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De-escalated Management of HPV-positive Oropharyngeal Carcinoma: Improving Outcomes with Personalized Approaches hpv阳性口咽癌的降级管理:个性化方法改善结果
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2025-03-14 DOI: 10.1016/j.semradonc.2025.01.004
Irini Yacoub , Achraf Shamseddine , Joshua Qian , Mary Youssef , Amir H. Safavi , Nancy Y. Lee
Human papilloma virus (HPV)-positive oropharyngeal cancer (OPC) is increasingly prevalent and has a favorable prognosis compared to HPV-negative OPC and other head and neck malignancies associated with smoking and alcohol. De-escalation of definitive therapy for HPV-positive OPC is an attractive strategy aiming to maintain oncologic efficacy while reducing short-term and long-term toxicities and improving quality of life. In this article, we outline approaches to de-escalation including use of alternative systemic therapies, reduction in dose of systemic therapy, and reductions in radiation dose and/or volume. We also highlight successes and cautionary outcomes from de-escalation studies and advocate for a personalized approach to future de-escalation trials in HPV-positive OPC.
人乳头瘤病毒(HPV)阳性口咽癌(OPC)越来越普遍,与HPV阴性口咽癌和其他与吸烟和酒精相关的头颈部恶性肿瘤相比,其预后良好。降低hpv阳性OPC的最终治疗升级是一种有吸引力的策略,旨在保持肿瘤疗效,同时减少短期和长期毒性并改善生活质量。在这篇文章中,我们概述了降低辐射升级的方法,包括使用替代全身治疗、减少全身治疗剂量、减少辐射剂量和/或体积。我们还强调了降级研究的成功和警示结果,并倡导在hpv阳性OPC的未来降级试验中采用个性化的方法。
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引用次数: 0
Oral Mucositis in Head and Neck Cancer Patients 头颈部肿瘤患者的口腔黏膜炎
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2025-03-14 DOI: 10.1016/j.semradonc.2025.02.011
Carryn Anderson , Deborah Saunders
Oral mucositis (OM) is a common side effect of radiation therapy for head and neck cancer (HNC). Despite the medical advances in cancer therapy, OM is still virtually inevitable in patients being irradiated for neoplasms of the head and neck. The initial signs of oral mucositis typically manifest after cumulative doses between 15 and 20 Gy, with ulceration formation by 30 Gy and reaching peak severity in the week after radiation treatment completion (generally 60-72 Gy in management of HNC), then resolving over the 3-4 weeks following treatment completion. Severe oral mucositis (SOM), defined as WHO grade 3 and grade 4, occurs in 65-70% of patients receiving concurrent cisplatin and radiation therapy for locoregionally advanced HNC. WHO grade 3 or 4 oral mucositis leads to risk of systemic infection, severe pain, reduced oral intake which can lead to dehydration, significant weight loss and malnutrition, need for feeding tube placement and hospitalization. The clinical and economic impact, not to mention the impact on patient quality of life from oral mucositis has been well studied. As mucositis is commonly the dose-limiting factor leading to disruption or delay in cancer therapy, establishment of evidence-based guidelines has been paramount in supportive care management of these patients. Improvements in the prevention and treatment of oral mucositis remain essential to better patient outcomes. Here we review the current standard of care, recent successes and failures in development of therapies to mitigate OM, share patient and provider educational resources, and describe on-going and future directions of research in this area.
口腔黏膜炎(OM)是头颈癌(HNC)放射治疗的常见副作用。尽管癌症治疗在医学上取得了进步,但对于因头颈部肿瘤而接受放射治疗的患者来说,OM实际上仍然是不可避免的。口腔黏膜炎的最初症状通常在累积剂量为15至20 Gy后出现,在30 Gy时形成溃疡,并在放射治疗完成后一周内达到严重程度高峰(HNC治疗通常为60-72 Gy),然后在治疗完成后3-4周内消退。重度口腔黏膜炎(SOM)被WHO定义为3级和4级,65-70%的局部晚期HNC患者同时接受顺铂和放射治疗。世卫组织3级或4级口腔黏膜炎可导致全身性感染、剧烈疼痛、可导致脱水的口服摄入量减少、体重显著减轻和营养不良、需要放置饲管和住院。口腔黏膜炎的临床和经济影响,更不用说对患者生活质量的影响已经得到了很好的研究。由于粘膜炎通常是导致癌症治疗中断或延迟的剂量限制因素,因此建立循证指南在这些患者的支持性护理管理中至关重要。改善口腔黏膜炎的预防和治疗对改善患者的预后至关重要。在这里,我们回顾了当前的护理标准,最近的成功和失败的治疗发展,以减轻OM,共享患者和提供者的教育资源,并描述了正在进行的和未来的研究方向在这一领域。
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引用次数: 0
De-escalation of Adjuvant Therapy in Operatively Managed HPV Associated Oropharyngeal Carcinoma: Current Status and Future Directions 手术治疗HPV相关口咽癌的辅助治疗降级:现状和未来方向
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2025-03-14 DOI: 10.1016/j.semradonc.2025.02.002
Daniel Ma MD, David M. Routman MD
Human papillomavirus (HPV) associated oropharyngeal carcinoma is currently the most frequently diagnosed head and neck cancer in the United States. Due to the generally high cure rates with standard therapies, de-intensification strategies are being explored to reduce acute and long-term side effects. For patients treated with definitive chemoradiation, unselected de-escalation has shown worse progression-free survival compared to standard therapy. Concurrently, surgical management is becoming more prevalent, and adjuvant de-escalation appears promising. Further research is required to identify optimal candidacy for adjuvant de-escalation and to understand the relationship between dose and volume de-escalation. Biomarkers such as ctDNA may assist in candidate selection, but validation and alignment with pathological criteria are necessary.
人乳头瘤病毒(HPV)相关的口咽癌是目前美国最常见的头颈部癌症。由于标准疗法的治愈率普遍较高,因此正在探索去强化策略以减少急性和长期副作用。对于接受明确放化疗的患者,与标准治疗相比,未选择的降级显示出更差的无进展生存期。与此同时,手术治疗变得越来越普遍,辅助治疗似乎很有希望。需要进一步的研究来确定佐剂降压的最佳候选资格,并了解剂量和体积降压之间的关系。生物标志物如ctDNA可能有助于候选人的选择,但验证和符合病理标准是必要的。
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引用次数: 0
Personalising Nasopharyngeal Cancer: Systemic Therapy and Radiotherapy Treatment Volumes 个体化鼻咽癌:全身治疗和放射治疗卷
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2025-03-14 DOI: 10.1016/j.semradonc.2025.01.003
Benjamin X.Z. Huang MD , Xin Zhang PhD , Megan P. Kang MBBS , Melvin L.K. Chua PhD
Nasopharyngeal carcinoma (NPC) is sensitive to chemotherapy and radiotherapy, with current treatment recommendations largely based on TNM-stage. Radiotherapy remains the backbone of treatment for NPC. Over the past decades, the addition of concurrent chemotherapy to radiotherapy for early-stage disease, and the combination of induction chemotherapy (IC) or adjuvant chemotherapy (AC) with chemoradiotherapy vs chemoradiotherapy alone for advanced disease have led to substantial improvements in survival of patients with NPC. Nonetheless, in the era of precision oncology, there is growing recognition that patients with NPC are clinically heterogeneous even within the same stage-group, and future advances must focus on individualisation of systemic therapy and radiotherapy. In this review, we summarised the published evidence on EBV DNA as a biomarker for clinical stratification and treatment response in NPC, and discussed some of the ongoing clinical trials of EBV DNA-directed personalisation of systemic therapy in locoregionally-advanced disease. Next, we assessed the evidence concerning individualised radiotherapy strategies for target volume delineation of the primary tumour and cervical nodes that ought to be based on individual tumour extent and IC response (for locoregionally-advanced NPC) as opposed to the historical one-size fits all approach. In the same vein, radiotherapy dose de-escalation may be considered in good responders to IC, whereas for the poor responders, altered fractionation or dose escalation may be required to target resistant disease. These concepts are particularly relevant in the era of combinatorial immune checkpoint blockade therapy with radiotherapy, where preservation of circulating immune cells is crucial to evoke immune-mediated antitumour cytotoxicity.
鼻咽癌(NPC)对化疗和放疗敏感,目前的治疗建议主要基于tnm分期。放疗仍然是鼻咽癌治疗的主要方法。在过去的几十年里,早期疾病在放疗的基础上增加了同步化疗,晚期疾病的诱导化疗(IC)或辅助化疗(AC)联合放化疗与单独放化疗相结合,使得鼻咽癌患者的生存得到了实质性的改善。然而,在精准肿瘤学时代,人们越来越认识到,即使在同一分期组中,鼻咽癌患者的临床异质性,未来的进展必须集中在全身治疗和放疗的个体化上。在这篇综述中,我们总结了EBV DNA作为鼻咽癌临床分层和治疗反应的生物标志物的已发表证据,并讨论了一些正在进行的针对局部区域晚期疾病的EBV DNA定向全身治疗的临床试验。接下来,我们评估了关于原发性肿瘤和宫颈结靶体积描绘的个体化放疗策略的证据,这些放疗策略应该基于个体肿瘤范围和IC反应(对于局部区域晚期鼻咽癌),而不是历史上的一刀切方法。同样,对于对IC有良好反应的患者,可以考虑放疗剂量递减,而对于反应较差的患者,可能需要改变分割或剂量递增以靶向耐药疾病。这些概念与放射疗法联合免疫检查点阻断疗法的时代特别相关,其中保存循环免疫细胞对于激发免疫介导的抗肿瘤细胞毒性至关重要。
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引用次数: 0
Metastatic Head and Neck Cancer: Immunotherapy and Beyond 转移性头颈癌:免疫治疗及其他
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2025-03-14 DOI: 10.1016/j.semradonc.2025.02.004
Kirsten V. Nguyen , Cody M. Lebeck Lee , Jennifer H. Choe
Head and neck cancer is estimated to result in 71,000 new cancer diagnoses and 16,000 deaths in 2024. Of these cases, approximately 14% will be metastatic. Recent changes in treatment paradigms have established immunotherapy as a cornerstone of treatment in the metastatic and recurrent setting. While immunotherapy has undoubtedly improved outcomes and can lead to long term durable responses in select patients, overall response rates remain suboptimal, with approximately 13%-20% of patients responding to immunotherapy in most studies. This review aims to provide an overview of the current treatment landscape of immunotherapies in head and neck malignancies. Additionally, we aim to discuss the future of immunotherapy, as well as novel targets and therapeutic platforms that may continue to change the treatment paradigm in this disease.
据估计,到2024年,头颈癌将导致7.1万例新的癌症诊断和1.6万例死亡。在这些病例中,大约14%会转移。最近治疗模式的变化已经确立了免疫治疗作为转移性和复发性肿瘤治疗的基石。虽然免疫治疗无疑改善了结果,并且可以在选定的患者中产生长期持久的反应,但总体反应率仍然不理想,在大多数研究中,大约13%-20%的患者对免疫治疗有反应。本文综述了目前头颈部恶性肿瘤免疫疗法的治疗概况。此外,我们的目标是讨论免疫治疗的未来,以及可能继续改变这种疾病治疗模式的新靶点和治疗平台。
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引用次数: 0
The Future of Head and Neck Radiotherapy: Not Your Father's Three-Field 头颈部放射治疗的未来:不再是你父亲的三个领域
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2025-03-14 DOI: 10.1016/j.semradonc.2025.02.010
David J. Sher MD, MPH , Yvonne M. Mowery MD, PhD
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引用次数: 0
Predictors of Radiation Resistance and Novel Radiation Sensitizers in Head and Neck Cancers: Advancing Radiotherapy Efficacy 头颈癌放射耐药和新型放射致敏剂的预测因素:提高放疗疗效
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2025-03-14 DOI: 10.1016/j.semradonc.2025.02.008
Aastha Sobti, Heath Skinner, Christopher T. Wilke
Radiation resistance in head and neck squamous cell carcinoma (HNSCC), driven by intrinsic and extrinsic factors, poses a significant challenge in radiation oncology. The key contributors are tumor hypoxia, cancer stem cells, cell cycle checkpoint activation, and DNA repair processes (homologous recombination and non-homologous end-joining). Genetic modifications such as TP53 mutations, KRAS mutations, EGFR overexpression, and abnormalities in DNA repair proteins like BRCA1/2 additionally affect radiation sensitivity.
Novel radiosensitizers targeting these pathways demonstrate the potential to overcome resistance. Hypoxia-activated drugs and gold nanoparticles enhance the efficacy of radiotherapy and facilitate targeted distribution. Integrating immunotherapy, especially immune checkpoint inhibitors, with radiation therapy, enhances anti-tumor responses and reduces resistance. Epigenetic alterations, such as DNA methylation and histone acetylation, significantly influence radiation response, with the potential for sensitization through histone deacetylase inhibitors and non-coding RNA regulators. Metabolic changes linked to glucose, lipid, and glutamine metabolism influence radiosensitivity, uncovering new targets for radiosensitization. Human papillomavirus (HPV)-associated malignancies exhibit increased radiosensitivity relative to other tumors due to impaired DNA repair mechanisms and heightened immunogenicity. Furthermore, understanding the interplay between HPV oncoproteins and p53 functionality can enhance treatment strategies for HPV-related cancers. Using DNA damage response inhibitors (PARP, ATM/ATR), cell cycle checkpoint inhibitors (WEE1, CHK1/2), and hypoxia-targeted agents as radiosensitizing strategies exhibit considerable promise. Immunomodulatory approaches, including PD-1 and CTLA-4 inhibitors in conjunction with radiation, enhance anti-tumor immunity.
Future directions emphasize personalized radiation therapy using genetics, sophisticated medication delivery systems, adaptive radiotherapy, and real-time monitoring. These integrated strategies seek to diminish radiation resistance and improve therapeutic efficacy in HNSCC.
头颈部鳞状细胞癌(HNSCC)的放射耐药是放射肿瘤学研究的一个重大挑战,由内在和外在因素驱动。关键因素是肿瘤缺氧、肿瘤干细胞、细胞周期检查点激活和DNA修复过程(同源重组和非同源末端连接)。遗传修饰如TP53突变、KRAS突变、EGFR过表达以及DNA修复蛋白如BRCA1/2的异常也会影响辐射敏感性。针对这些途径的新型放射增敏剂显示出克服耐药性的潜力。低氧活化药物和金纳米颗粒增强了放疗的疗效,有利于靶向分布。将免疫治疗,特别是免疫检查点抑制剂与放射治疗相结合,可以增强抗肿瘤反应并降低耐药性。表观遗传改变,如DNA甲基化和组蛋白乙酰化,显著影响辐射反应,并可能通过组蛋白去乙酰化酶抑制剂和非编码RNA调节剂致敏。与葡萄糖、脂质和谷氨酰胺代谢相关的代谢变化影响放射敏感性,揭示了放射增敏的新靶点。由于DNA修复机制受损和免疫原性增强,人乳头瘤病毒(HPV)相关的恶性肿瘤相对于其他肿瘤表现出更高的放射敏感性。此外,了解HPV癌蛋白和p53功能之间的相互作用可以提高HPV相关癌症的治疗策略。使用DNA损伤反应抑制剂(PARP, ATM/ATR),细胞周期检查点抑制剂(WEE1, CHK1/2)和低氧靶向药物作为放射增敏策略显示出相当大的前景。免疫调节方法,包括PD-1和CTLA-4抑制剂与放射联合使用,增强抗肿瘤免疫。未来的方向是强调个性化的放射治疗,包括遗传学、复杂的药物输送系统、自适应放疗和实时监测。这些综合策略旨在降低HNSCC的放射耐药并提高治疗效果。
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引用次数: 0
Head and Neck Cancer of Unknown Primary: A Surgical Perspective 原发不明的头颈癌:外科视角
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2025-03-14 DOI: 10.1016/j.semradonc.2025.02.007
Michael S. Chow , Umamaheswar Duvvuri
Head and neck squamous cell carcinoma of unknown primary (SSCUP) presents a clinically challenge disease process requiring elaborate multidisciplinary collaboration for effective treatment. With the rise in prevalence HPV associated squamous cell carcinoma, it has become the predominant etiology SCCUP of the head and neck. Advances in the diagnostic evaluation and treatment of SCCUP have led to higher detection rates of primary lesions, improved disease-free and overall survival outcomes, and reduced morbidity for patients. Furthermore, delineation of the molecular implications of HPV positivity and disease behavior has opened avenues for successful de-escalation of treatment. Transoral robotic surgery (TORS), as well as dose reduction protocols show significant promise for oncologic efficacy with minimization of treatment related morbidity.
未知原发头颈部鳞状细胞癌(SSCUP)是一种具有临床挑战性的疾病,需要多学科合作才能有效治疗。随着HPV相关鳞状细胞癌患病率的上升,它已成为头颈部SCCUP的主要病因。SCCUP在诊断评估和治疗方面的进步提高了原发病变的检出率,改善了无病和总体生存结果,降低了患者的发病率。此外,描述HPV阳性和疾病行为的分子意义为成功降低治疗水平开辟了途径。经口机器人手术(TORS),以及剂量减少方案显示出显著的肿瘤疗效与治疗相关的发病率最小化。
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引用次数: 0
Novel Survivorship Paradigms in Head/Neck Cancer 头颈癌新的生存模式
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2025-03-14 DOI: 10.1016/j.semradonc.2025.02.003
Maria Armache , Alexis Larson , Rachel Stemme , Callie Walsh-Bailey , Kelli Scott , Timothy Pearman , Katelyn O. Stepan , Michelle L. Mierzwa , Leila J. Mady , Laila A. Gharzai
Long-term care for head and neck cancer (HNC) survivors is complex. Despite an improvement in survival and the evolution of treatment paradigms (de-escalation, targeted therapy), notably in the context of human papillomavirus (HPV)-related oropharyngeal cancers, HNC survivors still experience a wide range of side effects and needs, which impact their functionality, quality of life, survival and require concerted, coordinated survivorship care. In this review, we perform an overview of existing HNC survivorship recommendations within the context of novel evidence, our current understanding of survivorship care, and incorporate them into the Nekhluydov Survivorship Care Framework. This framework provides a novel way to appreciate and comprehensively address all aspects of HNC survivorship care. Further research is crucial to develop evidence-based, patient-centered personalized approaches to survivorship care in different HNC populations and understand barriers to successful implementation.
头颈癌(HNC)幸存者的长期护理是复杂的。尽管生存改善和治疗模式的演变(降级,靶向治疗),特别是在人乳头瘤病毒(HPV)相关口咽癌的背景下,HNC幸存者仍然经历着广泛的副作用和需求,这影响了他们的功能,生活质量,生存和需要协调一致的生存护理。在这篇综述中,我们在新证据的背景下概述了现有的HNC幸存者建议,以及我们目前对幸存者护理的理解,并将其纳入Nekhluydov幸存者护理框架。该框架提供了一种新颖的方式来理解和全面解决HNC生存护理的各个方面。进一步的研究对于开发基于证据的、以患者为中心的个性化方法,在不同的HNC人群中进行生存护理,并了解成功实施的障碍至关重要。
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引用次数: 0
The contemporary spectrum of radiotherapy for hematologic malignancies involving the central nervous system: From focal therapy to craniospinal 涉及中枢神经系统的血液恶性肿瘤的当代放射治疗谱:从局灶治疗到颅脊髓。
IF 2.6 3区 医学 Q3 ONCOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.semradonc.2024.11.001
Gustav Y. Cederquist , Kathryn Tringale , Joachim Yahalom , Brandon S. Imber
The contemporary landscape of systemic therapy options for hematologic malignancies involving the central nervous system (CNS-HM) is rapidly evolving; a key question is how radiotherapy (RT) can be optimally integrated to improve patient outcomes. Historically, use of RT to treat CNS-HM was defined by broad fields and high doses. While effective, this approach raised concerns of potential neurotoxicity which significantly decreased RT utilization. RT was replaced by high-dose, CNS-penetrant, systemic therapies that offered durable control with lower perceived neurotoxic risk. But, as the therapeutic toolbox for CNS-HM expands, so too does the complexity and diversity of potential clinical scenarios where RT should be considered. In this review, we describe both well-established and emerging opportunities for RT integration, emphasizing how dose selection and field design could balance neurotoxicity risk and disease control. We propose an anatomical framework that captures the diverse utilization of RT for CNS-HM and serves as a practical guide for RT volume and dose design.
涉及中枢神经系统(CNS-HM)的血液恶性肿瘤的全身治疗方案正在迅速发展,其中一个关键问题是如何优化整合放射治疗(RT),以改善患者的预后。从历史上看,使用 RT 治疗中枢神经系统恶性肿瘤的定义是广域和高剂量。这种方法虽然有效,但却引起了对潜在神经毒性的担忧,从而大大降低了 RT 的使用率。大剂量、中枢神经系统穿透性的系统疗法取代了 RT,这些疗法可提供持久的控制,同时降低神经毒性风险。但是,随着 CNS-HM 治疗工具箱的扩大,应考虑 RT 的潜在临床情况也变得更加复杂和多样。在这篇综述中,我们描述了成熟的和新兴的 RT 整合机会,强调了剂量选择和治疗场设计如何平衡神经毒性风险和疾病控制。我们提出了一个解剖学框架,该框架捕捉到了 RT 在中枢神经系统疾病中的不同应用,并可作为 RT 容量和剂量设计的实用指南。
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引用次数: 0
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Seminars in Radiation Oncology
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