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Correction to: PITX1 suppresses osteosarcoma metastasis through exosomal LINC00662-mediated M2 macrophage polarization 更正为PITX1 通过外泌体 LINC00662 介导的 M2 巨噬细胞极化抑制骨肉瘤转移
IF 4 3区 医学 Q1 Medicine Pub Date : 2023-12-08 DOI: 10.1007/s10585-023-10247-1
Ying Zhang, Yelong Chen, Chuangzhen Chen, Huancheng Guo, Chunbin Zhou, Hu Wang, Zhaoyong Liu
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引用次数: 0
Management of melanoma: can we use gene expression profiling to help guide treatment and surveillance? 黑色素瘤的管理:我们能否利用基因表达谱来帮助指导治疗和监控?
IF 4 3区 医学 Q1 Medicine Pub Date : 2023-12-08 DOI: 10.1007/s10585-023-10241-7
Jonathan S. Zager, David M. Hyams

Although the incidence of cutaneous melanoma (CM) has been increasing annually, the mortality rate has been decreasing, likely due to better prevention, earlier detection, improved surveillance, and the development of new therapies. Current clinical management guidelines by the National Comprehensive Cancer Network (NCCN) are based on patient risk assignment using staging criteria established by the American Joint Committee on Cancer (AJCC). However, some patients with localized disease (stage I–II), generally considered to have a good prognosis, will develop metastatic disease and die, whereas some patients with later stage disease (stage III–IV) will be cured by surgery, adjuvant therapy, and/or systemic therapy. These results emphasize the importance of identifying patients whose risk may be over or underestimated with standard staging. Gene expression profile (GEP) tests are noninvasive molecular tests that assess the expression levels of a panel of validated genes, providing information about tumor prognosis, including the risk of recurrence, metastasis, and cancer-specific death. GEP tests can provide prognostic information beyond standard staging that may aid clinicians and patients in treatment and surveillance management decisions. This review describes how combining clinicopathologic staging with a robust assessment of tumor biology may provide information that will allow more refined intervention and long-term management.

虽然皮肤黑色素瘤(CM)的发病率每年都在增加,但死亡率却在下降,这很可能是由于更好的预防、更早的发现、更完善的监测以及新疗法的开发。美国国家综合癌症网络(NCCN)目前的临床管理指南是根据美国癌症联合委员会(AJCC)制定的分期标准对患者进行风险评估。然而,一些通常被认为预后良好的局部疾病(I-II 期)患者会出现转移性疾病并死亡,而一些晚期疾病(III-IV 期)患者则会通过手术、辅助治疗和/或全身治疗治愈。这些结果强调了识别那些标准分期可能高估或低估其风险的患者的重要性。基因表达谱(GEP)检测是一种非侵入性分子检测,可评估一系列有效基因的表达水平,提供有关肿瘤预后的信息,包括复发、转移和癌症特异性死亡的风险。GEP 检测可提供标准分期以外的预后信息,有助于临床医生和患者做出治疗和监控管理决策。本综述介绍了如何将临床病理分期与对肿瘤生物学的有力评估相结合,从而提供可进行更精细干预和长期管理的信息。
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引用次数: 0
Clinical characteristics, treatment, and outcome of patients with large cell neuroendocrine carcinoma of the lung and brain metastases – data from a tertiary care center 肺大细胞神经内分泌癌脑转移患者的临床特征、治疗和预后--来自一家三级医疗中心的数据
IF 4 3区 医学 Q1 Medicine Pub Date : 2023-12-08 DOI: 10.1007/s10585-023-10250-6
Petar Popov, Ariane Steindl, Ladislaia Wolff, Elisabeth S. Bergen, Franziska Eckert, Josa M Frischer, Georg Widhalm, Thorsten Fuereder, Markus Raderer, Anna S. Berghoff, Matthias Preusser, Barbara Kiesewetter

Large cell neuroendocrine carcinoma (LCNEC) of the lung is an aggressive malignancy, with brain metastases (BM) occurring in approximately 20% of cases. There are currently no therapy guidelines for this population as only few data on the management of LCNEC and BM have been published. For this retrospective single center study, patients with LCNEC and BM were identified from the Vienna Brain Metastasis Registry. Data on clinicopathological features, BM-specific characteristics, treatment, and outcome were extracted. In total, 52/6083 (0.09%) patients in the dataset had a diagnosis of LCNEC and radiologically verified BM. Median age at diagnosis of LCNEC and BM was 59.1 and 60.1 years, respectively. Twenty-seven (51.9%) presented with single BM, while 12 (23%) exhibited > 3 BM initially. Neurologic symptoms due to BM were present in n = 40 (76.9%), encompassing neurologic deficits (n = 24), increased intracranial pressure (n = 18), and seizures (n = 6). Initial treatment of BM was resection (n = 13), whole brain radiation therapy (n = 19), and/or stereotactic radiosurgery (n = 25). Median overall survival (mOS) from LCNEC diagnosis was 16 months, and mOS after BM diagnosis was 7 months. Patients with synchronous BM had reduced mOS from LCNEC diagnosis versus patients with metachronous BM (11 versus 27 months, p = 0.003). Median OS after BM diagnosis did not differ between LCNEC patients and a control group of small cell lung cancer patients with BM (7 versus 6 months, p = 0.17). Patients with LCNEC and BM have a poor prognosis, particularly when synchronous BM are present. Prospective trials are required to define optimal therapeutic algorithms.

肺大细胞神经内分泌癌(LCNEC)是一种侵袭性恶性肿瘤,约20%的病例会发生脑转移(BM)。目前还没有针对这一人群的治疗指南,因为有关 LCNEC 和 BM 治疗的数据很少。在这项回顾性单中心研究中,我们从维也纳脑转移登记处找到了LCNEC和脑转移患者。研究提取了临床病理特征、BM特异性特征、治疗和预后数据。数据集中共有52/6083(0.09%)例患者确诊为LCNEC和经放射学证实的BM。确诊 LCNEC 和 BM 的中位年龄分别为 59.1 岁和 60.1 岁。27名患者(51.9%)表现为单个BM,12名患者(23%)最初表现为> 3个BM。有 40 例(76.9%)患者因 BM 而出现神经系统症状,包括神经功能缺损(24 例)、颅内压增高(18 例)和癫痫发作(6 例)。BM的初始治疗为切除术(13例)、全脑放疗(19例)和/或立体定向放射手术(25例)。LCNEC确诊后的中位总生存期(mOS)为16个月,BM确诊后的中位总生存期为7个月。同步性骨髓瘤患者与间变性骨髓瘤患者相比,LCNEC确诊后的中位生存期缩短(11个月对27个月,P = 0.003)。LCNEC患者与对照组小细胞肺癌患者确诊BM后的中位OS没有差异(7个月对6个月,p = 0.17)。LCNEC和BM患者的预后较差,尤其是出现同步BM时。需要进行前瞻性试验来确定最佳治疗方案。
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引用次数: 0
Dissecting the tumor microenvironment in response to immune checkpoint inhibitors via single-cell and spatial transcriptomics 通过单细胞和空间转录组学剖析肿瘤微环境对免疫检查点抑制剂的反应
IF 4 3区 医学 Q1 Medicine Pub Date : 2023-12-08 DOI: 10.1007/s10585-023-10246-2
Wendi Liu, Anusha Puri, Doris Fu, Lee Chen, Cassia Wang, Manolis Kellis, Jiekun Yang

Cancer is a disease that undergoes selective pressure to evolve during its progression, becoming increasingly heterogeneous. Tumoral heterogeneity can dictate therapeutic response. Transcriptomics can be used to uncover complexities in cancer and reveal phenotypic heterogeneity that affects disease response. This is especially pertinent in the immune microenvironment, which contains diverse populations of immune cells, and whose dynamic properties influence disease response. The recent development of immunotherapies has revolutionized cancer therapy, with response rates of up to 50% within certain cancers. However, despite advances in immune checkpoint blockade specifically, there remains a significant population of non-responders to these treatments. Transcriptomics can be used to profile immune and other cell populations following immune-checkpoint inhibitor (ICI) treatment, generate predictive biomarkers of resistance or response, assess immune effector function, and identify potential immune checkpoints. Single-cell RNA sequencing has offered insight into mRNA expression within the complex and heterogeneous tumor microenvironment at single-cell resolution. Spatial transcriptomics has enabled measurement of mRNA expression while adding locational context. Here, we review single-cell sequencing and spatial transcriptomic research investigating ICI response within a variety of cancer microenvironments.

癌症是一种在发展过程中承受选择性压力而不断演变的疾病,其异质性越来越强。肿瘤的异质性可决定治疗反应。转录组学可用于揭示癌症的复杂性,揭示影响疾病反应的表型异质性。这一点在免疫微环境中尤为重要,免疫微环境包含多种免疫细胞群,其动态特性会影响疾病反应。近年来,免疫疗法的发展给癌症治疗带来了革命性的变化,某些癌症的应答率高达 50%。然而,尽管在免疫检查点阻断方面取得了具体进展,但仍有相当一部分人对这些疗法没有反应。转录组学可用于分析免疫检查点抑制剂(ICI)治疗后的免疫细胞群和其他细胞群,生成耐药性或反应的预测性生物标记物,评估免疫效应器功能,并确定潜在的免疫检查点。单细胞 RNA 测序能以单细胞分辨率深入了解复杂而异质的肿瘤微环境中的 mRNA 表达。空间转录组学在测量 mRNA 表达的同时还增加了定位背景。在此,我们回顾了单细胞测序和空间转录组学对各种癌症微环境中 ICI 反应的研究。
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引用次数: 0
High sensitivity flow cytometry immunophenotyping increases the diagnostic yield of malignant pleural effusions. 高灵敏度的流式细胞术免疫表型可提高恶性胸腔积液的诊断率。
IF 4 3区 医学 Q1 Medicine Pub Date : 2023-12-01 Epub Date: 2023-10-09 DOI: 10.1007/s10585-023-10236-4
Dolores Subirá, Fabiola Barriopedro, Jesús Fernández, Ruth Martínez, Luis Chara, Jorge Castelao, Eugenia García

Diagnosing malignant pleural effusions (MPE) is challenging when patients lack a history of cancer and cytopathology does not detect malignant cells in pleural effusions (PE). We investigated whether a systematic analysis of PE by flow cytometry immunophenotyping (FCI) had any impact on the diagnostic yield of MPE. Over 7 years, 570 samples from patients with clinical suspicion of MPE were submitted for the FCI study. To screen for epithelial malignancies, a 3-color FCI high sensitivity assay was used. The FCI results, qualified as "malignant" (FCI+) or "non-malignant" (FCI-), were compared to integrated definitive diagnosis established by clinicians based on all available information. MPE was finally diagnosed in 182 samples and FCI detected 141/182 (77.5%). Morphology further confirmed FCI findings by cytopathology detection of malignant cells in PE (n = 91) or histopathology (n = 29). Imaging tests and clinical history supported the diagnosis in the remaining samples. The median percentage of malignant cells was 6.5% for lymphoma and 0.23% for MPE secondary to epithelial cell malignancies. FCI identified a significantly lower percentage of EpCAM+ cells in cytopathology-negative MPE than in cytopathology-positive cases (0.02% vs. 1%; p < 0.0001). Interestingly, 29/52 MPE (55.8%) where FCI alerted of the presence of malignant cells were new diagnosis of cancer. Overall, FCI correctly diagnosed 456/522 samples (87.4%) suitable for comparison with cytopathology. These findings show that high sensitivity FCI significantly increases the diagnostic yield of MPE. Early detection of FCI + cases accelerates the diagnostic pathway of unsuspected MPE, thus supporting its implementation in clinical diagnostic work-up as a diagnostic tool.

当患者缺乏癌症病史且细胞病理学未检测到胸腔积液(PE)中的恶性细胞时,诊断恶性胸腔积液(MPE)是一项挑战。我们研究了通过流式细胞术免疫表型(FCI)对PE的系统分析是否对MPE的诊断率有任何影响。在7年多的时间里,来自临床怀疑MPE患者的570份样本被提交给FCI研究。为了筛选上皮恶性肿瘤,使用了三色FCI高灵敏度测定法。FCI结果被定性为“恶性”(FCI+)或“非恶性”(FCI-),与临床医生根据所有可用信息确定的综合明确诊断进行比较。在182个样本中最终诊断为MPE,检测到141/182(77.5%)的FCI。形态学通过对PE中恶性细胞的细胞病理学检测进一步证实了FCI的发现(n = 91)或组织病理学(n = 29)。影像学检查和临床病史支持其余样本的诊断。恶性细胞的中位百分比淋巴瘤为6.5%,继发于上皮细胞恶性肿瘤的MPE为0.23%。FCI发现EpCAM的百分比明显较低+ 细胞病理学阴性MPE中的细胞比细胞病理学阳性病例中的细胞多(0.02%vs.1%;p
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引用次数: 0
CT-based deep learning model: a novel approach to the preoperative staging in patients with peritoneal metastasis. 基于CT的深度学习模型:腹膜转移患者术前分期的一种新方法。
IF 4 3区 医学 Q1 Medicine Pub Date : 2023-12-01 Epub Date: 2023-10-05 DOI: 10.1007/s10585-023-10235-5
Jipeng Wang, Yuannan Hu, Hao Xiong, Tiantian Song, Shuyi Wang, Haibo Xu, Bin Xiong

Peritoneal metastasis (PM) is a frequent manifestation of advanced abdominal malignancies. Accurately assessing the extent of PM before surgery is essential for patients to receive optimal treatment. Therefore, we propose to construct a deep learning (DL) model based on enhanced computed tomography (CT) images to stage PM preoperatively in patients. All 168 patients with PM underwent contrast-enhanced abdominal CT before either open surgery or laparoscopic exploration, and peritoneal cancer index (PCI) was used to evaluate patients during the surgical procedure. DL features were extracted from portal venous-phase abdominal CT scans and subjected to feature selection using the Spearman correlation coefficient and LASSO. The performance of models for preoperative staging was assessed in the validation cohort and compared against models based on clinical and radiomics (Rad) signature. The DenseNet121-SVM model demonstrated strong patient discrimination in both the training and validation cohorts, achieving AUC was 0.996 in training and 0.951 validation cohort, which were both higher than those of the Clinic model and Rad model. Decision curve analysis (DCA) showed that patients could potentially benefit more from treatment using the DL-SVM model, and calibration curves demonstrated good agreement with actual outcomes. The DL model based on portal venous-phase abdominal CT accurately predicts the extent of PM in patients before surgery, which can help maximize the benefits of treatment and optimize the patient's treatment plan.

腹膜转移(PM)是晚期腹部恶性肿瘤的常见表现。术前准确评估PM的程度对于患者接受最佳治疗至关重要。因此,我们建议构建一个基于增强型计算机断层扫描(CT)图像的深度学习(DL)模型,以在患者术前对PM进行分期。所有168例PM患者在开放手术或腹腔镜探查前均进行了腹部CT增强扫描,并在手术过程中使用腹膜癌症指数(PCI)对患者进行评估。DL特征从门静脉期腹部CT扫描中提取,并使用Spearman相关系数和LASSO进行特征选择。在验证队列中评估了术前分期模型的性能,并与基于临床和放射组学(Rad)特征的模型进行了比较。DenseNet121 SVM模型在训练和验证队列中都表现出较强的患者辨别力,在训练和确认队列中实现的AUC分别为0.996和0.951,均高于Clinic模型和Rad模型。决策曲线分析(DCA)表明,使用DL-SVM模型,患者可能会从治疗中受益更多,校准曲线与实际结果吻合良好。基于门静脉期腹部CT的DL模型准确预测了患者术前PM的程度,有助于最大限度地提高治疗效果,优化患者的治疗计划。
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引用次数: 0
Congratulations to Prof. em. Garth L. Nicolson - co-founder of Clinical & Experimental Metastasis. 祝贺临床与实验转移瘤联合创始人Garth L.Nicolson教授。
IF 4 3区 医学 Q1 Medicine Pub Date : 2023-12-01 Epub Date: 2023-10-21 DOI: 10.1007/s10585-023-10239-1
Jörg Haier, Jonathan Sleeman
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引用次数: 0
Development and adaptations of the Graded Prognostic Assessment (GPA) scale: a systematic review. 分级预后评估(GPA)量表的发展和适应:一项系统综述。
IF 4 3区 医学 Q1 Medicine Pub Date : 2023-12-01 Epub Date: 2023-10-11 DOI: 10.1007/s10585-023-10237-3
Luana Marques Ribeiro, Fernanda Ferreira Bomtempo, Rebeka Bustamante Rocha, João Paulo Mota Telles, Eliseu Becco Neto, Eberval Gadelha Figueiredo

The Graded Prognostic Assessment (GPA) score has the best accuracy among prognostic scales for patients with brain metastases (BM). A wide range of GPA-derived scales have been established to different types of primary tumor BM. However, there is a high variability between them, and their characteristics have not been described altogether yet. We aim to summarize the features of the existent GPA-derived scales and to compare their predictor factors and their uses in clinical setting. Medline was searched from inception until January 2023 to identify studies related to the development, update, or validation of GPA. The initial search yielded 1,083 results. 16 original studies and 16 validation studies were included, comprising a total of 33,348 patients. 13 different scales were assessed, including: GPA, Diagnosis-Specific GPA, Extracranial Score, Lung-molGPA, Updated Renal GPA, Updated Gastrointestinal GPA, Modified Breast GPA, Integrated Melanoma GPA, Melanoma Mol GPA, Sarcoma GPA, Hepatocellular Carcinoma GPA, Colorectal Cancer GPA, and Uterine Cancer GPA. The most prevalent prognostic predictors were age, Karnofsky Performance Status, number of BM, and presence or absence of extracranial metastases. Treatment modalities consisted of whole brain radiation therapy, stereotactic radiosurgery, surgery, cranial radiotherapy, gamma knife radiosurgery, and BRAF inhibitor therapy. Median survival rates with no treatment and with a specific treatment ranged from 6.1 weeks to 33 months and from 3.1 to 21 months, respectively. Original GPA and GPA-derived scales are valid prognostic tools, but with heterogeneous survival results when compared to each other. More studies are needed to improve scientific evidence of these scales.

分级预后评估(GPA)评分在脑转移瘤(BM)患者的预后量表中具有最佳的准确性。针对不同类型的原发性肿瘤BM,已经建立了广泛的GPA衍生量表。然而,它们之间存在高度的可变性,并且它们的特征尚未完全描述。我们的目的是总结现有GPA衍生量表的特点,并比较它们的预测因素及其在临床环境中的应用。Medline从成立到2023年1月进行了搜索,以确定与GPA的开发、更新或验证相关的研究。最初的搜索得到了1083个结果。包括16项原始研究和16项验证研究,共包括33348名患者。评估了13种不同的量表,包括:GPA、诊断特异性GPA、颅外评分、Lung-molGPA、更新的肾脏GPA、升级的胃肠道GPA、修改的乳房GPA、整合的黑色素瘤GPA、黑色素瘤Mol GPA、肉瘤GPA、肝癌GPA、结直肠癌癌症GPA和癌症GPA。最常见的预后预测因素是年龄、Karnofsky表现状态、BM数量以及是否存在颅外转移。治疗方式包括全脑放射治疗、立体定向放射外科、手术、颅骨放射治疗、伽玛刀放射外科和BRAF抑制剂治疗。未接受治疗和接受特定治疗的中位生存率分别为6.1周到33个月和3.1到21个月。原始GPA和GPA衍生量表是有效的预后工具,但相互比较时存在异质性生存结果。需要更多的研究来改进这些量表的科学证据。
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引用次数: 0
PET/CT in assessment of colorectal liver metastases: a comprehensive review with emphasis on 18F-FDG. PET/CT在评估结直肠癌肝转移中的应用:以18F-FDG为重点的综述。
IF 4 3区 医学 Q1 Medicine Pub Date : 2023-12-01 Epub Date: 2023-09-08 DOI: 10.1007/s10585-023-10231-9
Mahdi Zirakchian Zadeh

Approximately 25% of those who are diagnosed with colorectal cancer will develop colorectal liver metastases (CRLM) as their illness advances. Despite major improvements in both diagnostic and treatment methods, the prognosis for patients with CRLM is still poor, with low survival rates. Accurate employment of imaging methods is critical in identifying the most effective treatment approach for CRLM. Different imaging modalities are used to evaluate CRLM, including positron emission tomography (PET)/computed tomography (CT). Among the PET radiotracers, fluoro-18-deoxyglucose (18F-FDG), a glucose analog, is commonly used as the primary radiotracer in assessment of CRLM. As the importance of 18F-FDG-PET/CT continues to grow in assessment of CRLM, developing a comprehensive understanding of this subject becomes imperative for healthcare professionals from diverse disciplines. The primary aim of this article is to offer a simplified and comprehensive explanation of PET/CT in the evaluation of CRLM, with a deliberate effort to minimize the use of technical nuclear medicine terminology. This approach intends to provide various healthcare professionals and researchers with a thorough understanding of the subject matter.

大约25%被诊断为结直肠癌癌症的患者将随着病情的发展而发展为结直肠癌肝转移(CRLM)。尽管诊断和治疗方法都有了重大改进,但CRLM患者的预后仍然很差,生存率很低。准确使用成像方法对于确定CRLM最有效的治疗方法至关重要。使用不同的成像模式来评估CRLM,包括正电子发射断层扫描(PET)/计算机断层扫描(CT)。在PET放射性示踪剂中,氟-18-脱氧葡萄糖(18F-FDG),一种葡萄糖类似物,通常用作评估CRLM的主要放射性示踪剂。随着18F-FDG-PET/CT在CRLM评估中的重要性不断增加,来自不同学科的医疗保健专业人员必须全面了解这一主题。本文的主要目的是对CRLM评估中的PET/CT进行简化和全面的解释,并尽量减少核医学技术术语的使用。这种方法旨在为各种医疗保健专业人员和研究人员提供对主题的全面了解。
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引用次数: 0
Travelling under pressure - hypoxia and shear stress in the metastatic journey. 在压力下旅行——转移过程中的缺氧和剪切应力。
IF 4 3区 医学 Q1 Medicine Pub Date : 2023-10-01 Epub Date: 2023-07-25 DOI: 10.1007/s10585-023-10224-8
Ece Su Ildiz, Ana Gvozdenovic, Werner J Kovacs, Nicola Aceto

Cancer cell invasion, intravasation and survival in the bloodstream are early steps of the metastatic process, pivotal to enabling the spread of cancer to distant tissues. Circulating tumor cells (CTCs) represent a highly selected subpopulation of cancer cells that tamed these critical steps, and a better understanding of their biology and driving molecular principles may facilitate the development of novel tools to prevent metastasis. Here, we describe key research advances in this field, aiming at describing early metastasis-related processes such as collective invasion, shedding, and survival of CTCs in the bloodstream, paying particular attention to microenvironmental factors like hypoxia and mechanical stress, considered as important influencers of the metastatic journey.

癌症细胞侵袭、血管内浸润和血流中的存活是转移过程的早期步骤,是使癌症扩散到远处组织的关键。循环肿瘤细胞(CTC)代表了癌症细胞的一个高度选择的亚群,它们驯服了这些关键步骤,更好地了解它们的生物学和驱动分子原理可能有助于开发新的预防转移的工具。在这里,我们描述了该领域的关键研究进展,旨在描述早期转移相关过程,如血液中CTC的集体侵袭、脱落和存活,特别关注缺氧和机械应力等微环境因素,这些因素被认为是转移过程的重要影响因素。
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引用次数: 1
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