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.

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.

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.

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.

Opioid Rotation and Conversion Ratios Used by Palliative Care Professionals: An International Survey.

Background: The opioid rotation ratios (ORRs) and conversion ratios (CRs) used worldwide among palliative care (PC) professionals to perform opioid rotations (ORs) and route conversions may have a wide variation. Methods: We surveyed PC professionals on opioid ratios used through email to the Multinational Association of Supportive Care in Cancer's PC study group and Twitter and Facebook posts between September and November 2020. Results: We received 370 responses from respondents from 53 countries: 276 (76%) were physicians, 46 (13%) advanced practice providers, 39 (11%) pharmacists, and 9 respondents did not report their profession. There were statistically significant variations in median CR from intravenous (IV) to oral morphine (2-3), IV to oral hydromorphone (2-4.5), ORR from IV hydromorphone to oral morphine (10-20), and ORR from transdermal fentanyl mcg/hour to oral morphine (2-3.5) across various groups. Conclusion: This survey highlights the wide variation in ORRs and CRs among PC clinicians worldwide and the need for further research to standardize practice.

Managing Nutrition Impact Symptoms in Cancer Cachexia: A Case Series and Mini Review.

Malnutrition is common in cancer patients and can occur throughout a patient's disease course. The contributors to the clinical syndrome of cancer cachexia are often multifactorial, and produced by the cancer and associated pro-inflammatory response. Since cancer cachexia is a multifactorial syndrome, a multimodal therapeutic approach is ideal. A key component of therapy is identifying and managing symptom barriers to adequate oral intake, known as nutritional impact symptoms (NIS). NIS are associated with reduced intake and weight loss in patients with advanced cancer, and aggregate NIS are a predictor of survival in patients with Head and Neck Cancer and in patients undergoing surgery for esophageal cancer. Currently, there are no guidelines regarding the specific management of NIS in oncology patients. Experience from specialist centers suggest relatively simple assessments and inexpensive interventions are available for the diagnosis and treatment of NIS. We present three patient cases from a cachexia clinic, where NIS management decreased symptom burden and improved clinical outcomes such as weight and physical performance.

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.

Comparison of opioid rotation on pain, symptoms, and daily opioid dose in a supportive care clinic.

BACKGROUND: Opioid rotation (OR) is used to decrease patients' cancer-related pain and mitigate opioid-induced adverse effects. There is limited evidence regarding its effect on symptoms and morphine equivalent daily dose (MEDD). The objective of this study was to investigate the effects of OR on pain scores, Edmonton Symptom Assessment Score (ESAS), and MEDD in patients with cancer. METHODS: Retrospective observational study in an outpatient supportive care clinic using a within-subject design to analyze data collected over 34 months. Study included 676 patients with 217 rotations identified in 128 patients at supportive care clinic at a National Cancer Institute (NCI) Cancer Center. OR were identified and analysis compared the pre-visit data with the subsequent post-visit data following OR using paired t-tests. Primary endpoints included pain scores, total ESAS, and MEDD for OR and these endpoints were compared amongst rotations to specific opioid analgesics. RESULTS: Following OR, there was a statistically significant reduction in mean pain scores from 6.25 at the pre-visit to 5.75 following OR. Of the 194 ORs, 29.90% were successful in reducing patients' pain by either 30% or by 2-points. Only rotations to morphine, oxycodone, and methadone correlated with significant decreases in pain scores. Overall, OR did not correlate with significant changes in ESAS or MEDD. Only rotations to methadone correlated with a significant reduction in MEDD. CONCLUSIONS: These findings suggest OR is associated with decreased pain scores without increasing MEDD. Of the agents compared, only rotations to methadone correlated with both a significant reduction in pain scores and in MEDD.

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.

Combination therapy with methadone and duloxetine for cancer-related pain: a retrospective study.

BACKGROUND: A comprehensive approach to pain management often requires multimodal therapy and a combination of medications. Oncology patients may be prescribed methadone and duloxetine as single agents or in combination for cancer-related pain, particularly neuropathic pain. Duloxetine is also prescribed for depression or anxiety in patients with cancer. METHODS: A retrospective chart review on patients with cancer-related pain prescribed duloxetine and methadone combination therapy at the Virginia Commonwealth University supportive care clinic (SCC) between 2012 and 2019. Edmonton Symptom Assessment System (ESAS) scores reported by patients on monotherapy were compared to scores after they started combination therapy. Of 131 patients identified on combination therapy, 43 met study criteria (2 with incomplete ESAS scores). RESULTS: ESAS total and subscores after combination therapy were lower than on monotherapy. Combination therapy decreased total, pain, and emotion subscores by 5.6 (SD =17.3, dz =-0.32, P=0.046), 0.9 (SD =3.0, dz =-0.30, P=0.052), and 1.8 (SD =5.1, dz =-0.36, P=0.023), respectively. On combination therapy, 28% of patients reported at least a two-point reduction in pain scores. All study participants reported cancer pain with neuropathic components; most had mixed pain syndromes comprising nociceptive and neuropathic components. Adherence rates were high as 81% of patients with follow-up appointments continued therapy. CONCLUSIONS: These results suggest the combination of duloxetine and methadone reduces cancer-related pain and emotional symptom burden compared to either medication as a single agent.

Key Developments in the Potential of Curcumin for the Treatment of Peripheral Neuropathies.

Peripheral neuropathies (PN) can be triggered after metabolic diseases, traumatic peripheral nerve injury, genetic mutations, toxic substances, and/or inflammation. PN is a major clinical problem, affecting many patients and with few effective therapeutics. Recently, interest in natural dietary compounds, such as polyphenols, in human health has led to a great deal of research, especially in PN. Curcumin is a polyphenol extracted from the root of Curcuma longa. This molecule has long been used in Asian medicine for its anti-inflammatory, antibacterial, and antioxidant properties. However, like numerous polyphenols, curcumin has a very low bioavailability and a very fast metabolism. This review addresses multiple aspects of curcumin in PN, including bioavailability issues, new formulations, observations in animal behavioral tests, electrophysiological, histological, and molecular aspects, and clinical trials published to date. The, review covers in vitro and in vivo studies, with a special focus on the molecular mechanisms of curcumin (anti-inflammatory, antioxidant, anti-endoplasmic reticulum stress (anti-ER-stress), neuroprotection, and glial protection). This review provides for the first time an overview of curcumin in the treatment of PN. Finally, because PN are associated with numerous pathologies (e.g., cancers, diabetes, addiction, inflammatory disease...), this review is likely to interest a large audience.

Management of Cancer Cachexia: ASCO Guideline.

PURPOSE: To provide evidence-based guidance on the clinical management of cancer cachexia in adult patients with advanced cancer. METHODS: A systematic review of the literature collected evidence regarding nutritional, pharmacologic, and other interventions, such as exercise, for cancer cachexia. PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and systematic reviews of RCTs published from 1966 through October 17, 2019. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: The review included 20 systematic reviews and 13 additional RCTs. Dietary counseling, with or without oral nutritional supplements, was reported to increase body weight in some trials, but evidence remains limited. Pharmacologic interventions associated with improvements in appetite and/or body weight include progesterone analogs and corticosteroids. The other evaluated interventions either had no benefit or insufficient evidence of benefit to draw conclusions on efficacy. Limitations of the evidence include high drop-out rates, consistent with advanced cancer, as well as variability across studies in outcomes of interest and methods for outcome assessment. RECOMMENDATIONS: Dietary counseling may be offered with the goals of providing patients and caregivers with advice for the management of cachexia. Enteral feeding tubes and parenteral nutrition should not be used routinely. In the absence of more robust evidence, no specific pharmacological intervention can be recommended as the standard of care; therefore, clinicians may choose not to prescribe medications specifically for the treatment of cancer cachexia. Nonetheless, when it is decided to trial a drug to improve appetite and/or improve weight gain, currently available pharmacologic interventions that may be used include progesterone analogs and short-term (weeks) corticosteroids.

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.

Evaluating Hospital Readmissions for Persons With Serious and Complex Illness: A Competing Risks Approach.

Hospital readmission rate is a ubiquitous measure of efficiency and quality. Individuals with life-limiting illnesses account heavily for admissions but evaluation is complicated by high-mortality rates. We report a retrospective cohort study examining the association between palliative care (PC) and readmissions while controlling for postdischarge mortality with a competing risks approach. Eligible participants were adult inpatients admitted to an academic, safety-net medical center (2009-2015) with at least one diagnosis of cancer, heart failure, chronic obstructive pulmonary disease, liver failure, kidney failure, AIDS/HIV, and selected neurodegenerative conditions. PC was associated with reduced 30-, 60-, and 90-day readmissions (subhazard ratios = 0.57, 0.53, and 0.52, respectively [all p < .001]). Hospital PC is associated with a reduction in readmissions, and this is not explained by higher mortality among PC patients. Performance measures only counting those alive at a given end point may underestimate systematically the effects of treatments with a high-mortality rate.

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.