The Impact of Immunotherapy on Sleep and Circadian Rhythms in Patients with Cancer.

Immunotherapy has revolutionized treatments for both early and advanced cancers, and as their role evolves, their impact on sleep and circadian rhythms continues to unfold. The recognition, evaluation, and treatment of sleep and circadian rhythm disturbance leads to improved symptom management, quality of life and treatment outcomes. An intricate complex relationship exists in the microenvironment with immunity, sleep and the tumor, and these may further vary based on the cancer, addition of standard chemotherapy, and pre-existing patient factors. Sleep and circadian rhythms may offer tools to better utilize immunotherapy in the care of cancer patients, leading to better treatment outcome, reduced symptom burden, and increased quality of life.

A Qualitative Study of Knowledge of Metabolic Syndrome, Attitudes about Lifestyle Modifications, and Preferences for Lifestyle Interventions among Patients with Cancer and Metabolic Syndrome.

Background: Nearly 60% of patients with cancer have metabolic syndrome, which increases the risk of mortality, but there is no clear guidance for oncology providers about its management. Here, we report on the qualitative component of a larger mixed methods study that aimed to understand cancer patients' knowledge, attitudes, and preferences regarding metabolic syndrome. Methods: Adult cancer patients with metabolic syndrome were recruited during 2022-2023 in the MD Anderson General Internal Medicine clinic and participated in semistructured interviews focused on metabolic syndrome and lifestyle interventions. Interviews were audio-recorded and transcribed verbatim. Participants' demographic information was collected. Interviews were analyzed using hybrid thematic analysis and constant comparison involving deductive and inductive coding. Researcher triangulation and debriefing were used to ensure rigor. Results: There were 19 participants, 12 female and 12 White. Eighteen had solid tumors, including gynecologic (n = 5), genitourinary (n = 4), colorectal (n = 3), and breast (n = 2). Analysis yielded 5 major themes: 1) patients' understanding of metabolic syndrome; 2) attitudes about and approaches to managing metabolic syndrome; 3) capacity and limitations regarding managing metabolic syndrome; 4) patient-led care; and 5) tailored intervention plans. Participants had limited knowledge of metabolic syndrome and its cancer-related consequences; most desired additional education. Many participants reported that their cancer or diabetes diagnosis motivated them to prioritize lifestyle Modifications. Participants expressed strong interest in personalized care plans focused on healthy lifestyle rather than simply weight loss. As part of their tailored intervention plans, participants desired clear communication with their medical team, coordination of care among team members, and collaboration with providers about treatment decisions. Conclusion: Cancer patients with metabolic syndrome want collaborative, patient-centered care. Shared decision-making based on respect for patients' distinctive needs and preferences is an essential component of the development of such collaborative care. Tailored interventions, practical implementation strategies, and personalized care plans are needed for cancer patients with metabolic syndrome. The study findings contribute to filling the gap in knowledge regarding clear guidance for oncology providers on managing metabolic syndrome and will inform the development of future lifestyle interventions for patients diagnosed with metabolic syndrome.

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.

A central role for apathy in the effectiveness of interventions for cancer-related fatigue.

OBJECTIVE: Cancer-related fatigue (CRF) affects a substantial number of cancer patients and survivors. Recommendations for CRF treatments are largely based on results of randomized controlled trials. The interpretability of such results is limited to patients eligible and willing to participate in these trials. We aimed to address this limitation in a retrospective study of patients seen at a CRF clinic in a comprehensive cancer center. The objectives were to (a) determine the effectiveness of clinician-initiated interventions for CRF and identify their mediators and (b) describe the frequency and effectiveness of patient-initiated physical activity (PA) behavior for alleviating CRF and identify determinants of this PA. METHODS: Data (patient-reported somatic and mood symptoms; clinical data; clinician-documented changes in medication and behavior) from n = 213 patients collected as part of the clinic's standard of care at initial clinical consult and follow-up 4 to 11 weeks later were included. Effects of clinician-initiated interventions and patient-initiated PA on change in fatigue were analyzed using linear models. RESULTS: Of all clinician-initiated interventions, only psychostimulant start was recorded frequent enough for further investigation and was associated with reduced fatigue; this association was mediated by a reduction in apathy. PA was also associated with reduced fatigue severity. PA initiation/increase after consult was associated with lower apathy at consult. CONCLUSIONS: These results demonstrate a major role for patient apathy in the effectiveness and initiation of CRF-targeting interventions. Behavioral therapies focusing on reduction in apathy should be considered as initial treatment of CRF in those with substantial apathy.

An effort expenditure perspective on cancer-related fatigue.

While fatigue is the most common and debilitating side effect of cancer and cancer treatment it is still poorly understood, partly because it is usually characterized by patient-reported outcomes. As patient-reports are inherently subjective, behavioral correlates of the symptom of fatigue are needed to increase our understanding of the symptom. We focused on motivational effort expenditure as a crucial behavior in cancer-related fatigue, using a validated computerized task contrasting high effort/high reward and low effort/low reward choices under different probabilities of success. Effort expenditure-choices were analyzed in 47 cancer patients differing by their status; current evidence for disease (n = 17) or post-treatment survivors with no evidence for disease (n = 30). In addition, patient-reported fatigue, negative and positive affect, and biomarkers of inflammation were assessed. Patient-reported general and motivational fatigue, negative affect, and plasma concentrations of pro-inflammatory biomarkers were related to higher effort expenditure while positive affect was associated with lower effort expenditure. As all four measures interacted with patient status, exploratory models were computed for patients and survivors separately. These analyses indicated that the effects of fatigue and negative affect were predominantly seen in survivors. In patients still under or shortly post treatment, general fatigue, but not motivational fatigue, was associated with lower effort expenditure but only in the most favorable reward condition. Negative affect did not have an effect. Thus, the effects observed seemed primarily driven by cancer survivors in whom both fatigue and negative affect were associated with higher effort expenditure. These findings are tentatively interpreted to suggest that a tendency to invest more effort despite feelings of fatigue is a vulnerability for developing chronic fatigue. Inflammation and negative affect might contribute to fatigue in some survivors through this effort investment pathway.

Cancer-related fatigue presenting with excessive daytime sleepiness.

Cancer-related fatigue is a common symptom in cancer patients which commonly occurs in relation to sleep disturbance. We report a case of a 35-year-old breast cancer survivor, in whom polysomnography and multiple sleep latency testing were utilized to objectively quantify the contribution of excessive daytime sleepiness to the patient's cancer-related fatigue.

High-Dose Asian Ginseng (Panax Ginseng) for Cancer-Related Fatigue: A Preliminary Report.

INTRODUCTION AND OBJECTIVE: Cancer-related fatigue (CRF) is the most common and severe symptom in patients with cancer. The number and efficacy of available treatments for CRF are limited. The objective of this preliminary study was to assess the safety of high-dose Panax ginseng (PG) for CRF. METHODS: In this prospective, open-label study, 30 patients with CRF (≥4/10) received high-dose PG at 800 mg orally daily for 29 days. Frequency and type of side effects were determined by the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. Scores on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale, Edmonton Symptom Assessment System (ESAS), and Hospital Anxiety and Depression Scale (HADS) were assessed at baseline, day 15, and day 29. Global Symptom Evaluation (GSE) was assessed at day 29. RESULTS: Of the 30 patients enrolled, 24 (80%) were evaluable. The median age was 58 years; 50% were females, and 84% were white. No severe (≥grade 3) adverse events related to the study drug were reported. Of the 24 evaluable patients, 21 (87%) had an improved (by ≥3 points) FACIT-F score by day 15. The mean ESAS score (standard deviation) for well-being improved from 4.67 (2.04) to 3.50 (2.34) (P = .01374), and mean score for appetite improved from 4.29 (2.79) to 2.96 (2.46) (P = .0097). GSE score of PG for fatigue was ≥3 in 15/24 patients (63%) with median improvement of 5. CONCLUSION: PG is safe and improves CRF fatigue as well as overall quality of life, appetite, and sleep at night. Randomized controlled trials of PG for CRF are justified.

A randomized, double-blind, 2-period, placebo-controlled crossover trial of a sustained-release methylphenidate in the treatment of fatigue in cancer patients.

PURPOSE: This study assessed the efficacy of methylphenidate versus placebo for cancer-related fatigue reduction. Other objectives were to analyze cytokine levels and to determine the effects of methylphenidate on other symptoms, cognitive function, work yield, and patients' perceptions and preferences. METHODS: Patients were randomly assigned (1:1) to receive methylphenidate-placebo or placebo-methylphenidate for 4 weeks. Patients crossed over after 2 weeks. Wilcoxon signed rank tests and McNemar tests were used to assess continuous and categorical variables. The primary efficacy endpoint was change in the level of worst fatigue on the Brief Fatigue Inventory (BFI) at the end of each 2-week period. RESULTS: The mean baseline BFI score was moderate (5.7). Methylphenidate treatment did not affect patients' worst level of fatigue or other symptoms. Results from the Wechsler Adult Intelligence Scale Digit Symbol Test and the Hopkins Verbal Learning Test with BFI interference questions and BFI activity questions showed significant improvement in the methylphenidate-treated patients' verbal learning, memory, visual perception, analysis, and scanning speed. Patients treated with methylphenidate missed significantly fewer work hours owing to health reasons and worked significantly more hours. After 4 weeks, 64% of patients reported that methylphenidate improved their cancer-related fatigue, and 58% wanted to continue treatment. Significant difference in interleukin 6R (positive), interleukin 10 (negative), and tumor necrosis factor α (positive) was noted between the methylphenidate and the placebo group. CONCLUSIONS: Low-dose methylphenidate did not improve cancer-related fatigue. Patients taking methylphenidate had better cognition and were able to work more hours. Patients tolerated methylphenidate well, and the majority felt better and wanted to continue treatment.

Outcomes of a cancer-related fatigue clinic in a comprehensive cancer center.

Cancer-related fatigue (CRF) is a significant issue for cancer patients and frequently precipitates increased stress and anxiety for patients and caregivers alike. CRF may present well after the initial phase of cancer diagnosis and treatment, regardless of whether the cancer is in remission, widely metastatic, or somewhere in between. Determining whether the etiology of fatigue is potentially reversible and whether it is an effect of treatment or another unrelated cause is often perplexing. Because of the significant impact of CRF on patients at our institution, we organized a CRF clinic and began evaluating patients for fatigue in 1998. Our goal has been to initiate a more focused and, at the same time, more comprehensive effort in educating, evaluating, and treating CRF. The purpose of this report was to present a retrospective review of patients treated in our CRF clinic between 1998 and 2005, to examine the outcomes of our patients, and to briefly describe some of the challenges encountered in treating these patients. This information may help reassess and improve approaches in addressing CRF and subsequently improve fatigue in these patients.

Oral moxifloxacin for outpatient treatment of low-risk, febrile neutropenic patients.

OBJECTIVES: Low-risk febrile neutropenic patients can be treated without hospitalization with oral antibiotic regimens. Combination regimens are recommended. Our objective was to evaluate the feasibility of quinolone monotherapy (moxifloxacin) in this setting. METHODS: In this open-label pilot study, eligible low-risk febrile neutropenic patients identified using pre-defined criteria (MASCC Risk Index) received oral moxifloxacin (400 mg) in our emergency center and were discharged after a 4-8 h observation period to ensure clinical stability. They subsequently received moxifloxacin 400 mg daily as outpatients. Success of monotherapy, outpatient management, the development of adverse events, and major medical complications were recorded. RESULTS: The trial was closed without reaching the target sample size of 40 patients due to slow accrual. Twenty-one evaluable patients were enrolled, with sarcoma and breast cancer being the predominant underlying neoplasms. Most patients (76%) were severely neutropenic (

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 and its risk factors in cancer patients who seek emergency care.

Cancer patients visiting the emergency center (EC) are seldom assessed or treated for severe fatigue, a common symptom in sick patients due to acute medical conditions arising from cancer and cancer treatment. We provide a profile of cancer-related fatigue within the EC setting. Using a single-item screening tool derived from the Brief Fatigue Inventory, 928 patients (636 with solid tumors, 292 with hematological malignancies) triaged in the EC of a tertiary cancer center rated their fatigue at its worst in the last 24 hours. Patient demographic and clinical factors were retrospectively reviewed from medical records. The chief complaints of patients seeking emergency care included fever, pain, gastrointestinal symptoms, dyspnea, fatigue, and bleeding. More than half (54%) reported severe fatigue (seven or higher on a 0-10 scale) upon EC admission. Moderate to severe pain was highly associated with fatigue severity. Patients with severe fatigue were more likely to be unstable and unable to go home after EC care. In multivariate logistic regression analysis for severe fatigue, the significant risk factors for patients with solid tumors included dizziness (odds ratio [OR]=3.59), severe pain (OR=1.98), poor performance status (OR=1.81), and being female (OR=1.56). Dyspnea was significantly associated with severe fatigue in patients with hematological malignancies (OR=4.74). Although fatigue was not the major reason for an ER visit, single-item fatigue-severity screening demonstrated highly prevalent severe fatigue in sicker EC cancer patients and in those patients who also suffered from other symptoms.

Once daily, oral, outpatient quinolone monotherapy for low-risk cancer patients with fever and neutropenia: a pilot study of 40 patients based on validated risk-prediction rules.

BACKGROUND: The objective of this study was to assess the feasibility of empiric, oral, outpatient quinolone monotherapy in 40 adult patients with fever and neutropenia who were at low risk for serious medical complications. METHODS: Patients with breast cancer or sarcoma who presented with fever and neutropenia and were identified as low risk received empiric, oral, quinolone monotherapy (gatifloxacin at a dose of 400 mg once daily). Patients who had a significant source/focus of infection on presentation were excluded. After an initial observation period of 4 to 8 hours in the emergency center, the remainder of their management was ambulatory. Patients were evaluated for response to therapy, development of complications and/or the need for hospital admission, and drug-related adverse events. RESULTS: Three of 43 patients studied were ineligible medically because of the presence of Common Toxicity Criteria (version 3.0) Grade>2 mucositis. Of the 40 eligible patients, 38 patients (95%) responded to gatifloxacin monotherapy, although 1 patient requested hospital admission (92% response for ambulatory management). The mean duration of therapy was 7 days, and the median number of days from enrollment to defervescence was 4 days. There were no serious medical complications, no drug-related adverse events, and no deaths on study or during 30 days of follow-up. CONCLUSIONS: The results from this study indicated that outpatient quinolone monotherapy in low-risk febrile neutropenic patients is safe, effective, and well received. These conclusions need to be validated in a randomized trial.

Outcomes of treatment pathways in outpatient treatment of low risk febrile neutropenic cancer patients.

BACKGROUND: We treated low-risk febrile neutropenic cancer patients utilizing two standard outpatient antibiotic pathways: oral ampicillin/clavulanate (500 mg) and ciprofloxacin (500 mg) or intravenous ceftazidime (2 g) and clindamycin (600 mg) every 8 h. The objectives were to determine the success of outpatient treatment of low-risk febrile neutropenia, to identify factors predicting outpatient failure, and to determine mortality related to the febrile episode. METHODS: Eligibility criteria included solid tumor diagnosis, stable vital signs, temperature > or =38.0 degrees C, absolute neutrophil count (ANC) of <1000/ml, patient compliance, no significant organ dysfunction, ability to tolerate oral medication and fluids for oral pathway, residence within 30 miles of the institution, 24-h caregiver, and telephone and transportation access. RESULTS: There were 257 febrile episodes in 191 patients meeting the criteria. Patients were treated during March 1998 through February 2000. Median age was 48 (range, 17-77) years, and 60% (n = 153) had an entry ANC of <100/ml; 205 (80%) febrile episodes successfully responded to outpatient treatment, and 52 (20%) were hospitalized. Logistic regression analysis showed the following were related to hospitalization: mucositis >grade 2 (p < 0.002); Zubrod performance status > or =2 (p = 0.029); ANC <100/ml (p = 0.039), and age > or =70 years (p = 0.048). CONCLUSIONS: Outpatient treatment of low-risk febrile neutropenic cancer patients utilizing standard treatment pathways is associated with minimal morbidity and mortality and should be considered an acceptable standard of care with appropriate infrastructure available to provide strict and careful follow-up while on treatment. Certain factors are associated with higher risk of hospitalization and should be further examined in eligible patients with low-risk febrile neutropenia.

The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis.

BACKGROUND: Mucositis is a common but poorly studied problem among patients with solid tumors. The authors examined the clinical and economic outcomes of oral and gastrointestinal (GI) mucositis among patients receiving myelosuppressive chemotherapy. METHODS: A retrospective, random sample of 599 patients who developed chemotherapy-induced myelosuppression was followed for development of oral or GI mucositis and for development of subsequent episodes of bleeding or infection. Multilevel regression models of the risk of bleeding and infection were fit with chemotherapy cycles nested within patients. RESULTS: Mucositis developed during 37% of 1236 cycles of chemotherapy. Episodes of bleeding were significantly more common during cycles with GI mucositis than during cycles without GI mucositis (13% vs. 8%; P = 0.04). Episodes of infection were significantly more common during cycles with mucositis (especially GI mucositis) than during cycles without mucositis (73% vs. 36%; P < 0.0001). The mean durations of hospitalization were 4 days, 6 days, and 12 days during cycles with no mucositis, oral mucositis, and GI mucositis, respectively. After accounting for the depth and duration of myelosuppression and for other predictive factors, GI mucositis was associated with both bleeding (odds ratio [OR], 2.0; P = 0.01) and infection (OR, 2.24; P < 0.0001), whereas oral mucositis was associated with infection only (OR, 2.4; P < 0.0001). CONCLUSIONS: Mucositis was clinically and economically significant among patients with solid tumors who were receiving myelosuppressive chemotherapy. New preventive and therapeutic agents are needed.

Treatment for cancer-related fatigue: an update.

Cancer-related fatigue is now a recognized phenomenon with an established diagnosis. Fatigue is the most common symptom experienced by cancer patients and in many cases, the challenge of alleviating its severity is daunting for the clinician. Occasionally, the clinician may be fortunate and discover a reversible cause of fatigue for which there is a readily available treatment. Most of the time, however, the etiology of cancer-related fatigue is multifactorial or treatment-related with unknown pathophysiologic abnormalities and the clinician must resort to a variety of modalities to attempt to relieve the fatigue. Research of cancer-related fatigue treatment is in its infancy and future clinical trials examining the effects of various pharmacologic and nonpharmacologic therapies for cancer-related fatigue are needed. The development of effective therapies for the treatment of cancer-related fatigue could profoundly affect the lives of many cancer patients.

Perioperative issues in patients with cancer.

The perioperative care of patients with cancer can be an exciting challenge. The physician must consider many factors, including the cancer diagnosis, the extent of disease, treatment received, the presence of comorbid conditions, and the patient's prognosis and must understand the impact of these factors on the planned surgical procedure. In this setting, the physician has the opportunity to perform an essential role in the perioperative management of patients with cancer.

A cancer-related fatigue clinic: opportunities and challenges.

Cancer-related fatigue (CRF) is the most prevalent symptom of cancer, occurring in 60% to 90% of patients and surpassing pain in frequency. CRF may increase patients' anxieties and hamper their quality of life. We developed a CRF clinic in 1998 because we believed there needed to be a more focused effort on the education, evaluation, and treatment of CRF for our patients. Since then, we have gained clinical insights into the planning, development, and evolution of this endeavor. Our objective is to share our experiences and provide preliminary analysis of the first 123 patients evaluated in this clinic.

Research into fatigue.

Evaluation and treatment of fatigue in cancer patients requires a multidisciplinary approach because it has many possible etiologies and several contributing factors. A comprehensive approach is required, especially for patients with moderate to severe fatigue, so that all possible contributing factors can be determined and an appropriate treatment plan can be created. New agents for the management of fatigue need to be evaluated in large, controlled, clinical trials. The short- and long-term effects of an exercise program on the fatigue levels and overall physical performance of cancer patients should be assessed in new studies. Clearly, much more research is needed not only to identify factors responsible for the fatigue but also to develop effective interventions for cancer-related fatigue.