Effectiveness and tolerance of electrochemotherapy as palliative therapy for patients with head and neck cancer and malignant melanoma and its relation to early skin reaction

Abstract Objectives To evaluate the efficacy and tolerance after the electrochemotherapy treatment for local therapy of cutaneous and subcutaneous metastases of head-and-neck tumors and malignant melanoma refractory to standard therapies, mainly in neck metastasis of squamous cell carcinoma. And, to evaluate the relation of this response according to the skin reaction (healing with ulcer or dry crust). Methods prospective pase II, observational clinical study of 56 patients with metastases of head-and-neck squamous cell carcinoma (n = 13), papillary thyroid carcinoma (n = 4), adenoid cystic carcinoma of parotid gland (n = 1) or malignant melanoma (n = 37, 5 in head). Patients were treated by electrochemotherapy (application of electrical pulses into the tumor) after the administration of a single intravenous dose of bleomycin. Kaplan-Meier curves were performed. The statistical significance was evaluated using log-rank test; p-value of less than 0.05 was considered as significant. Results Overall clinical response was observed in 47 patients (84%). Local side effects were mild in all the patients. Ten patients (76.9%) with neck metastasis of squamous cell carcinoma had some degree of response, but only in one was complete. Patients even with only partial response had a higher overall survival than patients without response (p = 0.02). Most of the patients with squamous cell carcinoma had diminution of pain and anxiety. Response rate and overall survival was higher in MM patients (86.5%) than in squamous cell cancer patients (76.9%) (p = 0.043). The healing process (dry crust/ulcer) was not associated with the overall survival (p = 0.86). Conclusions Electrochemotherapy is associated a higher overall survival and diminution of pain and anxiety. Therefore, it is an option as palliative treatment for patients with neck metastasis of squamous cell carcinoma refractory to other therapies or even as a concomitant treatment with newer immunotherapies. The type of healing of the surgical wound could not be associated with a higher rate of response or survival. Level of evidence III.

Caracterización de los pacientes con cáncer bucal en el Hospital Provincial Docente Oncológico María Curie de Camagüey

Introducción: El cáncer bucal continúa siendo una de las neoplasias malignas en ascenso, de acuerdo con su incidencia y el importante número de muertes cada año. En este sentido, se han desarrollado programas de salud para la población que garantizan la pesquisa, la prevención y la atención de las enfermedades. Objetivo: Caracterizar a los pacientes con cáncer bucal en el Hospital Provincial Docente Oncológico María Curie de la provincia Camagüey durante el período 2018-2022. Métodos: Se realizó un estudio descriptivo transversal en el Hospital Provincial Docente Oncológico María Curie de la provincia Camagüey en un universo de 218 pacientes, que acudieron al Servicio de Cirugía de Cabeza y Cuello del año 2018 al 2022 y tuvieron como diagnóstico cáncer bucal. La muestra se delimitó a 113 pacientes que cumplieron con los criterios de inclusión y exclusión. Resultados: El cáncer bucal predominó en el sexo masculino con 89 (78,76 %) en los años 2019 y 2021. Hubo mayor frecuencia en pacientes de piel blanca con 97 (85,84 %) y el año 2021 mostró mayor número de estos enfermos. La lengua fue la más afectada con 43 (30,05 %) pacientes, seguida por el suelo de boca en 18 (15,92 %) y las encías en 17 (15,04 %) pacientes. Según el estadio existió un predominio del IV en 61 (53,98 %) enfermos, seguido por el III con un 18,58 % de pacientes diagnosticados. Conclusiones: Prevaleció del sexo masculino en el grupo de 60 a 79 años y los pacientes de piel blanca fueron los más afectados. La localización de las lesiones se manifestó con mayor incidencia en la lengua y los estadios IV y III de la enfermedad son los más representativos en el momento del diagnóstico.

Introduction: Oral cancer continues to be one of the malignant neoplasms on the rise, according to its incidence and the significant number of deaths each year. In this sense, health programs have been developed for the population that guarantee screening, prevention and care of the diseases. Objective: To characterize patients with oral cancer at the María Curie Oncological Teaching Provincial Hospital in Camagüey province during the period 2018-2022. Methods: A cross-sectional descriptive study was carried out in the María Curie Oncological Teaching Provincial Hospital of Camagüey province in a universe of 218 patients, who attended the Head and Neck Surgery Service from 2018 to 2022 and had oral cancer as diagnosis. The sample was limited to 113 patients who met the inclusion and exclusion criteria. Results: Oral cancer predominated in the male sex with 89 (78.76%) in the years 2019 and 2021. There was a higher incidence in patients with white skin with 97 (85.84%) and the year 2021 showed a higher number of these patients. The tongue was the most affected with 43 (30.05%) patients, followed by the floor of the mouth in 18 (15.92%) and the gums in 17 (15.04%) patients. According to stage there was a predominance of stage IV in 61 (53.98%) patients, followed by stage III with 18.58% of patients diagnosed. Conclusions: Male sex prevailed in the 60 to 79 years age group and white skin patients were the most affected. The location of the lesions manifested with greater incidence on the tongue and stages IV and III of the disease are the most representative at the time of diagnosis.

Evaluación de guías prácticas y preservación de la glándula submandibular en la disección del cuello

Introducción: Las guías prácticas de atención al cáncer de cabeza y cuello abordan actualmente la preservación funcional de algunos órganos dentro del tratamiento oncoespecífico. Objetivos: Evaluar guías de práctica clínica y cómo abordan la preservación de la glándula submandibular en la disección del cuello. Métodos: Se realizó una investigación cuantitativa, descriptiva y transversal, donde se evaluaron seis guías de atención al cáncer de cabeza y cuello, en cuanto a su calidad metodológica y la preservación de la glándula submandibular en la disección del cuello. Se utilizó el instrumento Appraisal of Guidelines Research and Evaluation y se conformó un equipo compuesto por cuatro evaluadores que dieron su consentimiento y fueron capacitados en su uso. Para el análisis de la información se empleó el Statistical Package for Social Sciences versión 21 y se calculó la puntuación de calidad para cada dominio y el coeficiente de correlación intraclase. Resultados: La mayor puntuación de calidad correspondió a los dominios 1, 4 y 6. La guía con mayor puntuación de calidad fue la de la Sociedad Europea de Oncología Médica, con una media de 94,3 %, mientras que la de la Sociedad China de Oncología Clínica obtuvo el menor valor para un 71,5 %. Tres guías obtuvieron la máxima puntuación de calidad (7) en la evaluación global. La mayor fuerza de concordancia entre los evaluadores correspondió a la guía de la Sociedad Americana de Oncología Clínica (1) y la menor a la del Instituto Nacional de Oncología y Radiobiología (0,93). Conclusiones: Las guías de práctica clínica del cáncer de cabeza y cuello evaluadas presentaron una alta calidad metodológica y la preservación de la glándula submandibular en la disección del cuello no fue abordada en ninguna.

Introduction: Practical guidelines for head and neck cancer care currently address the functional preservation of some organs within oncospecific treatment. Objectives: To evaluate clinical practice guidelines and how they address the preservation of the submandibular gland in neck dissection. Methods: A quantitative, descriptive and cross-sectional research was carried out to evaluate six guidelines for head and neck cancer care, in terms of their methodological quality and the preservation of the submandibular gland in neck dissection. The Appraisal of Guidelines Research and Evaluation instrument was used, a team was composed by four evaluators who gave their consent and were trained to use such instrument. For the analysis of the information, the Statistical Package for Social Sciences version 21 was used and the quality score for each domain and the intraclass correlation coefficient were calculated. Results: The highest quality score corresponded to domains 1, 4 and 6. The guide with the highest quality score was that of the European Society of Medical Oncology reporting an average of 94.3%, while that of the Chinese Society of Clinical Oncology obtained the lowest value (71.5%). Three guidelines had the highest quality score (7) in the global evaluation. The highest strength of agreement between the evaluators corresponded to the guideline of the American Society of Clinical Oncology (1) and the lowest to that of the National Institute of Oncology and Radiobiology (0.93). Conclusions: The head and neck cancer clinical practice guidelines evaluated presented high methodological quality and the preservation of the submandibular gland in neck dissection was not addressed in any of them.

Eugene Nicholas Myers' Lecture on Head and Neck Cancer, 2020: The Surgeon as a Prognostic Factor in Head and Neck Cancer Patients Undergoing Surgery

Abstract This paper is a transcript of the 29th Eugene N. Myers, MD International Lecture on Head and Neck Cancer presented at the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) in 2020. By the end of the 19th century, the survival rate in treated patients was 10%. With the improvements in surgical techniques, currently, about two thirds of patients survive for > 5 years. Teamwork and progress in surgical reconstruction have led to advancements in ablative surgery; the associated adjuvant treatments have further improved the prognosis in the last 30 years. However, prospective trials are lacking; most of the accumulated knowledge is based on retrospective series and some real-world data analyses. Current knowledge on prognostic factors plays a central role in an efficient treatment decision-making process. Although the influence of most tumor- and patient-related prognostic factors in head and neck cancer cannot be changed by medical interventions, some environmental factors—including treatment, decision-making, and quality—can be modified. Ideally, treatment strategy decisions should be taken in dedicated multidisciplinary team meetings. However, evidence suggests that surgeons and hospital volume and specialization play major roles in patient survival after initial or salvage head and neck cancer treatment. The metrics of surgical quality assurance (surgical margins and nodal yield) in neck dissection have a significant impact on survival in head and neck cancer patients and can be influenced by the surgeon's expertise. Strategies proposed to improve surgical quality include continuous performance measurement, feedback, and dissemination of best practice measures.

Inpatient Decongestive Therapy for Lymphedema in Acute Postsurgical Head and Neck Cancer Patients

Abstract Introduction Head and neck lymphedema is an omnipresent morbidity related to head and neck cancer therapies. Studies on therapy for these patients in the acute postsurgical population have not been published to date. Objective To assess changes in the measurements of lymphedema in surgical head and neck cancer patients during the hospital stay with implementation of modified decongestive therapy (MDT). Methods Patients aged > 18 years undergoing neck dissection with or without primary-site resection or laryngectomy between 2016 and 2019 were included. Facial measurements were obtained prior to beginning MDT and again prior to discharge. A total facial composite measurement was calculated and used to assess change over time. Rates ≥ 2% of change were considered significant. Results A total of 38 patients were included (subsites: larynx = 27; thyroid =4; oral cavity = 3; and neck = 4). The mean number of days between surgery and the start of lymphedema therapy was 3.0 days. The mean number of days between measurements was 5.2 days. Reduction in the total composite score was observed in 37 (97%) patients, and 35 (92%) patients had a total composite reduction score > 2%. Tumor subsite and surgery type did not portend toward greater percent change, except for those patients treated with total laryngectomy, regional flap reconstruction, and neck dissection (p = 0.02). Conclusion Acute postsurgical inpatient MDT was associated with reduced total composite measurements in patients after head and neck surgery. As the first published study on lymphedema therapy in this acute postsurgical period, further prospective case-control studies are warranted to explore further benefits of acute therapy.

Comparison of Free Flap Outcomes at a University Hospital versus County Hospital Setting for Head and Neck Reconstruction

Abstract Introduction Patients at public county hospitals often have poorer access to healthcare with advanced disease on presentation. These factors, along with limited resources at county hospitals, may have an impact on outcomes for patients requiring complex head and neck reconstruction. Objectives To delineate differences in the frequency of complications in two different care settings, a public county hospital and a private university hospital. Methods Retrospective review of otolaryngology patients at a university hospital compared with a publicly-funded county hospital. The main outcome measure was major complications including total flap loss or unplanned reoperation in 30 days. Secondary outcome measures included medical complications, partial flap loss, and unplanned hospital readmission in 30 days. Results In the county hospital sample (n = 58) free flap failure or reoperation occurred in 20.7% of the patients, and minor complications, in 36.2% of the patients. In the university hospital sample (n = 65) flap failure or reoperation occurred in 9.2% of the patients, and minor complications, in 12.3% of the patients. Patients at the private hospital who had surgery in the oropharynx were least likely to have minor complications. Conclusions Patients at the county hospital had a higher but not statistically significant difference in flap failure and reoperation than those at a university hospital, although the county hospital experienced more minor postoperative complications. This is likely multifactorial, and may be related to poorer access to primary care preoperatively, malnutrition, poorly controlled or undiagnosed medical comorbidities, and differences in hospital resources.

Prognostic and predictive role of soluble programmed death ligand-1 in head and neck cancer

Abstract Objectives The aim of the study was to investigate clinical significance of soluble PD-L1 (sPD-L1) serum level in head and neck cancer and to evaluate its role as a possible prognostic and predictive biomarker. Methods A prospective analysis of sPD-L1 levels in 60 patients diagnosed and treated due to malignant and non-malignant lesions in the region of head and neck was performed in peripheral blood by an ELISA test. Results The range of sPD-L1 in the study group was 0.16-1.63 ng/mL, mean 0.64 ± 0.32. There were no differences in the mean sPD-L1 regarding patients' age, sex, and the localization of the lesion. Statistically significant difference was revealed in the average sPD-L1 level (p = 0.006) depending on the histopathological advancement of the lesions, 0.704 ± 0.349 and 0.512 ± 0.177 respectively in the malignant and benign group. The separate analysis of laryngeal lesions confirmed statistical difference in sPD-L1 (p = 0.002) for the malignant lesions (0.741 ± 0.353) compared with the benign (0.489 ± 0.175). The sPD-L1 level of 0.765 ng/mL or higher, revealed 35% sensitivity and 95.5% specificity for the diagnosis of head and neck malignant lesions (AUC = 0.664, 95% CI 0.529‒0.8, p-value = 0.039). The 1-year DFS was 83.3% in the group of patients with low sPD-L1 levels (< 0.765 ng/mL) and 53.8% in patients with high sPD-L1 (≥0.765 ng/mL). The 2-year OS were 68% and 69.2% respectively in both groups. The log-rank test confirmed statistically significant prognostic value of sPD-L1 level for 1-year DFS (p-value = 0.035). Conclusions sPD-L1 is a promising prognostic and early recurrence predictive biomarker for head and neck cancers, most significantly for laryngeal lesions. Level of evidence 3.

Dry eye disease in head and neck cancer patients undergoing radiotherapy

Purpose: To study the incidence of dry eye disease (DED) in head and neck cancer (HNC) patients undergoing external beam radiotherapy (EBRT), to find a correlation between tumor location and total radiation dose with DED, and to report various radiotherapy (RT) induced acute toxic effects on ocular and adnexal structures. Methods: A prospective cohort study was conducted at a tertiary eye?care center on 90 patients of HNC undergoing EBRT from March 2021 to May 2022. All underwent a thorough clinical history and complete ophthalmological examination including an ocular surface disease index (OSDI) questionnaire, visual acuity, anterior segment, angle and posterior segment examination, dry eye workup including the Schirmer test, tear meniscus height, tear break?up time, corneal fluorescein staining and grading, and meibography by auto?refractometer and its scoring at each visit. Patients were evaluated before the start of RT and then at 1 week, 4 weeks, and 12 weeks post?RT. Radiation records of all patients were noted. Data were analyzed using percentage and Microsoft Excel. Results: Of the 90 patients, 66 were male and 24 female (M: F ratio of 2.75) with a median age of 52.5 years (range 24 to 80 years). The most common HNC was the carcinoma oral cavity and lip. Most patients received a total radiation dose between 46 to 55 Gy. DED developed in 48 (53.3%) patients. The incidence of DED increased with the increase in total radiation dose (r = 0.987). DED was also found to be correlated with tumor location (r = 0.983). Conclusion: The incidence of DED positively correlated with the total radiation dose and tumor location.

Inmunoterapia para el tratamiento del cáncer de cabeza y cuello ¿dónde estamos y hacia dónde vamos? / Immunotherapy for the treatment of head and neck cancer: where are we and where are we going?

El cáncer de cabeza y cuello comprende a todos aquellos tumores que se desarrollan en el tracto aerodigestivo superior, una de las características de éstos es su diversidad, que no es solo desde el punto de vista histológico y etiológico, sino que incluyen diversas formas de presentación, progresión y enfoques terapéuticos. Son de causa multifactorial, siendo el alcohol y el tabaco los principales factores de riesgo asociados; en los últimos años se ha relacionado a ciertos virus con potencial oncogénico con la génesis tumoral, entre ellos al Virus del Papiloma Humano, lo que ha permitido modificar el sistema de estadificación tumor primario-nodos linfáticos cancerosos-metástasis (TNM); presentándolo ahora en dos grandes grupos acorde a la Proteína supresora de tumores P16: P16+ y P16-,los cuales tienen características y manejo diferente. En vista de la heterogeneidad de la enfermedad, son diversos los tratamientos que se ha empleados para el manejo de la misma, entre ellos cirugía, radioterapia, quimioterapia e/o inmunoterapia; ésta última terapéutica, está dirigida hacia la estimulación del sistema inmune del paciente con la finalidad de generar la destrucción de las células tumorales, se realizan previo a una intervención quirúrgica para reducir el tamaño del tumor. Una forma destacable, es la del bloqueo de puntos de control inmunitarios, especialmente hacia proteínas de control inmune moduladoras de respuesta de células T, como los anti-PD-1 y los anti-CTLA-4. La inmunoterapia cada vez va tomando más protagonismo en oncología, en especial las formas de evasión de las reacciones inmunitarias por parte de las células cancerígenas(AU)

Head and neck cancer includes all those tumors that develop in the upper aerodigestive tract, one of the characteristics of these is their heterogeneity, which is not only from the histological and etiological, but also include various forms of presentation, progression and therapeutic approaches.They have a multifactorial cause, with alcohol and tobacco being the main associated risk factors, however, in recent year scertain viruses with oncogenic potential have been linked to tumor genesis, including HPV, which has made it possible tomodify the TNM staging system; now presenting it in two large groups, P16+ and P16-, which have different characteristics and management. In view of the heterogeneity of the disease, there are various treatments that have been used to manageit, including surgery, radiotherapy, chemotherapy and/ orimmunotherapy which will be determined taking into account the location and tumor extension. The latter treatment, is aimedat stimulating the patient's immune system in order to generate the destruction of tumor cells, are performed prior to a surgical intervention to reduce the size of the tumor. A remarkable therapy is that of blocking immune checkpoints, especially anti-PD-1 and anti-CTLA. Immunotherapy is becoming more and more prominent, however, there is still much to discover, so we believe that we should continue investigating the ways of evasion of immune reactions by cancer cells(AU)

Comparative Analysis of the Quality of Life in the Pretreatment of Head and Neck Cancer Patients According to Tumor Site

Abstract Introduction Head and neck cancer (HNC) and its treatment can cause physical, psychological, and quality of life (QoL) damage, because it can disturb the physiology of eating, breathing, speaking, and compromise self-image. Objective To evaluate the QoL of the pretreatment of patients diagnosed with head and neck cancer according to the anatomical location of the tumor. Methods A descriptive, cross-sectional study was performed on a sample of 144 patients undergoing pretreatment for cancer from February 2017 to July 2019. The University of Washington QoL Questionnaire (version 4) was used to assess the QoL. The anatomical location data were obtained from medical records. The ANOVA test was used to compare the differences in QoL according to tumor location. Results A total of 144 participants were included, 66 (45.5%) of whom had the primary tumor located in the mouth. The median age of the patients was 62 years, with a higher prevalence of male (75.7%), Black (78.5%), single/divorced/widowed people (59%), and illiterates (32.6%); most of them were smokers (84.7%) and alcohol drinkers (79.2%). The mean QoL score was 830 for mouth cancer, 858 for pharynx cancer, and 891 for laryngeal cancer patients. Conclusion Based on the results of this study, it can be concluded that the QoL of patients with head and neck cancer was not influenced by tumor location. The most affected domains in the three groups were pain, appearance, chewing, swallowing, and speech (p < 0.05).

Stoichioproteomics study of differentially expressed proteins and pathways in head and neck cancer / Estudo estequioproteômico de proteínas e vias expressas diferencialmente no câncer de cabeça e pescoço

Abstract Hypoxia is a prominent feature of head and neck cancer. However, the oxygen element characteristics of proteins and how they adapt to hypoxia microenvironments of head and neck cancer are still unknown. Human genome sequences and proteins expressed data of head and neck cancer were retrieved from pathology atlas of Human Protein Atlas project. Then compared the oxygen and carbon element contents between proteomes of head and neck cancer and normal oral mucosa-squamous epithelial cells, genome locations, pathways, and functional dissection associated with head and neck cancer were also studied. A total of 902 differentially expressed proteins were observed where the average oxygen content is higher than that of the lowly expressed proteins in head and neck cancer proteins. Further, the average oxygen content of the up regulated proteins was 2.54% higher than other. None of their coding genes were distributed on the Y chromosome. The up regulated proteins were enriched in endocytosis, apoptosis and regulation of actin cytoskeleton. The increased oxygen contents of the highly expressed and the up regulated proteins might be caused by frequent activity of cytoskeleton and adapted to the rapid growth and fast division of the head and neck cancer cells. The oxygen usage bias and key proteins may help us to understand the mechanisms behind head and neck cancer in targeted therapy, which lays a foundation for the application of stoichioproteomics in targeted therapy and provides promise for potential treatments for head and neck cancer.

Resumo A hipóxia é uma característica proeminente do câncer de cabeça e pescoço. No entanto, as características do elemento oxigênio das proteínas e como elas se adaptam aos microambientes de hipóxia do câncer de cabeça e pescoço ainda são desconhecidas. Sequências do genoma humano e dados expressos de proteínas de câncer de cabeça e pescoço foram recuperados do atlas de patologia do projeto Human Protein Atlas. Em seguida, comparou o conteúdo do elemento de oxigênio e carbono entre proteomas de câncer de cabeça e pescoço, e células epiteliais escamosas da mucosa oral normal, localizações do genoma, vias e dissecção funcional associada ao câncer de cabeça e pescoço também foram estudadas. Um total de 902 proteínas expressas diferencialmente foi observado onde o conteúdo médio de oxigênio é maior do que as proteínas expressas de forma humilde em proteínas de câncer de cabeça e pescoço. Além disso, o conteúdo médio de oxigênio das proteínas reguladas positivamente foi 2,54% maior do que das outras. Nenhum de seus genes codificadores foi distribuído no cromossomo Y. As proteínas reguladas positivamente foram enriquecidas em endocitose, apoptose e regulação do citoesqueleto de actina. O conteúdo aumentado de oxigênio das proteínas altamente expressas e reguladas pode ser causado pela atividade frequente do citoesqueleto e adaptado ao rápido crescimento e divisão das células cancerosas de cabeça e pescoço. O viés do uso de oxigênio e as proteínas-chave podem nos ajudar a entender os mecanismos por trás do câncer de cabeça e pescoço na terapia direcionada, o que estabelece uma base para a aplicação da estequioproteômica na terapia direcionada e oferece uma promessa para potenciais tratamentos para o câncer de cabeça e pescoço.

Investigation and correlation analysis of financial toxicity and risk of suicide in the patients with head and neck cancer / 中国实用护理杂志

Objective:To understand the current state of financial toxicity and suicide risk in head and neck cancer patients, to investigate the correlation between the level of financial toxicity and suicide risk in head and neck cancer patients, and to provide a basis for reducing the level of financial toxicity and the risk of suicide in head and neck cancer patients.Methods:A cross-sectional survey was conducted, from March 1 to July 31, 2022, 150 head and neck cancer patients were selected from Oncology Department of East Hospital Affiliated to Tongji Universityby by convenient sampling method. The survey was carried out by means of the general questionnaire, Comprehensive Score for Financial Toxicity based on the Patient-Reported Outcome Measures (COST-PROM), Cancer Suicide Risk Scale (CSRS), and then analysis the datum.Results:The score of COST-PROM of 150 head and neck cancer patients was (18.00 ± 6.12) points, and the score of CSRS of head and neck cancer patients was (36.31 ± 8.51) points. The total score of economic toxicity was significantly negatively correlated with the total score of suicide risk and its dimensions ( r values were -0.446 to 0.235, all P<0.05). The total score of suicide risk was negatively correlated with the total score of economic toxicity and the scores of each dimension ( r values were -0.446 to -0.251, all P<0.05). Conclusions:Patients with head and neck cancer were at higher risk of suicide, and financial toxicity was a significant contributing factor to suicide risk, with higher levels of financial toxicity associated with a higher risk of suicide. Reducing the level of financial toxicity in patients with head and neck cancer has important implications for reducing their risk of suicide.

Deep learning-based dose prediction in radiotherapy planning for head and neck cancer / 南方医科大学学报

OBJECTIVE@#To propose an deep learning-based algorithm for automatic prediction of dose distribution in radiotherapy planning for head and neck cancer.@*METHODS@#We propose a novel beam dose decomposition learning (BDDL) method designed on a cascade network. The delivery matter of beam through the planning target volume (PTV) was fitted with the pre-defined beam angles, which served as an input to the convolution neural network (CNN). The output of the network was decomposed into multiple sub-fractions of dose distribution along the beam directions to carry out a complex task by performing multiple simpler sub-tasks, thus allowing the model more focused on extracting the local features. The subfractions of dose distribution map were merged into a distribution map using the proposed multi-voting mechanism. We also introduced dose distribution features of the regions-of-interest (ROIs) and boundary map as the loss function during the training phase to serve as constraining factors of the network when extracting features of the ROIs and areas of dose boundary. Public datasets of radiotherapy planning for head and neck cancer were used for obtaining the accuracy of dose distribution of the BDDL method and for implementing the ablation study of the proposed method.@*RESULTS@#The BDDL method achieved a Dose score of 2.166 and a DVH score of 1.178 (P < 0.05), demonstrating its superior prediction accuracy to that of current state-ofthe-art (SOTA) methods. Compared with the C3D method, which was in the first place in OpenKBP-2020 Challenge, the BDDL method improved the Dose score and DVH score by 26.3% and 30%, respectively. The results of the ablation study also demonstrated the effectiveness of each key component of the BDDL method.@*CONCLUSION@#The BDDL method utilizes the prior knowledge of the delivery matter of beam and dose distribution in the ROIs to establish a dose prediction model. Compared with the existing methods, the proposed method is interpretable and reliable and can be potentially applied in clinical radiotherapy.

Types and Incidence of Moderate and Severe Toxic Effects of Carbon Ion Radiotherapy for Head and Neck Cancer / 肿瘤防治研究

Head and neck tumors often have complex anatomical structures and are adjacent to important organs. Radiation injury caused by conventional radiotherapy technology is the main dose-limiting factor. Carbon ion beam has become the most ideal radiation to replace photon due to its excellent relative biological effect and Bragg peak. By 2019, 32 000 people worldwide have received carbon ion radiotherapy (CIRT). Despite the efficient tumor killing ability of this technology, radiation injury cannot be avoided. This article reviews the types and incidence of moderate to severe radiation injury caused by CIRT in head and neck cancer to provide a comprehensive understanding of the potential risks in CIRT.

A bioinformatic analysis of the role of TP53 status on the infiltration of CD8+ T cells into the tumor microenvironment

CD8+ T cells play basic roles in the immune system in a tumor microenvironment (TME) to fight cancer. Several reports have suggested signs of the involvement of tumor protein p53 (TP53) in a complex immune system network. Moreover, our previous research indicated that TP53 orchestrates the polarization and infiltration of macrophages into the TME. In the present study, the clinical function of TP53 status (wild/mutant) in CD8+ T cell infiltration was assessed using more than 10,000 The Cancer Genome Atlas (TCGA) samples from 30 cancer types through Tumor Immune Estimation (TIMER). Our investigation revealed that CD8+ T cell infiltration was higher in head and neck squamous cell carcinoma (HNSC) and uterine corpus endometrial carcinoma (UCEC) patients with wild-type TP53 than in those with mutant TP53. Wild-type TP53 conferred a good prognosis for HNSC and UCEC (P<0.05). In contrast, CD8+ T cell infiltration in lung adenocarcinoma (LUAD) patients with wild-type TP53 was much lower than in those with mutant TP53. Notably, clinical outcomes for LUAD with wild-type TP53 were poor (P<0.05). This study was the first to provide insights into the novel association of TP53 with CD8+ T cells infiltration in the TME in patients with HNSC, LUAD, and UCEC. Therefore, TP53 status acts as a prognostic marker, and this can be used as a basis to further study the effect of targeting TP53 in these patients. Furthermore, our study found that TP53 status was a reliable predictive factor and therapeutic target in patients with HNSC and UCEC.

Impacto na deglutição e manejo da mucosite hipofaríngea em pacientes submetidos à quimiorradioterapia na região de cabeça e pescoço: uma revisão integrativa da literatura / Management of hypopharyngeal mucositis in patients undergoing chemoradiotherapy in the head and neck region and its impact on swallowing: an integrative literature review

RESUMO Objetivo Investigar o impacto da mucosite hipofaríngea quimiorradioinduzida na deglutição e o seu manejo, a partir de uma revisão integrativa de literatura. Estratégia de pesquisa A busca e a seleção dos artigos foram realizadas nas seguintes bases de dados: PubMed, Embase, Scopus, ScienceDirect e LILACS. Critérios de seleção Os termos de busca utilizados foram ''Pharyngeal Mucositis", ''Radiotherapy" e ''Esophagitis", com auxílio do operador booleano (AND). A equação de busca utilizada foi: ''Pharyngeal Mucositis" AND "Radiotherapy" AND "Esophagitis". A seguinte questão central orientou o estudo: "Qual a forma de avaliação e manejo da mucosite hipofaríngea induzida pela radiação na região de cabeça e pescoço e seu impacto na deglutição?". Resultados Foram identificados 75 estudos, sendo que 6 foram excluídos devido à duplicidade e 60 foram excluídos por não se encaixarem nos critérios de inclusão; os artigos restantes foram lidos na íntegra e 4 foram selecionados para fazerem parte desta revisão integrativa da literatura. Conclusão Apesar da escassa literatura e das poucas informações sobre os métodos de avaliação da mucosite hipofaríngea, os artigos apontam que, independentemente da dose de radiação, a radioterapia na região cervical causa mucosite hipofaríngea. A mucosite hipofaríngea provoca grande impacto na deglutição, resultando na necessidade de uso de via alternativa de alimentação. Além da ausência de informações quanto à avaliação e graduação da mucosite hipofaríngea, os estudos não discutem o tratamento direto ou a prevenção desse tipo de doença.

ABSTRACT Purpose To investigate the impact of chemoradiation-induced hypopharyngeal mucositis on swallowing and its management, based on an integrative literature review. Research strategy Two researchers were responsible for the search and selection of articles, within the following databases: PubMed, Embase, Scopus, Science Direct, and Lilacs. Selection criteria The search terms used were "Pharyngeal Mucositis", "Radiotherapy" and "Esophagitis", with the aid of the Boolean operator (AND). The search equation used was "Pharyngeal Mucositis" AND Radiotherapy AND Esophagitis. The following central question guided the study: "What is the assessment and management of radiation-induced hypopharyngeal mucositis in the head and neck region and its impact on swallowing?" Results 75 studies were identified, of which 6 were excluded due to duplicity and 60 were excluded for not meeting the inclusion criteria; the remaining articles were read in full and 4 were selected to be part of the integrative literature review. Conclusion Despite the scarce literature and little information on methods for evaluating hypopharyngeal mucositis, the articles point out that, regardless of the radiation dose, radiotherapy in the cervical region causes hypopharyngeal mucositis. Hypopharyngeal mucositis causes a great impact on swallowing, resulting in the need to use an alternative feeding route. In addition to the lack of information regarding the assessment and grading of hypopharyngeal mucositis, the studies do not discussitsdirect treatment or prevention.

Asociación entre la infección por virus del papiloma humano y el carcinoma de laringe en adultos de 35-75 años de edad en el instituto nacional del cáncer rosa emilia sánchez pérez de tavarez (incart), en el período agosto 2012 - enero 2019, santo domingo, república dominicana / Association between human papillomavirus infection and laryngeal carcinoma in adults between 35 and 75 years of age at the Rosa Emilia Sánchez Pérez de Tavarez National Cancer Institute (INCART), in the period August 2012 - January 2019, Santo Domingo, Dominican Republic

Introducción: el carcinoma de cabeza y cuello comprende un grupo de neoplasias que comparten un origen anatómico similar. Ocupan el sexto lugar mundial entre las neoplasias de todas las localizaciones, y el sitio afectado con mayor frecuencia es la cavidad oral. Ahora se reconoce el rol del virus del papiloma humano como factor independiente en el desarrollo de estas neoplasias. En los últimos 15 años se ha observado un incremento en la incidencia de carcinoma de células escamosas inducido por virus del papiloma humano (VPH). Materiales y métodos: este es un estudio observacional de tipo descriptivo transversal. Se realizó un análisis documental de los expedientes clínicos de los pacientes que cumplan con los criterios de inclusión. Resultados: en este estudio fue encontrada una prevalencia del 14 % del VPH en cánceres laríngeos. El tipo 16 del VPH fue el único identificado y descrito entre los expedientes clínicos de este estudio y, este último, con una prevalencia de un 20 %. Discusión: el VPH puede estar involucrado en el desarrollo de algunos cánceres de laringe y su rol puede ser más predominante en hombres mayores de 50 años.

Introduction: Head and neck carcinoma comprises a group of neoplasms with similar anatomical origins. They occupy the sixth place in the world among the neoplasias of all the locations, and the most affected site is the oral cavity. The role of the Human Papillomavirus as an independent factor in the development of these neoplasms is now recognized. In the last 15 years, an increase in the incidence of squamous cell carcinoma induced by Human Papillomavirus (HPV) has been observed. Methods: This is an observational study of transversal descriptive type. A documental analysis of the clinical files of the patients that meet the inclusion criteria was performed. Results: in this study, a 14 % prevalence of HPV in laryngeal cancers was found. Type 16 HPV was the only one identified and described in the clinical files of this study and the latter with a prevalence of 20 % Discussion: HPV may be involved in the development of some laryngeal cancers and its role may be more predominant in men older than 50 years.

Comparison of Clinical and Pathological Staging in Patients with Head and Neck Cancer After Neck Dissection

Abstract Introduction Clinical and pathological staging plays an important role on the prognosis of head and neck cancer (HNC) patients. Objective The present study aims to compare clinical and pathological T, N and overall staging in patients with HNC, to identify factors associated with these discrepancies, and to analyze and compare survival or disease-free survival in staging disagreements. Methods Retrospective cohort including every patient submitted to neck dissection from January 2010 to December 2020 in the department of Otorhinolaryngology of a tertiary hospital center. Results A total of 79 patients were analyzed; their mean age was 58.52 ± 13.15 years old and 88.9% were male. Assessing overall staging, discrepancies were noted in 53% (36.4% upstaging and 16.6% downstaging) and were significantly associated with clinical overall staging (p = 0.006). Regarding T staging, differences were noted in 45.5% (30.3% upstaging and 15.2% downstaging) and were significantly associated with imaging modality (p = 0.016), clinical T staging (p = 0.049), and histology (p = 0.017). Discrepancies in N staging were noted in 38% (25.3% upstaging and 12.7% downstaging) and were significantly associated with age (p = 0.013), clinical N staging (p < 0.001), and presence of extranodal invasion (p < 0.001). Both in Overall, T, and N staging, the aforementioned disagreements were not associated with either higher mortality or higher disease relapse. Conclusion Overall, T, and N staging disagree in an important number of cases, and the overall stage can disagree in up to 53% of the cases. These disagreements do not seem to influence overall and disease-free survival.

Immunoexpression profile of hypoxia-inducible factor (HIF) targets in potentially malignant and malignant oral lesions: a pilot study

Abstract Oral potentially malignant disorders (OPMD) are associated with an increased risk of oral squamous cell carcinoma (OSCC). OSCC has an aggressive profile and is the most prevalent among different head and neck malignancies. Most OSCC patients are diagnosed with advanced stage tumors and have a poor prognosis. Cancer cells are able to reprogram their metabolism, even in the presence of oxygen, enhancing the conversion of glucose to lactate via the glycolytic pathway, a phenomenon mainly regulated by hypoxia-inducible factor (HIF) signaling. Thus, several glycometabolism-related biomarkers are upregulated. Objectives This study aimed to evaluate the immunoexpression of the HIF targets GLUT1, GLUT3, HK2, PFKL, PKM2, pPDH, LDHA, MCT4, and CAIX in OPMD and OSCC samples, in order to identify potential correlations between biomarkers' immunoexpression, clinicopathological features, and prognostic parameters. Methodology OSCC and OPMD samples from 21 and 34 patients (respectively) were retrospectively collected and stained for the different biomarkers by immunohistochemistry. Results CAIX and MCT4 expressions were significantly higher in OSCC samples when compared with OPMD samples, while the rest were also expressed by OPMD. GLUT3 and PKM2 alone, and the concomitant expression of more than four glycometabolism-related biomarkers were significantly correlated with the presence of dysplasia in OPMD. When considering OSCC cases, a trend toward increased expression of biomarkers and poor clinicopathological features was observed, and the differences regarding HK2, PFKL, LDHA and MCT4 expression were significant. Moreover, HK2 and CAIX were correlated with low survival rates. GLUT1 and GLUT3 were significantly associated with poor outcome when their expression was observed in the hypoxic region of malignant lesions. Conclusion OPMD and OSCC cells overexpress glycolysis-related proteins, which is associated with aggressive features and poor patient outcome. Further research is needed to deeply understand the glycolic phenotype in the process of oral carcinogenesis.

Stoichioproteomics study of differentially expressed proteins and pathways in head and neck cancer / Estudo estequioproteômico de proteínas e vias expressas diferencialmente no câncer de cabeça e pescoço

Hypoxia is a prominent feature of head and neck cancer. However, the oxygen element characteristics of proteins and how they adapt to hypoxia microenvironments of head and neck cancer are still unknown. Human genome sequences and proteins expressed data of head and neck cancer were retrieved from pathology atlas of Human Protein Atlas project. Then compared the oxygen and carbon element contents between proteomes of head and neck cancer and normal oral mucosa-squamous epithelial cells, genome locations, pathways, and functional dissection associated with head and neck cancer were also studied. A total of 902 differentially expressed proteins were observed where the average oxygen content is higher than that of the lowly expressed proteins in head and neck cancer proteins. Further, the average oxygen content of the up regulated proteins was 2.54% higher than other. None of their coding genes were distributed on the Y chromosome. The up regulated proteins were enriched in endocytosis, apoptosis and regulation of actin cytoskeleton. The increased oxygen contents of the highly expressed and the up regulated proteins might be caused by frequent activity of cytoskeleton and adapted to the rapid growth and fast division of the head and neck cancer cells. The oxygen usage bias and key proteins may help us to understand the mechanisms behind head and neck cancer in targeted therapy, which lays a foundation for the application of stoichioproteomics in targeted therapy and provides promise for potential treatments for head and neck cancer.

A hipóxia é uma característica proeminente do câncer de cabeça e pescoço. No entanto, as características do elemento oxigênio das proteínas e como elas se adaptam aos microambientes de hipóxia do câncer de cabeça e pescoço ainda são desconhecidas. Sequências do genoma humano e dados expressos de proteínas de câncer de cabeça e pescoço foram recuperados do atlas de patologia do projeto Human Protein Atlas. Em seguida, comparou o conteúdo do elemento de oxigênio e carbono entre proteomas de câncer de cabeça e pescoço, e células epiteliais escamosas da mucosa oral normal, localizações do genoma, vias e dissecção funcional associada ao câncer de cabeça e pescoço também foram estudadas. Um total de 902 proteínas expressas diferencialmente foi observado onde o conteúdo médio de oxigênio é maior do que as proteínas expressas de forma humilde em proteínas de câncer de cabeça e pescoço. Além disso, o conteúdo médio de oxigênio das proteínas reguladas positivamente foi 2,54% maior do que das outras. Nenhum de seus genes codificadores foi distribuído no cromossomo Y. As proteínas reguladas positivamente foram enriquecidas em endocitose, apoptose e regulação do citoesqueleto de actina. O conteúdo aumentado de oxigênio das proteínas altamente expressas e reguladas pode ser causado pela atividade frequente do citoesqueleto e adaptado ao rápido crescimento e divisão das células cancerosas de cabeça e pescoço. O viés do uso de oxigênio e as proteínas-chave podem nos ajudar a entender os mecanismos por trás do câncer de cabeça e pescoço na terapia direcionada, o que estabelece uma base para a aplicação da estequioproteômica na terapia direcionada e oferece uma promessa para potenciais tratamentos para o câncer de cabeça e pescoço.