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Contents lists available at ScienceDirect

Digestive and Liver Disease

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osition Paper

linical nutrition guidelines of the French Speaking Society of Clinicalutrition and Metabolism (SFNEP): Summary of recommendations fordults undergoing non-surgical anticancer treatment

rench Speaking Society of Clinical Nutrition and Metabolism (SFNEP)

r t i c l e i n f o

rticle history:eceived 20 December 2013ccepted 28 January 2014vailable online xxx

a b s t r a c t

Up to 50% of patients with cancer suffer from weight loss and undernutrition (as called cachexia) eventhough it is rarely screened or properly handled. Patients’ prognosis and quality of life could be greatlyimproved by simple and inexpensive means encompassing nutritional status assessment and effective

eywords:linical practicevidence-basedutritional care

nutritional care. These guidelines aim to give health professionals and patients practical and up-to-dateadvice to manage nutrition in the principal situations encountered during the cancer course accordingto the type of tumour and treatment (i.e. radio and/or chemotherapy). Specific suggestions are made forpalliative and elderly patients because of specific risks of undernutrition and related comorbidities in thissubset. Levels of evidence and grades of recommendations are detailed as stated by current literatureand consensus opinion of clinical experts in each field.

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. Introduction

Up to 50% of cancer patients undergo involuntary weight lossith deleterious consequences. Indeed, the disease itself and

ts related treatments often trigger taste and smell alterations,ppetite loss, swallowing disorders and enhanced catabolism lead-ng to an expected higher undernutrition risk [1].

Increased incidence of comorbidities (mainly infectious compli-ations), poorer tolerance, higher toxicity of treatments and altereduality of life are the common outcomes associated with under-utrition and bring about amplified hospital costs and mortality.owever patients’ nutritional status could be greatly improved by

imple screening steps and proper handling reflexes. It is there-

Please cite this article in press as: Senesse P, et al. Clinical nutrition guMetabolism (SFNEP): Summary of recommendations for adults undehttp://dx.doi.org/10.1016/j.dld.2014.01.160

ore crucial to develop appropriate and efficient strategies to reachetter nutritional care for oncology patients.

Pierre Senessea,*, Patrick Bachmannb, René-Jean Bensadounc, Isabelle Besnardd,sabelle Bourdel-Marchassone, Corinne Bouteloupf, Pascal Crenng, Franc oisoldwasserh, Olivier Guérind, Paule Latino-Marteli, Jocelyne Meuricj, Franc oiseay-Lévink, Mauricette Michalletl, Marie-Paule Vassonm, Xavier Hébuterned

a Department of Clinical Nutrition and Gastroenterology, Institut régional du Can-er – Montpellier (ICM) – Val d’Aurelle, Epsylon Laboratory, EA 4556, Universitiesontpellier 1 and 3. Siric Montpellier Cancer, , Montpellier, Franceb-m See Appendix A.∗ Corresponding author. SFNEP: Via Pierre Senesse, Montpellier Cancer Institute

MCI), Unit of Clinical Nutrition and Gastroenterology, 208, avenue des Apothicaires,arc Euromédecine, F-34298 Montpellier cedex 05, France. Tel.: +33 46 7618554;ax: +33 46 7613729.

E-mail address: pierre.senesse@icm.unicancer.fr (P. Senesse).

590-8658/$36.00 © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevierttp://dx.doi.org/10.1016/j.dld.2014.01.160

roenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The French-speaking Society for Clinical Nutrition andMetabolism (SFNEP) is a transversal organisation representing allhealth professionals interested in clinical nutrition (physicians,nurses, pharmacists, dieticians, and students). The first mission ofSFNEP is to support quality patient care, education and research inthe fields of clinical nutrition. Complete guidelines were publishedin French in December 2012 [2]. The clinical guidelines proposedin this paper are therefore the first to be internationally publishedby the SFNEP in adult anticancer treatment. This article resultsfrom a large-scale literature analysis (Supplementary methods inAppendix B) and is intended for health professionals deliveringcancer care outside the perioperative context [3].

2. Definitions

Because terminology used in different parts of the world may nothave the same meaning, the definitions referred to in this documentare as follows.

- In the curative phase, treatments may cure cancer. In the pallia-tive phase, cancer may not be cured but may be stabilised with apotential survival gain. In the advanced palliative phase, diseaserapidly progresses despite treatments and death occurs usuallywithin the next few months. Terminally-ill patients have a lifeexpectancy of one month or less.

idelines of the French Speaking Society of Clinical Nutrition andrgoing non-surgical anticancer treatment. Dig Liver Dis (2014),

- Disease-associated undernutrition, also called cachexia, is a patho-logical state resulting from both reduced food intake andmetabolic abnormalities such as inflammation, hypermetabolismand hypercatabolism [1]. Associated clinical signs are a general

Ltd. All rights reserved.

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state degradation, ≥2% or ≥5% weight loss and/or sarcopeniaand/or inflammation. Treatment of cancer-associated undernu-trition is multidimensional and involves nutritional care, exerciseand treatment of inflammation [4]. For clarity reasons andbecause all cited studies may not have referred exactly to thisdefinition, the term “undernutrition” will be used in this paper.

Personalised dietary counselling is performed by a nutrition expertall along and after treatment and generally consists of severaldietary consultations, including nutritional status and food intakeassessment as well as dietary advice.

Sip feeds, also called oral nutritional supplements, are dietaryproducts intended to special medical purposes. They are usuallyindustrially produced and ready-to-use.

Artificial nutrition includes enteral nutrition which is administereddirectly into the digestive tract (i.e. via nasogastric or nasojejunaltube, gastrostomy or jejunostomy) and parenteral nutrition whichis administered intravenously.

Immunonutrition corresponds to the use of nutritional substrates(immunonutrients) able to modulate (increase or decrease) theimmune functions of the organism.

. Nutritional evaluation

.1. Weight and anorexia

In the settings of radiotherapy, medical oncology or palliativereatments, weight loss is a factor associated with poor progno-is, reduced quality of life and increased morbidity. Among the 31nalysed clinical studies, weight loss incidence varied from 8.2%o 87% according to the type of tumour, the stage of disease, andhe defined weight loss thresholds [5]. In multivariate analysis28 studies), survival or toxicity were significantly associated witheight loss. In 15 studies, weight loss definition was based on aeriod of time without a specific threshold (i.e. six months, fromhe disease onset to weight loss assessment). However, the work-ng group recommends a 5% weight loss threshold as a marker ofndernutrition since this definition was chosen in ten studies [5].

Anorexia, defined as loss of appetite, contributes to a con-iderable extent to undernutrition. It occurs in 70.9% of patientsndergoing chemotherapy or radiotherapy and up to 90.7% ofnorexic patients suffer from weight loss [6]. Currently, anorexia isaken into account in most undernutrition screening tools. Indeed,norexia and weight loss were closely related in an observationalrospective cohort of 1000 non-palliative cancer patients [7]. Innother prospective study on 1115 patients with advanced lungr colorectal cancer, intake reduction and anorexia were the mostmportant factors associated with prognosis [8]. Furthermore, aevel 2 evidence study has recently confirmed the strong correlationetween intake assessed by analogue scales (verbal or visual) and

ntake assessed by dietary survey (P < 0.0001) [9]. In the subset ofatients suffering from or at risk of undernutrition, the likelihood ofeing undernourished exceeded 80% when the analogue scale scoreas less than 7. Finally, in a prospective study (level 2 evidence)

n 222 patients with oesophageal cancer, reduced oral intake wasignificantly associated with degree of weight loss (P < 0.001) [10].

.2. Body mass index

Body mass index (BMI) should not be used alone when screeningor undernutrition. In an observational prospective study on 7606n or outpatients, of which 1186 had cancer (15.6%), a BMI < 18.5

Please cite this article in press as: Senesse P, et al. Clinical nutrition guMetabolism (SFNEP): Summary of recommendations for adults undehttp://dx.doi.org/10.1016/j.dld.2014.01.160

redicted undernutrition with a sensitivity and specificity of 21%nd 95%, respectively when compared to a weight loss > 10% [11].n this study, a BMI < 18.5 was a poor predictor of undernutrition41% true positives).

PRESSr Disease xxx (2014) xxx–xxx

Consistently, a French observational prospective study showedthat a weight loss > 5% was observed in 40.9% of cancer patientseven though BMI values below 18.5 (<70-year-old patients) andbelow 21 (≥70-year-old patients) concerned only 8.4% and 4%of patients, respectively. Moreover, 38.8% of the obese patients(BMI ≥ 30) experienced a weight loss≥10% over the past 6 months[12].

3.3. Other predictive scores or tools

Several multidimensional assessment tools including SGA (Sub-jective Global Assessment), PG-SGA (Patient-Generated SubjectiveGlobal Assessment) and MNA (Mini Nutritional Assessment for>70-year-old subjects) are validated in the medical oncology set-ting [5]. Although these multidimensional assessment tools arenot included in the diagnostic of undernutrition as defined in thispaper, they may help clinicians screening cancer patients whichare at risk of undernutrition. SGA is significantly associated withlength of stay [13] and both SGA and PG-SGA are reliable predictivefactors for survival [14,15]. Concerning >70-year-old patients, theMNA score have a good predictive value for length of chemother-apy, progression-free survival and overall survival regardless of age[16,17]. Besides, SGA, PG-SGA and MNA are correlated with oneanother [5].

RecommendationsNutritional assessment is required at each visit (outpatients)

or hospitalisation (inpatients). The presence of undernutritionor cachexia is defined by a weight loss upper than 5% (grade B),and/or a body mass index (but not used alone) lower than 18.5or 21 for patients aged 70 and older (grade B). Patients shouldbe defined at risk of undernutrition or cachexia if the result of a10-point analogue scale estimating dietary intake is lower than7 (grade C). If a multidimensional assessment is used, PG-SGA orSGA (all patients) or MNA (geriatric oncology) are recommended(grade B).

4. Types of nutritional care according to treatment

4.1. Radiotherapy and radiochemotherapy

4.1.1. The role of dietary counselling, sip feeds and artificialnutrition

The literature focused on radiotherapy (head and neck cancer,oesophageal and rectal cancer) established a specific definitionfor personalised dietary counselling. This consists of early careof patients, ideally before any treatment, and includes a weeklyfollow-up until end of treatment and one to three months of posttreatment follow-up. When effectively completed, personaliseddietary counselling considerably improves protein and energyintake, nutritional status [18–24], and quality of life [18–21], whiledecreasing treatment-induced toxicities [18,22,24]. Additionally,the use of sip feeds, also known as oral nutritional supplements, hasbeen studied in five trials providing level 1[18,19], level 2 [25,26]and level 4 [27] evidence. Sip feeds may be used to increase totalcaloric and protein intake [25] or to reduce weight loss [26,27].In practice, dieticians use enriched diets, at times associated withsip feeds, even though only dietary counselling has been proved toimprove patient’s outcomes [18,19].

Nonetheless, dietary counselling and sip feeds remain some-times insufficient and artificial nutrition should be considered.

idelines of the French Speaking Society of Clinical Nutrition andrgoing non-surgical anticancer treatment. Dig Liver Dis (2014),

In radiotherapy alone, enteral nutrition should be proposedafter failure of personalised dietary counselling with or withoutsip feeds. According to experts, the nasogastric tube should bepreferred since oral mucositis usually starts only at the end of

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adiotherapy and lasts at the most one month (level 4 evidence)28–30].

In concomitant radiochemotherapy, a Cochrane meta-analysisublished in 2010 identified 100 randomised trials concerning thenteral nutrition methods used for patients with head and neckancer [31]. However, only a single study met the inclusion criteriaor quality of evidence. This randomised prospective study (level

evidence) compared the insertion of percutaneous endoscopicastrostomy (n = 15) to nasogastric tubes (n = 18) during radiothe-apy or radiochemotherapy in patients with 5-kg weight loss and/or50% decreased intake. No difference could be observed betweenhe two routes in terms of complications, pulmonary infections oruality of life [32].

Specific considerations in head and neck cancers. Undernutritions common in patients with head and neck cancer due to multi-actorial causes such as the tumour location, pre-existing nutritioneficiencies, and treatment-related morbidity. On one hand, com-ined radiotherapy and chemotherapy of the oropharyngeal area

s often associated with severe Grade 3–4 mucositis, occurring in0–45% of patients [33–35]. Such adverse events usually start inhe first weeks of treatment and last until about two months post-reatment, thereby greatly enhancing the risk of undernutrition. Onhe other hand, treatment interruption was reported to worsen theatient’s prognosis [36]. Indeed, although improving the nutritionaltatus of the patient is crucial, gastrostomy insertion during theourse of radiochemotherapy is not recommended (41% prevalencef local infection leading to treatment interruption) [37]. For theseeasons, nine recent studies suggesting prophylactic gastrostomyad been published by 2009. Two studies on patients with Stage

II or IV cancer showed that prophylactic gastrostomy significantlymproved quality of life compared to no gastrostomy (P = 0.001 [38]nd P = 0.02 [39]). Furthermore, three studies (level 4 evidence)eported that prophylactic gastrostomy could optimise the deliv-ry of radiochemotherapy by decreasing treatment interruptions40–42].

.1.2. The role of antioxidants and immunonutritionAccording to a systematic literature review, antioxidants should

e used with caution given the potential negative effect of aong-term administration [43]. Indeed, a randomised double blindlinical study against placebo on a head and neck cancer popula-ion reported that alpha-tocopherol (400 UI/d) and beta-carotene30 mg/d) supplementation was associated with a significantlyigher risk of cancer recurrence or development of a second can-er over the supplementation period (OR = 1.65; CI 95% = 1.21–2.25)44]. This risk was further increased in case of sustained tobacco useOR = 2.41; CI 95% = 1.25–4.64, level 1 evidence) [45].

Concerning immunonutrient-enriched sip feeds, a recentrospective non-randomised Phase II study estimated the rel-vance of oral supplementation with nutrient mixtures (e.g.-arginine, n-3 fatty acids, ribonucleic acids, antioxidants) duringhe five days preceding chemotherapy in a head and neck canceropulation (n = 40) exclusively treated with radio-chemotherapy46]. Twenty-one patients (52.5%) had, at least once, a Grade 3 orrade 4 toxicity, and only five (12.5%) a severe Grade 3 or Grade 4ucositis versus 45% in previous reports which were based on the

ame radiochemotherapy protocol but without supplementation33–35].

RecommendationsFor all cancers treated with radiotherapy or radiochemother-

py, if artificial nutrition is necessary, parenteral nutrition is not

Please cite this article in press as: Senesse P, et al. Clinical nutrition guMetabolism (SFNEP): Summary of recommendations for adults undehttp://dx.doi.org/10.1016/j.dld.2014.01.160

ecommended (experts’ opinion). Immunonutrition is also notecommended (grade C). In head and neck, oesophageal and rec-al cancers, dietary counselling, and sip feeds if necessary, areecommended (grade B). Especially in head and neck cancers,

PRESSr Disease xxx (2014) xxx–xxx 3

and in case of concomitant radiochemotherapy, recommenda-tions are as follows:

1. Oropharyngeal area irradiation and undernutrition: prophy-lactic gastrostomy is recommended (grade C),

2. Oropharyngeal area irradiation and no undernutrition: pro-phylactic gastrostomy is recommended (experts’ opinion),

3. No oropharyngeal area irradiation and undernutrition: pro-phylactic gastrostomy is recommended (experts’ opinion),

4. No oropharyngeal area irradiation and no undernutrition:prophylactic gastrostomy is not recommended (experts’opinion) and dietary counselling, and sip feeds if necessary,are recommended (grade B).

5. In oesophageal and head and neck cancers and for patientswith continued tobacco consumption, �-tocopherol and �-carotene complements without diagnosed deficiency are notrecommended (grade A).

4.2. Chemotherapy

4.2.1. The role of dietary counselling, sip feeds and artificialnutrition

Major advances have recently been achieved in chemotherapyand the therapeutic combinations necessary to obtain recovery orprolonged remission can last several years. For this reason, clini-cians should reconsider the nutritional counselling approach. Thisis a critical point since more than 50% of cancer patients experiencedysgeusia with altered quality of life [47]. However, up until nowfew studies on personalised dietary counselling and use of sip feedsduring chemotherapy have been published [48,49].

Currently, chemotherapy is more often administered to outpa-tients (instead of inpatients) and a patient is not likely to be referredto a dietician. Indeed, the probability of referral for patients with5–10% weight loss is only 39% within the first 12 months after firstassessment and is actually similar to patients with no weight loss[50].

Concerning artificial nutrition, up until now there is little datashowing the potential benefits of standard techniques in eitherdecreased treatment complications or improved survival rates inpatients with chemotherapy. Most of the available studies areobservational, with heterogeneous statistical power and varioustumour sites not allowing for establishment of reliable guidelines.

Just as for radio and radiochemotherapy treatments,chemotherapy alone can be associated with severe mucositiswhich worsen the patient undernutrition risk; in the presenceof severe mucositis clinicians should consider artificial nutrition.However, no study compared enteral and parenteral nutrition inthis case thus far [51]. Nevertheless, parenteral nutrition shouldnot be administered as first-line treatment since two majorreviews reported significantly increased infectious risks duringchemotherapy [52,53].

4.2.2. The role of antioxidants and immunonutritionRandomised trials on antioxidants were evaluated in recent sys-

tematic reviews [43,54]. Some findings suggested that glutathionereduces neurotoxicity and that melatonin reduces myelotoxicity,weight loss and asthenia (level 2 evidence). However, two pre-clinical studies stressed out that simultaneous administration ofantioxidants reduces chemotherapy effectiveness [55,56].

Some authors proposed immunonutrition with the aim of reduc-ing chemotherapy-related side effects. Oral or parenteral glutaminesupplementation was evaluated in 15 studies [57]. Results showed

idelines of the French Speaking Society of Clinical Nutrition andrgoing non-surgical anticancer treatment. Dig Liver Dis (2014),

that glutamine supplementation did not improve incidence orseverity of mucositis in agreement with two recent meta-analyses[58,59]. An in vitro study even showed that glutamine stimulatedtumour progression [60]. Conversely, several Phase II clinical trials

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nderlined the inhibitory effect of n-3 fatty acids on breast cancernd non-small-cell bronchial carcinoma progression [61,62].

RecommendationsFor all cancers treated with chemotherapy alone, systematic

ietary counselling is not recommended (grade C); systematicrtificial nutrition is not recommended (grade A); immunonu-rition is not recommended (grade C). In case of undernourishedr at risk patients, dietary counselling, and sip feeds if neces-ary, are recommended (experts’ opinion). If artificial nutritions necessary, parenteral nutrition is recommended only in casef unusable or inaccessible small intestine (grade C).

.3. Advanced palliative care

.3.1. The role of dietary counselling, sip feeds and artificialutrition

Literature regarding advanced palliative patients withouthemotherapy is very limited. Nevertheless, taste and smell dis-rders are known to be widespread in this population and oftenssociated with an altered quality of life. In a prospective studyn 66 advanced palliative patients without chemotherapy (medianurvival of 7.4 months), 15 patients (86%) experienced neurosen-ory disorders of which the most frequent were bad taste in theouth, altered taste perception and hypersensitivity to odours

63]. Significant correlations were found between chemosensoryamage, caloric intake reduction, weight loss and altered qual-

ty of life. In 2011, a systematic review of observational studiesrovided information about types of dietary counselling to beiven to cachectic cancer patients during off-treatment periods64]. In the investigated 20 studies, recommendations from expertsnclude increased energy provision (9 studies), increased proteinntake (1 study), numerous small meals (8 studies), high energyensity food (3 studies), sip feeds (9 studies), liquid food in thevent of eating disability (2 studies) and more easy-to-eat food1 study). Similarly, a positive correlation was found betweenood energy density and energy consumption (P < 0.001), therebyustifying dietary counselling as a means of enhancing inges-ion of energy-dense food (a smaller volume for more energy)65].

However, due to a lack of further confirmatory data on theubject, the working group recommends personalised dietaryounselling including, if necessary, sip feeds in case of undernu-rition and/or decreased intake (Visual Analog Scale for appetite7) and/or according to the patient’s or his family’s requestexperts’ opinion). Diets must be flexible in order to bet-er satisfy patients’ tastes and thus improve their quality ofife.

Regarding artificial nutrition, only one randomised prospectivetudy assessed specialised, nutrition-focused patient care [66]. Theatter consisted of oral nutritional support and home total par-nteral nutrition if needed (oral intake < 70% of needs: n = 104/309atients). As-treated analysis revealed that nutritional support

ncreases survival (median: 240 vs. 290 days, P < 0.01) and improvesxercise capacity (P < 0.04). However, intention-to-treat analysisid not confirm these results.

For palliative patients, artificial nutrition can be justified whenhe clinician reckons a higher risk for the patient to die fromndernutrition than from tumour progression. For instance, in thevent of peritoneal carcinomatosis with chronic bowel obstruction,nteral absorption is impaired. Hence, parenteral nutrition is oftenuggested to feed the patient but only non-randomised studieseported an improved survival [67].

Please cite this article in press as: Senesse P, et al. Clinical nutrition guMetabolism (SFNEP): Summary of recommendations for adults undehttp://dx.doi.org/10.1016/j.dld.2014.01.160

In terminally ill patients, parenteral nutrition does not generallyecrease anorexia. In fact, hunger and thirst are not always encoun-ered in this population, of which less than half complain of theseymptoms [68]; a light hydration usually suffices to prevent them

PRESSr Disease xxx (2014) xxx–xxx

[69]. In these cases, the main objective still consists in ensuring anacceptable quality of life and providing effective pain and symptommanagement.

4.3.2. The role of orexigens and immunonutritionIn advanced palliative situations, weight loss is common and

sometimes detrimental to patients. Concerning orexigens, studiesinvolved advanced palliative patients (about half of them) [70]. Wenoted two meta-analyses [71,72] and one Phase III trial [73] (all oflevel 1 evidence). Given the heterogeneity of studies, tumour typesand stages, it was not presently possible to draw a clear conclusion.However, megestrol acetate, medroxyprogesterone acetate andcorticoids already proved their efficiency on appetite and weight(level 1 evidence) when administered in short therapy (<1 monthfor corticoids and 2–3 months for anabolic progestational agents).Progestational agents are not recommended in the event of venousthrombosis though. In these studies, food intake and weight weresignificantly enhanced. However, no improvement of quality of lifewas observed.

Concerning immunonutrients, the principal trials studied oral orenteral n-3 fatty acids (18 trials of which 4 were of level 1 evidence[74–77]) [57]. Although their results may appear discordant onseveral parameters, association of sip feeds with eicosapentaenoicacid supplementation (2 g d−1) improved weight gain in three tri-als [75–77]. As for parenteral lipid emulsions, no study specificallyevaluated their anticachectic effect when administered to cancerpatients suffering from undernutrition.

RecommendationsFor all cancers treated with advanced palliative care, in case

of undernourished or at risk patients, dietary counselling andsip feeds if necessary, are recommended (experts’ opinion). Sys-tematic artificial nutrition is not recommended (grade A). Ifartificial nutrition is necessary, parenteral nutrition is recom-mended only in case of unusable or inaccessible small intestine(grade C). If artificial nutrition is introduced, a new evalu-ation should be done at 15 days (experts’ opinion). In caseof life expectancy <3 months or Karnofsky score ≤ 50 or per-formance status ≥ 3, artificial nutrition is not recommended(experts’ opinion). If the main objective is weight gain or stabili-sation, sip feeds enriched with n-3 fatty acids (2 g/d) for 8 weeksare recommended (grade B). Likewise, in the event of anorexia,orexigens associated with dietary counselling, and sip feeds ifnecessary, are recommended (if no contraindication) (experts’opinion).

4.4. Oncology-haematology

Significant progress has been achieved in recent years in the fieldof oncology–haematology on account of: (1) a large-scale increasein the number of haematopoietic stem cell transplantations espe-cially from unrelated donors, (2) the new sources of haematopoieticstem cells including cord blood cells and peripheral blood stemcells from patients (autograft) and related or unrelated donors(allograft), and (3) the parallel development of myeloablative andnon-myeloablative conditioning regimens. Consequences of theseadvances are a clear increase of allogeneic transplantations for newindications and of the number of older patients who often sufferfrom more advanced diseases and eventually comorbidities [78].

Concerning dietary counselling and sip feeds, published datain the specific oncology–haematology setting are not sufficientto elaborate strong reliable guidelines. Our recommendations

idelines of the French Speaking Society of Clinical Nutrition andrgoing non-surgical anticancer treatment. Dig Liver Dis (2014),

are therefore based upon experts’ opinions and are similar tothose for chemotherapy patients, including systematic nutritionalevaluation according to the undernutrition criteria defined in thispaper for all situations (see Section 3).

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Nonetheless, indications for artificial nutritional support arerequent: from 37% to 92% depending on the type of graft andonditioning [51]. Parenteral nutrition must be prescribed in thevent of severe mucositis (Grade 3–4), ileus or severe vomiting,nd as soon as oral/enteral intake become <60% of patients’ needs78,79]. In less acute situations, enteral nutrition by tube may behosen even in the absence of evidence from randomised trials80,81]. This strategy may decrease the risk and severity of graftersus host disease (GVHD) [80], and is most often applicable.isks and benefits of parenteral nutrition were assessed by com-aring it to sip feeds (level 2 [82] and level 4 evidence [83]) oro enteral nutrition and to standard hydration (level 2 [84] andevel 4 evidence [85]). In haematopoietic stem cell transplanta-ions setting, a Cochrane meta-analysis reported that parenteralutrition (compared to simple hydration) may lead to more infec-ious complications [79]. When parenteral nutrition is needed,t may be beneficial to complement with glutamine, which mayeduce the occurrence of bacteraemia [86]. However, such supple-entation did not significantly decrease either length of stay,ucositis severity, incidence and severity of GVHD or day 100ortality [79,87]. The efficiency of this practice had also been

ontested in former works (level 2 evidence)[82,88–91]. Finally,n the previously cited meta-analysis, 6 randomised controlledrials focused on the glutamine subject [79]. They concludedhat parenteral nutrition (when indicated) may be associatedith glutamine at doses of 0.3–0.6 g/kg/d of alanyl-glutamineipeptide.

In conclusion, owing to the patient and treatment hetero-eneity, appraisal of parenteral and enteral nutrition efficacy inncology–haematology setting remains difficult. Up until now, theikely advantages of enteral nutrition compared to parenteral nutri-ion during allogeneic haematopoietic stem cell transplantationsave not been formally demonstrated by prospective randomisedontrolled trials. It would indeed be interesting to conduct newtudies now that reduced intensity conditioning regimens are morend more widely employed.

pecific considerations in GVHDThe literature about the impact of nutritional support on GVHD

s still very limited [80,92,93]. Parenteral nutrition does not seemo decrease GVHD incidence and severity [92]. To our knowledge,here is no data on resolution of GVHD through nutritional supportut it appears logical and thus indicated to maintain a good nutri-ional intake in this specific clinical condition, by enteral route ifossible, especially in the event of enteropathy with protein leak-ge.

RecommendationsFor all haematological cancers, systematic artificial nutri-

ion is not recommended (experts’ opinion). In cases of oralntake of less than 2/3 of needs or of post-chemotherapy enteri-is lasting more than 7 days, artificial nutrition (preferentiallynteral) is recommended (grade B). In case of allografts only,nd if parenteral nutrition is necessary, glutamine supplemen-ation (0.3-0.6 g/kg) is recommended (grade B). In case of GVHD,utritional support is recommended (grade C).

.5. The elderly cancer patient

The prevalence of undernutrition is said to be either higher [94]r similar [12] in elderly cancer patients than in younger ones. Sincehe elderly are highly represented in cancer populations, they are

Please cite this article in press as: Senesse P, et al. Clinical nutrition guMetabolism (SFNEP): Summary of recommendations for adults undehttp://dx.doi.org/10.1016/j.dld.2014.01.160

resent in most nutritional support trials involving patients withancer. However, no separate analyses of efficiency/tolerance arevailable. It is nonetheless highly recommended to integrate nutri-ional care in geriatric treatment practices [95,96] so as to address

PRESSr Disease xxx (2014) xxx–xxx 5

comorbidity issues and to target the frailty status of this population[97].

RecommendationA nutritional care plan integrated in the global geriatric care

is recommended in all cancers (experts’ opinion).

5. Practical aspects

The quality of artificial nutrition care is essential and dependsnot only on nursing staff and patient training but also on mate-rial of which the choice, quality and installation procedures play akey role in acceptability and quality of life. After undernutritionscreening, needs assessment is a central step in patient nutri-tional care. In medical oncology, total protein-energy and proteinrequirements amount to 30–35 kcal/kg/d and to 1.2–1.5 g/kg/d,respectively. Moreover, it is important to remain cautious innutrition initiation, particularly in case of severe undernutri-tion (BMI ≤ 13, weight loss > 20% over three months or negligibleoral intake for 15 days or more). Indeed those patients areat high risk of developing a refeeding syndrome during theirnutritional care. In most cases, this syndrome associates waterand sodium retention with serious hydro-electrolyte disorders(hypophosphatemia, hypokalemia and hypomagnesaemia) whichmay entail the patient’s transfer to an intensive care unit. Sincethese disturbances are to be expected, it may be easy to pre-vent them, provided that patients are systematically screened[98,99].

In enteral nutrition, choice in routes of access, tubes and posi-tioning methods are crucial. Although no randomised study hasyet been published, very-low-diameter nasogastric tubes (≤10French Catheter Scale for silicone tubes or less for polyurethanetubes) should be preferred for their good tolerance (experts’opinion). Important factors include proper tube positioning pro-cedures and patients’ therapeutic education on enteral nutritionmanagement should be promoted (experts’ opinion). Regard-ing gastrostomies, techniques should be adapted to patients. Inthis respect, percutaneous endoscopic gastrostomy techniqueswithout gastropexy (i.e. pull-technique) are associated with cuta-neous metastasis risk in cases of head and neck or oesophagealcancer [100]. It is therefore recommended to use an “introducer-technique” in these conditions. Moreover, in cases of chemotherapyor when percutaneous gastrostomy is suggested, a security periodof 15 days before and after placement may be proposed toallow healing and to reduce infectious risks (experts’ opin-ion).

RecommendationsMinimum energy and protein needs in adult non-surgical

patients are 30–35 kcal/kg/d and 1.2–1.5 g protein/kg/d (gradeC). If artificial nutrition is used, the prevention of refeeding syn-drome is recommended if weight loss is greater than 20%, BMIis 13 or less, or the 10-point analogue scale result (estimatingdietary intake) is 3 or less during 15 days or more, (experts’opinion). In case of enteral nutrition via nasogastric tube, smalldiameter tubes (maximum 10 French Catheter Scale for sili-cone tubes and less for polyurethane tubes) are recommended(experts’ opinion). In case of enteral nutrition via gastrostomy,and if the patient suffers from head and neck or oesophagealnon-resected tumour, the placement by pull-technique is notrecommended (experts’ opinion). No chemotherapy should be

idelines of the French Speaking Society of Clinical Nutrition andrgoing non-surgical anticancer treatment. Dig Liver Dis (2014),

administered within 15 days before and after the placement ofa gastrostomy (experts’ opinion). Finally, in case of parenteralnutrition, other infusions should be discontinued (experts’opinion).

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ARTICLEDLD-2574; No. of Pages 8

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. Conclusions

Nutritional support plays a key role in every step of cancer treat-ent. Major advances have been achieved in the past 20 years but

igher quality clinical research is needed. Indeed, among 36 recom-endations, 16 were based upon experts’ opinion and only 3 were

f Grade A evidence. Nutrition remains a component of support-ve care and should be part of an integrated approach addressingoth anticancer therapy and improvement of patients’ quality of

ife. Given that nutrition is at the crossroads of “pure” medicine andocial sciences, emphasis should be placed on the development ofncillary social studies in future randomised clinical trials.

onflict of interestierre Senesse received funding from Aguettant, Baxter, Fresenius-abi, Nestlé, Nutricia for advisory activity. Patrick Bachmann is

member of the scientific committee of Nutrizoom of Nestlelinical Nutrition France, and was investigator in 2012–2013 forresenius-Kabi France. Corinne Bouteloup declares a conflict ofnterest with Fresenius-Kabi, Nutricia Clinical Nutrition SAS, Nestlélinical Nutrition, and Baxter. Pascal Crenn received funding fromestlé for educational activities. Marie-Paul Vasson declares a con-ict of interest with Nestlé for her work in a former clinical trial.avier Hébuterne received funding from Fresenius-Kabi, Nestlé andaxter for advisory activity, as a member on an advisory board, and

rom Nutricia, Abbott, and Schering-Plough for educational activi-ies.

All other authors declare no conflict of interest concerning theontent of this paper.

cknowledgements

We would like to acknowledge the editorial assistance of Julieourraud.

ppendix A. Co-author affiliations

Anticancer Center Léon-Bérard, Lyon, FranceRadiation Oncology Department, CHU Poitiers, Poitiers, FranceGastroenterology and Clinical Nutrition, CHU Nice, University ofice Sophia-Antipolis, Nice, FranceCHU de Bordeaux, Pôle de Gérontologie Clinique, Pessac; Univer-ity Bordeaux Segalen, RMSB, UMR 5536, Bordeaux; CNRS, RMSB,MR 5536, Bordeaux, FranceDigestive and Hepatobiliary Medicine department, CHU Clermont-errand; Human Nutrition Unit, Clermont University, Auvergneniversity; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-errand, FranceVersailles Saint Quentin en Yveline University (EA 4497), Assis-

ance Publique Hôpitaux de Paris (Raymond Poincaré Hospital),arches, FranceUniversitary Hospital Center Cochin, Assistance Publique Hôpi-

aux de Paris, Paris, FranceINRA, Réseau NACRe, CRJ, Jouy-en-Josas, FranceAnticancer Center Curie, Paris, FranceFrench League Against Cancer, Paris, FranceCHU Lyon-Sud, Pierre-Benite, France

Please cite this article in press as: Senesse P, et al. Clinical nutrition guMetabolism (SFNEP): Summary of recommendations for adults undehttp://dx.doi.org/10.1016/j.dld.2014.01.160

Anticancer Center Jean-Perrin, Clermont-Ferrand, France

ppendix B. Supplementary data

Supplementary material related to this article can be found, inhe online version, at http://dx.doi.org/10.1016/j.dld.2014.01.160.

PRESSr Disease xxx (2014) xxx–xxx

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