The Mediterranean diet (MD) is a known protective factor for head and neck cancer (HNC); however, there is still a lack of studies investigating this association by HNC subsite. The aim of the present study was therefore to evaluate the association between adherence to MD and HNC overall and by cancer subsite, as well as the effect of the individual food components on HNC risk. A case-control study was carried out at the Gemelli Hospital of Rome (Italy). A total of 500 HNC cases and 433 controls were interviewed. Dietary intake was assessed through a validated food frequency questionnaire that collected information on over 25 food items. Odds ratios (ORs) and 95% confidence intervals (CI) of HNC were calculated using a multiple logistic regression model. We found a reduced risk of both oral cavity and pharynx cancer (OR=0.61; CI: 0.54-0.70) and larynx cancer (OR=0.64; CI: 0.56-0.73) with increasing adherence to MD. We also found a high consumption of fruit, vegetables, and legumes to be significantly associated with a lower risk of larynx as well as oral cavity and pharynx cancers. Our study showed that adherence to MD acts protectively against HNC overall and by cancer subsite.

In head and neck squamous cell carcinoma (HNSCC) aerobic glycolysis is the key feature for energy supply of the tumor. Quantitative microdialysis (μD) offers an online method to measure parameters of the carbohydrate metabolism in vivo. The aim was to standardize a quantitative μD-study in patients with HNSCC and to prove if a ketogenic diet would differently influence the carbohydrate metabolism of the tumor tissue. Commercially available 100 kDa-CMA71-μD- catheters were implanted in tumor-free and in tumor tissue in patients with HNSCC for simultaneous measurements up to 5 days. The metabolic pattern and circadian rhythm of urea, glucose, lactate, and pyruvate was monitored during 24 h of western diet and subsequent up to 4 days ofketogenic diet. After 3 days of ketogenic diet the mean lactate concentration declines to a greater extent in the tumor tissue than in the tumor-free mucosa, whereas the mean glucose and pyruvate concentrations rise. The in vivo glucose metabolism of the tumor tissue is clearly influenced by nutrition. The decline of mean lactate concentration in the tumor tissue after ketogenic diet supports the hypothesis that HNSCC tumor cells might use lactate as fuel for oxidative glucose metabolism.

Photodynamic therapy (PDT) is a method to treat cancers using photosensitizer and light. PDT has been tried for several tumors. However, the clinical applications are limited by the toxicity of photosensitizer and narrow effect. Sulforaphane (SFN) is a material of isothiocyanate group and known to have anticancer effect. We evaluated the cytotoxic effect of PDT combined with SFN on human head and neck cancer cells. We measured the cell viability, extent of apoptosis and necrosis, reactive oxygen species (ROS) generation and caspase activation. Cell viability was decreased significantly by combination treatment. Cellular apoptosis and necrosis were increased in combination treatment compared to SFN or PDT. ROS generation was also higher in combination treatment than single treatment. In combination treatment group, apoptosis and necrosis were decreased by administration of sodium azide (SA) which is scavenger of ROS. Increased caspase activation in combination treatment was also inhibited by SA. Combination of PDT and SFN led to enhanced cytotoxic effect on head and neck cancer cells. Combination treatment promoted the ROS generation, which induced cell death through activation of caspase pathway.

PURPOSE:To explore, in a dose-escalation study, the feasibility of hyperbaric oxygen (HBO) treatments immediately before intensity modulated radiation therapy in conjunction with cisplatinum chemotherapy for squamous cell carcinoma of the head and neck (SCCHN).

METHODS AND MATERIALS:Eligible patients presented with SCCHN (stage III-IV [M0]), life expectancy>6 months, and Karnofsky performance status ≥70. Enrollees received intensity modulated radiation therapy, 70 Gy in 35 fractions over 7 weeks with weekly cisplatinum. Patients received HBO-100% oxygen, 2.4 atmospheres absolute (ATA) for 30 minutes-twice per week initially. Subsequent patients were escalated to 3 and then 5 times per week. Intensity modulated radiation therapy began within 15 minutes after HBO. Patients were followed for 2 years after RT with quality-of-life questionnaires (Performance Status Scale-Head and Neck Cancer and the Functional Assessment of Cancer Therapy-Head and Neck Cancer) and for 5+ years for local recurrence, distant metastases, disease-specific survival, and overall survival.

RESULTS:Twelve subjects enrolled from 3 centers. Two withdrew during radiation therapy and 1 within 14 weeks after radiation therapy. The remaining 9 had primary oropharyngeal disease and were stage IVA (7) or IVB (2). No dose-limiting toxicities were observed with daily HBO. Two patients (22%) required pressure equalization tubes. The average time between HBO and radiation therapy was 8.5 minutes, with 2 of 231 administrations delivered beyond 15 minutes (0.5%). Per-protocol analysis showed a clinical complete response in 7 and a pathologic complete response without tumor in salvage neck dissections in 2. With minimum follow-up of 61 months, per-protocol 5-year overall survival was 100%,local recurrence 0%, and distant metastases 11%. Patient-reported outcomes for quality of life (Functional Assessment of Cancer Therapy-Head and Neck Cancer) were comparable to published results for chemoradiotherapy without HBO.

CONCLUSIONS:While acknowledging the study's small size and early attrition of 3 patients, our in-depth review of the acquired data indicates the feasibility of combining HBO with chemoradiation.

Late effects of radiotherapy for head and neck cancer treatment have been increasingly investigated due to its impact on patients' quality of life. The purpose of this study was to evaluate the effect of low-level laser therapy on hyposalivation, low salivary pH, and quality of life in head and neck cancer patients post-radiotherapy. Twenty-nine patients with radiation-induced xerostomia received laser sessions twice a week, during 3 months (24 sessions). For this, a continuous wave Indium-Gallium-Aluminium-Phosphorus diode laser device was used punctually on the major salivary glands (808 nm, 0.75 W/cm(2), 30 mW, illuminated area 0.04 cm(2), 7.5 J/cm(2), 10 s, 0.3 J). Six extraoral points were illuminated on each parotid gland and three on each submandibular gland, as well as two intraoral points on each sublingual gland. Stimulated and unstimulated salivary flow rate, pH (two scales with different gradations), and quality of life (University Of Washington Quality of Life Questionnaire for Patients with Head andNeck Cancer) were assessed at baseline and at the end of the treatment. There were significant increases in both mean salivary flow rates (unstimulated: p = 0.0012; stimulated: p < 0.0001), mean pH values (p = 0.0002 and p = 0.0004), and mean score from the quality of life questionnaire (p < 0.0001). Low-level laser therapy seems to be effective to mitigate salivary hypofunction and increase salivary pH of patients submitted to radiotherapy for head and neck cancer, thereby leading to an improvement in quality of life.

PURPOSE:There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed.

METHODS:Narrative review and presentation of PBM parameters are based on current evidence and expert opinion.

RESULTS:PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows: wavelength, typically between 633 and 685 nm or 780-830 nm; energy density, laser or light-emitting diode (LED) output between 10 and 150 mW; dose, 2-3 J (J/cm(2)), and no more than 6 J/cm(2) on the tissue surface treated; treatment schedule, two to three times a week up to daily; emission type, pulsed (<100 Hz); and route of delivery, intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations.

CONCLUSION:PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT. The suggested PBM irradiation and dosimetric parameters, which are potentially effective for these complications, are intended to provide guidance for well-designed future studies. It is imperative that such studies include elucidating the effects of PBM on oncology treatment outcomes.

BACKGROUND:Head and neck cancer (HNC) is the seventh most-common type of cancer worldwide. Evidence regarding the potential protective effect of vitamins and carotenoids on HNC is limited and mostly based on case-control studies.

OBJECTIVE:We evaluated the association of intake of dietary vitamins C and E (including supplementation) and the most-common carotenoids (α-carotene, β-carotene, lutein plus zeaxanthin, lycopene, and β-cryptoxanthin) and risk on HNC and HNC subtypes in a large prospective study.

DESIGN:The Netherlands Cohort Study included 120,852 participants. For efficiency reasons, a case-cohort design was used. At baseline in 1986, participants completed a food-frequency questionnaire. A subcohort was randomly selected from the total cohort. After 20.3 y of follow-up, 3898 subcohort members and 415 HNC cases [131 oral cavity cancer (OCCs), 88 oro-/hypopharyngeal cancer (OHPs), and 193 laryngeal cancer cases] were available for analysis. Rate ratios and 95% CIs for highest (quartile 4) vs. lowest (quartile 1) quartiles of vitamin and carotenoid intake were estimated by using the Cox proportional hazards model.

RESULTS:A strong inverse association was shown between vitamin C and HNC overall (multivariable-adjusted rate ratio for quartile 4 vs. quartile 1: 0.39; 95% CI: 0.23, 0.66; P-trend<0.001), OCC (multivariable-adjusted rate ratio for quartile 4 vs. quartile 1: 0.35; 95% CI: 0.16, 0.77; P-trend<0.05), and OHPC (multivariable-adjusted rate ratio for quartile 4 vs. quartile 1: 0.29; 95% CI: 0.12, 0.67; P-trend<0.01). No statistically significant results were shown for vitamin E,α-carotene, β-carotene, lycopene, and lutein plus zeaxanthin. The association of vitamin E and HNC was modified by alcohol status (P-interaction = 0.003) with lower risks in alcohol abstainers.

CONCLUSIONS:With this study, we show an inverse association between intake of vitamin C and the incidence of HNC and HNC-subtypes. Future research is recommended to investigate the underlying mechanisms and to confirm our results, which may be promising for the prevention of HNC.