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The efficacy of trastuzumab-deruxtecan for the treatment of patients with advanced HER2-low breast cancer. 曲妥珠单抗-德鲁司坦治疗晚期 HER2 低乳腺癌患者的疗效。
IF 2.9 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2023-09-12 DOI: 10.1080/14737140.2023.2171993
Ilana Schlam, Sara M Tolaney, Paolo Tarantino

Introduction: Until recently, the available human receptor epidermal growth factor 2 (HER2) targeted agents were ineffective for treating patients with HER2-low expressing breast cancer (defined as immunohistochemical expression of 1+ or 2+ without amplification). The development of novel and potent HER2-directed antibody-drug conjugates, affective at treating HER2-low expressing breast cancers, have changed the way we think about HER2-low expression and expanded the treatment options for many patients with advanced disease.

Areas covered: In this review, we summarize the current management of HER2-low breast cancer and commonly encountered challenges such as treatment sequencing and toxicity management.

Expert opinion: trastuzumab deruxtecan (T-DXd) is a treatment option for patients with advanced, HER2-low breast cancer, irrespective of the hormone receptor status. The current optimal place in treatment algorithms is after the first line of chemotherapy, both in HR-positive and triple-negative breast cancer; however, other agents are available in this setting and risks and benefits for each should be considered in shared decision making. Up to 10-15% of patients receiving T-DXd develop interstitial lung disease. Patient and clinician education are key to safely implement T-DXd in clinical practice.

简介直到最近,现有的人类受体表皮生长因子 2(HER2)靶向药物对治疗 HER2 低表达乳腺癌患者(定义为免疫组化表达为 1+ 或 2+,无扩增)效果不佳。新型强效 HER2 靶向抗体-药物共轭物的开发可有效治疗 HER2 低表达乳腺癌,改变了我们对 HER2 低表达的看法,为许多晚期患者提供了更多的治疗选择:专家观点:无论激素受体状态如何,曲妥珠单抗德鲁司坦(T-DXd)都是晚期HER2低表达乳腺癌患者的治疗选择。目前,无论是HR 阳性还是三阴性乳腺癌,其最佳治疗方案都是在一线化疗之后;不过,在这种情况下也可使用其他药物,在共同决策时应考虑每种药物的风险和益处。在接受 T-DXd 治疗的患者中,高达 10-15% 的患者会出现间质性肺病。在临床实践中安全使用 T-DXd 的关键是对患者和临床医生进行教育。
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引用次数: 0
The diagnostic value of CYFRA 21-1 in oral squamous cell carcinoma: a meta-analysis. CYFRA 21-1 在口腔鳞状细胞癌中的诊断价值:一项荟萃分析。
IF 2.9 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-09-23 DOI: 10.1080/14737140.2024.2405225
Yuting Liang, Zhenke Yi, Jiajin Li, Jufeng Ye

Background: Previous studies have revealed the importance of CYFRA 21-1 in the diagnosis of oral squamous cell cancer (OSCC). However, the results are inconsistent. This meta-analysis is to evaluate CYFRA 21-1's efficacy in distinguishing OSCC.

Methods: Systematic searches of Web of Science, PubMed, and CNKI (1996-2024) were conducted following the Preferred Reporting ltems for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results: Analysis of 693 patients and 548 controls yielded combined sensitivity (SEN) of 0.71 (95% CI: 0.68, 0.75), specificity (SPE) of 0.88 (95% CI: 0.85, 0.90), and area under the curve (AUC) of 0.927. Subgroup analysis showed higher SEN (0.88), SPE (0.93), and AUC (0.962) in saliva versus serum. Enzyme-linked immunosorbent assay (ELISA) demonstrated superior performance over electrochemiluminescent immunoassay (ECLIA) (AUC: 0.968 vs. 0.868).

Conclusion: CYFRA 21-1 is effective in OSCC diagnosis, with ELISA showing better sensitivity. Saliva emerges as a promising diagnostic medium compared to serum.

Registration: PROSPERO CRD42024566835.

背景:以往的研究表明,CYFRA 21-1 在诊断口腔鳞状细胞癌(OSCC)中具有重要作用。然而,研究结果并不一致。本荟萃分析旨在评估 CYFRA 21-1 在鉴别 OSCC 方面的功效:方法:按照《系统综述和荟萃分析首选报告标准》(Preferred Reporting ltems for Systematic Reviews and Meta-Analyses,PRISMA)指南对 Web of Science、PubMed 和 CNKI(1996-2024 年)进行系统检索:对 693 例患者和 548 例对照进行分析后得出的综合灵敏度 (SEN) 为 0.71(95% CI:0.68, 0.75),特异性 (SPE) 为 0.88(95% CI:0.85, 0.90),曲线下面积 (AUC) 为 0.927。亚组分析显示,唾液的 SEN(0.88)、SPE(0.93)和 AUC(0.962)均高于血清。酶联免疫吸附测定(ELISA)的性能优于电化学发光免疫测定(ECLIA)(AUC:0.968 对 0.868):结论:CYFRA 21-1 可有效诊断 OSCC,ELISA 的灵敏度更高。结论:CYFRA 21-1 对 OSCC 诊断有效,ELISA 的灵敏度更高,与血清相比,唾液是一种很有前景的诊断介质:注册号:PREMCORD42024566835。
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引用次数: 0
Optimising CAR T therapy for the treatment of solid tumors. 优化治疗实体瘤的 CAR T 疗法。
IF 2.9 3区 医学 Q2 ONCOLOGY Pub Date : 2024-10-28 DOI: 10.1080/14737140.2024.2421194
Norhan Mobark, Caroline Malai Hull, John Maher

Introduction: Adoptive immunotherapy using chimeric antigen receptor (CAR)-engineered T cells has proven transformative in the management of B cell and plasma cel derived malignancies. However, solid tumors have largely proven to be resistant to this therapeutic modality. Challenges include the paucity of safe target antigens, heterogeneity of target expression within the tumor, difficulty in delivery of CAR T cells to the site of disease, poor penetration within solid tumor deposits and inability to circumvent the array of immunosuppressive and biophysical barriers imposed by the solid tumor microenvironment.

Areas covered: Literature was reviewed on the PubMed database, excluding occasional papers which were not available as open access publications or through other means.

Expert opinion: Here, we have surveyed the large body of technological advances that have been made in the quest to bridge the gap toward successful deployment of CAR T cells for the treatment of solid tumors. These encompass the development of more sophisticated targeting strategies to engage solid tumor cells safely and comprehensively, improved drug delivery solutions, design of novel CAR architectures that achieve improved functional persistence and which resist physical, chemical and biological hurdles present in tumor deposits. Prospects for combination therapies that incorporate CAR T cells are also considered.

简介:事实证明,使用嵌合抗原受体(CAR)工程化 T 细胞的采用性免疫疗法在治疗 B 细胞和浆细胞衍生的恶性肿瘤方面具有变革性意义。然而,实体瘤在很大程度上被证明对这种治疗方式具有抗药性。面临的挑战包括缺乏安全的靶抗原、肿瘤内靶点表达的异质性、难以将 CAR T 细胞递送到发病部位、在实体瘤沉积物内穿透力差以及无法绕过实体瘤微环境施加的一系列免疫抑制和生物物理障碍:对 PubMed 数据库中的文献进行了审查,但不包括偶尔出现的无法以开放获取出版物或其他方式获得的论文:在此,我们回顾了在成功应用 CAR T 细胞治疗实体瘤的道路上取得的大量技术进步。这些进步包括:开发了更复杂的靶向策略,以安全、全面地接触实体肿瘤细胞;改进了给药方案;设计了新型 CAR 架构,以提高功能持久性,并抵御肿瘤沉积物中存在的物理、化学和生物障碍。此外,还考虑了结合 CAR T 细胞的综合疗法的前景。
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引用次数: 0
The efficacy of Veliparib in combination with chemotherapy in the treatment of lung cancer: systematic review and meta-analysis. 维利帕尼联合化疗治疗肺癌的疗效:系统综述和荟萃分析。
IF 2.9 3区 医学 Q2 ONCOLOGY Pub Date : 2024-10-20 DOI: 10.1080/14737140.2024.2417770
Muataz Kashbour, Abdulhameed Alhadeethi, Sara Awwad, Mazen Yassin, Ahmed Amin, Mohamed Abed, Abubaker Abdelmalik, Yasmeen Jamal Alabdallat

Objective: This meta-analysis aims to examine the effectiveness of veliparib, a poly ADP-ribose polymerase inhibitor, in combination with chemotherapy in treating bronchogenic carcinoma.

Methods: PubMed, Cochrane, Scopus, and Web of Science were searched for eligible randomized controlled trials comparing veliparib plus chemotherapy to standard chemotherapy in adult lung cancer patients, until July 2023. The main outcomes were overall survival (OS) and progression-free survival (PFS).

Results: This meta-analysis included six studies encompassing 2,136 patients. Veliparib has a slight OS improvement over placebo, HR = 0.91, 95% CI [0.83 to 1.0], p = 0.05. Veliparib offers more OS benefit in the subpopulation of non-small cell lung cancer (NSCLC) than small-cell lung cancer (SCLC), HR = 0.89, 95% CI [0.81,0.99], p = 0.03 and HR = 1.00, 95% CI [0.79, 1.28], p = 0.97, respectively. There was no significant PFS benefit between the two groups, HR = 0.92, 95% CI [0.81-1.01], p = 0.08).

Conclusion: Veliparib has a marginal inclination for overall survival improvement, more so in NSCLC, with an acceptable safety profile. Our results merit the pursuit of better-powered trials to support further the extent of veliparib's effectiveness in lung cancer patients.

Registration: PROSPERO (CRD42023453705).

研究目的本荟萃分析旨在研究多ADP核糖聚合酶抑制剂veliparib联合化疗治疗支气管癌的有效性:方法:在PubMed、Cochrane、Scopus和Web of Science网站上检索了2023年7月之前在成人肺癌患者中比较veliparib联合化疗与标准化疗的符合条件的随机对照试验。主要结果为总生存期(OS)和无进展生存期(PFS):这项荟萃分析包括六项研究,共涉及2136名患者。与安慰剂相比,Veliparib的OS略有改善,HR = 0.91,95% CI [0.83 to 1.0],P = 0.05。在非小细胞肺癌(NSCLC)亚群中,Veliparib比小细胞肺癌(SCLC)带来更多的OS获益,分别为HR = 0.89,95% CI [0.81,0.99],p = 0.03和HR = 1.00,95% CI [0.79,1.28],p = 0.97。两组患者的 PFS 均无明显获益(HR = 0.92,95% CI [0.81-1.01],p = 0.08):结论:Veliparib在改善总生存期方面有微弱的倾向性,在NSCLC中更为明显,其安全性可接受。我们的研究结果值得进行更有力的试验,以进一步证实veliparib对肺癌患者的有效性:prospero(CRD42023453705)。
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引用次数: 0
The evolving role of multidisciplinary teams in optimizing non-muscle invasive bladder cancer care. 多学科团队在优化非肌层浸润性膀胱癌治疗中不断发展的作用。
IF 2.9 3区 医学 Q2 ONCOLOGY Pub Date : 2024-10-18 DOI: 10.1080/14737140.2024.2417768
Amanda A Myers, Alexis R Steinmetz, Ashish M Kamat

Introduction: Non-muscle invasive bladder cancer (NMIBC) represents a significant portion of bladder cancer cases and imposes a substantial economic burden, stemming from both direct treatment costs and long-term surveillance. As the treatment landscape evolves with advances in immunotherapy and targeted therapies, a multidisciplinary approach to management is increasingly crucial for optimizing patient outcomes and resource utilization.

Areas covered: A PubMed search from 2010 to 15 June 2024 was conducted. This review examines the evolving role of multidisciplinary team (MDT) care in NMIBC management. It explores the potential benefits of MDT care, including improved risk stratification and personalized treatment plans, while acknowledging the challenges to implementation and proposing strategies to overcome them.

Expert opinion: With a growing understanding of NMIBC and expanding therapeutic options, MDT care is pivotal in navigating patient care and maximizing outcomes. Strategic planning and collaborative efforts will facilitate the broader adoption of MDT care, enhancing the value of NMIBC treatment. MDT care holds promise for personalized, effective, and cost-efficient care for patients with NMIBC in the future.

导言:非肌层浸润性膀胱癌(NMIBC)在膀胱癌病例中占很大比例,其直接治疗费用和长期监测费用都造成了巨大的经济负担。随着免疫疗法和靶向疗法的发展,多学科的治疗方法对于优化患者预后和资源利用越来越重要:对 2010 年至 2024 年 6 月 15 日的 PubMed 进行了检索。本综述探讨了多学科团队 (MDT) 治疗在 NMIBC 管理中不断发展的作用。它探讨了多学科团队治疗的潜在益处,包括改进的风险分层和个性化治疗计划,同时也承认了实施过程中面临的挑战,并提出了克服这些挑战的策略:专家观点:随着人们对 NMIBC 的认识不断加深,治疗方案不断扩大,MDT 护理在指导患者护理和最大限度地提高疗效方面至关重要。战略规划和合作努力将促进更广泛地采用 MDT 护理,提高 NMIBC 治疗的价值。MDT 护理有望在未来为 NMIBC 患者提供个性化、有效和具有成本效益的治疗。
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引用次数: 0
Strategies for the prevention or reversal of PARP inhibitor resistance. 预防或逆转 PARP 抑制剂耐药性的策略。
IF 2.9 3区 医学 Q2 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-20 DOI: 10.1080/14737140.2024.2393251
Zahi Mitri, Shaun M Goodyear, Gordon Mills

Introduction: Advances in our understanding of tumor biology shed light on hallmarks of cancer development and progression that include dysregulated DNA damage repair (DDR) machinery. Leveraging the underlying tumor genomic instability and tumor-specific defects in DDR, Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) induced DNA damage emerges as a novel non-chemotherapy therapeutic opportunity. PARPis are currently approved in multiple tumor types, with the largest benefit seen in tumors with homologous recombination repair (HRR) deficiency, including germline and somatic mutations in BRCA1/2 genes (BRCA) and other pathway members such as PALB2 and Rad51c.

Areas covered: This review article summarizes the current approval landscape and known and proposed mechanisms of resistance to PARPi. Further, therapeutic strategies to overcome PARPi resistance are discussed, including ongoing clinical trials.

Expert opinion: PARPi have proven to be a safe and effective therapy and represents a cornerstone treatment across multiple solid tumor types. Elucidating innate and acquired mechanisms of resistance, coupled with the emergence of novel therapeutic options to capitalize on the activity of PARPi and prevent or reverse the acquisition of resistance, provides an opportunity to further expand the role of PARPi in cancer therapy.

导言:随着对肿瘤生物学认识的不断深入,人们发现了癌症发生和发展的特征,其中包括 DNA 损伤修复(DDR)机制失调。利用潜在的肿瘤基因组不稳定性和肿瘤特异性 DDR 缺陷,聚(ADP-核糖)聚合酶(PARP)抑制剂(PARPi)诱导的 DNA 损伤成为一种新的非化疗治疗机会。PARPi目前已被批准用于多种肿瘤类型,其中同源重组修复(HRR)缺陷的肿瘤获益最大,包括BRCA1/2基因(BRCA)和其他通路成员(如PALB2和Rad51c)的种系突变和体细胞突变:这篇综述文章概述了目前的批准情况以及已知和提出的 PARPi 耐药机制。此外,文章还讨论了克服PARPi耐药性的治疗策略,包括正在进行的临床试验:PARPi已被证明是一种安全有效的疗法,是多种实体瘤类型治疗的基石。阐明先天和后天的耐药性机制,加上利用 PARPi 的活性、预防或逆转耐药性的新型治疗方案的出现,为进一步扩大 PARPi 在癌症治疗中的作用提供了机会。
{"title":"Strategies for the prevention or reversal of PARP inhibitor resistance.","authors":"Zahi Mitri, Shaun M Goodyear, Gordon Mills","doi":"10.1080/14737140.2024.2393251","DOIUrl":"10.1080/14737140.2024.2393251","url":null,"abstract":"<p><strong>Introduction: </strong>Advances in our understanding of tumor biology shed light on hallmarks of cancer development and progression that include dysregulated DNA damage repair (DDR) machinery. Leveraging the underlying tumor genomic instability and tumor-specific defects in DDR, Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) induced DNA damage emerges as a novel non-chemotherapy therapeutic opportunity. PARPis are currently approved in multiple tumor types, with the largest benefit seen in tumors with homologous recombination repair (HRR) deficiency, including germline and somatic mutations in BRCA1/2 genes (BRCA) and other pathway members such as PALB2 and Rad51c.</p><p><strong>Areas covered: </strong>This review article summarizes the current approval landscape and known and proposed mechanisms of resistance to PARPi. Further, therapeutic strategies to overcome PARPi resistance are discussed, including ongoing clinical trials.</p><p><strong>Expert opinion: </strong>PARPi have proven to be a safe and effective therapy and represents a cornerstone treatment across multiple solid tumor types. Elucidating innate and acquired mechanisms of resistance, coupled with the emergence of novel therapeutic options to capitalize on the activity of PARPi and prevent or reverse the acquisition of resistance, provides an opportunity to further expand the role of PARPi in cancer therapy.</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982054","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
Efficacy of doxorubicin and lipiodol therapy by trans-arterial chemoembolization in hepatocellular carcinoma Egyptian patients and relation to genetic polymorphisms. 埃及肝细胞癌患者经动脉化疗栓塞治疗多柔比星和脂碘的疗效及与基因多态性的关系。
IF 2.9 3区 医学 Q2 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-21 DOI: 10.1080/14737140.2024.2391364
Rehab H Werida, Omnia A Abd El Baset, Safaa Askar, Marwa El-Mohamdy, Gamal A Omran, Radwa Samir Hagag

Background: Genetic polymorphisms play a crucial role in predicting treatment efficacy in patients with hepatocellular carcinoma (HCC). This study aims to evaluate the response to Transarterial Chemoembolization (TACE) in relation to the genetic polymorphisms of interleukin 28B (IL28B) and angiopoietin-2 (ANGPT2) in HCC patients.

Research design and methods: Prospective cohort study conducted on 104 eligible HCC Egyptian patients who underwent TACE using doxorubicin and lipiodol. Genotyping of the IL28B and ANGPT2 genes was performed with laboratory data analysis.

Results: At baseline IL28B rs12979860 genotypes C/T, C/C and T/T appeared in 43.9%, 34.6% and 21.5% while ANGPT2 rs55633437 genotypes C/C, C/A and A/A found in 71.03%, 28.04% and 0.93% of patients respectively. After one month of therapy, 51.4% of patients achieved a complete response. There was a significant difference in relation to IL28B rs12979860 genotypes (p = 0.017) whereas ANGPT2 rs55633437 genotypes (p = 0.432) showed no significant difference in patient response after one month of TACE.

Conclusion: This study demonstrates the effectiveness of TACE in Egyptian HCC patients, as evidenced by low recurrence rates. Furthermore, the IL28B rs12979860 (C/T) gene may be associated with the efficacy and prognosis of TACE treatment in HCC Egyptian patients.

Trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05291338).

背景:基因多态性在预测肝细胞癌(HCC)患者的治疗效果方面起着至关重要的作用。本研究旨在评估经动脉化疗栓塞术(TACE)对 HCC 患者的反应与白细胞介素 28B (IL28B)和血管生成素-2(ANGPT2)基因多态性的关系:前瞻性队列研究:对 104 名符合条件的 HCC 埃及患者进行了前瞻性队列研究,这些患者接受了使用多柔比星和脂肪碘的 TACE。通过实验室数据分析对 IL28B 和 ANGPT2 基因进行基因分型:基线IL28B rs12979860基因型为C/T、C/C和T/T的患者分别占43.9%、34.6%和21.5%,而ANGPT2 rs55633437基因型为C/C、C/A和A/A的患者分别占71.03%、28.04%和0.93%。治疗一个月后,51.4% 的患者获得了完全应答。IL28B rs12979860 基因型(p = 0.017)与 TACE 治疗一个月后患者的反应有显著差异,而 ANGPT2 rs55633437 基因型(p = 0.432)与 TACE 治疗一个月后患者的反应无显著差异。结论:本研究证明了 TACE 对埃及 HCC 患者的有效性,复发率低就是证明。此外,IL28B rs12979860 (C/T) 基因可能与埃及 HCC 患者 TACE 治疗的疗效和预后有关:该试验已在 ClinicalTrials.gov 注册(CT.gov 识别码:NCT05291338)。
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引用次数: 0
Current immunotherapy techniques in meningioma. 脑膜瘤的现有免疫疗法技术。
IF 2.9 3区 医学 Q2 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-04 DOI: 10.1080/14737140.2024.2399252
Alexandra J White, Maya Harary, Joshua Casaos, Richard G Everson

Introduction: Although meningiomas are the most common primary brain tumor, there are limited treatment options for recurrent or aggressive lesions. Compared to other brain tumors, meningiomas may be uniquely amenable to immunotherapy by virtue of their location outside the blood-brain barrier.

Areas covered: This review describes our current understanding of the immunology of the meninges, as well as immune cell infiltration and immune signaling in meningioma. Current literature on meningioma immunology and immunotherapy was comprehensively reviewed and summarized by a comprehensive search of MEDLINE (1/1/1990-6/1/2024). Further, we describe the current state of immunotherapeutic approaches, as well as potential future targets. Potential immunotherapeutic approaches include immune checkpoint inhibition, CAR-T approaches, tumor vaccine therapy, and immunogenic molecular markers.

Expert opinion: Meningioma immunotherapy is in early stages, as no immunotherapies are currently included in treatment guidelines. There is substantial heterogeneity in immune cell infiltration, immunogenicity, and immune escape across tumors, even within tumor grade. Furthering our understanding of meningioma immunology and tumor classification will allow for careful selection of tumors and patient populations that may benefit from primary or adjunctive immunotherapy for meningioma.

简介:尽管脑膜瘤是最常见的原发性脑肿瘤,但针对复发或侵袭性病变的治疗方案却十分有限。与其他脑肿瘤相比,脑膜瘤由于位于血脑屏障之外,可能是唯一适合采用免疫疗法的肿瘤:本综述介绍了我们目前对脑膜免疫学以及脑膜瘤免疫细胞浸润和免疫信号转导的认识。通过对 MEDLINE(1/1/1990-6/1/2024)的全面检索,我们对当前有关脑膜瘤免疫学和免疫疗法的文献进行了全面回顾和总结。此外,我们还介绍了免疫治疗方法的现状以及未来的潜在靶点。潜在的免疫治疗方法包括免疫检查点抑制、CAR-T方法、肿瘤疫苗疗法和免疫原分子标记物:脑膜瘤免疫疗法尚处于早期阶段,因为目前还没有将免疫疗法纳入治疗指南。不同肿瘤的免疫细胞浸润、免疫原性和免疫逃逸存在很大的异质性,甚至在肿瘤分级中也是如此。我们对脑膜瘤免疫学和肿瘤分类的进一步了解将有助于仔细选择可能从脑膜瘤主要或辅助免疫疗法中获益的肿瘤和患者群体。
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引用次数: 0
Intra-arterial administration of PSMA-targeted radiopharmaceuticals for brain tumors: is the era of interventional theranostics next? 动脉内注射 PSMA 靶向放射性药物治疗脑肿瘤:下一个是介入治疗学时代吗?
IF 2.9 3区 医学 Q2 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-29 DOI: 10.1080/14737140.2024.2398492
Valerio Da Ros, Luca Filippi, Francesco Garaci

In recent years, prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein, has emerged as a promising biomarker for theranostics, integrating diagnosis and therapy. PSMA's overexpression in various tumors, including brain metastases and high-grade gliomas, suggests its potential in neuro-oncology. Pruis et al. conducted a proof-of-concept study comparing intra-arterial (IA) and intravenous (IV) administration of 68Ga-PSMA-11 in brain tumor patients, aiming to enhance radioligand therapy (RLT) outcomes. Ten patients underwent IV and super-selective IA (ssIA) tracer administration, showing higher tumor uptake and more favorable biodistribution after ssIA administration on positron emission tomography (PET). Dosimetry modeling on the basis of PET data resulted in median absorbed radiation doses per tumor per cycle notably higher with ssIA with respect to IV administration, indicating its potential for RLT optimization. Challenges persist, notably in penetrating intact blood-brain barriers and targeting tumor cells effectively. To overcome these limitations, novel approaches like convection-enhanced delivery and focused ultrasound warrant exploration. Safety concerns, though minimal in this study, underscore the need for larger trials and AI-assisted procedures. PSMA's role in neuro-oncological theranostics is promising, but future research must address specificity and compare it with emerging targets.

近年来,前列腺特异性膜抗原(PSMA)--一种跨膜糖蛋白--已成为集诊断和治疗为一体的治疗学上一种很有前途的生物标记物。PSMA 在各种肿瘤(包括脑转移瘤和高级别胶质瘤)中的过度表达表明它在神经肿瘤学中的潜力。Pruis 等人进行了一项概念验证研究,比较了脑肿瘤患者动脉内(IA)和静脉内(IV)给药 68Ga-PSMA-11,旨在提高放射性配体疗法(RLT)的疗效。10名患者接受了静脉注射和超选择性IA(ssIA)示踪剂给药,正电子发射断层扫描(PET)显示ssIA给药后肿瘤摄取率更高,生物分布更有利。根据正电子发射计算机断层扫描数据建立的剂量测定模型显示,与静脉注射相比,ssIA每个肿瘤每个周期的中位吸收辐射剂量明显更高,这表明ssIA具有优化RLT的潜力。挑战依然存在,特别是在穿透完整的血脑屏障和有效靶向肿瘤细胞方面。为了克服这些限制,对流增强给药和聚焦超声等新方法值得探索。虽然这项研究中的安全性问题微乎其微,但它强调了进行更大规模试验和人工智能辅助手术的必要性。PSMA在神经肿瘤治疗学中的作用前景广阔,但未来的研究必须解决特异性问题,并将其与新兴靶点进行比较。
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引用次数: 0
Tumor grade and progesterone receptor status in predicting benefit of chemotherapy in high genomic risk breast cancer. 肿瘤分级和孕酮受体状态在预测高基因组风险乳腺癌化疗获益方面的作用。
IF 2.9 3区 医学 Q2 ONCOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-22 DOI: 10.1080/14737140.2024.2393749
Ke Liu, Gui-Ping Chen, Xue-Qin Chen, San-Gang Wu

Background: Not all eligible breast cancer (BC) patients could afford the expensive test of 21-gene recurrence score (RS) assay. This study aimed to identify clinicopathological factors associated with high-risk RS and examine whether these factors correlate with the benefit of chemotherapy.

Research design and methods: Patients diagnosed with early-stage BC, node-negative, and estrogen receptor-positive disease were identified from the Surveillance, Epidemiology, and End Results Oncotype DX database.

Result: We included 74,605 patients. Those with higher grade (p < 0.001) and progesterone receptor-negative (PR Neg) (p < 0.001) had the highest odds of a high-risk RS. Among them, 3.2%, 10.1%, 39.1%, 18.6%, 41.6%, and 80.1% had high-risk RS tumors in PR-positive (PR Pos)/well-differentiated (G1), PR Pos/moderately differentiated (G2), PR Pos/poorly and/or undifferentiated (G3), PR Neg/G1, PR Neg/G2, and PR Neg/G3 groups, respectively. Receipt of chemotherapy was associated with improved breast cancer-specific survival (p = 0.010) and overall survival (p < 0.001) in high-risk RS cohort. However, there were no survival benefits from chemotherapy in patients with PR Neg/G3 disease and other groups after stratification by grade and PR status (all p ≥ 0.05).

Conclusion: Our study aids in refining patient selection for the RS testing, which is crucial given its economic implications. However, 21-gene RS remains pivotal for treatment decision-making.

背景:并非所有符合条件的乳腺癌(BC)患者都能负担得起昂贵的21基因复发评分(RS)检测。本研究旨在确定与高风险RS相关的临床病理因素,并考察这些因素是否与化疗的获益相关:从监测、流行病学和最终结果 Oncotype DX 数据库中识别出被诊断为早期 BC、结节阴性和雌激素受体阳性的患者:我们共纳入了 74 605 名患者。结果:我们纳入了 74 605 名患者,其中分级(p p = 0.010)和总生存率(p p ≥ 0.05)较高的患者:我们的研究有助于完善 RS 检测的患者选择,考虑到其经济影响,这一点至关重要。然而,21 基因 RS 仍是治疗决策的关键。
{"title":"Tumor grade and progesterone receptor status in predicting benefit of chemotherapy in high genomic risk breast cancer.","authors":"Ke Liu, Gui-Ping Chen, Xue-Qin Chen, San-Gang Wu","doi":"10.1080/14737140.2024.2393749","DOIUrl":"10.1080/14737140.2024.2393749","url":null,"abstract":"<p><strong>Background: </strong>Not all eligible breast cancer (BC) patients could afford the expensive test of 21-gene recurrence score (RS) assay. This study aimed to identify clinicopathological factors associated with high-risk RS and examine whether these factors correlate with the benefit of chemotherapy.</p><p><strong>Research design and methods: </strong>Patients diagnosed with early-stage BC, node-negative, and estrogen receptor-positive disease were identified from the Surveillance, Epidemiology, and End Results Oncotype DX database.</p><p><strong>Result: </strong>We included 74,605 patients. Those with higher grade (<i>p</i> < 0.001) and progesterone receptor-negative (PR Neg) (<i>p</i> < 0.001) had the highest odds of a high-risk RS. Among them, 3.2%, 10.1%, 39.1%, 18.6%, 41.6%, and 80.1% had high-risk RS tumors in PR-positive (PR Pos)/well-differentiated (G1), PR Pos/moderately differentiated (G2), PR Pos/poorly and/or undifferentiated (G3), PR Neg/G1, PR Neg/G2, and PR Neg/G3 groups, respectively. Receipt of chemotherapy was associated with improved breast cancer-specific survival (<i>p</i> = 0.010) and overall survival (<i>p</i> < 0.001) in high-risk RS cohort. However, there were no survival benefits from chemotherapy in patients with PR Neg/G3 disease and other groups after stratification by grade and PR status (all <i>p</i> ≥ 0.05).</p><p><strong>Conclusion: </strong>Our study aids in refining patient selection for the RS testing, which is crucial given its economic implications. However, 21-gene RS remains pivotal for treatment decision-making.</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995582","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
期刊
Expert Review of Anticancer Therapy
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