Patients with head and neck cancer (HNC) present malnutrition rates that can vary between 19% and 67%, depending on the diagnostic tool used [1,2]. A study published in 2020 describes that the prevalence of malnutrition in patients with HNC was 22.6% (8% moderate, 13.3% severe), according to one malnutrition diagnostic tool [3]. Malnutrition in these patients is multifactorial [4]. Among the factors that influence nutritional commitment, the first factor to consider is cancer itself. On the one hand, cancer cells generate pro-inflammatory mediators and cytokines that cause anorexia, proteolysis, lipolysis, and metabolic disorders. On the other hand, tumor growth can generate mechanical obstruction, trismus, odynophagia, and dysphagia, which affect the consistency and amount of food tolerated [5]. Added to all this are the psychological effects that the disease can have and complications associated with oncological treatments, such as nausea, vomiting, xerostomia, mucositis, fatigue, dysgeusia, pain, and swallowing disorders, among others [2,6]. These symptoms can aggravate or accelerate a previous state of malnutrition. 

Malnutrition prior to diagnosis or treatment is associated with greater toxicity from chemotherapy and/or radiotherapy, increased postoperative complications, a lower quality of life, and shorter survival. For this reason, every patient diagnosed with HNC must undergo nutritional screening and, if necessary, be referred in a timely manner to a nutrition support team to implement nutritional interventions in the early stages of the disease [1,7].

Objectives

1. Provide nutritional management guidelines, aimed at the health team that cares for patients with HNC who are undergoing oncological treatments.
2. Guide the nutritional screening of patients with HNC who are malnourished or at nutritional risk.
3. Define interventions aimed at maintaining or recovering the nutritional status of patients.
4. Guide the use of enteral access and installation time.

A non-systematic review of the literature was carried out to evaluate the available information about nutritional support for patients with HNC. The search was carried out between September and December 2023 on the PubMed and Google Scholar platforms, searching for the following MeSH terms: "Head and Neck Neoplasms,"  "Nutrition Therapy," and "Immunonutrition Diet," using the AND and OR connectors. The references to each work were reviewed to collect references that were not indexed on these platforms. The most representative works from the last 15 years were reviewed. 

Nutritional Evaluation and Diagnosis

Nutritional Screening

The international guidelines for nutritional management in patients with HNC suggest screening at the time of oncological diagnosis to investigate and timely refer individuals who will benefit from specialized nutritional therapy. The objective of nutritional therapy is to improve the patient's clinical results, reducing the risk of infection and postoperative complications, positively contributing to tolerance to radiotherapy and chemotherapy, and helping to maintain quality of life [6,8-10].

Particularly for oncology patients, it has been difficult to define a standard questionnaire due to the large number of variables that could affect their nutritional status [11-13]. There are a large number of nutritional screening tools validated in the oncology population, which are summarized in Table 1. Each nutrition support team must choose the one that is easiest to apply and interpret. Screening should be applied periodically to reclassify the patient according to their clinical evolution [10].

Table 1: Nutritional Screening Tools Validated for the Oncology Population.

MUST, Malnutrition Universal Screening Tool; NRS-2002, Nutritional Risk Screening 2002; MNA, Mini Nutritional Assessment; MST, Malnutrition Screening Tool; PG-SGA, Patient Generated Subjective Global Assessment.

The Subjective Global Assessment (SGA) and the Patient-Generated Subjective Global Assessment (PG-SGA) are recommended in several countries as nutritional screenings for cancer patients, given their high sensitivity and specificity. However, the reading-writing management necessary in the second part of the PG-SGA could be a limitation for illiterate patients or those with cognitive difficulties [11]. Its application can be complex in centers with a high number of patients, as it requires more time to execute. On the contrary, it is an excellent tool if it must be applied to a small population of patients, since it investigates specific symptoms of oncological disease [14].

The Malnutrition Screening Tool (MST) is another validated screening for cancer patients and has high sensitivity (100%) and specificity (94.6%) [15-17]. This tool is easy to implement and reproduce since it includes only two aspects: weight loss and intake. It does not require calculations or measuring weight or height, so it can be applied by any health professional, facilitating the universality of screening in all patients at the time of oncological diagnosis (Table 2) [13,18]. To interpret the results, it is necessary to add the score given to each response, and if the sum is equal to or greater than 2, the patient presents nutritional risk and should be referred for a nutritional evaluation as soon as possible. In Figure 1, we propose an algorithm for nutritional screening and referral to the nutrition support team [57].

Table 2: Malnutrition Screening Tool (MST).

Figure 1: Algorithm for Nutritional Screening Algorithm and Referral to the Nutrition Support Team.

Nutritional Evaluation

Those patients with a risk of malnutrition, defined by nutritional screening, should be referred for evaluation by a specialized nutritional support team, with the aim of performing a nutritional diagnosis and planning appropriate strategies. 

To standardize nutritional diagnosis in clinical practice, the use of criteria developed in 2017 by an international consensus of nutrition societies known as GLIM criteria (acronym for Global Leadership Initiative on Malnutrition) has been proposed. Malnutrition defined by GLIM criteria could predict survival and postoperative complications in patients undergoing oncological treatments [19,20]. This tool includes phenotypic and etiological criteria, and the diagnosis of malnutrition is made when at least one phenotypic and one etiological criterion is present. The phenotypic criterion gives the degree of severity of malnutrition. Table 3 describes the GLIM criteria for malnutrition, and Table 4 describes its severity [21].

Table 3: GLIM Criteria for the Diagnosis of Malnutrition.

DEXA, dual-energy absorptiometry; CT, computed tomography; BIA, bioelectrical impedance analysis; MRI, magnetic resonance imaging.

*If not available, a physical examination or standard anthropometric measures may be used. Functional assessments such as hand-grip strength may be considered a supportive measure.

Table 4: Malnutrition Severity Classification According to GLIM Criteria [21].

* Requires 1 phenotypic criterion that meets this grade

**Per validated assessment methods

Weight loss equal to or greater than 10% of the usual weight within six months prior to treatment is associated with a higher risk of complications: infections, alterations in healing, muscle weakness, reduced response to radio chemotherapy treatment, and lower quality of life. Therefore, it is important to implement a more frequent monitoring protocol in this specific group of patients [8]. 

Once it is defined that the patient has malnutrition according to GLIM criteria, it is necessary to carry out a complete nutritional evaluation that considers changes in intake or consistency of feeding, symptoms of swallowing disorders, body composition parameters, biochemical tests, and muscle function, among others [10].

There are several studies that evaluate this tool in patients with oropharyngeal cancer. An example is the study by Einarsson et al. published in 2020, who used this tool to evaluate the prevalence of malnutrition in patients with head and neck cancer, describing a prevalence of 32% [22].

Nutritional support therapy refers to the provision of nutrients to treat or prevent states of malnutrition. This support can be done by oral route, enteral, or parenteral access, and the main objective is to maintain or recover an optimal nutritional status.

Forms of Nutritional Support

1. Nutritional counselling: consists of educating the patient and family on calorie-protein enrichment techniques for the daily diet, as well as changes in consistency and culinary modifications to increase intake. It is performed on patients who have good oral tolerance. A meta-analysis carried out in 2019, which evaluated the effect of nutritional counselling on cancer patients, determined that it is effective in improving patients' energy intake and quality of life [23].
2. Oral Nutritional Supplements (ONS): liquid, semi-solid, or powder formulas that provide macro- and/or micronutrients, designed as nutrient-dense solutions [24]. They are recommended for patients who do not meet their nutritional requirements exclusively orally and are used in conjunction with nutritional counselling.
3. Enteral Nutrition (EN): nutritional therapy administered via feeding tube or ostomy. The most common access is through the nasogastric tube (NGT), the nasojejunal tube (NJT), the gastrostomy (GTT), or the jejunostomy (JJT). The contribution is made mainly with commercial enteral formulas in liquid presentation, ready for administration (RTH: ready to hang), that consist of a closed infusion system. However, in the case of gastrostomy users, feeding tolerance can be evaluated through intermittent boluses with homemade blenderized food and powdered supplements to reconstitute [25,26]. EN can be total when the patient's nutrition depends exclusively on this route or supplementary when it is provided as a support to oral nutrition if the patient is unable to meet his or her requirements [24].
4. Parenteral Nutrition (PN): nutritional therapy provided through a venous line, whether central or peripheral, composed of amino acids, glucose, lipids, electrolytes, vitamins, and trace elements [24]. It can be total, when 100% of the requirements are provided parenterally, or supplementary, when the contribution of PN is complementary to nutrition delivered by any other route (oral or enteral). This type of nutritional support is indicated exclusively when no other route is available.

Choice of Feeding Route in Patients with Head and Neck Cancer

Whether due to the tumor or oncological treatments (surgery, chemotherapy, and radiotherapy), possible alterations in oral intake that may require artificial nutrition (swallowing disorder, tumor obstructions, and severe mucositis, among others) must be periodically evaluated. Choosing the nutrition route is a complex decision that must consider technical feasibility, available resources, associated risks, nutritional status, the patient's opinion, and quality of life. There is no consensus in different guidelines or studies about which is the best access route, so it must be evaluated on a personalized basis [27]. Figure 2 describes an algorithm to decide the best access route for the patient with HNC.

1. Oral Route: It is the route of choice as long as the patient can maintain adequate oral intake, which allows them to meet their nutritional requirements. It can be optimized with nutritional counseling, oral nutritional supplements, and consistency changes according to swallowing disorders, as necessary.
2. Enteral route: The start of enteral nutrition is suggested when the patient has an oral intake of <60% of their nutritional requirements for 1 to 2 weeks or is unable to have oral intake for more than 1 week [28]. The patient is required to have a functional gastrointestinal tract distal to the access route.

• Enteral access by tube: the most common are the nasogastric tube (NGT) and the nasojejunal tube (NJT). The use of a tube is suggested when it is estimated that the patient will require this route of nutrition for less than 4 to 6 weeks [27]. One of the cases where this feeding route is used is in the immediate postoperative period of oropharyngeal surgery, since patients frequently cannot feed orally during the first 7 to 10 days. Some risks associated with the use of tubes are obstruction, displacement, nasal pressure ulcers, sinusitis, and aspiration pneumonia [27,28].
• Enteral access through ostomy: The most frequently used in this population is the gastrostomy (GTT), which is generally through percutaneous endoscopic installation (PEG). Its use is suggested if the need for enteral nutrition is estimated for a period longer than 4 to 6 weeks [30]. Some of the complications associated with the use of GTT are the risk of infection and leakage at the insertion site, local pain, and erosion in the gastric wall [29].Figure 2: Algorithm to Define Nutritional Support Pathway in Patients with Head and Neck Cancer.

Choice of Enteral Access: Tube versus GTT

According to a systematic review from 2022, both accesses are similar in nutritional and oncological results and need to interrupt radiotherapy, survival, and quality of life [27]. The final decision about one access over another will depend on the estimated time of use, the availability of enteral formulas, the risk/benefit evaluation, and the patient's quality of life. In centres where the use of RTH enteral formulas is available, the decision will depend mainly on the estimated duration of use and the patient's preferences. On the contrary, if there is no easy access to these formulas, GTT would be a better alternative since it allows the administration of homemade blenderized foods plus nutritional supplements. The need to replace the enteral access must also be considered, with variable times depending on the material and type of access, being longer in the case of GTT, up to 12–18 months [25,29].

Deciding When to Install an Enteral Access: Prophylactic versus Reactive Approach

There is no consensus on the best timing to install an enteral access in patients with oropharyngeal cancer, either prior to the start of oncological treatment (prophylactic approach) or during or after it, when the patient is unable to meet their nutritional requirements orally or presents weight loss that cannot be reversed with supplementation (reactive approach) [31,32]. According to a systematic review published in 2021, patients with prophylactic GTT (pGTT) presented less weight loss and better quality of life 6 months after treatment compared to those with reactive GTT (rGTT). However, in the long term (12 months post-treatment), there were no significant differences in quality of life or disease-free survival [31]. Another systematic review published in 2022 defined that the use of pGTT and rGTT is similar when comparing nutritional outcomes, the need for radiotherapy interruption, and survival [27].

Because there is no conclusive evidence that favors the use of any of these strategies to substantially improve long-term results, we suggest considering the use of pGTT in those patients who meet any of the characteristics in Table 5. However, these recommendations should be adapted to the local reality and carried out according to the patient's preferences [33].

Table 5: Suggested Indications for the Installation of Prophylactic Gastrostomy.

Patients with HNC are susceptible to nutritional deterioration before, during, and after cancer treatment [34]. This is of utmost importance since an altered nutritional status has an impact in the short, medium, and long term, independent of the effectiveness of the treatments [35]. This is why nutritional monitoring must be continuous, with the aim of preventing or treating malnutrition in a timely manner. A study published in 2020 describes various risk factors for malnutrition in this patient population, some of which are listed in Table 6. According to this study, the highest percentage of malnourished patients was observed 7 weeks after the start of oncological treatment (42.4%), requiring closer follow-up in those with advanced tumor stages, treated with surgery and concomitant radio chemotherapy, and/or moderate or severe mucositis [36].

Table 6: Risk Factors for Malnutrition in Patients with Head and Neck Cancer.

RT, Radiotherapy; CRT, chemoradiotherapy

        a. Nutritional Requirements: Different international guidelines recommend a caloric intake between 25 and 35 kcal/kg/day and a protein intake between 1.0 and 1.5 g/kg/day [9,10,37]. However, it is necessary to individualize and differentiate clinical scenarios according to nutritional diagnosis and the type of scheduled oncological treatment.

        b. Refeeding Syndrome (RFS): It is defined as the set of symptoms and signs triggered by a sudden increase in caloric intake in previously malnourished patients with significant weight loss, prolonged underfeeding, or starvation. Due to the high rates of malnutrition in this specific group of patients, it is recommended to prevent and monitor the appearance of this syndrome. Table 7 describes the RFS risk criteria proposed by the American Society of Enteral and Parenteral Nutrition [38]. 

RFS occurs in response to the anabolic effect of insulin secreted when consuming carbohydrates, causing a shift in the use of energy substrates and causing serious, potentially fatal electrolyte alterations [39]. One of the main characteristics is the decrease in plasma levels of phosphorus, magnesium, and potassium. Some authors have suggested that hypophosphatemia is the most common electrolyte disturbance [39,40]. At the same time, the demand for thiamine increases considerably since this vitamin acts as a cofactor in carbohydrate metabolism [38]. 

The most commonly observed manifestations are tachycardia, tachypnea, edema, compromised consciousness, cardiac arrhythmias, respiratory disorders, and even death [38-40].

Table 7: ASPEN Consensus Criteria to Identify Adult Patients at Risk of Refeeding Syndrome [38].

In patients with moderate or high risk of RFS, a gradual initiation of caloric intake is suggested, calculating 5 to 10 kcal/kg/day depending on the severity of the risk. It is necessary to control levels of phosphorus, magnesium, and potassium before starting nutritional support and periodically during the first 2 weeks of refeeding. After this time frame, the risk of presenting this syndrome decreases. It is recommended that the caloric goal be reached between 7 and 10 days after the start of nutritional support. Prophylactic thiamine should also be initiated, at doses of 180 to 300 mg/day intravenously, for 7 to 10 days, depending on the risk. If electrolyte abnormalities occur, the start or increase in calories should be delayed until the laboratory abnormalities are corrected [38-40]. Figure 3 summarizes a proposal for managing refeeding syndrome.

Figure 3: Nutritional Management Algorithm in Refeeding Syndrome.

      c. Dietary Prescription: Before, during, and after oncological treatments, it is suggested to consider possible swallowing alterations with the purpose of establishing nutritional support through the most appropriate route (oral or enteral).  Early referral to the speech therapy team is recommended.

Nutritional support begins with dietary advice from the nutrition support team. Patients who can be fed orally require an evaluation to optimize feeding, emphasizing changes in consistency, control of symptoms produced by oncological therapy or the tumor, and education in protein-calorie densification techniques. 

Some techniques to optimize meal preparations include preferring foods with greater nutritional value, such as dairy products (milk, yogurt, cheeses, and milk desserts, among others), eggs, legumes, and fats of vegetable origin. The incorporation of protein/caloric modules, or ONS, is suggested. Recipes and culinary preparations that include ONS can be delivered to increase palatability and adherence to them. It is suggested to avoid infusions, broths, or jellies during main meals.

        d. Enteral Nutrition: In patients with enteral access, a polymeric formula is of first choice, and in cases of special needs, the use of a specific formula can be evaluated. It is suggested to start at an infusion rate of 10 to 20 ml/h, where tolerance should be evaluated through digestive symptoms and clinical evolution, and increase the infusion rate every 12 to 24 hours until the individual nutritional goal is achieved [41-43].

In those malnourished post-surgical patients in whom early oral intake is not possible, enteral nutritional support should be initiated within 24-48 hours following surgery, if the clinical condition allows it. In well-nourished patients, although early enteral nutrition should be prioritized, the start of this could be postponed for up to 5 days, depending on the patient's evolution, without affecting clinical results [37].

When the patient can swallow and begin oral feeding, a transition from the enteral route to the oral route begins through a mixed diet, which considers swallowing performance and coverage of the patient's nutritional requirements. To indicate the withdrawal of enteral access, it is necessary to ensure that at least 60 to 70% of the nutritional requirement is covered orally [28,44].

        e. Parenteral Nutrition: Exceptionally, patients with head and neck surgeries may require parenteral nutrition (PN); however, its routine use is not recommended. PN has specific indications and should be discussed with the Nutrition Support Team [37].

Prehabilitation refers to the continuum of care that the patient receives between the moment of diagnosis and the beginning of oncological treatment [45]. Nutritional prehabilitation aims to increase the functionality and physiological reserve of the malnourished patient, or those at nutritional risk, to improve their recovery in the postoperative period. It is performed by optimizing caloric-protein intake, whether orally, enterally, or parenterally, and is usually combined with an exercise program. Energy and protein contributions at this stage should consider at least 25–30 kcal/kg/day (which will be adjusted according to the patient's nutritional status and history) and at least 1.2 g of protein/kg/day.

The duration of prehabilitation is not well described in the literature for patients with HNC, but it is accepted that it should be at least 7 to 10 days in mildly malnourished patients and at least 10 to 14 days in severely malnourished patients [46]. It should be considered that this form of nutritional support may not generate immediately measurable changes in body composition or serum albumin levels [47].

Studies of surgical prehabilitation in patients with oropharyngeal cancer have shown benefits in caloric intake, a higher percentage of patients who manage to maintain their body weight, maintenance of serum albumin levels, a lower rate of hospitalizations, fewer visits to the emergency department, a shorter length of hospital stay, less severity of mucositis, and a higher quality of life [45,46].

Immunonutrition 

Immunonutrition is defined as a set of nutrients with pharmacological effects on the immune system [48]. Among them, the best known are arginine, nucleotides, omega-3 fatty acids, and glutamine, which have been incorporated into some enteral formulas to be administered orally or enterally.

A Cochrane systematic review in 2018 demonstrated that the use of formulas with immunonutrients in patients with HNC undergoing surgery decreased the risk of fistula formation, with no effect on length of hospital stay or mortality. It is important to highlight that this review included 19 randomized clinical trials, most with a low sample size (less than 25 patients) and substantial variations in terms of the time of administration (pre- and postoperative), duration, and type of immunonutrients used, making comparison between them difficult. The authors concluded that studies of better methodological quality were necessary to determine the effectiveness of immunonutrition in patients with HNC [49].

A systematic review carried out in 2023 aimed to evaluate the usefulness of immunonutrition in the perioperative period of patients with HNC and gastrointestinal cancer. The subgroup analysis showed that immunonutrition could reduce infectious complications in patients with HNC (RR 0.81, CI 0.67–0.98); however, there was no effect on reducing fistulas or other clinical outcomes. Once again, small sample sizes and high clinical heterogeneity stand out in the included studies, with important differences in combination and dose of immunonutrients, pre- and/or post-operative administration, duration of the intervention, and nutritional status of the patients studied [50].

In relation to the effectiveness of immunonutrition during chemo radiotherapy, a systematic review published in 2021 shows that glutamine could reduce the severity of grade 2-4 mucositis. However, the quality of the evidence is low, given the differences between types of supplementation and the lack of consensus on immunonutrient doses [51].

Given the low quality of the available evidence, the routine use of immunonutrition during chemo radiotherapy or surgery in patients with oropharyngeal cancer is not recommended at this time. Studies of better methodological quality are required to support its use in this population.

Nutritional Treatment of Symptoms Associated with Chemotherapy and Radiotherapy

Patients with HNC treated with radiotherapy, or concomitant radio chemotherapy, present a wide range of side effects determined by the type, dose, and duration of therapy.

Chemotherapy is a systemic treatment that acts on all cells in the body, whether malignant or non-malignant, predominantly rapidly dividing cells such as the gastrointestinal mucosa, bone marrow, gonads, and phanereal cells [52].

On the other hand, radiotherapy acts by preventing cell growth and division through ionizing radiation, achieving cell destruction in the irradiated area, affecting tumor cells, and, to a lesser extent, surrounding healthy tissue. The depletion of healthy cells will cause a functional decrease in the irradiated organ that is usually self-limiting, causing acute toxicities proportional to the volume of the treated organ, dose, fractionation, and individual susceptibility. These toxicities usually appear during the first weeks of treatment and disappear between 2 and 3 weeks after the completion of treatment. Less frequently, late side effects occur (appearing after 90 days of treatment), which constitute more complex processes that involve edema, fibrosis, atrophy, and hypoplasia of the connective tissue and can induce irreversible tissue changes and permanent damage [53].

Table 8 describes the most common toxicities caused by chemotherapy and radiotherapy in patients with HNC.

Table 8: Frequent Toxicities Caused By Radio and Chemotherapy in Patients with Head and Neck Cancer [54].

Nutritional support must consider the toxicities associated with antineoplastic treatments, since these interfere with oral intake, exacerbating weight loss and fatigue, decreasing tolerance to treatment, and deteriorating quality of life.

Table 9 describes general recommendations for the management of the most frequent symptoms associated with chemo and radiotherapy treatments [52,54].

Table 9: General Recommendations for the Management of Symptoms Associated with Radio and Chemotherapy Treatments in Patients with Head and Neck Cancer.

It is important to inform patients of the need to notify their healthcare team if these measures do not achieve optimal symptom management. If necessary, the medical team may indicate pharmacological treatment for symptomatic management and thus optimize dietary management measures.

Post-Treatment Follow-Up

It has been reported that patients may experience weight loss up to a year after radiotherapy, despite nutritional support and constant dietary advice [55]. Total weight loss can be close to 11% one year after completing treatment [56].

Patients with HNC who receive nutritional advice from a nutrition specialist could maintain their caloric intake, improve their quality of life, and regain more weight at three-month follow-up, compared to those patients who did not receive nutritional advice [34]. It is recommended that after oncological treatments, patients maintain outpatient follow-up by the nutrition support team, the frequency of which will depend on the nutritional evolution and other oncological treatments that are required during the course of the disease [57].

Patients with head and neck cancer present high rates of malnutrition, either due to the local effects of the tumor itself or due to symptoms secondary to treatments. It is extremely important to actively monitor the nutritional status of our patients, since malnutrition is associated with greater morbidity and mortality. The routine use of nutritional screening and timely referral to the nutrition support team are suggested. Nutritional support should be individualized based on the patient's nutritional status, current clinical condition, and scheduled treatments, which is why continuous nutritional monitoring is necessary. Given the complexity of nutritional management in this patient population, the formation of specialized nutrition support teams is suggested, which allows for adequate intervention and thus improves the patient's clinical results.

Statements and Declarations

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

The authors have no relevant financial or non-financial interests to disclose.

All authors contributed equally to the study conception and design, material preparation, data collection, and analysis. All authors participated in the first version of the manuscript.

The final version was revised by Thiare Olguin and Simona Minzer. All authors read and approved the final manuscript.

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

This is a narrative review; no ethical approval is required.

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