Cancer treatment reviews最新文献_第10页

The present and the future of immunotherapy in hepatocellular carcinoma and biliary tract cancers 肝细胞癌和胆道癌免疫治疗的现状和未来

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-05-09 DOI: 10.1016/j.ctrv.2025.102955

Giuseppe Cabibbo , Lorenza Rimassa , Angela Lamarca , Gianluca Masi , Bruno Daniele , David James Pinato , Andrea Casadei-Gardini

Hepatobiliary malignancies encompass a spectrum of invasive carcinomas arising in the liver [hepatocellular carcinoma (HCC), bile ducts [intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (EHC)] and the gallbladder. These malignancies represent a growing global health burden, with rising incidence and mortality rates and their overall prognosis remains poor because many patients present with advanced unresectable disease at diagnosis. In recent years, significant advancements in understanding HCC immunogenicity have reshaped the therapeutic scenario of advanced HCC with the immunotherapy revolutionizing the current HCC treatment landscape and patients’ prognosis. Moreover, the addition of immunotherapy to chemotherapy has recently established a new standard of care first-line treatment for patients with biliary tract cancers (BTCs) who had historically few therapeutic options. Currently, immunotherapy and immune checkpoint inhibitor (ICI)-based regimens stand as a valuable and practice-changing options in both HCC and BTC management. The mounting recent evidence supporting immunotherapy’s survival benefit demands clinicians to stay updated with a rapidly evolving treatment landscape as well as gain knowledge about patient selection, response rate compared with other systemic treatments and immune-mediated adverse events (imAEs) management. A panel of international Experts, comprising hepatologists and oncologists, gathered to explore the challenges in effectively integrating immunotherapy in routine clinical practice. The aim of this review is to present the Experts’ insights to inform treatment choice in HCC and BTC with a special emphasis on the role of currently available ICI-based therapies in shifting treatment paradigms and potentially reversing the natural course of these two deadly malignancies.

肝胆恶性肿瘤包括一系列发生在肝脏(肝细胞癌（HCC）、胆管（肝内胆管癌（ICC）和肝外胆管癌（EHC））和胆囊的浸润性癌。这些恶性肿瘤代表着日益增长的全球健康负担，发病率和死亡率不断上升，而且由于许多患者在诊断时已经出现晚期无法切除的疾病，因此其总体预后仍然很差。近年来，在了解HCC免疫原性方面取得的重大进展重塑了晚期HCC的治疗方案，免疫疗法彻底改变了当前HCC的治疗前景和患者预后。此外，在化疗的基础上增加免疫治疗最近为胆道肿瘤（btc）患者建立了一个新的护理标准，这些患者在历史上很少有治疗选择。目前，基于免疫治疗和免疫检查点抑制剂（ICI）的方案在HCC和BTC治疗中都是一种有价值的和改变实践的选择。最近越来越多的证据支持免疫疗法的生存益处，这要求临床医生跟上快速发展的治疗前景，并获得有关患者选择、与其他全身治疗相比的反应率和免疫介导的不良事件（imae）管理的知识。一个由肝病学家和肿瘤学家组成的国际专家小组聚集在一起，探讨在常规临床实践中有效整合免疫治疗的挑战。本综述的目的是介绍专家的见解，为HCC和BTC的治疗选择提供信息，特别强调目前可用的基于ci的治疗在改变治疗范式和可能逆转这两种致命恶性肿瘤自然病程中的作用。

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引用次数: 0

Chimeric antigen receptor NK cells for breast cancer immunotherapy 嵌合抗原受体NK细胞用于乳腺癌免疫治疗

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-04-23 DOI: 10.1016/j.ctrv.2025.102943

Nisha Wu , Ning Yang , Shiqi Zhang , Haoran Wu , Xuechun Fang , Wanying Lin , Yi Zhang , Xiaowei Qi , Ying Gong

Breast cancer, a predominant malignancy afflicting women globally, demands innovative therapeutic strategies beyond traditional treatments such as surgery, chemotherapy, radiotherapy, and endocrine therapy. Among the emerging therapies, immunotherapy has demonstrated substantial promise, particularly employing chimeric antigen receptor (CAR) technology. This review elucidates the prospect of CAR-modified natural killer (NK) cells in treating breast cancer. NK cells, vital components of the immune system, possess the capability to non-specifically target and extinguish neoplastic cells. Through genetic engineering, CAR constructs targeting specific breast cancer antigens, including HER2, EGFR, PD-L1, MSLN, and Trop2, are integrated into NK cells, thereby enhancing their tumor recognition and cytotoxicity. The review delves into the structural optimization of CAR-NK cells, discussing design elements such as scFv, hinge regions, and activation signals, and emphasizes strategies to augment CAR-NK cell functionality and persistence within the tumor microenvironment. Combining CAR-NK cells with other therapeutic modalities (such as chemotherapy and checkpoint inhibitors) is explored to enhance therapeutic efficacy. Preclinical researches emphasized the efficacy of CAR-NK cells in targeting breast cancer cells, paving the way for future clinical applications and offering hope for improved outcomes in breast cancer patients.

乳腺癌是困扰全球妇女的主要恶性肿瘤，需要创新的治疗策略，而不是传统的治疗方法，如手术、化疗、放疗和内分泌治疗。在新兴疗法中，免疫疗法已经显示出巨大的前景，特别是使用嵌合抗原受体（CAR）技术。本文综述了car修饰的自然杀伤细胞（NK）治疗乳腺癌的前景。NK细胞是免疫系统的重要组成部分，具有非特异性靶向和消灭肿瘤细胞的能力。通过基因工程，将靶向乳腺癌特异性抗原HER2、EGFR、PD-L1、MSLN和Trop2的CAR构建物整合到NK细胞中，从而增强NK细胞的肿瘤识别能力和细胞毒性。这篇综述深入研究了CAR-NK细胞的结构优化，讨论了scFv、铰链区域和激活信号等设计元素，并强调了增强CAR-NK细胞功能和肿瘤微环境内持久性的策略。将CAR-NK细胞与其他治疗方式（如化疗和检查点抑制剂）联合使用以提高治疗效果。临床前研究强调了CAR-NK细胞靶向乳腺癌细胞的功效，为未来的临床应用铺平了道路，为改善乳腺癌患者的预后带来了希望。

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引用次数: 0

Adjuvant CDK4/6 inhibitors in breast cancer: Interpreting trial design, evidence, and uncertainty 乳腺癌的辅助CDK4/6抑制剂：解释试验设计、证据和不确定性

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-04-20 DOI: 10.1016/j.ctrv.2025.102944

Saroj Niraula

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have transformed the treatment landscape for metastatic hormone receptor–positive, HER2-negative breast cancer by improving progression-free and Overall Survival (OS). In the adjuvant context, however, results have been discordant and remain immature. The PALLAS and PENELOPE-B trials of palbociclib reported no benefit, while monarchE and NATALEE demonstrated improvements in invasive disease-free survival (iDFS) with abemaciclib and ribociclib, respectively, leading to regulatory approvals despite no demonstrated OS benefit yet.

It remains possible that adjuvant CDK4/6 inhibition provides meaningful long-term benefit, but that has not been demonstrated. Concerns related to trial design: risk-enrichment, open-label conduct, high treatment-discontinuation rates, and potential informative censoring complicate interpretation. Although iDFS is a recognized intermediate endpoint with potential psychological validity, it is subject to bias in collection and communication, and has not been validated as a surrogate for OS in this setting. Moreover, early inhibition of CDK4/6 may induce resistance and compromise subsequent efficacy. Reported quality-of-life outcomes were preserved, not improved, which holds limited value considering added toxicity, inconvenience, and cost in a largely curable population.

If even half of eligible patients are treated, estimated annual costs in the United States would exceed $7 billion. As these agents are incorporated into clinical guidelines, it is critical to clarify whether they improve long-term outcomes, delay recurrence without affecting survival, or cause unintended harm. Impulse to intervene early is understandable, but emerging data must be carefully assessed to ensure adjuvant CDK4/6 inhibition offers meaningful benefit to patients and health systems.

细胞周期蛋白依赖性激酶4和6 （CDK4/6）抑制剂通过改善无进展和总生存期（OS），改变了转移激素受体阳性、her2阴性乳腺癌的治疗前景。然而，在辅助方面，结果是不一致的，仍然不成熟。palbociclib的PALLAS和PENELOPE-B试验报告没有获益，而monarchE和NATALEE分别显示abemaciclib和ribociclib改善了侵袭性无病生存期（iDFS），尽管尚未显示OS获益，但仍获得监管机构批准。佐剂抑制CDK4/6仍有可能提供有意义的长期益处，但尚未得到证实。与试验设计相关的问题：风险增加、开放标签行为、高治疗终止率和潜在的信息审查使解释复杂化。虽然iDFS是公认的具有潜在心理有效性的中间终点，但它在收集和交流中存在偏差，并且尚未被验证为OS的替代品。此外，早期抑制CDK4/6可能导致耐药性并影响后续疗效。报告的生活质量结果得到了保留，而不是改善，考虑到在大部分可治愈的人群中增加的毒性、不便和成本，其价值有限。即使有一半符合条件的患者得到治疗，美国每年的费用估计也将超过70亿美元。当这些药物被纳入临床指南时，明确它们是否能改善长期预后，延缓复发而不影响生存，或造成意外伤害是至关重要的。早期干预的冲动是可以理解的，但必须仔细评估新出现的数据，以确保辅助CDK4/6抑制为患者和卫生系统提供有意义的益处。

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引用次数: 0

Optimal bevacizumab treatment strategy in advanced ovarian cancer: A review 晚期卵巢癌的最佳贝伐单抗治疗策略：综述

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-04-20 DOI: 10.1016/j.ctrv.2025.102945

Bradley J. Monk , Domenica Lorusso , Keiichi Fujiwara , Jalid Sehouli

Bevacizumab was the first targeted therapy developed for newly diagnosed and recurrent advanced ovarian cancer (AOC). Although bevacizumab has been approved for the treatment of AOC for several years, identifying patients who may benefit most from this treatment is still debated. Bevacizumab has been associated with improved progression-free survival (PFS) regardless of clinical risk, but in some countries the use of bevacizumab in the treatment of newly diagnosed AOC has been restricted to higher-risk patients (stage III inoperable or suboptimally debulked disease, or stage IV disease); this is primarily due to the findings of exploratory subgroup analyses from phase III trials that suggest only higher-risk patients derive an overall survival (OS) advantage with bevacizumab. Recently reported post hoc analyses from the PAOLA-1 trial of maintenance olaparib plus bevacizumab versus bevacizumab alone for patients with newly diagnosed AOC and homologous recombination deficiency-positive tumors suggested PFS and OS benefit was achieved in both lower-risk (with stage III disease who had undergone upfront surgery and had complete resection) and higher-risk (with stage III disease who had undergone upfront surgery and had residual disease or who had received neoadjuvant chemotherapy, or with stage IV disease) patients, prompting reassessment of the role of bevacizumab in lower-risk patients. This review examines the role of bevacizumab in the AOC treatment pathway by discussing its efficacy and safety in the first-line, maintenance and recurrent settings, and evaluates the clinical implications of bevacizumab use across risk groups and lines of therapy.

贝伐单抗是首个针对新诊断和复发的晚期卵巢癌（AOC）开发的靶向治疗药物。尽管贝伐单抗已被批准用于治疗AOC多年，但确定可能从这种治疗中获益最多的患者仍存在争议。无论临床风险如何，贝伐单抗与改善无进展生存期（PFS）相关，但在一些国家，贝伐单抗用于治疗新诊断的AOC仅限于高风险患者（III期不能手术或次优减体积疾病，或IV期疾病）；这主要是由于来自III期试验的探索性亚组分析结果表明，只有高风险患者使用贝伐单抗获得总生存（OS）优势。最近报道的PAOLA-1试验的事后分析表明，对于新诊断的AOC和同源重组缺陷阳性肿瘤患者，维持奥拉帕尼加贝伐单抗与贝伐单抗单独治疗的患者，低风险（III期疾病患者接受了前期手术并完全切除）和高风险（III期疾病患者接受了前期手术并有残留疾病或接受了新辅助治疗）均获得了PFS和OS益处化疗，或IV期疾病)患者，促使重新评估贝伐单抗在低风险患者中的作用。本综述探讨了贝伐单抗在AOC治疗途径中的作用，讨论了其在一线、维持和复发环境中的有效性和安全性，并评估了贝伐单抗在危险人群和治疗线中的临床意义。

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引用次数: 0

Enhancing radiotherapy techniques for Triple-Negative breast cancer treatment 加强三阴性乳腺癌的放疗技术

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-04-17 DOI: 10.1016/j.ctrv.2025.102939

Saharnaz Sarlak, Gilles Pagès, Frédéric Luciano

Breast cancer is the most prevalent cancer among women worldwide, with various subtypes that require distinct treatment approaches. Among these, Triple-Negative Breast Bancer (TNBC) is recognized as the most aggressive form, often associated with poor prognosis due to its lack of targeted therapeutic options. This review specifically focuses on Radiotherapy (RT) as a treatment modality for TNBC, evaluating recent advancements and ongoing challenges, particularly the issue of radioresistance.

RT remains an essential part in the management of breast cancer, including TNBC. Over the years, multiple improvements have been made to enhance RT effectiveness and minimize resistance. The introduction of advanced techniques such as Stereotactic Body Radiation Therapy (SBRT) and Stereotactic Radiosurgery (SRS) has significantly improved precision and reduced toxicity. More recently, proton radiation therapy, a novel RT modality, has been introduced, offering enhanced dose distribution and reducing damage to surrounding healthy tissues. Despite these technological advancements, a subset of TNBC patients continues to exhibit resistance to RT, leading to recurrence and poor treatment outcomes.

To overcome radioresistance, there is an increasing interest in combining RT with targeted therapeutic agents that sensitize cancer cells to radiation. Radiosensitizing drugs have been explored to enhance the efficacy of RT by making cancer cells more susceptible to radiation-induced damage. Potential candidates include DNA damage repair inhibitors, immune checkpoint inhibitors, and small-molecule targeted therapies that interfere with key survival pathways in TNBC cells.

In conclusion, while RT remains a crucial modality for TNBC treatment, radioresistance remains a significant challenge. Future research should focus on optimizing RT techniques while integrating radiosensitizing agents to improve treatment efficacy. By combining RT with targeted drug therapy, a more effective and personalized treatment approach can be developed, ultimately improving patient outcomes and reducing recurrence rates in TNBC.

乳腺癌是全世界妇女中最普遍的癌症，有各种亚型，需要不同的治疗方法。其中，三阴性乳腺平衡癌（TNBC）被认为是最具侵袭性的形式，由于缺乏针对性的治疗选择，通常与预后不良相关。这篇综述特别关注放射治疗（RT）作为TNBC的一种治疗方式，评估最近的进展和正在面临的挑战，特别是放射耐药问题。放疗仍然是乳腺癌治疗的重要组成部分，包括TNBC。多年来，已经进行了多项改进，以提高RT的有效性并最大限度地减少耐药性。立体定向放射治疗（SBRT）和立体定向放射外科（SRS）等先进技术的引入，大大提高了精度和降低了毒性。最近，质子放射治疗，一种新的放射治疗方式，提供了增强剂量分布和减少对周围健康组织的损伤。尽管有这些技术进步，但一部分TNBC患者仍然表现出对RT的耐药性，导致复发和治疗效果不佳。为了克服放射耐药，人们越来越关注将放射治疗与靶向治疗药物相结合，使癌细胞对放射敏感。放射增敏药物已被探索，通过使癌细胞更容易受到辐射引起的损伤来增强放射治疗的疗效。潜在的候选药物包括DNA损伤修复抑制剂、免疫检查点抑制剂和干扰TNBC细胞关键存活途径的小分子靶向治疗。总之，虽然放疗仍然是TNBC治疗的关键方式，但放射耐药仍然是一个重大挑战。未来的研究应着眼于优化放疗技术，同时结合放射增敏剂提高治疗效果。通过将放疗与靶向药物治疗相结合，可以开发出更有效和个性化的治疗方法，最终改善患者预后并降低TNBC的复发率。

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引用次数: 0

Targeting pediatric adrenocortical carcinoma: Molecular insights and emerging therapeutic strategies 针对儿童肾上腺皮质癌：分子的见解和新兴的治疗策略

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-04-16 DOI: 10.1016/j.ctrv.2025.102942

Michaela Kuhlen , Maximilian Schmutz , Marina Kunstreich , Antje Redlich , Rainer Claus

Pediatric adrenocortical carcinoma (pACC) is an exceptionally rare and aggressive malignancy, accounting for only 0.2–0.3% of childhood cancers. Characterized by significant endocrine activity and often associated with genetic syndromes such as Li-Fraumeni syndrome, pACC exhibits distinct clinical and molecular profiles compared to adult adrenocortical carcinoma (ACC). Current treatment approaches, largely adapted from adult protocols, center on surgery and chemotherapy, including mitotane. However, the lack of pediatric-specific data and major clinical trials underscores a pressing need for tailored therapeutic strategies.

Advances in molecular profiling have unveiled actionable targets, such as alterations in the Wnt/β-catenin and MAP/ERK pathways, overexpression of IGF2, and epigenetic dysregulation. Emerging therapies, including immune checkpoint inhibitors, CAR T-cell therapy, and radiopharmaceuticals, hold promise but remain largely untested in pediatric populations. Targeting metabolic vulnerabilities, such as steroidogenesis and lipid metabolism, offers additional avenues for therapeutic innovation. Furthermore, improved diagnostic tools like liquid biopsy and steroid profiling may enhance disease monitoring and early detection.

Despite progress in understanding pACC biology, significant challenges remain in translating these insights into effective treatments. Collaborative efforts, such as the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT), and the development of pediatric-specific clinical trials are vital for advancing the field. Multidisciplinary care and international research initiatives will be pivotal in addressing the unmet needs of pACC patients.

By leveraging molecular insights and fostering global collaboration, the field can move toward personalized medicine, improving outcomes and quality of life for children with this challenging disease. Expanding clinical trials, refining diagnostic tools, and integrating novel therapies into treatment regimens will be critical in bridging the gap between pediatric and adult ACC treatment success.

小儿肾上腺皮质癌（pACC）是一种异常罕见的侵袭性恶性肿瘤，仅占儿童癌症的 0.2-0.3%。与成人肾上腺皮质癌（ACC）相比，小儿肾上腺皮质癌的特点是具有明显的内分泌活性，而且往往与遗传综合征（如李-弗劳米尼综合征）有关，在临床和分子特征方面表现出与成人肾上腺皮质癌截然不同的特点。目前的治疗方法主要沿用成人方案，以手术和化疗（包括米托坦）为中心。分子图谱分析的进展揭示了可操作的靶点，如 Wnt/β-catenin 和 MAP/ERK 通路的改变、IGF2 的过度表达以及表观遗传失调。包括免疫检查点抑制剂、CAR T 细胞疗法和放射性药物在内的新兴疗法前景广阔，但在儿科人群中基本上仍未得到验证。针对代谢弱点（如类固醇生成和脂质代谢）的疗法为治疗创新提供了更多途径。此外，液体活检和类固醇分析等诊断工具的改进可加强疾病监测和早期检测。尽管在了解 pACC 生物学方面取得了进展，但要将这些见解转化为有效的治疗方法仍面临巨大挑战。欧洲儿科罕见肿瘤合作研究小组（EXPeRT）等合作机构的努力以及儿科特定临床试验的发展对于推动该领域的发展至关重要。多学科治疗和国际研究计划对于满足儿童罕见肿瘤患者尚未得到满足的需求至关重要。通过利用分子洞察力和促进全球合作，该领域可以向个性化医疗迈进，改善这一具有挑战性疾病患儿的治疗效果和生活质量。扩大临床试验、完善诊断工具并将新型疗法纳入治疗方案，对于缩小儿童和成人 ACC 治疗成功率之间的差距至关重要。

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引用次数: 0

Management approaches for recurrent or metastatic head and neck squamous cell carcinoma after anti-PD-1/PD-L1 immunotherapy 抗pd -1/PD-L1免疫治疗后复发或转移性头颈部鳞状细胞癌的治疗方法

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-04-10 DOI: 10.1016/j.ctrv.2025.102938

Makoto Tahara , Darren Wan-Teck Lim , Bhumsuk Keam , Brigette Ma , Li Zhang , Chaojun Wang , Ye Guo

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer globally. For patients with recurrent or metastatic (R/M) HNSCC, immunotherapy represents an important advance in clinical practice as an effective and widely used first-line treatment. However, drug resistance following immunotherapy is an emerging problem and, despite the success of immunotherapy in R/M HNSCC, a proportion of patients will become immunotherapy resistant. The mechanisms of immunotherapy resistance are not yet fully understood and subsequent treatment options are limited. Therefore, there is an unmet need for effective and well tolerated treatments for patients who develop immunotherapy-resistant HNSCC.

In this review, we address these challenges by summarizing the current definitions of immunotherapy resistance (primary and acquired resistance) as well as knowledge of the mechanisms of resistance to immunotherapy in R/M HNSCC. We then review available clinical data on treatment strategies, including rechallenge with immunotherapy, chemotherapy ± cetuximab, other targeted treatments, antibody-drug conjugates, and bispecific antibodies. We also investigate future research directions by reviewing ongoing clinical trials.

Our review shows that the optimal therapeutic strategy for patients with R/M HNSCC remains unclear. While many therapies have reported promising preliminary results, prospective clinical trials are required to support their adoption in clinical practice. In particular, it appears that immunotherapy and antibody-drug conjugates have high potential in this setting. Our review also highlights the importance of further investigation of the mechanisms underlying immunotherapy-resistant R/M HNSCC, to inform selection of optimal therapeutic strategies on an individual patient basis and improve patient outcomes.

头颈部鳞状细胞癌（HNSCC）是全球第七大常见癌症。对于复发或转移性（R/M） HNSCC患者，免疫治疗作为一种有效且广泛使用的一线治疗方法，在临床实践中取得了重要进展。然而，免疫治疗后的耐药性是一个新出现的问题，尽管免疫治疗在R/M HNSCC中取得了成功，但仍有一部分患者会产生免疫治疗耐药性。免疫治疗耐药机制尚不完全清楚，后续治疗选择有限。因此，对免疫治疗耐药的HNSCC患者的有效和耐受性良好的治疗需求尚未得到满足。在这篇综述中，我们通过总结目前免疫治疗耐药的定义（原发性和获得性耐药）以及对R/M HNSCC免疫治疗耐药机制的了解来解决这些挑战。然后，我们回顾了现有治疗策略的临床数据，包括免疫治疗、化疗±西妥昔单抗、其他靶向治疗、抗体-药物偶联物和双特异性抗体的再挑战。我们还通过回顾正在进行的临床试验来探讨未来的研究方向。我们的综述显示，R/M型HNSCC患者的最佳治疗策略尚不清楚。虽然许多疗法已经报告了有希望的初步结果，但需要前瞻性临床试验来支持其在临床实践中的采用。特别是，免疫疗法和抗体-药物结合物在这种情况下具有很高的潜力。我们的综述还强调了进一步研究免疫治疗耐药R/M HNSCC的机制的重要性，这有助于在个体患者的基础上选择最佳治疗策略并改善患者的预后。

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引用次数: 0

From ICI to ICU: A systematic review of patients with solid tumors who are treated with immune checkpoint inhibitors (ICI) and admitted to the intensive care unit (ICU) 从ICI到ICU：对接受免疫检查点抑制剂（ICI）治疗并入住重症监护病房（ICU）的实体瘤患者的系统回顾

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-04-10 DOI: 10.1016/j.ctrv.2025.102936

Brigit van Dijk , Joséphine C. Janssen , Paul L.A. van Daele , Maja J.A. de Jonge , Arjen Joosse , Henk M.W. Verheul , Jelle L. Epker , Astrid A.M. van der Veldt

Purpose

Immune checkpoint inhibitors (ICIs) have improved the survival of patients with different solid tumors and even resulted in cure of metastatic disease. Since the introduction of ICIs, an increasing number of patients is admitted to the ICU for severe and potentially life-threatening immune related adverse events (irAEs). The outcome of patients who are admitted to the ICU because of severe irAEs is still unknown. The aim of this systematic review is to collect evidence on the outcomes of patients with solid tumors who are admitted to the ICU because of irAEs.

Methods

Medline, Embase, Cochrane central register of controlled trials and Google Scholar were searched systematically from 1975 to 24 September 2024. Articles were only included when describing patients with solid tumors who were admitted to the ICU because of irAEs after treatment with ICIs. Two independent reviewers extracted the data and assessed the risk of bias.

Results

A total of 183 articles were included: two prospective ICU population-based studies, four retrospective ICU population-based studies, 25 retrospective studies describing irAEs with incidental ICU admissions, one review of case reports, and 153 articles with a total of 177 case reports. The six ICU population-based studies contained a total of 169 patients who were admitted to the ICU due to irAEs. In these six studies, the most frequently reported irAEs were pneumonitis and neurological irAEs. Of these 169 patients, 26% of the patients died on the ICU and an additional 8% of patients in the three to six months thereafter due to irAEs or disease progression. In all 183 included articles, various irAEs were described and the reported mortality rate varied from 0 to 53%.

Conclusion

The potential favorable outcomes of both the solid tumors and irAEs will probably result in more need for ICU admissions. Prospective clinical trials are needed to optimize the treatment strategy of severe irAEs at the ICU. Based on the favourable outcomes after life-threatening irAEs, ICU admission should definitely be considered for patients with solid tumors who have life-threatening irAEs.

目的免疫检查点抑制剂（ICIs）提高了不同实体瘤患者的生存率，甚至导致转移性疾病的治愈。自引入ICIs以来，越来越多的患者因严重和可能危及生命的免疫相关不良事件（irAEs）而入住ICU。因严重irae而入住ICU的患者的预后尚不清楚。本系统综述的目的是收集因irae而入住ICU的实体肿瘤患者预后的证据。方法系统检索1975年至2024年9月24日的medline、Embase、Cochrane对照试验中心注册库和谷歌Scholar。文章仅在描述实体肿瘤患者在接受ICIs治疗后因irae而入住ICU时被纳入。两名独立审稿人提取数据并评估偏倚风险。结果共纳入183篇文章：2篇基于ICU人群的前瞻性研究，4篇基于ICU人群的回顾性研究，25篇描述irae附带ICU入院的回顾性研究，1篇病例报告综述，153篇共计177例病例报告。这6项基于ICU人群的研究共纳入了169名因irAEs入住ICU的患者。在这六项研究中，最常报道的irAEs是肺炎和神经系统irAEs。在这169名患者中，26%的患者死于ICU，另有8%的患者在此后的3至6个月内死于irae或疾病进展。在所有纳入的183篇文章中，描述了各种irae，报告的死亡率从0%到53%不等。结论无论是实体瘤还是irAEs，其潜在的良好预后都可能导致更多的ICU住院需求。需要前瞻性临床试验来优化ICU重症irae的治疗策略。基于危及生命的irAEs后的良好结局，对于危及生命的irAEs实体肿瘤患者，绝对应该考虑入住ICU。

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引用次数: 0

Primary testicular lymphoma 原发性睾丸淋巴瘤

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-04-10 DOI: 10.1016/j.ctrv.2025.102927

Brian T. Grainger , Chan Y. Cheah

Primary testicular lymphoma (PTL) is a rare extranodal lymphoma. The majority of cases are of diffuse large B cell lymphoma (DLBCL) histology (PT-DLBCL) with an activated B-cell-like (ABC) gene expression profile. These are characterised clinically by a high risk of contralateral testis and central nervous system (CNS) relapse, representing an ongoing area of unmet clinical need. Here, we review the epidemiology, clinical presentation and diagnostic evaluation of PT-DLBCL along with the advances in molecular biology that have occurred in the last decade, concerning the now-recognised molecular subtypes of DLBCL and their role of immune escape and sustained signalling in disease pathophysiology. We also appraise the retrospective and prospective clinical trials underpinning modern treatment recommendations, including the updated guidance on the role of radiotherapy and the latest evidence regarding strategies for preventing CNS relapse.

原发性睾丸淋巴瘤（PTL）是一种罕见的结外淋巴瘤。大多数病例为弥漫性大B细胞淋巴瘤（DLBCL）组织学（PT-DLBCL），具有活化的B细胞样（ABC）基因表达谱。这些临床特征是对侧睾丸和中枢神经系统（CNS）复发的高风险，这是一个未满足临床需求的持续领域。在这里，我们回顾了PT-DLBCL的流行病学、临床表现和诊断评估，以及过去十年来分子生物学的进展，包括现在公认的DLBCL分子亚型及其在疾病病理生理中的免疫逃逸和持续信号传导的作用。我们还评估了支持现代治疗建议的回顾性和前瞻性临床试验，包括关于放疗作用的最新指南和关于预防中枢神经系统复发策略的最新证据。

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Harnessing cytokine immunocomplexes and cytokine fusion proteins for cancer Therapy: Mechanisms and clinical potential 利用细胞因子免疫复合物和细胞因子融合蛋白治疗癌症：机制和临床潜力

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-04-09 DOI: 10.1016/j.ctrv.2025.102937

Wei Yang Kong , Amelia Soderholm , Andrew J. Brooks , Jazmina L. Gonzalez Cruz , James W. Wells

Cytokines are pivotal regulators of cellular functions and immune responses, making them highly promising targets for cancer immunotherapy. Despite their widespread clinical application, the effectiveness of cytokine immunotherapy is often hampered by their pleiotropic effects, short half-lives, uneven biodistribution, and severe side effects at high dosages. Recent advancements in cytokine biology have led to the development of cytokine-antibody immunocomplexes and cytokine fusion proteins, offering a new paradigm in cancer treatments. These innovations foster the ability of cytokines to selectively activate specific cancer-targeting immune cell populations, such as CD8 T cells and NK cells, effectively inhibiting tumour progression. Furthermore, both therapeutic approaches can mitigate systemic toxicities and prolong the biological activity of cytokines in the body. This review delves into the recent advancements of cytokine immunocomplexes and cytokine fusion proteins, with a particular focus on interleukin-2 (IL-2), IL-7 and IL-15, which are in clinical/preclinical development. Moreover, we discuss the therapeutic benefits of these approaches observed in recent preclinical and clinical studies, along with the challenges that must be addressed to fully unlock their potential in cancer immunotherapy.

细胞因子是细胞功能和免疫反应的关键调节因子，使其成为癌症免疫治疗的极有希望的靶点。尽管临床应用广泛，但细胞因子免疫治疗的有效性往往受到其多效性、半衰期短、生物分布不均匀以及高剂量时严重副作用的影响。细胞因子生物学的最新进展导致了细胞因子抗体免疫复合物和细胞因子融合蛋白的发展，为癌症治疗提供了新的范例。这些创新促进了细胞因子选择性激活特定癌症靶向免疫细胞群的能力，如CD8 T细胞和NK细胞，有效抑制肿瘤进展。此外，这两种治疗方法都可以减轻全身毒性并延长体内细胞因子的生物活性。本文综述了细胞因子免疫复合物和细胞因子融合蛋白的最新进展，重点介绍了处于临床/临床前开发阶段的白细胞介素-2 （IL-2）、IL-7和IL-15。此外，我们讨论了在最近的临床前和临床研究中观察到的这些方法的治疗益处，以及必须解决的挑战，以充分释放它们在癌症免疫治疗中的潜力。

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