Keywords

Introduction

Clinical outcome of patients with head and neck squamous cell carcinoma (HNSCC) is linked to patient, disease, and treatment characteristics, such as performance status, comorbidities, tumor stage, HPV status, and the availability and feasibility of adequate therapeutic approaches. However, the prediction of patient’s prognosis is challenging and at the same time it is a critical point to offer the patient an adequate counseling and treatment planning.

There are also other patient-specific variables and host factors related to the immune, inflammation, and nutritional status that influence the survival of HNSCC patients. In the complex interaction between the host and the tumour, these factors play an important even if sometimes underestimated role.

In a recent work, Yu et al. [1] evaluated almost 600 primary HNSCC patients treated with definitive or post-operative RT. The authors showed through a machine-learning model that the main predictors of patients’ overall survival were performance status, body-mass index (BMI) and the host factors reflecting the patients’ nutrition and inflammation status.

Malnutrition and Nutritional Interventions

Weight loss, BMI, loss of muscle mass and biochemical examinations indicative of nutritional status are important predictive factors to consider in HNSCC patients. These patients are among the most vulnerable ones in terms of cancer-related malnutrition (defined as an unwanted weight loss of >5% (or >10%) in three (or six) months, or a reduction of BMI to less than 21 kg/m2 [2]). Malnutrition in patients with HNSCC is a concern, as it is associated with increased treatment toxicity, number of admissions, health care costs, morbidity, and mortality [3]. In fact, the relative risk of dying of a severely malnourished patient is 1.8 times higher than for patients without malnutrition [4]. Furthermore, malnutrition in patients with HNSCC is associated with depression, [3] lower physical functioning and immune status, and also with impaired quality of life (QoL) [5].

According to these observations, it seems clear that a correct nutritional intervention is critical to improve the nutritional intake, general status, symptoms, and also the QoL of these patients [6].

In this regard, an individualized dietary counselling was found to be effective in maintaining weight and/or nutritional status when compared to standard nutritional advice, as demonstrated by the study of van den Berg et al. [7]. The individual approach of an expert allows to choose an appropriate diet that respects the needs of the individual subject also recommending, if necessary, additional nutritional supplements and/or enteral feeding [5].

In 2011, Jager-Wittenaar et al. reported that patients with head and neck cancer undergoing treatment with an intake of ≥ 35 kcal/kg/day and ≥1.5 g protein/kg/day lost significantly less body weight and lean mass than patient with a lower intake [8]. To achieve this caloric intake, patients with a BMI <20 kg/m2 or who are malnourished at baseline might find benefit in using dietary supplements [9].

Furthermore, international guidelines suggest that in the presence of head and neck cancer that interferes with swallowing, enteral nutrition (EN) should be recommended. Prophylactic tube feeding is also recommended if severe local mucositis is expected, which could interfere with swallowing, particularly when the irradiation of large fields of oral pharyngeal mucosa is foreseen [10]. There are still many debates about the preference to be given to nasogastric tubes or percutaneous endoscopic gastrostomies (PEG). Each strategy has advantages and disadvantages and should be chosen according to clinical factors and patient’s preference. Nasogastric tubes have a shorter duration, but a higher risk of tube dislodgement and may also cause more social discomfort to the patients. On the other hand, PEGs have other complications, including local wound infection, tube occlusion, tube leakage, cellulitis, eczema, or hypergranular tissue [11, 12].

Personalization of nutritional interventions should consider the baseline nutritional status, the biochemical inflammatory indexes, the planned radiation dose on oral/oropharyngeal mucosa and/or pharyngeal constrictor muscles and also the results of multiparameter risk scores (Fig. 21.1).

Fig. 21.1
A schema of nutritional support for head and neck cancer patients has four factors: Malnutritions have a biochemical exam, B M I, weight loss, and sarcopenia; Inflammatory insides have V E S, P C R, and P C T; Planned radiation dose has on oral and pharyngeal mucosa; Multiparameter risk score has M N S-S F, M S T, M U S T, N R S, N R I, and S G A.

Factors to be considered to tailor nutritional support in Head and Neck cancer patients

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Immunonutrition

Beyond their purely nutritious function, some nutrients have been associated with pharmacologic-like effects. These “immuno-nutrients” comprise a wide range of molecules including fats (ex. n-3 fatty acids), amino acids (ex. arginine, glutamine), vitamins (ex. vitamin E), and other substances (ex. nucleotides, antioxidants), which can be administered either by the enteral or parenteral route [13]. In particular, these agents could modulate the non-infectious pro-inflammatory state associated with oxidative stress that characterizes patients with head and neck cancer. In fact, immuno-nutrition can enhance immune cell responses through the modulation of their phenotypes and functions [14]. Several studies have reported an increase of T lymphocytes and their subsets, respectively, in head and neck cancer patients after the nutritional support enhanced with arginine, ω-3 fatty acids, and ribonucleic acids [15, 16].

In patients with systemic inflammatory response syndrome and multiple organ failure, serum C-reactive Protein (CRP) levels were lower in patients receiving immuno-nutritional support than in those taking standard nutrition [17]. It has been hypothesized that because of this immunomodulating effect, immuno-nutrition can also lead to better local control, greater treatment efficiency, and, when used in a pre- or perioperative context, may decrease the length of hospital’s stay and postoperative infectious complications [18]. However, we still need further evidence coming from well conducted clinical trials with large and homogeneous patient population before this strategy can be fully implemented in clinical practice.

Physical Activity and Quality of Life

Another aspect that needs to be considered in malnourished cancer patients is weight loss accompanied by muscle wasting. Muscle wasting may influence muscle function and leads to loss of strength, increased fatigue and decreased QoL [19]. In HNSCC patients, exercise has been shown to be feasible, safe and to have an impact on body composition, physical function, QoL, and fatigue management, during and after treatment [20]. Additionally, there is a growing body of evidence suggesting that regular physical activity leads to a reduction in the risk of cancer-specific mortality and all-cause mortality, compared with physically inactive patients. Exercise, including aerobic and active resistance exercises, can therefore be incorporated as a routine part of the HNSCC patient’s care [21]. In addition to the positive effects on physical function, aerobic capacity, lean body mass, and muscle strength, it has been shown that physical activity can improve QoL, sleep, depressive symptoms, pain, and emotional and cognitive functioning [22]. Physical activity interventions improve also domains that historically plague HNSCC patients such as reductions in cigarette cravings [23], improved abstinence rates with alcohol and illicit drugs [12]; improved QoL in physical, emotional, and social domains [24]; and improved symptoms of depression and anxiety [25]. These beneficial effects have been found with both traditional and alternative physical activities such as yoga and Tai Chi, which have demonstrated improvements in heart rate variability, vascular endurance index, QoL, and immune function in patients with HNSCC [22] (Fig. 21.2).

Fig. 21.2
A schema of physical exercises benefits; cardiovascular - heart rate variability, temperature increase, and hypoxia reduction; Musculoskeletal - physical strength increase, and body fat reduction; Disease history - pain control increase, and risk of cancer reduction; Quality of life - depression, anxiety improve, and cigarette carvings reduction.

Benefits of physical exercises in HNSCC survivors

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Prophylactic Measures

To improve the QoL of patients with head and neck cancer, in addition to the management of malnutrition and loss of muscle strength, the negative consequences of treatment in terms of late adverse effects must be considered. Of these, dysphagia is the most impactful. The sequelae of dysphagia include avoidance of eating or drinking, poor dietary intake, risk of ab ingestis pneumonia, reduced psychosocial functioning, and poor social engagement. Long-term swallowing function is strongly related to the ability to swallow before treatment in HNSCC patients. For this reason, it has been proposed to use a prophylactic approach to swallowing management, with “prehabilitation” programs. Prehabilitation aims to minimize the effect of dysphagia through the maintenance of muscle mass, strength, range of motion, coordination, and function. Prophylactic swallowing protocols have been found to improve functional swallowing outcomes, including the ability to manage a wider range of food and drinks; maintain muscle mass; improve mouth opening; improve taste, smell, and salivary function; and reduce the need for tube feeding [3]. The exercises performed are mainly aimed at training the mandible muscles, the tongue’s and neck’s mobility, and all movements necessary for swallowing. Some authors recommend starting with exercises that address anticipated function loss at a regimen of ten repetitions, three times a day, and supplementing these exercises with increased physical activity as well as consultation on nutrition and mental health [26] (Fig. 21.3).

Fig. 21.3
A schema of the pre-habilitation concept has four factors: Nutrition - nutritional counseling and personalized diet; Lifestyle - stopping smoking and alcohol, and daily physical activity; Mental health - meeting with a psychologist and relaxing exercise; Functional - medical optimization, coordination, and strength exercises.

The concept of pre-habilitation before the start of oncological treatments

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It is therefore clear that to provide the greatest benefit to head and neck cancer patients, it is necessary to use a multimodal interdisciplinary rehabilitation approach, which combines nutritional and psychological support with physical exercise [27].

Conclusion and Recommendations

It is important to increase the education and knowledge of physicians about the positive effects given by correct nutritional interventions and by physical exercise. The strategies to proactively engage physicians taking care of HNSCC patients in nutritional screening activities and in suggesting physical exercises to the patients may be different: integrating these educational aspects in their curriculum, putting these topics in each national guideline for cancer diagnosis and treatment, and creating checklists for assessment of nutritional status at baseline and periodically. Moreover, the possibility to support nutritional multidisciplinary working groups, the involvement of patients’ association and the integration of nutritional and exercises issues into clinical trials may offer other possibility to increase the relevance of these topics in the routine care.