A multi-national survey of experience and attitudes towards commencing home parenteral nutrition for patients with advanced cancer.

INTRODUCTION: Advanced cancer (AC) is increasingly an indication for home parenteral nutrition (HPN) but an area with possible variation in practice between geographical locations. The aims of this study are to explore the views and experiences of international multi-disciplinary teams to determine opinions and practices. METHODS: An online questionnaire was developed with members of the Home Artificial Nutrition and Chronic Intestinal Failure interest group of the European Society for Clinical Nutrition and Metabolism (ESPEN) and distributed to colleagues involved in managing patients with AC on HPN. RESULTS: A total of 220 responses were included from 5 continents including 36 countries, with 90% of all responses from Europe. Predicted survival was a key factor influencing the decision to commence HPN for most respondents 152/220 (75%), with the majority of participants reporting that patients should have a predicted survival of ≥3 months if considered for HPN (≥3 months: n = 124, 56% vs. <3 months: n = 47, 21%, p < 0.001). However, most respondents were not confident about predicting overall survival in more than 50% of cases (confident n = 40, 23% vs not confident n = 135, 77%, p < 0.001). Barriers to utilising HPN in AC included colleagues' objections (n = 91, 46%), lack of local expertise (n = 55, 28%) and funding restrictions (n = 34, 17%). CONCLUSIONS: Significant consensus was observed regarding AC as indication for HPN, while areas of variation exist. Survival prognostication is often used as an indication for commencing HPN in people with AC, although the majority of respondents were not confident in prognosticating, suggesting better clinical prognostication tools will be of assistance. Further studies are also required to better understand the obstacles faced by clinical teams to commencing HPN that may explain variations in clinical practice between countries, as well as adressing variation in funding.

Does nutrition for cancer patients feed the tumour? A clinical perspective.

This review aims to answer to two basic questions: a) Which substrates does a tumour utilize and is there a regimen that might potentially favour the host over the tumour? and b) Does nutritional intervention disproportionally affect tumour growth? Literature to date focuses on humans; although some references to molecular mechanisms regulating cancer cells metabolism derive from studies on experimental tumours and cell biology. Literature shows that some tumours, especially those of the brain and head/neck and lung, are glucose-dependent, and patients with these tumours could benefit from a normocaloric ketogenic diet provided these tumours exhibit high fluorodeoxyglucose (18F-FDG) captation. A high fat-protein, low carbohydrate diet appears to better fulfil the nutritional requirements of the cancer patient. Current evidence shows no improvement in tumoral response after restricting patients' caloric intake; whereas malnutrition is acknowledged as an important negative predictive and prognostic factor in all cancer patients.

Forcing the vicious circle: sarcopenia increases toxicity, decreases response to chemotherapy and worsens with chemotherapy.

Sarcopenia has recently emerged as a new condition that, independently from malnutrition, may adversely affect the prognosis of cancer patients. Purpose of this narrative review is to define the prevalence of sarcopenia in different primaries, its role in leading to chemotherapy toxicity and decreased compliance with the oncological therapy and the effect of some drugs on the onset of sarcopenia. Finally, the review aims to describe the current approaches to restore the muscle mass through nutrition, exercise and anti-inflammatory agents or multimodal programmes with a special emphasis on the results of randomized controlled trials. The examination of the computed tomography scan at the level of the third lumbar vertebra-a common procedure for staging many tumours-has allowed the oncologist to evaluate the muscle mass and to collect many retrospective data on the prevalence of sarcopenia and its clinical consequences. Sarcopenia is a condition affecting a high percentage of patients with a range depending on type of primary tumour and stage of disease. It is noteworthy that patients may be sarcopenic even if their nutritional status is apparently maintained or they are obese. Sarcopenic patients exhibited higher chemotherapy toxicity and poorer compliance with oncological treatments. Furthermore, several antineoplastic drugs appeared to worsen the sarcopenic status. Therapeutic approaches are several and this review will focus on those validated by randomized controlled trials. They include the use of ω-3-enriched oral nutritional supplements and orexigenic agents, the administration of adequate high-protein regimens delivered enterally or parenterally, and programmes of physical exercise. Better results are expected combining different procedures in a multimodal approach. In conclusion, there are several premises to prevent/treat sarcopenia. The oncologist should coordinate this multimodal approach by selecting priorities and sequences of treatments and then involving a nutrition health care professional or a physical therapist depending on the condition of the single patient.

ESPEN expert group recommendations for action against cancer-related malnutrition.

Patients with cancer are at particularly high risk for malnutrition because both the disease and its treatments threaten their nutritional status. Yet cancer-related nutritional risk is sometimes overlooked or under-treated by clinicians, patients, and their families. The European Society for Clinical Nutrition and Metabolism (ESPEN) recently published evidence-based guidelines for nutritional care in patients with cancer. In further support of these guidelines, an ESPEN oncology expert group met for a Cancer and Nutrition Workshop in Berlin on October 24 and 25, 2016. The group examined the causes and consequences of cancer-related malnutrition, reviewed treatment approaches currently available, and built the rationale and impetus for clinicians involved with care of patients with cancer to take actions that facilitate nutrition support in practice. The content of this position paper is based on presentations and discussions at the Berlin meeting. The expert group emphasized 3 key steps to update nutritional care for people with cancer: (1) screen all patients with cancer for nutritional risk early in the course of their care, regardless of body mass index and weight history; (2) expand nutrition-related assessment practices to include measures of anorexia, body composition, inflammatory biomarkers, resting energy expenditure, and physical function; (3) use multimodal nutritional interventions with individualized plans, including care focused on increasing nutritional intake, lessening inflammation and hypermetabolic stress, and increasing physical activity.

ESPEN guidelines on nutrition in cancer patients

Cancers are among the leading causes of morbidity and mortality worldwide, and the number of new cases is expected to rise significantly over the next decades. At the same time, all types of cancer treatment, such as surgery, radiation therapy, and pharmacological therapies are improving in sophistication, precision and in the power to target specific characteristics of individual cancers. Thus, while many cancers may still not be cured they may be converted to chronic diseases. All of these treatments, however, are impeded or precluded by the frequent development of malnutrition and metabolic derangements in cancer patients, induced by the tumor or by its treatment. These evidence-based guidelines were developed to translate current best evidence and expert opinion into recommendations for multi-disciplinary teams responsible for identification, prevention, and treatment of reversible elements of malnutrition in adult cancer patients. The guidelines were commissioned and financially supported by ESPEN and by the European Partnership for Action Against Cancer (EPAAC), an EU level initiative. Members of the guideline group were selected by ESPEN to include a range of professions and fields of expertise. We searched for meta-analyses, systematic reviews and comparative studies based on clinical questions according to the PICO format. The evidence was evaluated and merged to develop clinical recommendations using the GRADE method. Due to the deficits in the available evidence, relevant still open questions were listed and should be addressed by future studies. Malnutrition and a loss of muscle mass are frequent in cancer patients and have a negative effect on clinical outcome. They may be driven by inadequate food intake, decreased physical activity and catabolic metabolic derangements. To screen for, prevent, assess in detail, monitor and treat malnutrition standard operating procedures, responsibilities and a quality control process should be established at each institution involved in treating cancer patients. All cancer patients should be screened regularly for the risk or the presence of malnutrition. In all patients - with the exception of end of life care - energy and substrate requirements should be met by offering in a step-wise manner nutritional interventions from counseling to parenteral nutrition. However, benefits and risks of nutritional interventions have to be balanced with special consideration in patients with advanced disease. Nutritional care should always be accompanied by exercise training. To counter malnutrition in patients with advanced cancer there are few pharmacological agents and pharmaconutrients with only limited effects. Cancer survivors should engage in regular physical activity and adopt a prudent diet.

Defining malnutrition: A plea to rethink.

In a recent consensus report in Clinical Nutrition the undernourished category of malnutrition was proposed to be defined and diagnosed on the basis of a low BMI or unintentional weight loss combined with low BMI or FFMI with certain cut off points. The definition was endorsed by ESPEN despite recent endorsement of a very different definition. The approach aims to assess whether nutritional intake is sufficient but is imprecise because a low BMI does not always indicate malnutrition and individuals with increasing BMI's may have decreasing FFM's. The pathophysiology of individuals, considered to be malnourished in rich countries and in areas with endemic malnutrition, results predominantly from deficient nutrition combined with infection/inflammation. Both elements jointly determine body composition and function and consequently outcome of disease, trauma or treatment. When following the consensus statement only an imprecise estimate is acquired of nutritional intake without knowing the impact of inflammation. Most importantly, functional abilities are not assessed. Consequently it will remain uncertain how well the individual can overcome stressful events, what the causes are of dysfunction, how to set priorities for treatment and how to predict the effect of nutritional support. We therefore advise to consider the pathophysiology of malnourished individuals leading to inclusion of the following elements in the definition of malnutrition: a disordered nutritional state resulting from a combination of inflammation and a negative nutrient balance, leading to changes in body composition, function and outcome. A precise diagnosis of malnutrition should be based on assessment of these elements.

European Society of Coloproctology consensus on the surgical management of intestinal failure in adults.

Intestinal failure (IF) is a debilitating condition of inadequate nutrition due to an anatomical and/or physiological deficit of the intestine. Surgical management of patients with acute and chronic IF requires expertise to deal with technical challenges and make correct decisions. Dedicated IF units have expertise in patient selection, operative risk assessment and multidisciplinary support such as nutritional input and interventional radiology, which dramatically improve the morbidity and mortality of this complex condition and can beneficially affect the continuing dependence on parenteral nutritional support. Currently there is little guidance to bridge the gap between general surgeons and specialist IF surgeons. Fifteen European experts took part in a consensus process to develop guidance to support surgeons in the management of patients with IF. Based on a systematic literature review, statements were prepared for a modified Delphi process. The evidence for each statement was graded using Oxford Centre for Evidence-Based Medicine Levels of Evidence. The current paper contains the statements reflecting the position and practice of leading European experts in IF encompassing the general definition of IF surgery and organization of an IF unit, strategies to prevent IF, management of acute IF, management of wound, fistula and stoma, rehabilitation, intestinal and abdominal reconstruction, criteria for referral to a specialist unit and intestinal transplantation.

Development and validation of a nomogram to predict survival in incurable cachectic cancer patients on home parenteral nutrition.

BACKGROUND: The use of home parenteral nutrition (HPN) in incurable cancer patients is extremely varied across different countries and institutions. In order to assess the clinical impact implied, we previously conducted a survey of incurable cancer patients receiving HPN, which shows that survival was markedly affected by Karnofsky performance status (KPS), tumor spread, Glasgow prognostic score (GPS) and tumor site. The aim of this study was to develop a nomogram incorporating the above factors for survival prediction. PATIENTS AND METHODS: We gathered a series of 579 patients, all receiving HPN, which was randomly split into a training and a testing sample. Using Cox proportional hazard regression modeling, a nomogram was built in the training sample, in order to estimate median survival or survival probability at 3 and 6 months according to individual patient characteristics. The nomogram performance was then verified in the testing sample. RESULTS: In the training sample, median survival was 3.2 (95% CI 3.0-3.7) months. GPS, KPS, tumor site and spread were confirmed to be significant prognostic factors. A significant interaction was also shown between the site and spread while weight loss (WL), adjusted for body mass index, failed to provide any substantial prognostic contribution. In the testing sample, nomogram performance was good in terms of calibration and discreet regarding discrimination. CONCLUSION: With the growing availability of new oncological treatments and their tendency to transform the trajectory of the advanced cancer into a chronic condition characterized by progressive WL and poor nutrients intake, an increasing number of patients are expected to receive HPN. In such a setting, tools for predicting the survival outcome may play a role toward personalized medicine and for investigating novel experimental therapies. Our proposed nomogram is a step forward in this direction but needs to be made stronger in order to definitely have clinical utility.

Early recognition of malnutrition and cachexia in the cancer patient: a position paper of a European School of Oncology Task Force.

BACKGROUND: Weight loss and cachexia are common, reduce tolerance of cancer treatment and the likelihood of response, and independently predict poor outcome. METHODS: A group of experts met under the auspices of the European School of Oncology to review the literature and-on the basis of the limited evidence at present-make recommendations for malnutrition and cachexia management and future research. CONCLUSIONS: Our focus should move from end-stage wasting to supporting patients' nutritional and functional state throughout the increasingly complex and prolonged course of anti-cancer treatment. When inadequate nutrient intake predominates (malnutrition), this can be managed by conventional nutritional support. In the presence of systemic inflammation/altered metabolism (cachexia), a multi-modal approach including novel therapeutic agents is required. For all patients, oncologists should consider three supportive care issues: ensuring sufficient energy and protein intake, maintaining physical activity to maintain muscle mass and (if present) reducing systemic inflammation. The results of phase II/III trials based on novel drug targets (e.g. cytokines, ghrelin receptor, androgen receptor, myostatin) are expected in the next 2 years. If effective therapies emerge, early detection of malnutrition and cachexia will be increasingly important in the hope that timely intervention can improve both patient-centered and oncology outcomes.

The prognosis of incurable cachectic cancer patients on home parenteral nutrition: a multi-centre observational study with prospective follow-up of 414 patients.

BACKGROUND: The role of home parenteral nutrition (HPN) in incurable cachectic cancer patients unable to eat is extremely controversial. The aim of this study is to analyse which factors can influence the outcome. PATIENTS AND METHODS: We studied prospectively 414 incurable cachectic (sub)obstructed cancer patients receiving HPN and analysed the association between patient or clinical characteristics and surviving status. RESULTS: Median weight loss, versus pre-disease and last 6-month period, was 24% and 16%, respectively. Median body mass index was 19.5, median KPS was 60, median life expectancy was 3 months. Mean/median survival was 4.7/3.0 months; 50.0% and 22.9% of patients survived 3 and 6 months, respectively. At the multivariable analysis, the variables significantly associated with 3- and 6-month survival were Glasgow Prognostic Score (GPS) and KPS, and GPS, KPS and tumour spread, respectively. By the aggregation of the significant variables, it was possible to dissect several classes of patients with different survival probabilities. CONCLUSIONS: The outcome of cachectic incurable cancer patients on HPN is not homogeneous. It is possible to identify groups of patients with a ≥6-month survival (possibly longer than that allowed in starvation). The indications for HPN can be modulated on these clinical/biochemical indices.

ESPEN Guidelines on Parenteral Nutrition: non-surgical oncology.

Parenteral nutrition offers the possibility of increasing or ensuring nutrient intake in patients in whom normal food intake is inadequate and enteral nutrition is not feasible, is contraindicated or is not accepted by the patient. These guidelines are intended to provide evidence-based recommendations for the use of parenteral nutrition in cancer patients. They were developed by an interdisciplinary expert group in accordance with accepted standards, are based on the most relevant publications of the last 30 years and share many of the conclusions of the ESPEN guidelines on enteral nutrition in oncology. Under-nutrition and cachexia occur frequently in cancer patients and are indicators of poor prognosis and, per se, responsible for excess morbidity and mortality. Many indications for parenteral nutrition parallel those for enteral nutrition (weight loss or reduction in food intake for more than 7-10 days), but only those who, for whatever reason cannot be fed orally or enterally, are candidates to receive parenteral nutrition. A standard nutritional regimen may be recommended for short-term parenteral nutrition, while in cachectic patients receiving intravenous feeding for several weeks a high fat-to-glucose ratio may be advised because these patients maintain a high capacity to metabolize fats. The limited nutritional response to the parenteral nutrition reflects more the presence of metabolic derangements which are characteristic of the cachexia syndrome (or merely the short duration of the nutritional support) rather than the inadequacy of the nutritional regimen. Perioperative parenteral nutrition is only recommended in malnourished patients if enteral nutrition is not feasible. In non-surgical well-nourished oncologic patients routine parenteral nutrition is not recommended because it has proved to offer no advantage and is associated with increased morbidity. A benefit, however, is reported in patients undergoing hematopoietic stem cell transplantation. Short-term parenteral nutrition is however commonly accepted in patients with acute gastrointestinal complications from chemotherapy and radiotherapy, and long-term (home) parenteral nutrition will sometimes be a life-saving maneuver in patients with sub acute/chronic radiation enteropathy. In incurable cancer patients home parenteral nutrition may be recommended in hypophagic/(sub)obstructed patients (if there is an acceptable performance status) if they are expected to die from starvation/under nutrition prior to tumor spread.

ESPEN Guidelines on Parenteral Nutrition: surgery.

In modern surgical practice it is advisable to manage patients within an enhanced recovery protocol and thereby have them eating normal food within 1-3 days. Consequently, there is little room for routine perioperative artificial nutrition. Only a minority of patients may benefit from such therapy. These are predominantly patients who are at risk of developing complications after surgery. The main goals of perioperative nutritional support are to minimize negative protein balance by avoiding starvation, with the purpose of maintaining muscle, immune, and cognitive function and to enhance postoperative recovery. Several studies have demonstrated that 7-10 days of preoperative parenteral nutrition improves postoperative outcome in patients with severe undernutrition who cannot be adequately orally or enterally fed. Conversely, its use in well-nourished or mildly undernourished patients is associated with either no benefit or with increased morbidity. Postoperative parenteral nutrition is recommended in patients who cannot meet their caloric requirements within 7-10 days orally or enterally. In patients who require postoperative artificial nutrition, enteral feeding or a combination of enteral and supplementary parenteral feeding is the first choice. The main consideration when administering fat and carbohydrates in parenteral nutrition is not to overfeed the patient. The commonly used formula of 25 kcal/kg ideal body weight furnishes an approximate estimate of daily energy expenditure and requirements. Under conditions of severe stress requirements may approach 30 kcal/kg ideal body weights. In those patients who are unable to be fed via the enteral route after surgery, and in whom total or near total parenteral nutrition is required, a full range of vitamins and trace elements should be supplemented on a daily basis.

Locoregional treatment of peritoneal carcinomatosis from gastric cancer.

The authors reviewed the natural history and the main features of the peritoneal carcinomatosis from gastric cancer briefly and analyzed the pertinent literature concerning the locoregional modalities for prevention and for treatment. Results of the web based voting by experts were also summarized. As regards the peritoneal perfusion with cytotoxic drugs with or without hyperthermia for preventing peritoneal carcinomatosis in high risk patients, there are some randomized clinical trials and one meta-analysis supporting a benefit of the procedure. However, disparity in methodology (drugs, dosage, duration of the treatment, addition of hyperthermia, etc.) precludes the adoption of a shared protocol to be used in the clinical practice in high risk patients. Once the peritoneal carcinomatosis is established, the approach reported in literature is the peritonectomy associated with hyperthermic perfusion. However, data supporting benefits are scanty, and limited to few centers with a specific experience in this field. With regard to the main questions addressed to the experts' panel and concerning the indications for treatment and methodology, there was a general consistency among the experts and agreement with the findings of the literature. The need for a large multicenter trial to confirm the benefit and risk of intraperitoneal chemotherapy was recognized by both the experts and the authors.

Shall we operate? Preoperative assessment in elderly cancer patients (PACE) can help. A SIOG surgical task force prospective study.

BACKGROUND: A number of elderly cancer patients do not receive standard surgery for solid tumors because they are considered unfit for treatment as a consequence of inaccurate estimation of the operative risk. To tailor treatment to onco-geriatric series, oncologists are now beginning to use a comprehensive geriatric assessment (CGA). This study investigates the value of an extended CGA in assessing the suitability of elderly patients for surgical intervention. PATIENTS AND METHODS: Preoperative assessment of cancer in the elderly (PACE) incorporates validated instruments including the CGA, an assessment of fatigue and performance status and an anaesthesiologist's evaluation of operative risk. An international prospective study was conducted using 460 consecutively recruited elderly cancer patients who received PACE prior to elective surgery. Mortality, post-operative complications (morbidity) and length of hospital stay were recorded up to 30 days after surgery. RESULTS: Poor health in relation to disability (assessed using the instrumental activities of daily living (IADL)), fatigue and performance status (PS) were associated with a 50% increase in the relative risk of post-operative complications. Multivariate analysis identified moderate/severe fatigue, a dependent IADL and an abnormal PS as the most important independent predictors of post-surgical complications. Disability assessed by activities of daily living (ADL), IADL and PS were associated with an extended hospital stay. CONCLUSION: PACE represents a valuable tool in enhancing the decision process concerning the candidacy of elderly cancer patients for surgical intervention and can reduce inappropriate age-related inequity in access to surgical intervention. It is recommended that PACE be used routinely in surgical practice.

ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology.

Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility of increasing or ensuring nutrient intake in cases where normal food intake is inadequate. These guidelines are intended to give evidence-based recommendations for the use of ONS and TF in cancer patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards, are based on all relevant publications since 1985 and were discussed and accepted in a consensus conference. Undernutrition and cachexia occur frequently in cancer patients and are indicators of poor prognosis. EN should be started if undernutrition already exists or if food intake is markedly reduced for more than 7-10 days. Standard formulae are recommended for EN. Nutritional needs generally are comparable to non-cancer subjects. In cachectic patients metabolic modulators such as progestins, steroids and possibly eicosapentaenoic acid may help to improve nutritional status. EN is indicated preoperatively for 5-7 days in cancer patients undergoing major abdominal surgery. During radiotherapy of head/neck and gastrointestinal regions dietary counselling and ONS prevent weight loss and interruption of radiotherapy. Routine EN is not indicated during (high-dose) chemotherapy.