Melatonin Supplementation for Cancer-Related Fatigue in Patients With Early Stage Breast Cancer Receiving Radiotherapy: A Double-Blind Placebo-Controlled Trial.

BACKGROUND: Fatigue is common in patients undergoing radiotherapy (RT) and can significantly impact quality of life. Melatonin, a safe inexpensive natural supplement, may improve symptoms and attenuate the side effects of RT. The purpose of this randomized double-blind placebo-controlled phase III trial was to assess the effects of melatonin for preventing fatigue and other symptoms in patients with breast cancer undergoing RT. METHODS: Female early stage or Ductal carcinoma in situ patients with breast cancer ≥18 years of age with Eastern Cooperative Oncology Group (ECOG) performance status <3, hemoglobin ≥9 g/dL, planned for outpatient RT treatment with curative intent, were randomized 1:1 to melatonin 20 mg or placebo, orally, starting the night before RT initiation until 2 weeks post-RT. Randomization was stratified according to treatment duration (<3 weeks, ≥3 weeks) and prior chemotherapy. The primary endpoint was the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue scale), and secondary endpoints were FACIT-F subscales, Edmonton Symptom Assessment Scale (ESAS), and Patient-Reported Outcomes Measurement Information System (PROMIS) scores obtained at baseline, and 2 and 8 weeks post-RT. A 2-sided ANOVA F-test at a 4.5% significance level for the primary endpoint was used. Secondary analyses were reported using an F-test at a 5% significance level. The goal was to recruit approximately 140 patients with interim analysis planned mid-recruitment. RESULTS: Eighty-five patients were screened for eligibility; 79 patients were randomized: 40 to melatonin and 39 to placebo; 78 patients were treated and included in the interim analysis at the mid-recruitment point. Baseline patient characteristics of age, race, and ECOG performance status were similar in both arms. The treatment effect was studied using a longitudinal mixed effects model with the effect of treatment over time (treatment × time) as the primary outcome parameter. The treatment × time for FACIT-Fatigue did not demonstrate statistical significance (P-value .83) in the melatonin group compared to placebo. In addition, secondary analyses of FACIT physical, social, emotional, and functional well-being scores did not demonstrate statistical significance (P-values of .35, .06, .62, and .71, respectively). Total PROMIS scores, collected as secondary outcome reported by patients, did not demonstrate statistically significant change over time either (P-value is .34). The other secondary scale, ESAS, was analyzed for each individual item and found to be nonsignificant, anxiety (P = .56), well-being (.82), drowsiness (.83), lack of appetite (.35), nausea (.79), pain (.50), shortness of breath (.77), sleep (.45), and tiredness (.56). Depression was the only item demonstrating statistical significance with a decrease of 0.01 unit in the placebo group, a change not considered clinically significant. Melatonin was well-tolerated with no grade 3 or 4 adverse events reported. The most common side effects were headache, somnolence, and abdominal pain. No patients died while participating in this study. Two patients died within a year of study completion from breast cancer recurrence. Sixteen patients withdrew prior to study completion for various reasons including adverse events, hospitalizations unrelated to study drug, RT discontinuation, and COVID-19 precautions. CONCLUSIONS: In this double-blind placebo-controlled phase III trial, melatonin did not prevent or significantly improve fatigue and other symptoms in patients with early stage breast cancer undergoing RT. The analysis, showing little evidence of an effect, at mid-recruitment, assured early termination of the trial.

Anamorelin for the Treatment of Cancer Anorexia-Cachexia Syndrome.

PURPOSE OF REVIEW: The following review will highlight the development of anamorelin to treat cancer anorexia-cachexia syndrome (CACS) including the potential benefits, limitations, and future directions. RECENT FINDINGS: Ghrelin, a 28-amino acid peptide hormone, is secreted by the stomach mucosa and regulates appetite, promotes lipogenesis, increases body weight, improves gastric motility, reduces catabolic wasting and inflammation. Several randomized, double-blind, placebo-controlled clinical trials evaluating anamorelin, a ghrelin agonist, for the treatment of CACS have reported improvement in appetite and body composition including both lean body and fat mass; however, most studies noted no improvement in physical function as assessed by measuring non-dominant hand-grip strength. Common adverse effects of anamorelin include the development of diabetes mellitus, hyperglycemia, and less frequently, hepatic abnormalities and cardiovascular events including conduction abnormalities, hypertension, and ischemic cardiomyopathy. Anamorelin has the potential to stimulate appetite, improve gastric movement, and may have anti-inflammatory effects on patients with CACS. In patients with cancer, studies involving anamorelin combined with other multimodal treatments including nutrition counseling (branched chain amino acids, omega 3 fatty acids, and other nutrients), exercise, treatment of hormonal abnormalities including hypogonadism and hypovitaminosis D, and anti-inflammatory agents are needed. Compliance with multimodality treatment has been a barrier and future studies may need to incorporate motivational counseling to promote adherence.

Cannabis use among cancer survivors in the United States: Analysis of a nationally representative sample.

BACKGROUND: Research on cannabis use among those with a history of cancer is limited. METHODS: Prevalence of past-year cannabis use among individuals with and without a cancer history and predictors of use within these 2 groups were determined using data from the Population Assessment of Tobacco and Health study, a nationally representative, longitudinal survey conducted in the United States (waves 1-4; 2013-2018). Discrete time survival analyses were used to estimate baseline (wave 1) predictors (physical health status, mental health status, pain, and demographic variables) on past-year engagement with cannabis within individuals who reported a cancer diagnosis at wave 1 (n = 1022) and individuals who reported never having cancer at any wave (n = 19,702). RESULTS: At the most recent survey, 8% of cancer survivors reported past-year cannabis use, compared with 15% of those without a cancer history. Across 4 time points, an estimated 3.8% of cancer survivors engaged with cannabis, as compared to 6.5% of those without a cancer history. Across both groups, older age and having health insurance were associated with lower likelihood of engaging in cannabis use, whereas greater levels of pain were associated with higher likelihood of engaging in cannabis use. Among those without a cancer history, being female, White, and having better mental health status were associated with lower likelihood of engaging in cannabis use. CONCLUSIONS: Although cannabis use prevalence is lower among cancer survivors, the reasons for use are not markedly different from those without a cancer history. Continued monitoring of use, reasons for use, and harms or benefits is warranted. LAY SUMMARY: Results from this study, which uses data from the Population Assessment of Tobacco and Health Study, indicate that cannabis use is generally increasing across cancer survivors and those without a history of cancer. Cancer survivors are using cannabis at slightly lower rates than those without a history of cancer. Factors related to pain seem to be more prevalent in cancer populations relative to the general population, and could be contributing to cannabis use within cancer survivor populations.

Medical management of malignant bowel obstruction in patients with advanced cancer: 2021 MASCC guideline update.

BACKGROUND: Malignant bowel obstruction (MBO) is a frequent complication in patients with advanced cancer, particularly colon or gynecological malignancies. MASCC previously published a guideline for symptom management of MBO in 2017. This is a 5-year update. METHOD: A systematic search and review of relevant literature includes a review published in 2010 and 2017. The guideline update used the same literature search process as followed in 2015. The dates of the new search included 2015 up to February 2, 2021. The guidelines involved the pharmacologic management of nausea and vomiting in malignant bowel obstruction (MBO) only. Only randomized trials were included in the updated guideline as evidence. The evidence was reviewed by the panel and the MASCC criteria for establishing a guideline were followed using MASCC level of grading and category of evidence. RESULTS: There was one systematic review and 3 randomized trials accepted as evidence from 257 abstracts. Octreotide is effective in reducing gastrointestinal secretions and colic and thereby reduces nausea and vomiting caused by MBO. Scopolamine butylbromide is inferior to octreotide in the doses used in the comparison study. Olanzapine or metoclopramide may be effective in reducing nausea and vomiting secondary to partial bowel obstructions. The panel suggests using either drug. Additional studies are needed to clarify benefits. Haloperidol has been used by convention as an antiemetic but has not been subjected to a randomized comparison. Ranitidine plus dexamethasone may be effective in reducing nausea and vomiting from MBO but cannot be recommended until there is a comparison with octreotide. DISCUSSION: Octreotide remains the drug of choice in managing MBO. Ranitidine was used in one randomized trial in all participants and so its effectiveness as a single drug is not known until there is a randomized comparison with octreotide. Antiemetics such as metoclopramide and olanzapine may be effective, but we have very few randomized trials of antiemetics in MBO. CONCLUSION: The panel recommends octreotide in non-operable MBO. Randomized trials are needed to clarify ranitidine and antiemetic choices.

MASCC antiemetics in advanced cancer updated guideline.

BACKGROUND: Nausea and vomiting are a common clinical symptom in the advanced cancer patient. Pharmacologic management is important. Evidence for drug choices and guidelines are needed to help clinicians manage nausea and vomiting in this population METHODS: Evidence from a systematic review published in 2010, initial MASCC guidelines developed from a systematic review of literature to 2015, and a new systematic review of randomized trials published between 2015 and February 2, 2021, was combined to establish a new guideline. RESULTS: A search of the literature between 2015 and February 2, 2021, revealed 257 abstracts of which there was one systematic review and 4 randomized trials which were used to modify the guideline. The new guideline is as follows: First Line: Metoclopramide (II) multiple small RCTs including a placebo-controlled trial, haloperidol (II) multiple non-placebo-controlled RCTs, high consensus. Second line: Methotrimeprazine (II) 1 well-powered non-placebo-controlled RCT, olanzapine (II) 1 placebo-controlled pilot RCT, high consensus. Third line: Tropisetron (II) large unblinded lower quality non-placebo-controlled RCT, levosulpiride (II) 1 blinded non-placebo-controlled pilot RCT, high consensus. DISCUSSION: Haloperidol, metoclopramide, methotrimeprazine, olanzapine tropisetron, and levosulpiride have been antiemetics used in randomized trials with antiemetic activity demonstrated. There are only three placebo-controlled randomized trials we could find in our literature review. Placebo responses varied significantly between two randomized trials. More randomized placebo-controlled trials with either metoclopramide or haloperidol rescue are needed to clarify antiemetic choices in advanced cancer. CONCLUSION: First-line antiemetics for nausea and vomiting in advanced cancer are metoclopramide and haloperidol, and second-line medications are methotrimeprazine and olanzapine.

Delirium documentation in hospitalized pediatric patients with cancer.

OBJECTIVE: Screening tools for delirium are being used more consistently in pediatric critical care. However, screening is not universal, and delirium may be underdiagnosed, misdiagnosed, or undocumented in hospitalized patients. We evaluated the identification and documentation of delirium in pediatric oncology and bone marrow transplant patients. METHOD: A retrospective chart review on all hospitalized pediatric oncology and bone marrow transplant patients admitted to an Academic Cancer center between 2013 and 2016. Patients aged less than 21 years of age with active cancer were included. Patients with major psychiatric conditions, developmental delays, or autism were excluded. Data were collected to characterize documentation concerning the identification and diagnosis of delirium. RESULTS: Of 201 hospitalization records, 54 (26.9%) admissions from 109 unique patients had documentation of delirium. The overall documented incidence of delirium was 3.2% of hospitalizations or 8.2% of unique patients. Patients prescribed opioids and benzodiazepines were more likely to have documentation of delirium. ICD coding under-reported delirium while physician documentation was inaccurate in 26% (53/201) when compared with the chart review. SIGNIFICANCE OF RESULTS: Delirium was frequently undocumented or miscoded. Implementing a validated, universal screening tool for delirium may improve identification and clinical outcomes.

Best Practices in the Management of Nonmedical Opioid Use in Patients with Cancer-Related Pain.

INTRODUCTION: Nonmedical opioid use (NMOU) in patients with cancer is a term covering a spectrum of nonprescribed opioid use. The extent to which an individual uses opioids in a nonprescribed manner will influence propensity for adverse effects such as neurotoxicity, substance use disorder, overdose, and death. OBJECTIVES: The objectives of this study were to (A) evaluate current literature regarding management of NMOU in patients with cancer-related pain; (B) provide best practice recommendations based on evidence; and (C) integrate practices derived from the management of noncancer pain, where clinically appropriate or when the oncology literature is limited. METHODS: This study is a narrative review. IMPLICATIONS: Although harm from NMOU was thought to be rare among oncology patients, about one in five patients with cancer is at risk of adverse outcomes including prolonged opioid use, high opioid doses, and increased health care utilization. The management of NMOU can be challenging because pain is a multidimensional experience encompassing physical, psychological, and spiritual domains. An interdisciplinary team approach is most effective, and management strategies may include (A) education of patients and families; (B) harm reduction, including opioid switching, decreasing the overall daily dose, avoiding concurrent sedative use, and using adjuvant medications for their opioid-sparing potential; (C) managing psychological and spiritual distress with an interdisciplinary team and techniques such as brief motivational interviewing; and (D) risk mitigation by pill counts, frequent clinic visits, and accessing statewide prescription drug monitoring plans. CONCLUSION: Although many of the management strategies for NMOU in patients with cancer-related pain are modeled on those for chronic non-cancer-related pain, there is emerging evidence that education and harm-reduction initiatives specifically for cancer-related pain are effective. IMPLICATIONS FOR PRACTICE: Nonmedical opioid use (NMOU) in patients with cancer is a term covering a broad spectrum of nonprescribed opioid use. The extent to which an individual uses opioids in a nonprescribed manner will influence propensity for adverse effects such as neurotoxicity, substance use disorder, overdose, and death. This review evaluates the evidence for best practices in oncology and addresses limitations in the literature with supplemental evidence from noncancer chronic pain. Management recommendations for NMOU are provided, based on a combination of literature-based evidence and best clinical practice. Effective management of NMOU in oncology has the potential to improve quality of life, decrease health utilization, and improve survival.

Enteral and parenteral nutrition in cancer patients, a comparison of complication rates: an updated systematic review and (cumulative) meta-analysis.

INTRODUCTION: Weight loss in cancer patients is a worrisome constitutional change predicting disease progression and shortened survival time. A logical approach to counter some of the weight loss is to provide nutritional support, administered through enteral nutrition (EN) or parenteral nutrition (PN). The aim of this paper was to update the original systematic review and meta-analysis previously published by Chow et al., while also assessing publication quality and effect of randomized controlled trials (RCTs) on the meta-conclusion over time. METHODS: A literature search was carried out; screening was conducted for RCTs published in January 2015 up until December 2018. The primary endpoints were the percentage of patients achieving no infection and no nutrition support complications. Secondary endpoints included proportion of patients achieving no major complications and no mortality. Review Manager (RevMan 5.3) by Cochrane IMS and Comprehensive Meta-Analysis (version 3) by Biostat were used for meta-analyses of endpoints and assessment of publication quality. RESULTS: An additional seven studies were identified since our prior publication, leading to 43 papers included in our review. The results echo those previously published; EN and PN are equivalent in all endpoints except for infection. Subgroup analyses of studies only containing adults indicate identical risks across all endpoints. Cumulative meta-analysis suggests that meta-conclusions have remained the same since the beginning of publication time for all endpoints except for the endpoint of infection, which changed from not favoring to favoring EN after studies published in 1997. There was low risk of bias, as determined by assessment tool and visual inspection of funnel plots. CONCLUSIONS: The results support the current European Society of Clinical Nutrition and Metabolism guidelines recommending enteral over parenteral nutrition, when oral nutrition is inadequate, in adult patients. Further studies comparing EN and PN for these critical endpoints appear unnecessary, given the lack of change in meta-conclusion and low publication bias over the past decades.

Correction to: Enteral and parenteral nutrition in cancer patients, a comparison of complication rates: an updated systematic review and (cumulative) meta-analysis.

The appendices were incorrectly numbered in the original article. Please see below correcct appendices.

Prognostication in advanced cancer: update and directions for future research.

The objective of this review is to provide an update on prognostication in patients with advanced cancer and to discuss future directions for research in this field. Accurate prognostication of survival for patients with advanced cancer is vital, as patient life expectancy informs many important personal and clinical decisions. The most common prognostic approach is clinician prediction of survival (CPS) using temporal, surprise, or probabilistic questions. The surprise and probabilistic questions may be more accurate than the temporal approach, partly by limiting the time frame of prediction. Prognostic models such as the Glasgow Prognostic Score (GPS), Palliative Performance Scale (PPS), Palliative Prognostic Score (PaP), Palliative Prognostic Index (PPI), or Prognosis in Palliative Care Study (PiPS) predictor model may augment CPS. However, care must be taken to select the appropriate tool since prognostic accuracy varies by patient population, setting, and time frame of prediction. In addition to life expectancy, patients and caregivers often desire that expected treatment outcomes and bodily changes be communicated to them in a sensible manner at an appropriate time. We propose the following 10 major themes for future prognostication research: (1) enhancing prognostic accuracy, (2) improving reliability and reproducibility of prognosis, (3) identifying the appropriate prognostic tool for a given setting, (4) predicting the risks and benefits of cancer therapies, (5) predicting survival for pediatric populations, (6) translating prognostic knowledge into practice, (7) understanding the impact of prognostic uncertainty, (8) communicating prognosis, (9) clarifying outcomes associated with delivery of prognostic information, and (10) standardizing prognostic terminology.

Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN.

Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments. Our studies were designed to investigate whether nicotine can prevent and/or reverse paclitaxel-induced peripheral neuropathy in a mouse model of CIPN, while ensuring that nicotine will not stimulate lung tumor cell proliferation or interfere with the antitumor properties of paclitaxel. Male C57BL/6J mice received paclitaxel every other day for a total of four injections (8 mg/kg, i.p.). Acute (0.3-0.9 mg/kg, i.p.) and chronic (24 mg/kg per day, s.c.) administration of nicotine respectively reversed and prevented paclitaxel-induced mechanical allodynia. Blockade of the antinociceptive effect of nicotine with mecamylamine and methyllycaconitine suggests that the reversal of paclitaxel-induced mechanical allodynia is primarily mediated by the α7 nicotinic acetylcholine receptor subtype. Chronic nicotine treatment also prevented paclitaxel-induced intraepidermal nerve fiber loss. Notably, nicotine neither promoted proliferation of A549 and H460 non-small cell lung cancer cells nor interfered with paclitaxel-induced antitumor effects, including apoptosis. Most importantly, chronic nicotine administration did not enhance Lewis lung carcinoma tumor growth in C57BL/6J mice. These data suggest that the nicotinic acetylcholine receptor-mediated pathways may be promising drug targets for the prevention and treatment of CIPN.

Urine drug screen findings among ambulatory oncology patients in a supportive care clinic.

PURPOSE: Professional organizations provide no guidelines regarding assessment and management of opioid abuse risk in cancer. Universal precautions (UP) developed for non-cancer pain, include assessments for aberrant behavior, screening questionnaires, and urine drug screens (UDS). The role of UDS for identifying opioid abuse risk in cancer is uncertain. Our aim is to characterize inappropriate UDS, and identify a potential role for UDS in therapeutic decision-making. METHODS: An observational retrospective chart review of 232 consecutive supportive care clinic patients were seen during the study. Twenty-eight of the two hundred thirty-two did not meet inclusion criteria. One hundred fifty of the two hundred four had active cancer, while 54 had no evidence of active disease. Clinicians ordered UDS based on their clinical judgment of patients' substance misuse risk. Edmonton symptom assessment scores, history of substance abuse, alcohol use, tobacco use, aberrant behavior, and morphine equivalent daily dose (MEDD) were obtained. RESULTS: Pain scores and MEDD were higher (p = 0.021; p < 0.001) in the UDS group vs non-UDS. Forty percent of the patients (n = 82/204) had at least one UDS and 70% (60/82) had an inappropriate result. Thirty-nine percent (32) were inappropriately negative, showing no prescribed opioids. Forty-nine of the eighty-two were positive for non-prescribed opioids, benzodiazepine, or illicit substance. Eleven of the forty-nine had only cannabis metabolites in their urine. There were no significant differences between appropriate and inappropriate UDS groups regarding pain scores, MEDD or referral to psychology, psychiatry, or substance abuse specialists. CONCLUSIONS: UDS on the 82 oncology patients at high risk for substance misuse were frequently positive (46%) for non-prescribed opioids, benzodiazepines or potent illicit drugs such as heroin or cocaine, and 39% had inappropriately negative UDS, raising concerns for diversion.

Association between hypogonadism, symptom burden, and survival in male patients with advanced cancer.

BACKGROUND: A high frequency of hypogonadism has been reported in male patients with advanced cancer. The current study was performed to evaluate the association between low testosterone levels, symptom burden, and survival in male patients with cancer. METHODS: Of 131 consecutive male patients with cancer, 119 (91%) had an endocrine evaluation of total (TT), free (FT), and bioavailable testosterone (BT); high-sensitivity C-reactive protein (CRP); vitamin B12; thyroid-stimulating hormone; 25-hydroxy vitamin D; and cortisol levels when presenting with symptoms of fatigue and/or anorexia-cachexia. Symptoms were evaluated by the Edmonton Symptom Assessment Scale. The authors examined the correlation using the Spearman test and survival with the log-rank test and Cox regression analysis. RESULTS: The median age of the patients was 64 years; the majority of patients were white (85 patients; 71%). The median TT level was 209 ng/dL (normal: ≥ 200 ng/dL), the median FT was 4.4 ng/dL (normal: ≥ 9 ng/dL), and the median BT was 22.0 ng/dL (normal: ≥ 61 ng/dL). Low TT, FT, and BT values were all associated with worse fatigue (P ≤ .04), poor Eastern Cooperative Oncology Group performance status (P ≤ .05), weight loss (P ≤ .01), and opioid use (P ≤ .005). Low TT and FT were associated with increased anxiety (P ≤ .04), a decreased feeling of well-being (P ≤ .04), and increased dyspnea (P ≤ .05), whereas low BT was only found to be associated with anorexia (P = .05). Decreased TT, FT, and BT values were all found to be significantly associated with elevated CRP and low albumin and hemoglobin. On multivariate analysis, decreased survival was associated with low TT (hazards ratio [HR], 1.66; P = .034), declining Eastern Cooperative Oncology Group performance status (HR, 1.55; P = .004), high CRP (HR, 3.28; P < .001), and decreased albumin (HR, 2.52; P < .001). CONCLUSIONS: In male patients with cancer, low testosterone levels were associated with systemic inflammation, weight loss, increased symptom burden, and decreased survival. A high frequency of hypogonadism has been reported in male patients with advanced cancer. In the current study, an increased symptom burden, systemic inflammation, weight loss, opioid use, and poor survival were found to be associated with decreased testosterone levels in male patients with cancer. Cancer 2014;120:1586-1593. © 2014 American Cancer Society.

When and when not to use testosterone for palliation in cancer care.

Hypogonadism is common throughout the illness trajectory of patients with cancer. About two thirds of male patients with advanced cancer have hypothalamic-pituitary-gonadal dysfunction and low testosterone levels. Chronic inflammation, comorbidities, cachexia, chemotherapy, and medications such as opioids, megestrol acetate, and corticosteroids contribute to primary and secondary hypogonadism. Studies have reported increased symptom burden, diminished quality of life, and poor prognosis associated with low testosterone levels in males with cancer. The Endocrine Society has published clinical practice guidelines for replacing testosterone in symptomatic patients with chronic illness and in patients receiving opioids; however, the role of testosterone therapy specifically in patients with cancer is not addressed. This review explores the potential benefits and limitations of testosterone replacement on the basis of current evidence.

Updates in Cancer Cachexia: Clinical Management and Pharmacologic Interventions.

Despite a better understanding of the mechanisms causing cancer cachexia (CC) and development of promising pharmacologic and supportive care interventions, CC persists as an underdiagnosed and undertreated condition. CC contributes to fatigue, poor quality of life, functional impairment, increases treatment related toxicity, and reduces survival. The core elements of CC such as weight loss and poor appetite should be identified early. Currently, addressing contributing conditions (hypothyroidism, hypogonadism, and adrenal insufficiency), managing nutrition impact symptoms leading to decreased oral intake (nausea, constipation, dysgeusia, stomatitis, mucositis, pain, fatigue, depressed mood, or anxiety), and the addition of pharmacologic agents when appropriate (progesterone analog, corticosteroids, and olanzapine) is recommended. In Japan, the clinical practice has changed based on the availability of Anamorelin, a ghrelin receptor agonist that improved lean body mass, weight, and appetite-related quality of life (QoL) compared to a placebo, in phase III trials. Other promising therapeutic agents currently in trials include Espindolol, a non-selective ß blocker and a monoclonal antibody to GDF-15. In the future, a single therapeutic agent or perhaps multiple medications targeting the various mechanisms of CC may prove to be an effective strategy. Ideally, these medications should be incorporated into a multimodal interdisciplinary approach that includes exercise and nutrition.

Hepatocellular carcinoma and sarcopenia: a narrative review.

BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC) affects millions of people each year and is associated with high mortality and morbidity. Sarcopenia, a condition of muscle wasting, and decreased muscle performance is common among aging adults, and is associated with poor clinical outcomes. Individuals with HCC and chronic liver disease (CLD) are at high risk of sarcopenia because of the adverse effects of chronic inflammation, endocrine dysfunction, and hyperammonemia on muscle metabolism and adequate nutrition. Our aim is to review the clinical relationship between HCC and sarcopenia, and the assessment and management of these patients. METHODS: A narrative review based on a literature search using PubMed. Keywords related to HCC and sarcopenia were used to identify relevant articles, primarily those published 2018-2023. The information was synthesized to provide a narrative review focused on the most recent literature. KEY CONTENT AND FINDINGS: Sarcopenia frequently co-exists with HCC and increases risk for adverse clinical outcomes such as symptom burden, quality of life (QoL), survival, and side effects of antineoplastic therapy. Tools are available to screen, assess and manage patients with HCC, and although there is no specific pharmacologic agent approved for sarcopenia in the United States, multimodal therapy is feasible in daily practice. Comprehensive management by an interdisciplinary team should include nutritional counseling, an exercise regimen and control of symptoms affecting nutrition and function. CONCLUSIONS: Sarcopenia has adverse effects on prognosis and tolerability of surgical and medical therapy in HCC. Patients with CLD and/or HCC would benefit from early identification, assessment, and therapeutic intervention. Management should be comprehensive, interdisciplinary, and include both pharmacologic and non-pharmacologic treatments. Further research is needed to identify individual agents that may mitigate muscle wasting and trials are needed to evaluate the benefit of multimodal therapy in HCC.

Should Urine Drug Screen be Done Universally or Selectively in Palliative Care Patients on Opioids?

Urine drug screen (UDS) is a useful test conducted in patients receiving opioids for chronic pain to aid in validating patient adherence to opioid treatment and to detect any nonmedical opioid use (NMOU). One controversial topic regarding its use in palliative care is whether to conduct the test universally and randomly in all patients who are receiving opioids for chronic pain irrespective of their level of risk for NMOU, or to conduct the test selectively in only those with a high risk for engaging in NMOU behaviors. In this "Controversies in Palliative Care" article, 3 expert clinicians independently answer this question. Specifically, each expert provides a synopsis of the key studies that inform their thought processes, share practical advice on their clinical approach, and highlight the opportunities for future research. They all agreed that UDS has some utility in routine palliative care practice but acknowledged the insufficient existing evidence supporting its efficacy. They also underscored the need to improve clinician proficiency in UDS interpretation to enhance its utility. Two experts endorsed random UDS in all patients receiving opioids regardless of their risk profile while the other expert recommended targeted UDS until there is more clinical evidence to support universal, random testing. Use of more methodologically robust study designs in UDS research, examination of the cost-effectiveness of UDS tests, development of innovative programs to manage NMOU behaviors, and investigation of the impact of improved clinician proficiency in UDS interpretation on clinical outcomes, were important areas of future research that the experts identified.

The relationship between body composition and response to neoadjuvant chemotherapy in women with operable breast cancer.

INTRODUCTION: Overweight women diagnosed with breast cancer have greater recurrence and mortality risks. Recent studies in advanced cancer showed that the combination of sarcopenia and an overweight or obese body mass index (BMI) is associated with poor clinical outcomes. OBJECTIVES: To compare pathological complete response (pCR) cases with controls and evaluate associations among a pCR, survival outcome, and sarcopenia as well as the combination of both sarcopenia and a BMI ≥25 kg/m(2). METHODS: Sixty-seven breast cancer patients with a pCR to neoadjuvant chemotherapy (NC) were matched with controls who did not have a pCR to NC. Patients were matched by age, Black's nuclear grading system, clinical cancer stage, and estrogen receptor and progesterone receptor status. Body composition was analyzed using computed tomography images taken prior to NC. RESULTS: BMI was associated with pCR. Among normal weight patients, the pCR rate was higher in sarcopenic patients and the progression-free survival (PFS) interval was significantly longer than in overweight or obese BMI patients. The death hazard was 2% higher for each unit higher skeletal muscle index and 0.6% higher for each unit higher visceral adipose tissue. CONCLUSIONS: Overweight patients treated with NC had a lower pCR rate and shorter PFS time. Among patients with a normal BMI, the pCR rate was better in sarcopenic patients. More research is required to evaluate the negative impact of sarcopenic obesity on prognosis and the contributors to better response rates in operable, normal weight breast cancer patients with sarcopenia.