Clinical nutrition guidelines of the French Speaking Society of Clinical

Nutrition and Metabolism (SFNEP): summary of recommendations for adults

undergoing non-surgical anticancer treatment

French Speaking Society of Clinical Nutrition and Metabolism (SFNEP)

Pierre Senessea,*, Patrick Bachmannb, René-Jean Bensadounc, Isabelle Besnardd,

Isabelle Bourdel-Marchassone, Corinne Bouteloupf, Pascal Crenng, François

Goldwasserh, Olivier Guérind, Paule Latino-Marteli, Jocelyne Meuricj, Françoise May-

Lévink, Mauricette Michalletl, Marie-Paule Vassonm, Xavier Hébuterned

a Department of Clinical Nutrition and Gastroenterology, Institut régional du Cancer –

Montpellier (ICM) - Val d’Aurelle, Montpellier, France; Epsylon Laboratory, EA

4556, Universities Montpellier 1, 3 and St-Etienne, 4 boulevard Henri IV, F-34000

Montpellier, France, www.lab-epsylon.fr

b-m : see Appendix A

* Correspondence address : SFNEP: Via Pierre Senesse, Montpellier Cancer

Institute (MCI), Unit of Clinical Nutrition and Gastroenterology, 208, avenue des

Apothicaires, parc Euromédecine, F-34298 Montpellier cedex 05, France.

Tel.: +33 46 7618554; fax: +33 46 7613729.

E-mail address: pierre.senesse@icm.unicancer.fr

Word count: 4822

Abstract

Up to 50% of patients with cancer suffer from weight loss and undernutrition even

though it is rarely screened or properly handled. Patients’ prognosis and quality of life

could be greatly improved by simple and inexpensive means encompassing

nutritional status assessment and effective nutritional care. These guidelines aim to

give health professionals and patients practical and up-to-date advice to manage

nutrition in the principal situations encountered during the cancer course according to

the type of tumour and treatment (i.e. radio and/or chemotherapy). Specific

suggestions are made for palliative and elderly patients because of specific risks of

undernutrition and related comorbidities in this subset. Levels of evidence and

grades of recommendations are detailed as stated by current literature and

consensus opinion of clinical experts in each field.

Keywords: clinical practice; evidence-based; oncology; nutritional care.

1. Introduction

Up to 50% of cancer patients undergo involuntary weight loss with deleterious

consequences. Indeed, the disease itself and its related treatments often trigger taste

and smell alterations, appetite loss, swallowing disorders and enhanced catabolism

leading to an expected higher undernutrition risk [1].

Increased incidence of comorbidities (mainly infectious complications), poorer

tolerance, higher toxicity of treatments and altered quality of life are the common

outcomes associated with undernutrition and bring about amplified hospital costs and

mortality. However patients’ nutritional status could be greatly improved by simple

screening steps and proper handling reflexes. It is therefore crucial to develop

appropriate and efficient strategies to reach better nutritional care for oncology

patients.

The French-speaking Society for Clinical Nutrition and Metabolism (SFNEP) is a

transversal organisation representing all health professionals interested in clinical

nutrition (physicians, nurses, pharmacists, dieticians, and students). The first mission

of SFNEP is to support quality patient care, education and research in the fields of

clinical nutrition. Complete guidelines were published in French in December 2012

[2]. The clinical guidelines proposed in this paper are therefore the first to be

internationally published by the SFNEP in adult anticancer treatment. This article

results from a large-scale literature analysis (Supplementary methods in Appendix B)

and is intended for health professionals delivering cancer care outside the

perioperative context.

2. Definitions

Because terminology used in different parts of the world may not have the same

meaning, the definitions referred to in this document are as follows.

- In the curative phase, treatments may cure cancer. In the palliative phase, cancer

may not be cured but may be stabilised with a potential survival gain. In the

advanced palliative phase, disease rapidly progresses despite treatments and

death occurs usually within the next few months. Terminally-ill patients have a life

expectancy of one month or less.

- Disease-associated undernutrition, also called cachexia, is a pathological state

resulting from both reduced food intake and metabolic abnormalities such as

inflammation, hypermetabolism and hypercatabolism [1]. Associated clinical signs

are a general state degradation, ≥ 2 % or ≥ 5% weight loss and/or sarcopenia

and/or inflammation. Treatment of cancer-associated undernutrition is

multidimensional and involves nutritional care, exercise and treatment of

inflammation [4]. For clarity reasons and because all cited studies may not have

referred exactly to this definition, the term “undernutrition” will be used in this

paper.

- Personalised dietary counselling is performed by a nutrition expert all along and

after treatment and generally consists of several dietary consultations, including

nutritional status and food intake assessment as well as dietary advice.

- Sip feeds, also called oral nutritional supplements, are dietary products intended to

special medical purposes. They are usually industrially produced and ready-to-

use.

- Artificial nutrition includes enteral nutrition which is administered directly into the

digestive tract (i.e. via nasogastric or nasojejunal tube, gastrostomy or

jejunostomy) and parenteral nutrition which is administered intravenously.

- Immunonutrition corresponds to the use of nutritional substrates (immunonutrients)

able to modulate (increase or decrease) the immune functions of the organism.

3. Nutritional evaluation

3.1 Weight and anorexia

In the settings of radiotherapy, medical oncology or palliative treatments, weight loss

is a factor associated with poor prognosis, reduced quality of life and increased

morbidity. Among the 31 analysed clinical studies, weight loss incidence varied from

8.2% to 87% according to the type of tumour, the stage of disease, and the defined

weight loss thresholds [5]. In multivariate analysis (28 studies), survival or toxicity

were significantly associated with weight loss. In 15 studies, weight loss definition

was based on a period of time without a specific threshold (i.e. six months, from the

disease onset to weight loss assessment). However, the working group recommends

a 5% weight loss threshold as a marker of undernutrition since this definition was

chosen in ten studies [5].

Anorexia, defined as loss of appetite, contributes to a considerable extent to

undernutrition. It occurs in 70.9% of patients undergoing chemotherapy or

radiotherapy and up to 90.7% of anorexic patients suffer from weight loss [6].

Currently, anorexia is taken into account in most undernutrition screening tools.

Indeed, anorexia and weight loss were closely related in an observational

prospective cohort of 1,000 non-palliative cancer patients [7]. In another prospective

study on 1,115 patients with advanced lung or colorectal cancer, intake reduction and

anorexia were the most important factors associated with prognosis [8]. Furthermore,

a level 2 evidence study has recently confirmed the strong correlation between intake

assessed by analogue scales (verbal or visual) and intake assessed by dietary

survey (P < 0.0001) [9]. In the subset of patients suffering from or at risk of

undernutrition, the likelihood of being undernourished exceeded 80% when the

analogue scale score was less than 7. Finally, in a prospective study (level 2

evidence) on 222 patients with oesophageal cancer, reduced oral intake was

significantly associated with degree of weight loss (P < 0.001) [10].

3.2 Body Mass Index

Body mass index (BMI) should not be used alone when screening for undernutrition.

In an observational prospective study on 7,606 in or outpatients, of which 1,186 had

cancer (15.6%), a BMI<18.5 predicted undernutrition with a sensitivity and specificity

of 21% and 95%, respectively when compared to a weight loss>10% [11]. In this

study, a BMI < 18.5 was a poor predictor of undernutrition (41% true positives).

Consistently, a French observational prospective study showed that a weight loss >

5% was observed in 40.9% of cancer patients even though BMI values below 18.5 (<

70-year-old patients) and below 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 (Subjective Global

Assessment), PG-SGA (Patient-Generated Subjective Global Assessment) and MNA

(Mini Nutritional Assessment for >70-year-old subjects) are validated in the medical

oncology setting [5]. Although these multidimensional assessment tools are not

included in the diagnostic of undernutrition as defined in this paper, they may help

clinicians screening cancer patients which are at risk of undernutrition. SGA is

significantly associated with length of stay [13] and both SGA and PG-SGA are

reliable predictive factors for survival [14, 15]. Concerning >70-year-old patients, the

MNA score has a good predictive value for length of chemotherapy, progression-free

survival and overall survival regardless of age [16, 17]. Besides, SGA, PG-SGA and

MNA are correlated with one another [5].

Recommendation

Nutritional assessment is required at each visit (outpatients) or hospitalisation

(inpatients). The presence of undernutrition or cachexia is defined by a weight

loss upper than 5% (grade B), and/or a body mass index (but not used alone)

lower than 18.5 or 21 for patients aged 70 and older (grade B). Patients should

be defined at risk of undernutrition or cachexia if the result of a 10-point

analogue scale estimating dietary intake is lower than 7 (grade C). If a

multidimensional assessment is used, PG-SGA or SGA (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 artificial nutrition

The literature focused on radiotherapy (head and neck cancer, oesophageal and

rectal cancer) established a specific definition for personalised dietary counselling.

This consists of early care of patients, ideally before any treatment, and includes a

weekly follow-up until end of treatment and one to three months of post treatment

follow-up. When effectively completed, personalised dietary counselling considerably

improves protein and energy intake, nutritional status [18-24], and quality of life [18-

21], while decreasing treatment-induced toxicities [18, 22, 24]. Additionally, the use of

sip feeds, also known as oral nutritional supplements, has been 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 total caloric and protein intake [25] or to reduce weight loss [26,

27]. In practice, dieticians use enriched diets, at times associated with sip feeds,

even though only dietary counselling has been proved to improve patient’s outcomes

[18, 19].

Nonetheless, dietary counselling and sip feeds remain sometimes insufficient and

artificial nutrition should be considered.

In radiotherapy alone, enteral nutrition should be proposed after failure of

personalised dietary counselling with or without sip feeds. According to experts, the

nasogastric tube should be preferred since oral mucositis usually starts only at the

end of radiotherapy and lasts at the most one month (level 4 evidence) [28-30].

In concomitant radiochemotherapy, a Cochrane meta-analysis published in

2010 identified 100 randomised trials concerning the enteral nutrition methods used

for patients with head and neck cancer [31]. However, only a single study met the

inclusion criteria for quality of evidence. This randomised prospective study (level 2

evidence) compared the insertion of percutaneous endoscopic gastrostomy (n=15) to

nasogastric tubes (n=18) during radiotherapy or radiochemotherapy in patients with

5-kg weight loss and/or>50% decreased intake. No difference could be observed

between the two routes in terms of complications, pulmonary infections or quality of

life [32].

Specific considerations in head and neck cancers. Undernutrition is common in

patients with head and neck cancer due to multifactorial causes such as the tumour

location, pre-existing nutrition deficiencies, and treatment-related morbidity. On one

hand, combined radiotherapy and chemotherapy of the oropharyngeal area is often

associated with severe Grade 3-4 mucositis, occurring in 40-45% of patients [33-35].

Such adverse events usually start in the first weeks of treatment and last until about

two months post-treatment, thereby greatly enhancing the risk of undernutrition. On

the other hand, treatment interruption was reported to worsen the patient’s prognosis

[36]. Indeed, although improving the nutritional status of the patient is crucial,

gastrostomy insertion during the course of radiochemotherapy is not recommended

(41% prevalence of local infection leading to treatment interruption) [37]. For these

reasons, nine recent studies suggesting prophylactic gastrostomy had been

published by 2009. Two studies on patients with Stage III or IV cancer showed that

prophylactic gastrostomy significantly improved quality of life compared to no

gastrostomy (P = 0.001[38] and P = 0.02 [39]). Furthermore, three studies (level 4

evidence) reported that prophylactic gastrostomy could optimize the delivery of

radiochemotherapy by decreasing treatment interruptions [40-42].

4.1.2 The role of antioxidants and immunonutrition

According to a systematic literature review, antioxidants should be used with caution

given the potential negative effect of a long-term administration. [43]Indeed, a

randomised double blind clinical study against placebo on a head and neck cancer

population reported that alpha-tocopherol (400 UI/d) and beta-carotene (30 mg/d)

supplementation was associated with a significantly higher risk of cancer recurrence

or development of a second cancer over the supplementation period (OR=1.65 ; CI

95% = 1.21-2.25) [44]. This risk was further increased in case of sustained tobacco

use (OR=2.41 ; CI 95 %=1.25-4.64, level 1 evidence) [45].

Concerning immunonutrient-enriched sip feeds, a recent prospective non-

randomised Phase II study estimated the relevance of oral supplementation with

nutrient mixtures (e.g. L-arginine, n-3 fatty acids, ribonucleic acids, antioxidants)

during the five days preceding chemotherapy in a head and neck cancer population

(n = 40) exclusively treated with radio-chemotherapy [46]. Twenty-one patients

(52.5%) had, at least once, a Grade 3 or Grade 4 toxicity, and only five (12.5%) a

severe Grade 3 or Grade 4 mucositis versus 45% in previous reports which were

based on the same radiochemotherapy protocol but without supplementation [33-35].

Recommendation

For all cancers treated with radiotherapy or radiochemotherapy, if artificial

nutrition is necessary, parenteral nutrition is not recommended (experts’

opinion). Immunonutrition is also not recommended (grade C). In head and

neck, oesophageal and rectal cancers, dietary counselling, and sip feeds if

necessary, are recommended (grade B). Especially in head and neck cancers,

and in case of concomitant radiochemotherapy, recommendations are as

follows:

1. Oropharyngeal area irradiation and undernutrition: prophylactic

gastrostomy is recommended (grade C),

2. Oropharyngeal area irradiation and no undernutrition: prophylactic

gastrostomy is recommended (experts’ opinion),

3. No oropharyngeal area irradiation and undernutrition: prophylactic

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 patients with

continued tobacco consumption, α-tocopherol and β-carotene

complements without diagnosed deficiency are not recommended (grade

A).

4.2 Chemotherapy

4.2.1 The role of dietary counselling, sip feeds and artificial nutrition

Major advances have recently been achieved in chemotherapy and the therapeutic

combinations necessary to obtain recovery or prolonged remission can last several

years. For this reason, clinicians should reconsider the nutritional counselling

approach. This is a critical point since more than 50% of cancer patients experience

dysgeusia with altered quality of life [47]. However, up until now few studies on

personalised dietary counselling and use of sip feeds during chemotherapy have

been published [48, 49].

Currently, chemotherapy is more often administered to outpatients (instead of

inpatients) and a patient is not likely to be referred to a dietician. Indeed, the

probability of referral for patients with 5-10% weight loss is only 39% within the first

12 months after first assessment and is actually similar to patients with no weight loss

[50].

Concerning artificial nutrition, up until now there is little data showing the potential

benefits of standard techniques in either decreased treatment complications or

improved survival rates in patients with chemotherapy. Most of the available studies

are observational, with heterogeneous statistical power and various tumour sites not

allowing for establishment of reliable guidelines.

Just as for radio and radiochemotherapy treatments, chemotherapy alone can be

associated with severe mucositis which worsen the patient undernutrition risk; in the

presence of severe mucositis clinicians should consider artificial nutrition. However,

no study compared enteral and parenteral nutrition in this case thus far [51].

Nevertheless, parenteral nutrition should not be administered as first-line treatment

since two major reviews reported significantly increased infectious risks during

chemotherapy [52, 53].

4.2.2 The role of antioxidants and immunonutrition

Randomised trials on antioxidants were evaluated in recent systematic reviews [43,

54]. Some findings suggested that glutathione reduces neurotoxicity and that

melatonin reduces myelotoxicity, weight loss and asthenia (level 2 evidence).

However, two pre-clinical studies stressed out that simultaneous administration of

antioxidants reduces chemotherapy effectiveness [55, 56].

Some authors proposed immunonutrition with the aim of reducing chemotherapy-

related side effects. Oral or parenteral glutamine supplementation was evaluated in

15 studies [57]. Results showed that glutamine supplementation did not improve

incidence or severity of mucositis in agreement with two recent meta-analyses [58,

59]. An in vitro study even showed that glutamine stimulated tumour progression [60].

Conversely, several Phase II clinical trials underlined the inhibitory effect of n-3 fatty

acids on breast cancer and non-small-cell bronchial carcinoma progression [61, 62].

Recommendation

For all cancers treated with chemotherapy alone, systematic dietary

counselling is not recommended (grade C); systematic artificial nutrition is not

recommended (grade A); immunonutrition is not recommended (grade C). In

case of undernourished or at risk patients, dietary counselling, and sip feeds if

necessary, are recommended (experts’ opinion). If artificial nutrition is

necessary, parenteral nutrition is recommended only in case of unusable or

inaccessible small intestine (grade C).

4.3 Advanced palliative care

4.3.1 The role of dietary counselling, sip feeds and artificial nutrition

Literature regarding advanced palliative patients without chemotherapy is very

limited. Nevertheless, taste and smell disorders are known to be widespread in this

population and often associated with an altered quality of life. In a prospective study

on 66 advanced palliative patients without chemotherapy (median survival of 7.4

months), 15 patients (86%) experienced neurosensory disorders of which the most

frequent were bad taste in the mouth, altered taste perception and hypersensitivity to

odours [63]. Significant correlations were found between chemosensory damage,

caloric intake reduction, weight loss and altered quality of life. In 2011, a systematic

review of observational studies provided information about types of dietary

counselling to be given to cachectic cancer patients during off-treatment periods [64].

In the investigated 20 studies, recommendations from experts include increased

energy provision (9 studies), increased protein intake (1 study), numerous small

meals (8 studies), high energy density food (3 studies), sip feeds (9 studies), liquid

food in the event of eating disability (2 studies) and more easy-to-eat food (1 study).

Similarly, a positive correlation was found between food energy density and energy

consumption (P < 0.001), thereby justifying dietary counselling as a means of

enhancing ingestion of energy-dense food (a smaller volume for more energy) [65].

However, due to a lack of further confirmatory data on the subject, the working group

recommends personalised dietary counselling including, if necessary, sip feeds in

case of undernutrition and/or decreased intake (Visual Analog Scale for appetite<7)

and/or according to the patient’s or his family’s request (experts’ opinion). Diets must

be flexible in order to better satisfy patients’ tastes and thus improve their quality of

life.

Regarding artificial nutrition, only one randomised prospective study assessed

specialised, nutrition-focused patient care [66]. The latter consisted of oral nutritional

support and home total parenteral nutrition if needed (oral intake<70% of needs:

n=104/309 patients). As-treated analysis revealed that nutritional support increases

survival (median: 240 vs. 290 days, P<0.01) and improves exercise capacity

(P<0.04). However, intention-to-treat analysis did not confirm these results.

For palliative patients, artificial nutrition can be justified when the clinician reckons a

higher risk for the patient to die from undernutrition than from tumour progression.

For instance, in the event of peritoneal carcinomatosis with chronic bowel

obstruction, enteral absorption is impaired. Hence, parenteral nutrition is often

suggested to feed the patient but only non-randomised studies reported an improved

survival [67].

In terminally ill patients, parenteral nutrition does not generally decrease anorexia. In

fact, hunger and thirst are not always encountered in this population, of which less

than half complain of these symptoms [68]; a light hydration usually suffices to

prevent them [69]. In these cases, the main objective still consists in ensuring an

acceptable quality of life and providing effective pain and symptom management.

4.3.2 The role of orexigens and immunonutrition

In advanced palliative situations, weight loss is common and sometimes detrimental

to patients. Concerning orexigens, studies involved advanced palliative patients

(about half of them) [70]. We noted two meta-analyses [71, 72] and one Phase III trial

[73] (all of level 1 evidence). Given the heterogeneity of studies, tumour types and

stages, it was not presently possible to draw a clear conclusion. However, megestrol

acetate, medroxyprogesterone acetate and corticoids already proved their efficiency

on appetite and weight (level 1 evidence) when administered in short therapy (< 1

month for corticoids and 2 to 3 months for anabolic progestational agents).

Progestational agents are not recommended in the event of venous thrombosis

though. In these studies, food intake and weight were significantly enhanced.

However, no improvement of quality of life was observed.

Concerning immunonutrients, the principal trials studied oral or enteral n-3 fatty acids

(18 trials of which 4 were of level 1 evidence[74-77]) [57]. Although their results may

appear discordant on several parameters, association of sip feeds with

eicosapentaenoic acid supplementation (2 g.d-1) improved weight gain in three trials

[75-77]. As for parenteral lipid emulsions, no study specifically evaluated their

anticachectic effect when administered to cancer patients suffering from

undernutrition.

Recommendations

For all cancers treated with advanced palliative care, in case of undernourished

or at risk patients, dietary counselling and sip feeds if necessary, are

recommended (experts’ opinion). Systematic artificial nutrition is not

recommended (grade A). If artificial nutrition is necessary, parenteral nutrition

is recommended only in case of unusable or inaccessible small intestine

(grade C). If artificial nutrition is introduced, a new evaluation should be done

at 15 days (experts’ opinion). In case of life expectancy<3 months or Karnofsky

score ≤ 50 or performance status ≥ 3, artificial nutrition is not recommended

(experts’ opinion). If the main objective is weight gain or stabilisation, sip feeds

enriched with n-3 fatty acids (2 g/d) for 8 weeks are recommended (grade B).

Likewise, in the event of anorexia, orexigens associated with dietary

counselling, and sip feeds if necessary, are recommended (if no

contraindication) (experts’ opinion).

4.4 Oncology-haematology

Significant progress has been achieved in recent years in the field of oncology-

haematology on account of: (1) a large-scale increase in the number of

haematopoietic stem cell transplantations especially from unrelated donors, (2) the

new sources of haematopoietic stem cells including cord blood cells and peripheral

blood stem cells from patients (autograft) and related or unrelated donors (allograft),

and (3) the parallel development of myeloablative and non-myeloablative

conditioning regimens. Consequences of these advances are a clear increase of

allogeneic transplantations for new indications and of the number of older patients

who often suffer from more advanced diseases and eventually comorbidities [78].

Concerning dietary counselling and sip feeds, published data in the specific

oncology-haematology setting are not sufficient to elaborate strong reliable

guidelines. Our recommendations are therefore based upon experts’ opinions and

are similar to those for chemotherapy patients, including systematic nutritional

evaluation according to the undernutrition criteria defined in this paper for all

situations (see Section 3).

Nonetheless, indications for artificial nutritional support are frequent: from 37% to

92% depending on the type of graft and conditioning [51]. Parenteral nutrition must

be prescribed in the event of severe mucositis (Grade 3-4), ileus or severe vomiting,

and as soon as oral/enteral intake become<60% of patients’ needs [78, 79]. In less

acute situations, enteral nutrition by tube may be chosen even in the absence of

evidence from randomised trials [80, 81]. This strategy may decrease the risk and

severity of graft versus host disease (GVHD) [80], and is most often applicable. Risks

and benefits of parenteral nutrition were assessed by comparing it to sip feeds (level

2 [82] and level 4 evidence [83]) or to enteral nutrition and to standard hydration

(level 2 [84] and level 4 evidence [85]). In haematopoietic stem cell transplantations

setting, a Cochrane meta-analysis reported that parenteral nutrition (compared to

simple hydration) may lead to more infectious complications [79]. When parenteral

nutrition is needed, it may be beneficial to complement with glutamine, which may

reduce the occurrence of bacteraemia [86]. However, such supplementation did not

significantly decrease either length of stay, mucositis severity, incidence and severity

of GVHD or day 100 mortality [79, 87]. The efficiency of this practice had also been

contested in former works (level 2 evidence)[82, 88-91]. Finally, in the previously

cited meta-analysis, 6 randomised controlled trials focused on the glutamine subject

[79]. They concluded that parenteral nutrition (when indicated) may be associated

with glutamine at doses of 0.3 to 0.6 g/kg/d of alanyl-glutamine dipeptide.

In conclusion, owing to the patient and treatment heterogeneity, appraisal of

parenteral and enteral nutrition efficacy in oncology-haematology setting remains

difficult. Up until now, the likely advantages of enteral nutrition compared to

parenteral nutrition during allogeneic haematopoietic stem cell transplantations have

not been formally demonstrated by prospective randomised controlled trials. It would

indeed be interesting to conduct new studies now that reduced intensity conditioning

regimens are more and more widely employed.

Specific considerations in GVHD. The literature about the impact of nutritional

support on GVHD is still very limited [80, 92, 93]. Parenteral nutrition does not seem

to decrease GVHD incidence and severity [92]. To our knowledge, there is no data

on resolution of GVHD through nutritional support but it appears logical and thus

indicated to maintain a good nutritional intake in this specific clinical condition, by

enteral route if possible, especially in the event of enteropathy with protein leakage.

Recommendations

For all haematological cancers, systematic artificial nutrition is not

recommended (experts’ opinion). In cases of oral intake of less than 2/3 of

needs or of post-chemotherapy enteritis lasting more than 7 days, artificial

nutrition (preferentially enteral) is recommended (grade B). In case of allografts

only, and if parenteral nutrition is necessary, glutamine supplementation (0.3-

0.6 g/kg) is recommended (grade B). In case of GVHD, nutritional support is

recommended (grade C).

4.5 The elderly cancer patient

The prevalence of undernutrition is said to be either higher [94] or similar [12] in

elderly cancer patients than in younger ones. Since the elderly are highly

represented in cancer populations, they are present in most nutritional support trials

involving patients with cancer. However, no separate analyses of efficiency/tolerance

are available. It is nonetheless highly recommended to integrate nutritional care in

geriatric treatment practices [95, 96] so as to address comorbidity issues and to

target the frailty status of this population [97].

Recommendation

A 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 depends not only on nursing

staff and patient training but also on material of which the choice, quality and

installation procedures play a key role in acceptability and quality of life. After

undernutrition screening, needs assessment is a central step in patient nutritional

care. In medical oncology, total protein-energy and protein requirements amount to

30 to 35 kcal/kg/d and to 1.2 to 1.5 g/kg/d, respectively. Moreover, it is important to

remain cautious in nutrition initiation, particularly in case of severe undernutrition

(BMI≤13, weight loss>20% over three months or negligible oral intake for 15 days or

more). Indeed those patients are at high risk of developing a refeeding syndrome

during their nutritional care. In most cases, this syndrome associates water and

sodium retention with serious hydro-electrolyte disorders (hypophosphatemia,

hypokalemia and hypomagnesaemia) which may entail the patient’s transfer to an

intensive care unit. Since these disturbances are to be expected, it may be easy to

prevent them, provided that patients are systematically screened [98, 99].

In enteral nutrition, choice in routes of access, tubes and positioning methods are

crucial. Although no randomised study has yet been published, very-low-diameter

nasogastric tubes (≤ 10 French Catheter Scale for silicone tubes or less for

polyurethane tubes) should be preferred for their good tolerance (experts’ opinion).

Important factors include proper tube positioning procedures and patients’

therapeutic education on enteral nutrition management should be promoted (experts’

opinion). Regarding gastrostomies, techniques should be adapted to patients. In this

respect, percutaneous endoscopic gastrostomy techniques without gastropexy (i.e.

pull-technique) are associated with cutaneous metastasis risk in cases of head and

neck or oesophageal cancer [100]. It is therefore recommended to use an

“introducer-technique” in these conditions. Moreover, in cases of chemotherapy or

when percutaneous gastrostomy is suggested, a security period of 15 days before

and after placement may be proposed to allow healing and to reduce infectious risks

(experts’ opinion).

Recommendation

Minimum energy and protein needs in adult non-surgical patients are 30 to 35

kcal/kg/d and 1.2 to 1.5 g protein/kg/d (grade C). If artificial nutrition is used,

the prevention of refeeding syndrome is recommended if weight loss is greater

than 20%, BMI is 13 or less, or the 10-point analogue scale result (estimating

dietary intake) is 3 or less during 15 days or more, (experts’ opinion). In case of

enteral nutrition via nasogastric tube, small diameter tubes (maximum 10

French Catheter Scale for silicone 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 oesophageal non-resected

tumour, the placement by pull-technique is not recommended (experts’

opinion). No chemotherapy should be administered within 15 days before and

after the placement of a gastrostomy (experts’ opinion). Finally, in case of

parenteral nutrition, other infusions should be discontinued (experts’ opinion).

6. Conclusions

Nutritional support plays a key role in every step of cancer treatment. Major

advances have been achieved in the past 20 years but higher quality clinical

research is needed. Indeed, among 36 recommendations, 16 were based upon

experts’ opinion and only 3 were of Grade A evidence. Nutrition remains a

component of supportive care and should be part of an integrated approach

addressing both anticancer therapy and improvement of patients’ quality of life. Given

that nutrition is at the crossroads of “pure” medicine and social sciences, emphasis

should be placed on the development of ancillary social studies in future randomised

clinical trials.

Conflict of interest statement

Pierre Senesse received funding from Aguettant, Baxter, Fresenius-Kabi, Nestlé,

Nutricia for advisory activity. Patrick Bachmann is a member of the scientific

committee of Nutrizoom of Nestle Clinical Nutrition France, and was investigator in

2012-2013 for Fresenius-Kabi France. Corinne Bouteloup declares a conflict of

interest with Fresenius-Kabi, Nutricia Clinical Nutrition SAS, Nestlé Clinical Nutrition,

and Baxter. Pascal Crenn received funding from Nestlé for educational activities.

Marie-Paul Vasson declares a conflict of interest with Nestlé for her work in a former

clinical trial. Xavier Hébuterne received funding from Fresenius-Kabi, Nestlé and

Baxter for advisory activity, as a member on an advisory board, and from Nutricia,

Abbott, and Schering-Plough for educational activities.

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

Acknowledgements

We would like to acknowledge the editorial assistance of Julie Courraud.

Appendix A. Co-Author affiliations

b Anticancer center Léon-Bérard, 28, rue Laennec, F-69008 Lyon, France

c Radiation Oncology Department, CHU Poitiers, BP 577, F-86021 Poitiers cedex,

France

d Gastroenterology and Clinical Nutrition, CHU Nice, University of Nice Sophia-

Antipolis, F-06202, Nice Cedex 03, France

e CHU de Bordeaux, Pôle de Gérontologie Clinique, F-33000 Pessac, France;

University Bordeaux Segalen, RMSB, UMR 5536, F-33000 Bordeaux, France;

CNRS, RMSB, UMR 5536, F-33000 Bordeaux, France

f Digestive and Hepatobiliary Medicine department, CHU Clermont-Ferrand, F-63003

Clermont-Ferrand; Human Nutrition Unit, Clermont University, Auvergne

University, BP 10448, F-63000 Clermont-Ferrand; INRA, UMR 1019, UNH, CRNH

Auvergne, F-63000 Clermont-Ferrand, France

g Versailles Saint Quentin en Yveline University (EA 4497), Assistance Publique

Hôpitaux de Paris (Raymond Poincaré Hospital), 104, boulevard Raymond-

Poincaré, F-92380 Garches, France

h Universitary hospital center Cochin, Assistance Publique Hôpitaux de Paris, 27, rue

du Faubourg-Saint-Jacques, F-750014 Paris, France

i INRA, Réseau NACRe, CRJ, bâtiment 400, F-78352 Jouy-en-Josas cedex, France

j Anticancer center Curie, 26, rue D’Ulm, F-75005 Paris, France

k French league against cancer, 14, rue Corvisart, F-75013 Paris, France

l CHU Lyon-Sud, 165, chemin du Grand-Revoyet, F-69495 Pierre-Benite cedex,

France

m Anticancer center Jean-Perrin, 58, rue Montalembert, BP 392, F-63000 Clermont-

Ferrand, France

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