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Angiogenesis and thymic epithelial tumors: from preclinical insights to different therapeutic lines and combination strategies 血管生成和胸腺上皮肿瘤:从临床前的见解到不同的治疗线和联合策略。
IF 10.5 1区 医学 Q1 ONCOLOGY Pub Date : 2025-11-13 DOI: 10.1016/j.ctrv.2025.103049
D. Miliziano , C. Sciortino , S. Manglaviti , M. Ganzinelli , A. Lopez-Gutierrez , M. Occhipinti , C. Proto , F. De Braud , B. Besse , G. Lo Russo , J. Remon
Thymic epithelial tumors (TETs) are rare thoracic malignancies for which surgical resection remains the mainstay treatment, even in advanced stages. For patients with metastatic disease, platinum-based chemotherapy represents the current standard of care in the first-line, with no standard treatment at progression. Much preclinical evidence supports a potential role of angiogenesis in the pathogenesis and progression of TETs. This biological rationale has led to assess the efficacy of several antiangiogenic agents, either in monotherapy or in combination in pre-treated metastatic TET, reporting a clinical meaningful outcome. Despite this efficacy several challenges remain such as the optimal place of angiogenic agents in the treatment sequence, whether they should be applied as monotherapy or in combination, as well as the potential clinical activity of sequential antiangiogenic agents with different mechanisms of action. In this review, we provide a comprehensive overview of the preclinical and clinical evidence supporting angiogenesis as a therapeutic target in TETs. We also propose potential treatment algorithms based on the current literature, while highlighting the ongoing challenges in defining optimal dosing strategies and treatment sequences in this rare disease.
胸腺上皮肿瘤(TETs)是罕见的胸部恶性肿瘤,手术切除仍然是主要的治疗方法,即使在晚期。对于转移性疾病患者,铂类化疗是目前一线治疗的标准,进展时没有标准治疗。许多临床前证据支持血管生成在TETs发病和进展中的潜在作用。这一生物学原理导致了对几种抗血管生成药物的疗效进行评估,无论是单药治疗还是联合治疗转移性TET,报告了有临床意义的结果。尽管有这样的疗效,但仍存在一些挑战,如血管生成药物在治疗顺序中的最佳位置,它们是否应该作为单一疗法或联合应用,以及具有不同作用机制的顺序抗血管生成药物的潜在临床活性。在这篇综述中,我们提供了全面的临床前和临床证据支持血管生成作为治疗靶点的TETs。我们还根据现有文献提出了潜在的治疗算法,同时强调了在定义这种罕见疾病的最佳剂量策略和治疗序列方面的持续挑战。
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引用次数: 0
Diagnostic utility of urinary cell-free DNA in non-urothelial cancer: a systematic review, meta-analysis, & network meta-analysis 尿细胞游离DNA在非尿路上皮癌诊断中的应用:一项系统综述、荟萃分析和网络荟萃分析
IF 10.5 1区 医学 Q1 ONCOLOGY Pub Date : 2025-11-13 DOI: 10.1016/j.ctrv.2025.103047
Shugo Yajima, Kohei Hirose, Hitoshi Masuda

Purpose

Urinary cell-free DNA (ucfDNA) offers a noninvasive approach for cancer detection, but its diagnostic utility in non-urothelial cancers remains unclear. We systematically evaluated the diagnostic and prognostic value of ucfDNA for these cancers and compared its performance with other liquid biopsies through network meta-analysis.

Experimental design

We conducted a systematic search of PubMed, Cochrane Library, and other databases for studies from 2010 to 2025 evaluating ucfDNA for diagnosing or predicting prognosis in non-urothelial cancers. Primary outcomes were pooled diagnostic sensitivity and specificity; secondary outcomes included prognostic hazard ratios (HRs). Study quality was assessed using QUADAS-2, and Bayesian hierarchical models were employed for robust estimates.

Results

Twenty-eight studies involving 4,423 participants were included. Overall pooled sensitivity was 0.80 (95 % CI, 0.75–0.85) and specificity was 0.96 (95 % CI, 0.88–0.98), with significant heterogeneity (I2 > 82 %). Subgroup analysis of studies targeting short amplicons (<70 bp) showed improved specificity of 0.98 and substantially reduced heterogeneity (I2 = 0 % for specificity). Limited post-treatment ucfDNA reduction was a strong predictor of poor prognosis (pooled HR, 2.76; 95 % CI, 1.94–3.91). Exploratory network meta-analysis in non-small cell lung cancer comparing urine, plasma, and sputum showed overlapping confidence intervals, though the limited available data and wide confidence intervals preclude definitive conclusions regarding comparative performance. Mutation-based assays demonstrated significantly higher specificity than methylation-based approaches (99 % vs. 72 %, P < 0.01).

Conclusions

ucfDNA demonstrates high diagnostic specificity for non-urothelial cancers and provides significant prognostic information. Optimizing assays for ultrashort DNA fragments is critical for enhancing performance and reducing variability. These findings support the potential utility of ucfDNA, particularly as a complementary tool alongside established liquid biopsies like plasma cfDNA, to enhance non-invasive cancer diagnosis and monitoring. Its role as a standalone diagnostic requires further validation, and method standardization remains essential for broad implementation.

Clinical trial registration

PROSPERO CRD420251073863.
目的:尿无细胞DNA (ucfDNA)为癌症检测提供了一种无创方法,但其在非尿路上皮癌症诊断中的应用尚不清楚。我们系统地评估了ucfDNA对这些癌症的诊断和预后价值,并通过网络荟萃分析将其与其他液体活检的表现进行了比较。实验设计我们对PubMed、Cochrane图书馆和其他数据库进行了系统检索,检索2010年至2025年评估ucfDNA在非尿路上皮癌诊断或预测预后方面的研究。主要结局是合并诊断敏感性和特异性;次要结局包括预后风险比(hr)。使用QUADAS-2评估研究质量,并采用贝叶斯分层模型进行稳健估计。结果共纳入28项研究,共4423名受试者。总体合并敏感性为0.80 (95% CI, 0.75-0.85),特异性为0.96 (95% CI, 0.88-0.98),异质性显著(I2 > 82%)。针对短扩增子(<70 bp)的研究的亚组分析显示,特异性提高了0.98,异质性大大降低(特异性I2 = 0%)。治疗后有限的ucfDNA减少是不良预后的有力预测因子(总风险比2.76;95% CI 1.94-3.91)。探索性网络荟萃分析在非小细胞肺癌中比较尿液、血浆和痰液显示重叠的置信区间,尽管有限的可用数据和较宽的置信区间排除了关于比较表现的明确结论。基于突变的检测显示特异性明显高于基于甲基化的方法(99%对72%,P < 0.01)。结论sufdna对非尿路上皮癌具有较高的诊断特异性,可提供重要的预后信息。优化超短DNA片段的分析对于提高性能和减少变异至关重要。这些发现支持了ucfDNA的潜在效用,特别是作为一种补充工具,与已建立的液体活检(如血浆cfDNA)一起,加强非侵入性癌症诊断和监测。它作为独立诊断的作用需要进一步的验证,并且方法标准化对于广泛的实现仍然是必不可少的。临床试验注册号prospero CRD420251073863。
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引用次数: 0
Expert consensus on the combination of Anti-EGFR monoclonal antibodies and immune checkpoint inhibitors in the treatment of head and neck squamous cell carcinoma 抗egfr单克隆抗体联合免疫检查点抑制剂治疗头颈部鳞状细胞癌的专家共识
IF 10.5 1区 医学 Q1 ONCOLOGY Pub Date : 2025-11-12 DOI: 10.1016/j.ctrv.2025.103048
Liqiong Xue , Tingting Xu , Guochun Cao , Xiaozhong Chen , Meiyu Fang , Mei Feng , Lin Gui , Fei Han , Yaqian Han , Chuncheng Hao , Man Hu , Wenxiao Huang , Dongmei Ji , Hao Jiang , Shaojun Lin , Lei Liu , Zhigang Liu , Haijun Lu , Song Qu , Guoxin Ren , Chaosu Hu
Head and neck squamous cell carcinoma (HNSCC) is the most prevalent type of head and neck cancer; however, treatment outcomes and patient prognosis remain suboptimal. Although the survival of patients with HNSCC has improved with the widespread use of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) and immune checkpoint inhibitors (ICIs), there remains considerable potential for further improvement. Recent studies suggest that the combination of anti-EGFR monoclonal antibodies and ICIs demonstrates promising efficacy and safety, which has been recommended by international guidelines for patients with recurrent or metastatic disease. Nevertheless, the application of this combination therapy remains in the early stages of exploration, and numerous questions concerning its standardized clinical use remain unanswered, including the mechanisms underlying the synergistic effects of individual agents, therapeutic value across different patient populations, and safety considerations. The Expert Committee of Head and Neck Cancer of the Chinese Society of Clinical Oncology (CSCO) organized an expert panel to develop this expert consensus on the combination of anti-EGFR mAbs and ICIs in the treatment of HNSCC through multiple rounds of discussion based on evidence-based medicine and clinical practice experience. This consensus provides guidance on the mechanisms of treatment with anti-EGFR mAbs plus ICIs, stratified treatment approaches, applications in special populations, and safety management. It is hoped that this consensus will provide clearer and more practical guidance for clinicians, promote the rational application of this combination therapy in clinical practice, and offer more treatment options for patients with HNSCC.
头颈部鳞状细胞癌(HNSCC)是最常见的头颈部癌症类型;然而,治疗结果和患者预后仍然不理想。尽管随着抗表皮生长因子受体(EGFR)单克隆抗体(mab)和免疫检查点抑制剂(ICIs)的广泛使用,HNSCC患者的生存得到了改善,但仍有很大的进一步改善的潜力。最近的研究表明,抗egfr单克隆抗体与ICIs联合使用具有良好的疗效和安全性,已被国际指南推荐用于复发或转移性疾病患者。然而,这种联合治疗的应用仍处于探索的早期阶段,关于其标准化临床使用的许多问题仍未得到解答,包括单个药物协同作用的潜在机制,不同患者群体的治疗价值以及安全性考虑。中国临床肿瘤学会头颈部肿瘤专家委员会(CSCO)组织专家组,根据循证医学和临床实践经验,经过多轮讨论,就抗egfr单克隆抗体与ICIs联合治疗HNSCC达成专家共识。这一共识为抗egfr单克隆抗体加ICIs的治疗机制、分层治疗方法、特殊人群的应用和安全管理提供了指导。希望这一共识能够为临床医生提供更明确、更实用的指导,促进该联合治疗在临床中的合理应用,为HNSCC患者提供更多的治疗选择。
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引用次数: 0
CAR-T cell therapy in hepatocellular carcinoma: from mechanistic insights to clinical translation CAR-T细胞治疗肝细胞癌:从机制的见解到临床翻译
IF 10.5 1区 医学 Q1 ONCOLOGY Pub Date : 2025-11-10 DOI: 10.1016/j.ctrv.2025.103046
Reza Elahi , Yassine Alami Idrissi , Anwaar Saeed
Chimeric antigen receptor (CAR)-T cell therapy has transformed cancer immunotherapy, achieving durable complete remissions in hematologic cancers. Yet its translation to solid tumors like hepatocellular carcinoma (HCC), a leading cause of cancer-related deaths worldwide, faces formidable barriers, including immunosuppressive tumor microenvironments (TMEs), antigen heterogeneity, and risks of on-target/off-tumor toxicity. This review discusses the evolving role of CAR-T therapy in HCC across three domains: (1) foundational concepts in CAR-T design, mechanistic action, and antigen-targeting strategies; (2) breakthroughs from preclinical studies and early-phase clinical trials, such as glypican-3 (GPC3) and alpha-fetoprotein (AFP) directed CAR-T cells that have demonstrated preliminary safety and anti-tumor activity; and (3) innovative strategies to overcome TME-driven resistance, including metabolic reprogramming and stromal modulation. We highlight cutting-edge engineering solutions such as armored CAR-T cells engineered for cytokine support, dual-targeting constructs to mitigate antigen escape, and hypoxia-resistant designs alongside synergistic approaches combining CAR-T with immune checkpoint inhibitors or tyrosine kinase inhibitors. Furthermore, we dissect emerging tactics to disrupt TME immunosuppression. While CAR-T therapy holds promise for redefining HCC management, its success will depend on overcoming biological and logistical barriers through patient-tailored designs and robust translational pipelines. Future directions should prioritize biomarker-driven clinical trials, scalable manufacturing platforms, and integration with existing multimodal HCC therapies to maximize durable responses.
嵌合抗原受体(CAR)-T细胞疗法已经改变了癌症免疫疗法,实现了血液癌症的持久完全缓解。然而,将其转化为实体肿瘤,如肝细胞癌(HCC),这是全球癌症相关死亡的主要原因,面临着巨大的障碍,包括免疫抑制肿瘤微环境(TMEs)、抗原异质性和靶/非肿瘤毒性风险。本文从三个方面讨论了CAR-T治疗在HCC中的作用:(1)CAR-T设计的基本概念、机制作用和抗原靶向策略;(2)临床前研究和早期临床试验取得突破,如glypican-3 (GPC3)和甲胎蛋白(AFP)靶向CAR-T细胞已显示出初步的安全性和抗肿瘤活性;(3)克服tme驱动抗性的创新策略,包括代谢重编程和基质调节。我们重点介绍了尖端的工程解决方案,如为细胞因子支持而设计的装甲CAR-T细胞,减轻抗原逃逸的双靶向结构,以及抗缺氧设计,以及将CAR-T与免疫检查点抑制剂或酪氨酸激酶抑制剂结合的协同方法。此外,我们剖析了破坏TME免疫抑制的新策略。尽管CAR-T疗法有望重新定义HCC的治疗方法,但其成功与否将取决于通过为患者量身定制的设计和强大的转化管道来克服生物学和后勤障碍。未来的方向应该优先考虑生物标志物驱动的临床试验,可扩展的制造平台,以及与现有的多模式HCC治疗的整合,以最大限度地提高持久的疗效。
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引用次数: 0
Transformation from EGFR-mutant lung adenocarcinoma to small-cell lung cancer: from clonal evolution to lineage reprogramming 从egfr突变型肺腺癌到小细胞肺癌的转化:从克隆进化到谱系重编程
IF 10.5 1区 医学 Q1 ONCOLOGY Pub Date : 2025-11-04 DOI: 10.1016/j.ctrv.2025.103044
Haoxin Wang , Nan Gao , Lu Wang , Feiran Yang , Bin Liu , Xiwen Hu , Yufeng Zhao , Rui Sha , Xiurong Li , Huijie Li
EGFR-mutant lung adenocarcinoma (LUAD) that transforms into small-cell lung cancer (SCLC) following targeted therapy represents a clinically significant mechanism of acquired resistance, occurring in approximately 3–14 % of cases. This transformed variant, referred to as SCLC after transformation (SCLC-AT), follows an aggressive clinical course and carries a poor prognosis. SCLC-AT retains the original EGFR mutation but significantly down-regulates EGFR protein expression, eliminating its dependence on EGFR signaling while simultaneously acquiring a neuroendocrine phenotype. In nearly all cases, bi-allelic inactivation of both TP53 and RB1 is observed. In this overview, we provide a detailed examination of the molecular mechanisms underlying the transition from EGFR-mutant LUAD to SCLC. By integrating two primary biological concepts, clonal evolution and lineage reprogramming, we examine recent advances concerning the original cell or cells involved, as well as the genetic and epigenetic reprogramming and signaling pathway changes. While the transformation to SCLC is currently considered genetically and epigenetically irreversible, preclinical interventions targeting EZH2, AURKA, and DLL3 have shown potential in reversing the neuroendocrine phenotype or improving tumor immunogenicity. Future research should utilize single-cell and spatial multi-omics technologies to develop predictive models that can facilitate the early detection of impending transformation and guide precision therapies, ultimately enhancing patient outcomes.
egfr突变型肺腺癌(LUAD)在靶向治疗后转化为小细胞肺癌(SCLC)是一种具有临床意义的获得性耐药机制,发生在约3 - 14%的病例中。这种转化的变体,被称为转化后的SCLC (SCLC- at),具有侵袭性的临床病程,预后较差。SCLC-AT保留了原有的EGFR突变,但显著下调了EGFR蛋白的表达,消除了对EGFR信号的依赖,同时获得了神经内分泌表型。在几乎所有病例中,观察到TP53和RB1双等位基因失活。在这篇综述中,我们详细研究了egfr突变LUAD向SCLC转变的分子机制。通过整合两个主要的生物学概念,克隆进化和谱系重编程,我们研究了有关原始细胞或相关细胞,以及遗传和表观遗传重编程和信号通路变化的最新进展。虽然目前认为向SCLC的转化在遗传和表观遗传上是不可逆的,但针对EZH2、AURKA和DLL3的临床前干预已显示出逆转神经内分泌表型或改善肿瘤免疫原性的潜力。未来的研究应利用单细胞和空间多组学技术来开发预测模型,以促进即将发生的转化的早期发现并指导精确治疗,最终提高患者的治疗效果。
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引用次数: 0
Clinical trials for older cancer patients: A systematic review 老年癌症患者的临床试验:系统综述。
IF 10.5 1区 医学 Q1 ONCOLOGY Pub Date : 2025-11-04 DOI: 10.1016/j.ctrv.2025.103045
Roberta Fazio , Alessandro Audisio , Giacomo Bregni , Daniel Sur , Valentina Daprà , Chiara Conti , Fatima-Zahra Abbassi , Nada Benhima , Irene Assaf , Lissandra Dal Lago , Demetris Papamichael , Jean-Luc Van Laethem , Everardo D. Saad , Francesco Sclafani
Older adults are underrepresented in clinical trials, and studies specifically focused on older cancer patients are uncommon. By screening PubMed, EMBASE and proceedings from international meetings, we searched for trials testing systemic therapies in solid cancer patients aged ≥70 years. We identified age-unselected trials testing the same intervention in the same setting. The primary objective was to assess the proportion of older-age-selected trials meeting the target accrual. Secondary objectives included the analysis of the use of geriatric assessment (GA) tools and quality of life (QoL) questionnaires, and the comparison between older-age-selected and matching age-unselected trials.
We included 313 trials (10.9 % phase I, 78.6 % phase I/II-II, and 10.5 % phase III). 7.7 % were published in 1990–2000, 40.3 % in 2001–2011, and 52.1 % in 2012–2023. Of 234 evaluable trials, 77.8 % enrolled ≥90 % of the required patients. Premature study discontinuation occurred in 50 cases (5.9 % phase I, 14.2 % phase II, 39.4 % phase III). Among 232 evaluable trials, 60.3 % met the primary endpoint (63.7 % phase I/II-II, 35.5 % phase III). GA and QoL analyses were carried out in 28.1 % and 23 % of trials, respectively. Corresponding age-unselected trials were identified for 154 older-age-selected trials. Compared with age-unselected trials, a lower proportion of older-age-selected trials met the target accrual (83.5 % vs 94.8 %, p = 0.035) or the primary endpoint (63.9 % vs 81.5 %, p = 0.022). In conclusion, older-age-selected trials are increasingly performed but rarely include GA and QoL analyses. Effective strategies to meet target accrual should be implemented especially for phase III trials, which suffer from high rates of premature discontinuation.
老年人在临床试验中的代表性不足,专门针对老年癌症患者的研究并不常见。通过筛选PubMed、EMBASE和国际会议的会议记录,我们检索了年龄≥70岁的实体癌患者进行全身治疗的试验。我们确定了在相同环境下测试相同干预措施的非年龄选择试验。主要目的是评估符合目标累积的老年人选择试验的比例。次要目标包括分析老年评估(GA)工具和生活质量(QoL)问卷的使用情况,以及老年年龄选择试验和匹配年龄未选择试验之间的比较。我们纳入了313项试验(10.9%为I期,78.6%为I/II-II期,10.5%为III期)。7.7%发表于1990-2000年,40.3%发表于2001-2011年,52.1%发表于2012-2023年。在234项可评价试验中,77.8%的试验纳入了≥90%的所需患者。50例患者过早终止研究(I期5.9%,II期14.2%,III期39.4%)。在232项可评价试验中,60.3%达到了主要终点(63.7%为I/II-II期,35.5%为III期)。分别在28.1%和23%的试验中进行GA和QoL分析。在154项老年选择试验中确定了相应的年龄未选择试验。与未选择年龄的试验相比,较低比例的年龄较大的试验满足了目标累积(83.5% vs 94.8%, p = 0.035)或主要终点(63.9% vs 81.5%, p = 0.022)。总之,老年人选择的试验越来越多,但很少包括GA和QoL分析。应该实施有效的策略来实现目标收益,特别是对于患有高过早终止率的III期试验。
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引用次数: 0
Effectiveness of immune checkpoint inhibitor therapy in thyroid cancer: A systematic review 免疫检查点抑制剂治疗甲状腺癌的有效性:一项系统综述。
IF 10.5 1区 医学 Q1 ONCOLOGY Pub Date : 2025-10-27 DOI: 10.1016/j.ctrv.2025.103042
Jennifer Tasong, Rocco Sheldon, Avi Clements, Muhammad Temour Abid, Andrew Gan

Background

Thyroid cancer incidence has risen in recent years, with high mortality rates in aggressive subtypes. Clinical trials of immune checkpoint inhibitors (ICIs), indicate efficacy against a range of solid tumours. However, their role in the thyroid remains to be established. This systematic review (PROSPERO: CRD420250634944) assesses the effectiveness and safety of ICIs in thyroid cancer, reported following PRISMA guidelines.

Methods

Searches were performed in 6 databases (EMBASE, PubMed, CENTRAL, Scopus, Web of Science and Clinicaltrials.gov) from inception to 10th January 2025. All studies reporting efficacy outcomes for ICIs in thyroid cancer were included. Clinical trials databases were searched for the most recent results and ongoing trials. Study quality was assessed using the CASP checklist.

Results

Of 1,207 studies retrieved, 33 met the inclusion criteria. Of these trials, 14 investigated ICI plus tyrosine kinase inhibitors, and 5 studies each evaluated dual ICI combinations, ICI monotherapy, or ICIs plus chemotherapy or radiotherapy. Included studies reported variable efficacy and safety. Studies in anaplastic thyroid cancer (ATC) using biomarker-stratified ICI combinations demonstrated the greatest effectiveness. The safety profiles were generally manageable, with common adverse events including fatigue, anorexia, and increased lipase levels.

Conclusions

ICIs show promising responses in thyroid cancer, particularly in ATC. However, the current evidence is limited to non-randomised phase I-II studies, and no phase III trials have been conducted to date. Further investigation in larger, placebo-controlled trials is required to assess efficacy in clinical practice. Predictive biomarkers can help identify patients who may experience the greatest clinical benefit, maximising cost-effectiveness.
背景:近年来甲状腺癌发病率上升,侵袭性亚型死亡率高。免疫检查点抑制剂(ICIs)的临床试验表明,对一系列实体肿瘤有效。然而,它们在甲状腺中的作用仍有待确定。该系统综述(PROSPERO: CRD420250634944)评估了ICIs治疗甲状腺癌的有效性和安全性,报告遵循PRISMA指南。方法:在EMBASE、PubMed、CENTRAL、Scopus、Web of Science和Clinicaltrials.gov等6个数据库中进行检索,检索时间为2025年1月10日。所有报告ICIs治疗甲状腺癌疗效结果的研究均被纳入。在临床试验数据库中搜索最新的结果和正在进行的试验。使用CASP检查表评估研究质量。结果:在1207项研究中,33项符合纳入标准。在这些试验中,14项研究了ICI加酪氨酸激酶抑制剂,5项研究分别评估了双重ICI联合、ICI单药治疗或ICI加化疗或放疗。纳入的研究报告了不同的疗效和安全性。在间变性甲状腺癌(ATC)的研究中,使用生物标志物分层ICI组合显示出最大的效果。安全性一般是可控的,常见的不良事件包括疲劳、厌食症和脂肪酶水平升高。结论:ICIs在甲状腺癌,特别是ATC中显示出良好的疗效。然而,目前的证据仅限于非随机I-II期研究,迄今尚未进行III期试验。需要在更大规模的安慰剂对照试验中进行进一步的研究,以评估临床实践中的疗效。预测性生物标志物可以帮助识别可能获得最大临床效益的患者,从而最大限度地提高成本效益。
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引用次数: 0
Evolving treatment strategies for resectable gastric cancer: Bridging Asia-West disparities toward personalized and integrated therapy 可切除胃癌治疗策略的演变:弥合亚洲-西方在个性化和综合治疗方面的差异。
IF 10.5 1区 医学 Q1 ONCOLOGY Pub Date : 2025-10-24 DOI: 10.1016/j.ctrv.2025.103041
Xuesong Zhao , Qianyun Hao , Maria Alsina , Daniel Acosta , Florian Castet , Eduardo Terán , Kreina Vega Cano , Tamara Saurí , Ismael Macías , Takaki Yoshikawa , Sandra Castro , Hirokazu Shoji , Florian Lordick , Zhanlong Shen , Tian V. Tian , Teresa Macarulla
Gastric cancer (GC) remains a significant global health burden. Both Asian countries and Western nations, represented by Europe and North America, have long been pioneers in GC research and continue to lead advancements in the field. However, notable differences have historically existed between these regions in the treatment of resectable GC. In recent years, increasing convergence between Asian and Western approaches has emerged, driven by the growth of global collaborative studies. New definitive evidence suggests that the therapeutic landscape for resectable GC may undergo a significant transformation. In this review, we comprehensively examine the evolution of surgical approaches and perioperative chemotherapy strategies in Asia and the West. We summarize key clinical trials, highlight persistent survival disparities, and provide insight into current trends in perioperative management, including the recent advances in molecularly driven perioperative treatments. Finally, we outline key considerations for future multicenter perioperative trials to further guide global clinical practice.
胃癌(GC)仍然是一个重大的全球健康负担。亚洲国家和以欧洲和北美为代表的西方国家长期以来一直是气相色谱研究的先驱,并继续引领该领域的进步。然而,历史上这些区域在治疗可切除胃癌方面存在显著差异。近年来,在全球合作研究的推动下,亚洲和西方的研究方法越来越趋同。新的明确证据表明,可切除胃癌的治疗前景可能会发生重大转变。在这篇综述中,我们全面研究了亚洲和西方手术入路和围手术期化疗策略的发展。我们总结了关键的临床试验,强调了持续的生存差异,并提供了当前围手术期管理的趋势,包括分子驱动围手术期治疗的最新进展。最后,我们概述了未来多中心围手术期试验的关键考虑因素,以进一步指导全球临床实践。
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引用次数: 0
An umbrella review of systematic reviews on the diagnostic and prognostic utility of circulating tumor DNA and MicroRNA in colorectal cancer 综述了循环肿瘤DNA和MicroRNA在结直肠癌中的诊断和预后应用的系统综述
IF 10.5 1区 医学 Q1 ONCOLOGY Pub Date : 2025-10-20 DOI: 10.1016/j.ctrv.2025.103040
Sameh Hany Emile , Anjelli Wignakumar , Ajia Syed , Nir Horesh , Samer Hani Barsom , Zoe Garoufalia , Steven D. Wexner

Background

This umbrella review aimed to summarize and critically evaluate systematic reviews on the applications of circulating tumor DNA (ctDNA) and microRNA in colorectal cancer (CRC).

Methods

A PRISMA-compliant umbrella overview of systematic reviews was conducted. PubMed and Scopus were searched through October 2024 for systematic reviews that assessed the diagnostic and prognostic utility of ctDNA and microRNA in CRC. The diagnostic accuracy of ctDNA and microRNA in the detection of CRC and associated genetic mutations, and the association between ctDNA and disease recurrence and survival were assessed.

Results

26 systematic reviews were included. ctDNA had pooled sensitivity and specificity in detecting KRAS mutations of 75–83 % and 91–98 %, respectively. MicroRNA had a 59–76 % pooled sensitivity and 64–89 % pooled specificity in the detection of CRC. The detection of ctDNA after surgery for CRC was associated with increased recurrence, and the risk was higher when detection followed adjuvant chemotherapy. The detection of ctDNA was associated with an increased recurrence of colorectal metastases and worse overall survival. ctDNA was associated with an increased risk of rectal cancer recurrence and reduced odds of pathologic complete response when detected after neoadjuvant therapy and after surgery. The increased risk of recurrence associated with ctDNA was proportional to the disease stage; however, evidence on this observation is limited to one meta-analysis.

Conclusions

Detection of ctDNA before or after treatment of CRC, regardless of the stage, was associated with both increased recurrence and decreased survival. This negative impact was more notable when ctDNA was detected after locoregional treatment.
本综述旨在总结和批判性评价循环肿瘤DNA (ctDNA)和microRNA在结直肠癌(CRC)中的应用的系统综述。方法采用符合prisma标准的系统综述。到2024年10月,PubMed和Scopus检索了评估ctDNA和microRNA在结直肠癌诊断和预后应用的系统综述。评估ctDNA和microRNA检测结直肠癌及相关基因突变的诊断准确性,以及ctDNA与疾病复发和生存的关系。结果共纳入26篇系统评价。ctDNA检测KRAS突变的敏感性和特异性分别为75 - 83%和91 - 98%。MicroRNA检测CRC的总敏感性为59 - 76%,总特异性为64 - 89%。结直肠癌术后检测ctDNA与复发增加相关,且在辅助化疗后检测ctDNA风险更高。ctDNA的检测与结直肠转移的复发率增加和总生存率降低相关。在新辅助治疗和手术后检测到ctDNA与直肠癌复发风险增加和病理完全缓解几率降低相关。与ctDNA相关的复发风险增加与疾病分期成正比;然而,这一观察结果的证据仅限于一项荟萃分析。结论在CRC治疗前或治疗后检测ctDNA,无论分期如何,都与复发率增加和生存率降低相关。当局部区域治疗后检测到ctDNA时,这种负面影响更为显著。
{"title":"An umbrella review of systematic reviews on the diagnostic and prognostic utility of circulating tumor DNA and MicroRNA in colorectal cancer","authors":"Sameh Hany Emile ,&nbsp;Anjelli Wignakumar ,&nbsp;Ajia Syed ,&nbsp;Nir Horesh ,&nbsp;Samer Hani Barsom ,&nbsp;Zoe Garoufalia ,&nbsp;Steven D. Wexner","doi":"10.1016/j.ctrv.2025.103040","DOIUrl":"10.1016/j.ctrv.2025.103040","url":null,"abstract":"<div><h3>Background</h3><div>This umbrella review aimed to summarize and critically evaluate systematic reviews on the applications of circulating tumor DNA (ctDNA) and microRNA in colorectal cancer (CRC).</div></div><div><h3>Methods</h3><div>A PRISMA-compliant umbrella overview of systematic reviews was conducted. PubMed and Scopus were searched through October 2024 for systematic reviews that assessed the diagnostic and prognostic utility of ctDNA and microRNA in CRC. The diagnostic accuracy of ctDNA and microRNA in the detection of CRC and associated genetic mutations, and the association between ctDNA and disease recurrence and survival were assessed.</div></div><div><h3>Results</h3><div>26 systematic reviews were included. ctDNA had pooled sensitivity and specificity in detecting KRAS mutations of 75–83 % and 91–98 %, respectively. MicroRNA had a 59–76 % pooled sensitivity and 64–89 % pooled specificity in the detection of CRC. The detection of ctDNA after surgery for CRC was associated with increased recurrence, and the risk was higher when detection followed adjuvant chemotherapy. The detection of ctDNA was associated with an increased recurrence of colorectal metastases and worse overall survival. ctDNA was associated with an increased risk of rectal cancer recurrence and reduced odds of pathologic complete response when detected after neoadjuvant therapy and after surgery. The increased risk of recurrence associated with ctDNA was proportional to the disease stage; however, evidence on this observation is limited to one meta-analysis.</div></div><div><h3>Conclusions</h3><div>Detection of ctDNA before or after treatment of CRC, regardless of the stage, was associated with both increased recurrence and decreased survival. This negative impact was more notable when ctDNA was detected after locoregional treatment.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103040"},"PeriodicalIF":10.5,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145360443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Clinical course and treatment outcomes in solid-basaloid adenoid cystic carcinoma of the breast: A systematic review and case report 乳腺固体基底样腺样囊性癌的临床过程和治疗结果:系统回顾和病例报告
IF 10.5 1区 医学 Q1 ONCOLOGY Pub Date : 2025-10-20 DOI: 10.1016/j.ctrv.2025.103028
Stephanie Kim , Kyle Sheth , Xiaoying Yu , Laura Porterfield , Elizabeth M. Vaughan

Background

Adenoid Cystic Carcinoma (ACC) is a rare, indolent subtype of triple-negative breast cancer, accounting for < 0.1 % of cases. The solid-basaloid subtype (SBACC), comprising approximately one-quarter of breast ACCs, has a poorer prognosis. While ACC is typically managed with surgery and is chemo-resistant, SBACC is more aggressive and often treated with chemotherapy and, more recently, immunotherapy—though supporting evidence remains limited.

Aim

To assess clinical characteristics and treatment outcomes of SBACC of the breast.

Methods

This study presents a case of breast SBACC and a systematic review of five databases (inception–September 10, 2024). Eligible studies reported clinical course, treatment, and outcomes. Exclusions included duplicates, non-SBACC focus, animal studies, and those lacking clinical or with only pathological data. Descriptive statistics were used for binary and categorical variables. Risk of bias was assessed using JBI tools, following PRISMA 2020 guidelines. The review is registered in PROSPERO.

Results

Nineteen studies and one new case (134 patients, aged 19–89) were included. Except for three patients who had with metastatic disease at diagnosis, the rest (97 %) were treated with surgery; 55.6 % received chemotherapy. Among nine patients given neoadjuvant chemotherapy and/or immunotherapy, none achieved complete pathological response, and most had poor outcomes. In non-metastatic cases with reported treatment (n = 99), younger age predicted recurrence (p = 0.032) but not chemotherapy receipt (p = 0.082). Chemotherapy did not reduce recurrence risk (p = 0.819). Mastectomy versus breast-conserving surgery with radiation had similar outcomes (p = 0.197).

Conclusions

Although limited data are available for this rare cancer, evidence for the efficacy of chemotherapy and immunotherapy for SBACC treatment is lacking. Treatment plans should be individualized to reduce the physical, psychological, and financial burdens on both patients and healthcare systems.
背景:腺样囊性癌(ACC)是一种罕见的三阴性乳腺癌的惰性亚型,占病例的0.1%。固体基底样细胞亚型(SBACC)约占乳腺acc的四分之一,预后较差。虽然ACC通常采用手术治疗并且具有化疗耐药性,但SBACC更具侵袭性,通常采用化疗治疗,最近还采用免疫治疗,尽管支持证据仍然有限。目的探讨乳腺SBACC的临床特点及治疗效果。方法:本研究报告1例乳腺SBACC病例,并对5个数据库进行系统回顾(开始- 2024年9月10日)。符合条件的研究报告了临床过程、治疗和结果。排除包括重复、非sbacc焦点、动物研究以及缺乏临床或只有病理资料的研究。二元和分类变量采用描述性统计。根据PRISMA 2020指南,使用JBI工具评估偏倚风险。该评论已在PROSPERO上注册。结果纳入19项研究和1例新病例(134例,年龄19 ~ 89岁)。除3例确诊时已发生转移性疾病的患者外,其余患者(97%)均接受手术治疗;55.6%接受化疗。在接受新辅助化疗和/或免疫治疗的9例患者中,没有一例达到完全的病理反应,大多数预后较差。在接受治疗的非转移性病例中(n = 99),较年轻的年龄预测复发(p = 0.032),而不是化疗时间(p = 0.082)。化疗没有降低复发风险(p = 0.819)。乳房切除术与保乳放射手术的结果相似(p = 0.197)。结论尽管关于这种罕见癌症的数据有限,但化疗和免疫治疗对SBACC治疗的有效性证据缺乏。治疗方案应个性化,以减轻患者和医疗保健系统的身体、心理和经济负担。
{"title":"Clinical course and treatment outcomes in solid-basaloid adenoid cystic carcinoma of the breast: A systematic review and case report","authors":"Stephanie Kim ,&nbsp;Kyle Sheth ,&nbsp;Xiaoying Yu ,&nbsp;Laura Porterfield ,&nbsp;Elizabeth M. Vaughan","doi":"10.1016/j.ctrv.2025.103028","DOIUrl":"10.1016/j.ctrv.2025.103028","url":null,"abstract":"<div><h3>Background</h3><div>Adenoid Cystic Carcinoma (ACC) is a rare, indolent subtype of triple-negative breast cancer, accounting for &lt; 0.1 % of cases. The solid-basaloid subtype (SBACC), comprising approximately one-quarter of breast ACCs, has a poorer prognosis. While ACC is typically managed with surgery and is chemo-resistant, SBACC is more aggressive and often treated with chemotherapy and, more recently, immunotherapy—though supporting evidence remains limited.</div></div><div><h3>Aim</h3><div>To assess clinical characteristics and treatment outcomes of SBACC of the breast.</div></div><div><h3>Methods</h3><div>This study presents a case of breast SBACC and a systematic review of five databases (inception–September 10, 2024). Eligible studies reported clinical course, treatment, and outcomes. Exclusions included duplicates, non-SBACC focus, animal studies, and those lacking clinical or with only pathological data. Descriptive statistics were used for binary and categorical variables. Risk of bias was assessed using JBI tools, following PRISMA 2020 guidelines. The review is registered in PROSPERO.</div></div><div><h3>Results</h3><div>Nineteen studies and one new case (134 patients, aged 19–89) were included. Except for three patients who had with metastatic disease at diagnosis, the rest (97 %) were treated with surgery; 55.6 % received chemotherapy. Among nine patients given neoadjuvant chemotherapy and/or immunotherapy, none achieved complete pathological response, and most had poor outcomes. In non-metastatic cases with reported treatment (n = 99), younger age predicted recurrence (p = 0.032) but not chemotherapy receipt (p = 0.082). Chemotherapy did not reduce recurrence risk (p = 0.819). Mastectomy versus breast-conserving surgery with radiation had similar outcomes (p = 0.197).</div></div><div><h3>Conclusions</h3><div>Although limited data are available for this rare cancer, evidence for the efficacy of chemotherapy and immunotherapy for SBACC treatment is lacking. Treatment plans should be individualized to reduce the physical, psychological, and financial burdens on both patients and healthcare systems.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103028"},"PeriodicalIF":10.5,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145360768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
期刊
Cancer treatment reviews
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