Cancer treatment reviews最新文献_第5页

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 : 2025-09-20 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。

{"title":"Genomic distinctions in adolescent and young adult cancer: A comprehensive review","authors":"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","doi":"10.1016/j.ctrv.2025.103021","DOIUrl":"10.1016/j.ctrv.2025.103021","url":null,"abstract":"<div><div>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.</div><div>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.</div><div>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.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103021"},"PeriodicalIF":10.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Datopotamab deruxtecan: rational strategies, novel advancements, challenges, and future perspectives Datopotamab deruxtecan：理性策略、新进展、挑战和未来展望

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-09-18 DOI: 10.1016/j.ctrv.2025.103023

Vincenzo Di Lauro , Alessandro Rizzo , Margherita Tafuro , Emanuela Fina , Claudia Martinelli , Claudia Calderaio , Rossana Di Rienzo , Miriam Pirolo , Annarita Fanizzi , Raffaella Massafra , Michelino De Laurentiis

Antibody-drug conjugates have recently revolutionized the treatment scenario of several tumors, including breast cancer. Among these, Datopotamab deruxtecan (Dato-DXd) is an ADC composed of a humanized anti-TROP2 monoclonal antibody linked to a potent exatecan-derived topoisomerase I inhibitor payload, deruxtecan (DXd), via a plasma-stable, selectively cleavable linker. Dato-DXd has shown notable efficacy and an overall tolerable safety profile, according to available evidence. Herein, we provide an overview of the pharmacological features, mechanisms of action, clinical efficacy, and adverse events of Dato-DXd in breast cancer. Furthermore, the current review proposes strategies to optimize patient management and accelerate the clinical development of Dato-DXd in this setting.

抗体-药物偶联物最近彻底改变了包括乳腺癌在内的几种肿瘤的治疗方案。其中，Datopotamab deruxtecan （Dato-DXd）是一种ADC，由人源化抗trop2单克隆抗体组成，通过血浆稳定、选择性可切割的连接物与exatecan衍生的有效拓扑异构酶I抑制剂deruxtecan （DXd）连接。根据现有证据，Dato-DXd显示出显著的疗效和总体可耐受的安全性。本文就Dato-DXd治疗乳腺癌的药理特点、作用机制、临床疗效和不良事件进行综述。此外，本综述还提出了在这种情况下优化患者管理和加速Dato-DXd临床发展的策略。

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 : 2025-09-15 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

Does the benefit of neoadjuvant chemotherapy at six months predict long-term outcomes in colon or rectal cancer? A meta-analysis of randomised studies 6个月时新辅助化疗的益处能否预测结肠癌或直肠癌的长期预后？随机研究的荟萃分析

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-09-10 DOI: 10.1016/j.ctrv.2025.103020

Joanna Socha , Wojciech Michalski , Rob Glynne-Jones , Bengt Glimelius , Krzysztof Bujko

Introduction

The RAPIDO and PRODIGE-23 randomised trials of neoadjuvant versus adjuvant chemotherapy for rectal cancer showed that disease-free survival (DFS) curves diverged early, suggesting that much of the benefit from neoadjuvant chemotherapy occurred within six months. We aimed to determine whether the DFS benefit at six months in trials evaluating neoadjuvant chemotherapy can predict the benefit at 36 months, and to compare the timing of DFS benefit in trials of neoadjuvant versus in those of adjuvant chemotherapy.

Material and methods

A systematic review identified ten randomised trials comparing neoadjuvant with adjuvant chemotherapy and 37 randomised trials of adjuvant chemotherapy eligible for meta-analysis in rectal or colon cancer. Absolute differences in DFS between experimental and control groups at six and 36 months were extracted from Kaplan–Meier curves. The increment in the DFS benefit between the sixth and 36th months was calculated.

Results

In neoadjuvant chemotherapy trials, DFS benefit at six months (3.7 %, 95 % confidence interval [CI]: 1.9 to 5.4) did not differ significantly from that at 36 months (4.1 %, 95 % CI: 2.0 to 6.3), and the pooled absolute increment in DFS benefit between the sixth and 36th months was only 0.8 % (95 % CI: −1.6 to 3.2). The DFS benefit emerged earlier in neoadjuvant than in adjuvant chemotherapy trials.

Conclusion

In randomised trials comparing neoadjuvant with adjuvant chemotherapy, most of the DFS benefit from neoadjuvant chemotherapy manifests itself within the first six months. Therefore, assessing DFS at six months may potentially serve as an early indicator of long-term efficacy.

RAPIDO和PRODIGE-23对直肠癌新辅助化疗与辅助化疗的随机试验显示，无病生存（DFS）曲线较早出现分歧，表明新辅助化疗的大部分益处发生在6个月内。我们的目的是确定评估新辅助化疗的试验中6个月时的DFS获益是否可以预测36个月时的获益，并比较新辅助化疗与辅助化疗试验中DFS获益的时间。材料和方法一项系统评价确定了10项比较新辅助化疗与辅助化疗的随机试验和37项辅助化疗的随机试验，适合用于直肠癌或结肠癌的荟萃分析。从Kaplan-Meier曲线中提取实验组和对照组在6个月和36个月时的DFS的绝对差异。计算第六个月至第36个月间生活津贴的增加额。结果在新辅助化疗试验中，6个月时的DFS获益（3.7%，95%可信区间[CI]: 1.9 ~ 5.4）与36个月时的DFS获益（4.1%,95% CI: 2.0 ~ 6.3）无显著差异，第6个月和第36个月间DFS获益的总绝对增量仅为0.8% （95% CI:−1.6 ~ 3.2）。与辅助化疗试验相比，新辅助化疗试验的DFS获益出现得更早。结论在比较新辅助化疗与辅助化疗的随机试验中，大多数DFS受益于新辅助化疗在前6个月内表现出来。因此，在6个月时评估DFS可能作为长期疗效的早期指标。

{"title":"Does the benefit of neoadjuvant chemotherapy at six months predict long-term outcomes in colon or rectal cancer? A meta-analysis of randomised studies","authors":"Joanna Socha , Wojciech Michalski , Rob Glynne-Jones , Bengt Glimelius , Krzysztof Bujko","doi":"10.1016/j.ctrv.2025.103020","DOIUrl":"10.1016/j.ctrv.2025.103020","url":null,"abstract":"<div><h3>Introduction</h3><div>The RAPIDO and PRODIGE-23 randomised trials of neoadjuvant versus adjuvant chemotherapy for rectal cancer showed that disease-free survival (DFS) curves diverged early, suggesting that much of the benefit from neoadjuvant chemotherapy occurred within six months. We aimed to determine whether the DFS benefit at six months in trials evaluating neoadjuvant chemotherapy can predict the benefit at 36 months, and to compare the timing of DFS benefit in trials of neoadjuvant versus in those of adjuvant chemotherapy.</div></div><div><h3>Material and methods</h3><div>A systematic review identified ten randomised trials comparing neoadjuvant with adjuvant chemotherapy and 37 randomised trials of adjuvant chemotherapy eligible for <em>meta</em>-analysis in rectal or colon cancer. Absolute differences in DFS between experimental and control groups at six and 36 months were extracted from Kaplan–Meier curves. The increment in the DFS benefit between the sixth and 36th months was calculated.</div></div><div><h3>Results</h3><div>In neoadjuvant chemotherapy trials, DFS benefit at six months (3.7 %, 95 % confidence interval [CI]: 1.9 to 5.4) did not differ significantly from that at 36 months (4.1 %, 95 % CI: 2.0 to 6.3), and the pooled absolute increment in DFS benefit between the sixth and 36th months was only 0.8 % (95 % CI: −1.6 to 3.2). The DFS benefit emerged earlier in neoadjuvant than in adjuvant chemotherapy trials.</div></div><div><h3>Conclusion</h3><div>In randomised trials comparing neoadjuvant with adjuvant chemotherapy, most of the DFS benefit from neoadjuvant chemotherapy manifests itself within the first six months. Therefore, assessing DFS at six months may potentially serve as an early indicator of long-term efficacy.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103020"},"PeriodicalIF":10.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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 : 2025-09-05 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。

{"title":"Advances in treatment strategies for low-grade serous ovarian cancer","authors":"Lucia Musacchio , Domenica Lorusso , Giulia Sabetta , Alessandra Giustozzi , Elena Giudice , Maria Chiara Cannizzaro , Maria Teresa Perri , Anna Fagotti , Vanda Salutari","doi":"10.1016/j.ctrv.2025.103019","DOIUrl":"10.1016/j.ctrv.2025.103019","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103019"},"PeriodicalIF":10.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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 : 2025-08-27 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。

{"title":"Comparative review of KEYNOTE-689 and NIVOPOSTOP trials and their impact on perioperative immunotherapy in locally advanced head and neck cancer","authors":"Yoshinori Imamura , Masafumi Kanno , Shigeharu Fujieda","doi":"10.1016/j.ctrv.2025.103018","DOIUrl":"10.1016/j.ctrv.2025.103018","url":null,"abstract":"<div><h3>Aim</h3><div>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.</div></div><div><h3>Methods</h3><div>We conducted a narrative review comparing the design, patient populations, treatment protocols, and outcomes of KEYNOTE-689 and NIVOPOSTOP. Data sources included <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, presentations at major international oncology meetings, and peer-reviewed publications.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103018"},"PeriodicalIF":10.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Radioimmunotherapy for lung and head and neck cancers: A comparative review of clinical trial results and sequencing strategies 肺癌和头颈癌的放射免疫治疗：临床试验结果和测序策略的比较回顾

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-08-27 DOI: 10.1016/j.ctrv.2025.103017

Danny Lavigne , Yungan Tao , Cecile Le Péchoux , Angela Botticella , France Nguyen , Roger Sun , Pierre Blanchard , Jordi Remon , Eric Deutsch , Antonin Levy

Immunotherapy has become standard of care for numerous cancer types in the past decade. Combining radiotherapy and immunotherapy has the potential to further improve outcomes by taking advantage of their theoretical synergy on antitumoral immune response. Despite promising preclinical and early clinical studies, along with significant improvements reported in specific settings, results from larger trials attempting to expand radioimmunotherapy to diverse clinical scenarios are markedly inconsistent. This review examines published and ongoing clinical trials evaluating this treatment strategy in patients with lung and head and neck cancers, where various sequencing strategies and settings were explored, including the consolidation, concurrent, induction, resectable, and metastatic settings. We highlight similarities and differences between these two tumor sites, discussing factors contributing to the variable efficacy of this therapeutic approach across diverse clinical settings.

在过去的十年里，免疫疗法已经成为许多癌症类型的标准治疗方法。放射治疗和免疫治疗相结合，利用它们在抗肿瘤免疫反应上的理论协同作用，有可能进一步改善预后。尽管有临床前和早期临床研究的前景，以及在特定环境下的显著改善，但试图将放射免疫治疗扩大到各种临床情况的大型试验的结果明显不一致。本综述研究了已发表的和正在进行的临床试验，这些试验评估了肺癌和头颈癌患者的这种治疗策略，其中探索了各种测序策略和设置，包括巩固、并发、诱导、可切除和转移设置。我们强调了这两种肿瘤部位之间的异同，讨论了导致这种治疗方法在不同临床环境中产生不同疗效的因素。

{"title":"Radioimmunotherapy for lung and head and neck cancers: A comparative review of clinical trial results and sequencing strategies","authors":"Danny Lavigne , Yungan Tao , Cecile Le Péchoux , Angela Botticella , France Nguyen , Roger Sun , Pierre Blanchard , Jordi Remon , Eric Deutsch , Antonin Levy","doi":"10.1016/j.ctrv.2025.103017","DOIUrl":"10.1016/j.ctrv.2025.103017","url":null,"abstract":"<div><div>Immunotherapy has become standard of care for numerous cancer types in the past decade. Combining radiotherapy and immunotherapy has the potential to further improve outcomes by taking advantage of their theoretical synergy on antitumoral immune response. Despite promising preclinical and early clinical studies, along with significant improvements reported in specific settings, results from larger trials attempting to expand radioimmunotherapy to diverse clinical scenarios are markedly inconsistent. This review examines published and ongoing clinical trials evaluating this treatment strategy in patients with lung and head and neck cancers, where various sequencing strategies and settings were explored, including the consolidation, concurrent, induction, resectable, and metastatic settings. We highlight similarities and differences between these two tumor sites, discussing factors contributing to the variable efficacy of this therapeutic approach across diverse clinical settings.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103017"},"PeriodicalIF":10.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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 : 2025-08-25 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。

{"title":"Interpreting immunogenicity in oncology clinical trials","authors":"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","doi":"10.1016/j.ctrv.2025.103016","DOIUrl":"10.1016/j.ctrv.2025.103016","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103016"},"PeriodicalIF":10.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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 : 2025-08-22 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。

{"title":"Opportunities and challenges for non–small cell lung cancer brain metastases in the immunotherapy era","authors":"Ying Yu, Yuxi Luo, Fujuan Zeng, Anwen Liu","doi":"10.1016/j.ctrv.2025.103014","DOIUrl":"10.1016/j.ctrv.2025.103014","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103014"},"PeriodicalIF":10.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in the management of locally advanced rectal cancer: A shift toward a patient-centred approach to balance outcomes and quality of life 局部晚期直肠癌管理的进展：转向以患者为中心的方法来平衡结果和生活质量

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-08-19 DOI: 10.1016/j.ctrv.2025.103015

Marco Airoldi , Susana Roselló , Noelia Tarazona , Marisol Huerta , Leticia Pérez-Santiago , Tania Fleitas , Vicente Pla-Martí , Alberto Puccini , Desamparados Roda , Andrés Cervantes

The treatment of locally advanced rectal cancer (LARC) has undergone a significant evolution in recent years, shifting toward more selective strategies that balance oncological outcomes with quality of life (QoL) preservation. Total neoadjuvant treatment (TNT) has improved local control and reduced distant metastases, but its long-term toxicities have sparked growing interest in treatment de-escalation strategies aimed at minimizing adverse effects while maintaining efficacy. This review focuses on the therapeutic advancements for LARC, analysing both established standards and emerging innovations. We discuss the increasing adoption of organ-preserving approaches, particularly the Watch-and-Wait (WW) strategy for patients achieving a clinical complete response (cCR), and potentially the selective omission of radiotherapy in well-defined cases. Additionally, we explore and examine less invasive surgical techniques that preserve function without compromising cure rates. Beyond standard treatment approaches, we highlight the role of immunotherapy, particularly its breakthrough efficacy in LARC with deficient mismatch repair/microsatellite instability (dMMR/MSI), leading to the concept of immune-ablation: achieving complete tumor regression while sparing patients from chemotherapy, radiotherapy, and surgery. Ongoing research is investigating immunotherapy’s potential role also in proficient mismatch repair/microsatellite stable (pMMR/MSS) LARC. Finally, we discuss emerging predictive biomarkers, such as circulating tumor DNA (ctDNA) and radiomics, which might refine patient selection and guide treatment individualization. The future of LARC management lies in a precision-driven approach, where survival is optimized without compromising QoL. By embracing innovation and personalizing care, we are entering a new era where cure remains paramount, but never at the expense of the patient’s well-being.

近年来，局部晚期直肠癌（LARC）的治疗经历了重大演变，转向更具选择性的策略，以平衡肿瘤结果和生活质量（QoL）的保存。总的新辅助治疗（TNT）改善了局部控制并减少了远处转移，但其长期毒性引起了人们对治疗降级策略的兴趣，旨在尽量减少不良反应，同时保持疗效。本文综述了LARC的治疗进展，分析了现有的标准和新兴的创新。我们讨论了越来越多的器官保存方法的采用，特别是对达到临床完全缓解（cCR）的患者的观察和等待（WW）策略，以及在明确定义的病例中可能选择性省略放疗。此外，我们探索和检查微创手术技术，在不影响治愈率的情况下保留功能。除了标准治疗方法，我们强调了免疫治疗的作用，特别是其在LARC缺陷错配修复/微卫星不稳定性（dMMR/MSI）中的突破性疗效，导致了免疫消融的概念：在使患者免受化疗、放疗和手术的同时实现肿瘤完全消退。正在进行的研究正在调查免疫疗法在熟练错配修复/微卫星稳定（pMMR/MSS） LARC中的潜在作用。最后，我们讨论了新兴的预测性生物标志物，如循环肿瘤DNA （ctDNA）和放射组学，它们可能会改善患者选择和指导治疗个体化。LARC管理的未来在于一种精确驱动的方法，在不影响生活质量的情况下优化生存。通过拥抱创新和个性化护理，我们正在进入一个新的时代，在这个时代，治疗仍然是最重要的，但绝不以牺牲病人的健康为代价。

{"title":"Advances in the management of locally advanced rectal cancer: A shift toward a patient-centred approach to balance outcomes and quality of life","authors":"Marco Airoldi , Susana Roselló , Noelia Tarazona , Marisol Huerta , Leticia Pérez-Santiago , Tania Fleitas , Vicente Pla-Martí , Alberto Puccini , Desamparados Roda , Andrés Cervantes","doi":"10.1016/j.ctrv.2025.103015","DOIUrl":"10.1016/j.ctrv.2025.103015","url":null,"abstract":"<div><div>The treatment of locally advanced rectal cancer (LARC) has undergone a significant evolution in recent years, shifting toward more selective strategies that balance oncological outcomes with quality of life (QoL) preservation. Total neoadjuvant treatment (TNT) has improved local control and reduced distant metastases, but its long-term toxicities have sparked growing interest in treatment de-escalation strategies aimed at minimizing adverse effects while maintaining efficacy. This review focuses on the therapeutic advancements for LARC, analysing both established standards and emerging innovations. We discuss the increasing adoption of organ-preserving approaches, particularly the Watch-and-Wait (WW) strategy for patients achieving a clinical complete response (cCR), and potentially the selective omission of radiotherapy in well-defined cases. Additionally, we explore and examine less invasive surgical techniques that preserve function without compromising cure rates. Beyond standard treatment approaches, we highlight the role of immunotherapy, particularly its breakthrough efficacy in LARC with deficient mismatch repair/microsatellite instability (dMMR/MSI), leading to the concept of immune-ablation: achieving complete tumor regression while sparing patients from chemotherapy, radiotherapy, and surgery. Ongoing research is investigating immunotherapy’s potential role also in proficient mismatch repair/microsatellite stable (pMMR/MSS) LARC. Finally, we discuss emerging predictive biomarkers, such as circulating tumor DNA (ctDNA) and radiomics, which might refine patient selection and guide treatment individualization. The future of LARC management lies in a precision-driven approach, where survival is optimized without compromising QoL. By embracing innovation and personalizing care, we are entering a new era where cure remains paramount, but never at the expense of the patient’s well-being.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"140 ","pages":"Article 103015"},"PeriodicalIF":10.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144893040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0