Cancer-related Fatigue in Lung Cancer: A Research Agenda: An Official American Thoracic Society Research Statement.

Background: Fatigue is the most common symptom among cancer survivors. Cancer-related fatigue (CRF) may occur at any point in the cancer care continuum. Multiple factors contribute to CRF development and severity, including cancer type, treatments, presence of other symptoms, comorbidities, and medication side effects. Clinically, increasing physical activity, enhancing sleep quality, and recognizing sleep disorders are integral to managing CRF. Unfortunately, CRF is infrequently recognized, evaluated, or treated in lung cancer survivors despite more frequent and severe symptoms than in other cancers. Therefore, increased awareness and understanding of CRF are needed to improve health-related quality of life in lung cancer survivors. Objectives: 1) To identify and prioritize knowledge and research gaps and 2) to develop and prioritize research questions to evaluate mechanistic, diagnostic, and therapeutic approaches to CRF among lung cancer survivors. Methods: We convened a multidisciplinary panel to review the available literature on CRF, focusing on the impacts of physical activity, rehabilitation, and sleep disturbances in lung cancer. We used a three-round modified Delphi process to prioritize research questions. Results: This statement identifies knowledge gaps in the 1) detection and diagnostic evaluation of CRF in lung cancer survivors; 2) timing, goals, and implementation of physical activity and rehabilitation; and 3) evaluation and treatment of sleep disturbances and disorders to reduce CRF. Finally, we present the panel's initial 32 research questions and seven final prioritized questions. Conclusions: This statement offers a prioritized research agenda to 1) advance clinical and research efforts and 2) increase awareness of CRF in lung cancer survivors.

Risk factors associated with venous thromboembolism in breast cancer: a narrative review.

PURPOSE: To date, there is no universally acceptable risk assessment tool in clinical practice that accurately estimates the risk of venous thromboembolism (VTE) in patients with breast cancer, despite the large number of published studies. Thus, the aim of this narrative review was to summarize the most relevant risk factors for VTE in these patients. METHODS: We searched Ovid Embase and Ovid MEDLINE, from inception to March 26, 2021, to identify all articles that focused on breast cancer and multiple thromboembolic diseases. We also searched the references section of relevant articles to identify studies. We did not include case reports or case series with small sample size, N < 20. RESULTS: VTE in patients with breast cancer was strongly associated with patient-, tumor-, and non-tumor-related risk factors, such as age, disease stage, central catheter placement, and chemotherapy and tamoxifen use, especially within 2 years of breast cancer diagnosis. CDK inhibitors are emerging factors that may also increase the risk of VTE. CONCLUSIONS: The risk of VTE in patients with breast cancer depends on various patient-, tumor-, and non-tumor-related risk factors. Identifying these risk factors during breast cancer diagnosis and treatment is essential in developing a practical dynamic predictive tool that can help individualize strategies to prevent VTE.

Treatment of Cancer-Associated Venous Thromboembolism with Low-Molecular-Weight Heparin or Direct Oral Anticoagulants: Patient Selection, Controversies, and Caveats.

The treatment of venous thromboembolism (VTE) in patients with cancer is challenging because these patients have increased risks of both recurrent VTE and major bleeding, along with patient-specific and cancer-related factors that influence the approach to treatment. Historically, anticoagulant therapy with low-molecular-weight heparin (LMWH), given for both initial and long-term treatment, has been the preferred approach recommended by practice guidelines. Most recently, the National Comprehensive Cancer Network (NCCN) guidelines indicate that the direct oral anticoagulants (DOACs) apixaban, edoxaban, or rivaroxaban are preferred for patients without gastric or gastroesophageal lesions. DOACs have been associated with an increased risk of major bleeding in patients with gastrointestinal and possibly genitourinary cancers, and DOACs should either not be used (especially in those with intact intraluminal tumors) or be used with caution in patients with these cancers. Fatal or life-threatening bleeding occurs with similar frequency with DOACs or LMWH, and most major bleeding with DOACs can be managed with transfusion and standard measures. The patient's willingness and ability to comply with LMWH injections, and their treatment preference, should also be considered. Patients with cancer who have VTE should be treated with anticoagulation for a minimum of 6 months. Anticoagulation should be continued indefinitely while cancer is active or under treatment or if there are persistent risk factors for recurrent VTE. This article summarizes the evidence from clinical trials of LMWH and DOACs that underpins the NCCN guideline recommendations, addresses several controversies and caveats regarding anticoagulant treatment, and offers evidence-based, practical suggestions on patient selection for treatment with DOACs. IMPLICATIONS FOR PRACTICE: Several randomized trials support the addition of direct oral anticoagulants (DOACs) to the therapeutic armamentarium for cancer-associated venous thromboembolism (VTE). These agents come with unique risks and patient- and cancer-specific variables that must be evaluated during the course of a patient's cancer care. This narrative review discusses findings from clinical trials of low-molecular-weight heparin and DOACs for the treatment of cancer-associated VTE, evidence that supports the recent National Comprehensive Cancer Network guideline recommendations. A personalized approach to treatment is proposed that addresses patient selection for treatment with DOACs, factors that influence efficacy and safety, controversies and caveats, and suggestions for their resolution in clinical practice.

Prospective cohort study of cancer patients diagnosed with incidental venous thromboembolism on routine computed tomography scans.

PURPOSE: Venous thromboembolism (VTE) is a major complication of cancer with recent increasing reports of incidental VTE. The objectives are to estimate the prevalence of incidental VTE in cancer patients on staging CT scans, identify common symptoms, and determine VTE recurrence in a prospective study. PATIENTS AND METHODS: One thousand ninety patients were studied. Adult cancer patients scheduled for outpatient staging CT scans were eligible. VTE cases were followed for 6 months. Fisher's exact test for group comparisons of categorical variables and generalized linear modeling to estimate the prevalence of incidental VTE was used. RESULTS: The mean age was 58 years (range 18-87 years); 50% were male. The prevalence of incidental VTE was 1.8% (CI 1.15-2.87%). Significant symptoms in patients with VTE included fatigue (p = 0.004), stress (p = 0.0195), depression (p = 0.019), poorer quality of life (p = 0.0194), and poorer physical well-being (p = 0.0007). All the patients with VTE had at least one comorbidity (p = 0.03). No patient had recurrence within 6 months. CONCLUSION: The prevalence of incidental VTE on staging CT scans is lower than previously reported. Symptoms were associated with VTE; however, further work is needed to understand whether these are clinically relevant. No VTE recurrences were noted following 6 months.

Cancer-Related Fatigue, Version 2.2015.

Cancer-related fatigue is defined as a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning. It is one of the most common side effects in patients with cancer. Fatigue has been shown to be a consequence of active treatment, but it may also persist into posttreatment periods. Furthermore, difficulties in end-of-life care can be compounded by fatigue. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Related Fatigue provide guidance on screening for fatigue and recommendations for interventions based on the stage of treatment. Interventions may include education and counseling, general strategies for the management of fatigue, and specific nonpharmacologic and pharmacologic interventions. Fatigue is a frequently underreported complication in patients with cancer and, when reported, is responsible for reduced quality of life. Therefore, routine screening to identify fatigue is an important component in improving the quality of life for patients living with cancer.

The biology of cancer-related fatigue: a review of the literature.

PURPOSE: Understanding the etiology of cancer-related fatigue (CRF) is critical to identify targets to develop therapies to reduce CRF burden. The goal of this systematic review was to expand on the initial work by the National Cancer Institute CRF Working Group to understand the state of the science related to the biology of CRF and, specifically, to evaluate studies that examined the relationships between biomarkers and CRF and to develop an etiologic model of CRF to guide researchers on pathways to explore or therapeutic targets to investigate. METHODS: This review was completed by the Multinational Association of Supportive Care in Cancer Fatigue Study Group-Biomarker Working Group. The initial search used three terms (biomarkers, fatigue, cancer), which yielded 11,129 articles. After removing duplicates, 9145 articles remained. Titles were assessed for the keywords "cancer" and "fatigue" resulting in 3811 articles. Articles published before 2010 and those with samples <50 were excluded, leaving 75 articles for full-text review. Of the 75 articles, 28 were further excluded for not investigating the associations of biomarkers and CRF. RESULTS: Of the 47 articles reviewed, 25 were cross-sectional and 22 were longitudinal studies. More than half (about 70 %) were published recently (2010-2013). Almost half (45 %) enrolled breast cancer participants. The majority of studies assessed fatigue using self-report questionnaires, and only two studies used clinical parameters to measure fatigue. CONCLUSIONS: The findings from this review suggest that CRF is linked to immune/inflammatory, metabolic, neuroendocrine, and genetic biomarkers. We also identified gaps in knowledge and made recommendations for future research.

Characteristics of Cancer-Related Fatigue and Concomitant Sleep Disturbance in Cancer Patients.

CONTEXT: Cancer patients often experience cancer-related fatigue (CRF) and sleep disturbances due to cancer and cancer treatment, and symptoms can persist long after treatment. Despite these common occurrences, few studies simultaneously characterize CRF and sleep architecture among cancer patients. OBJECTIVES: The objective was to characterize CRF and the sleep architecture of patients seen in a CRF clinic and sleep clinic at the University of Texas MD Anderson Cancer Center. METHODS: CRF Clinic medical records were retrospectively reviewed from September 1, 2006, to September 30, 2010, for self-reported performance status, fatigue, pain, sleep disturbance, depression, anxiety, and sleepiness (n = 219). Polysomnography results were recorded for those referred for additional sleep consultation (n = 39). RESULTS: Notably, patients often reported fatigue, sleep disturbance, excessive daytime sleepiness, and a majority of patients referred for a sleep consultation were diagnosed with obstructive sleep apnea (n = 33). CONCLUSION: The results highlight the promise of an interdisciplinary collaboration between dedicated a CRF clinic and sleep clinic to conduct effective assessments to identify treatable CRF and sleep disorders.

Telehealth cancer-related fatigue clinic model for cancer survivors: a pilot randomised controlled trial protocol (the T-CRF trial).

INTRODUCTION: Cancer-related fatigue (CRF) is one of the most common and debilitating adverse effects of cancer and its treatment reported by cancer survivors. Physical activity, psychological interventions and management of concurrent symptoms have been shown to be effective in alleviating CRF. This pilot randomised controlled trial (RCT) will determine the feasibility of a telehealth CRF clinic intervention (T-CRF) to implement evidence-based strategies and assess the impact of the intervention on CRF and other clinical factors in comparison to usual care. METHODS AND ANALYSIS: A parallel-arm (intervention vs usual care) pilot RCT will be conducted at the Princess Alexandra Hospital in Queensland, Australia. Sixty cancer survivors aged 18 years and over, who report moderate or severe fatigue on the Brief Fatigue Inventory and meet other study criteria will be recruited. Participants will be randomised (1:1) to receive the T-CRF intervention or usual care (ie, specialist-led care, with a fatigue information booklet). The intervention is a 24-week programme of three telehealth nurse-led consultations and a personalised CRF management plan. The primary objective of this pilot RCT is to determine intervention feasibility, with a secondary objective to determine preliminary clinical efficacy. Feasibility outcomes include the identification of recruitment methods; recruitment rate and uptake; attrition; adherence; fidelity; apathy; and intervention functionality, acceptability and satisfaction. Clinical and resource use outcomes include cancer survivor fatigue, symptom burden, level of physical activity, productivity loss, hospital resource utilisation and carer's fatigue and productivity loss. Descriptive statistics will be used to report on feasibility and process-related elements additional to clinical and resource outcomes. ETHICS AND DISSEMINATION: This trial is prospectively registered (ACTRN12620001334998). The study protocol has been approved by the Metro South Health and Hospital Services Human Research Ethics Committee (MSHHS HREC/2020/QMS/63495). Findings will be disseminated through peer-reviewed publications, national and international conferences and seminars or workshops. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ID: ACTRN12620001334998; Pre-results. Trial Version: Version 1.1. Last updated 10 December 2020.

Survival in cancer patients after out-of-hospital cardiac arrest.

BACKGROUND: The survival of cancer patients who undergo cardiopulmonary resuscitation (CPR) after in-hospital cardiac arrest is poor. The survival of cancer patients who undergo CPR after out-of-hospital cardiac arrest is unknown. We sought to determine survival rates in such patients and to identify phrases in patient charts that might have prompted end-of-life discussions. METHODS: We performed a retrospective review of patients who had CPR in our Emergency Center after out-of-hospital cardiac arrest in 2000-2002, including an in-depth chart review of outpatient clinic visits by these patients in the 3 months preceding cardiac arrest. RESULTS: Of the 41 patients who had CPR in the Emergency Center, 18 (43%) had return of spontaneous circulation and were admitted to the intensive care unit (ICU). Seven patients were subsequently discharged alive to another facility. Only two (4.9%) of the 41 patients in our series were discharged alive to their home. More than half of the study patients had at least one clinic note that mentioned "disease progression" (n = 23), 44% mentioned "poor prognosis" (n = 18), and 27% mentioned "poor response" (n = 11). CONCLUSIONS: Survival of cancer patients who underwent CPR after out-of-hospital cardiac arrest was poor. Medical providers should consider discussing end-of-life issues, including out-of-hospital do-not-resuscitate orders, in the outpatient clinic setting with cancer patients nearing the end of life.

Accuracy of reporting current medications by cancer patients presenting to an emergency center.

BACKGROUND: Due to high coexistence of comorbidity, cancer patients take many medications and are susceptible to negative consequences of polypharmacy. To avoid adverse events during care transitions, patients need to correctly communicate their medications. The emergency center (EC) presents opportunities to assess patients' knowledge of medications and reconcile medication profiles. OBJECTIVE: The purpose was to evaluate the medication knowledge of cancer patients presenting to the EC and to identify factors associated with higher knowledge. DESIGN AND MEASUREMENTS: For the cross-sectional self-administered survey, 254 patients were enrolled and gave name, dose, frequency, route, and indication for medications. Responses were checked for accuracy against outpatient pharmacy dispensing records within or outside M. D. Anderson Cancer Center. Demographic data was obtained from medical records. For each patient, we calculated a patient medication knowledge (PMK-overall) score indicating percentage of correct responses. RESULTS: Median PMK-overall score was 80%. Patients who used a medication aid to fill out the survey were 6.5 times more likely to have a high level of medication knowledge, or PMK-overall score > or = 80%. Predictors of using a medication aid included lower education level, solid tumor, more than five medications, married, and using a medication list at home. CONCLUSIONS: Though our findings may not be generalizable to settings outside the EC, we found cancer patients to have high levels of medication knowledge. Future studies should validate the use of PMK scores to predict medication adherence and other outcomes. Patients should be encouraged to use a medication aid when presenting information to the health care system.

Schistosomiasis and liver disease: Learning from the past to understand the present.

To diagnose schistosomiasis, past medical history review should include recent travel to or from an endemic area, a history of elevated liver enzymes as well as contact with contaminated sources of water or farm animals.

Cancer-related fatigue: the approach and treatment.

As the volume of cancer survivors continues to increase, clinicians are being faced with a growing number of patients with cancer-related fatigue (CRF). Survivors with a variety of malignancies may experience fatigue. Many potential barriers to the identification of this symptom in a cancer survivor may exist, due in part to both the patient and the clinician. Assessment of patients for fatigue is important because it can profoundly effect their daily lives. Many factors contribute to CRF. Hence, the clinician may face a daunting challenge in attempting to alleviate CRF. Treatment modalities for CRF include nonpharmacologic interventions, such as psychosocial interventions, exercise, sleep therapy, and acupuncture. Pharmacologic interventions include stimulants, namely modafinil and methylphenidate. In some patients antidepressants may be beneficial. Clinicians should assess cancer survivors for the presence of fatigue and focus on its treatment in an attempt to ensure that these patients have the best possible symptom control.

Fatigue, symptom burden, and health-related quality of life in patients with myelodysplastic syndrome, aplastic anemia, and paroxysmal nocturnal hemoglobinuria.

BACKGROUND: Fatigue is distressing and affects quality of life (QoL) among patients with myelodysplastic syndrome (MDS), aplastic anemia (AA), and paroxysmal nocturnal hemoglobinuria (PNH). Limited data exist on the impact of fatigue, QoL, and related symptoms in these patients. OBJECTIVE: Prospectively assess fatigue (functional assessment of cancer therapy-anemia [FACT-An]); QoL (FACT-An subscales); pain (brief pain inventory); and depression, anxiety, and stress (depression anxiety stress scale-21) and strategies used to manage these symptoms in patients with MDS, AA, and PNH. METHODS: Surveys were administered via the AA and MDS International Foundation website and database from October 2014 through April 2015 in a cross-sectional study. Results were summarized using descriptive statistics. RESULTS: Of 303 patients, 145 (48%) had MDS, 84 (28%) had AA, and 74 (24%) had PNH; 31 (10%) had >1 diagnosis. The mean age was 57 years, 200 (66%) were female, and 195 (92%) were white. The mean fatigue scores were 25 (range 1-52) for the whole cohort, 28 for AA, 25 for MDS, and 24 for PNH (P = 0.117); these are all considered severe level. The mean QoL score was 68 (range 10-104) for the whole cohort, 67 for AA, 69 for MDS, and 67 for PNH (P = 0.821). The ranges for stress were normal; pain and depression, mild; and anxiety, moderate. The most common management strategies perceived as helpful for fatigue in the past month were preserving energy, physical activity, and naps. CONCLUSIONS: Many patients with MDS, AA, and PNH report severe fatigue. The helpfulness of fatigue management strategies may impact patients' continued use; whether these strategies are beneficial and decrease fatigue levels needs more study.

Cancer-Related Fatigue in Cancer Survivorship.

Cancer-related fatigue (CRF) significantly interferes with usual functioning because of the distressing sense of physical, emotional, and cognitive exhaustion. Assessment of CRF is important and should be performed during the initial cancer diagnosis, throughout cancer treatment, and after treatment using a fatigue scoring scale (mild-severe). The general approach to CRF management applies to cancer survivors at all fatigue levels and includes education, counseling, and other strategies. Nonpharmacologic interventions include psychosocial interventions, exercise, yoga, physically based therapy, dietary management, and sleep therapy. Pharmacologic interventions include psychostimulants. Antidepressants may also benefit when CRF is accompanied by depression.

Update of Targeted Therapy-Induced Hypertension: Basics for Non-Oncology Providers.

Over the past several years, cancer treatments have expanded from usual chemotherapy standards with introduction of newer targeted therapies. As with chemotherapy, the targeted therapies also have unique side effects affecting various organ systems producing toxicities, such as cardiac and renal. This manuscript focuses on hypertension induced by vascular endothelial growth factor (VEGF) inhibitors and tyrosine kinase inhibitors (TKI). Hypertension due to these cancer therapies is important because these agents are now frequently used in common cancers. In addition, patients with cancer may not be treated in a comprehensive cancer center with experts available to manage the cancer and other side effects either from the malignancy or treatment of the malignancy. Especially in rural areas, patients are often managed or co-managed by a primary care provider with input from an oncologist that may not be nearby. Our aim is to provide an overview of the latest Federal Drug Administration (FDA) approved VEGF inhibitors and TKI's causing hypertension so that others managing patients on these treatments may easily recognize hypertension attributable to these agents and feel comfortable and confident in providing appropriate management and treatment of this side effect. This update includes characteristics, such as mechanism of action, metabolism and route of administration, and management and treatment of hypertension with aspects such as the timing, duration and monitoring of these agents. In addition, an algorithm for monitoring and treating hypertension before, during and after treatment with these therapies is included. It is imperative for patients to have hypertension promptly treated to prevent complications so they may continue with these agents with the least interruption or discontinuation of treatment, ensuring the best benefit available in their cancer trajectory.

Hypertension in cancer patients seeking acute care: an opportunity to intervene.

BACKGROUND: The objectives were to describe clinical factors associated with hypertension or increased blood pressure in cancer patients seeking acute care, to describe the outcomes of these patients related to hypertension or increased blood pressure, and to determine whether these patients receive appropriate treatment and follow-up instructions. METHODS: We retrospectively reviewed the records of patients admitted to the emergency center at The University of Texas M. D. Anderson Cancer Center from May 1, 2001 through August 5, 2001. Patients were included in our analysis if their emergency center triage blood pressure was 140 mm Hg or greater, systolic, or 90 mm Hg or greater, diastolic and remained in this range at emergency center discharge or if they were treated with an antihypertensive medication in the emergency center. Descriptive statistics, chi and Student t tests were utilized in the analysis. RESULTS: Records of 143 patients were analyzed. The mean baseline, emergency center triage, and emergency center discharge blood pressure were 140/78 mm Hg, 159/84 mm Hg, and 153/81 mm Hg, respectively. Of 77 patients (54%) with controlled neoplastic disease, 54 (38%) were not receiving cancer treatment. Forty-one (30%) were admitted to the hospital and 27 (19%) returned to the emergency center with hypertension or possible hypertension-related events within 6 months. Discharge instructions regarding hypertension follow-up were documented in 9% of records. CONCLUSIONS: Most patients (54%) had controlled cancer; more than one third were not receiving cancer treatment and had good performance status. Such patients would be likely to benefit from management of hypertension. In addition, only 9% of hypertensive patients were given hypertensive specific discharge instructions. The emergency center may provide another opportunity to alert patients of abnormal blood pressures and assist in arranging follow-up.

Ongoing Screening and Treatment to Potentially Reduce Tyrosine Kinase Inhibitor-Related Fatigue in Renal Cell Carcinoma.

CONTEXT: Renal cell carcinoma (RCC) represents 1% to 4% of adult malignancies, and approximately 33% of patients with RCC present with metastatic disease and have a poor prognosis. Better understanding of RCC tumor biology has led to the development of several molecularly targeted agents, such as tyrosine kinase inhibitors (TKIs), to manage advanced disease. Although evolving data suggest these drugs may be beneficial in RCC, they are associated with significant toxicities. Cancer-related fatigue (CRF) is one of the most common toxicities associated with the TKIs used in RCC. OBJECTIVES: To review the incidence, pathophysiology, and management of CRF in patients with RCC who are undergoing targeted therapy with TKIs. METHODS: A comprehensive database search was performed using PubMed, Ovid, Embase, and MEDLINE. References of all cited articles also were reviewed. Data from articles published between 1975 and June 2014 were considered. A narrative review regarding the incidence, pathophysiology, and management of CRF in patients with RCC undergoing targeted therapy with TKIs was performed. RESULTS: CRF is one of the most common TKI toxicities in patients with metastatic RCC and often is the dose-limiting toxicity. Management of TKI-related CRF can be difficult and may necessitate various nonpharmacologic and pharmacologic interventions. CONCLUSION: TKI-related CRF in patients with RCC is a highly distressing complication of cancer therapy. CRF can substantially influence drug compliance, the ability to maximally treat, and quality of life. It is important to recognize this common, yet frequently underdiagnosed complication and initiate appropriate management strategies, to increase the likelihood for optimal outcomes.