Nutritional Interventions in Head and Neck Cancer Patients Undergoing Chemoradiotherapy: A Narrative Review

The present review aimed to define the role of nutritional interventions in the prevention and treatment of malnutrition in HNC patients undergoing CRT as well as their impact on CRT-related toxicity and survival. Head and neck cancer patients are frequently malnourished at the time of diagnosis and prior to the beginning of treatment. In addition, chemo-radiotherapy (CRT) causes or exacerbates symptoms, such as alteration or loss of taste, mucositis, xerostomia, fatigue, nausea and vomiting, with consequent worsening of malnutrition. Nutritional counseling (NC) and oral nutritional supplements (ONS) should be used to increase dietary intake and to prevent therapy-associated weight loss and interruption of radiation therapy. If obstructing cancer and/or mucositis interfere with swallowing, enteral nutrition should be delivered by tube. However, it seems that there is not sufficient evidence to determine the optimal method of enteral feeding. Prophylactic feeding through nasogastric tube or percutaneous gastrostomy to prevent weight loss, reduce dehydration and hospitalizations, and avoid treatment breaks has become relatively common. Compared to reactive feeding (patients are supported with oral nutritional supplements and when it is impossible to maintain nutritional requirements enteral feeding via a NGT or PEG is started), prophylactic feeding does not offer advantages in terms of nutritional outcomes, interruptions of radiotherapy and survival. Overall, it seems that further adequate prospective, randomized studies are needed to define the better nutritional intervention in head and neck cancer patients undergoing chemoradiotherapy.     

Pretreatment Glasgow Prognostic Score Correlated with Serum Histidine Level and Three-Year Mortality of Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma and Optimal Performance Status

Few prospective cohort trials have investigted the effect of pretreatment nutritional and inflammatory status on the clinical outcome of patients with cancer and optimal performance status and assessed the interplay between nutrition, inflammation, body composition, and circulating metabolites before treatment. Here, 50 patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2 were prospectively recruited along with 43 healthy participants. Before concurrent chemoradiotherapy, compared with healthy controls, the cancer group showed lower levels of histidine, leucine, and phenylalanine and had low values in anthropometric and body composition measurements; however, the group displayed higher ornithine levels, more malnutrition, and severe inflammation. Pretreatment advanced Glasgow prognostic score (1 and 2) status was the sole prognostic factor for 3-year mortality rate and was associated with age and serum histidine levels in patients with cancer. Thus, even at the same tumor stage and ECOG PS, patients with LAHNSCC, poor nutrition, and high inflammation severity at baseline may have inferior survival outcomes than those with adequate nutrition and low inflammation severity. Assessment of pretreatment nutritional and inflammatory status should be included in the enrollment criteria in future studies.     

The Effect of Exercise and Nutritional Interventions on Body Composition in Patients with Advanced or Metastatic Cancer: A Systematic Review

Advanced and metastatic cancers significantly alter body composition, leading to decreased lean mass and variable effects on fat mass. These effects on body composition are associated with significant physical dysfunction and poor prognosis in patients with cancer. Whilst exercise and nutritional interventions are likely to be of benefit in counteracting these effects, relatively little is known about using such interventions in patients with advanced or metastatic cancer. Therefore, in this systematic review we examine the effect of exercise and combined exercise and nutritional interventions on lean mass and fat mass among patients diagnosed with advanced or metastatic cancer. Following PRISMA guidelines, we identified 20 articles from PubMed, EMBASE, CINAHL, Cochrane CENTRAL, PEDro, SPORTDiscus, and REHABDATA. Overall, advanced or metastatic cancer populations comprising of mixed cancer types were most commonly examined (n = 8) with exercise or combined exercise and nutritional interventions being well-tolerated with few adverse effects. Both intervention approaches may preserve lean mass, while only combined interventions may lead to alterations in fat mass. However, further exercise and nutritional studies are needed to definitively understand their effects on body composition. As exercise and nutrition-related research continues in this understudied population, the knowledge gained will help guide supportive clinical treatments.     

Relationship between Preoperative Nutritional Status and Clinical Outcomes in Patients with Head and Neck Cancer

The nutritional status in cancer patients is related to cancer survival and surgical outcome. The objective of this study was to examine the relationship between preoperative prognostic nutritional index (PNI) and post-operative clinical outcomes in head and neck cancer (HNC) patients. A total of 1282 head and neck cancer patients receiving surgical resection in Changhua Christian Hospital between 1 January 2010 and 30 August 2021 were recruited in the final analysis after undergoing propensity score matching analysis. The logistic regression model was used to assess the association of the PNI group with overall and various complications. The patients in the high PNI group had a significant lower incidence of overall complications, medical complications, and pulmonary complications; but not significant surgical complications. The high PNI group had lower mortality risk. The results in this study revealed that PNI score was a significant independent predictor of postoperative complications in HNC patients undergoing surgical resection. We recommend preoperative testing and evaluation of HNC patients to identify low PNI and high-risk groups for postoperative surveillance.     

Combination Treatment of Withalongolide a Triacetate with Cisplatin Induces Apoptosis by Targeting Translational Initiation,Migration, and Epithelial to Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma

Treatment regimens for head and neck squamous cell carcinoma (HNSCC) typically include cisplatin and radiotherapy and are limited by toxicities. We have identified naturally derived withalongolide A triacetate (WGA-TA) from Physalis longifolia as a lead compound for targeting HNSCC. We hypothesized that combining WGA-TA with cisplatin may allow for lower, less toxic cisplatin doses. HNSCC cell lines were treated with WGA-TA and cisplatin. After treatment with the drugs, the cell viability was determined by MTS assay. The combination index was calculated using CompuSyn. The expression of proteins involved in the targeting of translational initiation complex, epithelial to mesenchymal transition (EMT), and apoptosis were measured by western blot. Invasion and migration were measured using the Boyden-chamber assay. Treatment of MDA-1986 and UMSCC-22B cell lines with either WGA-TA or cisplatin alone for 72 h resulted in a dose dependent decrease in cell viability. Cisplatin in combination with WGA-TA resulted in significant synergistic cell death starting from 1.25 μM cisplatin. Combination treatment with WGA-TA resulted in lower cisplatin dosing while maintaining the downregulation of translational initiation complex proteins, the induction of apoptosis, and the blockade of migration, invasion, and EMT transition. These results suggest that combining a low concentration of cisplatin with WGA-TA may provide a safer, more effective therapeutic option for HNSCC that warrants translational validation.     

New,Immunomodulatory, Oral Nutrition Formula for Use Prior to Surgery in Patients With Head and Neck Cancer: An Exploratory Study

Background: The perioperative use of immunomodulatory nutrition formulas in patients with head and neck cancer reduces the number of postoperative infections and the length of hospital stay. Objective: An exploratory, randomized, controlled, blind, clinical trial was designed to examine the effect of the preoperative consumption of a new, immunomodulatory, oral nutrition formula in patients with head and neck cancer. Methods: Thirty‐eight patients were randomized to receive either 400 mL/d of either the new immunomodulatory formula (IF) or that commonly used in clinical practice (CF) over 10 days prior to surgery. Thirty‐three patients completed the study. Compliance, tolerance, the length of hospital stay, the incidence of infections and noninfectious complications before discharge, and the same up to 15 and 30 days after discharge were recorded. Results: The percentage of patients who developed infections before discharge was significantly lower in the IF than in the CF group (P = .013), as was the number of infections/100 patients/d (P = .035). The length of hospital stay was significantly shorter in the IF group (P = .001). Both formulas were safe and well tolerated. No other differences were detected. These results suggest preoperative consumption of the new formula to be beneficial for patients with neck and head cancer. Further trials are needed to confirm these results and to test the efficacy of the formula in patients with other conditions. Conclusion: The new formula can be safely prescribed as part of the preoperative treatment of patients with head and neck cancer and might reduce the problem of postoperative infection.     

The Role of Pretreatment Percutaneous Endoscopic Gastrostomy in Facilitating Therapy of Head and Neck Cancer and Optimizing the Body Mass Index of the Obese Patient

Background: Chemoradiation of head and neck cancer induces severe dysphagia and malnutrition, which may lead to interruptions in therapy and reduction in its efficacy. Percutaneous endoscopic gastrostomy (PEG) feedings bypass the oropharynx, allowing administration of nutrients and medications into the stomach, thus preventing malnutrition, dehydration, and treatment interruption. Methods: Medical records of 161 patients treated for head and neck cancer who had PEGs placed prior to chemoradiation and 2 PEGs placed during chemoradiation were reviewed from the date of PEG placement throughout treatment and utilization. The objective was to determine the contribution of pretreatment PEGs to the therapy of patients with head and neck cancer and to optimize their body mass index. Results: Severe chemoradiation‐induced dysphagia developed in 160 patients (98%), necessitating PEG utilization for feeding and hydration. PEGs were used for a mean 251 ± 317 days. Significant complications related to PEG placement and utilization were infrequent. PEG feeding allowed chemoradiation to continue without interruption in 93% of patients. Individualized feeding regimens optimized body mass index in obese and overweight patients with a decline from 33.0 ± 3.4 to 28.4 ± 4.8 kg/m² (P < .001) and 27.3 ± 1.5 to 24.6 ± 2.7 kg/m² (P < .001), respectively. Radiation‐induced strictures developed in 12% of patients, requiring endoscopic dilatation. Conclusions: Enteral feeding through prechemoradiation‐placed PEGs is an effective and safe method for nutrition and hydration of patients with head and neck cancer undergoing chemoradiation. PEGs allowed chemoradiation to proceed with minimal interruptions despite severe dysphagia, which excluded oral intake for prolonged periods.     

Relationship between Seasonal Changes in Food Intake and Energy Metabolism,Physical Activity,and Body Composition in Young Japanese Women

We investigated seasonal changes in food intake, energy metabolism, and physical activity (PA) and explored their associations with body composition. In total, 28 women aged 20–23 years in the Kansai area of Japan participated in this year-long study spanning the winter, spring, and summer seasons. A dietary investigation was performed using the weight recording method, and the amount of histidine in the diet, which may be related to the regulation of energy intake, was calculated. Resting metabolic rate (RMR), body composition, and PA were measured using indirect calorimetry, bioelectrical impedance analysis, and uniaxial accelerometry, respectively. The results showed that energy intake was highest in winter, decreased significantly with increasing temperature, and decreased by 25% in summer. As the intake of histidine in the diet did not increase in summer, it did not seem to be involved in the suppression of energy intake. RMR was highest in winter and decreased significantly in summer by 20%. The amount of PA was low in winter, increased significantly in the spring, and decreased again in summer. Body weight increased in winter, with an accumulation of fat in the trunk and arms, and decreased in summer, with a reduction in the amount of fat. Greater energy intake and less PA in winter induced an increment in body weight despite the increase in RMR. There were no significant changes in lean body mass between the seasons; however, the muscle weight of the lower limbs increased significantly in spring and in summer compared with that in winter (p < 0.001). Thus, seasonal changes in food intake, energy metabolism, and PA occur, with resultant changes in the body composition under comfortable air-conditioned environments.     

Comparison of Nutritional and Clinical Outcomes in Patients with Head and Neck Cancer Undergoing Chemoradiotherapy Utilizing Prophylactic versus Reactive Nutrition Support Approaches

Background

The optimal method of tube feeding for patients with head and neck cancer remains unclear. A validated protocol is available that identifies high-nutritional-risk patients who would benefit from prophylactic gastrostomy tube placement. Adherence to this protocol is ultimately determined by clinical team discretion or patient decision.

Perioperative Immunonutrition in Well-Nourished Patients Undergoing Surgery for Head and Neck Cancer: Evaluation of Inflammatory and Immunologic Outcomes

Limited work is available on the benefits of nutritional support enriched with arginine and n-3 fatty acids in surgical patients with head and neck cancer, particularly if well-nourished. We conducted a pilot study in these patients to examine effects on inflammatory markers and clinical outcome. Patients scheduled for radical resection of the oral cavity were randomised to 5 day preoperative and 5 day postoperative Impact^® (IMN, n = 4), or no preoperative supplementary nutrition and Isosource^® postoperatively (STD, n = 4). Plasma fatty acids, C-reactive protein (CRP), tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were measured at baseline, day of surgery and on postoperative days (POD) 2, 4 and 10. Postoperative complications were recorded. The (eicosapentaenoic acid plus docosahexaenoic acid) to arachidonic acid ratio was significantly higher in IMN patients on POD 2, 4 and 10 (P < 0.01). While not statistically significant, CRP, TNF-α, and IL-6 concentrations were higher in the STD group on POD2 while IL-10 was lower. Median length of stay was 10 (range 10–43) days in the IMN group and 21.5 (7–24) days in the STD group. Five complications were seen in the STD group and two in the IMN group. The results support the need for a larger trial focusing on clinical outcome.     

A Multi-Site,International Audit of Malnutrition Risk and Energy and Protein Intakes in Patients Undergoing Treatment for Head Neck and Esophageal Cancer: Results from INFORM

Patients with foregut tumors are at high risk of malnutrition. Nutrition care focuses on identifying individuals at risk of malnutrition and optimizing nutrient intake to promote the maintenance of body weight and lean body mass. This multi-center prospective, longitudinal study audited nutrition care practices related to screening for risk of malnutrition (Patient-Generated Subjective Global Assessment Short Form; PG-SGA SF), and nutrition interventions prescribed (route; adequacy of energy and protein intakes). Audits occurred at four time periods: baseline (before treatment) and at 2, 4, and 6 months after starting cancer treatment; 170 patients (esophageal (ESO; n = 51); head and neck (HN; n = 119)) were enrolled. Nutrition risk (PG-SGA SF score ≥ 4) was prevalent at every time period: HN (baseline: 60%; 6 months 66%) and ESO (77%; 72%). Both groups had significant (p < 0.001) weight losses over the 6 month audit period (HN = 13.2% ESO = 11.4%). Enteral nutrition (EN) was most likely to be prescribed at 2 months for HN and at 4 and 6 months for ESO. Target prescribed energy and protein intakes were not met with any nutrition intervention; although adequacy was highest for those receiving EN. Nutrition care practices differed for HN and ESO cancers and there may be time points when additional nutrition support is needed.