J.A.E. Langius

Low Levels of Circulating Invariant Natural Killer T Cells Predict Poor Clinical Outcome in Patients With Head and Neck Squamous Cell Carcinoma

PURPOSE Evading antitumor immune responses is an important aspect of the pathogenesis of head and neck squamous cell carcinoma (HNSCC). Invariant CD1d-restricted natural killer T (iNKT) cells play an allegedly pivotal role in such responses via transactivation of immune effector cells. It has been reported that iNKT cells are reduced in peripheral blood of cancer patients compared with healthy controls. Here, we investigated whether the extent of this deficiency affected disease outcome in HNSCC patients. PATIENTS AND METHODS In a prospective study, circulating iNKT cell numbers were evaluated in 47 patients before radiotherapy. Patients were stratified in three groups based on iNKT cell levels, and clinical data were obtained during a median follow-up period of 31 months. RESULTS A small, compared with an intermediate or large, circulating iNKT cell fraction was significantly associated with decreased 3-year overall survival rate (39% v 75% and 92%, respectively), disease-specific survival rate (43% v 87% and 92%, respectively), and locoregional control rate (31% v 74% and 92%, respectively) in HNSCC patients. Cox regression revealed that the iNKT cell level, as well as clinical T stage, was an independent prognostic parameter even after correction for the confounding effect of age. CONCLUSION A severe circulating iNKT cell deficiency was related to poor clinical outcome in HNSCC patients, suggesting their critical contribution to antitumor immune responses. Furthermore, screening for iNKT cell levels may be useful for determining which patients can benefit from immunotherapeutic adjuvant therapies aimed at reconstitution of the circulating iNKT cell pool.

Oral Nutritional Supplements Containing (n-3) Polyunsaturated Fatty Acids Affect the Nutritional Status of Patients with Stage III Non-Small Cell Lung Cancer during Multimodality Treatment

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), (n-3) fatty acids from fish oil, have immune-modulating effects and may improve nutritional status in cancer. The objective of this study was to investigate the effects of an oral nutritional supplement containing (n-3) fatty acids on nutritional status and inflammatory markers in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment. In a double-blind experiment, 40 patients with stage III NSCLC were randomly assigned to receive 2 cans/d of a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids (2.0 g EPA + 0.9 g DHA/d) or an isocaloric control supplement. EPA in plasma phospholipids, energy intake, resting energy expenditure (REE), body weight, fat free mass (FFM), mid-upper arm circumference (MUAC), and inflammatory markers were assessed. Effects of intervention were analyzed by generalized estimating equations and expressed as regression coefficients (B). The intervention group (I) had a better weight maintenance than the control (C) group after 2 and 4 wk (B = 1.3 and 1.7 kg, respectively; P < 0.05), a better FFM maintenance after 3 and 5 wk (B = 1.5 and 1.9 kg, respectively; P < 0.05), a reduced REE (B = -16.7% of predicted; P = 0.01) after 3 wk, and a trend for a greater MUAC (B = 9.1; P = 0.06) and lower interleukin-6 production (B = -27.9; P = 0.08) after 5 wk. After 4 wk, the I group had a higher energy and protein intake than the C group (B = 2456 kJ/24 h, P = 0.03 and B = 25.0 g, P = 0.01, respectively). In conclusion, a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids beneficially affects nutritional status during multimodality treatment in patients with NSCLC.

Oral nutritional supplements containing n-3 polyunsaturated fatty acids affect quality of life and functional status in lung cancer patients during multimodality treatment: an RCT

Background/Objectives:Our objective was to investigate effects of an oral nutritional supplement containing n-3 polyunsaturated fatty acids (FAs) on quality of life, performance status, handgrip strength and physical activity in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment.Subjects/Methods:In a double-blind experiment, 40 patients with stage III NSCLC were randomised to receive 2 cans/day of a protein- and energy-dense oral nutritional supplement containing n-3 polyunsaturated FAs (2.02 g eicosapentaenoic acid+0.92 g docosahexaenoic acid/day) or an isocaloric control supplement, during multimodality treatment. Quality of life, Karnofsky Performance Status, handgrip strength and physical activity (by wearing an accelerometer) were assessed. Effects of intervention were analysed by generalised estimating equations. P-values <0.05 were regarded as statistically significant.Results:The intervention group reported significantly higher on the quality of life parameters, physical and cognitive function (B=11.6 and B=20.7, P<0.01), global health status (B=12.2, P=0.04) and social function (B=22.1, P=0.04) than the control group after 5 weeks. The intervention group showed a higher Karnofsky Performance Status (B=5.3, P=0.04) than the control group after 3 weeks. Handgrip strength did not significantly differ between groups over time. The intervention group tended to have a higher physical activity than the control group after 3 and 5 weeks (B=6.6, P=0.04 and B=2.5, P=0.05).Conclusion:n-3 Polyunsaturated FAs may beneficially affect quality of life, performance status and physical activity in patients with NSCLC undergoing multimodality treatment.

Critical weight loss is a major prognostic indicator for disease-specific survival in patients with head and neck cancer receiving radiotherapy.

Background:Pre-treatment weight loss (WL) is a prognostic indicator for overall survival (OS) in head and neck cancer (HNC) patients. This study investigates the association between WL before or during radiotherapy and disease-specific survival (DSS) in HNC patients.Methods:In 1340 newly diagnosed HNC patients, weight change was collected before and during (adjuvant) radiotherapy with curative intent. Critical WL during radiotherapy was defined as >5% WL during radiotherapy or >7.5% WL until week 12. Differences in 5-year OS and DSS between WL groups were analysed by Cox’s regression with adjustments for important socio-demographic and tumour-related confounders.Results:Before radiotherapy, 70% of patients had no WL, 16% had ⩽5% WL, 9% had >5–10% WL, and 5% had >10% WL. Five-year OS and DSS rates for these groups were 71%, 59%, 47%, and 42% (P<0.001), and 86%, 86%, 81%, and 71%, respectively (P<0.001). After adjustment for potential confounders, >10% WL before radiotherapy remained significantly associated with a worse OS (HR 1.7; 95% CI 1.2–2.5; P=0.002) and DSS (HR 2.1; 95% CI 1.2–3.5; P=0.007).The 5-year OS and DSS rates for patients with critical WL during radiotherapy were 62% and 82%, compared with 70% and 89% for patients without critical WL (P=0.01; P=0.001). After adjustment, critical WL during radiotherapy remained significantly associated with a worse DSS (HR 1.7; 95% CI 1.2–2.4; P=0.004).Conclusion:Weight loss both before and during radiotherapy are important prognostic indicators for 5-year DSS in HNC patients. Randomised studies into the prognostic effect of nutritional intervention are needed.

Perioperative arginine-supplemented nutrition in malnourished patients with head and neck cancer improves long-term survival

BACKGROUND Plasma arginine concentrations are lower in patients with cancer, which indicates that arginine metabolism may be disturbed in these patients. Arginine supplementation has been associated with positive effects on antitumor mechanisms and has been shown to reduce tumor growth and to prolong survival. Furthermore, the prognosis of patients with head and neck cancer remains disappointing. Insufficient intake frequently leads to malnutrition, which contributes to high morbidity and mortality rates. OBJECTIVE The aim of this study was to assess the long-term effects of perioperative arginine supplementation in severely malnourished patients with head and neck cancer. DESIGN In this double-blind, randomized, controlled trial, we randomly assigned 32 severely malnourished patients with head and neck cancer to receive 1) standard perioperative enteral nutrition (n = 15) or 2) arginine-supplemented perioperative enteral nutrition (n = 17). The primary outcome was long-term (≥10 y) survival. Secondary outcomes included the long-term appearance of locoregional recurrence, distant metastases, and second primary tumors. RESULTS No significant differences in baseline characteristics were observed between groups. The group receiving arginine-enriched nutrition had a significantly better overall survival (P = 0.019) and better disease-specific survival (P = 0.022). Furthermore, the arginine-supplemented group had a significantly better locoregional recurrence-free survival (P = 0.027). No significant difference in the occurrence of distant metastases or occurrence of a second primary tumor was observed between the groups. CONCLUSION Perioperative arginine-enriched enteral nutrition significantly improved the long-term overall survival and long-term disease-specific survival in malnourished patients with head and neck cancer.

Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer

PURPOSE Low muscle mass is present in approximately 40% of patients with metastatic colorectal cancer (mCRC) and may be associated with poor outcome. We studied change in skeletal muscle during palliative chemotherapy in patients with mCRC and its association with treatment modifications and overall survival. PATIENTS AND METHODS In 67 patients with mCRC (mean age ± standard deviation, 66.4 ± 10.6 years; 63% male), muscle area (square centimeters) was assessed using computed tomography scans of the third lumbar vertebra before and during palliative chemotherapy. Treatment modifications resulting from toxicity were evaluated, including delay, dose reduction, or termination of chemotherapy. Multiple regression analyses were performed for the association between change in muscle area and treatment modification and secondly overall survival. RESULTS Muscle area of patients with mCRC decreased significantly during 3 months of chemotherapy by 6.1% (95% CI, -8.4 to -3.8; P < .001). Change in muscle area was not associated with treatment modifications. However, patients with muscle loss during treatment of 9% or more (lowest tertile) had significantly lower survival rates than patients with muscle loss of less than 9% (at 6 months, 33% v 69% of patients alive; at 1 year, 17% v 49% of patients alive; log-rank P = .001). Muscle loss of 9% or more remained independently associated with survival when adjusted for sex, age, baseline lactate dehydrogenase concentration, comorbidity, mono-organ or multiorgan metastases, treatment line, and tumor progression at first evaluation by computed tomography scan (hazard ratio, 4.47; 95% CI, 2.21 to 9.05; P < .001). CONCLUSION Muscle area decreased significantly during chemotherapy and was independently associated with survival in patients with mCRC. Further clinical evaluation is required to determine whether nutritional interventions and exercise training may preserve muscle area and thereby improve outcome.

More than 10% weight loss in head and neck cancer patients during radiotherapy is independently associated with deterioration in quality of life.

The authors prospectively assessed the independent association between weight loss and deterioration in quality of life (QOL) in patients treated by radiotherapy for head and neck cancer. In 533 head and neck cancer patients treated by curative radiotherapy, changes in weight and QOL were assessed between baseline (before radiotherapy) and follow-up (12 wk after the start of radiotherapy). Patients were categorized into 4 weight loss categories: 0%, 0.1%–5.0%, 5.1%–10.0%, and >10% weight loss. The association between weight loss and change in QOL was analyzed by linear regression analysis, adjusted for sociodemographic and tumor-related characteristics, and additionally for disease specific symptoms and tube feeding. Thirty percent of patients lost 0.1%–5.0% weight, 26% lost 5.1%–10.0% weight, and 24% lost >10% weight. Adjusted regression analyses showed a significant association between weight loss and deterioration of global QOL, physical functioning, social functioning, social eating, and social contact. After additional adjustment for disease-specific symptoms and tube feeding, weight loss (>10%) remained significantly associated with global QOL, social eating, and social contact (P < 0.05). More than 10% weight loss during and directly after radiotherapy has a significant impact on social eating, social contact, and QOL in head and neck cancer patients.

Radiotherapy on the neck nodes predicts severe weight loss in patients with early stage laryngeal cancer

BACKGROUND AND PURPOSE Although patients with early stage (T1/T2) laryngeal cancer (LC) are thought to have a low incidence of malnutrition, severe weight loss is observed in a subgroup of these patients during radiotherapy (RT). The objective of this study was to evaluate weight loss and nutrition-related symptoms in patients with T1/T2 LC during RT and to select predictive factors for early identification of malnourished patients. METHODS Of all patients with T1/T2 LC, who received primary RT between 1999 and 2007, the following characteristics were recorded: sex, age, TNM classification, tumour location, radiation schedule, performance status, quality of life, weight loss, and nutrition-related symptoms. The association between baseline characteristics and malnutrition (>5% weight loss during RT) was investigated by Cox regression analysis. RESULTS The study population consisted of 238 patients. During RT, 44% of patients developed malnutrition. Tumour location, TNM classification, RT on the neck nodes, RT dose, nausea/vomiting, pain, swallowing, senses problems, trouble with social eating, dry mouth and the use of painkillers were all significantly associated with malnutrition. In the multivariate analysis, RTs on both the neck nodes (HR 4.16, 95% CI 2.62-6.60) and dry mouth (HR 1.72, 95% CI 1.14-2.60) remained predictive. Nevertheless, RT on the neck nodes alone resulted in the best predictive model for malnutrition scores. CONCLUSIONS Patients with early stage laryngeal cancer are at risk of malnutrition during radiotherapy. Radiotherapy on the neck nodes is the best predictor of malnutrition during radiotherapy. Therefore, we suggest to offer nutritional counselling to all the patients who receive nodal irradiation.

n−3 PUFAs in cancer, surgery, and critical care: a systematic review on clinical effects, incorporation, and washout of oral or enteral compared with parenteral supplementation

BACKGROUND n-3 (omega-3) Fatty acids (FAs) may have beneficial effects in patients with cancer or in patients who undergo surgery or critical care. OBJECTIVE Our aim was to systematically review the effects of oral or enteral and parenteral n-3 FA supplementation on clinical outcomes and to describe the incorporation of n-3 FAs into phospholipids of plasma, blood cells, and mucosal tissue and the subsequent washout in these patients. DESIGN We investigated the supplementation of n-3 FAs in these patients by using a systematic literature review. RESULTS In cancer, the oral or enteral supplementation of n-3 FAs contributed to the maintenance of body weight and quality of life but not to survival. We did not find any studies on parenteral supplementation of n-3 FAs in cancer. In surgical oncology, we did not find any studies on enteral supplementation of n-3 FAs. However, postoperative parenteral supplementation in surgical oncology may reduce the length of a hospital stay. For general surgery, we did not find any studies on enteral supplementation of n-3 FAs, and evidence on parenteral supplementation was insufficient. In critical care, enteral supplementation of n-3 FAs had beneficial effects on clinical outcomes; evidence on parenteral supplementation in critical care was inconsistent. The incorporation of n-3 FAs in plasma and blood cells was slower with enteral supplementation (4-7 d) than with parenteral supplementation (1-3 d). The washout was 5-7 d. CONCLUSIONS This review shows the beneficial effects of n-3 FA supplementation in cancer, surgical oncology, and critical care patients. Supplementation in these specific patient populations could be considered with the route of administration taken into account.

High Waste Contributes to Low Food Intake in Hospitalized Patients

BACKGROUND The prevalence of disease-related malnutrition in hospital inpatients is high; many patients do not meet individual nutrition requirements while hospitalized. To better understand the reasons for inadequate nutrition intake, this study describes patient satisfaction, food provision, food intake, and waste of hospital meals. METHODS Over 6 days, 150 hospital meals were weighed and nutrient composition was calculated. On return from the wards, waste was weighed. In addition, nutrition intake was compared to nutrition requirements in 42 patients. In a separate study, the authors studied patient satisfaction with the hospital food service using interviews (n = 112). RESULTS The 3 main meals accounted for a mean of 1809 ± 143 kcal and 76 ± 13 g of protein per day. In total, 38% of the food provided by the kitchen was wasted. As a consequence, the main meals supplied an average of 1105 ± 594 kcal and 47 ± 27 g of protein to patients. Sixty-one percent of patients had an energy intake <90% and 75% had a protein intake <90% of requirements. Most patients were satisfied or fairly satisfied with the choices, taste, and presentation of the main meals. Satisfaction with snack meals and information was inadequate. CONCLUSIONS The standard meals provided by the hospital kitchen provide adequate amounts of energy and protein. However, most patients do not consume complete meals. It may be concluded that food waste is largely attributed to the inadequate intake of many hospitalized patients. Patients who experienced the worst health status ate the least.