Disparities in Head and Neck Cancer: A Case for Chemoprevention with Vitamin D.

Blacks experience disproportionate head and neck cancer (HNC) recurrence and mortality compared to Whites. Overall, vitamin D status is inversely associated to HNC pointing to a potential protective linkage. Although hypovitaminosis D in Blacks is well documented it has not been investigated in Black HNC patients. Thus, we conducted a prospective pilot study accessing vitamin D status in newly diagnosed HNC patients stratified by race and conducted in vitro studies to investigate mechanisms associated with potential cancer inhibitory effects of vitamin D. Outcome measures included circulating levels of vitamin D, related nutrients, and risk factor characterization as well as dietary and supplemental estimates. Vitamin D-based in vitro assays utilized proteome and microRNA (miR) profiling. Nineteen patients were enrolled, mean circulating vitamin D levels were significantly reduced in Black compared to White HNC patients, 27.3 and 20.0 ng/mL, respectively. Whites also supplemented vitamin D more frequently than Blacks who had non-significantly higher vitamin D from dietary sources. Vitamin D treatment of HNC cell lines revealed five significantly altered miRs regulating genes targeting multiple pathways in cancer based on enrichment analysis (i.e., negative regulation of cell proliferation, angiogenesis, chemokine, MAPK, and WNT signaling). Vitamin D further altered proteins involved in cancer progression, metastasis and survival supporting a potential role for vitamin D in targeted cancer prevention.

Feasibility Outcomes of a Pilot Randomized Clinical Trial to Increase Cruciferous and Green Leafy Vegetable Intake in Posttreatment Head and Neck Cancer Survivors.

BACKGROUND: Higher intakes of cruciferous vegetables (CVs) and green leafy vegetables (GLVs) in observational studies are associated with improvements in survival and cancer-related biomarkers in patients diagnosed with head and neck cancer (HNC). These results have yet to be corroborated in a randomized clinical trial (RCT). OBJECTIVE: Determine the feasibility of implementing a 12-week RCT to increase CV and GLV intake in posttreatment HNC survivors. DESIGN AND PARTICIPANTS: This was a two-arm RCT conducted among 24 posttreatment HNC survivors. Survivors were recruited from a southeastern, National Cancer Institute-designated Comprehensive Cancer Center between January 2015 and September 2016. INTERVENTION: There were two groups: (1) an experimental group (n=12) receiving weekly 15- to 30-minute telephone dietary counseling from a registered dietitian nutritionist stressing 2.5 cups per week CVs and 3.5 cups per week GLVs, and (2) an attention control group (n=12) receiving weekly 15- to 30-minute telephone dietary counseling from a registered dietitian nutritionist focusing on general healthy eating for cancer survivors. Participants completed a baseline survey, three 24-hour dietary recalls, phlebotomy, and anthropometric measures prior to randomization and at the end of the 12-week study period. The experimental group also completed weekly vegetable record recalls. MAIN OUTCOME MEASURES: Primary outcomes included feasibility, recruitment, retention, adherence, and safety. Secondary outcomes included inflammatory markers and carotenoids. STATISTICAL ANALYSES PERFORMED: Descriptive statistics were generated for demographic, epidemiological, and clinical variables as well as the primary feasibility outcomes. Between- and within-group comparisons of mean serum cytokine and carotenoid levels were performed using appropriate statistical tests depending on their respective distributions for the purpose of generating preliminary effect sizes. RESULTS: Overall, 350 incident HNC cases were screened for eligibility, and 98 were eligible for study participation. Reasons for ineligibility and exclusion included deceased (n=93); wrong or inactive telephone numbers, or unable to be reached, or lost to follow-up (n=93); not meeting inclusion criteria (n=39); and too ill to participate (n=27). Of the 98 eligible HNC cases, 24 agreed to participate, for an enrollment rate of 25%. The most common reason for nonparticipation was distance (n=48), as participants were asked to report for two on-site assignments. The retention rate was 96%. Mean intervention adherence rates for weekly goals were 67% CV, 74% GLV, and 71% overall. Completion rate of weekly counseling calls was 90%. The experimental group reported an overall mean increase of 5.5 cups GLV and 3.5 cups CV per week from baseline intake, respectively. No significant between- or within-arm differences were observed for inflammatory markers or carotenoids. CONCLUSION: A posttreatment intervention aimed at increasing CV and GLV intake in HNC survivors is feasible. A larger RCT is needed to assess the efficacy of this intervention on disease outcomes.

SERUM ELECTROLYTES AND OUTCOME IN PATIENTS UNDERGOING ENDOSCOPIC GASTROSTOMY.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a gold standard for long term enteral feeding. Neurologic dysphagia and head/neck cancer are the most common indications for PEG as they can lead to protein-energy malnutrition and serum electrolyte abnormalities, with potential negative impact on metabolic balance. Refeeding syndrome may also be related with severe electrolyte changes in PEG-fed patients and contribute to poor prognosis. OBJECTIVE: This study aims to evaluate the changes in serum concentrations of the main electrolytes and its possible association with the outcome. METHODS: Retrospective study of patients followed in our Artificial Nutrition Clinic, submitted to PEG from 2010 to 2016, having head/neck cancer or neurologic dysphagia, who died under PEG feeding. Serum electrolytes (sodium, potassium, chlorine, magnesium, calcium and phosphorus) were evaluated immediately before the gastrostomy procedure. Survival after PEG until death was recorded in months. RESULTS: We evaluated 101 patients, 59 with electrolyte alterations at the moment of the gastrostomy. Sodium was altered in 32 (31.7%), magnesium in 21 (20.8%), chlorine in 21 (20.8%), potassium in 14 (13.8%), calcium in 11 (10.9 %) and phosphorus in 11 (10.9%). The survival of patients with low sodium (<135 mmol/L) was significantly lower when compared to patients with normal/high values, 2.76 months vs 7.80 months, respectively (P=0.007). CONCLUSION: Changes in serum electrolytes of patients undergoing PEG were very common. More than half showed at least one abnormality, at the time of the procedure. The most frequent was hyponatremia, which was associated with significantly shorter survival, probably reflecting severe systemic metabolic distress.

Eletrólitos séricos e prognóstico em doentes submetidos a gastrostomia endoscópica / Serum electrolytes and outcome in patients undergoing endoscopic gastrostomy

ABSTRACT BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a gold standard for long term enteral feeding. Neurologic dysphagia and head/neck cancer are the most common indications for PEG as they can lead to protein-energy malnutrition and serum electrolyte abnormalities, with potential negative impact on metabolic balance. Refeeding syndrome may also be related with severe electrolyte changes in PEG-fed patients and contribute to poor prognosis. OBJECTIVE: This study aims to evaluate the changes in serum concentrations of the main electrolytes and its possible association with the outcome. METHODS: Retrospective study of patients followed in our Artificial Nutrition Clinic, submitted to PEG from 2010 to 2016, having head/neck cancer or neurologic dysphagia, who died under PEG feeding. Serum electrolytes (sodium, potassium, chlorine, magnesium, calcium and phosphorus) were evaluated immediately before the gastrostomy procedure. Survival after PEG until death was recorded in months. RESULTS: We evaluated 101 patients, 59 with electrolyte alterations at the moment of the gastrostomy. Sodium was altered in 32 (31.7%), magnesium in 21 (20.8%), chlorine in 21 (20.8%), potassium in 14 (13.8%), calcium in 11 (10.9 %) and phosphorus in 11 (10.9%). The survival of patients with low sodium (<135 mmol/L) was significantly lower when compared to patients with normal/high values, 2.76 months vs 7.80 months, respectively (P=0.007). CONCLUSION: Changes in serum electrolytes of patients undergoing PEG were very common. More than half showed at least one abnormality, at the time of the procedure. The most frequent was hyponatremia, which was associated with significantly shorter survival, probably reflecting severe systemic metabolic distress.

RESUMO CONTEXTO: A gastrostomia endoscópica percutânea (PEG) é a via de eleição preferencial para a nutrição entérica de longa duração. A disfagia neurológica e as neoplasias cervico-faciais constituem as principais indicações para PEG por poderem conduzir a desnutrição energético-proteica e alterações hidroeletrolíticas, com potencial impacto negativo no equilíbrio metabólico. A síndrome de realimentação pode também estar associada a alterações hidroeletrolíticas graves em doentes alimentados por PEG e contribuir para um mau prognóstico. OBJETIVO: Avaliar as alterações das concentrações séricas dos principais eletrólitos e a eventual associação entre os valores séricos alterados e o prognóstico dos doentes gastrostomizados. Métodos - Estudo retrospetivo realizado em doentes seguidos na Consulta de Nutrição Artificial do Hospital Garcia de Orta, propostos e submetidos a PEG, de 2010 a 2016 e que faleceram sob nutrição por PEG. Consideraram-se os valores séricos dos iões em estudo avaliados imediatamente antes do procedimento endoscópico de gastrostomia, obtidos por consulta do processo clínico. A sobrevida, após a realização da PEG até à morte foi registrada em meses. RESULTADOS: Avaliaram-se 101 doentes. A sobrevida média pós-gastrostomia foi 6,55 meses. Destes, 59 apresentaram alterações de alguns iões no momento da realização da PEG. O sódio estava alterado em 31 (30,6%), magnésio em 20 (19,8%), cloro em 19 (18,8%), potássio em 14 (13,8%), cálcio em 10 (9,9%) e o fósforo em 9 (8,9%). Quando comparada a sobrevida dos doentes com valores de sódio baixo (<135 mmol/L) com a dos doentes com valores normais/elevados, esta foi 2,76 meses vs 7,80 meses, respectivamente (P=0,007). CONCLUSÃO: As alterações dos eletrólitos séricos nos doentes submetidos a PEG foram muito frequentes, com mais de metade dos doentes a apresentarem pelo menos uma alteração aquando da realização do procedimento. A alteração mais frequente foi a hiponatrémia, associando-se a pior prognóstico com sobrevida significativamente mais curta, refletindo provavelmente um grave compromisso metabólico sistêmico.

Prospective randomized investigation implementing immunonutritional therapy using a nutritional supplement with a high blend ratio of ω-3 fatty acids during the perioperative period for head and neck carcinomas.

OBJECTIVES: The purpose of this study is to evaluate whether a nutritional supplement with a high blend ratio of ω-3 fatty acids can minimize weight loss and attenuate increases in inflammatory marker levels during the perioperative period in patients undergoing surgery for head and neck carcinoma. METHODS: Patients with ≥5% weight loss within 6 months were considered as targets for aggressive nutritional intervention. Among these patients, those with head and neck squamous cell carcinoma, who underwent major invasive surgery with free flap reconstruction were included in the present study. The patients were randomized into two groups: the 'nutritional supplementation group' and the 'non-intervention group'. The nutritional supplementation group received two packs of Prosure® (an eicosapentaenoic acid [EPA]-enriched oral nutritional supplement) per day for 28 days during the perioperative period. RESULTS: Compliance with the Prosure® dosage was very good at 6277/6720 ml (average) before surgery (93%) and 5229/6720 ml after surgery (78%), and a significant increase in EPA concentration was shown in the group that received Prosure® (P < 0.0001: Welch's t-test). However, 28 days of nutritional supplementation did not lead to further weight change or changes in the inflammatory marker levels of patients were already showing cachexia (based on weight loss). Interestingly, no further change in the mean weight was noted in these patients. The incidence of postoperative complications did not differ between the two groups. CONCLUSION: In this trial, immunonutritional therapy using a nutritional supplement with a high blend ratio of ω-3 fatty acids from 2 weeks before surgery until 2 weeks after surgery was not effective for maintaining the nutritional status of head and neck carcinoma patients.

A Randomized Double-Blind Placebo-Controlled Trial of Fruit and Vegetable Concentrates on Intermediate Biomarkers in Head and Neck Cancer.

BACKGROUND: Head and neck cancer (HNC) patients are at an increased risk for developing second primary tumors (SPTs). Diets rich in fruits and vegetables (FVs) may lower HNC risk. FV concentrates may offer a potential alternative to increasing FV intake. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to evaluate whether Juice PLUS+ (JP; a commercial product with multiple FV concentrates) has an effect on p27 and Ki-67, biomarkers associated with the risk of SPTs. During 2004-2008, we randomized 134 HNC patients to 12 weeks of JP (n = 72) or placebo (n = 62). Oral cavity mucosal biopsies and whole blood were obtained at baseline and after 12 weeks. All participants were given the opportunity to receive JP for 5 years following the end of the intervention period, and they were followed yearly for the development of SPTs. RESULTS: After 12 weeks, patients on JP had significantly higher serum α-carotene ( P = .009), ß-carotene ( P < .0001), and lutein ( P = .003) but did not differ significantly in p27 ( P = .23) or Ki-67 ( P = .95). JP use following the initial 12-week trial was not significantly associated with SPT prevention. CONCLUSIONS: Despite increased serum micronutrient levels, our results do not suggest a clinical benefit of JP in HNC patients. Future studies should focus on longer intervention periods and/or modified supplement formulations with demonstrated chemopreventive properties.

Premedication with intravenous magnesium has a protective effect against cisplatin-induced nephrotoxicity.

PURPOSE: Magnesium supplementation is an effective protective method against cisplatin-induced nephrotoxicity (CIN); however, there are few reports regarding the mechanism of its nephroprotective effect. The aim of this study was to determine whether premedication with intravenous magnesium prevents CIN and to determine the relationship between its nephroprotective effect and serum magnesium level. METHODS: Fifty-eight patients with head and neck cancer who received cisplatin, docetaxel, and 5-fluorouracil (DCF) were retrospectively investigated. Grade 2 or more serum creatinine elevation was defined as CIN. The incidence of CIN was compared between a magnesium sulfate (20 mEq, 2.46 g) premedication group and a non-magnesium group during the first cycle and in all cycles. RESULTS: CIN did not occur in any patients receiving magnesium premedication but did occur in 5 of 29 patients during the first cycle and in 6 patients during all subsequent cycles in patients who did not receive magnesium premedication. Furthermore, the variation of creatinine clearance was significantly worse in the non-magnesium group than in the magnesium premedication group from baseline. There was no difference in adverse effects or response rate between the two groups. Univariate analysis suggested that magnesium premedication significantly reduced the risk of CIN. On the other hand, serum magnesium depletion was seen in both groups to equal degrees despite supplementation. CONCLUSION: Intravenous magnesium premedication has a protective effect on cisplatin-induced nephrotoxicity without the influence on the serum magnesium level. Magnesium premedication is a simple nephroprotective method that does not influence other adverse effects or rate of response to chemotherapy.

Prospective study of serum cysteine and cysteinylglycine and cancer of the head and neck, esophagus, and stomach in a cohort of male smokers.

BACKGROUND: The nonessential amino acid cysteine is known to be involved in many antioxidant and anticarcinogenic pathways. Cysteinylglycine is a pro-oxidant metabolite of glutathione and a precursor of cysteine. OBJECTIVE: To examine the relation between serum cysteine and cysteinylglycine and risk of gastric adenocarcinomas, esophageal squamous cell carcinomas, and head and neck squamous cell carcinomas, we conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study of male Finnish smokers aged 50-69 y at baseline. DESIGN: In total, 170 gastric adenocarcinomas, 68 esophageal squamous cell carcinomas, and 270 head and neck squamous cell carcinomas (identified from the Finnish Cancer Registry) were matched one-to-one with cancer-free control subjects on age and the date of serum collection. We calculated ORs and 95% CIs with the use of a multivariate-adjusted conditional logistic regression. RESULTS: Cysteine had a U-shaped association with gastric adenocarcinomas; a model that included a linear and a squared term had a significant global P-test (P = 0.036). Serum cysteinylglycine was inversely associated with adenocarcinomas of the gastric cardia (OR for above the median compared with below the median: 0.07; 95% CI: 0.01, 0.70; n = 38 cases) but not for other sites. Both cysteine and cysteinylglycine were not associated with esophageal squamous cell carcinoma or head and neck squamous cell carcinoma. CONCLUSIONS: We observed associations between serum cysteine and cysteinylglycine with upper gastrointestinal cancer risk. Future studies are needed to replicate these findings. This trial was registered at clininicaltrials.gov as NCT00342992.

Early parathyroid hormone laboratory abnormalities related to therapeutic radiation of neck: an Egyptian experience.

The effect of neck radiation on parathyroid hormone (PTH) is studied on concern as late effect of radiotherapy for benign or malignant diseases. However, the early effect on PTH is still in debate and need further evaluations. We aimed, in our study, to assess early effect of neck radiation on PTH, and related calcium and phosphorus levels. Patients diagnosed with breast or head and neck cancer who planned to received radiotherapy to neck as a definite or a part of their treatment enrolled in this prospective single-arm study from June 2012 to June 2013. Laboratory assessment of PTH, serum calcium, phosphorus and albumin was obtained before starting radiotherapy, 3 weeks and 3 months after radiation. Fifty-two patients included 24 (46.2 %) males and 28(53.8 %) females. Median age of diagnosis was 55 years. Thirty-six patients had head and neck cancer, while 16 patients were diagnosed as breast cancer. The difference in PTH and calcium levels before and after radiotherapy was statistically significant (P = 0.014 and P = 0.001 for 3 weeks and P = 0.015 and P = 0.004 for 3 months, respectively); even after correction of calcium level according to albumin level, the same results were obtained, while there was no significant difference in their levels after 3 weeks in comparison with 3 months after radiotherapy. The variation of level of phosphorus was not significant. PTH and calcium can be affected early with neck radiation, so follow-up of calcium and PTH level is mandatory for cases that will receive neck radiotherapy.

Enteral glutamine supplementation in surgical patients with head and neck malignancy: A randomized controlled trial.

BACKGROUND: Glutamine supplementation is a novel approach to perioperative nutritional management. METHODS: This study was a prospective randomized clinical trial of effects of enteral glutamine supplementation in surgical patients with head and neck malignancy in a tertiary center. This study measured the effects of supplementation within 4 weeks of the postoncologic surgical period in relation to fat-free mass, serum albumin, and quality of life scores. RESULTS: The study population consisted of 44 patients. There was significant difference in serum albumin (p < .001), fat-free mass (p < .001), and quality of life scores (p < .05) between control and interventional groups. Significant correlation exists between fat-free mass and quality of life score difference in our study population (p < .05). CONCLUSION: Enteral glutamine supplementation significantly improves fat-free mass, serum albumin, and quality of life scores postoperatively and maintenance of lean body mass correlated with improved postoperative outcomes in terms of the patient's quality of life.

Long-term effects of varying consumption of ω3 fatty acids in ear, nose and throat cancer patients: assessment 1 year after radiotherapy.

A prospective 1-year follow-up study in ear, nose, and throat (ENT) cancer patients was carried out one year after radiotherapy to assess the effect of varying consumption of ω3 fatty acid according to whether they consumed more or less than the 50th percentile of ω3 fatty acids. Clinical, analytical, inflammatory (CRP and IL-6), and oxidative variables (TAC, GPx, GST, and SOD) were evaluated. The study comprised 31 patients (87.1% men), with a mean age of 61.3 ± 9.1 years. Hematological variables showed significant differences in the patients with a lower consumption of ω3 fatty acids. A lower mortality and longer survival were found in the group with ω3 fatty acid consumption ≥50th percentile but the differences were not significant. No significant difference was reached in toxicity, inflammation, and oxidative stress markers. The group with ω3 fatty acid consumption <50th percentile significantly experienced more hematological and immune changes.

Synthetic curcumin analog UBS109 inhibits the growth of head and neck squamous cell carcinoma xenografts.

The natural compound curcumin has been investigated as an anticancer agent in many cellular systems, in animal models and in the clinic. The overriding negative characteristics of curcumin are its low solubility, weak potency and poor bioavailability. We have examined the efficacy and mechanism of action of a synthetic curcumin analog, UBS109, in head and neck squamous cell carcinoma. By nephelometry, this analog exhibits considerably greater solubility than curcumin. Pharmacokinetic studies of a single oral dose of UBS109 in mice revealed that peak plasma concentrations were reached at 0.5 hours post-dose (Tmax) with average plasma concentrations (Cmax) of 131 and 248 ng/mL for oral doses of 50 and 150 mg/kg, respectively. The terminal elimination half-lives (T½) for these doses averaged 3.7 and 4.5 hours, respectively. In both in vitro and in vivo studies, we found that UBS109 decreased the levels of phosphorylated IKKß and phosphorylated p65 and, unexpectedly, increased the levels of phosphorylated IκBα by Western blot analysis. These observations may suggest that UBS109 suppresses tumor growth through, in part, inhibition of NF-κB p65 phosphorylation by PKAc and not through IκBα. Finally, we demonstrate that UBS109 is efficacious in retarding the growth of Tu212 (head and neck) squamous cell carcinoma (SCC) xenograft tumors in mice and may be useful for treating head and neck SCC tumors.

Trace metals and total antioxidant potential in head and neck cancer patients.

BACKGROUND/OBJECTIVE: There are pieces of evidence suggesting that oxidative stress and immune responses play significant roles in the etiopathogenesis of some malignant diseases. Also increased oxidative stress in patients with certain cancer may result from changes in the levels of certain trace elements. Therefore antioxidants either in the form of trace metals or enzymes are important tools in the study of these conditions. This study aimed at measuring the level of oxidative stress in the head and neck cancer patients by using plasma total antioxidant potential and the plasma level of some antioxidant trace metals. MATERIALS AND METHODS: Twenty cases of head and neck squamous cell carcinoma recruited from the Oral and Maxillofacial surgery and Radiotherapy clinics of the University College Hospital, Ibadan were included in the study. While total antioxidant status was measured by ferric reducing antioxidant power (FRAP) assay of Benzie and Strain (1996), the plasma trace metals were assayed by atomic absorption spectrophotometry. RESULT: The total antioxidant potential was significantly reduced in the study group when compared with controls. Zinc, iron, and selenium were also found to be significantly lower in the study group compared with controls. CONCLUSION: The result suggests a state of oxidative stress in the head and neck cancer patients with likely impact on disease process and treatment outcome.

A randomized clinical trial with two doses of a omega 3 fatty acids oral and arginine enhanced formula in clinical and biochemical parameters of head and neck cancer ambulatory patients.

INTRODUCTION: Postsurgical patients with head and neck cancer could have a high rate of ambulatory complications. The aim was to investigate whether oral ambulatory nutrition of head and neck cancer patients with recent weight loss, using two different doses of an omega 3 fatty acids and arginine enhanced diets could improve nutritional parameters. DESIGN: At Hospital discharge post surgical head and neck cancer patients (n=37) were asked to consume two or three cans per day of a designed omega 3 fatty acid and arginine enhanced supplement for a twelve week period. RESULTS: Albumin, prealbumin, transferrin and lymphocytes levels improved in both groups. Weight, fat mass and fat free mass improved during supplementation in group II (3 bricks per day). No differences were detected in anthropometric parameters in group I. Gastrointestinal tolerance with both formulas was good, no episodes were reported. There are no differences between both formulas on postsurgical complications rates. CONCLUSIONS: Omega 3 and arginine enhanced formulas improved blood protein concentrations and lymphocyte levels in ambulatory postoperative head and neck cancer patients. A high dose of arginine and omega 3 fatty acids formula improved weight, too.

Effect of serum selenium levels on radiotherapy-related toxicity in patients undergoing radiotherapy for head and neck cancer.

AIM: To investigate whether there is a difference in selenium levels before and after radiotherapy (RT) and to study the effects of serum selenium levels on RT-related toxicity in patients undergoing RT for head and neck cancer. PATIENTS AND METHODS: A population of 47 consecutive patients was enrolled in the study. RT was given by conventional fractionation. RT-related acute toxicity was evaluated once a week. Blood samples were obtained before and after RT to evaluate selenium levels. RESULTS: There was no significant difference between the levels of selenium before and after RT (58.09 ± 1.36 µg/l and 56.34 ± 1.11 µg/l, p-value=0.747, respectively). Grade III-IV mucositis, dysphagia, radiodermatitis, and nausea were seen in 6 (12.7%), 32 (68.2%), 24 (51.1%), and 3 (6.4%) patients, respectively. It was found that there was no statistically significant difference in the levels of selenium before and after RT, and no observed differences in regard to RT-related toxicities. CONCLUSION: The serum selenium levels do not affect RT-related toxicities.

Dietary vitamin D intake and serum 25-hydroxyvitamin D level in relation to disease outcomes in head and neck cancer patients.

Low pretreatment vitamin D status has been associated with worsened disease outcomes in patients with cancer at various sites. Its prognostic significance in head and neck cancer (HNC) patients has not been studied. Patients with HNC who participated in a randomized trial were evaluated for: (i) total intake of vitamin D from diet and supplements using a validated food frequency questionnaire (all trial participants, n = 540) and (ii) pretreatment serum 25-hydroxyvitamin D through a radioimmunoassay (n = 522). The association of dietary/serum measures of vitamin D status with HNC recurrence, second primary cancer (SPC) incidence, and overall mortality was evaluated using multivariate Cox proportional hazard models. There was no significant association between dietary or serum vitamin D measures and the three HNC outcomes. The hazard ratios (HRs) comparing the highest with the lowest quartile of dietary/supplemental vitamin D intake were 1.10 (95% confidence interval (CI): 0.66-1.84) for recurrence, 1.05 (95% CI: 0.63-1.74) for SPC, and 1.27 (95% CI: 0.87-1.84) for overall mortality. HRs comparing the uppermost to the lowest quartile of serum 25-hydroxyvitamin D levels were 1.12 (95% CI: 0.65-1.93) for recurrence, 0.72 (95% CI: 0.40-1.30) for SPC, and 0.85 (95% CI: 0.57-1.28) for overall mortality. There was no effect modification by cancer stage, season of initial treatment, or trial arm. Among patients with HNC, vitamin D status before treatment does not influence disease outcomes. Our results contrast with those from most published studies, which suggest prognostic significance of vitamin D status in cancer patients at least in subgroups.

Postradiotherapy plasma lutein, alpha-carotene, and beta-carotene are positively associated with survival in patients with head and neck squamous cell carcinoma.

The aim of our study was to compare plasma carotenoids (i.e., biomarkers of fruits and vegetables intake) and tocopherols in 29 head and neck squamous cell carcinoma (HNSCC) patients with 51 healthy controls and to explore the possibility whether these plasma antioxidants could be related to outcome among patients. The patients' blood samples were taken at the end of radiotherapy. We observed that plasma lutein, zeaxanthin, alpha-carotene, beta-carotene, lycopene, and total carotenoids were significantly lower in HNSCC patients than controls. Among the patients, 18 died and 11 were still alive during median follow-up of 55 mo for survivors. We found a significant positive association between postradiotherapy plasma carotenoids (lutein, alpha-carotene, and beta-carotene) and progression-free survival in these patients. This study indicates that increasing postradiotherapy plasma carotenoid concentration may reduce risk of premature death or recurrence of tumor in HNSCC patients. Increasing plasma carotenoid concentration should be done by increasing intake of carotenoid-rich fruits and vegetables, as other studies have shown either no or negative effects due to use of carotenoid supplements.

[Arginine enhanced enteral nutrition, effect on blood inflammatory markers in head and neck cancer patients]. / Efecto de una fórmula enteral enriquecida en arginina sobre los marcadores inflamatorios en pacientes con tumores de cabeza y cuello.

BACKGROUND AND OBJECTIVE: Although immune dysfunction in cancer patients could be multifactorial, the immune system may be modulated by specific nutritional substrates, such as arginine. The aim of our study was to evaluate the effect of enteral nutrition supplemented with a high dose of arginine on c-reactive protein (CRP), interleukin 6 (IL6) and tumoral necrosis factor (TNF alpha) in surgical head and neck cancer patients. SUBJECTS AND METHODS: At surgery, patients were randomly allocated to two groups: (a) enteral diet supplements with arginine (group I, n=18); (b) isocaloric, isonitrogenous enteral formula (group II, n=23). Perioperatively and on the postoperative day 6 the following parameters were evaluated: serum values of prealbumin, transferrin, lymphocytes, IL6, TNF alpha and CRP. RESULTS: The mean age (standard deviation) was 60.9 (10.6) years. Prealbumin and transferrin improved in both groups, CRP decreased in both groups, (group I: 105.1 (62.8)mg/dl vs 53.2 (51)mg/dl: p<0.05 and group II: 103.3 (62)mg/dl vs 61.9 (57.4)mg/dl: p<0.05). IL6 improved in both groups (group I: 38.35 (14.2)pg/ml vs 15.6 (9.1)pg/ml: p<0.05 and group II: 32.8 (35)pg/ml vs 6.8 (4.9)pg/ml: p<0.05) TNF alpha and lymphocytes did not change. CONCLUSIONS: Both formulas improved IL6 and CRP levels. A high dose of enteral arginine in these patients did not add biochemical advantages as compared to a standard enteral formula.

Efecto de una fórmula enteral enriquecida en arginina sobre los marcadores inflamatorios en pacientes con tumores de cabeza y cuello / Arginine enhanced enteral nutrition, effect on blood inflammatory markers in head and neck cancer patients

Fundamento y objetivo: aunque la disfunción inmunológica en los pacientes con tumores de cabeza y cuello puede ser multifactorial, esta respuesta puede modularse mediante nutrientes específicos, como por ejemplo el aminoácido arginina. El objetivo de nuestro trabajo fue evaluar el efecto de una fórmula de nutrición enteral enriquecida en arginina respecto a los valores séricos de proteína C reactiva (PCR), interleucina 6 (IL-6) y factor de necrosis tumoral alfa (TNFα) en pacientes con tumores de cabeza y cuello sometidos a cirugía resectiva. Pacientes y método: se aleatorizó a los pacientes en 2 grupos: a) fórmula enteral enriquecida con arginina (grupo I, n=18), y b) fórmula enteral isocalórica e isonitrogenada (grupo II, n=23). Antes de la cirugía y en el día 5 del postoperatorio se determinaron: prealbúmina (mg/dl), transferrina (mg/dl), número total de linfocitos (106/ml), IL-6 (pg/ml), TNFα (pg/ml) y PCR (mg/dl). Resultados: la edad media (desviación estándar) fue de 60,9 (10,6) años (5 mujeres/36 varones). La prealbúmina y la transferrina mejoraron en ambos grupos. La PCR disminuyó en ambos grupos (grupo I: 105,1 [62,8]mg/dl frente a 53,2 [51]mg/dl, p<0,05; y grupo II: 103,3 [62]mg/dl frente a 61,9 [57,4]mg/dl, p<0,05). Los valores de IL-6 mejoraron en ambos grupos (grupo I: 38,35 [14,2]pg/ml frente a 15,6 [9,1]pg/ml, p<0,05; y grupo II: 32,8 [35] pg/ml frente a 6,8 [4,9]pg/ml, p<0,05). Los valores de TNFα y linfocitos no se modificaron. Conclusión: la fórmula enriquecida en arginina y la fórmula control mejoran los valores séricos de IL-6 y PCR. Por tanto, una dosis alta de arginina en estos pacientes no añade ventajas sobre los marcadores inflamatorios ante la utilización de una fórmula estandar (AU)

Background and objective: Although immune dysfunction in cancer patients could be multifactorial, the immune system may be modulated by specific nutritional substrates, such as arginine. The aim of our study was to evaluate the effect of enteral nutrition supplemented with a high dose of arginine on c-reactive protein (CRP), interleukin 6 (IL6) and tumoral necrosis factor (TNFα) in surgical head and neck cancer patients. Subjects and methods: At surgery, patients were randomly allocated to two groups: (a) enteral diet supplements with arginine (group I, n=18); (b) isocaloric, isonitrogenous enteral formula (group II, n=23). Perioperatively and on the postoperative day 6 the following parameters were evaluated: serum values of prealbumin, transferrin, lymphocytes, IL6, TNFα and CRP. Results: The mean age (standard deviation) was 60.9 (10.6) years. Prealbumin and transferrin improved in both groups, CRP decreased in both groups, (group I: 105.1 (62.8)mg/dl vs 53.2 (51)mg/dl: p<0.05 and group II: 103.3 (62)mg/dl vs 61.9 (57.4)mg/dl: p<0.05). IL6 improved in both groups (group I: 38.35 (14.2)pg/ml vs 15.6 (9.1)pg/ml: p<0.05 and group II: 32.8 (35)pg/ml vs 6.8 (4.9)pg/ml: p<0.05) TNFα and lymphocytes did not change. Conclusions: Both formulas improved IL6 and CRP levels. A high dose of enteral arginine in these patients did not add biochemical advantages as compared to a standard enteral formula (AU)

Pharmacokinetic evaluation of platinum derived from cisplatin administered alone and with pemetrexed in head and neck cancer patients.

PURPOSE: This phase I study characterized the pharmacokinetics of free and total platinum derived from cisplatin administered alone and in combination with pemetrexed. Secondary objectives were to assess the pharmacokinetics of pemetrexed when it is combined with cisplatin as well as to evaluate the safety profile and document antitumor activity associated with this combination. METHODS: An open-label, two-arm, cross-over phase 1 study was performed in patients with squamous cell carcinoma of the head and neck, age > or =18 years, an Eastern Cooperative Oncology Group performance status of 0-2, and adequate organ function. Blood samples were taken and pharmacokinetics evaluated for the first two cycles using noncompartmental analysis. Patients received either pemetrexed (500 mg m(-2)) plus cisplatin (75 mg m(-2)) administered in cycle 1 followed by cisplatin alone in cycle 2; or in the reverse order (i.e., cisplatin alone in cycle 1 followed by pemetrexed plus cisplatin in cycle 2). Each treatment cycle was 21 days and patients received folic acid, vitamin B(12) supplementation, and dexamethasone prophylaxis. After the first two cycles, patients continued study treatment with pemetrexed plus cisplatin every 3 weeks up to a maximum of six total treatment cycles. Toxicities were graded by the investigators according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE), version 3.0. RESULTS: A total of 13 patients were treated; one patient was discontinued from the study after cycle 1 for failure to meet baseline eligibility criteria for renal function. The ratios and 90% confidence intervals (CI) comparing the pharmacokinetics for cisplatin administered with pemetrexed to those for cisplatin administered alone for free platinum were: C(max) = 1.08 (CI: 0.92, 1.27) and AUC = 0.93 (CI: 0.82, 1.06); and, total platinum were: C(max) = 0.97 (CI: 0.88, 1.06) and AUC = 0.87 (CI: 0.81, 0.93). These results indicate that platinum pharmacokinetics (free and total) are similar, whether cisplatin is administered alone or combined with pemetrexed. The pemetrexed pharmacokinetic results were consistent with those from previous single-agent pemetrexed studies and a previous study of pemetrexed in combination with cisplatin. The combination of pemetrexed and cisplatin did not show any unexpected toxicities. Consistent with the platinum pharmacokinetic results, co-administration with pemetrexed did not appear to enhance cisplatin-related toxicities. Of the 13 treated patients, 11 had stable disease as the best overall response and 2 had progressive disease. CONCLUSIONS: The pharmacokinetics of free platinum derived from cisplatin were not altered by co-administration with pemetrexed, and in agreement with this, no unexpected cisplatin-induced toxicities were observed when these drugs were combined.