Cancer treatment reviews最新文献_第6页

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

Cancer treatment reviews

Pub Date : 2025-12-01 Epub 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

Interpreting immunogenicity in oncology clinical trials 肿瘤临床试验中免疫原性的解释

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-11-01 Epub Date: 2025-08-25 DOI: 10.1016/j.ctrv.2025.103016

Peter R. Galle , Martin Reck , David J. Pinato , Rosario Garcia-Campelo , Richard S. Finn , Sophie Cousin , Jim Zanghi , Coen A. Bernaards , Steven J. Swanson , Stefanie Morris , Yuan Song , Solange Peters

Immunogenicity of a therapeutic protein product may elicit an unintended immune response, and is a critical aspect evaluated in oncology clinical trials. The development of anti-drug antibodies (ADAs) can impact the pharmacokinetics, pharmacodynamics, efficacy, and safety of these therapies. We review the background and nomenclature of immunogenicity assessment in oncology studies and emphasize the complexities in ADA detection arising from assay sensitivity, drug interference, and notably, the frequency of patient sampling for ADA analysis. The applicability of common nomenclature, however, has limitations in the context of oncology. Of prime consideration for physicians is that the clinical impact of ADA is far more important than just their presence. Furthermore, the interpretation of immunogenicity data in oncology is complicated by patient-specific factors, concomitant treatments, and potential survivorship bias. Regulatory guidelines acknowledge these complexities, mandating specific statements on product labels cautioning against cross-trial comparisons of ADA incidence due to variations in assay methods and sampling schedules. Accurate interpretation of immunogenicity data, considering assay methodologies, study design, and sampling frequency, is crucial for clinicians to assess the clinical relevance of ADA findings and make informed treatment decisions for patients receiving therapeutic protein products in oncology. The focus should be on the clinical relevance of ADAs rather than simply their incidence.

治疗性蛋白产品的免疫原性可能引起意想不到的免疫反应，是肿瘤临床试验评估的一个关键方面。抗药物抗体（ADAs）的发展会影响这些疗法的药代动力学、药效学、疗效和安全性。我们回顾了肿瘤研究中免疫原性评估的背景和术语，并强调了ADA检测的复杂性，包括检测敏感性，药物干扰，特别是ADA分析的患者采样频率。通用命名法的适用性，然而，在肿瘤学的背景下有局限性。医生首要考虑的是，ADA的临床影响远比他们的存在更重要。此外，肿瘤免疫原性数据的解释因患者特异性因素、伴随治疗和潜在的生存偏差而变得复杂。监管指南承认这些复杂性，要求在产品标签上作出具体说明，警告由于检测方法和采样计划的差异，不要进行ADA发病率的交叉试验比较。考虑到检测方法、研究设计和采样频率，准确解释免疫原性数据对于临床医生评估ADA结果的临床相关性以及为接受肿瘤治疗性蛋白产品的患者做出明智的治疗决策至关重要。重点应放在副副性痴呆的临床相关性上，而不仅仅是其发病率。

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引用次数: 0

Impact of brain metastases on systemic renal cell carcinoma treatment outcomes: A systematic literature review 脑转移对全身性肾细胞癌治疗结果的影响：系统文献综述

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-11-01 Epub Date: 2025-09-24 DOI: 10.1016/j.ctrv.2025.103024

Natalie Charnley , Kate Fife , Daniel Y.C. Heng , James Larkin , John McGrane , Sylvie Négrier , Naveen Vasudev , Balaji Venugopal , Alison Chisholm , Alessia Ogareva , Áine Prendergast , Laurence Albiges

Introduction

Brain metastases (BrM) are a negative prognostic factor in renal cell carcinoma (RCC) populations. Patients with RCC and BrM (RCC BrM + ) may receive systemic therapy and/or brain-targeted (local) treatment. We performed a systematic literature review to identify clinical trials and non-interventional studies reporting data on BrM impact on systemic treatment outcomes in patients with RCC.

Methods

We systematically searched the MEDLINE and Embase databases in January 2024 for publications reporting efficacy/effectiveness and/or safety/tolerability outcomes by BrM status from phase 2 and phase 3 clinical trials and non-interventional studies of systemic RCC therapies. Data were extracted from publications meeting predefined criteria (PROSPERO registration, CRD42023494896) and reported in accordance with PRISMA guidelines.

Results

Sixty-two publications (of 651 screened) were eligible (4 from prospective trials) and included 4,637 patients with RCC BrM + treated with systemic therapy. The most evaluated systemic therapies were sunitinib, nivolumab, ipilimumab + nivolumab, cabozantinib and sorafenib. Tolerability was generally consistent with known safety profiles in RCC trial populations. In the clinical trials, systemic treatment benefits for patients with RCC BrM + were equivocal. In non-interventional studies, survival was generally poorer in patients with RCC BrM + than reference groups (overall/BrM–). Survival and intracranial control benefits in patients with RCC BrM + were reported for some multimodal (systemic plus local) treatment strategies. There were no robust comparative data to guide systemic treatment selection.

Conclusion

We identified a need for robust data on intracranial and extracranial responses to systemic therapy in patients with RCC BrM+, taking into account prior local therapy exposure.

脑转移（BrM）是肾细胞癌（RCC）人群的一个负面预后因素。RCC和BrM （RCC BrM +）患者可接受全身治疗和/或脑靶向（局部）治疗。我们进行了系统的文献综述，以确定报告BrM对RCC患者全身治疗结果影响的临床试验和非介入性研究。方法：我们于2024年1月系统地检索了MEDLINE和Embase数据库，从系统性RCC治疗的2期和3期临床试验和非介入性研究中，根据BrM状态报告疗效/有效性和/或安全性/耐受性结果的出版物。数据从符合预定义标准的出版物中提取（PROSPERO注册号，CRD42023494896），并按照PRISMA指南进行报告。结果62篇（筛选的651篇）出版物（4篇来自前瞻性试验）符合条件，包括4,637例接受全身治疗的RCC BrM +患者。评估最多的全身疗法是舒尼替尼、纳武单抗、伊匹单抗+纳武单抗、卡博赞替尼和索拉非尼。在碾压细胞试验人群中，耐受性与已知的安全性基本一致。在临床试验中，RCC BrM +患者的全身治疗效果尚不明确。在非介入性研究中，RCC BrM +患者的生存率通常低于对照组（总体/BrM -）。一些多模式（全身加局部）治疗策略对RCC BrM +患者的生存和颅内控制有好处。没有可靠的比较数据来指导系统的治疗选择。结论：考虑到先前的局部治疗暴露，我们确定需要关于RCC BrM+患者对全身治疗的颅内和颅外反应的可靠数据。

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引用次数: 0

Genomic distinctions in adolescent and young adult cancer: A comprehensive review 青少年和青年癌症的基因组差异：一项全面的综述

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-11-01 Epub Date: 2025-09-20 DOI: 10.1016/j.ctrv.2025.103021

Jeffrey van Putten , Lina H. Lankhorst , Adrianus Johannes de Langen , Anthonie J. van der Wekken , Jeanine Roodhart , Karen Bolhuis , Sjoukje F. Oosting , Marloes van Dongen , Marleen Kok , Marjolein Geurts , Johan A.F. Koekkoek , Edwin Cuppen , Hilde H. Nienhuis , Winette T.A. van der Graaf

Cancer in Adolescents and Young Adults (AYAs) represents a unique biological intersection, encompassing malignancies typical of both paediatric and older adults, as well as age-specific cancers. Yet, diagnostic and treatment approaches are not tailored to AYAs, potentially overlooking age-specific molecular characteristics. This review examines genomic differences between AYAs and paediatric and older patients, emphasising trends in cancer driver genes and identifying knowledge gaps that limit our understanding of AYA cancer biology.

Across studies and cancer types, the AYA age range varies but is typically defined as 15–39 years. Remarkably, for nearly half of cancers diagnosed in AYAs, little or no literature exists on genomic differences or similarities compared to other age groups. Common cancers like testicular cancer and gynaecological cancer are underrepresented, while other typical AYA cancers such as thyroid cancer entirely lack comparative literature. In contrast, less common AYA cancers such as lung cancer and colorectal cancer are investigated extensively. Although genomic differences are reported across cancer types and in pan-cancer analyses, findings are often not generalisable to relevant subtypes or inconsistent, and insights gained are limited by the use of single-gene assays or small gene panels.

This review reveals an imbalance between the global incidence of AYA cancers and the scope of comparative genomic studies, as well as a lack of broader comprehensive molecular profiling. Addressing these gaps through broader genomic research, particularly in underexplored cancers, is essential to determine whether AYA tumour biology is indeed distinctive, and how age-appropriate, genomics-driven precision oncology should be delivered.

青少年和年轻人的癌症（AYAs）代表了一个独特的生物学交叉点，包括儿科和老年人典型的恶性肿瘤，以及年龄特异性癌症。然而，诊断和治疗方法并不是针对aya量身定制的，可能会忽略年龄特异性分子特征。这篇综述检查了AYA与儿科和老年患者之间的基因组差异，强调了癌症驱动基因的趋势，并确定了限制我们对AYA癌症生物学理解的知识差距。在不同的研究和癌症类型中，AYA的年龄范围各不相同，但通常定义为15-39岁。值得注意的是，与其他年龄组相比，近一半的aya患者诊断出的癌症，很少或根本没有关于基因组差异或相似性的文献。常见的癌症，如睾丸癌和妇科癌的代表性不足，而其他典型的AYA癌症，如甲状腺癌，完全缺乏比较文献。相比之下，不太常见的AYA癌症，如肺癌和结直肠癌，得到了广泛的研究。尽管在癌症类型和泛癌症分析中报告了基因组差异，但研究结果往往不能推广到相关亚型或不一致，并且所获得的见解受到单基因测定或小基因小组使用的限制。这篇综述揭示了全球AYA癌症发病率与比较基因组研究范围之间的不平衡，以及缺乏更广泛的综合分子谱。通过更广泛的基因组研究来解决这些差距，特别是在未被充分探索的癌症中，对于确定AYA肿瘤生物学是否确实与众不同，以及如何提供适合年龄的、基因组学驱动的精确肿瘤学至关重要。

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引用次数: 0

Comparative review of KEYNOTE-689 and NIVOPOSTOP trials and their impact on perioperative immunotherapy in locally advanced head and neck cancer KEYNOTE-689和nivoopstop试验的比较综述及其对局部晚期头颈癌围手术期免疫治疗的影响

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-11-01 Epub Date: 2025-08-27 DOI: 10.1016/j.ctrv.2025.103018

Yoshinori Imamura , Masafumi Kanno , Shigeharu Fujieda

Aim

To critically review the emerging evidence from two randomised trials—KEYNOTE-689 and NIVOPOSTOP—on perioperative immune checkpoint inhibition in resectable, locally advanced head and neck squamous cell carcinoma, and to elucidate how these positive results may redefine the current and future treatment paradigms.

Methods

We conducted a narrative review comparing the design, patient populations, treatment protocols, and outcomes of KEYNOTE-689 and NIVOPOSTOP. Data sources included ClinicalTrials.gov, presentations at major international oncology meetings, and peer-reviewed publications.

Results

KEYNOTE-689 adopted a broad perioperative strategy using pembrolizumab both pre- and postoperatively, with (chemo)radiotherapy administered based on pathological risk. NIVOPOSTOP employed a focused adjuvant approach, using nivolumab alongside postoperative chemoradiotherapy only in high-risk patients. Despite distinct strategies, both trials demonstrated significant improvements in event-free survival (KEYNOTE-689; hazard ratio 0.73; 95% confidence interval, 0.58–0.92) and disease-free survival (NIVOPOSTOP; hazard ratio 0.76; 95% confidence interval, 0.60–0.98). KEYNOTE-689 reduced distant recurrence, while NIVOPOSTOP improved loco-regional control. Although overall survival data remain immature, both show favourable trends. Treatment adherence and treatment-related serious adverse events were lower in KEYNOTE-689.

Conclusions

Perioperative immune checkpoint inhibition is emerging as the first new standard in two decades for resectable locally advanced head and neck squamous cell carcinoma. KEYNOTE-689 highlights early immune priming, whereas NIVOPOSTOP offers a pragmatic, high-risk–targeted model with high compliance. Treatment selection should be tailored by recurrence risk, programmed death-ligand 1 expression, and multidisciplinary evaluation. Future priorities include refining patient selection and immune checkpoint blockade schedule, optimizing neoadjuvant regimens, implementing response-adapted de-escalation, and assessing cost-effectiveness.

目的：对keynote -689和nivoopstop两项随机试验中关于可切除的局部晚期头颈部鳞状细胞癌围手术期免疫检查点抑制的新证据进行批判性回顾，并阐明这些阳性结果如何重新定义当前和未来的治疗范式。方法对KEYNOTE-689和nivoopstop的设计、患者群体、治疗方案和结局进行回顾性分析。数据来源包括ClinicalTrials.gov、主要国际肿瘤学会议的报告和同行评审的出版物。keynote -689采用了广泛的围手术期策略，术前和术后均使用派姆单抗，并根据病理风险给予（化疗）放疗。NIVOPOSTOP采用集中辅助方法，仅在高危患者中使用纳武单抗和术后放化疗。尽管策略不同，但两项试验均显示无事件生存期（KEYNOTE-689；风险比0.73；95%可信区间0.58-0.92）和无病生存期（nivoopstop；风险比0.76；95%可信区间0.60-0.98）有显著改善。KEYNOTE-689减少了远处复发，而nivoopstop改善了局部区域控制。尽管总体生存数据仍不成熟，但两者都显示出有利的趋势。KEYNOTE-689组的治疗依从性和治疗相关的严重不良事件较低。结论手术免疫检查点抑制是近20年来首个可切除局部晚期头颈部鳞状细胞癌的新标准。KEYNOTE-689强调早期免疫启动，而nivoopstop提供了一种实用的、高风险的靶向模型，具有高依从性。治疗选择应根据复发风险、程序性死亡-配体1表达和多学科评估进行调整。未来的优先事项包括改进患者选择和免疫检查点封锁计划，优化新辅助方案，实施适应反应的降级，以及评估成本效益。

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引用次数: 0

Overcoming the barriers to treatment of rare cancer patients in the era of precision oncology: A call to action 在精准肿瘤学时代克服治疗罕见癌症患者的障碍：行动呼吁

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-11-01 Epub Date: 2025-08-14 DOI: 10.1016/j.ctrv.2025.103013

Winette T.A. van der Graaf , Nina S. Heiss , Carolyn L. Hynes , Simone P. Keller , Ariane Weinman , Jean-Yves Blay , Pedro Franco , Rachel H. Giles , Denis Lacombe , Philipp Schlatter , David M. Thomas , Sahar Barjesteh van Waalwijk van Doorn-Khosrovani , Max Williamson , Ruth Plummer

Rare cancers account for a quarter of cancer diagnoses in Europe yet clinical research, diagnosis, treatment access, and survival outcomes lag significantly behind common cancers. Despite the potential of precision oncology, the consistent implementation of comprehensive genomic profiling in routine clinical practice and robust evidence-generation remains a challenge in this population, compounded by regulatory hurdles and a lack of investment in drug development. A concerted effort across all stakeholders is required to optimise diagnostics, including access to molecular profiling, to expedite clinical trials and treatment access, and to gather high-quality data, including patient-reported outcomes, in rare cancers. Some initiatives are already showing promise including the establishment of national expert reference centres and European Reference Networks such as EURACAN. However, further collaboration is required to speed up the diagnostic trajectory so that rare cancer patients present with less late-stage disease, and to facilitate clinical trials leading to wider access to precision oncology drugs shown to be safe and effective. In the context of so many hurdles (diagnosis, treatment, research, development and regulatory), there is an even greater role for patient and clinical trial organisations and funders to help fill the aforementioned gaps. Innovative solutions are urgently required to address the high unmet medical need for patients with rare cancers.

罕见癌症占欧洲癌症诊断的四分之一，但临床研究、诊断、治疗可及性和生存结果明显落后于常见癌症。尽管精准肿瘤学具有潜力，但在常规临床实践中持续实施全面的基因组图谱和强有力的证据生成仍然是这一人群面临的挑战，再加上监管障碍和药物开发投资不足。需要所有利益攸关方共同努力，优化诊断，包括获得分子图谱，加快临床试验和治疗获取，并收集罕见癌症的高质量数据，包括患者报告的结果。一些倡议已经显示出希望，包括建立国家专家参考中心和欧洲参考网络，例如EURACAN。然而，需要进一步的合作来加快诊断轨迹，以减少罕见癌症患者出现的晚期疾病，并促进临床试验，从而更广泛地获得安全有效的精准肿瘤药物。在如此多的障碍（诊断、治疗、研究、开发和监管）的背景下，患者和临床试验组织以及资助者在帮助填补上述空白方面发挥着更大的作用。迫切需要创新的解决方案来解决罕见癌症患者未得到满足的高度医疗需求。

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引用次数: 0

Novel therapies targeting delta-like ligand 3 (DLL3) in pulmonary and gastroenteropancreatic neuroendocrine carcinomas 靶向δ样配体3 （DLL3）治疗肺和胃肠胰神经内分泌癌的新疗法

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-11-01 Epub Date: 2025-09-15 DOI: 10.1016/j.ctrv.2025.103022

María Alameda-Guijarro , Antonio Rueda-Lara , Gema Martin-Montalvo , Oliver Higuera , Laura Gutiérrez-Sainz , Diego Jiménez-Bou , Julia Villamayor , Javier de Castro , Ana Custodio , Pablo Pérez-Wert

引用次数: 0

Opportunities and challenges for non–small cell lung cancer brain metastases in the immunotherapy era 免疫治疗时代非小细胞肺癌脑转移的机遇与挑战

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-11-01 Epub Date: 2025-08-22 DOI: 10.1016/j.ctrv.2025.103014

Ying Yu, Yuxi Luo, Fujuan Zeng, Anwen Liu

Brain radiotherapy (BRT) has traditionally been the mainstay of treatment for non-small cell lung cancer brain metastases (NSCLC-BM), given the low intracranial efficacy of conventional systemic therapies. In recent years, immune checkpoint inhibitors (ICIs) have emerged as a standard treatment for advanced NSCLC without actionable driver mutations and have shown promising benefits in patients with BM. However, their intracranial efficacy remains modest, as the highest reported intracranial objective response rate and median intracranial progression-free survival in first-line populations reaching only 56.3 % and 12.7 months, respectively, which is likely explained by restricted blood-brain barrier permeability, the immunosuppressive tumor microenvironment within BM, and both primary and acquired resistance to ICIs. Preclinical evidence suggests that BRT can synergize with ICIs by enhancing antitumor immunity and overcoming immune resistance, primarily through blood-brain barrier disruption and tumor microenvironment remodeling. Consistently, encouraging clinical outcomes have been reported with the combination of BRT and ICI (BRT-ICI) in NSCLC-BM, while prospective data remain scarce. A recent phase II trial reported some of the most favorable outcomes to date with BRT-ICI plus chemotherapy, showing an intracranial objective response rate of 82.5 %, a median intracranial progression-free survival of 16.1 months, and a median overall survival of 20.9 months in treatment-naive patients with NSCLC-BM. Despite these advances, the optimal schedule of BRT-ICI remains controversial, with ongoing debates on treatment sequencing, timing, and radiation dose-fractionation. Additionally, critical challenges persist, including the risk of neurological toxicity, particularly radiation necrosis, and the absence of predictive biomarkers for patient selection. This review summarizes the current advances in ICI-based systemic therapies for NSCLC-BM, discusses the existing opportunities and progress of BRT-ICI, and reflects on challenges in optimizing this strategy in the immunotherapy era.

鉴于常规全身治疗的颅内疗效较低，脑放疗（BRT）传统上一直是治疗非小细胞肺癌脑转移（NSCLC-BM）的主要方法。近年来，免疫检查点抑制剂（ICIs）已成为无可操作驱动突变的晚期非小细胞肺癌的标准治疗方法，并在BM患者中显示出有希望的益处。然而，它们的颅内疗效仍然不高，据报道，在一线人群中，最高的颅内客观缓解率和中位颅内无进展生存期分别仅为56.3%和12.7个月，这可能与血脑屏障通透性受限、脑基内免疫抑制的肿瘤微环境以及对ICIs的原发性和获得性耐药有关。临床前证据表明，BRT可通过破坏血脑屏障和重塑肿瘤微环境，增强抗肿瘤免疫并克服免疫抵抗，从而与ICIs协同作用。一贯地，BRT联合ICI （BRT-ICI）治疗NSCLC-BM的临床结果令人鼓舞，但前瞻性数据仍然很少。最近的一项II期试验报告了迄今为止BRT-ICI +化疗的一些最有利的结果，显示未接受治疗的NSCLC-BM患者的颅内客观缓解率为82.5%，中位颅内无进展生存期为16.1个月，中位总生存期为20.9个月。尽管取得了这些进展，BRT-ICI的最佳时间表仍然存在争议，关于治疗顺序、时间和辐射剂量分级的争论正在进行中。此外，关键的挑战仍然存在，包括神经毒性的风险，特别是放射性坏死，以及缺乏用于患者选择的预测性生物标志物。本文综述了目前基于ici的NSCLC-BM全身治疗的进展，讨论了BRT-ICI存在的机遇和进展，并反思了在免疫治疗时代优化该策略所面临的挑战。

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引用次数: 0

Fecal microbiota transplantation to enhance cancer treatment outcomes across different cancer types: A systematic literature review 粪便微生物群移植提高不同癌症类型的癌症治疗效果：系统文献综述。

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-11-01 Epub Date: 2025-09-25 DOI: 10.1016/j.ctrv.2025.103025

Demi Wekking , Tom van den Ende , Maarten F. Bijlsma , Andrés Vidal-Itriago , Max Nieuwdorp , Hanneke W.M. van Laarhoven

Background

The gut microbiome is increasingly recognized as a critical modulator of cancer therapy response. This systematic review evaluates Fecal Microbiota Transplantation (FMT)’s impact on cancer treatment outcomes and treatment-related toxicity and explores its mode of action.

Methods

A systematic search was conducted for prospective or retrospective clinical studies published until May 2025 that investigated FMT in cancer patients undergoing immunotherapy, chemotherapy, radiotherapy, targeted therapy, or a combination regimen.

Results

45 studies were included. No large-scale RCTs with published efficacy data were available, and most findings were derived from studies that lacked statistical power to assess efficacy. The majority of the articles demonstrated the safety and feasibility of FMT. Most toxicities reported were grade 1 or 2. Mechanistically, donor FMT restores gut microbiota diversity and reprograms the gut ecosystem, with increases in tumor-infiltrating lymphocytes and lower levels of regulatory T cells being observed. Furthermore, studies reported clinical improvement and endoscopic and/or histologic remission of treatment-induced colitis following FMT, alongside decreased colonic CD8+ T cell infiltration.

Conclusion

Donor FMT appears to be a safe and feasible adjunctive strategy during both first and later-line therapy and has potential for managing treatment-related colitis; however, its efficacy and its role in preventing immune-related adverse events remain to be elucidated in RCTs, as well as its application for graft-versus-host disease. The variability in clinical outcomes and context-dependent microbiota-host interactions that result in inconsistent findings underscores the complexity of FMT as a therapeutic modality. Furthermore, subclassifying recipient cancer patients could (based on gut microbiome ecosystem features) enhance biomarker identification for treatment responses.

背景：肠道微生物组越来越被认为是癌症治疗反应的关键调节剂。本系统综述评估了粪便微生物群移植（FMT）对癌症治疗结果和治疗相关毒性的影响，并探讨了其作用模式。方法：系统检索到2025年5月之前发表的前瞻性或回顾性临床研究，这些研究调查了接受免疫治疗、化疗、放疗、靶向治疗或联合治疗的癌症患者的FMT。结果：纳入45项研究。没有发表疗效数据的大规模随机对照试验，大多数研究结果来自缺乏评估疗效的统计能力的研究。大多数文章论证了FMT的安全性和可行性。报告的大多数毒性为1级或2级。从机制上讲，供体FMT恢复肠道微生物群多样性并重新编程肠道生态系统，观察到肿瘤浸润淋巴细胞增加和调节性T细胞水平降低。此外，研究报告了FMT后治疗性结肠炎的临床改善和内镜和/或组织学缓解，同时结肠CD8+ T细胞浸润减少。结论：在一线和后期治疗中，供体FMT似乎是一种安全可行的辅助策略，并具有管理治疗相关性结肠炎的潜力；然而，其在预防免疫相关不良事件中的作用及其在移植物抗宿主病中的应用仍有待于在随机对照试验中阐明。临床结果的可变性和环境依赖的微生物-宿主相互作用导致不一致的结果，强调了FMT作为一种治疗方式的复杂性。此外，对受体癌症患者进行亚分类（基于肠道微生物组生态系统特征）可以增强对治疗反应的生物标志物识别。

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引用次数: 0

Advances in treatment strategies for low-grade serous ovarian cancer 低级别浆液性卵巢癌的治疗策略进展

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-11-01 Epub Date: 2025-09-05 DOI: 10.1016/j.ctrv.2025.103019

Lucia Musacchio , Domenica Lorusso , Giulia Sabetta , Alessandra Giustozzi , Elena Giudice , Maria Chiara Cannizzaro , Maria Teresa Perri , Anna Fagotti , Vanda Salutari

Low-grade serous ovarian carcinoma (LGSOC) represents a unique therapeutic challenge in gynecologic oncology. While it accounts for a minority of epithelial ovarian cancers (EOC), its distinct molecular landscape and limited sensitivity to conventional chemotherapy underscore the urgent need for alternative treatment paradigms. Over the past decade, advances in genomic profiling have led to a deeper understanding of its biology, revealing recurrent alterations in key signaling pathways such as (mitogen-activated protein kinase) MAPK, PI3K, and cell cycle regulators. These insights have catalyzed a shift toward precision medicine, with targeted agents and endocrine strategies emerging as promising avenues. However, despite encouraging signals from clinical trials, the rarity of LGSOC continues to hinder the development of robust, evidence-based standards. In this review, we critically examine the current treatment landscape and explore evolving therapeutic strategies, including ongoing efforts to integrate molecular biomarkers into clinical decision-making. By synthesizing recent evidence and highlighting key areas of unmet need, this review aims to provide a forward-looking perspective on the treatment of LGSOC. Future progress will depend on collaborative research, biomarker-driven clinical trial design, and a commitment to tailoring therapy based on the unique biology of this rare tumor type.

低级别浆液性卵巢癌（LGSOC）是妇科肿瘤学中一个独特的治疗挑战。虽然它在上皮性卵巢癌（EOC）中占少数，但其独特的分子结构和对常规化疗的有限敏感性强调了对替代治疗范例的迫切需要。在过去的十年中，基因组图谱的进步使人们对其生物学有了更深入的了解，揭示了关键信号通路如（丝裂原活化蛋白激酶）MAPK、PI3K和细胞周期调节因子的反复改变。这些见解催化了向精准医疗的转变，有针对性的药物和内分泌策略成为有前途的途径。然而，尽管临床试验显示出令人鼓舞的信号，LGSOC的稀缺性继续阻碍着强有力的循证标准的发展。在这篇综述中，我们批判性地审视了当前的治疗前景，并探索了不断发展的治疗策略，包括将分子生物标志物整合到临床决策中的持续努力。通过综合最近的证据和突出未满足需求的关键领域，本综述旨在为LGSOC的治疗提供前瞻性的视角。未来的进展将取决于合作研究，生物标志物驱动的临床试验设计，以及基于这种罕见肿瘤类型独特生物学的定制治疗的承诺。

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