Clinical and Translational Oncology (2019) 21:87–93 https://doi.org/10.1007/s12094-018-02009-3 CLINICAL GUIDES IN ONCOLOGY SEOM clinical guidelines on nutrition in cancer patients (2018) R. de las Peñas1 · M. Majem2 · J. Perez‑Altozano3 · J. A. Virizuela4 · E. Cancer5 · P. Diz6 · O. Donnay7 · A. Hurtado8 · P. Jimenez‑Fonseca9 · M. J. Ocon10 Received: 3 December 2018 / Accepted: 5 December 2018 / Published online: 8 January 2019 © The Author(s) 2019 Abstract Nutritional deficiency is a common medical problem that affects 15–40% of cancer patients. It negatively impacts their qual- ity of life and can compromise treatment completion. Oncological therapies, such as surgery, radiation therapy, and drug therapies are improving survival rates. However, all these treatments can play a role in the development of malnutrition and/ or metabolic alterations in cancer patients, induced by the tumor or by its treatment. Nutritional assessment of cancer patients is necessary at the time of diagnosis and throughout treatment, so as to detect nutritional deficiencies. The Patient-Generated Subjective Global Assessment method is the most widely used tool that also evaluates nutritional requirements. In this guideline, we will review the indications of nutritional interventions as well as artificial nutrition in general and according to the type of treatment (radiotherapy, surgery, or systemic therapy), or palliative care. Likewise, pharmacological agents and pharmaconutrients will be reviewed in addition to the role of regular physical activity. Keywords Nutrition · Cancer · Guideline · Nutritional assessment 1 * R. de las Peñas Medical Oncology Department, Consorcio Hospital ramon.delaspenas@hospitalprovincial.es Provincial de Castellón, Av. Doctor Clara, 19, 12002 Castellón de la Plana, Spain M. Majem 2 MMajem@santpau.cat Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain J. Perez‑Altozano 3 jpaltozano@hotmail.com Medical Oncology Department, Hospital Virgen de los Lirios, Alcoy, Spain J. A. Virizuela 4 javirizuelae@seom.org Medical Oncology Department, Hospital Virgen Macarena, Sevilla, Spain E. Cancer 5 emilia.cancer@salud.madrid.org Endocrinology and Nutrition Department, Hospital Universitario de Fuenlabrada, Madrid, Spain P. Diz 6 pilardiz@tudiscovirtual.com Medical Oncology Department, Hospital de León, León, Spain O. Donnay 7 olga_donnay@telefonica.net Medical Oncology Department, Hospital Universitario de la Princesa, Madrid, Spain A. Hurtado 8 aliciahn76@hotmail.com Medical Oncology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain P. Jimenez‑Fonseca 9 palucaji@hotmail.com Medical Oncology Department, Hospital Universitario Central de Asturias, Oviedo, Spain M. J. Ocon 10 mjocon@salud.aragon.es Endocrinology and Nutrition Department, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain 13 Vol.:(0123456789) 88 Clinical and Translational Oncology (2019) 21:87–93 Introduction stage of cancer [11]. Patients with tumors of the gastrointes- tinal tract, head and neck, and liver and lung cancers are at Disease-related malnutrition has been defined as a condition high risk for malnutrition [2]. Consequently, the incidence resulting from the activation of the systemic inflammatory of malnutrition increases over the course of disease until response by an underlying disease, in this case, cancer [1, it affects 80% of all cancer patients [12, 13]. The Spanish 2]. This inflammatory response causes anorexia and tissue NUPAC study [13], designed to determine the prevalence degradation, which, in turn, can lead to significant weight of malnutrition in advanced cancer, confirmed a 52% rate loss, alterations in body composition, and decreased func- of moderate or severe malnutrition, with a distribution of tional capacity [2, 3]. 57.7% in esophageal, 50% in gastric, and 47.1% in laryngeal Specifically, cancer cachexia is a multifactorial syndrome cancers. More recently, a sub-analysis of the PREDYCES characterized by an involuntary, sustained loss of weight and study revealed that 36.4% of oncology patients were at nutri- skeletal muscle mass accompanied or not by a loss of fat tional risk at the time of hospital discharge. It also demon- mass. It cannot be fully reversed by conventional nutritional strated its significant association with longer hospital stays support and it leads to severe functional decline. There are and higher healthcare costs. Despite all of this, only 1/3 of several stages of cancer cachexia: precachexia, cachexia, and patients at nutritional risk received nutritional support [14]. refractory cachexia [2, 4]. Precachexia is characterized by It is a well-known fact that nutrition plays an important the presence of early clinical and metabolic signs, such as role in the prevention and treatment of cancer. The presence anorexia and glucose intolerance that precede the loss of of malnutrition negatively affects patients’ evolution and weight and muscle mass. The risk of progression to cachexia their quality of life, increasing the incidence of infection, varies and depends on the kind of cancer, the stage of dis- hospital stay, and mortality [11–13]. The aim of nutritional ease, the degree of systemic inflammation, the intake and intervention in cancer focuses on identifying and treating response to antineoplastic therapy [6]. Refractory cachexia malnutrition, maintaining, or improving muscle mass, as can result from a highly advanced or rapidly progressive well as intervening whenever possible to address metabolic cancer that does not respond to treatment. In this stage, and nutritional disturbances that hinder recover and survival active management of weight loss is no longer possible and in these individuals [3, 4]. life expectancy is less than 3 months [6, 7]. On the other hand, sarcopenia is a loss of muscle mass. In this case, asthenia is common; strength may be decreased, Methodology and functional capacity, limited [8]. Both cachexia [9] and sarcopenia entail a higher risk of antineoplastic treatment- This SEOM Guideline has been developed with the consen- related toxicity, reduced treatment response, worse surgical sus of ten physicians from medical oncology and endocri- outcomes, and lower survival rates [8]. We must pay special nology. We decided to use the US Agency for Healthcare attention to sarcopenic obesity, as it is an important predictor Research and Quality Service Grading System (USPSTF) of treatment-emergent adverse events [10]. to assign a level of evidence and a grade of recommenda- The proportion of patients who present weight loss at tion to the different statements contained in this guideline diagnosis is between 15 and 40%, depending on the type and (Table 1) [5]. Table 1  Levels of evidence and grades of recommendation Levels of evidence (I–V) Grades of recommendation (A–E) Evidence from at least one large randomized, controlled trial Strong evidence for efficacy with a substantial clinical benefit, strongly rec- of good methodological quality (low potential for bias) or ommended meta-analyses of well-conducted randomized trials without heterogeneity Small randomized trials or large randomized trials with Strong or moderate evidence for efficacy but with a limited clinical benefit, a suspicion of bias (lower methodological quality) or generally recommended meta-analyses of such trials or of trials with demonstrated heterogeneity Prospective cohort studies Insufficient evidence for efficacy or benefit does not outweigh risks or disad- vantages (adverse events, costs,…), optional Retrospective cohort studies or case–control studies Moderate evidence against efficacy or for adverse outcome, generally not recommended Studies without control group, case reports, expert opinions Strong evidence against efficacy or for adverse outcome, never recommended 13 Clinical and Translational Oncology (2019) 21:87–93 89 General concepts should be evaluated, especially in certain situations in which there are associated hydroelectrolyte disturbances. Screening and nutritional assessment The administration of high-doses of vitamins and trace elements is not recommended, except in cases of estab- Nutritional guidelines consistently advise screening for lished deficit [3, 15] (strength of recommendation: strong; nutritional risk at an early stage of cancer, followed by full level of evidence: moderate). nutritional assessment when risk is present with the aim of establishing nutritional intervention [2]. All oncology Types of nutritional interventions patients should be screened at the time of diagnosis and throughout treatment using a malnutrition screening tool Nutritional support is indicated when there is malnutrition validated in the setting in which the tool is intended for or risk of malnutrition; when the patient is not expected to use. Survivors should also be included in this evaluation be able to eat food for 1 week or more, or if their intake is [3, 15]. less than 60% of their needs for more than 1–2 weeks [3]. We recommend evaluating nutritional intake, weight Nutritional intervention is classified into: changes, and BMI obtained either directly or by means of validated nutrition screening tools: Malnutrition Uni- • Nutritional counseling (including oral nutritional sup- versal Screening Tool (MUST) for the outpatient clinic, plements) is the first and most commonly utilized inter- Nutrition Risk Screening 2002 (NRS-2002) for inpatients, vention to manage malnourished cancer patients and a Mini Nutritional Assessment Short Form (MNA-SF) for functioning gastrointestinal tract. This nutritional therapy the elderly, and the Malnutrition Screening Tool (MST) for has been shown to improve body weight, energy intake, inpatient and outpatient settings (strength of recommenda- PG-VSG scores, and certain aspects of quality of life, tion: strong; level of evidence: very low). albeit not survival [1, 3]. The Subjective Global Assessment Generated by the Patient (PG-SGA) is a tool that combines qualitative and Nutrition counseling (including oral nutritional supple- semi-quantitative data; it is valid and reliable in identify- ments) should be recommended to all cancer patients who ing malnutrition as part of a comprehensive nutritional able to eat, but are malnourished or at risk for malnutrition, assessment in oncology patients in both ambulatory and especially those who are undergoing oncological treatment acute care settings [3, 4]. Reduction in muscle mass can be (strength of recommendation: strong; level of evidence: recognized by dual X-ray absorptiometry (DEXA), com- moderate). puted tomography scans at lumbar level 3, or bioimped- ance analysis (BIA). Physical performance can be rated • Artificial nutrition (enteral and parenteral nutrition) is using scales (ECOG, Karnofsky), dynamometry, or gait selected depending on the type of cancer, its extent, com- speed. Systemic inflammation can be estimated by serum plications, treatment, and prognosis, and on the patient’s C-reactive protein (CRP) and albumin [3, 15]. status, needs, and duration of nutritional support [3, 15]. Nutritional assessment of food intake, muscle mass, physical performance, and systemic inflammation is rec- Enteral nutrition by tube is indicated if intake oral ommended for all patients identified as being at risk for is < 60% of requirement despite nutritional interventions per malnutrition by nutrition screening (strength of recom- os, and gastrointestinal function is preserved. When enteral mendation: strong; level of evidence: very low). nutrition is expected to last for more than 4–6 weeks, ostomy is preferred. If there is a risk of reflux, gastroparesis, or bron- choaspiration, jejunostomy or nasojejunal tube is preferred Energy and nutritional requirements over nasogastric or gastrostomy nutrition. Parenteral nutrition is indicated when it is not possible Cancer patients have similar nutritional requirements to to use the gastrointestinal tract, oral feeding and/or enteral the healthy population, around 25–30 kcal/kg/day, with a nutrition does not suffice, and there are expectations of balance between calorie intake and expenditure, including improvement in the patient’s quality of life and functional- the degree of physical activity (strength of recommenda- ity with the patient’s express desire. In cases of severe intes- tion: strong; level of evidence: low). tinal insufficiency due to radiation enteritis, chronic bowel Protein requirements are estimated to be between 1.2 obstruction, short bowel syndrome, or peritoneal carcino- and 1.5 g/kg/day. These values should be modified accord- matosis, nutritional status can be maintained by parenteral ing to patients’ renal function, as well as any other meta- nutrition. In order to prescribe home PN, the patient’s life bolic disturbances. The contribution of water and minerals expectancy must be more than 2–3 months and they must accept it. 13 90 Clinical and Translational Oncology (2019) 21:87–93 We recommend enteral nutrition (EN) if oral intake enteritis associated with radio/chemotherapy and on clini- remains inadequate despite nutritional counseling, and par- cal outcomes in patients with hematopoietic cell transplant, enteral nutrition if EN is not sufficient or feasible (strength results have been inconclusive [3, 4, 15, 17]. Due to the pos- of recommendation: strong; level of evidence: very low). sible increased rate of tumor relapse in hematopoietic stem cell transplant patients, its use is not recommended in these Role of physical exercise in nutritional status subjects [3]. A systematic review has demonstrated that the administration of enteral arginine significantly reduces the Endurance exercises, aerobic training, and activities such as incidence of fistulae and hospital stay in patients undergoing daily grooming or walking are considered effective strategies surgery for head and neck cancer, although the evidence is to enhance muscle strength and overall fitness. A systematic insufficient to recommend its use on this population [17, 18]. review reported that both aerobic and resistance exercise improves upper and lower body muscle strength more than Specific interventions based on cancer treatment usual care and there is some evidence that resistance exer- and stage of neoplastic disease cise is perhaps more effective for improving muscle strength than aerobic exercise [3]. Surgery We recommended physical exercise in cancer patients to support or improve muscle mass and function (strength of The enhanced recovery after surgery (ERAS) program recommendation: strong; level of evidence: high). seeks to lessen surgical stress, minimize catabolism, main- tain nutritional status, reduce complications, and optimize Pharmaconutrients recovery, making it both better and faster. The nutritional components of ERAS are: avoiding preoperative fasting, Pharmaconutrients are specific nutrients that have a modu- preoperative carbohydrate treatment, reestablishment of oral lating effect on the immune and metabolic function and can feeding on the first postoperative day, and early mobilization. have beneficial effects on clinical outcomes in malnourished As per this program, every patient should be screened for patients or those with advanced cancer and cachexia [16]. malnutrition and if deemed at risk, they should be provided Some clinical studies have proven that the use of fish- nutritional support [17]. derived, omega-3 polyunsaturated fatty acids (2 gr/day) in Management within an ERAS program is recommended individuals with advanced cancer receiving chemotherapy for all cancer patients undergoing either curative or pallia- improve appetite, energy zx intake, body weight, muscle tive surgery (strength of recommendation: strong; level of mass, and/or physical activity [3, 4]. Other studies have not evidence: high). revealed these same results [3]. Given its clinical safety, fish oil can be suggested for mal- Radiotherapy nourished patients with advanced cancer receiving chemo- therapy (strength of recommendation: weak; level of evi- Several RCTs and non-RCTs have demonstrated that indi- dence: low). vidualized nutritional counseling and/or oral nutritional There is strong scientific evidence from several meta- supplements improves nutritional intake, body weight, and analyses that show that enteral and oral immuno-nutrition QoL, enabling patients to avoid treatment interruptions and (a combination of arginine, nucleotides, and omega-3) sig- complete scheduled RT [3, 4, 19]. nificantly reduce postoperative infectious complications and All patients undergoing radiation of the gastrointestinal hospital stays in patients with cancer and upper gastrointes- tract or head and neck region should receive thorough nutri- tinal tract surgery [17]. tional assessment, individualized nutritional counseling and, The use of enteral immuno-nutrition in oncological if necessary, oral nutritional supplements (strength of rec- patients undergoing upper gastrointestinal surgery is rec- ommendation: strong; level of evidence: moderate). ommended (strength of recommendation: strong; level of Prospective and retrospective observational trials in evidence: high). patients with inadequate food intake have demonstrated that With the aim of increasing muscle mass, the use of cer- enteral feeding reduces weight loss and treatment interrup- tain branched-chain amino acids has been studies, such as tions and rehospitalizations compared to oral feeding [3]. leucine or its metabolite, Hydroxymethylbutyrate (HMB), Nasogastric tube feeding or gastrostomy results in simi- yielding clinically inconsistent results. Likewise, there is lar nutritional and clinical outcomes and overall quality of insufficient scientific evidence to recommend the combina- life, although the risk of tube dislodgement is lower and tion of glutamine-arginine-HMB [3]. certain quality-of-life domains fare better with PEG, while When evaluating the effect of oral or parenteral glu- nasogastric tubes are associated with less dysphagia and tamine on the prevention and treatment of mucositis/ earlier weaning after completion of radiotherapy. The risks 13 Clinical and Translational Oncology (2019) 21:87–93 91 of pneumonia and other infections are similar [20, 21]. In therapy has failed to prove a beneficial effect on survival cases in which the primary site is hypopharyngeal, the tumor [26]. Studies comparing EN to PN have shown that EN is is T4, or combined radio-chemotherapy, prophylactic tube feasible and possibly associated with lower complication and feeding (either nasogastric or gastrostomy) compared to infection rates, as fewer cases of decreased tumor response, reactive tube feeding (initiated after development of dys- compared to PN [3]. phagia), demonstrates improvements in weight loss, quality Cancer patients who are malnourished or losing weight of life, and decreases rehospitalization and treatment inter- and receiving anticancer treatment who are expected to be ruptions [22]. unable to consume and/or absorb adequate nutrients for In severe mucositis or in obstructive tumors of the head more than 1–2 weeks are candidates for artificial nutrition, or neck or thorax, enteral feeding is recommended using preferably by the enteral route. If EN is not sufficient or nasogastric or gastrostomy tubes (strength of recommenda- possible, PN is recommended (strength of recommendation; tion: strong; level of evidence: low). level of evidence: very low). PN is ineffective and probably harmful in oncological patients in whom there is no gastrointestinal reason for intes- Patients with advanced cancer receiving tinal failure [23]. In chronic radiation enteritis that evolves no anticancer treatment into intestinal failure, home PN appears to be a reasonable treatment option and is possibly superior to surgery [24, 25]. It is recommended that the nutritional status of patients with PN is only recommended if adequate oral/enteral nutri- advanced cancer be assessed, since deficits are associated tion is not possible (severe radiation enteritis or malabsorp- with worse quality of life and performance status [28]. Nutri- tion) (strength of recommendation: strong; level of evidence: tional support should be carefully contemplated, taking into moderate). account the patient’s expected survival, nutritional status, potential benefit, and the expectations and wishes of both Curative or palliative pharmacological cancer patient and their close relatives [29]. There is little evidence treatment of benefit of nutritional support in advanced cancer patients, particularly in the last weeks of life. Weight loss and low muscle mass prior to chemotherapy We recommend that all patients with advanced cancer are associated with increased risk of toxicity, worse perfor- be routinely screened for nutritional status. However, nutri- mance status, impaired quality of life, and shorter survival tional intervention should be raised only after considering [3]. Targeted therapies (particularly multikinase inhibitors) the potential benefit. In advanced, terminal phases of the have been commonly reported to result in weight loss and disease, artificial nutrition are unlikely to provide any benefit skeletal muscle wasting. On the other hand, weight stabili- for most patients (strength of recommendation: strong; level zation in gastrointestinal and lung cancer patients is corre- of evidence: low). lated with significant improvements in survival [3]. Dietary counseling and/or oral nutritional supplements may improve nutritional intake and quality of life, as well as stabilize body Cancer survivors weight [3]. During anticancer drug treatment, personalized dietary As cancer survivors are at higher risk for developing second counseling with oral nutritional supplements if necessary primary cancers and other chronic diseases, a diet rich in is recommended in cases of frank malnutrition and patients vegetables, fruits, and whole grains, and low in fats, red with decreased oral intake (strength of recommendation: meats, and alcohol is recommended [3]. A review of the strong; level of evidence: moderate). literature suggests that diet and exercise can have a posi- Use of artificial nutrition (enteral or parenteral nutri- tive impact on progressive disease and overall survival [27] tion) as “routine” in all cancer patients receiving cytotoxic (Table 2). 13 92 Clinical and Translational Oncology (2019) 21:87–93 Table 2  Final recommendations Recommendations Strength of Quality recommenda- of evi- tion dence Screening and nutritional assessment All cancer patients should be screened at the time of diagnosis and throughout treatment using a validated malnutri- A IV tion screening tool Nutritional assessment is recommended for all patients who are identified to be at risk for malnutrition by nutrition A IV screening Energy and nutricional requirements Cancer patients’ nutritional requirements are largely similar to those of the healthy population B III Proteins, water, and minerals requirements should be evaluated especially in certain situations. The administration B III of high-doses of vitamins and trace elements is not recommended Types of nutritional interventions Nutrition counseling should be recommended to all cancer patients who able to eat, but are malnourished or at risk B III for malnutrition Enteral nutrition, if oral intake remains inadequate despite nutritional counseling, and parenteral nutrition, if enteral B V nutrition is not sufficient or feasible Role of physical exercise in nutritional status Physical exercise in cancer patients to support or improve muscle mass and function A II Pharmaconutrients The use of fish oil in malnourished patients with advanced cancer receiving chemotherapy C IV The use of enteral immuno-nutrition in cancer patients undergoing upper gastrointestinal surgery A II Interventions relevant to specific patients categories Management within an ERAS program is recommended for all cancer patients undergoing either curative or pallia- A II tive surgery Nutritional assessment, individualized nutritional counseling, and, if necessary, oral nutritional supplements in all B III patients undergoing radiation of the gastrointestinal tract or of the head and neck In severe mucositis or in obstructive tumors of the head-neck or thorax, enteral feeding is recommended using B IV nasogastric or gastrostomy tubes Parenteral nutrition is recommended if adequate oral/enteral nutrition is not possible (severe radiation enteritis or B III malabsorption) During anticancer drug treatment, personalized dietary counseling, with oral nutritional supplements if necessary, is B III recommended in cases of frank malnutrition and patients with decreased oral intake Malnourished cancer patients receiving anticancer treatment who are expected to be unable to ingest and/or absorb B V adequate nutrients for more than 1–2 weeks are candidates for artificial nutrition (enteral or parenteral) In advanced terminal phases of the disease, artificial nutrition is unlikely to provide any benefit for most patients B IV In cancer survivors: maintaining a BMI between 18.5 and 25 kg/m2, physical activity, and a healthy diet B IV We recommend that a BMI of between 18.5 and 25 kg/m2 Ethical approval (Research involving human participants and/or ani- be maintained, in addition to physical activity and a healthy mals) The current study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and diet (strength of recommendation: strong; level of evidence: its later amendments. low). Informed Consent Informed Consent is not required for this type of Compliance with ethical standards study. Conflict of interest RP has nothing to disclose. MM has nothing to OpenAccess This article is distributed under the terms of the Crea- disclose. JPA reports speaker honoraria from Nestle, Abbott and Nu- tive Commons Attribution 4.0 International License (http://creat​iveco​ tricia, outside the submitted work. JAV reports honoraria from Baxter, mmons​.org/licen​ses/by/4.0/), which permits unrestricted use, distribu- outside the submitted work. EC has nothing to disclose. PD reports tion, and reproduction in any medium, provided you give appropriate grants, personal fees and non-financial support from Bristol Myers credit to the original author(s) and the source, provide a link to the Squibb, Roche and MSD, grants and personal fees from Astrazeneca, Creative Commons license, and indicate if changes were made. Boehringer Ingelheim and Lilly, outside the submitted work. 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