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Recent Advancements and Future Perspectives on Molecular Biomarkers in Adult Lower-Grade Gliomas. 成人低级别胶质瘤分子标志物研究进展及展望
IF 2.6 4区 医学 Q3 ONCOLOGY Pub Date : 2025-01-01 DOI: 10.1097/PPO.0000000000000758
Jessica L Fleming, Arnab Chakravarti

Abstract: There has been a significant paradigm shift in the clinical management of lower-grade glioma patients given the recent updates to the 2021 World Health Organization classification along with long-term results from randomized phase III clinical trials. As a result, we are now better able to diagnose and assign patients to the most appropriate treatment course. This review provides a comprehensive summary of the most robust and reliable molecular biomarkers for adult lower-grade gliomas and discusses current challenges facing this patient population that future correlative biology studies combined with advancements in technologies could help overcome.

摘要:鉴于最近更新的2021年世界卫生组织分类以及随机III期临床试验的长期结果,低级别胶质瘤患者的临床管理模式发生了重大转变。因此,我们现在能够更好地诊断并为患者分配最合适的治疗方案。本文综述了成人低级别胶质瘤最可靠的分子生物标志物,并讨论了该患者群体目前面临的挑战,未来相关生物学研究结合技术进步可以帮助克服这些挑战。
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引用次数: 0
Management of Low-Grade Gliomas. 低级别胶质瘤的治疗。
IF 2.6 4区 医学 Q3 ONCOLOGY Pub Date : 2025-01-01 DOI: 10.1097/PPO.0000000000000760
Maria Diaz, Peter C Pan

Abstract: The term "low-grade glioma" historically refers to adult diffuse gliomas that exhibit a less aggressive course than the more common high-grade gliomas. In the current molecular era, "low-grade" refers to World Health Organization central nervous system grade 2 gliomas almost always with an isocitrate dehydrogenase (IDH) mutation (astrocytomas and oligodendrogliomas). The term "lower-grade gliomas" has emerged encompassing grades 2 and 3 IDH-mutant astrocytomas and oligodendrogliomas, to acknowledge that histological grade is not as important a prognostic factor as molecular features, and distinguishing them from grade 4 glioblastomas, which lack an IDH mutation. These grades 2 and 3 IDH-mutant tumors are characterized by indolent growth but are ultimately incurable in most cases, presenting significant management challenges. Physicians must carefully weigh all available evidence to balance improvements in survival from new treatments against treatment toxicities. This review summarizes the evidence guiding the treatment of these patients.

摘要:“低级别胶质瘤”一词历史上是指成人弥漫性胶质瘤,其表现出比更常见的高级别胶质瘤更低的侵袭性。在当前的分子时代,“低级别”是指世界卫生组织中枢神经系统2级胶质瘤,几乎总是伴有异柠檬酸脱氢酶(IDH)突变(星形细胞瘤和少突胶质细胞瘤)。“低级别胶质瘤”一词已经出现,包括2级和3级IDH突变星形细胞瘤和少突胶质细胞瘤,承认组织学级别并不像分子特征那样是一个重要的预后因素,并将它们与缺乏IDH突变的4级胶质母细胞瘤区分开来。这些2级和3级idh突变肿瘤的特点是生长缓慢,但在大多数情况下最终无法治愈,提出了重大的管理挑战。医生必须仔细权衡所有可获得的证据,以平衡新疗法对生存的改善和治疗毒性。本文综述了指导这些患者治疗的证据。
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引用次数: 0
Introduction. 介绍。
IF 2.6 4区 医学 Q3 ONCOLOGY Pub Date : 2025-01-01 DOI: 10.1097/PPO.0000000000000761
Arnab Chakravarti
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引用次数: 0
Severe Lymphopenia Predicts Poorer Survival in Patients With Rectal Cancer Undergoing Neoadjuvant Chemoradiation. 严重淋巴细胞减少预示着接受新辅助放化疗的直肠癌患者较差的生存率。
IF 2.6 4区 医学 Q3 ONCOLOGY Pub Date : 2025-01-01 DOI: 10.1097/PPO.0000000000000749
Daniel W Kim, Grace Lee, Elise M Cai, David P Ryan, Aparna R Parikh, Jill N Allen, Bruce J Giantonio, David L Berger, Hiroko Kunitake, Rocco Ricciardi, James C Cusack, Hannah J Roberts, Theodore S Hong, Jennifer Y Wo

Purpose: Chemoradiation-induced lymphopenia is common and associated with poorer survival in multiple solid malignancies. However, the association between chemoradiation-related lymphopenia and survival outcomes in rectal cancer is yet unclear. The objective of this study was to evaluate the prognostic impact of lymphopenia and its predictors in patients with rectal cancer undergoing neoadjuvant chemoradiation.

Methods: The inclusion criteria for this single-institution retrospective study were as follows: (1) biopsy-proven diagnosis of rectal adenocarcinoma, (2) receipt of neoadjuvant chemoradiation followed by surgery, and (3) absolute lymphocyte count available prior to and within 12 weeks of chemoradiation. In general, chemoradiation consisted of 5-fluorouracil or capecitabine and radiotherapy with 50.4 Gy over 28 fractions. Lymphopenia was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The primary variable of interest was absolute lymphocyte count nadir within 12 weeks of chemoradiation, dichotomized by <500/μL (grade 3 or worse lymphopenia). The primary endpoint was overall survival. Cox modeling and Kaplan-Meier methods were used to perform survival analyses.

Results: A total of 193 patients were identified with a median follow-up of 68 months. Overall clinical stage was 2 in 21% and 3 in 76%. Median baseline lymphocyte count for the entire cohort was 1700/μL. One hundred ten patients (57%) experienced chemoradiation-related severe lymphopenia. Pathologic complete response rate was 21%; 83% received adjuvant chemotherapy. Lower baseline lymphocyte count was significantly associated with increased risk for chemoradiation-related severe lymphopenia (odds ratio, 1.71). On multivariable Cox regression analysis, chemoradiation-related severe lymphopenia was significantly associated with worse disease-free survival (hazard ratio, 2.64) and overall survival (hazard ratio, 4.32). Five-year overall survival was 79% versus 92%, and 5-year disease-free survival was 70% versus 86% in the cohort that experienced versus did not experience severe lymphopenia, respectively.

Discussion: Chemoradiation-induced lymphopenia is common and a prognostic marker of poorer survival in rectal cancer. Closer observation in high-risk patients and treatment modifications may be potential approaches to mitigating treatment-related lymphopenia. Our findings also suggest an important role of the host immunity in rectal cancer outcomes and support future studies investigating ways to reduce treatment-induced lymphopenia.

目的:放化疗引起的淋巴细胞减少症在多发性实体恶性肿瘤中很常见,并与较差的生存率相关。然而,直肠癌放化疗相关淋巴细胞减少与生存结果之间的关系尚不清楚。本研究的目的是评估淋巴细胞减少症及其预测因素对接受新辅助放化疗的直肠癌患者的预后影响。方法:这项单机构回顾性研究的纳入标准如下:(1)经活检证实的直肠腺癌诊断,(2)手术后接受新辅助放化疗,(3)放化疗前和12周内的绝对淋巴细胞计数。一般来说,放化疗包括5-氟尿嘧啶或卡培他滨和放疗,放疗剂量为50.4 Gy,超过28个分数。根据不良事件通用术语标准5.0版对淋巴细胞减少症进行分级。主要研究变量是放化疗后12周内的绝对淋巴细胞计数最低点,根据结果进行二分类:共有193例患者被确定,中位随访时间为68个月。总临床分期为2 / 21%,3 / 76%。整个队列的中位基线淋巴细胞计数为1700/μL。110名患者(57%)经历了与放化疗相关的严重淋巴细胞减少症。病理完全缓解率为21%;83%接受了辅助化疗。较低的基线淋巴细胞计数与放化疗相关的严重淋巴细胞减少的风险增加显著相关(优势比,1.71)。在多变量Cox回归分析中,放化疗相关的严重淋巴细胞减少与较差的无病生存(风险比为2.64)和总生存(风险比为4.32)显著相关。在经历和未经历严重淋巴细胞减少的队列中,5年总生存率分别为79%和92%,5年无病生存率为70%和86%。讨论:放化疗引起的淋巴细胞减少是常见的,是直肠癌较差生存的预后标志。对高危患者进行更密切的观察和修改治疗方法可能是减轻治疗相关性淋巴细胞减少症的潜在途径。我们的研究结果还表明,宿主免疫在直肠癌预后中的重要作用,并支持未来研究减少治疗性淋巴细胞减少的方法。
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引用次数: 0
Future Directions in the Treatment of Low-Grade Gliomas. 低级别胶质瘤治疗的未来方向。
IF 2.6 4区 医学 Q3 ONCOLOGY Pub Date : 2025-01-01 DOI: 10.1097/PPO.0000000000000759
Connor J Kinslow, Minesh P Mehta

Abstract: There is major interest in deintensifying therapy for isocitrate dehydrogenase-mutant low-grade gliomas, including with single-agent cytostatic isocitrate dehydrogenase inhibitors. These efforts need head-to-head comparisons with proven modalities, such as chemoradiotherapy. Ongoing clinical trials now group tumors by intrinsic molecular subtype, rather than classic clinical risk factors. Advances in imaging, surgery, and radiotherapy have improved outcomes in low-grade gliomas. Emerging biomarkers, targeted therapies, immunotherapy, radionuclides, and novel medical devices are a promising frontier for future treatment. Diverse representation in glioma research and clinical trials will help to ensure that advancements in care are realized by all groups.

摘要:人们对异柠檬酸脱氢酶突变型低级别胶质瘤的去强化治疗非常感兴趣,包括单药细胞抑制剂异柠檬酸脱氢酶抑制剂。这些努力需要与已证实的治疗方式(如放化疗)进行正面比较。正在进行的临床试验现在根据固有的分子亚型而不是经典的临床危险因素对肿瘤进行分组。影像学、手术和放疗的进步改善了低级别胶质瘤的预后。新兴的生物标志物、靶向治疗、免疫治疗、放射性核素和新型医疗设备是未来治疗的一个有希望的前沿。胶质瘤研究和临床试验的多样化代表将有助于确保所有群体都能实现护理的进步。
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引用次数: 0
The Evolving Role of Stereotactic Body Radiation Therapy in Personalized Oncologic Care. 立体定向体外放射治疗在个性化肿瘤治疗中不断发展的作用。
IF 2.6 4区 医学 Q3 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.1097/PPO.0000000000000757
Elizabeth M Jaworski, Theodore S Lawrence
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引用次数: 0
Technical and Quality Considerations for Stereotactic Radiation Treatment Techniques. 立体定向放射治疗技术的技术和质量考虑因素。
IF 2.6 4区 医学 Q3 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.1097/PPO.0000000000000756
Elizabeth L Covington, Richard A Popple

Abstract: Stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT), collectively termed SRS-SBRT, are advanced treatment modalities delivering high doses of radiation in a single treatment or condensed treatment phase. Due to the small margins and steep dose gradient used in SRS-SBRT, the technical and safety considerations are more stringent than traditional radiation therapy and may include more advanced simulation, patient immobilization, treatment planning, and treatment delivery techniques. Respiratory motion management and intrafraction motion monitoring are often used during SRS-SBRT to ensure treatments are robust to both internal organ motion and patient movement during treatment. To ensure optimal treatment quality, SRS-SBRT programs should use multidisciplinary coordination of care to ensure patient-specific treatment strategies are used for optimal patient outcomes. Quality and safety considerations are presented, including peer review and external validation, for optimizing quality and adhering to national guidelines for stereotactic techniques.

摘要:立体定向放射外科(SRS)和立体定向体放射治疗(SBRT)统称为 SRS-SBRT,是在单次治疗或浓缩治疗阶段提供高剂量放射的先进治疗方式。由于 SRS-SBRT 的边缘小、剂量梯度大,其技术和安全考虑因素比传统放疗更为严格,可能包括更先进的模拟、病人固定、治疗计划和治疗实施技术。在 SRS-SBRT 治疗过程中,通常会使用呼吸运动管理和分段内运动监测,以确保治疗过程中内部器官运动和患者运动都能得到有效控制。为确保最佳治疗质量,SRS-SBRT 计划应采用多学科协调护理,以确保采用针对患者的治疗策略,从而获得最佳的患者疗效。本文介绍了质量和安全方面的注意事项,包括同行评审和外部验证,以优化质量并遵守立体定向技术的国家指导方针。
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引用次数: 0
Shifting the Landscape of Spine and Non-Spine Bone Metastases: A Review of Stereotactic Body Radiotherapy. 改变脊柱和非脊柱骨转移瘤的格局:立体定向体放射治疗综述》。
IF 2.6 4区 医学 Q3 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.1097/PPO.0000000000000755
Cristian Udovicich, Simon S Lo, Matthias Guckenberger, Arjun Sahgal

Abstract: Both spine and nonspine bone metastases are frequent sites of spread from solid organ malignancies. As bone metastases frequently cause significant morbidity for patients, it is critical to offer a treatment that can achieve rapid and durable symptomatic relief and local control, without being associated with serious risks of toxicity. Conventional palliative radiation therapy has a key treatment component in the multidisciplinary management of these patients; however, over the past decade, it has evolved to routinely deliver high biologically effective doses with precision in the form of stereotactic body radiation therapy. This change in paradigm is a result of the shifting landscape in cancer care, such that short-term pain relief is no longer the sole therapeutic aim for selected patients, and durable symptom relief and local tumor control are the goals. This review discusses the randomized prospective evidence, ongoing trials, approach to surveillance imaging, and treatment delivery for stereotactic body radiation therapy, to both spine and nonspine bone metastases, with a specific section on sacral metastases.

摘要:脊柱和非脊柱骨转移都是实体器官恶性肿瘤的常见扩散部位。由于骨转移瘤经常会给患者带来严重的发病率,因此提供一种既能快速、持久地缓解症状和控制局部病情,又不会带来严重毒性风险的治疗方法至关重要。传统的姑息放射治疗是这些患者多学科治疗中的关键治疗组成部分;然而,在过去十年中,它已发展为以立体定向体放射治疗的形式,常规地精确提供高生物有效剂量。这种模式的变化是癌症治疗格局转变的结果,短期缓解疼痛不再是选定患者的唯一治疗目标,持久缓解症状和局部肿瘤控制才是目标。本综述讨论了针对脊柱和非脊柱骨转移瘤的立体定向体放射治疗的随机前瞻性证据、正在进行的试验、监测成像方法和治疗方法,其中特别讨论了骶骨转移瘤。
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引用次数: 0
Stereotactic Body Radiation Therapy: Opportunities and Limitations. 立体定向体放射治疗:机遇与局限。
IF 2.6 4区 医学 Q3 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.1097/PPO.0000000000000751
Elizabeth M Jaworski, Theodore S Lawrence
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引用次数: 0
A Review of Stereotactic Body Radiotherapy in the Management of Gastrointestinal Malignancies. 胃肠道恶性肿瘤治疗中的立体定向体放射治疗回顾。
IF 2.6 4区 医学 Q3 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.1097/PPO.0000000000000752
Emily Hollis, David W Nganga, Ted K Yanagihara

Abstract: In this review, we explore the role of stereotactic body radiotherapy (SBRT) and other advanced radiotherapy techniques in the treatment of gastrointestinal malignancies, which primarily involves primary and secondary liver cancers and pancreatic cancers. The review examines radiotherapy in both curative and palliative settings, emphasizing the evolution of SBRT and hypofractionation as alternatives to conventional radiotherapy. We review the recent literature evaluating radiotherapy in the management of unresectable, borderline resectable, and metastatic pancreatic cancer, highlighting recent advances in radiotherapy techniques that aim to improve local control, reduce toxicity, and increase resectability in appropriate patients. For primary liver cancers (hepatocellular carcinoma and cholangiocarcinoma), SBRT has emerged as a potential noninvasive alternative to surgery, particularly in patients with unresectable tumors or those awaiting liver transplantation. The review also provides insights into ongoing clinical trials, comparative studies between SBRT and other local therapies such as radiofrequency ablation, and the use of radiotherapy in managing liver metastases from various primary cancers. Throughout, we emphasize limitations in the available literature and highlight areas of ongoing and future investigation.

摘要:在这篇综述中,我们探讨了立体定向体放射治疗(SBRT)和其他先进放疗技术在治疗胃肠道恶性肿瘤(主要包括原发性和继发性肝癌和胰腺癌)中的作用。这篇综述探讨了治疗性和姑息性放疗,强调了SBRT和低分量放疗作为传统放疗替代疗法的发展。我们回顾了近期评估放疗治疗不可切除、边缘可切除和转移性胰腺癌的文献,重点介绍了放疗技术的最新进展,这些技术旨在改善局部控制、减少毒性并提高合适患者的可切除性。对于原发性肝癌(肝细胞癌和胆管癌),SBRT 已成为手术的潜在无创替代疗法,尤其是对于肿瘤无法切除或等待肝移植的患者。本综述还深入探讨了正在进行的临床试验、SBRT 和其他局部疗法(如射频消融)之间的比较研究,以及放疗在治疗各种原发性癌症肝转移方面的应用。我们强调了现有文献的局限性,并重点介绍了正在进行的和未来将开展的研究领域。
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引用次数: 0
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Cancer journal
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