How NCCN Guidelines Can Help Young Adults and Older Adolescents With Cancer and the Professionals Who Care for Them

From 1975 to 2009, adolescents and young adults with cancer in the United States had less mortality reduction and survival improvement than either children or older adults with cancer. An NCI Progress Review Group (PRG) convened in 2005 issued a variety of recommendations to overcome the lack of progress, including the establishment of care guidelines. The outcome of 15- to 39-year-olds with cancer in the United States in 2009 was ascertained from the SEER registry, and the first guidelines for this age group, presented by NCCN, were reviewed. For the first time, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adolescent and Young Adult Oncology provide specific algorithm-based care recommendations for 15- to 39-year-olds with cancer, who as an age group have the greatest potential patient-years of life to be saved. A special emphasis on psychosocial evaluation and care is included, commensurate with the unique needs of persons in this age group. Although how widely the NCCN Guidelines will be used remains to be seen, they are timely, comprehensive, responsive to the NCI PRG recommendations, and a valuable resource for medical oncologists, hematologists, gynecologic oncologists, oncologic surgeons, and pediatric oncologists who care for patients between 15 and 40 years of age. A patient version will have mutually beneficial effects for families and professionals.     

Recommendations for Palliative and Hospice Care in NCCN Guidelines for Treatment of Cancer

BackgroundIntegration of specialist palliative care into routine oncologic care improves patients’ quality of life and survival. National Comprehensive Cancer Network (NCCN) cancer treatment guidelines are instrumental in standardizing cancer care, yet it is unclear how palliative and hospice care are integrated in these guidelines. In this study, we examined the frequency of occurrence of “palliative care” and “hospice care” in NCCN guidelines and compared between solid tumor and hematologic malignancy guidelines.Materials and MethodsWe reviewed all 53 updated NCCN Guidelines for Treatment of Cancer. We documented the frequency of occurrence of “palliative care” and “hospice care,” the definitions for these terms if available, and the recommended timing for these services.ResultsWe identified a total of 37 solid tumor and 16 hematologic malignancy guidelines. Palliative care was mentioned in 30 (57%) guidelines (24 solid tumor, 6 hematologic). Palliative care was mentioned more frequently in solid tumor than hematologic guidelines (median, 2 vs. 0; p = .04). Among the guidelines that included palliative care in the treatment recommendation, 25 (83%) only referred to NCCN palliative care guideline. Specialist palliative care referral was specifically mentioned in 5 of 30 (17%) guidelines. Only 14 of 24 (58%) solid tumor guidelines and 2 of 6 (33%) hematologic guidelines recommended palliative care in the front line setting for advanced malignancy. Few guidelines (n = 3/53, 6%) mentioned hospice care.Conclusion“Palliative care” was absent in almost half of NCCN cancer treatment guidelines and was rarely discussed in guidelines for hematologic malignancies. Our findings underscored opportunities to standardize timely palliative care access across NCCN guidelines.Implications for PracticeIntegration of specialist palliative care into routine oncologic care is associated with improved patient outcomes. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology have an important role to standardize palliative care involvement for cancer patients. It is unclear how often palliative care referral is recommended in these guidelines. In this study involving 53 NCCN Guidelines for Treatment of Cancer, the researchers found that palliative care was not mentioned in over 40% of NCCN guidelines and was rarely discussed in guidelines for hematologic malignancies. These findings underscored opportunities to standardize timely palliative care access across NCCN guidelines.     

Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.     

First-line systemic therapy practice patterns and concordance with NCCN guidelines for patients diagnosed with metastatic NSCLC treated at NCCN institutions

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) allow many systemic therapy options for patients with metastatic non-small cell lung cancer (NSCLC). This analysis uses the NCCN NSCLC Outcomes Database to report on first-line therapy practice patterns and concordance with NCCN Guidelines. The analysis was limited to patients diagnosed with metastatic NSCLC between September 2006 and November 2009 at 1 of 8 participating NCCN Member Institutions. Patient characteristics, regimens used, and guidelines concordance were analyzed. Institutional variation and changes in practice over time were also measured. A total of 1717 patients were included in the analysis. Of these, 1375 (80%) were treated with systemic therapy, most often in the form of a carboplatin-based doublet (51%) or carboplatin-based doublet with targeted therapy (17%). Overall, 76% of patients received care that was concordant with NCCN Guidelines. Among patients with good performance status (n = 167), the most common reasons for not receiving first-line therapy were that therapy was not recommended (39%) or death occurred before treatment (33%). The most common reason for receiving nonconcordant drug therapy was the administration of pemetrexed or erlotinib before its incorporation into the NCCN Guidelines for first-line therapy (53%). Most patients in this cohort received care that was concordant with NCCN Guidelines. The NSCLC Outcomes Database is a valuable resource for evaluating practice patterns and concordance with NCCN Guidelines among patients with NSCLC.     

Prostate Cancer, Version 3.2012 Featured Updates to the NCCN Guidelines

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer provide multidisciplinary recommendations for the clinical management of patients with prostate cancer. These NCCN Guidelines Insights highlight notable recent updates. Abiraterone acetate is a first-in-class hormonal agent that represents a new standard of care for patients with metastatic castration-recurrent prostate cancer who have previously received docetaxel (category 1 recommendation). Abiraterone acetate also received category 2B recommendations in the prechemotherapy setting for asymptomatic patients or symptomatic patients who are not candidates for docetaxel. The NCCN Prostate Cancer Panel also added new indications for existing agents, including the option of sipuleucel-T as second-line therapy. In addition, brachytherapy in combination with external beam radiation therapy with or without androgen deprivation therapy is now an alternative for patients with high-risk localized tumors or locally advanced disease.     

Clinical assessment of breast cancer risk based on family history

Family history is a key component of breast cancer risk assessment. Family history provides clues as to the likelihood of a hereditary breast cancer syndrome and the need for a cancer genetics referral and can be used in the setting of a breast cancer risk assessment model to estimate a woman's risk. Appropriate breast cancer screening and risk reduction management plans rely on an accurate assessment of a patient's family history. This article reviews the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer Risk Reduction and provides insight into the application of the guidelines in clinical practice.     

Anal Carcinoma, Version 2.2012: featured updates to the NCCN guidelines

The workup and management of squamous cell anal carcinoma, which represents the most common histologic form of the disease, are addressed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Anal Carcinoma. These NCCN Guidelines Insights provide a summary of major discussion points of the 2012 NCCN Anal Carcinoma Panel meeting. In summary, the panel made 4 significant changes to the 2012 NCCN Guidelines for Anal Carcinoma: 1) local radiation therapy was added as an option for the treatment of patients with metastatic disease; 2) multifield technique is now preferred over anteroposterior-posteroanterior (AP-PA) technique for radiation delivery and the AP-PA technique is no longer recommended as the standard of care; 3) PET/CT should now be considered for radiation therapy planning; and 4) a section on risk reduction was added to the discussion section. In addition, the panel discussed the use of PET/CT for the workup of anal canal cancer and decided to maintain the recommendation that it can be considered in this setting. They also discussed the use of PET/CT for the workup of anal margin cancer and for the assessment of treatment response. They reaffirmed their recommendation that PET/CT is not appropriate in these settings.     

Metastatic breast cancer, version 1.2012: featured updates to the NCCN guidelines

These NCCN Guidelines Insights highlight the important updates/changes specific to the management of metastatic breast cancer in the 2012 version of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer. These changes/updates include the issue of retesting of biomarkers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2) on recurrent disease, new information regarding first-line combination endocrine therapy for metastatic disease, a new section on monitoring of patients with metastatic disease, and new information on endocrine therapy combined with an mTOR inhibitor as a subsequent therapeutic option.     

Hodgkin lymphoma, version 2.2012 featured updates to the NCCN guidelines

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin Lymphoma (HL) include the clinical management of classical HL and lymphocyte-predominant HL (LPHL). Major changes have been incorporated into these guidelines since their inception. In the 2012 NCCN Guidelines for HL, PET scans are not recommended for interim restaging of patients with stage I to II favorable disease. After reevaluating the available evidence on the use of interim PET imaging, the panel recommends the use of diagnostic CT scan of involved sites for interim restaging after completion of chemotherapy for this group of patients. Maintenance rituximab for 2 years is included as an option for patients with stage IB to IIB or stage III to IV LPHL treated with rituximab alone in the first-line setting. Brentuximab vedotin is included as an option for patients with progressive disease or relapsed disease after second-line chemotherapy or high-dose therapy with autologous stem cell rescue.     

Cancer- and chemotherapy-induced anemia

Anemia is prevalent in 30% to 90% of patients with cancer. Anemia can be corrected through either treating the underlying cause or providing supportive care through transfusion with packed red blood cells or administration of erythropoiesis-stimulating agents (ESAs), with or without iron supplementation. Recent studies showing detrimental health effects of ESAs sparked a series of FDA label revisions and a sea change in the perception of these once commonly used agents. In light of this, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer- and Chemotherapy-Induced Anemia underwent substantial revisions this year. The purpose of these NCCN Guidelines is twofold: 1) to operationalize the evaluation and treatment of anemia in adult cancer patients, with an emphasis on those who are receiving concomitant chemotherapy, and 2) to enable patients and clinicians to individualize anemia treatment options based on patient condition.     

Acute myeloid leukemia

Acute myeloid leukemia (AML) remains the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML provide recommendations on the diagnostic evaluation and workup for AML, risk assessment based on cytogenetic and molecular features, treatment options for induction and consolidation therapies for younger and older (age ≥ 65 years) adult patients, and key supportive care considerations.     

Acute lymphoblastic leukemia

The inaugural NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for acute lymphoblastic leukemia (ALL) were developed as a result of meetings convened by a multi-disciplinary panel of experts in 2011. These NCCN Guidelines provide recommendations on the diagnostic evaluation and workup for ALL, risk assessment, risk-stratified treatment approaches based on the Philadelphia chromosome status and age (adults vs. adolescents/young adults), assessment of minimal residual disease, and supportive care considerations. It is recommended that patients be treated at specialized centers with expertise in the management of ALL.     

Level of evidence used in recommendations by the National Comprehensive Cancer Network (NCCN) guidelines beyond Food and Drug Administration approvals

BackgroundA previous analysis of 113 National Comprehensive Cancer Network® (NCCN®) recommendations reported that NCCN frequently recommends beyond Food and Drug Administration (FDA)-approved indications (44 off-label recommendations) and claimed that the evidence for these recommendations was weak.MethodsIn order to determine the strength of the evidence, we carried out an in-depth re-analysis of the 44 off-label recommendations listed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).ResultsOf the 44 off-label recommendations, 14 were later approved by the FDA and/or are supported by randomized controlled trial (RCT) data. In addition, 13 recommendations were either very minor extrapolations from the FDA label (n = 8) or were actually on-label (n = 5). Of the 17 remaining extrapolations, 8 were for mechanism-based agents applied in rare cancers or subsets with few available treatment options (median response rate = 43%), 7 were based on non-RCT data showing significant efficacy (>50% response rates), and 2 were later removed from the NCCN Guidelines because newer therapies with better activity and/or safety became available.ConclusionOff-label drug use is a frequent component of care for patients with cancer in the United States. Our findings indicate that when the NCCN recommends beyond the FDA-approved indications, the strength of the evidence supporting such recommendations is robust, with a significant subset of these drugs later becoming FDA approved or supported by RCT. Recommendations without RCT data are often for mechanism-based drugs with high response rates in rare cancers or subsets without effective therapies.     

Selecting targeted therapies for patients with renal cell carcinoma

Advanced renal cell carcinoma (RCC) is a heterogeneous disease with variable histology, biology, and response to treatment. In the past 5 years, 6 new agents have been approved for the treatment of RCC, and many more are in clinical development. With an ever-increasing number of treatment options, selecting among them for a particular patient can be a daunting task for clinicians. This article describes how treatment choice can be guided by the disease setting and histology, as well as patient characteristics, comorbidities, and preference within the context of available data. Results from clinical trials are combined with practical considerations to make recommendations for first-line and subsequent treatment of patients with clear cell and non-clear cell RCC. These recommendations should supplement the current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for the treatment of advanced RCC.     

Assessing fatigue in persons with cancer: an instrument development and testing study

BACKGROUND: Cancer-related fatigue (CRF) is a highly prevalent, subjective experience of patients with and survivors of cancer. Effective assessment of the attributes of CRF from the patient's perspective is essential. The current study developed a measure of CRF from the patient's perspective and determined its psychometric properties for patients with cancer undergoing chemotherapy. METHODS: Chemotherapy outpatients in a free-standing metropolitan area cancer clinic participated in the current multiphase study. In the instrument development phase, 42 items were generated from a qualitative study with 10 semistructured individual interviews and 6 daily fatigue diaries. These items were revised based on content evaluation by 20 cancer patient content experts. In the instrument analysis phase, the 30 content-validated items were pilot tested by 30 patients with breast carcinoma using cognitive interview techniques. The psychometric properties of the resulting 16-item, 5-point CRF rating scale were tested with 82 patients with breast carcinoma. RESULTS: Principal axis factoring gave a one-factor solution accounting for 59% variance. Coefficient alpha reliability was 0.95 for the final 15-item scale. Convergent validity with the Schwartz Cancer Fatigue Scale was 0.84, concurrent validity with the Geriatric Depression Scale was 0.61, and predictive validity with the Cancer-Related Fatigue Distress Scale was 0.83. CONCLUSIONS: This newly developed instrument to assess the subjective fatigue symptoms of patients with cancer demonstrated effective use of diary and interview methods in instrument development and both cognitive interviewing and traditional psychometric techniques in instrument analysis. The instrument has promising psychometric properties, but confirmatory testing is needed.     

Pan-Asian adapted Clinical Practice Guidelines for the management of patients with metastatic non-small-cell lung cancer: a CSCO–ESMO initiative endorsed by JSMO,KSMO, MOS,SSO and TOS

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of metastatic non-small-cell lung cancer (NSCLC) was published in 2016. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Chinese Society of Clinical Oncology (CSCO) to convene a special guidelines meeting immediately after the Chinese Thoracic Oncology Group Annual Meeting 2018, in Guangzhou, China. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic NSCLC cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic NSCLC representing the oncological societies of China (CSCO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the six participating Asian countries. During the review process, the updated ESMO 2018 Clinical Practice Guidelines for metastatic NSCLC were released and were also considered, during the final stages of the development of the Pan-Asian adapted Clinical Practice Guidelines.     

Breast Cancer Diagnosis and Treatment in Low- and Mid-Resource Settings: the Role of Resource-Stratified Clinical Practice Guidelines

Purpose of Review

One of the most important recent advances in the management of cancer patients have become the development of guidelines. Guidelines are usually evidence-based or international consensus guidelines. Those guidelines may not be applicable worldwide, especially where resources are limited. This prompted initiatives for the development of resource-stratified guidelines so that health care providers and authorities can do the best they can with the resources they have, while working on improving their resources. We will describe the process of development of those guidelines and briefly review recommendations for awareness, screening, diagnosis, and treatment of breast cancer, focusing on countries and special populations with limited resources.

Recent Findings

The World Health Organization (WHO) described three resource scenarios (low-resource, middle-resource, and high-resource scenarios) in order to facilitate the establishment of national cancer control plans. The Breast Health Global Initiative (BHGI), as an initiative group with goals to improve the care of patients with breast cancer in low- and mid-resource settings, identified four levels of resource availability (basic, limited, enhanced, and maximal) with comprehensive sets of recommendations for each. BHGI published resource-stratified breast cancer guidelines starting in 2006, and later on updated them and focused on implementation and health systems. The National Comprehensive Cancer Network (NCCN) initiated a program, building upon the BHGI experience to resource stratify cancer treatment guidelines across multiple cancer types and published NCCN Framework for resource stratification in breast cancer in 2016. Subsequently, the NCCN has published multiple additional resource stratification frameworks that use slightly different definitions of resource level than use by the BHGI. The American Society of Clinical Oncology (ASCO) has also assembled a Guidelines Advisory Group for Resource Stratification for different cancers, and published its first comprehensive resource-stratified guidelines for cancer of the cervix.

Summary

International efforts to improve management and reduce disparities in the outcome of breast cancer patients’ worldwide focus on recommendations for better allocation of available resources in different countries. The WHO, BHGI, NCCN, ASCO, and other international initiatives issued various resource-stratified guidelines (RSG) based on levels of resources in different countries. We shed the light on the development of these guidelines and discuss awareness, prevention of advanced disease at presentation, and management. Future research is needed to update and improve dissemination and implementation of RSG, as well as building infrastructure, reforming of health systems, and better allocating resources.

     

Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting

Before the introduction of the serotonin receptor antagonists (5-HT3 receptor antagonists) in the early 1990s, limited effective options were available to prevent and treat chemotherapy-induced nausea and vomiting (CINV). In 1985, the FDA approved 2 cannabinoid derivatives, dronabinol and nabilone, for the treatment of CINV not effectively treated by other agents. Today, the standard of care for prevention of CINV for highly and moderately emetogenic chemotherapy is a 5-HT3 receptor antagonist, dexamethasone, with or without aprepitant or fosaprepitant. With the approval of safer and more effective agents, cannabinoids are not recommended as first-line treatment for the prevention of CINV and are reserved for patients with breakthrough nausea and vomiting. Because of medical and legal concerns, the use of marijuana is not recommended for management of CINV and is not part of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Antiemesis. Although patients may like to pursue this treatment option in states that have approved the use of marijuana for medical purposes, its use remains legally and therapeutically controversial.     

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.     

解读美国国家综合癌症网络食管癌临床诊疗指南

 美国国家综合癌症网络（National Comprehensive Cancer Network，NCCN）是由美国21个国际顶尖水平的癌症中心组成的协作组织，其主要任务是制定各类肿瘤的临床诊疗指南，目的是改善肿瘤治疗的质量、有效性和效率，以使患者更好地生存。目前，NCCN的肿瘤临床诊疗指南已经广泛应用于临床，并且根据最新的临床研究结果每年更新。关于NCCN食管癌临床诊疗指南目前国内还没有正式版本，也没有在临床推广执行。现对2007年NCCN食管癌临床诊疗指南进行解读，并与中国目前临床实践进行对照。