Seminars in oncology最新文献_第2页

PARP inhibitors: A review of the pharmacology, pharmacokinetics, and pharmacogenetics PARP抑制剂：药理学、药代动力学和药物遗传学综述。

IF 4 3区医学 Q1 Medicine

Seminars in oncology

Pub Date : 2024-02-01 DOI: 10.1053/j.seminoncol.2023.09.005

Yi Zeng , Oluwatobi Arisa , Cody J. Peer , Antonio Fojo , William D. Figg

PARP inhibitors have emerged as a promising class of anticancer agents approved for the treatment of ovarian, breast, prostate, and pancreatic cancer. These inhibitors target PARP enzymes involved in DNA repair pathways and exhibit remarkable efficacy in cancers with genetic deficiencies in the homologous recombination pathway responsible for mending DNA double-strand breaks. While all PARP inhibitors demonstrate potent and selective inhibition of PARP1 and PARP2, the key enzymes involved in DNA repair, each agent within the class possesses unique pharmacological profiles distinguishing them from one another.

This review aims to comprehensively examine the properties of the entire PARP inhibitor class while emphasizing individual pharmacologic and pharmacokinetic distinctions that inform clinical recommendations. Currently, four agents, namely olaparib, rucaparib, niraparib, and talazoparib, have obtained approval in the United States and Europe. Olaparib, the first approved PARP inhibitor, has been extensively studied and is indicated for a wider range of cancer types.

Niraparib and talazoparib, the more recent additions to the PARP inhibitor class, possess the longest half-lives and are formulated for convenient once-daily dosing, alleviating the pill burden for patients when compared to older agents. Moreover, talazoparib undergoes minimal hepatic metabolism, reducing the potential for drug-drug interactions. Notably, niraparib is the sole PARP inhibitor recommended for dose reduction in hepatically impaired populations, whereas talazoparib and olaparib should be dose reduced in renally impaired populations. The mechanisms underlying these dose adjustment recommendations are further explored in this review.

Additionally, this review briefly covers veliparib, a PARP inhibitor under development, and two recently approved PARP inhibitors in China, fuzuloparib and pamiparib. Although significant progress has been made in understanding PARP inhibitors, there are several unanswered questions that remain, necessitating further research across a broader spectrum of cancer types within this evolving class of anticancer agents.

PARP抑制剂已成为一类有前景的抗癌药物，被批准用于治疗卵巢癌、乳腺癌、前列腺癌和胰腺癌癌症。这些抑制剂靶向参与DNA修复途径的PARP酶，并在负责修复DNA双链断裂的同源重组途径中存在遗传缺陷的癌症中表现出显著疗效。虽然所有PARP抑制剂都对参与DNA修复的关键酶PARP1和PARP2表现出有效和选择性的抑制作用，但该类药物中的每一种都具有独特的药理学特征，将它们彼此区分开来。本综述旨在全面检查整个PARP抑制剂类别的特性，同时强调个体药理学和药代动力学差异，为临床建议提供依据。目前，olaparib、rucaparib、niraparib和talazoparib四种制剂已在美国和欧洲获得批准。奥拉帕尼是首个获得批准的PARP抑制剂，已被广泛研究，适用于更广泛的癌症类型。Niraparib和talazoparib是PARP抑制剂类别中最新添加的药物，具有最长的半衰期，配方方便，每天给药一次，与较老的药物相比，减轻了患者的药物负担。此外，他拉唑帕尼的肝脏代谢最小，降低了药物相互作用的可能性。值得注意的是，尼拉帕利是唯一推荐用于减少肝功能受损人群剂量的PARP抑制剂，而塔拉佐帕尼和奥拉帕尼应在肾功能受损人群中减少剂量。本综述将进一步探讨这些剂量调整建议的机制。此外，本综述还简要介绍了正在开发的PARP抑制剂veliparib，以及中国最近批准的两种PARP抑制剂，呋唑帕利和帕帕帕利。尽管在理解PARP抑制剂方面取得了重大进展，但仍有几个悬而未决的问题，需要在这类不断发展的抗癌药物中对更广泛的癌症类型进行进一步研究。

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引用次数: 0

Beyond BRCA: Diagnosis and management of homologous recombination repair deficient pancreatic cancer 超越BRCA:同源重组修复缺陷胰腺癌的诊断和治疗

IF 4 3区医学 Q1 Medicine

Seminars in oncology

Pub Date : 2024-02-01 DOI: 10.1053/j.seminoncol.2023.11.001

Meredith LaRose, Gulam A. Manji, Susan E. Bates

Approximately 4%–7% of patients diagnosed with pancreatic adenocarcinoma (PDAC) are found to harbor deleterious germline mutations in BRCA1 and/or BRCA2. Loss of function of BRCA1 and/or BRCA2 results in deficiency in homologous recombination repair (HRR), a critical DNA repair pathway, and confers sensitivity to certain DNA damaging agents, including platinum chemotherapy and PARP inhibitors. The PARP inhibitor olaparib is food and drug administration (FDA) approved for use in pancreatic cancer based on the POLO trial, which found that maintenance olaparib significantly prolonged progression free survival compared to placebo among patients with germline BRCA1 or BRCA2 mutations and metastatic PDAC that had not progressed following frontline platinum-based chemotherapy. Recently, there has been considerable interest in identifying patients without BRCA inactivation whose tumors also exhibit properties of HRR deficiency and thus may be susceptible to therapies with proven benefit in cancers harboring BRCA mutations. Here, we discuss methods for identification of HRR-deficiency and review the management of HRR-deficient cancers with a focus on HRR-deficient PDAC.

大约4%-7%的胰腺腺癌(PDAC)患者被发现携带有害的BRCA1和/或BRCA2种系突变。BRCA1和/或BRCA2功能缺失导致同源重组修复(HRR)缺失，这是一种关键的DNA修复途径，并对某些DNA损伤剂(包括铂化疗和PARP抑制剂)敏感。基于POLO试验，PARP抑制剂奥拉帕尼被FDA批准用于胰腺癌，该试验发现，与安慰剂相比，维持奥拉帕尼显着延长了生殖系BRCA1或BRCA2突变和转移性PDAC患者的无进展生存期，这些患者在一线铂基化疗后没有进展。最近，人们对识别没有BRCA失活的患者产生了相当大的兴趣，这些患者的肿瘤也表现出HRR缺乏的特性，因此可能容易接受已证实对BRCA突变的癌症有益的治疗。在这里，我们讨论了识别hrr缺乏症的方法，并回顾了hrr缺乏症癌症的管理，重点是hrr缺乏症的PDAC。

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引用次数: 0

CDK4/6 inhibitors in the treatment of metastatic breast cancer: Focus on toxicity and safety 治疗转移性乳腺癌的 CDK4/6 抑制剂：关注毒性和安全性

IF 4 3区医学 Q1 Medicine

Seminars in oncology

Pub Date : 2024-01-13 DOI: 10.1053/j.seminoncol.2024.01.002

Demi Wekking, Matteo Lambertini, Mariele Dessì, Nerina Denaro, Fabio Bardanzellu, Ornella Garrone, Mario Scartozzi, Cinzia Solinas

The development of oral cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors, including palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for patients with hormone-receptor-positive (HR+) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (BC). When combined with an aromatase inhibitor or fulvestrant, these agents have been approved as first-line therapy in the metastatic setting. Abemaciclib has also gained FDA approval for patients with HR-positive, HER2-negative, node-positive, early BC at high risk of recurrence. Moreover, ribociclib has recently improved disease-free survival in patients with stage II or III HR+/HER2-negative early BC. CDK4/6 inhibitors have favorable safety profiles. However, the available agents have different toxicity profiles that must be clearly discussed with the patients for optimal clinical decisions. This manuscript aims to review CDK4/6 inhibitor-related treatment-associated adverse events, identify risk factors for intolerable adverse events, and assess their safety in special patient populations such as the elderly and those with renal insufficiency. Enhanced knowledge and understanding of CDK4/6 inhibitor-related toxicities can improve treatment strategies and ultimately enhance patient care.

口服细胞周期蛋白依赖性激酶4和6（CDK4/6）抑制剂（包括palbociclib、ribociclib和abemaciclib）的开发彻底改变了激素受体阳性（HR+）和人表皮生长因子受体2（HER2）阴性转移性乳腺癌（BC）患者的治疗格局。当与芳香化酶抑制剂或氟维司群联合使用时，这些药物已被批准作为转移性乳腺癌的一线疗法。Abemaciclib 也获得了 FDA 批准，用于治疗 HR 阳性、HER2 阴性、结节阳性、复发风险高的早期 BC 患者。此外，ribociclib最近也改善了II期或III期HR+/HER2阴性早期BC患者的无病生存期。CDK4/6 抑制剂具有良好的安全性。然而，现有的药物具有不同的毒性特征，必须与患者进行明确讨论，以做出最佳临床决策。本手稿旨在回顾CDK4/6抑制剂治疗相关不良事件，识别不可耐受不良事件的风险因素，并评估其在老年人和肾功能不全患者等特殊患者群体中的安全性。加强对CDK4/6抑制剂相关毒性的认识和理解可以改善治疗策略，最终提高患者护理水平。

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引用次数: 0

Cancer genetic mutation prevalence in sub-Saharan Africa: A review of existing data 撒哈拉以南非洲的癌症基因突变流行率：现有数据回顾

IF 4 3区医学 Q1 Medicine

Seminars in oncology

Pub Date : 2023-12-27 DOI: 10.1053/j.seminoncol.2023.12.001

Joshua Shain, Alissa Michel, Michael S. May, Lindor Qunaj, Wafaa El-Sadr, Wendy K. Chung, Paul S. Appelbaum, Judith S. Jacobson, Jessica Justman, Alfred I. Neugut

Background

Cancer represents a leading cause of death worldwide. Germline mutations in several genes increase the risk of developing several cancers, including cancers of the breast, ovary, pancreas, colorectum, and melanoma. An understanding of the population prevalence of pathogenic germline mutations can be helpful in the design of public health interventions, such as genetic testing, which has downstream implications for cancer screening, prevention, and treatment. While population-based studies of pathogenic germline mutations exist, most such studies have been conducted in White populations. Limited data exist regarding the prevalence of germline mutations within sub-Saharan African populations.

Materials and Methods

We identified countries defined as sub-Saharan Africa by the World Bank and conducted a scoping literature review using PubMed. For each country, we identified and summarized studies that focused on the prevalence of germline genetic mutations with sample sizes >10 and in a population directly from sub-Saharan Africa, either with or without diseases associated with the relevant genetic mutations. Studies that evaluated the prevalence of somatic or likely benign variants were excluded.

Results

Within the 48 countries in sub-Saharan Africa, we identified 34 studies which meet the inclusion criteria. Twenty studies were conducted in South Africa, Nigeria, or Burkina Faso; four countries had more than two published papers. We found that 33 of 48 countries in sub-Saharan Africa lacked any genetic studies. Notably, there has been an increase in relevant studies starting in 2020. Importantly, of the 34 studies identified, 29 included data on BRCA1 or BRCA2. Data on the prevalence of mutations contributing to familial cancer syndromes other than BRCA1 and BRCA2 was limited.

Conclusions

While some progress has been made towards understanding the prevalence of germline mutations in cancer susceptibility genes, the characterization of genetic mutations among sub-Saharan African populations remains strikingly incomplete. Given the genetic diversity in the region, there remains a great need for large-scale, population-based studies to understand the prevalence of germline pathogenic mutations and adequately capture all the subpopulations in this part of the world.

背景癌症是导致全球死亡的主要原因之一。几种基因的种系突变会增加罹患几种癌症的风险，包括乳腺癌、卵巢癌、胰腺癌、结直肠癌和黑色素瘤。了解致病性种系突变在人群中的流行程度有助于设计公共卫生干预措施，如基因检测，这对癌症筛查、预防和治疗具有下游影响。虽然存在基于人群的致病性种系突变研究，但大多数此类研究都是在白人人群中进行的。有关撒哈拉以南非洲人群种系突变患病率的数据有限。材料与方法我们确定了世界银行定义为撒哈拉以南非洲的国家，并使用 PubMed 进行了范围性文献综述。对于每个国家，我们都确定并总结了重点关注种系基因突变患病率的研究，这些研究的样本大小为 10，研究对象直接来自撒哈拉以南非洲地区的人群，无论是否患有与相关基因突变有关的疾病。结果在撒哈拉以南非洲的 48 个国家中，我们发现了 34 项符合纳入标准的研究。其中有 20 项研究是在南非、尼日利亚或布基纳法索进行的；有 4 个国家发表了两篇以上的论文。我们发现，在撒哈拉以南非洲的 48 个国家中，有 33 个国家缺乏任何基因研究。值得注意的是，从 2020 年开始，相关研究有所增加。重要的是，在已发现的 34 项研究中，29 项包含了 BRCA1 或 BRCA2 的数据。结论虽然在了解癌症易感基因种系突变的发生率方面取得了一些进展，但撒哈拉以南非洲人群的基因突变特征描述仍然非常不完整。鉴于该地区的遗传多样性，仍然非常有必要开展大规模、基于人群的研究，以了解种系致病基因突变的流行情况，并充分掌握世界上这一地区的所有亚人群。

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引用次数: 0

Primary adrenal insufficiency induced by immune checkpoint inhibitors: Biological, clinical, and radiological aspects 免疫检查点抑制剂诱发的原发性肾上腺功能不全：生物学、临床和放射学方面

IF 4 3区医学 Q1 Medicine

Seminars in oncology

Pub Date : 2023-12-06 DOI: 10.1053/j.seminoncol.2023.11.003

Serafina Martella, Minke Lucas, Michele Porcu, Laura Perra, Nerina Denaro, Andrea Pretta, Giulia Deias, Karen Willard-Gallo, Hector Soto Parra, Luca Saba, Mario Scartozzi, Demi Wekking, Marleen Kok, Marco Maria Aiello, Cinzia Solinas

Immune checkpoint inhibitors (ICI) have become a cornerstone in medical oncology, continually evolving therapeutic strategies and applications. These monoclonal antibodies, designed to enhance immune responses, have revealed a spectrum of immune-related adverse events (irAEs). While many irAEs exhibit favorable responses to corticosteroid or immunosuppressive therapy, most ICI-related endocrinopathies necessitate lifelong replacement therapy and pose significant clinical challenges. Adrenal insufficiency (AI), a noteworthy endocrine irAE, can manifest as primary AI (PAI) or secondary AI (SAI), resulting from adrenal or pituitary gland dysfunction, respectively. ICI-induced AI, albeit relatively infrequent, occurs in 1%–2% of patients receiving single-agent anti-Programmed Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) or Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) therapies and in a higher range of 4%–9% when ICIs are used in combinations. Recognizing and addressing ICI-induced PAI is crucial, as it often presents with acute and potentially life-threatening symptoms, especially considering the expanding use of ICI therapy. This review provides an updated overview of ICI-induced PAI, exploring its clinical, diagnostic, and radiological aspects.

免疫检查点抑制剂（ICI）已成为肿瘤内科学的基石，其治疗策略和应用也在不断发展。这些旨在增强免疫反应的单克隆抗体揭示了一系列免疫相关不良事件（irAEs）。虽然许多 irAEs 对皮质类固醇或免疫抑制疗法表现出良好的反应，但大多数 ICI 相关内分泌病症都需要终身替代治疗，给临床带来了巨大挑战。肾上腺功能不全（AI）是一种值得注意的内分泌虹膜AE，可表现为原发性AI（PAI）或继发性AI（SAI），分别由肾上腺或垂体功能障碍引起。ICI 诱导的 AI 虽然相对较少，但在接受单药抗程序性死亡-1/程序性死亡配体 1（PD-1/PD-L1）或细胞毒性 T 淋巴细胞抗原 4（CTLA-4）疗法的患者中发生率为 1%-2%，在 ICIs 联合使用时发生率更高，为 4%-9%。识别和处理 ICI 诱导的 PAI 至关重要，因为它通常表现为急性和潜在的危及生命的症状，特别是考虑到 ICI 治疗的使用正在不断扩大。本综述对 ICI 诱导的 PAI 进行了最新概述，探讨了其临床、诊断和放射学方面的问题。

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引用次数: 0

Overcoming barriers to opioid-induced constipation management in cancer patients. 克服阿片类药物引起的癌症患者便秘管理的障碍

IF 4 3区医学 Q1 Medicine

Seminars in oncology

Pub Date : 2023-12-01 Epub Date: 2023-07-31 DOI: 10.1053/j.seminoncol.2023.07.001

Esther Holgado Martín, Ana Blasco Cordellat, Marta Guix Arnau, Rosa Villatoro Roldán, Almudena Sanz Yagüe, Diana Monge Martín, Fernando Caballero Martínez, Francisco J Campos Lucas, Almudena García Castaño

Purpose: Opioid-induced constipation (OIC) is a common adverse effect of opioid therapy. We aim to identify the main barriers hindering clinical recommendations implementation and propose consensus solutions to improve OIC control in cancer patients.

Methods: Following collaborative and prioritization techniques, a scientific committee generated statements addressing possible barriers to optimal OIC management (related to patients, health providers and health care system), and potential interventions to overcome these barriers. An expert panel of 36 oncologists assessed the statements to reach a consensus.

Results: The survey consisted of 70 statements. Consensus was reached on 12/45 items related to barriers (26.6%) and on 19/25 items about corrective interventions (76%). The panel considered that patients are unaware of the existence of a specific OIC treatment, and their information sources are highly variable and unreliable. Regarding health providers, the panel considered that the oncologists prioritize symptoms such as diarrhea, pain, anxiety, or other treatment toxicities, over constipation. Work overload and bureaucratic requirements were the main barriers related to health care system. Regarding potential interventions, best-rated proposals included specific training programs development for primary care physicians and nurses, and multiplatform informative resources development for patients and caregivers, including precisely written instructions about OIC recognition and management. Oncologists assessed positively measures aiming to improve coordination between primary care physicians and oncologists, and nursing consultations implementation. The panel considered useful the OIC treatment algorithms simplification.

Conclusions: The expert panel identified the main barriers to optimal OIC management and suggested some feasible approaches to overcome these barriers.

目的：阿片类药物引起的便秘（OIC）是阿片类治疗的常见不良反应。我们旨在确定阻碍临床建议实施的主要障碍，并提出共识解决方案，以改善癌症患者的OIC控制。方法：遵循协作和优先排序技术，一个科学委员会发表声明，解决伊斯兰会议组织最佳管理的可能障碍（与患者、医疗服务提供者和医疗保健系统有关），以及克服这些障碍的潜在干预措施。一个由36名肿瘤学家组成的专家小组对这些声明进行了评估，以达成共识。结果：调查包括70项陈述。就与障碍有关的12/45项（26.6%）和关于纠正干预措施的19/25项（76%）达成共识。专家组认为，患者不知道特定OIC治疗的存在，他们的信息来源高度多变且不可靠。关于医疗服务提供者，专家组认为肿瘤学家优先考虑腹泻、疼痛、焦虑或其他治疗毒性等症状，而不是便秘。超负荷工作和官僚主义要求是与医疗保健系统相关的主要障碍。关于潜在的干预措施，评分最高的提案包括为初级保健医生和护士制定具体的培训计划，为患者和护理人员开发多平台信息资源，包括关于OIC识别和管理的精确书面说明。肿瘤学家积极评估了旨在改善初级保健医生和肿瘤学家之间协调的措施，以及护理咨询的实施情况。专家组认为简化OIC处理算法是有用的。结论：专家小组确定了伊斯兰会议组织最佳管理的主要障碍，并提出了克服这些障碍的一些可行办法。

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引用次数: 0

Immune-checkpoint inhibitors in anal squamous cell carcinoma: a systematic review and meta-analysis 免疫检查点抑制剂在肛门鳞状细胞癌中的应用:一项系统综述和荟萃分析

IF 4 3区医学 Q1 Medicine

Seminars in oncology

Pub Date : 2023-11-24 DOI: 10.1053/j.seminoncol.2023.11.002

Laura Pala, Tommaso De Pas, Erika Stucchi, Chiara Catania, Emilia Cocorocchio, Maria Giulia Zampino, Giovanna Rossi, Emma Zattarin, Antonio Di Muzio, Daniele Laszlo, Sara Stucchi, Fabio Conforti

Introduction

Squamous cell carcinoma of the anus (SCCA) is a rare tumor. While most patients with locally advanced disease are cured with chemo-radiotherapy, about a quarter eventually experience metastatic recurrence. Standard treatment for advanced disease is chemotherapy, but recently evidence on the activity of immunotherapy has been reported. We performed a systematic review and meta-analysis of prospective trials testing immune-checkpoint inhibitors (ICIs) in patients with SCCA.

Objective

We aimed to evaluate the overall response rate (ORR) and the disease control rate (DCR) of ICIs in patients with advanced SCCA.

Methods

We systematically searched PubMed, Embase, and Scopus, through December 31, 2022, for prospective trials assessing ICIs in patients with advanced SCCA. The primary and secondary endpoints were respectively ORR and DCR.

Results

Six prospective trials were included in the analysis, one of which was randomized. Overall, seven treatment arms and 347 patients have been analyzed. Five treatment arms tested ICIs as monotherapy and two arms examined ICIs in combination with cetuximab and bevacizumab, respectively. The pooled ORR was 13% (95%CI, 10%–17%), with a DCR of 57% (95%CI, 40%–74%). Results did not change in a sensitivity analysis, which excluded the two treatment arms testing the combination of ICIs with other drugs.

Conclusions

The efficacy of ICIs in SCCAs is low. Combination strategies with targeted drugs or chemotherapy might represent a better therapeutic strategy for these patients. Further studies are awaited to identify resistance mechanisms to ICIs and optimize their efficacy.

肛门鳞状细胞癌(SCCA)是一种罕见的肿瘤。虽然大多数局部晚期患者可以通过化疗治愈，但大约四分之一的患者最终会出现转移性复发。晚期疾病的标准治疗是化疗，但最近有证据表明免疫疗法具有活性。我们对SCCA患者免疫检查点抑制剂(ICIs)的前瞻性试验进行了系统回顾和荟萃分析。目的评价ICIs治疗晚期SCCA患者的总有效率(ORR)和疾病控制率(DCR)。方法系统检索PubMed、Embase和Scopus，截至2022年12月31日，以评估晚期SCCA患者的ICIs的前瞻性试验。主要和次要终点分别为ORR和DCR。结果6项前瞻性试验纳入分析，其中1项为随机试验。总共分析了7个治疗组和347名患者。5个治疗组将ICIs作为单一疗法进行测试，2个治疗组分别将ICIs与西妥昔单抗和贝伐单抗联合进行测试。合并ORR为13% (95%CI, 10%-17%)， DCR为57% (95%CI, 40%-74%)。敏感性分析的结果没有改变，该分析排除了两个治疗组测试ICIs与其他药物联合使用的结果。结论ICIs治疗scca的疗效较低。联合靶向药物或化疗可能是这些患者更好的治疗策略。进一步的研究有待于确定对ICIs的耐药机制并优化其疗效。

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引用次数: 0

Practice change: No benefit of extended lymphadenectomy at radical cystectomy in patients with muscle invasive bladder cancer 实践改变：在肌浸润性膀胱癌症患者中，扩大淋巴结切除术在根治性膀胱切除术中没有益处。

IF 4 3区医学 Q1 Medicine

Seminars in oncology

Pub Date : 2023-06-01 DOI: 10.1053/j.seminoncol.2023.09.001

Omar Fahmy , Maxim Kochergin , Anastasios D. Asimakopoulos , Georgios Gakis

For many decades, extended pelvic lymph node dissection has been an integral part during radical cystectomy for patients with muscle invasive bladder cancer. This practice was based on large retrospective meta-analyses suggesting an oncologic benefit to an extended dissection. This mini review and meta-analysis includes the two available randomized trials in the current literature. Therefore, it can be considered as the strongest level of evidence regarding the prognostic benefit of an extended pelvic lymphadenectomy. Based on current randomized data, standard pelvic lymph node dissection up to the level of iliac bifurcation is sufficient, and extension of the dissection above this level does not provide any additional oncologic benefit.

几十年来，对于肌侵犯性膀胱癌症患者，扩大盆腔淋巴结清扫一直是根治性膀胱切除术中不可或缺的一部分。这种做法是基于大型回顾性荟萃分析，表明扩大解剖对肿瘤学有益。这篇小型综述和荟萃分析包括了当前文献中可用的两项随机试验。因此，它可以被认为是关于扩大盆腔淋巴结切除术预后益处的最强证据。根据目前的随机数据，标准的盆腔淋巴结清扫达到髂分叉水平就足够了，并且将清扫范围扩大到该水平以上并不能提供任何额外的肿瘤学益处。

引用次数: 0

Bone-modifying agents for non–small-cell lung cancer patients with bone metastases during the era of immune checkpoint inhibitors: A narrative review 免疫检查点抑制剂时代骨转移非小细胞肺癌癌症患者的骨改性剂：叙述性综述。

IF 4 3区医学 Q1 Medicine

Seminars in oncology

Pub Date : 2023-06-01 DOI: 10.1053/j.seminoncol.2023.09.002

Jinyoung Kim , Chaiho Jeong , Jeongmin Lee , Jeonghoon Ha , Ki-Hyun Baek , Seohyun Kim , Tai Joon An , Chan Kwon Park , Hyoung Kyu Yoon , Jeong Uk Lim

During the course of lung cancer progression, bone metastases occur in about 40% of patients. Common complications associated with bone metastases in lung cancer patients include musculoskeletal pain, pathologic fractures, spinal cord compression, and hypercalcemia. We discuss the efficacy of bone-modifying agents (BMAs) in reducing skeletal-related events (SREs) and improving cancer-related outcomes, particularly in patients with stage IV non–small-cell lung cancer with bone metastases. In addition, the combined effects of BMAs with radiotherapy or immunotherapy in reducing SREs in patients with lung cancer and bone metastases are explored.

在癌症进展过程中，约40%的患者发生骨转移。癌症患者骨转移的常见并发症包括肌肉骨骼疼痛、病理性骨折、脊髓压迫和高钙血症。我们讨论了骨改性剂（BMAs）在减少骨相关事件（SRE）和改善癌症相关结果方面的疗效，特别是在IV期非小细胞肺癌癌症骨转移患者中。此外，还探讨了BMA与放疗或免疫疗法在减少癌症和骨转移患者SRE方面的联合作用。

引用次数: 0

Efficacy of memantine in preventing neurocognitive dysfunction induced by radiation therapy in patients with brain metastases: A systematic review of clinical trials 美金刚预防脑转移患者放射治疗引起的神经认知功能障碍的疗效：临床试验的系统综述。

IF 4 3区医学 Q1 Medicine

Seminars in oncology

Pub Date : 2023-06-01 DOI: 10.1053/j.seminoncol.2023.09.004

Haripriya Parapparambil Surendran , Sujit Kumar Sah , Dhanya Mary Louis , Sruthi Kalavagunta , Narmadha Mukunthu Poornachary , Selin Chiriyankandath Joy , Debnarayan Dutta

Purpose

About 50%–90% of patients with brain metastases who receive radiation therapy experience cognitive impairment. This systematic review aims to gather credible sources of comprehensive information on the efficacy of memantine in preventing cognitive dysfunction.

Methods

A comprehensive review conducted in compliance with the PRISMA statement and systematic search was performed across five databases included PubMed^Ⓡ, Embase^Ⓡ, Scopus^Ⓡ, Cochrane Library^Ⓡ, and ClinicalTrial.gov.in from inception until November 2021.

Results

A total of four eligible studies were selected in this review that included 1,444 patients with brain metastases who received radiation therapy (Intervention group [n = 729] and control group [n = 715]). Overall, three of the four studies reported some improvement in neurocognitive function in at least one or more parameters such as recall and recognition (P = .39, P = .10 and P = .05), verbal fluency (P = .03 and P < .0001), complex attention (P = .59) executive function (P = .92) and normal appearing white matter (P = .01) following memantine therapy compared to control group. Further, two of the four studies reported an improvement in the patients’ quality of life following memantine therapy compared to the control group, and there was no significant difference in the toxicity profile of the interventional compared to the control group as reported from two studies.

Conclusion

This review embraces the comprehensive evidence that the use of memantine therapy in patients with brain metastases to prevent radiation-induced neurocognitive dysfunction has a modest and statistically significant beneficial impact in improving quality of life and preserving some neurocognitive function without any complications. Pending the completion of additional ongoing studies, one can argue that memantine is a reasonable treatment to consider in patients with brain metastases while they receive whole brain radiation therapy.

目的：接受放射治疗的脑转移患者中，约有50%-90%出现认知障碍。这篇系统综述旨在收集关于美金刚在预防认知功能障碍方面的疗效的全面信息的可靠来源。方法：根据PRISMA声明进行全面审查，并在五个数据库中进行系统搜索，包括PubMedⓇ、Embase 9415，和ClinicalTrial.gov.in。结果：本综述共选择了四项符合条件的研究，其中包括1444名接受放射治疗的脑转移患者（干预组 = 729]和对照组[n = 715]）。总体而言，四项研究中有三项报告称，在至少一个或多个参数（如回忆和识别）方面，神经认知功能有所改善（P = .39，P = .10和P = .05）、语言流利性（P = .03和P<.0001）、复杂注意（P = .59）执行功能（P=.92）和正常白质（P = .01）。此外，四项研究中有两项报告称，与对照组相比，美金刚治疗后患者的生活质量有所改善，两项研究报告称，介入治疗的毒性特征与对照组没有显著差异。结论：这篇综述包含了全面的证据，即在脑转移患者中使用美金刚治疗来预防辐射诱导的神经认知功能障碍，在没有任何并发症的情况下，对提高生活质量和保留一些神经认知功能具有适度且统计学上显著的有益影响。在其他正在进行的研究完成之前，有人可以说，在接受全脑放射治疗的脑转移患者中，美金刚是一种合理的治疗方法。

{"title":"Efficacy of memantine in preventing neurocognitive dysfunction induced by radiation therapy in patients with brain metastases: A systematic review of clinical trials","authors":"Haripriya Parapparambil Surendran , Sujit Kumar Sah , Dhanya Mary Louis , Sruthi Kalavagunta , Narmadha Mukunthu Poornachary , Selin Chiriyankandath Joy , Debnarayan Dutta","doi":"10.1053/j.seminoncol.2023.09.004","DOIUrl":"10.1053/j.seminoncol.2023.09.004","url":null,"abstract":"<div><h3>Purpose</h3><p><span><span>About 50%–90% of patients with brain metastases who receive radiation therapy experience </span>cognitive impairment. This </span>systematic review<span> aims to gather credible sources of comprehensive information on the efficacy of memantine in preventing cognitive dysfunction.</span></p></div><div><h3>Methods</h3><p>A comprehensive review conducted in compliance with the PRISMA statement and systematic search was performed across five databases included PubMed<sup>Ⓡ</sup><span>, Embase</span><sup>Ⓡ</sup><span>, Scopus</span><sup>Ⓡ</sup><span>, Cochrane Library</span><sup>Ⓡ</sup>, and ClinicalTrial.gov.in from inception until November 2021.</p></div><div><h3>Results</h3><p>A total of four eligible studies were selected in this review that included 1,444 patients with brain metastases who received radiation therapy (Intervention group [n = 729] and control group [n = 715]). Overall, three of the four studies reported some improvement in neurocognitive function in at least one or more parameters such as recall and recognition (<em>P</em> = .39, <em>P</em> = .10 and <em>P</em> = .05), verbal fluency (<em>P</em> = .03 and <em>P</em> < .0001), complex attention (<em>P</em> = .59) executive function (<em>P =</em> .92) and normal appearing white matter (<em>P</em><span> = .01) following memantine therapy compared to control group. Further, two of the four studies reported an improvement in the patients’ quality of life following memantine therapy compared to the control group, and there was no significant difference in the toxicity profile of the interventional compared to the control group as reported from two studies.</span></p></div><div><h3>Conclusion</h3><p>This review embraces the comprehensive evidence that the use of memantine therapy in patients<span><span> with brain metastases to prevent radiation-induced neurocognitive dysfunction has a modest and statistically significant beneficial impact in improving quality of life and preserving some neurocognitive function without any complications. Pending the completion of additional ongoing studies, one can argue that memantine is a reasonable treatment to consider in patients with brain metastases while they receive </span>whole brain radiation therapy.</span></p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41150643","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}

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