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Purpose: This article aims to comprehensively analyze the unique challenges in managing patients with metastatic Differentiated Thyroid Cancer (DTC) that develop radioiodine-refractory disease, especially in developing countries in Latin America. We discuss key contentious aspects of their treatment, such as the optimal timing for initiating systemic therapy, the choice of first-line medications, the appropriate timing for requesting molecular interrogation, and the challenges associated with accessing these drugs and molecular panels., Methods: To illustrate these challenges and enhance understanding, we present five real clinical cases from the authors' experiences., Results: Patients with Differentiated Thyroid Cancer (DTC) generally have an excellent prognosis, with an overall 10-year survival rate exceeding 97%. However, approximately 5% of DTC patients, especially those with distant metastases, may develop radioiodine-refractory disease, reducing survival rates. Access to medications remains difficult and time-consuming, particularly for patients within the public healthcare system. Urgent discussions on drug pricing involving all stakeholders are imperative. To break free from complacency, stakeholders must prioritize patient well-being by advocating for evidence-based drug pricing, increased participation in clinical trials, and streamlined regulatory processes., Conclusion: Beyond the recognized need for prospective randomized clinical trials to determine the optimal first-line drug and the timing of molecular testing, this type of manuscript plays a pivotal role in stimulating discussions and disseminating comprehensive knowledge about the challenges associated with treating and monitoring patients with radioiodine-refractory thyroid carcinoma, especially in developing countries., Competing Interests: Compliance with ethical standards Conflict of interest Gustavo C. Penna is a speaker and participant of the Advisory Boards for Ipsen and Knight. Fabian Pitoia is a speaker and participated in Advisory Boards for Bayer and Raffo, PI Bayer, Roche, and Novartis. Aline L. F. Chaves is a speaker and participates in Advisory Boards for Merck Serono, Merck Sharpe and Dhome, Ipsen, Knight, Bayer, Eli Lilly. Kamilla M. A. Brandão Rajão is a speaker for Knight. The other authors have no financial interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery-oral cavity, Clinical oncology-oral cavity, Head and neck surgery-oropharynx, Clinical oncology-oropharynx, Head and neck surgery-larynx, Head and neck surgery-larynx/hypopharynx, Clinical oncology-larynx/hypopharynx, Clinical oncology-recurrent and metastatic head and neck cancer, Head and neck surgery-reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.

Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.

Changes in metabolism are mechanisms that are largely implicated in the development, progression, and metastasis of head and neck squamous cell carcinoma (HNSCC) and also in resistance to different anticancer therapies. Identification of biomarkers for differentiation between cancerous and normal epithelium, treatment design and prognosis remain a vital issue in the field of head and neck cancer. The present study analyzed the main biochemical changes that occur in HNSCC tumors by through mechanisms involving oxidative stress. The release of substances reactive to thiobarbituric acid was significantly lower in HNSCC tumor tissue as compared to healthy tissue. The assays related to the lipid profile assays showed changes in membrane biophysics of tumor cells due to an increase in total phospholipids and total cholesterol, as well as an increased activity and expression of the α1 subunit of Na, K-ATPase, which is fundamental in the process of carcinogenesis. The modulation of the antioxidant system was also affected, with a decrease in the catalytic activity of the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as a reduction of glutathione (GSH) content and an increase in H 2 O 2 content. A reduction in catalase (CAT) activity was observed. The data presented here are in accordance with important findings described by us in a previous study, involving the same individuals, but with a focus on the damage generated in red blood cells, resulting from tumor installation. Therefore, it was possible to conclude that the biochemical alterations found in HNSCC cells are fundamental for transformation and maintenance of the tumor cell and once it is installed, it is also capable of generating injuries in the patients' red blood cells. Our data demonstrate that this could be a promising biomarker for HNSCC., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mucositis is one of the more frequent and costly adverse events following cancer treatment. To evaluate and report the direct economic outcomes associated with the management of mucositis across several cancer treatments we conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Scopus, MEDLINE/PubMed, and Embase were searched electronically and a total of 37 relevant studies were included. The costs attributable to mucositis in the hematopoietic stem cell transplantation setting ranged from 1124,47 US dollars (USD) to 299 214,14 USD per patient. The radiotherapy/chemoradiotherapy/radiotherapy plus molecular targeted therapy accounted for mucositis costs that ranged from 51,23 USD to 33 560,58 USD per patient. Costs for mucositis in the chemotherapy setting ranged from 4,18 USD to 31 963,64 USD per patient. When the cancer treatment was not specified, costs of mucositis ranged from 565,85 USD to as high as 20 279, 12 USD per patient. Mucositis costs from multimodal therapy ranged from 12,42 USD to 5670,46 USD per patient. The molecular targeted therapy setting included only one study and depending on the healthcare providers' perspective of each country evaluated, mucositis' costs ranged from 45,78 USD to 3484,91 USD per patient. Mucositis is associated with increased resource use, consultations, hospitalizations and extended hospitalizations, leading to a substantial incremental cost that exacerbates the economic burden on the patient, health plan and health system across several cancer treatments and diagnosis. More studies with a prospective evaluation of the economic costs associated with mucositis management are needed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to estimate the frequency of oral leukoplakia and oral erythroplakia in young patients., Study Design: The systematic review was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and performed in the following electronic databases: PubMed, Scopus, and Embase. The studies included were cross-sectional, cohort, and diagnostic, which provided with clinical and microscopic data of patients younger than 40 years. The Critical Appraisal Checklist for Prevalence Studies from the Joanna Briggs Institute and the Quality Assessment Tool for Diagnostic Accuracy Studies were used to assess the risk of bias., Results: Five studies met eligibility criteria and were included. The total number of patients from the studies was 1246, of which 115 were young patients (9.2%) with oral leukoplakia as the only oral potentially malignant disorder reported. Oral epithelial dysplasia was identified in 40 cases (34.7%), of which 8 (6.9%) presented malignant transformation., Conclusions: The frequency of oral leukoplakia is low in young patients. Observational studies are necessary for understanding oral leukoplakia and other oral potentially malignant disorders in younger patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background  With the COVID-19 pandemic, the clinical practice of physicians who work in the head and neck field in Brazil dropped dramatically. The sustained impact of the pandemic is not known. Methods  An anonymous online survey was distributed to Brazilian otolaryngologists, head and neck surgeons, medical and radiation oncologists, asking about their clinical practice in the third to fourth months of the pandemic. Results  The survey was completed by 446 specialists. About 40% reported reduction of more than 75% in outpatient care. A reduction of 90% to 100% in airway endoscopies was reported by 50% of the responders, and the same rate of reduction regarding surgeries (pediatric or nasosinusal) was reported by 80% of them. Family income decreased by 50%, and the psychological burden on physicians was considerable. The availability of personal protective equipment and safety precautions were limited, especially in the public sector. Conclusion  COVID-19 is still impacting the head and neck field, and safety concerns may hinder the prompt resumption of elective care., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (Fundação Otorrinolaringologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous and complex disease, both from a clinical and molecular point of view. The prolonged use of alcohol and tobacco, along with the release of tumor secretions can modulate blood cells, such as erythrocytes. Here, this study was conducted with 24 patients diagnosed with HNSCC and an equal number of healthy individuals are matched by age and gender. The levels of lipid peroxidation were measured using the individual plasma, while for lipid concentrations, identification and quantification Na, K-ATPase activity and osmotic fragility, the red blood cell concentrate were used. The release of TBARS was significantly higher in patients with HNSCC. The lipid profile assays demonstrated a rearrangement of the erythrocyte membrane due to a decrease in total phospholipids and phosphatidylethanolamine followed by an increase in total cholesterol and phosphatidylcholine. Na, K-ATPase activity also increased. Erythrocytes were more fragile in patients with HNSCC than in health individuals. Therefore, the membrane of erythrocytes were rearranged and Na, K-ATPase function altered in the HNSCC patients. Our findings suggests that the alcohol, tobacco and tumor secretion modulate in a specific manner that the erythrocytes membranes of these patients making this system a potential tool for HNSCC biomarker of tumor progression.

Objectives: to provide accurate information about the global prevalence of human papillomavirus (HPV) in oropharyngeal squamous cell carcinomas (OPSCC)., Material and Methods: a systematic review was performed using three main electronic databases. Studies were independently assessed by two reviewers based on established eligibility criteria, to identify the prevalence of HPV-driven OPSCC following criteria defined by the American Society of Clinical Oncology. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Statistical software MedCalc was used to perform meta-analyses., Results: from 2215 records found, 15 were included, reporting data from 6009 patients (time period range: 1980-2016), distributed in 11 countries. Eleven studies were considered as presenting low risk, and four as moderate risk of bias. Using proportion meta-analysis, pooled prevalence of HPV-driven OPSCC was 44.8 % (95 %CI: 36.4-53.5 %; i 2 = 97.6 %), with the highest rates in New Zealand (74.5 %; 95 %CI: 60.9-85.3 %), and the lowest in Brazil (11.1 %; 95 %CI: 4.5-21.5 %). HPV prevalence was similar between males (45.7 %; 95 %CI: 36.5-55.0 %; i 2 = 96.4 %) and females (42.2 %; 95 %CI: 34.3-50.5 %; i 2 = 85.4 %). Mean/median age ranged from 59.1-67.1 years in the HPV-negative group, and from 55.7-63.5 years in the HPV-positive group. There was an overall discordance between testing by p16 (49.4 %; 95 %CI, 38.2-60.5 %; i 2 = 96.2 %) and p16+ISH/PCR (44.7 %; 95 %CI, 33.5-56.2 %; i 2 = 96.4 %)., Conclusion: Overall pooled prevalence of HPV-driven OPSCC was approximately 45 %, with similar distribution among males and females. Double p16/HPV-DNA/RNA testing may be considered to increase specificity and prognostic accuracy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction  Coronavirus disease 2019 (COVID-19) is an acute infection caused by the new coronavirus (SARS-CoV-2) and it is highly transmissible, especially through respiratory droplets. To prepare the health system for the care of these patients also led to a restriction in the activity of several medical specialties. Physicians who work with patients affected by diseases of the head and neck region constitute one of the populations most vulnerable to COVID-19 and also most affected by the interruption of their professional activities. Objective  The aim of the present study was to assess the impact of the COVID-19 pandemic on the practice of head and neck surgeons and otorhinolaryngologists in Brazil. Methods  An anonymous online survey of voluntary participation was applied, containing 30 questions regarding demographic aspects, availability of personal protective equipment (PPE), and impact on the routine of head and neck surgeons and otorhinolaryngologists, as well as clinical oncologists and radiation oncologists who work with head and neck diseases. Results  Seven hundred and twenty-nine answers were received in a period of 4 days, ∼ 40 days after the 1 st confirmed case in Brazil. With professionals working in public and private services, there was a high level of concerns with the disease and its consequences, limited availability of PPE and a significant decrease in the volume of specialized medical care. Conclusion  The study demonstrated a direct impact of the COVID-19 pandemic on the clinical practice of specialties related to the treatment of patients with diseases of the head and neck region already in the beginning of the illness management in Brazil., Competing Interests: Conflict of Interests The authors declare no potential conflict of interests.

Background: Incidence and mortality rates of childhood cancer represent a global public health issue, however, the worldwide prevalence of head and neck cancer in pediatric patients (HNCPP) is still unknown. Therefore, this study aimed to describe the frequency and distribution of HNCPP worldwide., Methods: A specific search strategy was performed using MEDLINE, Scopus, and EMBASE to include studies based on hospital records, national cancer registries, and pathology files. Studies quality was assessed using the risk of bias checklist of the Joanna Briggs Institute Critical Appraisal., Results: Nineteen publications (15,970 cases) were included. Global frequency ranged from 0.25 % to 15 %. Male patients older than 10 years of age were most affected by lymphomas, followed by carcinomas and sarcomas. Non-Hodgkin lymphoma, Hodgkin lymphoma, rhabdomyosarcoma, thyroid carcinoma, and nasopharyngeal carcinoma were the main histopathological subtypes. Neck/lymph nodes were anatomical hotspots., Conclusions: This HNCPP global overview may guide secondary prevention strategies and future etiological studies., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to evaluate the immunohistochemical expressions of PD1, CD4 + , and CD8 + in premalignant lesions (OPML) that were transformed into oral squamous cell carcinoma OSCC (OPML-OSCC), in OSCC and also in premalignant lesions that were not transformed into OSCC (OPML-NOSSC)., Materials and Methods: Retrospective analyses were performed in order to verify the demographic characteristics of the patients. CD4, CD8, and PD1 IMH studies were carried out on OPML and OSCC samples from 11 patients with OPML-OSCC and OPML, together with samples from 14 patients with OPML-NOSCC. The differences between OPML-OSCC and OPML-NOSCC were analyzed., Results: Non-homogenous leukoplakia, together with the related oral subsite, and the lack of an exposure to tobacco, were all associated with malignant transformations. There were no statistical differences in the PD1 expression and the CD4 + cells in OPML-OSCC and OPML-NOSCC. A significant increment in the CD8 + cells was noted in the OPML that evolved into carcinomas when compared with OPML-NOSCC (p = 0.05), whereas there were higher CD8 + cells levels in the carcinomas when compared with the OPML that evolved into carcinomas (p = 0.027)., Conclusions: CD8 + cells infiltrate more in OPML-NOSCC than in OPML-OSCC. Carcinoma is more infiltrated by CD8 + cells than its associated OPML., Clinical Relevance: Understanding immunological factors associated with malignant transformation of oral premalignant lesions can open a new way to treat this disease.

Squamous-cell carcinoma of the head and neck (SCCHN) is an important problem in Brazil, where epidemiological and socioeconomic features often create barriers to the implementation of combined modalities with curative potential. Cisplatin improves the efficacy of radiotherapy in the adjuvant treatment of localized SCCHN and in the definitive therapy of locally advanced disease. However, the addition of high-dose cisplatin to radiotherapy increases treatment toxicity and is not always warranted. A panel of experts convened in Sao Paulo, Brazil, for discussions and recommendations regarding the use of high-dose cisplatin in combination with radiotherapy in SCCHN. In addition to discussing their professional experience, panel members used the current literature to provide evidence-based, practical recommendations regarding sociodemographic or medical criteria that may preclude safe administration of cisplatin. It is hoped that the application of these recommendations in clinical practice may improve therapeutic results in Brazil and other countries with similar health-care environments., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The primary goal of treatment in advanced laryngeal cancer is to achieve optimal oncologic outcomes while preserving function and quality of life. Combination of chemotherapy and radiation has been popularized as an alternative to surgery for patients facing total laryngectomy. However, survival analyses from large, population-based databases have not duplicated results reported from randomized trials., Methods: A comprehensive literature review was undertaken to try to better understand the reasons why results differ among randomized trials and population cohort studies., Results: A variety of reasons are discussed, including differences in patient staging, selection bias, complexity bias, inconsistent terminology, patient compliance and treatment expertise., Conclusions: Personalized treatment considering all factors is critical for optimal outcomes. In general, evidence supports total laryngectomy for patients with T4 cancers. Definitive chemoradiotherapy strategies are acceptable alternatives for T3 cancers, provided that all resources for the administration of the treatment, follow-up and surgical salvage are available., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)