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De-Escalation of Therapy for Prostate Cancer. 减轻前列腺癌的治疗。
Tarik Esen, Baris Esen, Kosj Yamaoh, Ugur Selek, Derya Tilki

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men with around 1.4 million new cases every year. In patients with localized disease, management options include active surveillance (AS), radical prostatectomy (RP; with or without pelvic lymph node dissection), or radiotherapy to the prostate (with or without pelvic irradiation) with or without hormonotherapy. In advanced disease, treatment options include systemic treatment(s) and/or treatment to primary tumour and/or metastasis-directed therapies (MDTs). Specifically, in advanced stage, the current trend is earlier intensification of treatment such as dual or triple combination systemic treatments or adding treatment to primary and MDT to systemic treatment. However, earlier treatment intensification comes with the cost of increased morbidity and mortality resulting from drug-/treatment-related side effects. The main goal is and should be to provide the best possible care and oncologic outcomes with minimum possible side effects. This chapter will explore emerging possibilities to de-escalate treatment in PCa driven by enhanced insights into disease biology and the natural course of PCa such as AS in intermediate-risk disease or salvage versus adjuvant radiotherapy in post-RP patients. Considerations arising from advancements in PCa imaging and technological advancements in surgical and radiation therapy techniques including omitting pelvic lymph node dissection in the era of prostate-specific membrane antigen positron emitting tomography, the potential of MDT to delay/omit systemic treatment in metachronous oligorecurrence, and the efficacy of hypofractionation schemes compared with conventional fractionated radiotherapy will be discussed.

前列腺癌(PCa)是男性第二大常见癌症,每年新增病例约 140 万例。对于局部疾病患者,治疗方案包括积极监测(AS)、根治性前列腺切除术(RP;无论是否进行盆腔淋巴结清扫)或前列腺放疗(无论是否进行盆腔照射),无论是否使用激素疗法。对于晚期疾病,治疗方案包括全身治疗和/或原发肿瘤治疗和/或转移导向疗法(MDTs)。具体来说,对于晚期患者,目前的趋势是提前强化治疗,如双重或三重联合系统治疗,或在系统治疗的基础上增加原发肿瘤治疗和 MDT 治疗。然而,提前强化治疗的代价是药物/治疗相关副作用导致的发病率和死亡率增加。我们的主要目标是而且应该是在尽可能减少副作用的情况下提供最佳治疗和肿瘤结果。本章将探讨对疾病生物学和 PCa 自然病程的深入了解所带来的 PCa 降级治疗的新可能性,例如中危疾病的 AS 或 RP 后患者的挽救性放疗与辅助性放疗。还将讨论 PCa 成像技术的发展以及手术和放疗技术的进步所带来的各种考虑因素,包括在前列腺特异性膜抗原正电子发射断层扫描时代省略盆腔淋巴结清扫、MDT 推迟/省略系统性治疗的潜力、以及低分次方案与传统分次放疗相比的疗效。
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引用次数: 0
Treatment of Oligometastatic GI Cancers. 治疗寡转移性消化道癌症。
Clayton T Marcinak, Patrick B Schwartz, Mustafa M Basree, Newton Hurst, Michael Bassetti, Jeremy D Kratz, Nataliya V Uboha

Oligometastatic state is believed to potentially represent a transitional stage between early, locoregional state disease and widely metastatic disease. Historically, locoregional approaches, particularly in advanced colorectal cancers, have demonstrated efficacy in select patients with limited burden of metastatic disease. Recent strides in systemic therapies, including biomarker-based treatments and immunotherapy, alongside innovations in surgical techniques and novel locoregional approaches such as stereotactic radiotherapy and ablation, have ushered in a new era of therapeutic possibilities across all oligometastatic GI cancers. Despite these advancements, there remains a significant gap in high-quality prospective evidence guiding patient selection and treatment decisions across various disease types. Ongoing clinical trials are anticipated to provide crucial insights into oligometastatic states, fostering the refinement of disease-specific oligometastatic state definitions and treatment algorithms. This article reviews existing data on the management of oligometastatic GI cancer, summarizes current state of knowledge for each disease state, and provides updates on ongoing studies in this space.

少转移状态被认为可能代表早期局部状态疾病与广泛转移疾病之间的过渡阶段。从历史上看,局部治疗方法,尤其是晚期结直肠癌的局部治疗方法,已在转移性疾病负担有限的特定患者中显示出疗效。最近,全身疗法(包括基于生物标记物的治疗和免疫疗法)取得了长足进步,外科技术和新型局部方法(如立体定向放射治疗和消融术)也有了创新,这为所有寡转移性消化道癌症的治疗开创了新纪元。尽管取得了这些进展,但在指导不同疾病类型的患者选择和治疗决策方面,高质量的前瞻性证据仍存在巨大差距。正在进行的临床试验预计将为寡转移状态提供重要的见解,促进疾病特异性寡转移状态定义和治疗算法的完善。本文回顾了有关寡转移消化道癌症管理的现有数据,总结了每种疾病状态的知识现状,并提供了该领域正在进行的研究的最新情况。
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引用次数: 0
Update on Biomarkers in Renal Cell Carcinoma. 肾细胞癌生物标志物的最新进展。
Renée M Saliby, Eddy Saad, Soki Kashima, David A Schoenfeld, David A Braun

Immune checkpoint inhibitors have significantly transformed the treatment paradigm for metastatic renal cell carcinoma (RCC), offering prolonged overall survival and achieving remarkable deep and durable responses. However, given the multiple ICI-containing, standard-of-care regimens approved for RCC, identifying biomarkers that predict therapeutic response and resistance is of critical importance. Although tumor-intrinsic features such as pathological characteristics, genomic alterations, and transcriptional signatures have been extensively investigated, they have yet to provide definitive, robust predictive biomarkers. Current research is exploring host factors through in-depth characterization of the immune system. Additionally, innovative technological approaches are being developed to overcome challenges presented by existing techniques, such as tumor heterogeneity. Promising avenues in biomarker discovery include the study of the microbiome, radiomics, and spatial transcriptomics.

免疫检查点抑制剂大大改变了转移性肾细胞癌(RCC)的治疗模式,延长了患者的总生存期,并取得了显著的深度和持久反应。然而,鉴于已批准了多种含 ICI 的 RCC 标准治疗方案,确定预测治疗反应和耐药性的生物标志物至关重要。虽然病理特征、基因组改变和转录特征等肿瘤内在特征已被广泛研究,但它们尚未提供明确、可靠的预测性生物标志物。目前的研究正在通过深入分析免疫系统的特征来探索宿主因素。此外,还在开发创新技术方法,以克服肿瘤异质性等现有技术带来的挑战。生物标志物发现方面前景广阔的途径包括微生物组、放射组学和空间转录组学研究。
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引用次数: 0
Immuno-Oncology Advances in Genitourinary Cancers. 泌尿生殖系统癌症的免疫肿瘤学进展。
Peter D Zang, Arkhjamil Angeles, Tanya B Dorff, Sumanta K Pal, Shilpa Gupta

Immuno-oncology (IO) has made monumental gains in the past decade in the genitourinary space. In this review, we highlight advances with IO in renal cell carcinoma where it now has become standard-of-care frontline therapy in the metastatic setting but also discuss challenges with the initial approach. In urothelial carcinoma, we discuss the growing use of IO including exciting recent updates with IO-based regimens that may soon become the new standard of care. We further discuss difficulties with IO in prostate cancer, germ cell tumors, and penile squamous cell carcinoma. Finally, we highlight advances in IO approaches beyond checkpoint inhibition including the role of the gut microbiome and T-cell redirecting therapies.

过去十年,免疫肿瘤学(IO)在泌尿生殖领域取得了巨大进步。在这篇综述中,我们将重点介绍 IO 在肾细胞癌领域取得的进展,IO 目前已成为转移性肾细胞癌一线治疗的标准疗法,但我们也将讨论初始疗法面临的挑战。在尿路上皮癌方面,我们讨论了 IO 越来越广泛的应用,包括最近令人兴奋的基于 IO 的最新疗法,这些疗法可能很快就会成为新的治疗标准。我们进一步讨论了 IO 在前列腺癌、生殖细胞肿瘤和阴茎鳞状细胞癌中的困难。最后,我们重点介绍了检查点抑制以外的 IO 方法的进展,包括肠道微生物组的作用和 T 细胞重定向疗法。
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引用次数: 0
Updates on Systemic Therapy for Hepatocellular Carcinoma. 肝细胞癌系统疗法的最新进展。
Panagiotis Ntellas, Ian Chau

This review explores the dynamic landscape of hepatocellular carcinoma (HCC) treatment, emphasizing on recent developments across various stages and therapeutic approaches. Although curative strategies such as hepatectomy and thermal ablation are standard for early-stage cases, high relapse rates drive investigations into adjuvant and perioperative treatment. Adjuvant therapies face hurdles, but noteworthy advances include IMbrave050 setting a new standard with atezolizumab/bevacizumab. Locoregional treatments gain significance, especially for multifocal HCC, with the integration of innovative combinations with systemic therapies, showing improved outcomes. In the advanced setting, the evolution from sorafenib as the primary first-line option to new standards, such as atezolizumab/bevacizumab and tremelimumab/durvalumab, to other emerging therapies such as tislelizumab and pembrolizumab with lenvatinib, is explored. Additionally, second-line treatments and insights into the interplay between immunotherapies and antiangiogenic agents, as well as novel combination strategies that add complexity to treatment decisions, are discussed.

这篇综述探讨了肝细胞癌(HCC)治疗的动态发展,强调了不同阶段和治疗方法的最新进展。虽然肝切除术和热消融等根治性策略是早期病例的标准治疗方法,但高复发率促使人们研究辅助治疗和围手术期治疗。辅助治疗面临重重障碍,但值得注意的进展包括 IMbrave050 为阿特珠单抗/贝伐单抗设定了新标准。局部治疗的重要性日益凸显,尤其是对于多灶性 HCC,创新的联合疗法与全身疗法相结合,显示出更好的疗效。在晚期病例中,探讨了从索拉非尼作为主要一线选择到新标准(如atezolizumab/bevacizumab和tremelimumab/durvalumab),再到其他新兴疗法(如tislelizumab和pembrolizumab与lenvatinib)的演变过程。此外,还讨论了二线治疗方法、免疫疗法与抗血管生成药物之间的相互作用以及增加治疗决策复杂性的新型联合策略。
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引用次数: 0
Team-Based Care in Oncology: The Impact of the Advanced Practice Provider. 肿瘤学团队护理:高级实践提供者的影响。
Todd Pickard, Stephanie Williams, Eric Tetzlaff, Camille Petraitis, Heather Hylton

Integration of APPs into care teams affects quality and safety for the oncology patient. Learn the best practices and understand the concepts of onboarding, orientation, mentorship, scope of practice, and top of license. Review how productivity and other incentive programs can be adapted to integrate APPs and focus on team-based metrics.

将应用程序集成到护理团队中影响肿瘤患者的质量和安全。学习最佳实践并理解入职、定向、指导、实践范围和最高许可的概念。审查如何调整生产力和其他激励计划以整合应用程序,并关注基于团队的指标。
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引用次数: 0
Novel Immunotherapeutics: Perspectives on Checkpoints, Bispecifics, and Vaccines in Development. 新型免疫疗法:检查点、双特异性和正在开发的疫苗的观点。
Firas Y Kreidieh, Hussein A Tawbi, Aikaterini Alexaki, Hossein Borghaei, Lana E Kandalaft

Over the past decade, the advent of molecular techniques and deeper understanding of the tumor microenvironment (TME) have enabled the development of a multitude of immunotherapy targets and approaches. Despite the revolutionary advancement in immunotherapy, treatment resistance remains a challenge leading to decreased response rate in a significant proportion of patients. As such, there has recently been an evolving focus to enhance efficacy, durability, and toxicity profiles of immunotherapy. Although immune checkpoint inhibitors have revolutionized cancer treatment with many already-approved antibodies and several others in the pipeline, bispecific antibodies build on their success in an attempt to deliver an even more potent immune response against tumor cells. On the other hand, vaccines comprise the oldest and most versatile form of immunotherapy. Peptide and nucleic acid vaccines are relatively simple to manufacture compared with oncolytic virus-based vaccines, whereas the dendritic cell vaccines are the most complex, requiring autologous cell culture. Nevertheless, a crucial question in the development of cancer vaccines is the choice of antigen whereby shared and patient-private antigen approaches are currently being pursued. There is hope that cancer vaccines will join the repertoire of successful novel immunotherapeutics in the market. Better insights into the impact of immunotherapy on effector T cells and other immune cell populations in the TME shall be a major priority across the immune-oncology discipline and can help identify predictive biomarkers to evaluate response to treatment and identify patients who would most likely benefit from immunotherapy.

在过去的十年中,分子技术的出现和对肿瘤微环境(TME)的深入了解使得多种免疫治疗靶点和方法得以发展。尽管免疫疗法取得了革命性的进步,但治疗耐药性仍然是一个挑战,导致相当一部分患者的反应率下降。因此,最近有一个不断发展的焦点是提高免疫治疗的疗效、持久性和毒性。尽管免疫检查点抑制剂已经用许多已经被批准的抗体和其他几种正在开发中的抗体彻底改变了癌症治疗,但双特异性抗体在其成功的基础上,试图提供针对肿瘤细胞的更有效的免疫反应。另一方面,疫苗是最古老和最通用的免疫疗法。与基于溶瘤病毒的疫苗相比,肽疫苗和核酸疫苗的制造相对简单,而树突状细胞疫苗则是最复杂的,需要自体细胞培养。然而,开发癌症疫苗的一个关键问题是抗原的选择,因此目前正在寻求共享和患者私人抗原方法。癌症疫苗有望加入市场上成功的新型免疫疗法的行列。更好地了解免疫治疗对TME中效应T细胞和其他免疫细胞群的影响将是整个免疫肿瘤学学科的主要优先事项,并有助于确定预测性生物标志物,以评估治疗反应,并确定最有可能从免疫治疗中受益的患者。
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引用次数: 0
High Cost of Chimeric Antigen Receptor T-Cells: Challenges and Solutions. 嵌合抗原受体t细胞的高成本:挑战和解决方案。
Edward R Scheffer Cliff, Amar H Kelkar, David A Russler-Germain, Frazer A Tessema, Adam J N Raymakers, William B Feldman, Aaron S Kesselheim

Chimeric antigen receptor (CAR) T-cells are a cellular immunotherapy with remarkable efficacy in treating multiple hematologic malignancies but they are associated with extremely high prices that are, for many countries, prohibitively expensive. As their use increases both for hematologic malignancies and other indications, and large numbers of new cellular therapies are developed, novel approaches will be needed both to reduce the cost of therapy, and to pay for them. We review the many factors that lead to the high cost of CAR T-cells and offer proposals for reform.

嵌合抗原受体(CAR) t细胞是一种细胞免疫疗法,在治疗多种血液系统恶性肿瘤方面疗效显著,但价格极高,在许多国家,价格高得令人望而却步。随着它们在血液恶性肿瘤和其他适应症中的应用增加,以及大量新的细胞疗法被开发出来,将需要新的方法来降低治疗成本,并支付治疗费用。我们回顾了导致CAR - t细胞高成本的许多因素,并提出了改革建议。
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引用次数: 3
Erratum: Metastatic Hormone-Sensitive Prostate Cancer: Toward an Era of Adaptive and Personalized Treatment. 勘误:转移性激素敏感前列腺癌:迈向适应性和个性化治疗的时代。
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引用次数: 0
Erratum: Molecular Profiling in Neuro-Oncology: Where We Are, Where We're Heading, and How We Ensure Everyone Can Come Along. 勘误:神经肿瘤学的分子分析:我们在哪里,我们在哪里,以及我们如何确保每个人都能一起来。
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引用次数: 0
期刊
American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting
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