Cancer Anorexia-cachexia Syndrome Research Articles

Anamorelin for the Treatment of Cancer Anorexia-Cachexia Syndrome.

The following review will highlight the development of anamorelin to treat cancer anorexia-cachexia syndrome (CACS) including the potential benefits, limitations, and future directions. 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.

Cancer anorexia-cachexia syndrome is characterized by more than one inflammatory pathway.

The interdependence of cytokines and appetite-modifying hormones implicated in cancer anorexia-cachexia syndrome (CACS) remains unclear. This study aimed to regroup these cytokines and hormones into distinct inflammatory (or non-inflammatory) pathways and determine whether these pathways can classify patients with CACS phenotypes. Clinical characteristics of 133 patients [61.7% male; mean age=63.4 (SD: 13.1) years] with advanced cancer prior to oncology treatments were documented, including weight loss history. Patients completed the Functional Assessment of Anorexia-Cachexia Therapy (FAACT) questionnaire and Timed Up and Go test and had their sex-standardized skeletal muscle index(z-SMI) and fat mass index (z-FMI) derived using computed tomography scans. Their plasma levels of cytokines and appetite-modifying hormones were also determined. Date of death was recorded. Exploratory factor analysis (EFA) was used to regroup 15 cytokines and hormone into distinct inflammatory pathways (factors). For each patient, regression factor scores (RFS), which tell how strongly the patient associates with each factor, were derived. Two-step cluster analysis on the RFS was used to classify patients into groups. CACS phenotypes were correlated with RFS and compared between groups. Groups' survival was estimated using Kaplan-Meier analysis. Patients had low z-SMI (mean=-3.78cm2 /m2 ; SD: 8.88) and z-FMI (mean=0.08kg2 /m2 ; SD: 56.25), and 62 (46.6%) had cachexia. EFA identified three factors: (F-1) IFN-γ, IL-1β, Il-4, IL-6, IL-10, IL-12, TGFβ1 (positive contribution), and IL-18 (negative); (F-2) IL-8, IL-18, MCP-1, TGFβ1, TNF-α (positive), and ghrelin (negative); and (F-3) TRAIL and leptin (positive), and TGFβ1 and adiponectin (negative). RFS-1 was associated with cachexia (P=0.002); RFS-2, with higher CRP (P<0.0001) and decreased physical function (P=0.01); and RFS-3 with better appetite (P=0.04), lower CRP (P=0.002), higher z-SMI (P = 0.04) and z-FMI (P < 0.0001), and less cachexia characteristics (all P<0.001). Four patient groups were identified with specific RFS clusters aligning with the CACS continuum from no cachexia to pre-cachexia, cachexia, and terminal cachexia. Compared to the other two groups, groups 1 and 2 had higher plasma levels of IL-18 and TRAIL. Group 1 also had lower inflammatory cytokines, adiponectin, and CRP compared to the other three groups. Group 3 had inflammatory cytokine levels similar to group 2, except for TNF-α and leptin which were lower. Group 4 had very high inflammatory cytokines, adiponectin, and CRP compared to the other 3 groups (all P<0.0001). Groups 3 and 4 had worse cachexia characteristics (P<0.05) and shorter survival (log rank: P=0.0009) than the other two groups. This exploratory study identified three distinct pathways of inflammation, or lack thereof, characterizing different CACS phenotypes.

A Review of Olanzapine in the Treatment of Cancer Anorexia-Cachexia Syndrome.

Cancer anorexia-cachexia syndrome (CAS) is a multifactorial condition that is highly prevalent in advanced cancer patients and associated with significant reduction in functional performance, reduction in quality of life, and increased mortality. Currently, no medications are approved for this indication. Recently, the American Society of Clinical Oncology (ASCO) released a rapid recommendation suggesting that low-dose olanzapine once daily may be used to treat cancer cachexia. Many questions still exist on how to use olanzapine for this indication in clinical practice. The objective of this review is to identify existing knowledge on the use of olanzapine for CAS. A comprehensive search was conducted to identify the primary literature that involved olanzapine for anorexia and cachexia in cancer patients between 2000 and 2023. Seven articles were identified and are discussed here, including two randomized double-blinded placebo-controlled studies, one randomized comparative study, two prospective open-label studies, one retrospective chart review, and one case report. Low dose olanzapine (2.5-5 mg once daily) may be useful in the treatment of CAS for increasing appetite, reducing nausea and vomiting, and promoting weight gain. Further large-scale multi-center randomized placebo-controlled studies will be needed to investigate the impact of olanzapine on weight change in CAS patients.

Atractylodin alleviates cancer anorexia-cachexia syndrome by regulating NPY through hypothalamic Sirt1/AMPK axis-induced autophagy

Cancer anorexia-cachexia syndrome (CACS) is a complex syndrome associated with loss of muscle and adipose tissue and weight loss, and is a major lethal factor in the later stages of cancer. The mechanism of action of CACS is not fully understood and there are no drugs specifically approved for its treatment. Atractylodin, the main active component of Atractylodes lancea, is widely used in the treatment of digestive disorders and has the ability to reduce IL-1, IL-6 and TNF-α levels. Our results showed that gavage with Atractylodin increased body weight, muscle and fat weight and reduced tumor weight and volume as well as abnormally high serum concentrations of the muscle atrophy-causing cytokines IL-1β, IL-6 and TNF-α in CACS model mice. RT-PCR data revealed that Atractylodin promoted the expression of the pro-feeding NPY and suppressed the expression of the anorexia POMC in the hypothalamus. Western blot results showed that Atractylodin promoted the expression of Sirt1 and p-AMPK in the hypothalamus, accompanied by an increase in autophagy. Furthermore, the Sirt1 inhibitor EX527 or AMPK inhibitor Compound C (CC) reversed Atractylodin-induced beneficial effects in CACS model mice. In hypothalamic cells subjected to glucose deprivation, Atractylodin increased NPY mRNA expression by enhancing AMPK-modulated autophagy; while EX527 or Compound C blunted Atractylodin-induced autophagy enhancement effect in vitro. In conclusion, Atractylodin can be used as an anti-cachexia drug and the underlying mechanism may involve the promotion of NPY expression by Sirt1/AMPK-regulated autophagy.

Efficacy of Curcumin on Treating Cancer Anorexia-Cachexia Syndrome in Locally or Advanced Head and Neck Cancer: A Double-Blind, Placebo-Controlled Randomised Phase IIa Trial (CurChexia).

Background Cancer anorexia-cachexia syndrome (CAS) is a significant comorbidity among all patients with cancer, increasing the mortality rate. Almost all patients with head and neck cancer experience this syndrome. CAS causes increased energy expenditure by increasing systemic inflammation and decreasing energy consumption due to anorexia. It leads to skeleton muscle breakdown and reduces the quality of life. Nutritional interventions and primary cancer treatment are the mainstays to manage this situation. However, a vicious cycle causes CAS to persist, especially in head and neck cancer, where tumour location and its treatment interfere with nutritional interventions. Curcumin shows anti-inflammatory effects, including modulated CAS in animal and in vitro studies. Objective The study aimed to determine the effect of curcumin to treat cancer anorexia-cachexia syndrome among current patients with locally advanced or advanced head and neck cancer. Methods This constitutes a randomised, double-blind, placebo-controlled phase IIa study. Twenty patients with CAS in locally advanced or advanced head and neck cancer adequately nourished via a feeding tube were enrolled and randomised in a 1 : 1 ratio to receive oral curcumin (at a dose of 4000 mg daily) (n = 10) or placebo (n = 10) for 8 weeks. The primary endpoint was body composition (muscle mass, body fat mass, and basal metabolic rate). The secondary endpoints were handgrip muscle strength, body mass index, absolute lymphocyte count, and safety and toxicity. Result There was a statistically significant benefit from curcumin on improving muscle mass compared with placebo (2.16% [95% confidence interval; CI, −0.75 to 5.07] vs. −3.82% [95% CI, −8.2 to 0.57]; P=0.019). The other parameters of body composition were not significant but tended to favour curcumin benefit. The body fat mass (−0.51 [95% CI, −21.89 to 20.86] vs. −8.97% [95% CI, −19.43 to 1.49]; P=0.432) and percentage of mean change in the basal metabolic rate were noted (BMR) (0.54% [95% CI, −1.6 to 2.67] vs. −1.61% [95% CI, −4.05 to 0.84]; P=0.153). Notably, patients treated with curcumin exhibited less reduction in handgrip muscle strength and absolute lymphocyte count but was not significant. Similarly, most adverse events were grade 1 in both groups. Conclusion The curcumin add-on resulted in a significant increase in muscle mass than standard nutritional support. Furthermore, it may improve and delay a decrease in the other body composition parameters, handgrip strength, and absolute lymphocyte count. Curcumin was safe and well tolerated. This constitutes an unmet need for clinical trials. This trial is registered with NCT04208334.

Assessment and nonpharmacological management for patients with cancer anorexia-cachexia syndrome: a best practice implementation project.

Cancer anorexia-cachexia syndrome (CACS) is a common multifactorial syndrome, which affects up to 80% patients with advanced cancer. At present, evidence to support the benefit of pharmacological intervention in the management of CACS is limited. Patients would benefit from standard procedures for early assessment and identification of cancer anorexia-cachexia, and using nonpharmacological strategies to manage patients with CACS. This best practice implementation project aimed to implement an evidence-based practice in assessing and managing patients with CACS, thereby improving the compliance of clinical practice with the best evidence and the quality of life of patients with CACS. This was an evidence-based audit and feedback project that used a three-phase approach at a public hospital in China. Phase 1 included the development of seven evidence-based audit criteria and carrying out a baseline audit on 30 patients using the JBI's Practical Application of Clinical Evidence System in the Department of Radiation Oncology of Nanfang Hospital. Phase 2 utilized the Getting Research into Practice component of the Practical Application of Clinical Evidence System to identify barriers to compliance with best practice principles and developed strategies and resources to improve compliance. Phase 3 involved conducting a follow-up audit using the same sample size and audit criteria to assess the results of interventions implemented to improve practice and identify issues that would be addressed in future audit. The compliance rates of audit criteria 1, 2 and 6 were 100% at both baseline and follow-up audit. After the application of evidence, the compliance rate increased from 0 to 100% for audit criterion 3, from 0 to 76.6% for audit criterion 4, from 23 to 70% for audit criterion 5, and from 0 to 40% for audit criterion 5. The best evidence for the assessment and nonpharmacological management of cancer patients with CACS can improve clinical practice, the quality of clinical nursing, and patient satisfaction. The application of electronic informatization promotes the implementation and maintenance of best practice.

Anamorelin for cancer cachexia.

Cancer anorexia-cachexia syndrome is a multifactorial condition characterized by significant weight loss due to muscle loss. It is associated with functional impairment, changes in body composition and nutritional disorders. Ghrelin receptors are involved in the release of growth hormone (GH) in the pituitary gland and increase appetite via the hypothalamus. The secretion of GH from the pituitary gland stimulates the liver to secrete insulin-like growth factor 1 (IGF-1), which promotes muscle protein synthesis. Anamorelin is a ghrelin receptor agonist used to treat cancer cachexia. It promotes GH secretion via ghrelin receptor activation and increases appetite, resulting in increased muscle mass and weight. Clinical trials of anamorelin have demonstrated a significant increase in lean body mass index, improved cachexia and no significant increase in serious adverse events. The present review describes the processes leading to the approval of anamorelin in Japan, focusing on pharmacology, metabolism, efficacy, safety and clinical trials.

Updates in Cancer-Related Symptom Management of Anorexia and Cachexia Syndrome.

To provide current evidence and updates in cancer-related symptom management of cancer anorexia-cachexia syndrome (CACS). Textbooks, journal articles, and the internet. Nutrition and the treatment of CACS plays a pivotal role in multimodal cancer care. The pathophysiology of nutrition in patients with cancer is complex and requires active screening and interventions. Treatment of CACS should focus on antitumor treatment, nutrition intervention, supportive pharmacologic intervention and/or other interventions that improve clinical outcomes. Oncology nurses are in a pivotal position to provide proactive screening, assessment, clarify treatment options, and follow-up for patients with cancer and associated nutritional issues.

1679P A double-blind, placebo-controlled, randomized phase IIa trial, evaluating the effect of curcumin for the treatment of cancer anorexia-cachexia syndrome in patients with stage III-IV head and neck cancer (CurChexia)

Cancer anorexia-cachexia syndrome (CAS) is a significant comorbidity in all cancer patients that increase the mortality rate. Almost all head and neck cancer (HNC) patients suffered from this syndrome. CAS causes increased energy expenditure by increased systemic inflammation and decreased energy consumption due to anorexia. This leads to skeleton muscle breakdown and affects the quality of life. Nutritional interventions and cancer treatment are the mainstays to treat this situation. However, a vicious cycle causes CAS to persist, especially in HNC, where tumor location and its treatment interfere with nutritional intervention.

A Dynamic Energy Budget (DEB) based modeling framework to describe tumor-in-host growth inhibition and cachexia onset during anticancer treatment in in vivo xenograft studies.

Cancer anorexia-cachexia syndrome (CACS) is a very severe complication of cancer for which an adequate therapeutic strategy has not yet been defined. Recently, a notable number of new animal models of human CACS has been made available for translational purposes. Under the assumption that tumor-induced adaptations of host metabolism and tumor-host energetic competition play a major role in CACS (together with possible toxicities induced by the anticancer treatment), we developed a new Dynamic Energy Budget (DEB)-based framework, modeling tumor-in-host growth dynamics and cachexia onset in preclinical animal models during anticancer treatments. The tumor-in-host modeling approach was successfully applied on a multitude of in vivo preclinical studies involving different host species, tumor cell lines, type of anticancer agents and experimental settings among which standard xenograft studies. Obtained results strongly suggested the adoption of the tumor-in-host DEB-based approach in the preclinical oncological setting for a joint assessment of drug efficacy and toxicity and for a better design of the experiments. Further applications of the DEB-based approach to the context of poly-targeted combination therapy, anti-cachectic treatments and preclinical to clinical translation are under investigation with extremely encouraging preliminary results.

Abstract 2354: Downregulating the glutamine transporter, SLC1A5, significantly reduces cachexia in a PDAC xenograft

Abstract Cachexia occurs with high frequency and severity in pancreatic ductal adenocarcinoma (PDAC) patients [1]. Cachectic patients experience a wide range of symptoms affecting the function of organs such as muscle, liver, brain, and heart, causing significant morbidity [2]. In high-resolution 1H magnetic resonance spectroscopy (MRS) studies of extracts, we previously observed significant perturbation of glutamine in the brain and plasma of mice with a cachexia-inducing PDAC xenograft [3] that prompted us to evaluate the effects of modifying tumor glutamine metabolism on cachexia. We investigated tumors derived from cachexia-inducing Pa04C cells engineered to express shRNA against the glutamine transporter, SLC1A5, glutaminase (GLS) 1, and GLS 2. Patient-derived cachexia-inducing Pa04C cells were stably transduced with virions that expressed shRNA against GLS1 or GLS2 or SLC1A5. Pooled clones were obtained with puromycin selection. Empty vector (EV) cells were also established. Downregulation of target genes was confirmed with mRNA and protein expression characterization. The effects of gene knockdown on tumor growth and weight-loss were determined following subcutaneous inoculation of engineered cells or wild type cells in SCID mice. Longitudinal tumor growth, weights and percent weight changes were determined in 7 wild type (WT), 7 EV, 9 GLS1 downregulated, 9 GLS2 downregulated, and 9 SLC1A5 downregulated tumor bearing mice. Once tumors were ~500 mm3 in volume, tumors were harvested from euthanized mice, and snap frozen for molecular analysis. Protein and mRNA obtained from tumors was validated for downregulation of target genes. Efficient downregulation of SLC1A5, GLS1 and GLS2 mRNA and protein was confirmed in tumors. Downregulating SLC1A5 significantly reduced tumor growth. But, downregulating GLS1 or GLS2 did not reduce tumor growth and, in fact, GLS1 downregulated tumors grew significantly faster than WT or EV tumors. Importantly, for comparable tumor volumes, we found that body weight loss was markedly reduced in mice with SLC1A5 downregulated tumors. Although GLS1 downregulated tumors grew faster than WT tumors, weight loss was attenuated at comparable tumor volumes in these tumors although not to the same extent as in SLC1A5 downregulated tumors. These data highlight potential role of SLC1A5 in PDAC tumor treatment and in the treatment of PDAC-induced cachexia, and support targeting the glutamine/glutamate axis in PDAC to reduce or reverse cachexia.Supported by NIH R35 CA209960 and R01 CA193365. 1. Fearon KC, Baracos VE. Cachexia in pancreatic cancer: new treatment options and measures of success. 2010; 2. Inui A. Cancer anorexia-cachexia syndrome: current issues in research and management. CA Cancer J Clin. 2002; 3. Winnard PT, Jr., et al., Brain metabolites in cholinergic and glutamatergic pathways are altered by pancreatic cancer cachexia. J Cachexia Sarcopenia Muscle. 2020. Citation Format: Balaji Krishnamachary, Ishwarya Sivakumar, Yelena Mironchik, Raj Kumar Sharma, Santosh Kumar Bharti, Marie-France Penet, Paul Winnard, Flonne Wildes, Eibhlin Goggins, Anirban Maitra, Michael G. Goggins, Zaver M. Bhujwalla. Downregulating the glutamine transporter, SLC1A5, significantly reduces cachexia in a PDAC xenograft [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2354.

Cannabinoid use for appetite stimulation and weight gain in cancer care: Does recent evidence support an update of the European Society for Clinical Nutrition and Metabolism clinical guidelines?

Cannabinoids have been used medicinally for thousands of years. Clinical trials support their use for treatment of chemotherapy-induced nausea and vomiting and HIV- and AIDS-related anorexia. Cancer anorexia cachexia syndrome (CACS) is a common debilitating condition and is associated with poor prognosis. The 2016 European Society for Parenteral and Enteral Nutrition clinical guidelines on nutrition in cancer patients concluded that "there are insufficient consistent clinical data to recommend cannabinoids to improve taste disorders or anorexia in cancer patients." The increased attention that cannabinoids have received in recent years warrants an updated evaluation of the literature on this topic, as practitioners are likely to encounter cancer patients interested in cannabinoid use. A systematic literature search was performed to assess the current body of evidence concerning cannabinoid use for the stimulation of appetite and oral intake by cancer patients. Over the past 20 years, 6 randomized controlled trials have evaluated the impact of cannabinoids on appetite-related outcomes in oncology patients in comparison with a control group or placebo. Based on this literature, cannabinoids do not appear to improve appetite, oral intake, weight, chemosensory function, or appetite-related quality of life. Limitations of the literature include small sample sizes, lack of adjustment for confounding variables, and difficulties conducting true placebo-controlled trials with a drug that may result in psychoactive side effects. Further exploration of the impact of cannabinoid use on CACS by using large, well-designed clinical trials is needed.

Virtual Teaming: Leveraging Team Science Sense-Making During COVID-19.

Individuals with cancer anorexia cachexia syndrome (CACS) experience multifaceted distress. To address CACS patient concerns regarding their experience of care, our cancer center established a specialized CACS clinic in 2016. We applied the team science principle of the team mental model (TMM) to support development of an effective interprofessional collaborative CACS care team. In 2020, cessation of CACS clinic in-person visits during coronavirus disease 2019 (COVID-19) threatened the viability of the entrenched TMM and once again jeopardized the patient experience of care.We present a case-based vignette as a representative composite of patient experiences to illustrate the challenges. A 48-year-old female was referred to our CACS clinic for pancreatic cancer-associated appetite and weight loss during COVID-19. To reduce risk of infection, in-person clinic visits were curtailed. When informed about the resulting need to defer the CACS assessment, the patient and her spouse expressed concern that postponement would adversely affect her ability to undergo anticancer treatments or achieve beneficial outcomes.To minimize delays in CACS treatment and optimize the patient experience of care, we applied the team science principle of sense-making to help the team rapidly reformulate the TMM to provide interprofessional collaborative CACS care via telemedicine. The sense-making initiative highlights opportunities to examine sense-making within health care teams more broadly during and after the pandemic. The application of sense-making within interprofessional cancer care teams has not been described previously.

Anorexia-cachexia syndrome in cancer patients: pathogenetic aspects and treatment options

Background. Modern standards for the treatment of both solid tumors and tumors of the blood system provide a mandatory assessment of the objective status of the patient. One of the important criteria of which is nutritional status. Underestimating the role of nutritional support in the treatment of cancer patients leads to a deterioration of treatment results due to the progressive deterioration of nutritional status and the development of cancer anorexia cachexia syndrome (CACS), which is an independent adverse factor leading to the death of the patient. The increase in the number of cancer patients with risk factors for CACS development requires not only close attention of clinicians to this problem, but also the development of clear recommendations for the diagnosis and management of such patients. This can contribute to solving several problems at once. First, it will allow optimizing monitoring of cancer patients predisposed to CACS development during anticancer treatment. Secondly, it will provide an opportunity to develop a diagnostic algorithm to prevent it. Third, the use of the identified criteria for predicting and outcome of complications both on an outpatient basis and in a hospital will be aimed at creating favorable conditions for anticancer therapy and thereby improving long-term treatment results and patients quality of life. Studying the mechanisms of development of CACS, the possibilities of correcting this condition, indicate the need for a multimodal concept and the rejection of the search for a “magic pill”. The results of a multicenter, prospective randomized study conducted in the oncology and hematology departments of healthcare institutions.Objective: to evaluate the effectiveness of FortiCare oral nutritional support in cancer patients under the real clinical practice.Materials and methods. The study included 96 patients with stage II–IV tumors. Radiation therapy was received by 28 patients, chemotherapy ‒ by 68 patients. Patient information was collected using an individual registration card. The patients were randomized according to nutritional support tactics (1:1). In the study group, with radiation (n = 14) and chemotherapy (n = 34), patients received enteral nutrition Forticare orally 125 ml 3 times a day in parallel with their usual diet. Patients in the control group during radiation therapy (n = 14) received the required amount of calories from their usual diet. During chemotherapy, patients in the control group (n = 34) with a lack of daily calorie intake received additional parenteral nutrition.Results and conclusion. While taking FortiCare, there was a smaller loss of body weight (p ≤0.05), a frequency of mucositis of the oral cavity, and esophagitis (p &gt;0.05). With chemotherapy, the incidence of diarrhea (p &lt;0.001) and constipation (p &lt;0.05) was detected less frequently than in the control group. A decrease in the frequency of hematological toxicity (leukopenia, thrombocytopenia) was noted (p &gt;0.05).

Cachexia and anorexia in cancer; a systematic review

The treatment strategy for cancer cachexia is based on the cachexia stage of the cancer and its phenotypes, therefore interventions and expected outcomes vary. In order for the patient to get the most out of the treatment, it should be done based on the mechanism of intervention and the quality of life of patients should be addressed, including aspects of rehabilitation and reduction of the patient’s suffering using a multidisciplinary team. Given the importance of the subject, the present study aims to investigate cachexia and anorexia in cancer. From the electronic databases, PubMed, Cochrane Library, Embase, Web of Sciences have been used to perform a systematic literature until 2020. Therefore, a software program (Endnote X8) has been utilized for managing electronic titles. Searches were performed with mesh terms. This review recommended that clinicians establish an interaction between cancer anorexia-cachexia syndrome (CACS) treatments and chronic pain treatments and choose the best treatment option.

Prospects for the use of additional oral nutrition (siping) in nutritional support of cancer patients

Most of cancer patients are faced with various nutritional disorders at the process of anticancer treatment. Cancer-inducedmetabolic abnormalities are impeded muscle recovery even with normal nutritional support. As a result, malnutrition candevelop into the cancer anorexia-cachexia syndrome, aggravate the disease and adversely affect the outcome of treatment.Purpose of the study. Evaluate the effectiveness of oral nutritional support in cancer patients at different stages ofantitumor treatment.Materials and methods. The literature research was conducted with keywords «quality of life», «nutritional support»,«oral nutrition», «cancer» in such databases as eLIBRARY and MEDLINE in Russian and English. There was performed ananalytical review of various methods of quality of life assessing, methods for assessing nutritional status and measuresof choice for the necessary nutritional therapy in cancer patients.Results. Nutritional support at all stages of treatment for cancer patients may have an impact on treatment outcomesand the incidence of complications. In case of palliative care, nutritional support can be aimed at improving patient'squality of life and reducing the severity of a number of clinical symptoms, in particular, such as nausea and vomiting.Conclusion. It has been shown, that individual and intensive elimination of nutritional defects improves the quality of lifeof patients, especially if this occurs at an early stage of the disease. Further study of the effect from nutrition-orientedinterventions in cancer patients undergoing treatment, is needed.

Brainstem prolactin-releasing peptide contributes to cancer anorexia-cachexia syndrome in rats

Up to 80% of cancer patients are affected by the cancer anorexia-cachexia syndrome (CACS), which leads to excessive body weight loss, reduced treatment success and increased lethality. The area postrema/nucleus of the solitary tract (AP/NTS) region emerged as a central nervous key structure in this multi-factorial process. Neurons in this area are targeted by cytokines and signal to downstream sites involved in energy homeostasis. NTS neurons expressing prolactin-releasing peptide (PrRP) are implicated in the control of energy intake and hypothalamus-pituitary-adrenal (HPA) axis activation, which contributes to muscle wasting. To explore if brainstem PrRP neurons contribute to CACS, we selectively knocked down PrRP expression in the NTS of hepatoma tumor-bearing rats by an AAV/shRNA gene silencing approach. PrRP knockdown reduced body weight loss and anorexia compared to tumor-bearing controls treated with a non-silencing AAV. Gastrocnemius and total hind limb muscle weight was higher in PrPR knockdown rats. Corticosterone levels were increased in the early phase after tumor induction at day 6 in both groups but returned to baseline levels at day 21 in the PrRP knockdown group. While we did not detect significant changes in gene expression of markers for muscle protein metabolism (MuRF-1, myostatin, mTOR and REDD1), mTOR and REDD1 tended to be lower after disruption PrRP signalling. In conclusion, we identified brainstem PrRP as a possible neuropeptide mediator of CACS in hepatoma tumor-bearing rats. The central and peripheral downstream mechanisms require further investigation and might involve HPA axis activation.

Open-label, randomized, multicenter, phase IV trial comparing parenteral nutrition using multi-chamber bags (Eurotubes) versus traditional 2/3-chamber bags in subjects with metastatic or locally advanced inoperable cancer requiring parenteral nutrition: The PEKANNUSS trial of the AIO.

TPS7086 Background: Approximately 50% of all cancer subjects suffer from cancer anorexia-cachexia syndrome accompanied by an inadequate food intake and predicting mortality, poor therapeutic response, diminished functional capacity, and reduced QoL. Especially in the advanced stages, parenteral nutrition (PN) is often required and accompanied by an increased risk of blood stream infections associated with increased mortality and other serious medical conditions such as sepsis. Furthermore, the switch from oral food intake to PN changes the patient’s everyday life leading to reduced autonomy and flexibility (e.g. due to dependency on home nursing services). This study aims at evaluating the incidence of catheter-related infections (CRI) and the frequency of self-administered parenteral nutrition at home (HPN) in patients receiving standard PN via A) traditional two- or three-chamber bags (often requiring addition of vitamins and/or medications by home care service) or B). the multi-chamber bags Eurotubes (minimizing additional supplements and enabling self-administration by patients at home). In addition, one group of patients will receive low glucose HPN via Eurotubes to investigate a possible benefit on clinical outcome. Methods: This is an open-label, randomized, multicenter, investigator-initiated, phase IV trial. Overall, 350 patients with inoperable metastatic or locally advanced solid tumors who have an indication for parenteral nutrition will be enrolled. Patients will be randomized 1:1:1 ratio to Arm A (Standard PN using Eurotubes) or Arm B (Standard PN using 2/3-chamber bags), or to Arm A-1 (low glucose using Eurotubes). Patients will be assessed (physical exam, ECOG, weight, QoL, lab tests, AEs, HPN documentation) every 4 weeks during the 12 months HPN treatment period. Co-primary endpoints are incidence of CRI and patient autonomy (rate of self-administered PN at home). Secondary endpoints comprise weight change, change in albumin and CRP levels, overall survival, QoL, and safety. Recruitment has just started; first patient in was on February 5th, 2020. Clinical trial information: NCT04105777 .

Nutritional insufficiency and therapy for cancer patients. Modern view on the problem

Background. Metabolic changes due to the progression of cancer and its aggressive treatment, lead to decreased food intake, related with development of cancer anorexia-cachexia syndrome (CACS) because of the complex interactions between pro-inflammatory cytokines and host metabolism. Beyond the physical and the metabolic consequences, cancer patients are often suffering from psychological distress, including depression. Material and Methods . A literature search and analysis of data was conducted in PubMed and Medline databases since 2000 with the purpose to evaluate the effectiveness of additional oral methods of nutritional support for cancer patients. Results. Nutritional support has a positive effect on response to cancer therapy and reduces the incidence of complications by optimizing the balance between energy expenditure and food consumption. In palliative care, nutritional support aims at improving patient’s quality of life by controlling symptoms such as nausea, vomiting and pain related to food intake. Conclusion. The literature review confirms that nutritional intervention has a direct impact on quality of life and should be integrated into the global cancer care because of its significant contribution to QoL. Furthermore, monitoring and correction of nutritional status should be an integral part of the quality of life assesses with the aim to optimize its adequacy to the patient’s needs and expectations.

Ketone Bodies Attenuate Wasting in Models of Atrophy.

BackgroundCancer Anorexia Cachexia Syndrome (CACS) is a distinct atrophy disease negatively influencing multiple aspects of clinical care and patient quality of life. Although it directly causes 20% of all cancer‐related deaths, there are currently no model systems that encompass the entire multifaceted syndrome, nor are there any effective therapeutic treatments.MethodsA novel model of systemic metastasis was evaluated for the comprehensive CACS (metastasis, skeletal muscle and adipose tissue wasting, inflammation, anorexia, anemia, elevated protein breakdown, hypoalbuminemia, and metabolic derangement) in both males and females. Ex vivo skeletal muscle analysis was utilized to determine ubiquitin proteasome degradation pathway activation. A novel ketone diester (R/S 1,3‐Butanediol Acetoacetate Diester) was assessed in multifaceted catabolic environments to determine anti‐atrophy efficacy.ResultsHere, we show that the VM‐M3 mouse model of systemic metastasis demonstrates a novel, immunocompetent, logistically feasible, repeatable phenotype with progressive tumor growth, spontaneous metastatic spread, and the full multifaceted CACS with sex dimorphisms across tissue wasting. We also demonstrate that the ubiquitin proteasome degradation pathway was significantly upregulated in association with reduced insulin‐like growth factor‐1/insulin and increased FOXO3a activation, but not tumor necrosis factor‐α‐induced nuclear factor‐kappa B activation, driving skeletal muscle atrophy. Additionally, we show that R/S 1,3‐Butanediol Acetoacetate Diester administration shifted systemic metabolism, attenuated tumor burden indices, reduced atrophy/catabolism and mitigated comorbid symptoms in both CACS and cancer‐independent atrophy environments.ConclusionsOur findings suggest the ketone diester attenuates multifactorial CACS skeletal muscle atrophy and inflammation‐induced catabolism, demonstrating anti‐catabolic effects of ketone bodies in multifactorial atrophy.