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The Association between Carotenoids and Head and Neck Cancer Risk.
Brewczyński, A, Jabłońska, B, Kentnowski, M, Mrowiec, S, Składowski, K, Rutkowski, T
Nutrients. 2021;(1)
Abstract
Head and neck cancer (HNC) includes oral cavity cancer (OCC), pharyngeal cancer (PC), and laryngeal cancer (LC). It is one of the most frequent cancers in the world. Smoking and alcohol consumption are the typical well-known predictors of HNC. Human papillomavirus (HPV) is an increasing etiological factor for oropharyngeal cancer (OPC). Moreover, food and nutrition play an important role in HNC etiology. According to the World Cancer Research Fund and the American Institute for Cancer Research, an intake of non-starchy vegetables and fruits could decrease HNC risk. The carotenoids included in vegetables and fruits are well-known antioxidants which have anti-mutagenic and immune regulatory functions. Numerous studies have shown the relationship between carotenoid intake and a lower HNC risk, but the role of carotenoids in HNC risk is not well defined. The goal of this review is to present the current literature regarding the relationship between various carotenoids and HNC risk.
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2.
Hypoxia dynamics on FMISO-PET in combination with PD-1/PD-L1 expression has an impact on the clinical outcome of patients with Head-and-neck Squamous Cell Carcinoma undergoing Chemoradiation.
Rühle, A, Grosu, AL, Wiedenmann, N, Mix, M, Stoian, R, Niedermann, G, Baltas, D, Werner, M, Weber, WA, Kayser, G, et al
Theranostics. 2020;(20):9395-9406
Abstract
Tumor-associated hypoxia influences the radiation response of head-and-neck cancer (HNSCC) patients, and a lack of early hypoxia resolution during treatment considerably deteriorates outcomes. As the detrimental effects of hypoxia are partly related to the induction of an immunosuppressive microenvironment, we investigated the interaction between tumor hypoxia dynamics and the PD-1/PD-L1 axis in HNSCC patients undergoing chemoradiation and its relevance for patient outcomes in a prospective trial. Methods: 49 patients treated with definitive chemoradiation for locally advanced HNSCC were enrolled in this trial and received longitudinal hypoxia PET imaging using fluorine-18 misonidazole ([18F]FMISO) at weeks 0, 2 and 5 during treatment. Pre-therapeutic tumor biopsies were immunohistochemically analyzed regarding the PD-1/PD-L1 expression both on immune cells and on tumor cells, and potential correlations between the PD-1/PD-L1 axis and tumor hypoxia dynamics during chemoradiation were assessed using Spearman's rank correlations. Hypoxia dynamics during treatment were quantified by subtracting the standardized uptake value (SUV) index at baseline from the SUV values at weeks 2 or 5, whereby SUV index was defined as ratio of maximum tumor [18F]FMISO SUV to mean SUV in the contralateral sternocleidomastoid muscle (i.e. tumor-to-muscle ratio). The impact of the PD-1/PD-L1 expression alone and in combination with persistent tumor hypoxia on locoregional control (LRC), progression-free survival (PFS) and overall survival (OS) was examined using log-rank tests and Cox proportional hazards models. Results: Neither PD-L1 nor PD-1 expression levels on tumor-infiltrating immune cells influenced LRC (HR = 0.734; p = 0.480 for PD-L1, HR = 0.991; p = 0.989 for PD-1), PFS (HR = 0.813; p = 0.597 for PD-L1, HR = 0.796; p = 0.713 for PD-1) or OS (HR = 0.698; p = 0.405 for PD-L1, HR = 0.315; p = 0.265 for PD-1). However, patients with no hypoxia resolution between weeks 0 and 2 and PD-L1 expression on tumor cells, quantified by a tumor proportional score (TPS) of at least 1%, showed significantly worse LRC (HR = 3.374, p = 0.022) and a trend towards reduced PFS (HR = 2.752, p = 0.052). In the multivariate Cox regression analysis, the combination of absent tumor hypoxia resolution and high tumoral PD-L1 expression remained a significant prognosticator for impaired LRC (HR = 3.374, p = 0.022). On the other side, tumoral PD-L1 expression did not compromise the outcomes of patients whose tumor-associated hypoxia declined between week 0 and 2 during chemoradiation (LRC: HR = 1.186, p = 0.772, PFS: HR = 0.846, p = 0.766). Conclusion: In this exploratory analysis, we showed for the first time that patients with both persistent tumor-associated hypoxia during treatment and PD-L1 expression on tumor cells exhibited a worse outcome, while the tumor cells' PD-L1 expression did not influence the outcomes of patients with early tumor hypoxia resolution. While the results have to be validated in an independent cohort, these findings form a foundation to investigate the combination of hypoxic modification and immune checkpoint inhibitors for the unfavorable subgroup, moving forward towards personalized radiation oncology treatment.
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3.
Immune checkpoint-mediated myositis and myasthenia gravis: A case report and review of evaluation and management.
Kang, KH, Grubb, W, Sawlani, K, Gibson, MK, Hoimes, CJ, Rogers, LR, Lavertu, P, Yao, M
American journal of otolaryngology. 2018;(5):642-645
Abstract
BACKGROUND We present a case of myositis and possible overlapping neuromuscular junction disorder following treatment with nivolumab for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). METHODS We report a 75-year-old man with recurrent stage IVA, T1N2cM0 oral cavity HNSCC treated with weight-dosed nivolumab who presented three weeks later with severe fatigue, generalized weakness, and bilateral ptosis. Evaluation demonstrated elevated creatine kinase and myopathic motor units on electromyography, supporting a diagnosis of an underlying muscle disease. Elevated serum acetylcholine receptor binding antibodies raised the possibility of concurrent myasthenia gravis. RESULTS He received corticosteroids and plasmapheresis without improvement in muscle weakness. His course was complicated by bacteremia, cardiac arrest, and concerns for recurrent malignancy. Following a two-month hospital stay, he was made comfort care and died. CONCLUSIONS With increasing usage of checkpoint inhibitors in HNSCC, clinicians must be aware of and vigilant for associated rare but serious adverse events.
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4.
Nutritional considerations for head and neck cancer patients: a review of the literature.
Alshadwi, A, Nadershah, M, Carlson, ER, Young, LS, Burke, PA, Daley, BJ
Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 2013;(11):1853-60
Abstract
PURPOSE Approximately 35% to 60% of all patients with head and neck cancer are malnourished at the time of their diagnosis because of tumor burden and obstruction of intake or the anorexia and cachexia associated with their cancer. The purpose of this article is to provide a contemporary review of the nutritional aspects of care for patients with head and neck cancer. MATERIALS AND METHODS A literature search was performed in Medline, Cochrane, and other available databases from 1990 through 2012 for the clinical effectiveness of nutritional support, treatment modalities, and methods of delivery in relation to patients with head and neck malignancies. Human studies published in English and having nutritional status and head and neck cancer as a predictor variable were included. Randomized controlled trials, meta-analyses, prospective clinical studies, and systemic reviews were selected based on their relevance to the abovementioned subtitles. The resultant articles were analyzed and summarized into the definition, impact, assessment, treatment, and modes of administration of nutrition on the outcome of patients with head and neck cancer. RESULTS Articles were reviewed that focused on the etiology and assessment of malnutrition and current nutritional treatments for cancer-induced anorexia and cachexia. Two hundred forty-eight articles were found: 2 clinical trials, 10 meta-analyses, 210 review studies, and 26 systematic reviews. Because of the lack of prospective data, a summative review of the conclusions of the studies is presented. CONCLUSION Nutritional interventions should be initiated before cancer treatment begins and these interventions need to be ongoing after completion of treatment to ensure optimal outcomes for patients. A nutritional assessment must be part of all comprehensive treatment plans for patients with head and neck cancer. Alternative medical interventions, such as immune-enhancing nutrients or anticytokine pharmaceutical agents, also may be effective as adjuvant therapies, but more research is needed to quantify their clinical effect.
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5.
A randomized clinical trial with oral Immunonutrition (omega3-enhanced formula vs. arginine-enhanced formula) in ambulatory head and neck cancer patients.
de Luis, DA, Izaola, O, Aller, R, Cuellar, L, Terroba, MC
Annals of nutrition & metabolism. 2005;(2):95-9
Abstract
OBJECTIVE The aim of our study was to investigate whether oral ambulatory nutrition of head and neck cancer patients, using an omega3 fatty acid-enhanced diet (low ratio omega6/omega3 fatty acids) versus an arginine-enhanced diet, could improve nutritional variables as well as clinical outcome, postoperative infectious and wound complications. RESEARCH METHODS A population of 73 ambulatory postsurgical patients with oral and laryngeal cancer were enrolled. At discharge from hospital the postsurgical head and neck cancer patients were asked to consume two units per day of either a specially designed omega3 fatty acid-enhanced supplement (group 1) or an arginine-enhanced supplement (group 2) for a 12-week period. RESULTS No significant intergroup differences in the trend of the three serum proteins and lymphocytes were detected. Differences were detected in weight (group 1: 65.5 +/- 11.5 kg vs. 70.4 +/- 11.1 kg; p < 0.05) with a significant increase in fat mass in group 1 (15.4 +/- 6.6 vs. 18.1 +/- 8.4 kg; p < 0.05) and in tricipital skinfold. The postoperative infectious complications were similar in both groups (0 in group 1 and 8.57% in group 2; nonsignificant). No local complications were detected in the surgical wound. Gastrointestinal tolerance (diarrhea and vomiting episodes) of both formulas was good. CONCLUSIONS At the dose taken, the omega3-enhanced formula improved fat mass and proteins in ambulatory postoperative head and neck cancer patients. The arginine-enhanced formula improved proteins. Further studies are required to examine the potential role of immune-enhanced supplements.
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6.
Cell-mediated immunity and head and neck cancer: with special emphasis on betel quid chewing habit.
Chang, MC, Chiang, CP, Lin, CL, Lee, JJ, Hahn, LJ, Jeng, JH
Oral oncology. 2005;(8):757-75
Abstract
Betel quid (BQ) chewing is popular in Taiwan, India, and many southeast-Asian countries. BQ chewing has strong association with the risk of oral leukoplakia (OL), oral submucous fibrosis (OSF), and oral cancer (OC). BQ components exhibit genotoxicity and may alter the structure of DNA, proteins and lipids, resulting in production of antigenicity. BQ ingredients are also shown to induce keratinocyte inflammation by stimulating the production of prostaglandins, TNF-alpha, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in keratinocytes. These events may provoke tissue inflammation, early cell-mediated immunity (CMI), and immune surveillance in BQ chewers. However, BQ components also directly affect the functional activities of immunocompotent cells, and moreover tumor cells may hypo-respond to the CMI via diverse mechanisms such as induction of apoptosis of lymphocytes, induction of production of suppressor T cells, downregulation of MHC molecules in tumor cells, etc. Clinically, an alteration in lymphocyte subsets, a decrease in total number of lymphocytes, and a reduction in functional activities of CMI have been observed in isolated peripheral blood mononuclear cells (PBMC) and tumor infiltrated lymphocytes (TIL) in patients with OSF, OL or OC. Adaptation of tumor cells to immune system may promote clonal selection of resistant tumor cells, leading to immune tolerance. Future studies on effects of BQ components on CMI and humoral immunity in vitro and in vivo can be helpful for chemoprevention of BQ-related oral mucosal diseases. To elucidate how virus infection, tobacco, alcohol and BQ consumption, and other environmental exposure affect the immune status of patients with oral premalignant lesions or OC will help us to understand the immunopathogenesis of OC and to develop immunotherapeutic strategies for OC.
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7.
Preoperative nutritional support at home in head and neck cancer patients: from nutritional benefits to the prevention of the alcohol withdrawal syndrome.
Bertrand, PC, Piquet, MA, Bordier, I, Monnier, P, Roulet, M
Current opinion in clinical nutrition and metabolic care. 2002;(4):435-40
Abstract
PURPOSE OF REVIEW Preoperative nutritional support in severely malnourished patients decreases complications after major surgery. This review summarizes previous studies on head and neck cancer patients undergoing surgery, and offers recommendations on preoperative nutritional support based on the literature and our experience. RECENT FINDINGS Head and neck cancer has a large impact on the patient's quality of life and a high mortality rate. Aggressive surgical resection followed by soft-tissue and osseous reconstruction is the gold standard of treatment. The incidence of postoperative complications is high at 20-50%. Malnutrition and alcohol withdrawal syndrome are often present, and are considered risk factors for developing wound infection after head and neck cancer surgery. Proactive intervention by preoperative nutritional support may correct nutrient deficiencies, minimize malnutrition-related morbidity and mortality, reduce the length and cost of hospitalization, and may prevent alcohol withdrawal syndrome. Nutritional support given preoperatively for 7-10 days decreases postoperative complications by approximately 10% in malnourished patients with weight loss of 10% or more. Oral liquid supplements and enteral nutrition are useful to support head and neck cancer patients preoperatively. Enteral nutrition is safer, more physiological, less expensive and practicable at home compared with parenteral nutrition, which is not usually indicated in these patients. SUMMARY Enteral nutrition is efficient in preoperative phase to prevent postoperative complications. However evidence is insufficient to conclude that preoperative immune-enhancing enteral feeding provides any supplementary benefit by comparison with a standard diet. Our experience with the preoperative approach in head and neck cancer patients is reported in this paper.