How to improve the implementation of guidelines on cancer-related thrombosis

Venous thromboembolism (VTE; defined by deep-vein thrombosis, central venous catheter-related thrombosis or pulmonary embolism) is a major therapeutic issue in cancer patients. VTE is reported in 15–20% of patients with cancer and is an independent prognostic factor and a leading cause of death. In this population, low-molecular-weight heparins have been shown to be superior to vitamin K antagonists. The Italian Association of Medical Oncology, the National Comprehensive Cancer Network, the American Society of Clinical Oncology, the French ‘Institut National du Cancer’, the European Society of Medical Oncology and the American College of Chest Physicians have all published specific guidelines, but their implementation is still low in clinical practice. Methodological assessment of these guidelines was performed using the Appraisal of Guidelines Research & Evaluation Instrument. None of the guidelines on thrombosis and cancer have sought for patients’ preferences, nor were they tested among target users. VTE in cancer patients requires a multidisciplinary approach but downstream of the guidelines publication, the potential organisational barriers in applying the recommendations have not been discussed. Tolerance and cost–effectiveness of long-term use of low-molecular-weight heparin may account for the large heterogeneity seen in daily clinical practice. Homogenization of guidelines in international consensus working groups followed by educational and active implementation strategies would be very valuable in order to improve the care of VTE in cancer patients.     

The NCCN Clinical Practice Guidelines on Venous Thromboembolic Disease: strategies for improving VTE prophylaxis in hospitalized cancer patients

The risk for venous thromboembolism (VTE) is high in hospitalized cancer patients, and is associated with an elevated risk for recurrent thrombosis, bleeding complications, and use of health care resources. Thromboembolism is the second leading cause of death in hospitalized cancer patients. Thromboprophylaxis with unfractionated heparin or low-molecular-weight heparins has been clinically proven to reduce the risk for VTE and improve outcomes. However, VTE prophylaxis continues to be underprescribed in cancer patients. Recognizing the clinical burden of VTE in cancer patients, the National Comprehensive Cancer Network (NCCN) recently released guidelines for VTE prevention and management. These NCCN guidelines recommend evidence-based prophylactic anticoagulant therapy for all patients admitted to hospital with a diagnosis of cancer who do not have contraindications to anticoagulant use. However, there continue to be barriers to the implementation of clinical practice guidelines and appropriate use of VTE prophylaxis. Multifaceted active educational and electronic interventions are necessary to raise awareness and reduce the burden of cancer-associated thrombosis and its attendant consequences.     

SEOM guidelines on thrombosis in cancer patients

The association between cancer and thrombosis is well established. Venous thromboembolism (VTE) is considered a main cause of mortality and morbidity in cancer patients and is commonly underestimated by oncologists. In recent years the incidence rates of VTE have notably increased. Several studies have clearly shown that cancer patients who are diagnosed with VTE present a poorer prognosis. The Spanish Society of Medical Oncology (SEOM) presents the guidelines for thrombosis and cancer in order to improve the prevention and management of VTE.     

Prevention of venous thromboembolism in cancer patients: current approaches and opportunities for improvement

Venous thromboembolism (VTE), a common complication in patients with cancer, is associated with increased risk of morbidity, mortality, and recurrent VTE. Risk factors for VTE in cancer patients include the type and stage of cancer, comorbidities, age, major surgery, and active chemotherapy. Evidence-based guidelines for thromboprophylaxis in cancer patients have been published: the National Comprehensive Cancer Network and American Society for Clinical Oncology guidelines recommend thromboprophylaxis for hospitalized cancer patients, while the American College of Chest Physician guidelines recommend thromboprophylaxis for surgical patients with cancer and bedridden cancer patients with an acute medical illness. Guidelines do not generally recommend routine thromboprophylaxis in ambulatory patients during chemotherapy, but there is evidence that some of these patients are at risk of VTE; some may be at higher risk while on active chemotherapy. Approaches are needed to identify those patients most likely to benefit from thromboprophylaxis, and, to this end, a risk assessment model has been developed and validated. Despite the benefits, many at-risk patients do not receive any thromboprophylaxis, or receive prophylaxis that is not compliant with guideline recommendations. Quality improvement initiatives have been developed by the Centers for Medicare and Medicaid Services, National Quality Forum, and Joint Commission to encourage closure of the gap between guideline recommendations and clinical practice for prevention, diagnosis, and treatment of VTE in hospitalized patients. Health-care institutions and providers need to take seriously the burden of VTE, improve prophylaxis rates in patients with cancer, and address the need for prophylaxis across the patient continuum.     

Thromboprophylaxis with low‐molecular‐weight heparin in medical patients with cancer

Venous thromboembolism (VTE) is a frequent complication of cancer and cancer treatment and is associated with multiple clinical consequences, including recurrent VTE, bleeding, and an increase in the risk of death. Although the risks associated with VTE have been well recognized in surgical cancer patients, there is also considerable and increasing risk in medical cancer patients. VTE risk factors in medical cancer patients include the type and stage of cancer, major comorbid illnesses, current hospitalization, active chemotherapy, hormone therapy, and antiangiogenic agents. Low‐molecular‐weight heparins (LMWHs) are recommended commonly for the prevention of VTE in hospitalized cancer patients and in higher risk ambulatory cancer patients because of their favorable risk‐to‐benefit profile. These agents have demonstrated effectiveness in both the primary and secondary prevention of VTE in medical cancer patients. Extended‐duration anticoagulant therapy is often recommended to reduce the risk of VTE recurrence in patients with cancer. LMWHs are often used for long‐term prophylaxis because of a reduced need for coagulation monitoring, few major bleeding episodes, and once‐daily dosing. Despite clinical and practical benefits, a substantial proportion of medical cancer patients do not receive VTE prophylaxis. To improve the appropriate prevention and treatment of VTE in cancer patients, guidelines have been published recently by the American Society of Clinical Oncology and the National Comprehensive Cancer Network. Widespread dissemination and application of these guidelines are encouraged to improve the appropriate use of these agents and to improve clinical outcomes in medical cancer patients at risk for VTE and its complications. Cancer 2009. © 2009 American Cancer Society.     

VTE as a quality indicator

Venous thromboembolism (VTE) is still the most common preventable cause of hospital death, with cancer a known significant risk factor for its development. Prophylaxis to prevent VTE in hospitalized surgical and medical patients has been suboptimal, and efforts for improvement have been unsuccessful. Recent practice guidelines on VTE in oncology from the National Comprehensive Cancer Network and American Society of Clinical Oncologists have further highlighted this relationship and could bridge performance measures and outcomes that can affect the strategies for preventing deep venous thrombosis and pulmonary embolism in oncology patients. Hospitals and physicians with poor performance data will have problems with payment from the Centers for Medicare & Medicaid Services and contracting the best rates from other payors. Hospital accreditation from The Joint Commission could be an issue for poorly performing institutions, as could consumer acceptance. The authors believe that specific oncology VTE measures should be developed to help decrease the current poor rates of VTE prophylaxis and also improve hospital and physician compliance.     

Venous thromboembolism in the patient with cancer: focus on burden of disease and benefits of thromboprophylaxis

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in patients with cancer. The risk of VTE varies over the natural history of cancer, with the highest risk occurring during hospitalization and after disease recurrence. Patient and disease characteristics are associated with further increased risk of VTE in this setting. Specific factors include cancer type (eg, pancreatic cancer, brain cancer, lymphoma) and the presence of metastatic disease at the time of diagnosis. VTE is a significant predictor of increased mortality during the first year among all types and stages of cancer, with metastatic disease reported to be the strongest predictor of mortality. VTE is also associated with early death in ambulatory patients with cancer. These data highlight the need for close monitoring, prompt treatment, and appropriate preventive strategies for VTE in patients with cancer. The American Society of Clinical Oncology and the National Comprehensive Cancer Network have issued guidelines regarding the prophylaxis and treatment of patients with cancer. This review summarizes the impact of VTE on patients with cancer, the effects of VTE on clinical outcomes, the importance of thromboprophylaxis in this population, relevant ongoing clinical trials examining the prevention of VTE, and new pharmacologic treatment options.     

Guidelines for the adjuvant treatment of postmenopausal women with endocrine-responsive breast cancer: past, present and future recommendations

Treatment guidelines are useful tools that enable physicians to integrate the latest clinical research into their practices. The large volume of rapidly evolving clinical data in breast cancer has been summarised and incorporated into treatment recommendations by well-known and reliable institutions, including the National Comprehensive Cancer Network, the American Society for Clinical Oncology, the European Society for Medical Oncology and the St. Gallen International Consensus Panel. Adjuvant therapy is a key component of breast cancer treatment, and many of the current consensus guidelines now recognise the important role of the aromatase inhibitors as an alternative to or in sequence after tamoxifen, hitherto the standard adjuvant treatment of choice for receptor-positive women. Data from ongoing trials such as the Breast International Group 1-98 trial and those still in the accrual phase will be forthcoming and will likely result in a further refinement of treatment recommendations over the course of the next few years. Despite the availability of such guidelines, however, there is evidence that adherence to and implementation of treatment recommendations is less than optimal. Further research is needed to determine more effective means of disseminating those clinical recommendations that can have a significant impact on treatment strategies and ultimately improve outcomes in breast cancer.     

抗凝对非小细胞肺癌治疗的机制研究

近年来越来越多的研究开始关注恶性肿瘤患者并发的凝血功能异常,不仅导致血栓形成,还与肿瘤的生长、浸润侵袭、转移等密切相关,从而直接影响预后。肝素作为传统抗凝剂已众所周知,且抗凝药物已出现在恶性肿瘤治疗指南中。美国临床肿瘤学会（ASCO）、欧洲肿瘤内科学会（ESMO）以及美国临床药学学会（ACCP）等机构推荐低分子肝素作为治疗癌症相关血栓的首选,然而预防性应用抗凝药物对控制恶性肿瘤、延长PFS 及OS的机制仍不明确。本文将从多方面介绍抗凝药物对控制恶性肿瘤的复发转移及延长生存的病理生理学机制。      

原发性肝癌放疗的指南推荐解读

基于循证医学证据的治疗指南为临床肿瘤医生提供了较为合理的治疗策略推荐。目前,巴塞罗那临床肝癌(BCLC)、欧洲肝病研究学会及欧洲癌症治疗研究组织(EASL-EORTC)、美国肝病研究学会(AASLD)、美国国家综合癌症网络(NCCN)、亚太地区原发性肝癌专家(APPLE)、韩国肝癌研究组及国立癌症中心(KLCSG-NCC)和中华医学会放射肿瘤治疗学分会(CSTRO)等国内外多个组织均发布了原发性肝癌治疗指南。尽管肝癌放疗在临床上早已广泛开展,但是却未被一部分指南推荐。本文拟对国内外指南中针对放疗的推荐进行解读,探讨肝癌放疗的现状和未来前景。     

中国小细胞肺癌放射治疗临床指南(2020版)

小细胞肺癌(SCLC)是严重威胁患者生命的常见恶性肿瘤之一。为了充分发挥好放疗在SCLC综合治疗中的重要作用,为患者带来生存获益,中华医学会放射肿瘤治疗学分会、中国医师协会放射肿瘤治疗医师分会、中国抗癌协会放射治疗专业委员会和中国临床肿瘤学会肿瘤放疗专家委员会,组织相关专家,在SCLC现有临床研究证据的基础上,结合专家意见,制订了本指南。内容主要包括概述、诊断、不同分期SCLC的放疗和综合治疗原则、放疗技术等方面,以期为我国临床医生和患者提供针对SCLC放疗的循证医学指南,指导临床实践。     

État des lieux du traitement multidisciplinaire du cancer du rectum

In the last 10 years, a number of important European randomized published studies investigated the optimal management of rectal cancer. In order to define an evidence-based approach of the clinical practice based, an international consensus conference was organized in Italy under the endorsement of European Society of Medical Oncology (ESMO), European Society of Surgical Oncology (ESSO) and European Society of Therapeutic Radiation Oncology (ESTRO). The aim of this article is to present highlights of multidisciplinary rectal cancer management and to compare the conclusions of the international conference on ‘Multidisciplinary Rectal Cancer Treatment: looking for an European Consensus’ (EURECA-CC2) with the new National Comprehensive Cancer Network (NCCN) guidelines.     

Japanese Society of Clinical Oncology clinical practice guidelines 2010 for antiemesis in oncology: executive summary

The purpose of this article is to disseminate the standard of antiemetic therapy for Japanese clinical oncologists. On the basis of the Appraisal of Guidelines for Research and Evaluation II instrument, which reflects evidence-based clinical practice guidelines, a working group of the Japanese Society of Clinical Oncology (JSCO) reviewed clinical practice guidelines for antiemesis and performed a systematic review of evidence-based domestic practice guidelines for antiemetic therapy in Japan. In addition, because health-insurance systems in Japan are different from those in other countries, a consensus was reached regarding standard treatments for chemotherapy that induce nausea and vomiting. Current evidence was collected by use of MEDLINE, from materials from meetings of the American Society of Clinical Oncology National Comprehensive Cancer Network, and from European Society of Medical Oncology/Multinational Association of Supportive Care in Cancer guidelines for antiemesis. Initially, 21 clinical questions (CQ) were selected on the basis of CQs from other guidelines. Patients treated with highly emetic agents should receive a serotonin (5-hydroxytryptamine; 5HT₃) receptor antagonist, dexamethasone, and a neurokinin 1 receptor antagonist. For patients with moderate emetic risk, 5HT₃ receptor antagonists and dexamethasone were recommended, whereas for those receiving chemotherapy with low emetic risk dexamethasone only is recommended. Patients receiving high-emetic-risk radiation therapy should also receive a 5HT₃ receptor antagonist. In this paper the 2010 JSCO clinical practice guidelines for antiemesis are presented in English; they reveal high concordance of Japanese medical circumstances with other antiemetic guidelines that are similarly based on evidence.     

结直肠癌NCCN、NICE及ESMO指南的对比分析和解读

结直肠癌的规范化治疗是患者得到正确合理治疗的一个重要保障。国外有很多重要诊断治疗指南指导结直肠癌的规范化治疗,其中影响力最大的指南分别是结直肠癌NCCN指南、ESMO指南和NICE指南。NCCN指南是由美国牵头制定的极具影响力的规范化治疗指南,ESMO指南是由欧洲肿瘤内科学会颁布,NICE指南是由英国国家卫生与临床优化研究所发布的成人结直肠癌诊断和管理临床实践指南。这三个指南在结直肠癌的诊断和治疗上存在着一些共同和不同之处,拟就其中的一些关注点进行分析解读,希望对我国的结直肠癌规范化治疗能起到一些参考借鉴作用。     

中国非小细胞肺癌放射治疗临床指南(2020版)

随着先进技术的迅速发展,放射治疗已进入精确放疗时代,精确放疗显著提高了肿瘤控制效果、降低了不良反应,对非小细胞肺癌(NSCLC)不同期别均发挥着重要作用。近年来,靶向治疗、免疫治疗等新疗法取得了突破性进展,为患者带来了生存获益。中华医学会放射肿瘤治疗学分会、中国医师协会放射肿瘤治疗医师分会、中国抗癌协会放射治疗专业委员会和中国临床肿瘤学会肿瘤放疗专家委员会联合组织相关专家,在NSCLC现有医学证据基础上,结合专家意见制订了《中国非小细胞肺癌放射治疗临床指南(2020版)》,内容主要包括概述、诊断、早中晚期治疗原则、放疗技术和随访等,以期为中国临床医生和患者提供针对放疗的NSCLC循证医学指南,指导临床实践。     

Screening,evaluation, and management of cancer‐related fatigue: Ready for implementation to practice?

Answer questions and earn CME/CNE Evidence regarding cancer‐related fatigue (fatigue) has accumulated sufficiently such that recommendations for screening, evaluation, and/or management have been released recently by 4 leading cancer organizations. These evidence‐based fatigue recommendations are available for clinicians, and some have patient versions; but barriers at the patient, clinician, and system levels hinder dissemination and implementation into practice. The underlying biologic mechanisms for this debilitating symptom have not been elucidated completely, hindering the development of mechanistically driven interventions. However, significant progress has been made toward methods for screening and comprehensively evaluating fatigue and other common symptoms using reliable and valid self‐report measures. Limited data exist to support the use of any pharmacologic agent; however, several nonpharmacologic interventions have been shown to be effective in reducing fatigue in adults. Never before have evidence‐based recommendations for fatigue management been disseminated by 4 premier cancer organizations (the National Comprehensive Cancer, the Oncology Nursing Society, the Canadian Partnership Against Cancer/Canadian Association of Psychosocial Oncology, and the American Society of Clinical Oncology). Clinicians may ask: Are we ready for implementation into practice? The reply: A variety of approaches to screening, evaluation, and management are ready for implementation. To reduce fatigue severity and distress and its impact on functioning, intensified collaborations and close partnerships between clinicians and researchers are needed, with an emphasis on system‐wide efforts to disseminate and implement these evidence‐based recommendations. CA Cancer J Clin 2015;65: 190–211. © 2015 American Cancer Society.     

SEOM clinical guideline of venous thromboembolism (VTE) and cancer (2019)

Clinical and Translational Oncology - In 2011, the Spanish Society of Medical Oncology (SEOM) first published a clinical guideline of venous thromboembolism (VTE) and cancer. This guideline was...     

Granulocyte colony-stimulating factors: finding the right indication

PURPOSE OF REVIEW: Neutropenic complications including febrile neutropenia represent major dose-limiting toxicities of cancer chemotherapy. Recommendations for the use of recombinant myeloid growth factors to reduce the risk of neutropenic complications and sustain dose intensity continue to evolve. RECENT FINDINGS: Several randomized controlled trials and meta-analyses have confirmed that the myeloid growth factors reduce the risk of neutropenic complications and may facilitate delivered dose intensity in patients receiving cancer chemotherapy. Older age and certain comorbidities significantly increase the risk of febrile neutropenia and its consequences. Three new clinical practice guidelines for the use of the myeloid growth factors have been published by major professional oncology organizations including the American Society of Clinical Oncology, the European Organization for Research and Treatment of Cancer and the National Comprehensive Cancer Network. The recommendations and evidence basis for these guidelines are presented here. All three new or updated guidelines recommend prophylactic use of the myeloid growth factors in cancer patients receiving chemotherapy at 20% or greater risk of febrile neutropenia and in those with important variables that increase individual risk of neutropenic complications. SUMMARY: Consistent clinical practice guidelines based on multiple randomized control trials and meta-analyses should further guide the appropriate and cost-effective use of these agents.     

Japanese Society of Medical Oncology Clinical Guidelines: Molecular Testing for Colorectal Cancer Treatment,Third Edition

The Japanese Society of Medical Oncology (JSMO) previously published 2 editions of the clinical guidelines: “Japanese guidelines for testing of KRAS gene mutation in colorectal cancer” in 2008 and “Japanese Society of Medical Oncology Clinical Guidelines: RAS (KRAS/NRAS) mutation testing in colorectal cancer patients” in 2014. These guidelines have contributed to the proper use of KRAS and RAS mutation testing, respectively. Recently, clinical utility, particularly for colorectal cancer (CRC) patients with BRAF V600E mutation or DNA mismatch‐repair (MMR) deficiency, has been established. Therefore, the guideline members decided these genetic alterations should also be involved. The aim of this revision is to properly carry out testing for BRAF V600E mutation and MMR deficiency in addition to RAS mutation. The revised guidelines include the basic requirements for testing for these genetic alterations based on recent scientific evidence. Furthermore, because clinical utility of comprehensive genetic testing using next‐generation sequencing and somatic gene testing of analyzing circulating tumor DNA has increasingly evolved with recent advancements in testing technology, we noted the current situation and prospects for these testing technologies and their clinical implementation in the revised guidelines.     

基因突变状态与肿瘤相关性静脉血栓关系的研究进展

肿瘤相关性静脉血栓栓塞疾病（venous thromboembolic disease，VTE）已成为当下肿瘤患者的第二大死因，诸多学者提出多种血栓风险模型，从而筛选出血栓发生风险可能较高的患者进行药物及物理干预措施，减少肿瘤相关性VTE的发生。随着精准医学的不断发展，现有结论已不能满足医务人员探索肿瘤相关性VTE相关问题的要求。基因检测已经成为肿瘤患者的“基线”检查，检测常见的驱动基因如表皮生长因子受体（epidermal growth factor receptor，EGFR）、间变性淋巴瘤激酶（anaplastic lymphoma kinase，ALK）、v-ros UR2肉瘤病毒癌基因同源物1（v-ros UR2 sarcoma virus oncogene homolog 1，ROS1）和鼠类肉瘤病毒致癌基因（kirsten ras sarcoma，KRAS）等已成为常态且被指南推荐应用于临床，基因突变状态在影响临床预后和治疗决策方面的地位日益凸显。基因突变状态与肿瘤相关性VTE之间是否存在关联，可否根据基因状态筛选出具有较高血栓风险的癌症人群，从而为更好地实施预防管理策略提供理论基础。本文旨在对基因突变状态与肿瘤相关性VTE之间关系的研究进展及其潜在机制进行综述。