Adherence to intensive nutrition care in head and neck cancer patients undergoing radiotherapy.

PURPOSE: The aim of this study was to determine the prevalence and effect of adherence to intensive nutritional care on nutritional outcomes and survival in head and neck cancer patients undergoing radiotherapy. METHODS: Three-hundred and seventeen head and neck cancer patients referred to intensive nutrition support during radiotherapy were retrospectively analyzed. Patients who missed less than 25% of their appointments with the dietitian were considered adherent. Primary outcome was percentage weight loss during treatment. Secondary outcomes were overall survival and patients' capacity to accomplish their caloric and protein recommendations. Logistic regression was used to examine predictors of weight loss and Kaplan-Meier to estimate survival. RESULTS: Less than half of the patients (n = 145, 45.7%) were adherent. Statistically significant less weight loss in the adherent group (42.8% vs 55.8%; p = 0.02) was found, despite no difference in energy or protein intake. Logistic regression models after adjusting for other variables demonstrated that adherence resulted in 43% protection from significant weight loss (odds ratio 0.57, 95% CI 0.34-0.97). Overall survival was not different between groups. CONCLUSION: Findings demonstrated that patients who were adherent to weekly contacts with the dietitian had less weight loss, but not better survival or nutritional intake. Additional investigation of factors that may act as barriers or enablers for adherence could help improve the outcomes in this population.

Effectiveness of screening for oral cancer and oral potentially malignant disorders (OPMD): A systematic review.

Oral cancer (OC) is a debilitating disease with a high mortality rate when diagnosed in advanced stage. Conversely, early-stage OC has a high survival rate, supporting a need for early detection programmes. A previous systematic review of clinical trials evaluating efficacy of screening for OC was inconclusive. This systematic review aimed to determine the impact of screening for oral lesions on reducing mortality and incidence of OC by looking at a broader spectrum of evidence. The search for randomized controlled trials and observational studies with a control group was conducted in PubMed, OVID, Cochrane, CINAHL and grey literature sources. Risk of bias for included studies was assessed with the tools developed by the Cochrane collaboration. Six out of two identified randomized trials and five observational studies had moderate to high risk of bias. Nevertheless, the predictions on impact of OC screening on incidence and mortality were similar across the majority of the studies. The meta-analysis concluded on a 26% decrease in OC mortality, and an 19% decrease in advanced OC cases as a result of OC screening in high-risk population. Three out of four studies did not identify an impact of screening on OC incidence. No positive impact of OC screening on incidence or mortality among general population was identified in the only available randomized trial. Consistency in the outcomes and the limitations of the few available studies suggest a need for real-life setting research to evaluate the overall effectiveness of screening for OC in high-risk population.

Clinically significant changes in health-related quality of life in head and neck cancer patients following intensive nutritional care during radiotherapy.

PURPOSE: This study aimed to explore whether adherence to intensive nutritional care during radiotherapy would avoid a meaningful worsening in quality of life in head and neck cancer patients; and whether adherence was associated with better nutritional outcomes. METHODS: Observational prospective study that assessed head and neck cancer patients treated with radiotherapy at a large oncology hospital, between August 2018 and April 2019. The main outcome was minimal clinically important difference in quality of life, assessed with EORTC QLQ-C30 and EORTC QLQ H&N35, between baseline and 12 weeks. To illustrate clinically significant changes in quality of life over timeby adherence, a heat map analysis was performed. We also evaluated nutritional outcomes. RESULTS: Eighty patients were included, half of them (53.8%) were considered adherent. There were no significant difference in quality of life between groups at baseline, with the exception of swallowing (p = 0.029) and coughing (p < 0.01). After treatment, the heat map demonstrated that adherent patients had nonsignificant clinical change in function scales, while non-adherent patients had a clinically significant worsening in physical, cognitive and social function. The prevalence of malnutrition increased significantly only in non-adherent patients (p < 0.01). CONCLUSION: Adherence to intensive nutritional care may be able to avoid a meaningful worsening in quality of life and result in better nutritional outcomes in head and neck cancer patients. Our results may help to increase the awareness of the assessment of adherence and minimal clinically important difference in quality of life for research purposes and clinical practice.

Comprehensive Molecular Landscape of Cetuximab Resistance in Head and Neck Cancer Cell Lines.

Cetuximab is the sole anti-EGFR monoclonal antibody that is FDA approved to treat head and neck squamous cell carcinoma (HNSCC). However, no predictive biomarkers of cetuximab response are known for HNSCC. Herein, we address the molecular mechanisms underlying cetuximab resistance in an in vitro model. We established a cetuximab resistant model (FaDu), using increased cetuximab concentrations for more than eight months. The resistance and parental cells were evaluated for cell viability and functional assays. Protein expression was analyzed by Western blot and human cell surface panel by lyoplate. The mutational profile and copy number alterations (CNA) were analyzed using whole-exome sequencing (WES) and the NanoString platform. FaDu resistant clones exhibited at least two-fold higher IC50 compared to the parental cell line. WES showed relevant mutations in several cancer-related genes, and the comparative mRNA expression analysis showed 36 differentially expressed genes associated with EGFR tyrosine kinase inhibitors resistance, RAS, MAPK, and mTOR signaling. Importantly, we observed that overexpression of KRAS, RhoA, and CD44 was associated with cetuximab resistance. Protein analysis revealed EGFR phosphorylation inhibition and mTOR increase in resistant cells. Moreover, the resistant cell line demonstrated an aggressive phenotype with a significant increase in adhesion, the number of colonies, and migration rates. Overall, we identified several molecular alterations in the cetuximab resistant cell line that may constitute novel biomarkers of cetuximab response such as mTOR and RhoA overexpression. These findings indicate new strategies to overcome anti-EGFR resistance in HNSCC.

HPV-Induced Oropharyngeal Squamous Cell Carcinomas in Brazil: Prevalence, Trend, Clinical, and Epidemiologic Characterization.

BACKGROUND: Tobacco or human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCC) represent different clinical and epidemiologic entities. This study investigated the prevalence of HPV-positive and HPV-negative OPSCC in a reference cancer hospital in Brazil and its association with clinical and demographic data, as well as its impact on overall survival. METHODS: HPV infection was determined by p16-IHC in pre-treatment formalin-fixed paraffin-embedded samples from all patients with OPSCC diagnosed at Barretos Cancer Hospital between 2008 and 2018. The prevalence of HPV-positive cases and its temporal trend was assessed, and the association of clinical and demographic data with HPV infection and the impact on patient overall survival was evaluated. RESULTS: A total of 797 patients with OPSCC were included in the study. The prevalence of HPV-associated tumors in the period was 20.6% [95% confidence interval, 17.5-24.0] with a significant trend for increase of HPV-positive cases over the years (annual percentage change = 12.87). In a multivariate analysis, the variables gender, level of education, smoking, tumor sublocation, region of Brazil, and tumor staging had a significant impact in HPV positivity, and a greater overall survival (OS) was observed in HPV-positive patients (5-year OS: 47.9% vs. 22.0%; P = 0.0001). CONCLUSIONS: This study represents the largest cohort of Brazilian patients with OPSCC characterized according to HPV status. We report significant differences in demographics and clinical presentation according to HPV status, and an increasing trend in prevalence for HPV-induced tumors. IMPACT: These findings can potentially contribute to a better stratification and management of patients as well as assist in prevention strategies.

Tissue eosinophilia and its association with tumoral invasion of oral cancer.

This study investigated if tumor-associated tissue eosinophilia (TATE) could be associated with the process of tissue invasion in oral squamous cell carcinomas (OSCCs) and its influence on patient's prognosis. Forty-three patients treated for OSCCs with or without lymph nodes involvement, at A. C. Camargo Cancer Hospital, Brazil, were selected for TATE analysis. Two degrees of tissue eosinophilia were established in OSCC: absent/mild and intense. The TATE was evaluated in relation to the clinicopathological features and prognostic value using chi( 2) test and the Kaplan-Meier method. Most of the patients with OSCC in advanced clinical stage presented muscular infiltration and significantly intense TATE whereas those with tumors in early stage frequently showed absent/mild eosinophilia (P = .009). The TATE showed no prognostic value for 5-year and 10-year survival rates of the OSCC. These findings suggest that intense TATE seems to reflect the stromal invasion of the OSCCs that occur in advanced clinical stage.

Serum, plasma and saliva biomarkers for head and neck cancer.

INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) encompasses tumors arising from several locations (oral and nasal cavities, paranasal sinuses, salivary glands, pharynx, and larynx) and currently stands as the sixth most common cancer worldwide. The most important risk factors identified so far are tobacco and alcohol consumption, and, for a subgroup of HNSCCs, infection with high-risk types of human papillomavirus (HPV). Despite several improvements in the treatment of these tumors in the last decades, overall survival rates have only improved marginally, mainly due to the advanced clinical stage at diagnosis and the high rates of treatment failure associated with this late diagnosis. Areas covered: This review will focus on the feasibility of evaluating molecular-based biomarkers (mRNA, microRNA, lncRNA, DNA methylation and protein expression) in body fluids (serum, plasma, and saliva) as markers for diagnosis, prognosis, and surveillance. Expert commentary: The potential use of those markers in the clinical setting would allow for early diagnosis, prediction of treatment response, improvement in treatment selection and provide disease monitoring for early detection of tumor recurrence. It can ultimately be translated into better survival rates and improved quality of life for HNSCC patients.

Head and Neck Non-Melanoma Skin Cancer Treated By Superficial X-Ray Therapy: An Analysis of 1021 Cases.

INTRODUCTION: To report a single-institutional experience with the use of Superficial X-Ray Therapy (SXRT) for head and neck non-melanoma skin cancer (N-MSC) and to compare outcomes by prescribed fractionation schedules. MATERIALS AND METHODS: The medical records of 597 patients with 1021 lesions (720 BCC, 242 SCC, 59 SCC in situ) treated with kilovoltage radiation from 1979-2013 were retrospectively reviewed. The majority of patients were treated according to 1 of 3 institutional protocols based on the discretion of the radiation oncologist: 1) 22 x 2.5 Gy; 2) 20 x 2.5 Gy; 3) 30 x 2.0 Gy. "T" stage at first presentation was as follows: Tis (59); T1 (765); T2 (175); T3 (6), T4 (9); Tx, (7). All patients were clinical N0 and M0 at presentation. Chi-square test was used to evaluate any potential association between variables. The Kaplan-Meier method was used to analyze survival with the Log Rank test used for comparison. A Cox Regression analysis was performed for multivariate analysis. RESULTS: The median follow up was 44 months. No significant difference was observed among the 3 prescribed fractionation schemes (p = 0.78) in terms of RTOG toxicity. There were no failures among SCC in situ, 37 local failures (23 BCC, 14 SCC), 5 regional failures (all SCC) and 2 distant failures (both SCC). For BCC, the 5-year LC was 96% and the 10-year LC was 94%. For SCC the corresponding rates of local control were 92% and 87%, respectively (p = 0.03). The use of >2.0 Gy daily was significantly associated with improved LC on multivariate analysis (HR: 0.17; CI 95%: 0.05-0.59). CONCLUSION: SXRT for N-MSC of the head and neck is well tolerated, achieves excellent local control, and should continue to be recommended in the management of this disease. Fractionation schedules using >2.0 Gy daily appear to be associated with improved LC.

Prognostic significance of monocarboxylate transporter expression in oral cavity tumors.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer. The majority of patients present advanced stage disease and has poor survival. Therefore, it is imperative to search for new biomarkers and new alternative and effective treatment options. Most cancer cells rely on aerobic glycolysis to generate energy and metabolic intermediates. This phenotype is a hallmark of cancer, characterized by an increase in glucose consumption and production of high amounts of lactate. Consequently, cancer cells need to up-regulate many proteins and enzymes related with the glycolytic metabolism. Thus, the aim of this study was to characterize metabolic phenotype of oral cavity cancers (OCC) by assessing the expression pattern of monocarboxylate transporters (MCTs) 1, 2 and 4 and other proteins related with the glycolytic phenotype. MATERIAL AND METHODS: We evaluated the immunohistochemical expression of MCT1, MCT4, CD147, GLUT1 and CAIX in 135 human samples of OCC and investigated the correlation with clinicopathological parameters and the possible association with prognosis. RESULTS: We observed that all proteins analyzed presented significantly higher plasma membrane expression in neoplastic compared to non-neoplastic samples. MCT4 was significantly associated with T-stage and advanced tumoral stage, while CD147 was significantly correlated with histologic differentiation. Interestingly, tumors expressing both MCT1 and MCT4 but negative for MCT2 were associated with shorter overall survival. CONCLUSION: Overexpression of MCT1/4, CD147, GLUT1 and CAIX, supports previous findings of metabolic reprograming in OCC, warranting future studies to explore the hyper-glycolytic phenotype of these tumors. Importantly, MCT expression revealed to have a prognostic value in OCC survival.

Efficacy and safety of a cisplatin and paclitaxel induction regimen followed by chemoradiotherapy for patients with locally advanced head and neck squamous cell carcinoma.

BACKGROUND: The purpose of this phase II trial was to evaluate the tolerability, safety, and efficacy of a non-5-fluorouracil (5-FU)-based induction chemotherapy followed by chemoradiotherapy (CRT) for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). METHODS: Sixty patients with stage III to IV HNSCC were treated with induction paclitaxel and cisplatin (TP; paclitaxel 175 mg/m(2) and cisplatin 80 mg/m(2) , 3 cycles) followed by CRT (cisplatin 100 mg/m(2) ; D1, 22, and 43 of radiotherapy). RESULTS: Fifty-six patients (93.3%) completed 3 cycles of induction TP (no treatment-related deaths), 52 (86.7%) completed definitive CRT per protocol (adverse event [AE] grade ≥2 in 53.3%). The overall response rate after induction TP was 82.5% for patients with resectable disease and 55.5% for unresectable disease (p = .023), and complete response (CR) rate after CRT was 70.0% for patients with resectable disease and 30.0% for unresectable disease (p = .005). CONCLUSION: Induction TP followed by cisplatin based-CRT was well-tolerated, safe, and had high overall response rate in selected patients with locally advanced HNSCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E970-E980, 2016.

Pesquisa do linfonodo sentinela em carcinomas espinocelulares de cavidade oral classificados como T1 e T2 N0 / Sentinel lymph node in oral cavity squamous cell carcinoma classified as T1 and T2 N0

Introdução: A abordagem cervical em pacientes portadores decarcinoma epidermoide (CE) de cavidade oral classificados comoT1 ou T2 N0 ainda é controversa. A pesquisa do linfonodo sentinela(PLS), representa um menor risco de morbidades para o pacientecom uma boa acurácia para detecção de metástases ocultas.Objetivo: Avaliar a evolução de pacientes submetidos à PLS empescoço clinicamente N0. Método: É um estudo retrospectivoque avaliou os pacientes portadores de CE de cavidade oralclassificados como T1 ou T2 N0 submetidos ressecção do tumorprimário e PLS entre Junho de 2008 até Fevereiro de 2011 noHospital de Câncer de Barretos. Resultados: Foram incluídos 26pacientes, a maioria eram homens (73,0%), a média de idade foide 58 anos e o local mais frequente dos CE foi a língua (50,0%).Os carcinomas foram estadiados como T1 em 8 pacientes (33,3%)e T2 em 16 (66,7%). A PLS mostrou-se positiva em 5 pacientes(19,2%). Todos os pacientes em que a pesquisa do LS mostrousepositiva, foram submetidos a esvaziamento cervical seletivo.O seguimento médio dos pacientes foi de 11 meses, nesteperíodo a recorrência no pescoço homolateral a PLS ocorreu em2 pacientes (7,7%). Conclusão: Neste estudo o LS foi positivo19,2% e a recidiva cervical ocorreu em 7,7%. Observou-se que atécnica de PLS é factível e segura como único procedimento paraestadiamento do pescoço apresentando resultados oncológicoscomparáveis à realização do esvaziamento cervical seletivo comoprimeira opção para estes pacientes.