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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: [email protected]
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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