST)在HER2阳性(HER2+)乳腺癌的治疗中至关重要。方法从监测、流行病学和最终结果数据库中筛选出 7961 例患者。采用多变量 Cox 分析确定了独立的预后因素。使用亚组分析和卡普兰-梅耶分析来模拟不同高危特征的 NAST 是否会带来生存获益。结果 在纳入的 7961 例患者中,有 1137 例(14.3%)接受了 NAST。在所有患者中,NAST与较差的总生存期(OS)和乳腺癌特异性生存期(BCSS)相关(OS:P = 0.00093;BCSS:P < 0.0001)。多变量 Cox 分析证实,NAST 会明显影响入组患者的预后。此外,还观察到 T、N、年龄、亚型与预后之间存在直接关联。亚组分析显示,在T1c、激素受体阴性和61-69岁这三个亚组中,NAST和AST的OS相当,而NAST的BCSS较差。值得注意的是,即使在 N3 组中,我们仍然没有观察到 NAST 有任何额外的益处。计算得出的 C 指数分别为 0.72 和 0.73,证实了提名图的可预测性。结论我们的研究结果表明,即使存在淋巴结转移、T1c 或激素受体阴性,NAST 也不会给 T1 HER2+ 乳腺癌患者带来额外的益处。这项研究有助于实施个体化管理策略。
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Clinical and Translational Oncology
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