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Intratumoral Approaches for the Treatment of Melanoma 瘤内方法治疗黑色素瘤
Pub Date : 2017-01-01 DOI: 10.1097/PPO.0000000000000234
P. Bommareddy, A. Silk, H. Kaufman
Abstract There have been significant advances in the immunotherapy of melanoma over the last decade. The tumor microenvironment is now known to promote an immune-suppressive milieu that can block effective immune-mediated tumor rejection. Several novel strategies designed to overcome local immunosuppression hold promise for treatment of melanoma and other cancers. These approaches include oncolytic viruses, plasmid DNA delivery, Toll-like receptor agonists, inflammatory dyes, cytokines, checkpoint inhibitors, immunomodulatory agents, and host and pathogenic cell-based vectors. In addition, there are several novel methods for local drug delivery, including direct injection, image-guided, electroporation, and nanodelivery techniques under study. The approval of talimogene laherparepvec (Imlygic), an attenuated, recombinant oncolytic herpesvirus, for melanoma treatment is the first intratumoral agent to receive regulatory approval for the treatment of patients with melanoma. This review will focus on the rationale for intratumoral treatment in melanoma, describe the clinical and safety data for some of the agents in clinical development, and provide a perspective for future clinical investigation with intratumoral approaches. Melanoma has been a paradigm tumor for progress in targeted therapy and immunotherapy and will likely also be the tumor to establish the therapeutic role of intratumoral treatment for cancer.
在过去的十年中,黑色素瘤的免疫治疗取得了重大进展。肿瘤微环境可以促进免疫抑制环境,从而阻断有效的免疫介导的肿瘤排斥反应。一些旨在克服局部免疫抑制的新策略有望治疗黑色素瘤和其他癌症。这些方法包括溶瘤病毒、质粒DNA递送、toll样受体激动剂、炎症染料、细胞因子、检查点抑制剂、免疫调节剂以及宿主和病原细胞载体。此外,还有一些新的局部给药方法,包括直接注射、图像引导、电穿孔和纳米给药技术正在研究中。talmogene laherparepvec (Imlygic)是一种减毒重组溶瘤疱疹病毒,被批准用于黑色素瘤治疗,是首个获得监管机构批准用于黑色素瘤患者治疗的瘤内药物。本文将重点介绍肿瘤内治疗黑色素瘤的基本原理,描述临床开发中一些药物的临床和安全性数据,并为未来肿瘤内治疗方法的临床研究提供展望。黑色素瘤已经成为靶向治疗和免疫治疗进展的典范肿瘤,也可能成为肿瘤内治疗癌症的治疗作用。
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引用次数: 46
Novel Targeted Therapies for Metastatic Melanoma 转移性黑色素瘤的新靶向治疗
Pub Date : 2017-01-01 DOI: 10.1097/PPO.0000000000000242
W. Iams, J. Sosman, S. Chandra
Abstract Oncogene-targeted therapy is a major component of precision oncology, and although patients with metastatic melanoma have experienced improved outcomes with this strategy, there are a number of potential therapeutic targets currently under study that may further increase the drug armamentarium for this patient population. In this review, we discuss the landscape of targeted therapies for patients with advanced melanoma, focusing on oncogene mutation-specific targets. In patients with typical BRAF V600–mutant melanoma, combination BRAF and MEK inhibition has surpassed outcomes compared with monotherapy with BRAF or MEK inhibition alone, and current strategies seek to address inevitable resistance mechanisms. For patients with NRAS-mutant melanoma, MEK inhibitor monotherapy and combined MEK and CDK4/6 inhibition are burgeoning strategies; for patients with KIT-mutant melanoma, tyrosine kinase inhibition is being leveraged, and for NF-1–mutant melanoma, mTOR and MEK inhibition is being actively evaluated. In patients with atypical, non–V600 BRAF–mutant melanoma, MEK inhibitor monotherapy is the potential novel targeted approach on the horizon. For advanced uveal melanoma, novel targets such as IMCgp100 and glembatumumab have shown activity in early studies. We review additional strategies that remain in the preclinical and early clinical pipeline, so there is much hope for the future of targeted agents for distinct molecular cohorts of patients with advanced melanoma.
肿瘤基因靶向治疗是精确肿瘤学的一个重要组成部分,尽管转移性黑色素瘤患者通过这种策略获得了改善的结果,但目前仍有许多潜在的治疗靶点正在研究中,可能会进一步增加该患者群体的药物储备。在这篇综述中,我们讨论了晚期黑色素瘤患者靶向治疗的前景,重点是癌基因突变特异性靶点。在典型BRAF v600突变黑色素瘤患者中,与单独BRAF或MEK抑制的单药治疗相比,BRAF和MEK联合抑制的效果更好,目前的策略寻求解决不可避免的耐药机制。对于nras突变型黑色素瘤患者,MEK抑制剂单药治疗和MEK与CDK4/6联合抑制是新兴的策略;对于kit突变型黑色素瘤患者,酪氨酸激酶抑制正在被利用,对于nf -1突变型黑色素瘤,mTOR和MEK抑制正在被积极评估。在非典型、非v600 braf突变黑色素瘤患者中,MEK抑制剂单药治疗是一种潜在的新型靶向治疗方法。对于晚期葡萄膜黑色素瘤,IMCgp100和glembatumumab等新靶点在早期研究中显示出活性。我们回顾了仍在临床前和早期临床管道中的其他策略,因此针对晚期黑色素瘤患者不同分子群的靶向药物的未来有很大的希望。
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引用次数: 26
Advances in Interventional Oncology: Lung Cancer 介入肿瘤学进展:肺癌
Pub Date : 2016-11-01 DOI: 10.1097/PPO.0000000000000229
P. Dempsey, C. Ridge, S. Solomon
AbstractImage-guided lung intervention in the oncologic patient includes transthoracic needle biopsy, thermal ablation, fiducial placement, and tunneled pleural catheter placement and is made possible by technical advancements in computed tomography, fluoroscopy, and ultrasound technology, as well as the proliferation of available thermal ablation modalities such as radiofrequency, microwave, and cryoablation. With increasingly earlier cancer diagnoses being made and a greater patient demand for minimally invasive therapies, interventional oncology has many options to offer the patient with thoracic malignancies. The indications, technique, outcomes, and complications of these diagnostic and therapeutic procedures are described in detail in this review article.
影像引导下的肿瘤患者肺部干预包括经胸穿刺活检、热消融、基准放置和隧道胸膜导管放置,这些干预通过计算机断层扫描、透视和超声技术的技术进步以及可用的热消融方式(如射频、微波和冷冻消融)的扩散而成为可能。随着越来越多的早期癌症诊断和越来越多的患者对微创治疗的需求,介入肿瘤学为胸部恶性肿瘤患者提供了许多选择。这些诊断和治疗方法的适应症、技术、结果和并发症在这篇综述文章中详细描述。
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引用次数: 7
Palliative Interventional Oncology 姑息性介入肿瘤学
Pub Date : 2016-11-01 DOI: 10.1097/PPO.0000000000000230
A. Fairchild, W. Rilling
AbstractInterventional oncologists are playing an ever greater role in improving the quality of life of their patients through minimally invasive procedures, many of which can be performed on an outpatient basis. Some of the most common palliative procedures currently performed will be discussed including management of intractable ascites and pleural effusions, neurolytic plexus blocks, and palliation of pain and bleeding associated with metastatic tumors.
摘要介入肿瘤学家通过微创手术在提高患者生活质量方面发挥着越来越大的作用,其中许多手术可以在门诊进行。我们将讨论目前实施的一些最常见的姑息治疗方法,包括顽固性腹水和胸腔积液的治疗、神经溶解性丛神经阻滞以及转移性肿瘤相关疼痛和出血的姑息治疗。
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引用次数: 4
Increasing Role of Image-Guided Ablation in the Treatment of Musculoskeletal Tumors 影像引导消融在肌肉骨骼肿瘤治疗中的作用日益增强
Pub Date : 2016-11-01 DOI: 10.1097/PPO.0000000000000233
A. Kurup, M. Callstrom
AbstractIn the last decade, percutaneous treatment of musculoskeletal (MSK) tumors has become more established in routine clinical care while also undergoing a number of advancements. Ablative techniques to palliate painful skeletal metastases have gained wide acceptance, while goals for ablation have evolved to include local control of oligometastases and desmoid tumors. Bone consolidation or augmentation is now frequently used in conjunction with or instead of ablation of skeletal tumors to stabilize pathologic fractures or prevent further morbidity that could result from fractures caused by tumor progression. These procedures have traditionally been performed with cement injection, although additional percutaneous consolidation or stabilization devices have been developed. Techniques to monitor the ablation zone and adjacent structures intraprocedurally are now applied to increase the number of tumors amenable to treatment. These include methods to depict, displace, or monitor critical structures adjacent to targeted MSK tumors. Finally, the role of ablation in the comprehensive care of patients with MSK tumors continues to change with the evolving triage of patients between radiation therapy, surgical resection and stabilization, and percutaneous ablative and consolidative management.
在过去的十年中,经皮治疗肌肉骨骼(MSK)肿瘤在常规临床护理中已经越来越成熟,同时也取得了一些进展。消融技术用于缓解疼痛的骨骼转移已被广泛接受,而消融的目标已发展到包括局部控制少转移瘤和硬纤维瘤。骨巩固或骨增强术现在经常与骨骼肿瘤消融联合使用或代替消融,以稳定病理性骨折或防止肿瘤进展引起的骨折可能导致的进一步发病率。这些手术传统上是通过水泥注射进行的,尽管已经开发了额外的经皮巩固或稳定装置。术中监测消融区和邻近结构的技术现在被应用于增加可接受治疗的肿瘤数量。这些方法包括描述、置换或监测靶向MSK肿瘤附近的关键结构。最后,消融在MSK肿瘤患者综合护理中的作用随着患者在放射治疗、手术切除和稳定、经皮消融和巩固治疗之间的分类不断变化。
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引用次数: 10
New Developments in Interventional Oncology: Liver Metastases From Colorectal Cancer 介入肿瘤学的新进展:结直肠癌肝转移
Pub Date : 2016-11-01 DOI: 10.1097/PPO.0000000000000226
J. Kallini, A. Gabr, N. Abouchaleh, R. Ali, A. Riaz, R. Lewandowski, R. Salem
AbstractColorectal cancer is the third leading cause of cancer death in the United States. Although hepatic excision is the first-line treatment for colorectal liver metastasis (CRLM), few patients are candidates. Locoregional therapy (LRT) encompasses minimally invasive techniques practiced by interventional radiology. These include ablative treatments (radiofrequency ablation, microwave ablation, and cryosurgical ablation) and transcatheter intra-arterial therapy (hepatic arterial infusion chemotherapy, transarterial “bland” embolization, transarterial chemoembolization, and radioembolization with yttrium 90). The National Comprehensive Cancer Network recommends LRT for unresectable CRLM refractory to chemotherapy. The following is a review of LRT in CRLM, including salient features, advantages, limitations, current roles, and future considerations.
摘要结直肠癌是美国癌症死亡的第三大原因。虽然肝切除是结肠直肠癌肝转移(CRLM)的一线治疗方法,但很少有患者是候选的。局部治疗(LRT)包括介入放射学实践的微创技术。这些治疗包括消融治疗(射频消融、微波消融和冷冻消融)和经导管动脉内治疗(肝动脉输注化疗、经动脉“温和”栓塞、经动脉化疗栓塞和用钇90放射栓塞)。国家综合癌症网络推荐LRT治疗化疗难切除的CRLM。以下是对CRLM中LRT的回顾,包括显著的特点、优势、限制、当前的角色和未来的考虑。
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引用次数: 11
Interventional Oncology in Hepatocellular Carcinoma: Progress Through Innovation 肝细胞癌介入肿瘤学:通过创新取得进展
Pub Date : 2016-11-01 DOI: 10.1097/PPO.0000000000000227
L. Mu, J. Chapiro, J. Stringam, J. Geschwind
AbstractThe clinical management of hepatocellular carcinoma has evolved greatly in the last decade mostly through recent technical innovations. In particular, the application of cutting-edge image guidance has led to minimally invasive solutions for complex clinical problems and rapid advances in the field of interventional oncology. Many image-guided therapies, such as transarterial chemoembolization and radiofrequency ablation, have meanwhile been fully integrated into interdisciplinary clinical practice, whereas others are currently being investigated. This review summarizes and evaluates the most relevant completed and ongoing clinical trials, provides a synopsis of recent innovations in the field of intraprocedural imaging and tumor response assessment, and offers an outlook on new technologies, such as radiopaque embolic materials. In addition, combination therapies consisting of locoregional therapies and systemic molecular targeted agents (e.g., sorafenib) remain of major interest to the field and are also discussed. Finally, we address the many substantial advances in immune response pathways that have been related to the systemic effects of locoregional therapies. Knowledge of these new developments is crucial as they continue to shape the future of cancer treatment, further establishing interventional oncology along with surgical, medical, and radiation oncology as the fourth pillar of cancer care.
摘要近十年来,肝细胞癌的临床治疗有了很大的发展,主要是由于近年来的技术创新。尤其是尖端影像引导技术的应用,使得复杂临床问题的微创解决方案得以实现,介入肿瘤学领域取得了快速发展。许多图像引导的治疗方法,如经动脉化疗栓塞和射频消融,已经完全融入跨学科的临床实践,而其他治疗方法目前正在研究中。本文总结和评价了最相关的已完成和正在进行的临床试验,概述了术中成像和肿瘤反应评估领域的最新创新,并展望了新技术,如不透射线栓塞材料。此外,由局部区域治疗和全身分子靶向药物(如索拉非尼)组成的联合治疗仍然是该领域的主要兴趣,也被讨论。最后,我们讨论了与局部区域治疗的全身效应有关的免疫反应途径的许多实质性进展。了解这些新发展至关重要,因为它们将继续塑造癌症治疗的未来,进一步将介入肿瘤学与外科、内科和放射肿瘤学一起建立为癌症治疗的第四大支柱。
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引用次数: 6
Liver Metastases From Noncolorectal Malignancies (Neuroendocrine Tumor, Sarcoma, Melanoma, Breast) 非结直肠恶性肿瘤(神经内分泌肿瘤、肉瘤、黑色素瘤、乳腺)肝转移
Pub Date : 2016-11-01 DOI: 10.1097/PPO.0000000000000232
E. Alexander, M. Soulen
AbstractPatients with noncolorectal hepatic metastases often face limited treatment options and a dismal prognosis. Over the last decade, the advent of targeted immunotherapies has transformed the treatment of certain metastatic cancers, such as sarcoma and melanoma; however, these patients eventually develop resistance. Metastatic sarcoma, melanoma, and breast and neuroendocrine tumors are notoriously treatment resistant once they have metastasized to the liver. For these cancers, minimally invasive transarterial and ablation therapies have emerged as safe, palliative therapies that can provide symptom control and even prolong survival.
摘要非结直肠肝转移患者通常面临有限的治疗选择和惨淡的预后。在过去的十年中,靶向免疫疗法的出现改变了某些转移性癌症的治疗方法,如肉瘤和黑色素瘤;然而,这些患者最终会产生耐药性。转移性肉瘤、黑色素瘤、乳腺和神经内分泌肿瘤一旦转移到肝脏,就很难治疗。对于这些癌症,微创经动脉和消融治疗已经成为安全的姑息性治疗,可以提供症状控制,甚至延长生存期。
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引用次数: 6
Era of a Single Population-Based Payment to a Cancer Center: Delivering the Value of Interventional Oncology in Accountable Care Organizations 以人群为基础向癌症中心支付单一费用的时代:在负责任的护理组织中提供介入肿瘤学的价值
Pub Date : 2016-11-01 DOI: 10.1097/PPO.0000000000000231
J. Jia, R. Lencioni, H. Forman, H. S. Kim
AbstractTo curtail increasing health care costs, the government has ushered in the era of the Accountable care organization (ACO). The purposes of this review are to evaluate the effects the ACO will have on the practice of interventional oncology and its role in cancer care and to explore methods to assimilate. Proposed action points include integration into the modern-day cancer center, adoption of an outpatient clinic, mandatory performance measures, and workflow and cost analysis. If adaptations are made, interventional oncology can continue its role in cancer treatment, will provide more effective care, and reach more patients in the new ACO.
摘要为了遏制不断增长的医疗成本,政府已经迎来了问责医疗组织(ACO)的时代。本综述的目的是评估ACO对介入肿瘤学实践的影响及其在癌症治疗中的作用,并探讨吸收的方法。建议的行动点包括整合到现代癌症中心,采用门诊诊所,强制性绩效指标,以及工作流程和成本分析。如果做出调整,介入肿瘤学可以继续其在癌症治疗中的作用,将提供更有效的护理,并在新的ACO中覆盖更多的患者。
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引用次数: 1
Kidney Cancer 肾癌
Pub Date : 2016-11-01 DOI: 10.1097/PPO.0000000000000225
R. Motzer, N. Agarwal, C. Beard, S. Bhayani, G. Bolger, M. Carducci, Sam S. Chang, T. Choueiri, S. Hancock, G. Hudes, E. Jonasch, D. Josephson, T. Kuzel, E. Levine, D. Lin, K. Margolin, M. Michaelson, T. Olencki, R. Pili, T. W. Ratliff, B. Redman, C. Robertson, C. Ryan, J. Sheinfeld, P. Spiess, Jue Wang, R. Wilder
AbstractThe number of new cases of renal cell carcinoma has been steadily increasing since the 1960s, reaching 62,000 and 89,000 annually in the United States and Europe, respectively, in 2016. The current standard of care for early-stage disease is nephron-sparing surgery, which has a demonstrated long-term disease-free survival and an acceptable safety profile. Technical developments (thin, powerful probes and real-time image guidance systems) have allowed image-guided percutaneous ablation to become a viable option for stage I renal cell carcinoma. Because of the widespread use of cross-sectional imaging, most renal tumors (75%) are indeed detected incidentally at stage I (75%). As a result, ablation is a potentially curable intervention and one that could mitigate surgical risks. All 3 ablative modalities (radiofrequency ablation, microwave ablation, and cryoablation) have been extensively applied. The utilization of ablation was initially hampered by the lack of prospective, long-term oncologic data. As a result, ablation was reserved for specific subgroups of patients, for example, patients with solitary kidney, chronic kidney disease, or bilateral disease; poor surgical candidates; or patients with syndromes that predispose them to renal cell cancer. Recently, however, studies on percutaneous ablation for early-stage renal cancer have yielded prospective, long-term oncologic data, affirming the earlier, lower-level-evidence studies. The reported efficacy of ablation for stage I renal cancer (especially cryoablation) appears to rival that of the accepted standard of care (nephron-sparing surgery), whereas its safety profile is a decided advantage. In conclusion, image-guided percutaneous ablation should be considered a viable, curative option for stage IA renal cell carcinoma.
自20世纪60年代以来,肾细胞癌的新发病例数一直在稳步增长,2016年美国和欧洲分别达到每年6.2万和8.9万例。目前早期疾病的标准治疗是保留肾单元的手术,它具有长期无病生存和可接受的安全性。技术的发展(薄而强大的探针和实时图像引导系统)使得图像引导的经皮消融术成为治疗I期肾细胞癌的可行选择。由于横断成像的广泛应用,大多数肾肿瘤(75%)确实在I期偶然发现(75%)。因此,消融术是一种潜在的可治愈的干预措施,可以降低手术风险。所有三种消融方式(射频消融、微波消融和冷冻消融)已被广泛应用。由于缺乏前瞻性、长期的肿瘤学数据,消融的应用最初受到阻碍。因此,消融被保留给特定的患者亚组,例如,单发肾、慢性肾脏疾病或双侧疾病患者;手术条件差;或者患有易患肾细胞癌的综合征的患者。然而,最近关于经皮消融治疗早期肾癌的研究已经获得了前瞻性、长期的肿瘤学数据,证实了早期的低水平证据研究。据报道,I期肾癌消融(尤其是冷冻消融)的疗效似乎与公认的治疗标准(保留肾单元的手术)相媲美,而其安全性是一个确定的优势。总之,图像引导下的经皮消融术应该被认为是治疗IA期肾细胞癌的可行选择。
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引用次数: 42
期刊
The Cancer Journal
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